Results

Contents

Section – I
Role of Interventional Radiology in the management of Hepatic Tumors

1. Hepatocellular Carcinoma – Diagnostic and Therapeutic Pathways

2. Chemoembolisation & Radiofrequency Ablation of Liver Tumors

3. Management of Hepatic Metastases

4. Portal Vein Embolisation

5. Isotope therapy for Primary and Secondary Hepatic Malignancy

Section II
Role of Interventional Radiology in the management of Lung Malignancy

1. Image – Guided Radiofrequency ablation in Lung Malignancy

Section III
Role of Interventional Radiology in Pain Management in Interventional Oncology.

1. Current Status of Vertebroplasty in Metastatic Disease.

2. Management of Painful Skeletal Metastases (RFA / Osteoplasty)

3. Image guided nerve blocks

Section IV

Role of Interventional Radiology in Thrombosis Management in oncology.

1. Deep Venous Thrombosis

2. Endovascular Management of Deep Venous Thrombosis

3. Endovascular Management of Pulmonary embolism

4. Venous strokes in Malignancy

Section V

Role of Functional Imaging in Interventional Oncology.

1. PET guided Biopsy

2. PET in RFA surveillance

3. SPECT in Carotid Test Occlusion for Skull Base Tumors

Dr. (Ms.) K.A. Dinshaw,
29 February, 2008 DMRT (Lond), FRCR (Lond)
Mumbai, India Director, Tata Memorial Centre

Hepatocellular Carcinoma - Diagnostic & Therapeutic Pathways

HEPATOCELLULAR CARCINOMA

Hepatocellular carcinoma (HCC) is the commonest primary neoplasm of the liver. Untreated, the disease has a very poor prognosis with less than 5% survival at 5 years. Majority of cases are associated with hepatitis B and C infections and the prevalence is on an increase world over.

Surgical resection provides the best chance for long term survival in patients with HCC.However only about 20% of patients are surgical candidates at presentation either due to advanced loco regional disease or comorbidities, especially decompensated cirrhosis.

Interventional radiology plays a major role in the triage of patients with HCC.Minimally invasive treatment modalities are the mainstay of palliative therapy in patients with unresectable disease. These methods are also increasingly being used in the surgical candidates either as a bridge to transplantation or to make resection safer in patients with suboptimal future liver remnant.

Table 1: Interventional Therapies for HCC
I. Thermal Ablation
i. Radiofrequency Ablation
ii. Laser Ablation
iii. Cryoablation
iv. Microwave ablation
II. Chemical Ablation
i. Percutaneous Ethanol Injection (PEI)
III. Transarterial Therapies
i. Transarterial chemoembolization(TACE)
l Conventional
l Drug eluting beads
l Newer chemotherapeutic drugs
ii. Selective Internal Radiation Therapy(SIRT)
l Yttrium-90 radioactive particles
l Rhenium-188 lipiodol
iii. Transarterial Embolisation (TAE)
IV. Portal Vein Embolisation (PVE)
V. Emerging Modalities
i. High Intensity Focused Ultrasound
l MR guided
l US guided
ii. Portal Vein Chemotherapy

Diagnostic Algorithm:

• A focal liver lesion in a patient with cirrhosis is highly likely to be a HCC.
• A raised serum Alfa Feto Protein (AFP) level confirms the diagnosis and further investigations are only required to guide selection of the most appropriate therapy.
• If AFP is normal, further imaging with Triphasic CT, MRI or Lipiodol CT will allow a confident diagnosis of HCC to be made, thus obviating the need for a biopsy.
• Biopsy is rarely required for the diagnosis and is best avoided especially in the potentially resectable lesions in view of tumor seeding in the biopsy tract.

STAGING

At present, multiple staging systems for HCC are recognized. The AJCC/UICC staging system is based on the standard TNM system and is well validated. It incorporates anatomic and histopathological findings at resection. Therefore this system is more applicable for patients undergoing surgical treatment i.e. resection or transplantation.

Several other staging systems that incorporate various clinical and radiologic parameters also have been used and validated. These clinical staging systems are most applicable to patients with advanced disease who are not considered candidates for surgery. This is also the patient group receiving minimally invasive therapies and therefore is of practical relevance to the interventional radiologist. Okuda and CLIP are more useful to the interventional radiologists as they help in proper selection and prognostication of patients.

NOTE. Stage 1 = 0; stage 2 = 1 or 2; stage 3 = 3 or 4.

Goals of ablative therapies:

1. Bridge to surgical resection or transplantation

I. Downsize

II. Stabilize disease while patient is on waiting list for transplant or resection.

2. Prolong survival in patients with unresectable disease.

3. Improve quality of life.

SURGICAL MANAGEMENT:

Resection and transplantation are the surgical treatment options in HCC.

Complete surgical resection and hepatic transplantation offer the best chance of a cure for HCC with a 34-59 % 5 year survival rate.Only 20% of patients are candidates for surgical resection due to advanced locoregional disease or poor functional reserve.

Surgical resection is ideal for small, unifocal tumors without vascular invasion, hepatic insufficiency, and clinically significant comorbidities.
Resection is reserved for Child-Pugh Class A patients or Child-Pugh Class B patients with compensated liver function.

Significant hepatic dysfunction predisposes patients to post operative complications.

Hepatic transplantation potentially offers long-term cure but is reserved for patients with small tumors and Child-Pugh class C disease, who are not likely to tolerate even a limited resection.

Milan criteria for selection of patients for transplantation:

Single tumor < 5cm,

Maximum of 3 tumors with none > 3cm;

Chemoembolisation & Radiofrequency Ablation

CHEMOEMBOLIZATION FOR HCC

(Synonym TACE - Transarterial Chemoembolization)

Aim of the procedure is to obtain cytoreduction by inducing ischemia and depriving the tumor of its nutrients to achieve a reduction or stabilization in the tumor load.

Indications:

1. Hepatoma confined to liver.

2. Patients with minimal or indolent extrahepatic disease may also be candidates for chemoembolization if the liver disease is considered to be the dominant source of morbidity and mortality.

Contraindicatons:

I. Contraindications for administration of chemotherapy

a. Severe thrombocytopenia or leucopenia

b. Cardiac or renal insuffiency

II. Contraindications for hepatic artery embolisation

a. Hepatic encephalopathy or jaundice.

b. Biliary obstruction.

III. Limited Hepatic Reserve

III. Contraindications for angiography

a. Severe contrast reaction

b. Uncorrectable coagulopathy

c. Severe renal insufficiency

Relative Contraindications:

Portal vein thrombosis: Safety of TACE in patients with portal vein thrombosis is well documented.Segmental embolization is mandatory in patients with portal vein thrombosis.Imaging (Colour Doppler or arterio-portography) should document hepatopetal flow.

Pre-treatment assessment:

1. Tissue diagnosis or convincing clinical diagnosis.(e.g. liver mass in a patient with HBV infection with raised AFP )

2. Cross sectional imaging of abdomen and pelvis.(CT or MRI). Triphasic CT is the preferred modality.

3. Exclusion of extra-hepatic disease

4. Laboratory evaluation:

           a. CBC

           b. PT, PTT

           c. LFT and RFT

           d. Tumor marker (AFP)

Risk Stratification:

Increased risk of post procedure hepatic failure in patients with:

1. Involvement of more than 50% liver parenchyma.

2. LDH > 425 IU/L

3. AST > 100IU/L

4. Total bilirubin of 2 mg/dl or greater.

Prior biliary surgery,sphincterotomy and biliary drainage increase the risk of infection and abscess formation following chemoembolization.

Prognostication:

Child-Pugh scoring system is a better predictor of long term survivor than MELD score.

Child-Pugh class A or B with Serum Albumin > 3.4 mg/dl is associated with better survival.

MELD score of > 10 and CLIP score of > 2 - Negative predictors of survival.

Patient preparation:

Vigorous Hydration is initiated prior to the procedure.

Prophylactic antibiotics are given in accordance with hospital antibiotic policy.Aim is to cover enteric gram negative organisms.

Procedural considerations:

Initial angiography to document the anatomy of celiac axis and SMA with careful attention to anatomical variants.
Documentation of portal venous phase to look for patency, collaterals and hepatopetal flow.

Assessment of collateral arteries which may supply the tumor especially after previous chemoembolization including internal mammary, inferior phrenic and intercostal arteries.

Cystic artery should be identified and bypassed almost as a rule.This helps to reduce the severity of post-embolization syndrome.

Choice of angiographic catheter is operator depenent but 4 Fr Simmons or Cobra catheter are most commonly used to select the celiac axis.Further superselective catheterization requires a microcatheter.

Chemoembolization protocol:

Most commonly used protocol consists of a combination of

           100-150 mg cisplatin
           50 mg doxorubicin and/or
           10-20 mg mitomycin C emulsified with 10-20 ml of ethiodized oil (lipiodol).

Intra-arterial injection of chemotherapeutic mixture is followed by particulate embolization with 200-300 micron size PVA particles.

Embolization end point is typically described as the ‘tree-in-winter’ appearance.It is never done to achieve complete stasis.
Intermittent injections of lignocaine helps reduce pain associated with injection of chemotherapeutic agents.

Arterio-portal or arterio hepatic venous fistulae:

Arterio-venous fistulae resulting from previous biopsy may be treated with coil embolization followed by chemoembolization as routine.

Post-procedure management:

Vigorous hydration is initiated until oral intake is adequate.

IV antiobiotics till oral intake is adequate.Choice of antibiotic depends on hospital antibiotic policy.

Antiemetics

Analgesics

Post procedure evaluation:

Typically done at 4-6 wks.

Imaging:

CT-Lipiodol retention and lack of arterial phase enhancement are accepted signs of tumor necrosis on CT.

Persistent enhancement on arterial phase and nodular enhancement on portal venous phase suggest residual tumor.

Size reduction,stabilization or increase are noted.

MRI-Absence of enhancement

Changes in diffusion parameters and spectroscopy to suggest necrosis are increasingle being used for surveillance.

Tumor markers:

AFP levels may be used for follow-up in patients in whom it was elevated pre-treatment.

A significant number of patients may have normal AFP levels to begin with.

Repeat treatment:

Patients with residual or recurrent tumors need repeat treatment on the same lines.

Complications:

1. Post-embolization syndrome requiring hospitalization is the commonest complication and is seen in around 5% of patients.

2. Liver failure is the second commonest complicaton seen in around 2.5% of patients.

3. Infective complication in the form of abscess formation is seen in < 1% of patients with an intact sphincter of Oddi.The risk increases significantly in patients who have prior bilio-enteric anastomosis.


4. Reported treatment related mortality rate (within 30 days) is around 1%

Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma.

Lo CM, Ngan H, Tso WK, Liu CL, Lam CM, Poon RT, Fan ST, Wong J

Hepatology 2002; 35:1164-71.

This randomized, controlled trial assessed the efficacy of transarterial Lipiodol chemoembolization in patients with unresectable hepatocellular carcinoma. From March 1996 to October 1997, 80 out of 279 Asian patients with newly diagnosed unresectable hepatocellular carcinoma fulfilled the entry criteria and were randomly assigned to treatment with chemoembolization using a variable dose of an emulsion of cisplatin in Lipiodol and gelatin-sponge particles injected through the hepatic artery (chemoembolization group, 40 patients) or symptomatic treatment (control group, 40 patients). Chemoembolization resulted in a marked tumor response, and the actuarial survival was significantly better in the chemoembolization group (1 year, 57%; 2 years, 31%; 3 years, 26%) than in the control group (1 year, 32%; 2 years, 11%; 3 years, 3%; P =.002). When adjustments for baseline variables that were prognostic on univariate analysis were made with a multivariate Cox model, the survival benefit of chemoembolization remained significant (relative risk of death, 0.49; 95% CI, 0.29-0.81; P =.006). Although death from liver failure was more frequent in patients who received chemoembolization, the liver functions of the survivors were not significantly different. In conclusion, in Asian patients with unresectable hepatocellular carcinoma, transarterial Lipiodol chemoembolization significantly improves survival and is an effective form of treatment.

Arterial embolisation or chemoembolization versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial

Llovet JM, Real MI, Montana X, et al.

Lancet. 2002;359:1734–1739.

The authors conducted a randomized trial with the aim of documenting the survival advantage of chemoembolization in patients with unresectable hepatocellular carcinoma.Patients were randomized to receive repeated arterial embolisation with gelatin sponge or chemoembolization with doxorubicin and gelatin sponge. A third group of patients received conservative treatment. A total of 903 patients were assessed and 112 patients were finally included in the study. The primary endpoint was survival. Analyses were by intention to treat.The trial was stopped when the ninth sequential inspection showed that chemoembolization had survival benefits compared with conservative treatment (hazard ratio of death 0·47 [95% CI 0·25–0·91], p=0·025). 25 of 37 patients assigned embolisation, 21 of 40 assigned chemoembolization, and 25 of 35 assigned conservative treatment died. Survival probabilities at 1 year and 2 years were 75% and 50% for embolisation; 82% and 63% for chemoembolization, and 63% and 27% for control (chemoembolization vs. control p=0·009). Chemoembolization induced objective responses sustained for at least 6 months in 35% (14) of cases, and was associated with a significantly lower rate of portal-vein invasion than conservative treatment. Treatment allocation was the only variable independently related to survival (odds ratio 0·45 [95% CI 0·25–0·81], p=0·02).Chemoembolization improved survival of stringently selected patients with unresectable hepatocellular carcinoma.There was no significant difference in the outcome between chemoembolization and bland embolisation groups.

Prospective cohort study of transarterial chemoembolization for unresectable hepatocellular carcinoma in 8510 patients.

Takayasu K, Arii S, Ikai I, Omata M, Okita K, Ichida T, Matsuyama Y, Nakanuma Y, Kojiro M, Makuuchi M, Yamaoka Y; Liver Cancer Study Group of Japan.

Gastroenterology. 2006 Aug;131(2):461-9.

BACKGROUND & AIMS: To elucidate the survival of the patients with unresectable hepatocellular carcinoma (HCC) who underwent transcatheter arterial lipiodol chemoembolization (TACE) and to analyze the factors affecting the survivals.
RESULTS: For overall survival rates by TACE, median and 1-, 3-, 5-, and 7-year survivals were 34 months, 82%, 47%, 26%, and 16%, respectively. Both the degree of liver damage and the tumor-node-metastasis (TNM) system proposed by the Liver Cancer Study Group of Japan demonstrated good stratification of survivals (P = .0001). The multivariate analyses showed significant difference in degree of liver damage (P = .0001), alpha-fetoprotein value (P = .0001), maximum tumor size (P = .0001), number of lesions (P = .0001), and portal vein invasion (P = .0001). The last 3 factors could be replaced by TNM stage. The TACE-related mortality rate after the initial therapy was .5%.

CONCLUSIONS: TACE showed safe therapeutic modality with a 5-year survival of 26% for unresectable HCC patients. The degrees of liver damage, TNM stage, and alpha-fetoprotein values were independent risk factors for patient survival.

Chemoembolization is a safe and effective procedure for palliative treatment of unresectable HCC.It confers survival advantage to patients with HCC.

Hepatic chemoembolization: safety with portal vein thrombosis.

Pentecost MJ, Daniels JR, Teitelbaum GP, Stanley P

J Vasc Interv Radiol ; 4:347-51.

The authors treated 9 patients with unresectable hepatic malignancy and portal vein thrombosis with hepatic chemoembolization using 10 mg/mL of cross-linked collagen, 10 mg/mL of mitomycin, 3 mg/mL of doxorubicin, and 3 mg/mL of cisplatin. Six patients had primary malignancies (hepatocellular carcinoma in five, hepatoblastoma in one), and three had metastatic tumor (adenocarcinoma of the colon in two, glucagonoma in one). Each patient was treated until flow in the hepatic artery ceased completely.

All treatments were technically successful. Eight patients responded to treatment, including two long-term survivors (> 2 years). One patient died 31 days after treatment of progressive hepatic malignancy and atherosclerotic disease. No patient developed hepatic infarction or insufficiency as a result of treatment. Follow-up ranged from 1 to 26 months (mean, 13 months).

The authors conclude that portal vein thrombosis should not be considered an absolute contraindication to hepatic chemoembolization. Hepatic chemoembolization can be performed safely in

Chemoembolization can be safely performed in patients with portal vein thrombosis.A segmental approach is mandatory as portal vein thrombosis is a risk factor for development of complications in TACE

Treatment of HCC in patients awaiting liver transplantation.

Schwartz M, Roayaie S, Uva P.

Am J Transplant. 2007 Aug;7(8):1875-81. Epub 2007 May 26.

Liver transplantation (LT) is the treatment of choice for many patients with unresectable hepatocellular carcinoma (HCC), but long waiting time due to the shortage of donor organs can result in tumor progression and drop-out from LT candidacy. Furthermore, even in candidates meeting the restrictive Milan criteria there is risk of HCC recurrence; this risk rises significantly when patients with more advanced HCC are included. In an effort to address these issues, treatment of HCC in patients awaiting LT has become widespread practice. In this review the various modalities employed in the pre-LT setting are presented, and the evidence for benefit with regard to (1) improvement of post-LT survival, (2) down-staging of advanced HCC to within Milan criteria and (3) preventing waiting list drop-out is considered. Chemoembolization, radiofrequency ablation and ethanol injection all have well-documented antitumor activity; however, there is no high level evidence that waiting list HCC treatment with these modalities is effective in achieving any of the three above-mentioned aims. Nevertheless, particularly in the United States, where continued waiting list priority depends on maintaining HCC within Milan criteria, use of nonsurgical HCC treatment will likely continue in an effort to forestall tumor progression and waiting list drop-out.

Liver Transpl. 2006 Aug;12(8):1260-7.

Response to transarterial chemoembolization as a biological selection criterion for liver transplantation in hepatocellular carcinoma.

Otto G, Herber S, Heise M, Lohse AW, Mönch C,
Bittinger F, Hoppe-Lotichius M, Schuchmann M,
Victor A, Pitton M.

Criteria to select patients with hepatocellular carcinoma (HCC) for liver transplantation (LT) are based on tumor size and number of nodules rather than on tumor biology. The present study was undertaken to assess the role of transarterial chemoembolization (TACE) in selecting patients with tumors suitable for LT. Ninety-six consecutive patients with HCC were treated by repeatedly performed TACE, 62 of them exceeding the Milan criteria. Patients meeting the Milan criteria were immediately listed, and patients beyond the listing criteria were listed upon downstaging of the tumor following successful TACE. Fifty patients were finally transplanted. Of these 50 patients, 34 exceeded the Milan criteria. In these 96 patients, overall 5-year survival was 51.9%. However, it was 80.9% for patients undergoing LT and 0% for patients without transplantation (P < 0.0001). Tumor recurrence was primarily influenced by the control of the disease through continued TACE during the waiting time. Freedom from recurrence after 5 years was 94.5% in patients (n = 39) with progress-free TACE during the waiting time. Tumor recurrence was significantly higher in patients (n = 11) who after initial response to TACE progressed again before LT (freedom from recurrence 35.4%; P = 0.0017). Progress-free course of TACE during the waiting time (P = 0.006; risk ratio, 8.95), and a limited number of tumor nodules as assessed in the surgical specimen (P = 0.025; risk ratio, 0.116) proved to be significant predictors for freedom from recurrence in the multivariate analysis. Milan criteria were without impact on recurrence. Our data suggest that sustained response to TACE is a better selection criterion for LT than the initial assessment of tumor size or number.

Preliminary studies suggest a role for TACE in patients awaiting transplantation or resection.Patients responding to TACE appear to have a better long term survival.

Transcatheter arterial chemoembolization of hepatocellular carcinoma with hepatic arteriovenous shunt after temporary balloon occlusion of hepatic vein.

Lee JH, Won JH, Park SI, Won JY, Lee do Y, Kang BC.
J Vasc

Interv Radiol. 2007 Mar; 18(3):377-82.

Purpose Hepatocellular carcinoma with hepatic artery to hepatic vein (AV) shunt has increased risk of pulmonary complications during transcatheter arterial chemoembolization (TACE). The purpose of this study is to assess temporary balloon occlusion as a means of preventing pulmonary complications during TACE of hepatocellular carcinoma with AV shunt. Materials and Methods Eleven hepatocellular carcinoma patients (M: F = 9:2; mean age, 48 years) with angiographically evident AV shunt underwent TACE with occlusion of the shunt-draining hepatic veins using temporary occlusion balloon catheters. All tumors were in the right lobe, and all AV shunts were between the right hepatic artery and right hepatic vein. The occlusion balloon was inserted via femoral (n = 6) or jugular (n = 5) venous access. The balloon diameter ranged from 8.5 to 11.5 mm and time of ballooning was 3 to 15 minutes (mean, 9.5 minutes). TACE was performed using emulsion of iodized oil and doxorubicin, followed by Gelfoam embolization. The balloon was deflated immediately after chemoembolization, and physical examination and chest adiography were performed. Follow-up computed tomography was performed within 2 weeks after TACE to evaluate the result and pulmonary complications. Results The technical success rate was 100%. There was no symptom, sign, or radiographic evidence of pulmonary complication. Follow-up computed tomography revealed complete iodized oil uptake by the tumor in eight patients and incomplete uptake by the tumor in three patients. There was no iodized oil uptake in the lungs. Conclusions Temporary balloon occlusion of the hepatic vein in hepatocellular carcinoma with AV shunt allowed completion of TACE using conventional method while preventing pulmonary complications.

Postbiopsy arterioportal fistula in patients with hepatocellular carcinoma: clinical significance in transarterial chemoembolization.

Park HS, Lee SH, Kim YI, Lee JS, Lim MK, Park JW, Lee JH, Kim CM.

AJR Am J Roentgenol. 2006 Feb;186(2):556-61.

OBJECTIVE: The purpose of this study was to determine, retrospectively, the frequency of postbiopsy arterioportal fistula in hepatocellular carcinoma and its significance in transarterial chemoembolization (TACE).

RESULTS: Twenty-three (56.1%) of 41 patients in the biopsy group and 19 (11.8%) of 161 patients in the control group had an arterioportal fistula (p < 0.001). The rate of tumor response to TACE was 87.8% (36/41) in the biopsy group and 87.0% (140/161) in the control group (p = 0.5932). Of the possible related factors, only tumor size correlated negatively with the occurrence of arterioportal fistula.

CONCLUSION: Percutaneous liver biopsy in hepatocellular carcinoma patients apparently increases the rate of arterioportal fistula but does not seem to affect the rate of tumor response to TACE.

Arterio-hepatic venous and portal venous fistulae donot preclude TACE.Temporary balloon occlusion of hepatic vein or coil embolization of the arterio-portal fistula can be done and conventional TACE can be accomplished.

Chemoembolization of hepatocellular carcinoma with drug eluting beads: efficacy and doxorubicin pharmacokinetics.

Varela M, Real MI, Burrel M, Forner A, Sala M, Brunet M, Ayuso C, Castells L, Montañá X, Llovet JM, Bruix J.

J Hepatol. 2007 Mar;46(3):474-81. Epub 2006 Nov 29.

Liver Unit, IMDM, Barcelona Clínic Liver Cancer (BCLC) Group, Hospital Clínic, CIBER HEPAD, University of Barcelona, Institut d’Investigacions Biomèdiques August Pi I Sunyer, IDIBAPS, Barcelona, Spain.

BACKGROUND/AIMS: This study assesses the safety, pharmacokinetics and efficacy of transarterial chemoembolization using drug eluting beads (DEB), an embolizing device that slowly releases chemotherapy to decrease systemic toxicity.

RESULTS: DEB-TACE was well tolerated with an acceptable safety profile. Two cases developed liver abscess, one leading to death. Response rate was 75% (66.6% on intention-to-treat). After a median follow-up of 27.6 months, 1- and 2-year survival is 92.5% and 88.9%, respectively.

CONCLUSIONS: Chemoembolization using DEBs is an effective procedure with a favorable pharmacokinetic profile.

Trans-arterial chemoembolization (TACE) of liver metastases from colorectal cancer using irinotecan-eluting beads: preliminary results.

Aliberti C, Tilli M, Benea G, Fiorentini G.

Anticancer Res. 2006 Sep-Oct;26(5B):3793-5.

Department of Interventional Radiology Delta Hospital, via delle Tombe 65, 47023 Lagosanto, Ferrara, Italy. camy.ali@libero.it

PURPOSE: The purpose of the study was to evalutate the feasibility of irinotecan drug-eluting beads (DC Bead) administered as trans-arterial chemoembolization (TACE) in patients with liver metastases from colorectal cancer (CRC).

RESULTS: TACE with irinotecan eluting beads was found to be feasible and well-tolerated. Right upper quadrant pain (RUQP) lasting 4 days (range 2-7) was reported by all the patients. After 30 days, a reduction >50% of CEA levels and of the lesional contrast enhancement was observed in all the patients. Conclusion: Irinotecan drug-eluting beads administered as TACE were shown to be active and safe in patients with liver metastases from CRC.

Use of drug eluting beads appears to be safe and effective.Long term data and large clinical series are not available yet.Favourable pharmacokinetic profile makes this therapy attractive and promising.

Response Evaluation

Completeness of treatment in hepatocellular carcinomas treated with image-guided tumor therapies: Evaluation of positive predictive value of contrast-enhanced CT with histopathologic correlation in the explanted liver specimen.

Kim YS, Rhim H, Lim HK, Park CK, Lee WJ, Do YS, Cho JW

J Comput Assist Tomogr. 2006 Jul-Aug;30(4): 578-82.

OBJECTIVE: To evaluate the positive predictive value of contrast-enhanced multiphase computed tomography (CT) in determining the completeness of treatment, after radiofrequency (RF) ablation and/or transcatheter arterial chemoembolization, based on histopathologic correlation in the explanted liver specimen.

RESULTS: The last CT examinations had been obtained 1-37 days before surgery. The overall necrosis rate of HCC for both RF ablation and transcatheter arterial chemoembolization on microscopic examination was 92.9% +/- 12.3%. The positive predictive value of contrast-enhanced CT in determining completeness of treatment was 69.0% (20/29). The tumor necrosis rate for the RF ablation-only group (n = 12) was 91.5% +/- 15.2% with a positive predictive value of 58.3% (7/12) and that of the transcatheter arterial chemoembolization-only group (n = 11) was 91.4% +/- 19.2% with a positive predictive value of 72.7% (8/11).

CONCLUSIONS: Our results suggest that contrast-enhanced CT is limited in accurately determining the completeness of treatment after image-guided tumor ablation for HCC.

The role of functional MR imaging in the assessment of tumor response after chemoembolization in patients with hepatocellular carcinoma.

Kamel IR, Bluemke DA, Eng J, Liapi E, Messersmith W, Reyes DK, Geschwind JF.

J Vasc Interv Radiol. 2006 Mar;17(3):505-12.

PURPOSE: To assess treatment response of hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) with use of diffusion and dynamic contrast medium-enhanced magnetic resonance (MR) imaging.

RESULTS: The study included 38 lesions with a mean diameter of 8.0 cm. Mean reduction in tumor diameter was 8 mm after treatment (t test; P = .0005), which did not fulfill Response Evaluation Criteria in Solid Tumors for complete or partial response. Reduction in tumor enhancement in the arterial (30%) and venous (47%) phases was statistically significant (signed-rank test; P = .0003 and P < 0.00005, respectively). Tumor ADC value increased from 0.0015 mm(2)/sec to 0.0018 mm(2)/sec after treatment (t test; P = .026), whereas the ADC values for the liver, spleen, and muscle remained unchanged. Median patient survival was 19 months.

CONCLUSIONS: After TACE, tumors demonstrated decreased size and enhancement with increases in ADC values. In this cohort, diffusion and dynamic contrast medium-enhanced MR imaging parameters were significantly altered after TACE, and these could be useful tools in the assessment of tumor response.

Multiphase CT is commonly used for response evaluation following chemoembolization or RFA but has limitations in predicting completeness of ablation.MRI with diffusion and spectroscopy appears more objective.

Radiofrequency Ablation of Liver Tumors

Radiofrequency ablation (RFA) is a new and promising technical advance in the percutaneous ablation of liver tumors.

RFA involves ablation of neoplastic tissue by direct intralesional thermocoagulation.

RFA can be performed with a monopolar or a bipolar electrode system.In a monopolar system, the circuit is completed through the patient’s body whereas in the bipolar system it is completed locally.

Mechanism of Action

The main tumoricidal effect of RFA occurs because the deposition of electromagnetic energy induces thermal injury to the tissue.

RF ablation is achieved clinically by depositing electromagnetic energy via a monopolar needle electrode in the tissue of interest with resultant thermal injury of the target tissue. In order for the energy to be deposited, a closed loop circuit is created by placing a generator, a large dispersive electrode (grounding pad), the patient, and the needle electrode in series. The dispersive and needle electrodes are active, while the patient acts as a resister, thereby producing an alternating electric current within the target tissue of the patient. For adequate tumor destruction, it is important that the entire volume of the lesion be subjected to cytotoxic temperatures. Ideal temperatures for tissue death are between 60°C and 100°C. In this range, there is practically instantaneous protein coagulation and irreversible damage to key intracellular enzymes and nucleic-acid complexes.A well circumscribed area of coagulative necrosis without intervening areas of viable tumor develops within 72 h of treatment.Although cell death occurs at between 46°C and 60°C, the time needed to induce cytotoxicity is markedly reduced above 60°C. Temperatures above 100°C to 105°C result in tissue vaporization and carbonization (charring). Formation of gas bubbles and charred tissue diminishes energy transmission by increasing the impedance to the flow of electrical current. Gas bubbles also form a thermal insulator limiting the spread of thermal energy. Therefore, avoidance of these extreme temperatures is desirable.

Technical aspects:

Guidance:

Percutaneous RFA can be done under CT or ultrasound guidance.CT is the preferred modality as complete coverage of the lesion can be monitored.Also,vascular complications can be immediately diagnosed with CT.
Ultrasound is the most commonly used modality for monitoring ablation.Development of intralesional gas bubbles however interferes with the visualization of the lesion as ablation progresses.

Open RFA is done under intra-operative ultrasound guidance.

Monopolar vs bipolar electrode system:

Monopolar electrode system is the modality of choice. The multi-tined expandable electrode system has the advantage of covering larger tumor volume and creating spherical ablation zones.It has a particular advantage in the liver as the electrode anchors itself by virtue of its self-expanding nature.

Bipolar electrode systems are preferred in patients who have indwelling orthopedic implants and cardiac pacemakers to avoid implant heating and arrhythmias respectively.This system can also be used while performing ablation close to the heart.Bipolar systems create cylindrical ablation zones.

Internally cooled electrodes:

These electrodes are specially designed to prevent tissue charring.

Ablation protocol:

The ablation protocol including target temperature and time duration for ablation will depend upon the target tissue and will vary according to the RFA system that is being used.The protocol charts will be available with the RFA system.

Anesthesia considerations:

General anesthesia is preferred.It gives an advantage of controlling patient’s respiration and is particularly helpful for ablation of lesions at difficult locations.

RFA can also be performed under deep sedation.

Patient Selection for RFA

HCC:

1. Solitary HCC less than or equal to 3 cm in size.

2. Solitary HCC less than or equal to 5 cm in size. The chances of residual unabated tumor are higher in patients with tumors larger than 3 cm therefore these patients need to be treated with some other local ablative therapy like chemoembolization for adequate local control of disease.

3. RFA can also be extended to patients who have upto 3 tumors in the liver provided all are 3 cm or less in size.

Metastases:

1. Patients with liver dominant or liver only disease are eligible for RFA provided the number of lesions is 3 or less.Size cut-off of 3 cm also applies to liver metastases to ensure complete ablation.

2. Anatomical or functional imaging (PET scan) should be done to exclude extra-hepatic disease.

Pre-RFA work up:

1. Cross-sectional imaging for exact localization of the lesion and planning of the trajectory.Relation of the lesions to major blood vessels is also important to note.

2. Laboratory evaluation for liver and renal function tests and coagulation profile.

3. Baseline tumor marker levels are useful for follow-up.

4. PET scan is an important tool to assess completeness of RFA in patients with metastases.A baseline PET scan is valuable and may be performed pre-RFA if available.

Lesion coverage:

For complete coverage of the lesion and achieving total necrosis, a 1cm margin of tissue on all sides of the lesion should be ablated.( The diameter of the zone of ablation has to be 2 cm greater than the lesion).

Important Strategies for RFA:

1. Ablation of small evanescent lesions which are seen only on arterial phase may be difficult. A lipiodol CT done prior to RFA may help localize the lesion due to lipiodol retention within the tumor.

2. Overlapping ablations:Creation of multiple overlapping ablation zones is required to cover larger lesions.

3. Ablation of subcapsular lesions: Can be done.The RFA tract should be preferably through liver parenchyma.

4. Ablation close to vessels: Large blood vessels carry away heat and interfere with the efficacy of ablation.Temporary balloon occlusion of the portal vein or hepatic artery have been described to create larger ablation zones.These maneuvers are seldom necessary in practice.

Ablation end-points:

Most important measure is the maintainance of target temperature throughout the duration of RFA.Uniformity in the target temperature throughout the lesion is desirable to ensure uniform ablation.

Immediate fall in the temperatures within 30 sec after RFA may suggest a need for reablation.

Track ablation:

This is a critical step in RFA as it ensures that the potential of needle tract seeding is avoided.Track ablation should also be done if the needle position has to be adjusted prior to RFA.

Monitoring completeness of RFA:

Immediate post procedure imaging:

Local vascular complications like hematomas,arterial pseudoaneurysms and portal vein thrombosis must be looked for.
A thin rim of enhancement surrounding the zone of ablation and outlining the ablation track is the usual finding and represents the inflammatory response to RFA.

This has been termed benign perilesional enhancement and is the imaging equivalent of complete ablation.

Nodular rim enhancement or persistent arterial phase enhancement is suggestive of residual tumor.

Surveillance:

Imaging:

Response:

1. Absence of internal enhancement

2. Reduction in size of the lesion

3. Retraction of hepatic capsule.

Recurrence:

1. Nodular rim enhancement

2. Internal enhancement.

Tumor Markers :Appropriate tumor marker levels are evaluated.A decreasing trend in the tumor marker levels is suggestive of response to RFA.

Complications:

1. Arterial injury leading to pseudoaneurysms and perihepatic hematomas may need emergent angiography and embolisation.

2. Portal vein thrombosis

3. Perihepatic collections

4. Bile duct injury.

Safety and efficacy of RFA

Percutaneous radiofrequency ablation for hepatocellular carcinoma. An analysis of 1000 cases.

Tateishi R, Shiina S, Teratani T, Obi S, Sato S, Koike Y, Fujishima T, Yoshida H, Kawabe T, Omata M.

Cancer. 2005 Mar 15;103(6):1201-9.

BACKGROUND: Radiofrequency ablation (RFA) was introduced recently as a therapeutic modality for hepatocellular carcinoma (HCC), an alternative to percutaneous ethanol injection therapy (PEIT), which is coming into use worldwide. Previously reported treatment efficacy and complication rates have varied considerably.

METHODS: Between February 1999 and February 2003, the authors performed 1000 treatments of RFA to 2140 HCC nodules in 664 patients with a cooled-tip electrode at the University of Tokyo Hospital (Tokyo, Japan). Short-term and long-term complications were analyzed by treatment and session basis. Cumulative survival was also assessed in 319 patients who received RFA as primary treatment (naive patients) and 345 patients who received RFA for recurrent tumor after previous treatment including resection, PEIT, microwave coagulation therapy, and transarterial embolization (nonnaive patients).

RESULTS: A total of 40 major complications (4.0% per treatment, 1.9% per session) and 17 minor complications (1.7% per treatment, 0.82% per session) were observed during the observation period until March 31, 2004. There were no treatment-related deaths. Surgical intervention was required in one case each of bile peritonitis and duodenal perforation. The cumulative survival rates at 1, 2, 3, 4, and 5 years were 94.7%, 86.1%, 77.7%, 67.4%, and 54.3% for naive patients, whereas the cumulative survival rates were 91.8%, 75.6%, 62.4%, 53.7%, and 38.2% for nonnaive patients, respectively
.
CONCLUSIONS: The authors confirmed the safety and efficacy of RFA for HCC in a large-scale series and long-term prognosis was satisfactory.

Radio-frequency ablation of large, nonresectable hepatic tumors.

Morgan JH 3rd, Royer GM, Hackett P, Gamblin TC, McCampbell BL Conforti A, Dale PS.

Am Surg. 2004 Dec;70(12):1035-8.

Patients with nonresectable hepatic metastases who are not treated survive an average of 6 months. We report our experience with radio-frequency ablation (RFA) of nonresectable hepatic tumors 4 cm or greater in size. A retrospective chart review of all patients undergoing RFA of hepatic tumors 4 cm or greater from October 1, 1999, through August 31, 2002, was performed. Thirty-six patients were identified who underwent RFA of tumors 4 cm or greater. There were a total of 81 tumors ablated in the 36 patients. Twenty patients underwent RFA only; seven patients received RFA plus a wedge resection. Five patients were treated with RFA followed by chemoembolization. Two patients underwent RFA plus placement of a hepatic artery infusion pump. The median tumor size was 5 cm (range, 4-14 cm). Median patient follow-up was 26 months (range, 1-54 months). Patients with metastatic colon cancer had the longest median survival of 28 months (range, 1 and 48 months). The survival of primary hepatocellular carcinoma was worse with a median survival of 20 months (range, 1-36 months). At last follow-up, 11 (30%) of the patients remain alive and disease free. There were no perioperative deaths and one intraoperative complication. In our experience, RFA of larger tumors is effective and safe. Tumor size should not be an absolute contraindication to RFA of nonresectable hepatic tumors.

Percutaneous ablation procedures in cirrhotic patients with hepatocellular carcinoma submitted to liver transplantation: Assessment of efficacy at explant analysis and of safety for tumor recurrence.

Pompili M, Mirante VG, Rondinara G, Fassati LR, Piscaglia F, Agnes S, Covino M, Ravaioli M, Fagiuoli S, Gasbarrini G, Rapaccini GL.

Aims of this retrospective study were to analyze the efficacy and safety of percutaneous ethanol injection (PEI) and radiofrequency ablation (RFA) in cirrhotic patients with hepatocellular carcinoma (HCC) submitted to orthotopic liver transplantation (OLT). We studied 40 patients undergoing OLT in whom 46 HCC nodules had been treated with PEI (13 nodules), RFA (30 nodules), or PEI+RFA (3 nodules). Child-Turcotte-Pugh class was A in 18 cases, B in 18, and C in 4. The mean waiting time for OLT was 9.5 months. The effectiveness of ablation techniques was evaluated by histological examination of the explanted livers. Complete necrosis was found in 19 nodules (41.3%), partial or absent necrosis in 27 nodules (58.7%). Among the 30 nodules treated by RFA, 14 were completely necrotic (46.7%) and 16 demonstrated partial necrosis (53.3%). Considering the 13 neoplasms undergoing PEI, 3 nodules showed complete necrosis (23.1%), 6 partial necrosis (46.1%), and 4 absent necrosis (30.8%). The rate of complete necrosis was 53.1% for nodules smaller than 3 cm and 14.3% for larger lesions (P = 0.033) but increased to 61.9% when considering only the lesions smaller than 3 cm treated by RFA. During the follow up, HCC recurred in 3 patients treated by PEI. No cases of HCC recurrence at the abdominal wall level were recorded. Percutaneous ablation procedures are effective treatments in cirrhotic patients with HCC submitted to OLT and are not associated to an increased risk of tumor recurrence. RFA provides complete necrosis in most nodules smaller than 3 cm, and appears to be the best treatment option in these cases.

Hepatocellular carcinoma: radio-frequency ablation of medium and large lesions.

Livraghi T, Goldberg SN, Lazzaroni S, Meloni F, Ierace T, Solbiati L, Gazelle GS.

Radiology. 2000 Mar;214(3):761-8.

PURPOSE: To study local therapeutic efficacy, side effects, and complications of radio-frequency (RF) ablation in the treatment of medium and large hepatocellular carcinoma (HCC) lesions in patients with cirrhosis or chronic hepatitis.
MATERIALS AND METHODS: One-hundred fourteen patients who were under conscious sedation or general anesthesia had 126 HCCs greater than 3.0 cm in diameter treated with RF by using an internally cooled electrode. Eighty tumors were medium (3.1-5.0 cm), and 46 were large (5.1-9.5 cm). The mean diameter for all tumors was 5.4 cm. At imaging, 75 tumors were considered noninfiltrating, and 51 were considered infiltrating.

RESULTS: Complete necrosis was attained in 60 lesions (47.6%), nearly complete (90%-99%) necrosis in 40 lesions (31.7%), and partial (50%-89%) necrosis in the remaining 26 lesions (20.6%). Medium and/or noninfiltrating tumors were treated successfully significantly more often than large and/or infiltrating tumors. Two major complications (death, hemorrhage requiring laparotomy) and five minor complications (self-limited hemorrhage, persistent pain) were observed. The single death was due to a break in sterile technique rather than to the RF procedure itself.

CONCLUSION: RF ablation appears to be an effective, safe, and relatively simple procededure for the treatment of medium and large HCCs.

Percutaneous RFA is a safe and effective treatment modality for liver tumors.It can be applied to small as well as large tumors.The ability to induce complete necrosis appears to be limited by size and proximity to blood vessels.

RFA vs Surgical Resection

Sustained complete response and complications rates after radiofrequency ablation of very early hepatocellular carcinoma in cirrhosis: Is resection still the treatment of choice?

Livraghi T, Meloni F, Di Stasi M, Rolle E, Solbiati L, Tinelli C, Rossi S.

Hepatology. 2008 Jan; 47(1):82-9.

If liver transplantation is not feasible,
partial resection is considered the treatment of choice for hepatocellular carcinoma (HCC) in patients with cirrhosis. However, in some centers the first-line treatment for small, single, operable HCC is now radiofrequency ablation (RFA). In the current study, 218 patients with single HCC <or= 2.0 cm (very early or T1 stage) underwent RFA. We assessed 2 primary end points that could be easily compared with those reported for resective surgery: (1) the rate of sustained, local, complete response and (2) the rate of treatment-related complications. The secondary end point was 5-year survival in the 100 patients whose tumors had been considered potentially operable. After a median follow-up of 31 months, sustained complete response was observed in 216 patients (97.2%). In the remaining 6, percutaneous ethanol injection, selective intraarterial chemoembolization, or resection were used as salvage therapy. Perioperative mortality, major complication, and 5-year survival rates were 0%, 1.8%, and 68.5%, respectively. Conclusion: Compared with resection, RFA is less invasive and associated with lower complication rate and lower costs. RFA is also just as effective for ensuring local control of stage T1 HCC, and it is associated with similar survival rates (as recently demonstrated by 2 randomized trials). These data indicate that RFA can be considered the treatment of choice for patients with single HCC <or= 2.0 cm, even when surgical resection is possible. Other approaches can be used as salvage therapy for the few cases in which RFA is unsuccessful or unfeasible.

The comparative results of radiofrequency ablation versus surgical resection for the treatment of hepatocellular carcinoma.

Cho CM, Tak WY, Kweon YO, Kim SK, Choi YH,
Hwang YJ, Kim YI.

Korean J Hepatol. 2005 Mar;11(1):59-71.

BACKGROUND/AIMS: Although surgical resection remains the gold standard of therapy for hepatocellular carcinoma (HCC), only selected patients can undergo resection because of the severity of the underlying cirrhosis or due to the diffuse distribution of the tumor. Radiofrequency ablation (RFA) has recently shown comparable results to surgical resection for the treatment of HCC. We compared the results of RF ablation and surgical resection for the treatment of HCC.

METHODS: From January 2000 to December 2002, one hundred-sixty patients who had undergone surgical resection or RFA were analyzed retrospectively. The patients with a tumor size less than 5 cm in diameter, with less than 3 tumors in number, with tumor having a Child-Pugh class A classification and no evidence of extrahepatic metastasis were enrolled in the study. The recurrence pattern was classified into local and distant recurrence. We compared the recurrence patterns, the survival rates, the recurrence rates and the complications between the two groups.

RESULTS: 1) The local recurrence rate was 9.8% for surgical resection and 18.2% for RFA and the distant recurrence rate were 32.8% and 28.3%, respectively. 2) The 1-, 2- and 3-year overall cumulative survival rates after RFA and surgery were 95.8%, 86.8%, 80.0%, 98.3%, 87.0% and 77.4%, respectively. 3) The incidence of complication was similar between the two groups.

CONCLUSIONS: Radiofrequency ablation shows comparable results to surgical resection for the treatment of HCC. Therefore, RFA should be considered as the treatment of choice those patients who are not candidates for resection. However, intrahepatic recurrence of tumor after RFA was as frequent as that seen after surgical resection. Further investigation is warranted to clarify whether the current RFA technology could offer improved long-term results.

Survival rates and patterns and rates of local and distant intrahepatic recurrences appear to compare favourably between resection and RFA for HCC.RFA has an advantage of low morbidity and repeatability over surgery and appears to be the treatment of choice for recurrent HCC after resection.Surgery appears to be superior to RFA for colorectal metastases.

Long Term Outcomes of Rfa

Radiofrequency ablation of hepatocellular carcinoma: Long-term outcome and prognostic factors.

Yan K, Chen MH, Yang W, Wang YB, Gao W, Hao CY, Xing BC, Huang XF.

Eur J Radiol. 2007 Aug 30

PURPOSE: To investigate the efficacy of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC), and the prognostic factors for post-RFA survival rate.

METHODS: From 1999 to 2006, 266 patients with 392 HCCs underwent ultrasound guided RFA treatment. They were 216 males and 50 females, average age 59.4+/-15.4 years (24-87 years). The HCC were 1.2-6.7cm in diameters (average 3.9+1.3cm). There were 158 patients with single tumor, and the rest had multiple (2-5) tumors. Univariate and multivariate analysis with 19 potential variables were examined to identify prognostic factors for post-RFA survival rate.

RESULTS: The overall post-RFA survival rates at 1st, 3rd, and 5th year were 82.9%, 57.9% and 42.9%, respectively. In the 60 patients with stage I HCC (AJCC staging), the 1-, 3-, 5-year survival rate were 94.8%, 76.4% and 71.6%, significantly higher than the 148 patients with stage II-IV tumors (81.8%, 57.6% and 41.2%, P=0.006). For the 58 patients with post-surgery recurrent HCC, the survival rates were 73.2%, 41.9% and 38.2% at the 1st, 3rd, and 5th year, which were significantly lower than those of stage I HCC (P=0.005). Nine potential factors were found with significant effects on survival rate, and they were number of tumors, location of tumors, pre-RFA liver function enzymes, Child-Pugh classification, AJCC staging, primary or recurrent HCC, tumor pathological grading, using mathematical protocol in RFA procedure and tumor necrosis 1 month after RFA. After multivariate analysis, three factors were identified as independent prognostic factors for survival rate, and they were Child-Pugh classification, AJCC staging and using mathematical protocol.

CONCLUSION: Identifying prognostic factors provides important information for HCC patient management before, during and after RFA. This long-term follow-up study on a large group of HCC patients confirmed that RFA could not only achieve favorable outcome on stage I HCC, but also be an effective therapy for stage II-IV or recurrent HCC.

Survival after radiofrequency ablation of colorectal liver metastases: 10-year experience.

Siperstein AE, Berber E, Ballem N, Parikh RT.

Ann Surg. 2007 Oct;246(4):559-65;

OBJECTIVE: To assess factors affecting long-term survival of patients undergoing radiofrequency ablation (RFA) of colorectal hepatic metastases, with attention to evolving chemotherapy regimens.

METHODS: Prospective evaluation of 235 patients with colorectal metastases who were not candidates for resection and/or failed chemotherapy underwent laparoscopic RFA. Preoperative risk factors for survival and pre- and postoperative chemotherapy exposure were analyzed.

RESULTS: Two hundred and thirty-four patients underwent 292 RFA sessions from 1997 to 2006, an average of 8 months after initiation of chemotherapy. Twenty-three percent had extrahepatic disease preoperatively. Patients averaged 2.8 lesions, with a dominant diameter of 3.9 cm. Kaplan-Meier actuarial survival was 24 months, with actual 3 and 5 years survival of 20.2% and 18.4%, respectively. Median survival was improved for patients with <or=3 versus >3 lesions (27 vs. 17 months, P=0.0018); dominant size<3 versus >3 cm (28 vs. 20 months, P=0.07); chorioembryonic antigen<200 versus >200 ng/mL (26 vs. 16 months, P=0.003). Presence of extrahepatic disease (P=0.34) or type of pre/postoperative chemotherapy (5-FU-leucovorin vs. FOLFOX/FOLFIRI vs. bevacizumab) (P=0.11) did not alter median survival.

CONCLUSIONS: To our knowledge, this is both the largest and longest follow-up of RFA for colorectal metastases. The number and dominant size of metastases, and preoperative chorioembryonic antigen value are strong predictors of survival. Despite classic teaching, extrahepatic disease did not adversely affect survival. In this group of patients who failed chemotherapy, newer treatment regimens (pre- or postoperatively) had no survival benefit. The actual 5-year survival of 18.4% in these patients versus near zero survival for chemotherapy alone argues for a survival benefit of RFA

Significant long-term survival after radiofrequency ablation of unresectable hepatocellular carcinoma in patients with cirrhosis.

Raut CP, Izzo F, Marra P, Ellis LM, Vauthey JN,
Cremona F, Vallone P, Mastro A, Fornage BD, Curley SA.

Ann Surg Oncol. 2005 Aug;12(8):616-28

BACKGROUND: Radiofrequency ablation (RFA) offers an alternative treatment in some unresectable hepatocellular carcinoma (HCC) patients with disease confined to the liver. We prospectively evaluated survival rates in patients with early-stage, unresectable HCC treated with RFA.

METHODS: All patients with HCC treated with RFA between September 1, 1997, and July 31, 2002, were prospectively evaluated. Patients were treated with RFA by using a percutaneous or open intraoperative approach with ultrasound guidance and were evaluated at regular intervals to determine disease recurrence and survival.

RESULTS: A total of 194 patients (153 men [79%] and 41 women [21%]) with a median age of 66 years (range, 39-86 years) underwent RFA of 289 sonographically detectable HCC tumors. All patients were followed up for at least 12 months (median follow-up, 34.8 months). Percutaneous and open intraoperative RFA was performed in 140 (72%) and 54 (28%) patients, respectively. The median diameter of tumors treated with RFA was 3.3 cm. Disease recurred in 103 (53%) of 194 patients, including 69 (49%) of 140 patients treated percutaneously and 34 (63%) of 54 treated with open RFA (not significant). Local recurrence developed in nine patients (4.6%). Most recurrence was intrahepatic. The overall complication rate was 12%. Overall survival rates at 1, 3, and 5 years for all 194 patients were 84.5%, 68.1%, and 55.4%, respectively.

CONCLUSIONS: Treatment with RFA can produce significant long-term survival rates for cirrhotic patients with early-stage, unresectable HCC. RFA can be performed in these patients with relatively low complication rates. Confirmation of these results in randomized trials should be considered

RFA alone or in combination with other modalities gives satisfactory long term survival advantage to patients with unresectable HCC.

RFA as a Bridge to Transplantation

Radiofrequency ablation of small hepatocellular carcinoma in cirrhotic patients awaiting liver transplantation: a prospective study.

Mazzaferro V, Battiston C, Perrone S, Pulvirenti A, Regalia E, Romito R, Sarli D, Schiavo M, Garbagnati F, Marchianò A, Spreafico C, Camerini T, Mariani L, Miceli R, Andreola S.

Ann Surg. 2004 Nov;240(5):900-9.

OBJECTIVE: Determine the histologic response-rate (complete versus partial tumor extinction) after single radiofrequency ablation (RFA) of small hepatocellular carcinoma (HCC) arising in cirrhosis. Investigate possible predictors of response and assess efficacy and safety of RFA as a bridge to liver transplantation (OLT).

RESULTS: Mean interval RFA—>OLT was 9.5 months. Post-RFA complete response rate was 55%, rising to 63% for HCC </=3 cm. Tumor size was the only prognostic factor significantly related to response (P = 0.007). Tumor satellites and/or new HCC foci (56 nodules) were unaffected by RFA and significantly correlated with HCC >3 cm (P = 0.05). Post-RFA tumor persistence probability increased with time (12 months: 59%; 18 months: 70%). Radiologic response rate was 70%, not significantly different from histology. Major post-RFA morbidity was 8%. No mortality, Child deterioration, patient withdrawal because of tumor progression was observed. Post-OLT 3-year patient/graft survival was 83%.

CONCLUSIONS: RFA is a safe and effective treatment of small HCC in cirrhotics awaiting OLT, although tumor size (>3 cm) and time from treatment (>1 year) predict a high risk of tumor persistence in the targeted nodule. RFA should not be considered an independent therapy for HCC.

Percutaneous radiofrequency ablation for hepatocellular carcinoma before liver transplantation: a prospective study with histopathologic comparison.

Brillet PY, Paradis V, Brancatelli G, Rangheard AS, Consigny Y, Plessier A, Durand F, Belghiti J, Sommacale D, Vilgrain V.

AJR Am J Roentgenol. 2006 May;186(5 Suppl): S296-305.

OBJECTIVE: The aims of this study were to determine the feasibility and efficacy of percutaneous radiofrequency ablation in patients with hepatocellular carcinoma waiting for liver transplantation and to compare the radiologic and pathologic findings. ed.

RESULTS: Percutaneous radiofrequency ablation was performed in 21 (81%) patients for 28 tumors. Both minor and major complications occurred in three patients (10% each per session). The rates of primary technique effectiveness, secondary technique effectiveness for percutaneous radiofrequency ablation alone (seven tumors), and combined percutaneous radiofrequency ablation and transcatheter arterial chemoembolization (three tumors) were 56%, 76%, and 86%, respectively. After a mean follow-up of 11.9 months, 16 patients (76%) received transplants, whereas five patients were excluded from the waiting list because of distant tumor progression (n =3, 14%) or other causes (n = 2, 10%). After transplantation, tumor recurred in one (6%) of 16 patients.Histopathologic examinations were performed for 13 (81%) of 16 patients and showed complete necrosis and satellite nodules in, respectively, 12 (75%) and seven (44%) of 16 tumors.

CONCLUSION: Percutaneous radiofrequency ablation can be performed on hepatocellular carcinoma patients waiting for transplantation, allows most patients to undergo transplantation, and does not impair posttransplantation outcomes. The procedure produces complete necrosis of the treated tumor in most cases but is associated with a high rate of satellite nodules.

RFA appears to be an effective modality as a bridge to transplantation.

RFA of Subcapsular Tumors

Percutaneous Radiofrequency Ablation Therapy of Hepatocellular Carcinoma Using Multitined Expandable Electrodes: Comparison of Subcapsular and Nonsubcapsular Tumors

Yun Ku Cho1, Hyunchul Rhim2, Yong Sik Ahn1, Mi Young Kim1 and Hyo Keun Lim2

OBJECTIVE. Our objective was to compare the prognosis of subcapsular and nonsubcapsular hepatocellular carcinoma after percutaneous radiofrequency ablation using multitined expandable electrodes.

RESULTS. No significant differences in initial complete ablation rate (100% vs 96.7%, p = 1.000) or local tumor progression rate (0% vs 10.0%, p = 0.545) were found between subcapsular and nonsubcapsular tumors. No procedure-related major complication or mortality occurred. The overall 1- and 3-year survival rates were 89.3% and 60.3%, respectively.

CONCLUSION. The rates of local tumor progression and complications for radiofrequency ablation using multitined expandable electrodes for subcapsular hepatocellular carcinomas were comparable to those for nonsubcapsular hepatocellular carcinomas.

RFA of subcapsular tumors can be safely performed.The efficacy and complication rates are not different than that for non-subcapsular tumors.

RFA for Metastases

Percutaneous radio-frequency ablation of hepatic metastases from colorectal cancer: long-term results in 117 patients.

Solbiati L, Livraghi T, Goldberg SN, Ierace T, Meloni F, Dellanoce M, Cova L, Halpern EF, Gazelle GS.

Radiology. 2001 Oct;221(1):159-66.

PURPOSE: To describe the results of an ongoing radio-frequency (RF) ablation study in patients with hepatic metastases from colorectal carcinoma.

RESULTS: Estimated median survival was 36 months (95% CI; 28, 52 months). Estimated 1, 2, and 3-year survival rates were 93%, 69%, and 46%, respectively. Survival was not significantly related to number of metastases treated. In 77 (66%) of 117 patients, new metastases were observed at follow-up. Estimated median time until new metastases was 12 months (95% CI; 10, 18 months). Percentages of patients with no new metastases after initial treatment at 1 and 2 years were 49% and 35%, respectively. Time to new metastases was not significantly related to number of metastases. Seventy (39%) of 179 lesions developed local recurrence after treatment. Of these, 54 were observed by 6 months and 67 by 1 year. No local recurrence was observed after 18 months. Frequency and time to local recurrence were related to lesion size (P < or =.001).

CONCLUSION: RF ablation is an effective method to treat hepatic metastases from colorectal carcinoma.

Surgery. 2007 Jul;142(1):10-9.
Laparoscopic radiofrequency ablation of neuroendocrine liver metastases: a 10-year experience evaluating predictors of survival. Mazzaglia PJ, Berber E, Milas M, Siperstein AE.

BACKGROUND: A decade ago we reported the first use of laparoscopic radiofrequency thermal ablation (RFA) for the treatment of neuroendocrine hepatic metastases. This study analyzes our 10-year experience and determines characteristics predictive of survival.

RESULTS: There were 22 women and 41 men, age 54.4 +/- 1.5 years followed for 2.8 +/- 0.3 years (range, 0.1 to 7.8). Tumor types included 36 carcinoid, 18 pancreatic islet cell, and 9 medullary thyroid cancer. RFA was performed 1.6 +/- 0.3 years after the diagnosis of liver metastases. Number of lesions treated was 6 +/- 0.5 (range, 1 to 16). Forty-nine patients underwent 1 ablation session, and 14 (22%) had repeat sessions caused by disease progression. Mean hospital stay was 1.1 days. Perioperative morbidity was 5%, with no 30-day mortality. Fifty-seven percent of patients exhibited symptoms. One week postoperatively 92% of these reported at least partial symptom relief, and 70% had significant or complete relief. Duration of symptom control was 11 +/- 2.3 months. CT follow-up demonstrated 6.3% local tumor recurrence. Larger dominant liver tumor size and male gender adversely impacted survival (P < .05). Median survival times were 11.0 years postdiagnosis of primary tumor, 5.5 years postdiagnosis of neuroendocrine hepatic metastases, and 3.9 years post-1st RFA. Survival for patients undergoing repeat ablation sessions was not significantly lower.

CONCLUSIONS: This study represents the largest series of neuroendocrine hepatic metastases treated by RFA. In this group of patients with aggressive neuroendocrine tumor metastases and limited treatment options, RFA provides effective local control with prompt symptomatic improvement

RFA of liver metastases is safe and effective in properly selected patients

Management of Hepatic Metastases

LIVER METASTASES:

Metastatic deposit is the commonest liver tumor. Management of metastatic liver disease is a challenging problem in oncology.

Interventional radiology plays an important role in the management of select patients with metastatic liver disease.
Surgical resection is the preferred treatment modality for liver metastases.

Tumors that develop metastases despite a treatable primary tumor are amenable to interventional radiological treatments.These include colorectal carcinoma, ocular melanoma, neuroendocrine tumors, and gastrointestinal sarcoma.
Most of these diseases have a favourable biology and therefore aggressive treatment of the metastatic liver disease is justified.Surgical resection is the only chance of long term cure for patients with liver metastases but less than 30% of patients are surgical candidates.

Improvements in chemotherapeutic regimens particularly for colorectal carcinoma (oxaliplatin and the monoclonal antibodies-cetuximab and bevacuzimab ) have led to a change in selection pattern for chemoembolization.

Indications for interventional radiological treatment in liver metastases:
1. Hepatic metastases unresponsive to standard chemotherapeutic regimens.
2. Palliative treatment in patients with multiple metastases.
3. Adjuvant chemotherapy following liver resection.
4. Downstaging of unresectable disease
5. Control of hormonal symptoms in neuroendocrine metastases.

Colorectal metastases

Selective chemoembolization in the management of hepatic metastases in refractory colorectal carcinoma: a phase II trial.

Sanz-Altamira PM, Spence LD, Huberman MS, Posner MR, Steele G Jr, Perry LJ, Stuart KE.

Dis Colon Rectum. 1997 Jul;40(7):770-5.

PURPOSE: Metastatic involvement of the liver frequently determines the evolution of the clinical picture in colorectal cancer patients. We examined the efficacy and toxicity of chemoembolization in this setting, identifying prognostic factors to define patients most likely to benefit from the procedure.

RESULTS: Overall median survival from date of first chemoembolization was ten months. Factors that predicted a longer median survival included favorable performance status (24 months), serum alkaline phosphatase and lactate dehydrogenase levels less than three times normal (24 and 12 months, respectively), and metastatic disease confined to the liver (14 months). Most patients tolerated the procedure well. The most common side effects were transient fevers, abdominal pain, and fatigue. Three patients died within one month from the procedure.

CONCLUSION: This study suggests that chemoembolization of hepatic metastases in colorectal cancer should be further evaluated; it may be beneficial in patients who have failed systemic chemotherapy, have a good performance status, and have metastatic disease confined to the liver.

Intraarterial hepatic chemoembolization of liver metastases from colorectal cancer adopting irinotecan-eluting beads: results of a phase II clinical study.

Fiorentini G, Aliberti C, Turrisi G, Del Conte A, Rossi S, Benea G, Giovanis P.

In Vivo. 2007 Nov-Dec; 21(6):1085-91.

Since November 2005 a clinical trial of intraarterial hepatic chemoembolization (TACE) with irinotecan-eluting beads has been ongoing in 20 patients affected by liver metastases from colorectal cancer in a palliative setting. A high response rate (80%), with reduction of lesional contrast enhancement in all responding patients was found. The procedure was well tolerated by most patients, with a median duration of hospitalization of 3 days (range 1-10 days). The most important adverse event was abdominal pain during the injection. Adequate supportive treatment with antibiotic and antiemetic prophylaxis, dexamethasone, and intravenous hydration is strictly necessary until the serum levels of transaminases are stabilized and in order to prevent infections. Major analgesics such as morphine must be used before and after the procedure. Our results suggest that TACE using irinotecan-eluting beads is feasible and active in pretreated patients with liver metastases from CRC.

Comparison of FDG-PET, PET/CT and MRI for follow-up of colorectal liver metastases treated with radiofrequency ablation: Initial results.

Kuehl H, Antoch G, Stergar H, Veit-Haibach P, Rosenbaum-Krumme S, Vogt F, Frilling A, Barkhausen J, Bockisch A.

Eur J Radiol. 2007 Dec 21

PURPOSE: Morphologic imaging after radiofrequency ablation (RFA) of liver metastases is hampered by rim-like enhancement in the ablation margin, making the identification of local tumor progression (LTP) difficult. Follow-up with PET/CT is compared to follow-up with PET alone and MRI after RFA.

METHODS AND MATERIALS: Sixteen patients showed 25 FDG-positive colorectal liver metastases in pre-interventional PET/CT. Post-interventional PET/CT was performed 24h after ablation and was repeated after 1, 3 and 6 months and then every 6 months. PET and PET/CT data were compared with MR data sets acquired within 14 days before or after these time points. Either histological proof by biopsy or resection, or a combination of contrast-enhanced CT at fixed time points and clinical data served as a reference.

RESULTS: The 25 metastases showed a mean size of 20mm and were treated with 39 RFA sessions. Ten lesions which developed LTP received a second round of RFA; four lesions received three rounds of treatment. The mean follow-up time was 22 months. Seventy-two PET/CT and 57 MR examinations were performed for follow-up. The accuracy and sensitivity for tumor detection was 86% and 76% for PET alone, 91% and 83% for PET/CT and 92% and 75% for MRI, respectively.
CONCLUSIONS: In comparison to PET alone, PET/CT was significantly better for detecting LTP after RFA. There were no significant differences between MRI and PET/CT

Chemoembolization is safe and effective palliative therapy for patients with colorectal liver metastases.It is largely being used as a reserve modality in patients who have chemo-resistant disease.The advent of newer chemotherapeutic agents including the monoclonal antibodies is likely to influence the referral pattern for interventional therapies with the latter being reserved for patients who have failed systemic chemotherapy and have good performance status.Role of TACE in the neo-adjuvant setting is not defined.

Neuroendocrine Metastases

Hepatic artery embolization and chemoembolization for treatment of patients with metastatic carcinoid tumors: the M.D. Anderson experience.

Gupta S, Yao JC, Ahrar K, Wallace MJ, Morello FA, Madoff DC, Murthy R, Hicks ME, Ajani JA

Cancer J ; 9:261-7.
Abstract

BACKGROUND: Carcinoid tumors have a predilection for metastasizing to the liver. The presence of liver metastases is associated with poor prognosis and also results in significant deterioration of patient’s quality of life. Several reports suggest that hepatic artery embolization or chemoembolization can be used for control of liver disease in these patients. We retrospectively reviewed our experience with the use of hepatic arterial embolization or chemoembolization in patients with liver-dominant metastatic carcinoid disease, evaluating the clinical and radiologic response rates, duration of response, and progression-free and overall survival rates of these patients.

RESULTS: Eighty-one patients (48 men and 33 women; age range, 38-79 years) were included in this study. The mean duration of disease from the initial discovery of liver metastases until embolization was 24.5 months. Fifty patients were treated with bland hepatic artery embolization, and 31 underwent chemoembolization. Of the 69 patients in whom radiologic response could be evaluated, partial response was observed in 46 patients (67%), minimal response (MR) in six (8.7%), stable disease in 11 (16%), and progressive disease in six (8.7%). The median duration of response in the 42 patients with partial response was 17 months (range, 4-51 months). Sixty-three percent of patients had a reduction in their tumor-related symptoms. The median progression-free survival duration was 19 months (95% confidence interval, 17-21 months); the probability of progression-free survival was 75%, 35%, and 11% at 1, 2, and 3 years, respectively. The median overall survival time was 31 months (95% confidence interval, 23-38 months); the survival probability was 93% at 1 year, 62% at 2 years, and 24% at 5 years.

CONCLUSIONS: Hepatic arterial occlusive therapy using hepatic artery embolization or chemoembolization results in symptomatic and radiologic response in most patients with carcinoid metastases in the liver. The progression-free survival of 19 months achieved with embolization in our study is encouraging, given that most patients had extensive liver involvement and had shown disease progression while receiving systemic treatment.

Particle embolization of hepatic neuroendocrine metastases for control of pain and hormonal symptoms.

Brown KT, Koh BY, Brody LA, Getrajdman GI, Susman J, Fong Y, Blumgart LH

J Vasc Interv Radiol 1999; 10:397-403

Abstract

PURPOSE: To evaluate treatment outcome with respect to the indication for treatment in patients with neuroendocrine tumors metastatic to the liver undergoing hepatic artery embolization with polyvinyl alcohol (PVA) particles.

MATERIALS AND METHODS: Charts and radiographs were reviewed of 35 patients undergoing 63 separate sessions of embolotherapy between January 1993 and July 1997. Patient demographics, tumor type, indication for embolization, and complications were recorded. Symptomatic and morphologic responses to therapy were noted, as well as duration of response.

RESULTS: Fourteen men and 21 women underwent embolization of 21 carcinoid and 14 islet cell tumors metastatic to the liver. These patients underwent 63 separate episodes of embolotherapy. Of 48 episodes that could be evaluated, response to treatment was noted following 46 episodes (96%). The duration of response was longest in patients treated for hormonal symptoms with (17.5 months) or without (16 months) pain, and was shortest (6.2 months) when the indication was pain alone. Complications occurred after 11 of the 63 embolizations (17%), including four (6%) deaths. Cumulative 5-year survival following embolotherapy was 54%.

CONCLUSION: Hepatic artery embolization with PVA particles is beneficial for patients with neuroendocrine tumors metastatic to the liver and may be used for control of pain as well as hormonal symptoms. This therapy should be used cautiously when more than 75% of the hepatic parenchyma is replaced by tumor.

Long-term outcome after chemoembolization and embolization of hepatic metastatic lesions from neuroendocrine tumors.

Ho AS, Picus J, Darcy MD, Tan B, Gould JE, Pilgram TK, Brown DB.

AJR Am J Roentgenol. 2007 May; 188(5):1201-7.

OBJECTIVE: Hepatic artery chemoembolization and hepatic artery embolization (HAE) are accepted treatments of patients with hepatic metastasis from neuroendocrine tumors. Long-term outcome data are limited. We present our experience in the use of hepatic artery chemoembolization in the treatment of patients with hepatic metastasis from neuroendocrine tumors..

CONCLUSION: The overall survival time after hepatic artery chemoembolization or HAE among patients with neuroendocrine tumors is approximately 3.5 years. The progression-free survival time approaches 1.5 years. The presence of extrahepatic metastasis or an unresected primary tumor should not limit the use of hepatic artery chemoembolization or HAE.

Chemoembolization ,bland embolization and RFA used alone or in combination with surgical resection improve the hormonal symptoms and slow disease progression in patints with neuroendocrine metastases.

Portal Vein Embolization

With advances in surgical techniques and post-operative critical care,more and more patients are now being considered for curative resections of primary and secondary hepatic tumors.

Percutaneous portal vein embolization has matured into a well validated treatment modality for inducing hypertrophy of the Future Liver Remnant (FLR) in patients with small FLR.

How PVE works?

PVE takes advantage of the excellent regenerating capacity of the liver. The aim of the procedure is to induce hypertrophy of the non-diseased portion of the liver so that the diseased portion can be safely removed without compromising synthetic liver function.

This is achieved by embolizing the portal vein branches in the tumor bearing liver which is to be resected.

As a consequence of this,the entire portal venous inflow is directed to the FLR,which undergoes hypertrophy under the influence of various trophic factors like Hepatocyte growth factor (HGF) and Insulin.The mechanisms of liver regeneration following PVE are not fully understood.

The hepatocytes in the FLR undergo increase in size whereas those in the embolized liver undergo apoptosis.Apoptotic cell death explains the absence of inflammatory response to embolisation.

Rates of liver regeneration:
Liver regeneration peaks within first 2 weeks after PVE.

Regeneration rates are slower in diabetics and cirrhotics.

How PVE helps the surgeon?
1. Increased cell mass in the remnant liver helps minimize metabolic dysfunction.
2. Minimizes sudden elevation of portal pressure in the residual liver at resection. This prevents hepatic congestion.

Indications:
Proper patient selection is critical and is done on the basis of liver volumetry performed with CT.

Some important parameters are considered in all patients who are undergoing liver resections.They are:
1. Future Liver Remnant (FLR): It is the volume of the (non-diseased) remnant liver that remains after resection.
2. Total Liver Volume: Volume of the entire liver measured with CT.
3. Total Estimated Liver Volume (TELV) can be calculated based on the body weight or body mass index.

A ratio of FLR/TELV is calculated.

Patients are selected for PVE based on this ratio as follows:
I. FLR/TELV < 25% for normal liver
II. FLR/TELV < 40% for compromised liver function (cirrhosis or high dose chemotherapy)

Diabetic patients have limited regenerating capacity and may benefit from PVE.

Contraindications:

There are no absolute contraindications for PVE. PVE is relatively contraindicated in patients with
1. Uncorrectable coagulopathy
2. Tumor thrombus in portal vein
3. Portal hypertension
4. Distant metastases or other factors which may preclude surgery after PVE.

Pre-procedure evaluation:
Laboratory evaluation:
1. CBC
2. LFT and RFT
3. Prothrombin Time

Imaging evaluation:
Multiphasic spiral CT with volumetrics is the mainstay of evaluation to document:
1. Extent of disease
2. FLR size and
3. Portal venous anatomy.

Technical aspects:
PVE can be done using the transhepatic or the transileocolic venous approach.

Transileocolic venous approach involves surgical exposure of the ileocolic vein followed by cannulation of the portal circulation.Transhepatic approach to the portal venous system can be ipsilateral (from the side to be embolized ) or contralateral ( through the FLR ).

Transhepatic approach through the FLR is avoided if possible.

Procedural details:
Ultrasound guided portal vein access using 22 G Chiba needle followed by placement of 6Fr vascular sheath in the portal vein branch.

Portal venogram is performed with a pigtail catheter. Multiple projections are obtained to clarify the segmental portal venous anatomy.

Selective cannulation of the target segmental branches is done using a reverse curve catheter (for ipsilateral approach) or visceral angiographic catheter (for contralateral approach).

A coaxially placed microcatheter is used for delivering the embolizing material.

PVA particles of 300-500 micron size and metallic coils are used most commonly.

NBCA (glue) and lipiodol combination can also be used depending on the operator preference and experience.

Embolization is performed to achieve complete stasis.

Post procedure care:

Includes clinical and lab evaluation to monitor the development of post-embolization syndrome or liver insufficiency.

Potential Complications:
Hemorrhage and infection.
Portal vein thrombosis
Portal hypertension.
Post procedure surveillance and timing the resection:

Repeat CT at 2-4 wks to assess FLR hypertrophy.

Preoperative portal vein embolization for major liver resection: a meta-analysis.

Abulkhir A, Limongelli P, Healey AJ, Damrah O, Tait P, Jackson J, Habib N, Jiao LR.

Ann Surg. 2008 Jan;247(1):49-57.

INTRODUCTION: Preoperative portal vein embolization (PVE) is used clinically to prevent postoperative liver insufficiency. The current study examined the impact of portal vein embolization on liver resection.

METHOD: A comprehensive Medline search to identify all registered literature in the English language on portal vein embolization. Meta-analysis was performed to assess the result of PVE and its impact on major liver resection.

RESULT: A total of 75 publications met the search criteria but only 37 provided data sufficiently enough for analysis involving 1088 patients. The overall morbidity rate for PVE was 2.2% without mortality. Four weeks following PVE, 85% patients underwent the planned hepatectomy (n = 930). Twenty-three patients had transient liver failure following resection after PVE (2.5%) but 7 patients developed acute liver failure and died (0.8%).The reason for nonresection following PVE (n = 158, 15%) included inadequate hypertrophy of remnant liver (n = 18), severe progression of liver metastasis (n = 43), extrahepatic spread (n = 35), refusal to surgery (n = 1), poor general condition (n = 1), altered treatment to transcatheter artery embolization or chemotherapy (n = 24), complete remission after treatment with 3 cycles of fluoracil and interferon alpha in a patient with hepatocellular carcinoma (n = 1), incomplete pre- or postembolization scanning (n = 8). Of those who underwent laparotomy without resection, (n = 27) reasons included intraoperative finding of peritoneal dissemination (n = 15), portal node metastasis (n = 2), severe invasion of the tumor to the hepatic artery and portal vein (n = 1), and gross tumoral extension precluding curative resection (n = 9).Two techniques were used for portal vein embolization: percutaneous transhepatic portal embolization, (PTPE) and transileocolic portal embolization, (TIPE). The increase in remnant liver volume was much greater in PTPE than TIPE group (11.9% vs. 9.7%; P = 0.00001). However, the proportion of patients who underwent resection following PVE was 97% in TIPE and 88% PTPE, respectively (P = <0.00001). Although there was no significant difference in patients who had major complications post-PVE, the rate for minor complications was significantly higher among patients who had PTPE (53.6% vs. 0%, P = <0.0001).

CONCLUSION: PVE is a safe and effective procedure in inducing liver hypertrophy to prevent postresection liver failure due to insufficient liver remnant.

Comparison of two methods of future liver remnant volume measurement.

Chun YS, Ribero D, Abdalla EK, Madoff DC,
Mortenson MM, Wei SH, Vauthey JN.

J Gastrointest Surg. 2008 Jan;12(1):123-8.
Epub 2007 Oct 9.

BACKGROUND: In liver transplantation, a minimum graft to patient body weight (BW) ratio is required for graft survival; in liver resection, total liver volume (TLV) calculated from body surface area (BSA) is used to determine the future liver remnant (FLR) volume needed for safe hepatic resection. These two methods of estimating liver volume have not previously been compared. The purpose of this study was to compare FLR volumes standardized to BW versus BSA and to assess their utility in predicting postoperative hepatic dysfunction after hepatic resection.

RESULTS: Regression analysis revealed that the FLR/TLV and FLR/BW ratios were highly correlated (Pearson correlation coefficient, 0.98). The area under the ROC curve was 0.85 for FLR/TLV and 0.84 for FLR/BW (95% confidence interval, 0.71-0.97). Sixteen of the 68 patients developed postoperative hepatic dysfunction. The ROC curve analysis yielded a cutoff FLR/BW value of </=0.4, which had a positive predictive value (PPV) of 78% and a negative predictive value (NPV) of 85%. The corresponding FLR/TLV cutoff value of </=20% had a PPV of 80% and a NPV of 86%.

CONCLUSIONS: Based on the strong correlation between the FLR measurements standardized to BW and BSA and their similar ability to predict postoperative hepatic dysfunction, both methods are appropriate for assessing liver volume. In noncirrhotic patients, a FLR/BW ratio of </=0.4 and FLR/TLV of </=20% provide equivalent thresholds for performing safe hepatic resection.

Portal vein embolization before major hepatectomy and its effects on regeneration, resectability and outcome.

Ribero D, Abdalla EK, Madoff DC, Donadon M, Loyer EM, Vauthey JN.

Br J Surg. 2007 Nov;94(11):1386-94.

BACKGROUND: This study evaluated the safety of portal vein embolization (PVE), its impact on future liver remnant (FLR) volume and regeneration, and subsequent effects on outcome after liver resection.

METHODS: Records of 112 patients were reviewed. Standardized FLR (sFLR) and degree of hypertrophy (DH; difference between the sFLR before and after PVE), complications and outcomes were analysed to determine cut-offs that predict postoperative hepatic dysfunction.

RESULTS: Ten (8.9 per cent) of 112 patients had PVE-related complications. Postoperative complications occurred in 34 (44 per cent) of 78 patients who underwent hepatic resection and the 90-day mortality rate was 3 per cent. A sFLR of 20 per cent or less after PVE or DH of not more than 5 per cent (versus sFLR greater than 20 per cent and DH above 5 per cent) had a sensitivity of 80 per cent and a specificity of 94 per cent in predicting hepatic dysfunction. Overall, major and liver-related complications, hepatic dysfunction or insufficiency, hospital stay and 90-day mortality rate were significantly greater in patients with a sFLR of 20 per cent or less or DH of not more than 5 per cent compared with patients with higher values.

CONCLUSION: DH contributes prognostic information additional to that gained by volumetric evaluation in patients undergoing PVE.

Preoperative Percutaneous Portal Vein Embolization: Evaluation of Adverse Events in 188 Patients1

Donatella R. Di Stefano, MD, Thierry de Baere, MD, Alban Denys, MD, Antoine Hakime, MD, Gilles Gorin, MD, Michel Gillet, MD, Jean Saric, MD, Hervé Trillaud, MD, Philippe Petit, MD, Jean-Michel Bartoli, MD, Dominique Elias, MD and Jean-Robert Delpero, MD

PURPOSE: To retrospectively assess the frequency of adverse events related to percutaneous preoperative portal vein embolization (PPVE).

RESULTS: Adverse events occurred in 24 (12.8%) of 188 patients, including 12 complications and 12 incidental imaging findings. Complications included thrombosis of the portal vein feeding the future remnant liver (n = 1); migration of emboli in the portal vein feeding the future remnant liver, which necessitated angioplasty (n = 2); hemoperitoneum (n = 1); rupture of a metastasis in the gallbladder (n = 1); transitory hemobilia (n = 1); and transient liver failure (n = 6). Incidental findings were migration of small emboli in nontargeted portal branches (n = 10) and subcapsular hematoma (n = 2). Among the 187 patients in whom PPVE was technically successful, there was a significant difference (P < .001) between the occurrence of liver failure after PPVE in patients with cirrhosis (five of 30) and those without (one of 157). Sixteen liver resections were cancelled due to cancer progression (n = 12), insufficient hypertrophy of the nonembolized liver (n = 3), and complete portal thrombosis (n = 1).

CONCLUSION: PPVE is a safe adjuvant technique for hypertrophy of the initially insufficient liver reserve. Post-PPVE transient liver failure is more common in patients with cirrhosis than in those without cirrhosis.

Two hundred forty consecutive portal vein embolizations before extended hepatectomy for biliary cancer: surgical outcome and long-term follow-up.

Nagino M, Kamiya J, Nishio H, Ebata T, Arai T, Nimura Y.

Ann Surg. 2006 Mar;243(3):364-72.

OBJECTIVE: To assess clinical benefit of portal vein embolization (PVE) before extended, complex hepatectomy for biliary cancer. SUMMARY BACKGROUND DATA: Many investigators have addressed clinical utility of PVE before simple hepatectomy for metastatic liver cancer or hepatocellular carcinoma, but few have reported PVE before hepatectomy for biliary cancer due to the limited number of surgical cases.

CONCLUSIONS: PVE has the potential benefit for patients with advanced biliary cancer who are to undergo extended, complex hepatectomy. Along with the use of PVE, further improvements in surgical techniques and refinements in perioperative management are necessary to make difficult hepatobiliary resections safer.

Portal vein embolization is a safe and effective procedure for inducing hypertrophy of the future liver remnant (FLR) in patients with a suboptimal FLR volume.Ipsilateral approach is safer as it avoids access through the FLR.PVE can be used in patients with HCC,metastases and biliary cancer.PVE widens the safety margin for liver resection.

Isotope therapy for Primary and Secondary Hepatic Malignancy

Yttrium 90 (Y) micro spheres are 20-40 uM particles that emit beta radiation. Because these microspheres are delivered via the hepatic arterial route, the process can be considered as internal rather than external radiation. The treatment algorithm is analogous to that followed with transarterial chemoembolization, TACE. Clinical history, physical examination, laboratory values and performance status are evaluated. Patients conditioned are initially evaluated and they are disease s staged with cross sectional imaging techniques- CECT, MRI& imaging/ PET.

Theraspheres – yttrium -90 Glass microspheres has US approval under humanitarian device exemption for the treatment of HCC for primary treatment, with or without PVT and is the bridge to transplantation /resection. It is approved for the treatment of liver neoplasia in Canada, Europe, India and Russia. Y-90 Theraspheres is an integral constituent of the insoluble, biocompatible glass mark. Theraspheres is pY2o3.qSiO2.aAl2O3-Y-90. It is of 20-30uM size. The product is categorized as sealed source and is handled using standard containment procedures for radioactive liquids.The expected radiation from this source is 0.54mSv/Hr when the source is 1.5GBq, at 5 cms behind a 1cm of plexiglass shielding. In comparison the skin dose rate from fluoroscopy is 0.6-6Sv/hr. Maximum surface dose rate are 3uSv/hr to 0.15 mSv/hr. dose rates at 1 meter is <0.02uSv/hr.

Dose calculation:

Treatment activity GBq = [desired dose (Gy)] [target mass (kgs)]/50

Desired dose varies clinically between 80-150Gys.

Handling of the dose and safe disposal of the waste must be as per the regulatory requirement.

Activity required TA= treatment activity =Gy*CC*0.00103/50

Dosing vial activity =TA+ shunt fraction*TA

Lung Shunt evaluation is estimated from the Region of interests drawn over the liver and the lungs, following the instillation of 4mCi 99mTc MAA through a catheter placed through the liver. The data is acquired as planar or SPECT and the ration of liver to lung ROIs are estimated as the shunt fraction. All these are completed on the first day or (angiography day).

Once the dose estimate is calculated, the dose is ordered and is injected through the hepatic catheter. This is done on another day as another procedure( treatment day)

Patient Preparation:
The following are the different goals for the therapy
1. Definitive therapy
2. Bridge/downstage to transplant
3. Downstage to resection
4. Salvage therapy for chemotherapy
5. bridge to chemotherapy(“ Chemobreak”)

New referral workup:
1. Histopathology
2. Triple phase CECT/MRI – done less than 30 days
3. PET/CT if indicated and available
4. Lab Investigations: CBC, LFT, RFT, PT/INR
5. Tumor markers:

• AFP for HCC
• CEA for Liver mets from CRC
• Chromogranin A – Neuroendocrine
• CA27-29 – Liver mets from breast Ca
• CA 19-9 – mets from hepatobiliary tumors

Patient selection:
Performance status – ECOG (0-2)
ECOG Performance Status
0 – Asymptomatic and fully active
1- Symptomatic; fully ambulatory; restricted in physically strenuous activity
2- Symptomatic; ambulatory; capable of self care ;> 50% of waking hours spent out of bed
3- Symptomatic; limited self care; spends >50%of time in bed
4- Completely disabled; no self care; bedridden

Liver Enzymes- PT/Albumin/T Bil (1.5 mg/dl)
Portal vein thrombosis – Minimally embolic therapy
Size/vascularity of tumor – hyper vascular

Previous Procedure:
TACE/RFA
Surgery/Whipples/Biliary stenting
External Beam RT

Individual Conditions:
Carcinoid Tumors:
1. Majority located in GI tract(55%) and bronchopulmonary system (30%) GI tract-
2. Small intestine (45% -ileum)
3. Rectum (20%)
4. Appendix (16%)
5. Stomach (7%)

Carcinoid Syndrome:

• 75-80% have small bowel carcinoid
• does not occur without liver metastases in intestinal carcinoid
• flushing
• diarrhea
• valvular heart disease ( R>L)
• bronchoconstriction

Carcinoid Crisis:

• profound flushing
• extreme changes in Blood Pressure
• bronchoconstriction
• Arrhythmias
• Confusion or stupor
• Administration of 200mcg of sandostatin prior to treatment can prevent the crisis

Day one: for Mapping Angiogram:

• Identification of anatomy
• Coil embolization of GDA/Right gastric
• 99mTc MAA instillation followed by Nuclear Scan
• from CECT 3D reconstruction for lobar volume and target vascular bed
• 6-8 hrs of activity for the patient
• Dose estimation done and order is placed.

Day two: Day of treatment:

Baseline laboratory investigations
Angiography and delivery of dose

Discharge and Followup:
Prescription medications including Ciprofloxacillin and prednisolone

After 1 month: triphasic CT/MRI, PET if indicated, Laboratory and Tumor Markers

Expected adverse effects:

• Fatigue (50-60%) usually lasts 10-12 days
• Mild abdominal Pain or discomfort (<15%)
• Paraneoplastic fever
• Bulky disease or in neuroendocrine
• Cytokine release from tumor necrosis
• Night sweats
• Rule out other causes

References:
Recommendations for radioembolization of hepatic malignancies using yttrium-90 microsphere brachytherapy: a consensus panel report from the radioembolization brachytherapy oncology consortium.

Kennedy A, Nag S, Salem R, Murthy R, McEwan AJ, Nutting C, Benson A 3rd, Espat J, Bilbao JI, Sharma RA, Thomas JP, Coldwell D.

Int J Radiat Oncol Biol Phys. 2007 May 1;68(1):13-23.A total of 14 recommendations are made with category 2A consensus. Key findings include the following. Sufficient evidence exists to support the safety and effectiveness of Y90 microsphere therapy. A meticulous angiographic technique is required to prevent complications. Resin microsphere prescribed activity is best estimated by the body surface area method. By virtue of their training, certification, and contribution to Y90 microsphere treatment programs, the disciplines of radiation oncology, nuclear medicine, and interventional radiology are all qualified to use Y90 microspheres. The panel strongly advocates the creation of a treatment registry with uniform reporting criteria. Initiation of clinical trials is essential to further define the safety and role of Y90 microspheres in the context of currently available therapies.

• Radioembolization with 90Yttrium microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies. Part 1: Technical and methodologic considerations
  Salem R, Thurston KG.
  J Vasc Interv Radiol. 2006 Aug;17(8):1251-78l
• Radioembolization with 90yttrium microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies. Part 2: special topics.
  Salem R, Thurston KG.
  J Vasc Interv Radiol. 2006 Sep;17(9):1425-39.
• Radioembolization with yttrium-90 microspheres: a state-of-the-art brachytherapy treatment for primary and secondary liver malignancies: part 3: comprehensive literature review and future direction.
  Salem R, Thurston KG.
  J Vasc Interv Radiol. 2006 Oct;17(10):1571-93.
• Selective Internal Radiation Therapy (SIRT) for liver metastases secondary to colorectal adenocarcinoma.
  Welsh JS, Kennedy AS, Thomadsen B.
  Int J Radiat Oncol Biol Phys. 2006;66(2 Suppl):S62-73.l
• Radioembolization of liver metastases from colorectal cancer using yttrium-90 microspheres with concomitant systemic oxaliplatin, fluorouracil, and leucovorin chemotherapy
  Sharma RA, Van Hazel GA, Morgan B, Berry DP, Blanshard K, Price D, Bower G, Shannon JA, Gibbs P, Steward WP.
  J Clin Oncol. 2007 Mar 20;25(9):1099-106
• The maximum-tolerated dose was 60 mg/m2 of oxaliplatin for the first three cycles, with full FOLFOX4 doses thereafter. This chemoradiation regime merits evaluation in phase II-III trials.
• Complete eradication of hepatic metastasis from colorectal cancer by Yttrium-90 SIRT.
  Garrean S, Muhs A, Bui JT, Blend MJ, Owens C, Helton WS, Espat NJ.
  World J Gastroenterol. 2007 Jun 7;13(21):3016-9.
• Radioembolization with Yttrium-90 microspheres: review of an emerging treatment for liver tumors.
  Gates VL, Atassi B, Lewandowski RJ, Ryu RK, Sato KT, Nemcek AA, Omary R, Salem R.
  Future Oncol. 2007 Feb;3(1):73-81.
  
  Rhenium 188 is a generator produced Isotope that is labeled with lipoidol or its analogues and used similar to Y90 Microspheres. The advantage is that since it is generator produced , it is more readily available and cheaper and the disadvantage is that it needs a hospital Radiopharmacy to make the radiopharmaceutical for use.
  
  References:
• Intra-Arterial Rhenium-188 Lipiodol in the Treatment of Inoperable Hepatocellular Carcinoma: Results of an IAEA-Sponsored Multination Study.
  Bernal P, Raoul JL, Vidmar G, Sereegotov E, Sundram FX, Kumar A, Jeong JM, Pusuwan P, Divgi C, Zanzonico P, Stare J, Buscombe J, Minh CT, Saw MM, Chen S, Ogbac R, Padhy AK.
  Int J Radiat Oncol Biol Phys. 2007 Dec 1;69(5):1448-55.
• Inoperable hepatocellular carcinoma: transarterial 188Re HDD-labeled iodized oil for treatment—prospective multicenter clinical trial.
  Radiology. 2007 May;243(2):509-19.
  Kumar A, Srivastava DN, Chau TT, Long HD, Bal C, Chandra P, Chien le T, Hoa NV, Thulkar S, Sharma S, Tam le H, Xuan TQ, Canh NX, Pant GS, Bandopadhyaya GP.
• Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival
  
  Salem R, Lewandowski RJ, Atassi B, Gordon SC, Gates VL, Barakat O,
  
  Sergie Z, Wong CY, Thurston KG.J Vasc Interv Radiol. 2005 Dec;16(12):1627.

Section II
Role of Interventional Radiology in the Management of Lung Malignancy

Contributors:
Dr. M. H. Thakur
Dr. Suyash Kulkarni
Dr. Manas Kar
Dr. Mehul Sangani

Image – Guided Radiofrequency ablation in Lung Malignancy

Lung cancer is the leading cause of death worldwide surpassing the death rate from Colon, Prostate & breast cancer.
Approximately 80% of new lung lesions are of non – small – cell carcinoma with an overall estimated 5yrs. survival rates of 10-18%. At present surgical resection remains the mainstay treatment modality in early non small cell cancer in selected patient and with limited pulmonary metastasis from extra pulmonary primary tumors.

In practice, only 1/3rd patients are eligible for surgical Intervention. In majority cases co-existent medical morbid condition like poor cardiopulmonary reserve & advanced stage of the disease at time of diagnosis are found to be unsuitable for surgery. In these group of patient treatment option relay on Radiotherapy with / or without Chemotherapy. However, in a meta- analysis study determining the effectiveness of radical radiotherapy for medically inoperable non-small-cell cancer patients, overall survival ranges from 0 – 42% when subjected for Radiotherapy +/- Chemotherapy.(1)

These factors have led to a search for alternative modalities which could accomplish tumour destruction / complete eradication, complementing, improving or potentially replacing the existing modalities. Radio Frequency Ablation (Percutaneous image guided) has recently been used as a minimally invasive approach for variety of solid tumours including both primary and secondary of Liver, Kidney, Breast, Bone, Adrenal & lung.

Advantages of RFA :

• RFA of lung malignancies is a revolutionary concept. Its safety profile is similar to percutaneous image guided lung biopsies.
  
• Almost all RFA procedures can be done on outpatient setting with conscious sedation.
  
• Multiple applications can be performed without any additional risk.

It is cost effective and devoid of major post procedural complication as compared to surgery

Patient Selection:

RFA of lung malignancies are done for two basic reasons:-

1) Definitive therapy.

2) Palliative treatment

1) First group includes, patients who are not candidates for surgery due to –

a. Co morbid conditions like – poor cardio pulmonary reserve

b. Patient not willing for surgery

2) Second group includes, patients in advanced stage of disease as a palliative measure

a. To achieve debulking of tumour before Chemotherapy.

b. To palliate local symptoms related to aggressive tumour growth, like chest pain in chest wall invasion / dyspnea.

c. To palliate pain from hematogenous painful bone metastatic disease

d Tumour recurrence in patients who are not suitable for repeat radiation / surgery

Patient selection (for definitive treatment)(2)

Inclusion Criteria:

1) It is to Pathological diagnosis of tumor

2) Types of Lung tumors

a. Non Small cell lung cancer (stage I)

b. Colorectal, Breast and Renal metastasis

3) Maximum tumour diameter 3.5cm

4) Numbers of tumour nodules 2

5) Tumour surrounded by aerated parenchyma adjacent to the mediastinum or major vessels.

6) Refusal of surgery as a treatment option as mentioned above

Exclusion Criteria:

- Non – Small cell cancer stage II – IV

- Extra pulmonary spread

- Tumour involving main stem bronchi, Trachea and / or mediastinum

- Patient with pulmonary colo-rectal metastases with active extra-pulmonary disease

- Uncontrolled bleeding diathesis.- Recent use of anti coagulants

- Platelets count < 50,000 mm3 and /or increased prothrombin time

- Concomitant diseases with life expectancy less than 6 months
- Refusal for RFA

• Mechanism of RFA (3)
  
  Radiofrequency ablation works by converting RF waves into heat through ionic vibration.
  
  - It involves image guided placement of an electrode into tumour bed and application of alternating RF current to attain frictional heating of the tissue leading to coagulation necrosis.
  
  - RF generators supply power to the tissue through the target (active) electrodes which is made of insulated metal shaft except for exposed conductive tip which is in direct contact with the target and a reference electrode (grounding pad) which is placed in contact with the patient skin usually on thigh or back
  
  - The RF generator produces voltage between the (two electrodes) target and reference electrodes
  
  - Establishing the lines of electric field that oscillate with the alternating RF current, which causes oscillation of ions in the tissue in proportion to the field intensity
  
  - Motion of ions caused due to ionic current ,causes releasing of frictional heat
  
  - Heating of tissue causes coagulation necrosis and cell death.
  
  - Temperature should be maintained between 50 – 1000 c throughout the target volume which is considered lethal to target tissue.
  
  - The ability to achieve a satisfactory ablation based on the energy balance between the heat conduction of localized RF energy and heat convection from extracellular fluid.
  
  - In the lung RF energy can be efficiently deposited, as the surrounding air act as an insulator and concentrates energy in the target tissue. Secondly , the high vascular flow of the normal lungs result in a “heat sink” effect , dissipating heat from the normal adjacent tissue, there by concentrating the energy within the solid component of the lesion.
  
  Technique and Procedures:-
  
  RF system (RITA) consists of a generators an active electrode and grounding pads. Digital display on the front of the device indicates power in Joules, current out put, temperature achieved, impedances value and procedure time. The active electrodes which used are capable of creating thermal lesions upto 5cm.
  
  RF ablation is performed under general anesthesia or with conscious sedation. Intravenous broad spectrum antibiotic coverage should be started three hours prior and to be continued upto seventy two hours post procedure.
  
  Patient who are stable and suitable for CT guided biopsy are suitable for the procedure
  
  CT scan images of the target area was scanned with 2 – 5mm collimation, depending on the size and location of the lesion
  Grounding pads are applied to both thighs.
  
  Under all aseptic measures, the active electrode is introduced into the center of the lesion with the help of CT guidance
  
  Depending upon the size and volume of the lesion. the placement of the electrode and opening of the multitined electrodes is planned.
  
  Electrode is then connected to RF generator and temperature set for a particular lesion based on manufactures specification followed by tract ablation.
  
  Post ablation CT Scan of the ablated area and adjacent lungs is done to rule out any pneumothorax / Hemothorax.
  
  Patient should be observed in the recovery room for at least two hours post procedure.
  
  Complications of RFA(4)
  
  – Mild to moderate pain, which is usually gets resolved with post RFA analgesic drugs.
  
  – Mild fever upto 1 week after ablation
  
  – Skin burns due to wrong application of grounding pads.
  
  – Pneumothorax
  
  – Hemothorax / post procedural pleural effusion.
  
  – Localized abscess formation at the ablation site.
  
  Incidence of complications:

– £48 – 72hrs. ablated lesion shows wrinkling of edge and surrounding ground glass opacification representing the ablated zone.

– 1 week -1 month post RFA – Lesion appears as an area of consolidation or nodules with means diameter which is larger than the pre-ablation size. It may also show some cavitations and bubble lucencies within it.

– 2 – 6 months post RFA: - Shows no change or decrease size of the lesion post RFA as compared to base Line study in patient with complete response.

Assessment of post RFA response:-(2)

CT Scan is the most commonly and widely accepted tools for assessment of post RFA lesion after 4 – 6 weeks.

• Presence of non enhancing area at the tumour site larger than the treated area is considered as complete tumour necrosis.
  
• Presence of enhancing tissue at the tumour site indicates incomplete treatment. In such patients RFA can be repeated.
  
• Presence of enhancing tissue at the repeatedly treated tumour site is considered as treatment failure.

PET –CT Scan is a useful tool for the follow up of large heterogeneous appearing tumour. In post RFA patients in whom contrast enhancement is not properly appreciated
Post ablation the follow up with CT scan is recommended every three months for first year and every six months thereafter.

Conclusion:

The minimally invasive technique of RFA has a potential to substantially impact the treatment of non – surgical candidates, RFA is a safe and effective alternative for local control of NSCLC and pulmonary colorectal-Metastatic nodules <3.5 cm in diameter. Advantage of RFA includes

– Precise control– Relatively low cost

– Decrease post procedural morbidity and mortality and

– Can be done in outpatient setting.

The clinical impact and long-term results of radiofrequency thermal ablation need to be confirmed in a larger series of patients, and radiofrequency thermal ablation can be ideally be compared with surgery.

Reference:

1. Ginsberg RJ, Vokes EE, Raben A: Cancer of lung :non-small-cell lung cancer, in pass HI, Mitchel JB, Johnson DH,Turrisi AT(eds): Lung cancer:Principle and Practice of Oncology(ed 5). Philadelphia,PA, Lippincott-Raven, 1996, pp 849-857.

2. S. Rossi*, R. Dore# ,et al:Percutaneous computed tomography guided radiofrequency thermal ablation of small unresectable lung tumours, Eur Respir J 2006; 27: 556–563

3. Goldberg SN, Dupuy DE: Image-guided radiofrequency tumour ablation: Challenges and opportunities- part-1 . J Vasc Interv Radiology 12:1021-1032,2001.

4. Namita S. Gandhi, MD, and Damian E.Dupuy,MD: Image guided radiofrequency ablation as a new treatment option for pt. with lung cancer .Seminars in roentgenology, vol-40,no-2,april 2005:pp-171-181.

Survival Benefit of Lung RFA

Midterm local efficacy and survival after radiofrequency ablation of lung tumors with minimum follow-up of 1 year: prospective evaluation.

de Baère T, Palussière J, Aupérin A, Hakime A, Abdel-Rehim M, Kind M, Dromain C, Ravaud A, Tebboune N, Boige V, Malka D, Lafont C, Ducreux M.

Radiology. 2006 Aug;240(2):587-96.

PURPOSE: To prospectively evaluate the local efficacy of radiofrequency (RF) ablation of lung neoplasms, with a minimum follow-up period of 1 year.

MATERIALS AND METHODS: Sixty patients (34 men and 26 women; age range, 27-81 years; mean

age, 66 years) with 100 lung tumors gave written informed consent to be enrolled in a prospective study that was approved by the local ethics committee. RF ablation was performed in tumors by using computed tomographic (CT) guidance.

RESULTS: Ninety-seven of 100 targeted tumors were treated and required 163 RF ablations (1.68 per tumor), each lasting 14 minutes +/- 8, delivered during 74 procedures. The 18-month estimated rate of incomplete local treatment at CT was 7% (95% confidence interval: 3%, 14%) per tumor and 12% (95% confidence interval: 5%, 23%) per patient. An ablation area at least four times larger than the initial tumor was predictive of complete ablation treatment (P = .02).

There was a trend toward better efficacy for tumors smaller than 2 cm in diameter (P = .066). Overall survival and lung disease-free survival at 18 months were 71% and 34%, respectively.

The main adverse event was a pneumothorax, which occurred in 54% of procedures, but a chest tube was required in only 9% of the procedures. No modification of respiratory function was found when spirometry measurements obtained before and within 2 months after RF ablation were compared
(P = .51).
CONCLUSION: RF ablation has a high local efficacy and is well tolerated.

Percutaneous radiofrequency ablation of lung neoplasms: initial therapeutic response.

Akeboshi M, Yamakado K, Nakatsuka A, Hataji O, Taguchi O, Takao M, Takeda K.

J Vasc Interv Radiol. 2004 May;15(5):463-70.

PURPOSE: To evaluate the feasibility, safety, and initial therapeutic effect of radiofrequency (RF) ablation in the treatment of unresectable malignant lung tumors.

MATERIALS AND METHODS: Fifty-four lung neoplasms in 31 patients were treated with RF ablation. with a mean size of 2.7 +/- 1.3 cm. After the RF electrode was placed in the tumor with computed tomographic (CT) fluoroscopic guidance, RF energy was applied. Complete necrosis rates were evaluated according to tumor size and type (primary or secondary lung neoplasm).

RESULTS: RF ablation was technically successful in all lesions. Complete necrosis was achieved in 32of the 54 tumors (59%) after initial RF session. There was a significant difference in the rate of complete tumor necrosis between tumors 3 cm or less and tumors larger than 3 cm (69% vs. 39%; P <.05). Tumor type did not influence complete necrosis rates. Lung abscesses developed in two patients with large tumors.

CONCLUSION: Lung RF ablation is a feasible, relatively safe, and promising treatment for unresectable lung neoplasms. Tumor size is an important factor in achieving complete tumor necrosis.

Pulmonary RadiofrequencynAblation: Long-term Safety and Efficacy in 153 Patients

1Caroline J. Simon,MD,Damian E. Dupuy,MD, Thomas A. DiPetrillo,MD Howard P. Safran,MD C. Alexander Grieco,MD Thomas Ng,MD William W. Mayo-Smith,MD

Purpose: To retrospectively evaluate long-term survival, local tumor progression, and complication rates for all percutaneous computed tomographic (CT)-guided lung tumor radiofrequency (RF) ablations performed at a tertiary care cancer hospital in patients who refused or who were not candidates for surgery.

Materials and Methods: This HIPAA-compliant study was approved by the institutional review board; informed consent was waived.Kaplan-Meier method was used to estimate overall survival and disease-free survival (progression) as a function of time since RF ablation. Comparisons between survival functions were performed by using the log-rank statistic;

Results: The overall 1-, 2-, 3-, 4-, and 5-year survival rates, respectively, for stage I non–small cell lung cancer were 78%, 57%, 36%, 27%, and 27%; rates for colorectal pulmonary metastasis were 87%, 78%, 57%, 57%, and 57%. The 1-,2-, 3-, 4-, and 5-year local tumor progression–free rates, respectively, were 83%, 64%, 57%, 47%, and 47% for tumors 3 cm or smaller and 45%, 25%, 25%, 25%, and 25% for tumors larger than 3 cm. The difference between the survival curves associated with large (>3 cm) and small (<3 cm) tumors was significant (P < .002).

The overall pneumothorax rate was 28.4% (52 of 183 ablation sessions), with a 9.8% (18 of 183 ablation sessions) chest tube insertion rate. The overall 30-day mortality rate was 3.9% (six of 153 patients), with a 2.6% (four of 153patients) procedure-specific 30-day mortality rate.

Conclusion: Lung RF ablation appears to be safe and linked with promising long-term survival and local tumor progression outcomes, especially given the patient population treated.

“ Radiofrequency Ablation of Pulmonary Tumors Response Evaluation (RAPTURE) Trial: 2-Year Survival Outcomes,” Riccardo Lencioni, MD, In this multicenter study, in which seven centers from United States, Europe, and Australia took part, 106 patients with a total of 186 tumors were treated. RFA was technically feasible in 99% of the patients. Diagnoses included non-small cell lung cancer (NSCLC) in 33 patients, metastasis from colorectal adenocarcinoma in 52 patients, and metastasis from other primary malignancy in 15 patients.

Overall survival was 69% at 1 year and 49% at 2 years in patients with NSCLC; and 86% at 1 year and 62% at 2 years in patients with CRC metastases. Cancer-specific survival was 91% at 1 year and 91% at 2 years in patients with NSCLC; and 88% at 1 year and 72% at 2 years in patients with CRC metastases.

Radiofrequency Ablation of Pulmonary tumors shows promising survival benefit ; however long term follow up studies are needed.

Section III
Role of Interventional Radiology in Pain Management in Oncology

Contributors:
Chapter 1 – Dr. Amol Bhalekar
Dr. Anish Bansal
Chapter 2 – Dr. Diptiman Roy
Chapter 3 – Dr. P. N. Jain

Current status of Vertebroplasty in Metastatic Disease

Introduction

Percutaneous cementoplasty is a minimally invasive technique developed in France by Dr. Deramond and his colleagues in 1984. ‘Percutaneous vertebroplasty is defined as the injection of radiopaque bone cement (polymethyl methacrylate) into a painful osteoporotic compression fracture or painful pathologic vertebral body (e.g. multiple myeloma, metastatic disease, and hemangioma) with use of image guidance.’

Its aim is to consolidate weight-bearing bone and to treat pain.

Indications of vertebroplasty are:

1. Painful primary and secondary osteoporotic vertebral compression fracture(s) refractory to medical therapy.

2. Painful vertebrae with extensive osteolysis or invasion secondary to benign or malignant tumor (i.e. hemangioma, multiple myeloma, or metastatic disease).

3. Painful vertebral fracture associated with osteonecrosis (Kummell Disease).

Contraindications

In interventional oncology the most frequently encountered absolute contraindications are hemorrhagic diathesis and infection. Patients with more than five, or diffuse metastases are not indicated for cementoplasty. Lesions with epidural extension require careful injection to prevent epidural overflow.

Absolute Contraindications

1. Asymptomatic vertebral body compression fractures

2. Patient improving orotic patients

4. Ongoing local or systemic infection

5. Retropulsed bone fragment resulting in myelopathy

6. Spinal canal compromise secondary to tumor resulting in myelopathy


7. Uncorrectable coagulopathy

8. Allergy to bone cement or opacification agenton medical therapy

3. Prophylaxis in osteop

Relative Contraindications

1. Radiculopathy in excess of vertebral pain, caused by a compressive syndrome unrelated to vertebral collapse

. Occasionally preoperative percutaneous vertebroplasty can be performed before a spinal decompressive procedure.

2. Asymptomatic retropulsion of a fracture fragment causing significant spinal canal compromise

3. Asymptomatic tumor extension into the epidural space.

Technique
The safest guidance technique seems to be combined computed tomography (CT) and fluoroscopy.
This combination allows precise needle placement, reduces complications, and increases operator comfort. Fluoroscopy and bi-plane fluoroscopy can be used for percutaneous vertebroplasty by a well-trained interventional radiologist.
The patient is placed in a prone or rarely in lateral decubitus position on the CT table. The entry point and pathway are selected on the CT scan. The 10- or 14-gauge vertebroplasty needle is safely guided under CT. The approach is anterolateral at the cervical level. The optimal approach is transpedicular in both thoracic and lumbar levels, but the intercostovertebral route can be used in the thoracic level and the posterolateral route in the lumbar level. The use of CT for planning the pathway and positioning the needle affords a medial positioning of the needle tip in the anterior third of the vertebral body. In this way, a contralateral access is seldom necessary to obtain a good vertebral filling. Cortical perforation can require the aid of a surgical hammer. When the needle is in the optimal position (needle tip in the anterior third of the vertebral body or in the anterior portion of the tumor), the imaging mode is switched to fluoroscopy.
The appropriate radiographic profile for a pedicular approach is a straight anteroposterior view, with 5°-10° angulation. The pedicle is localized with fluoroscopy and appears oval in shape. The needle is advanced into the pedicle under fluoroscopic control. The needle tip is positioned in the anterior part of the vertebral body. With this technique, the needle is placed in the ipsilateral half of the vertebra. With this technique, a bipediculate approach is often necessary for an optimal filling of the vertebral body. After injection of the cement on one side, placement of the needle in the opposite pedicle prolongs duration of the procedure as well as increases the risk of extravasation.
Vertebral venography is only performed in hyper-vascularised lesions.In the other cases, the contrast media is washed out too slowly and can interfere with the injection of the cement.

The acrylic cement is prepared by mixing 40 g of powder and 20 ml of fluid monomer. As the acrylic cement alone is not radio-opaque enough, 3 g of tantalum (depending on patient morphology) is added to the 20 ml mixture. Barium or tungsten can also be used. The radiopaque cements for vertebroplasty are: Osteopal V (Biomet-Merck) and Vertebroplastic (Johnson and Johnson). During the first 30-50 s after mixing, the cement is very thin in consistency. It then becomes pasty and thick. The acrylic cement has to be injected during its pasty polymerization phase to prevent distal venous migration. Between 2 and 7 ml of acrylic cement are injected using 2-ml Luer Lock syringes. Methylmethacrylate is too viscous to be handled without difficulty in this conventional way because injection time is short. The operator is left with little time and must fumble with multiple syringes. The injection set on the market (Cemento Optimed, Germany) allows aspiration and direct injection of the cement from the same syringe in a continuous flow with minimum effort.

The injection of cement is carefully controlled with strict lateral fluoroscopy for the spine. The injection of acrylic cement is stopped immediately whenever a leak is observed. In the majority of cases, the injection of the cement is painful and the patient needs conscious sedation during this phase of the procedure.

After vertebral filling, the stylet of the needle is re-inserted and the needle is then removed before the cement begins to set. Approximately 6-7 min after mixing, the methylmethacrylate begins to harden. During hardening, the temperature of the cement can rise to a maximum of 90°C.

Outcome

The success rate of percutaneous vertebroplasty has been discussed under following criteria:

Complications
There is no relation between the volume of cement injected and the pain relief obtained, particularly in tumor patients.
The major complication during acrylic cement injection is epidural overflow with spinal nerve compression. Monitoring the vertebral filling by lateral fluoroscopy during the injection of the pasty cement minimizes this risk. The next most serious complication is infection; to avoid this complication, strict sterility during the intervention is mandatory.
Spinal cord compression is an emergency and urgent surgery is mandatory to avoid neurologic complications. The injection of acrylic cement should be performed under a high-quality fluoroscopy unit. The injection is immediately interrupted if the cement reaches the posterior cortex of the vertebral body.

(SIR STANDARDS OF PRACTICE COMMITTEE CLASSIFICATION OF COMPLICATIONS BY OUTCOME)

Adequate radio-opacity of acrylic cement (with the addition of tantalum, barium, or tungsten) is mandatory and the cement should be injected during its pasty polymerization phase.
Epidural cement leak can cause neuralgia without the presence of spinal cord compression and this must be avoided.
Radiculopathy is the major risk with neural foramina leaks. The radiculopathy is particularly difficult to treat at the cervical and lumbar levels. Epidural vein filling does not necessarily cause neuralgia. Cement leaks towards the disk are usually without clinical consequence, although the risk of adjacent vertebral collapse is increased.

To avoid major pulmonary infarction, the cement should be injected, slowly during its pasty polymerization phase under fluoroscopy control and the injection should immediately be stopped if venous leakage is observed.

The stylet should be repositioned before removal of the needle whenever possible in all cases. If the stylet could not be re-inserted, the needle is removed under fluoroscopy control to detect leak

International Guidelines
1. Society of Interventional Radiology Quality Improvement Guidelines for Percutaneous Vertebroplasty. J. Kevin McGraw, MD, John Cardella, MD, John Dean Barr, MD, John M. Mathis, MD, Orestes Sanchez, MD, Marc S. Schwartzberg, MD, Timothy L. Swan, MD, and David Sacks, MD, for the Society of Interventional Radiology Standards of Practice Committee. J Vasc Interv Radiol 2003; 14:S311–S315
2. Quality assurance guidelines for Percutaneous Vertebroplasty. Afshin Gangi, Tarun Sabharwal, Farah .G. Irani, Xavier B./www.cirse.org/files/File/07_qig.pdf
3. Interventional procedure overview of Percutaneous vertebroplasty (methyl methacrylate) December 2003. www.nice.org.uk/IP076overview

Pain Relief by Verteroplasty

Back stab: Percutaneous vertebroplasty for severe back pain.

Banerjee S, Baerlocher MO, Asch MR.Faculty of Medicine at the University of Ottawa in Ontario.

Can Fam Physician. 2007 Jul; 53(7):1169-75.

OBJECTIVE: To review the evidence supporting use of percutaneous vertebroplasty for relief of pain and mechanical stability in patients with vertebral compression fractures unrelieved by conventional measures.

QUALITY OF EVIDENCE:Ovid MEDLINE was searched from January 1966 to December2006 for all English-language papers on vertebroplasty. The quality of evidence in these papers was graded according to the 4-point classification system of evidence-based medicine. Level II evidence currently supports use of vertebroplasty.

MAIN MESSAGE: Vertebroplasty alleviates pain from vertebral compression fractures that result from osteoporosis, hemangiomas, malignancies, and vertebral osteonecrosis. Vertebroplasty has provided substantial pain relief in 60% to 100% of patients; has decreased analgesic use in 34% to 91% of patients; and has improved physical mobility in 29% to 100% of patients. Contraindications to vertebroplasty include asymptomatic compression fractures of the vertebral body, vertebra plana, retropulsed bone fragments or tumours, active infection, uncorrectable coagulopathy, allergy to the bone cement or opacification agent, severe cardiopulmonary disease, pregnancy, and pre-existing radiculopathy. The short-term complication rate was found to be 0.5% to 54%. Rare but serious complications include compression of the spinal cord or nerve root, infection, cement embolization causing pulmonary infarct and clinical symptoms, paradoxical embolization of the cerebral artery, and severe hematomas.

CONCLUSION:Vertebroplasty is a safe and effective treatment for vertebral fractures that cannot be treated using conservative measures.

Vertebroplasty, first 1000 levels of a single center: evaluation of the outcomes and complications.

Layton KF, Thielen KR, Koch CA, Luetmer PH, Lane JI, Wald JT, Kallmes DF.

AJNR Am J Neuroradiol. 2007 Apr; 28(4):683-9.

Department of Radiology, Mayo Clinic, Rochester, MN, USA.

BACKGROUND AND PURPOSE: We reviewed the experience with our first 1000 consecutively treated vertebral compression fractures in an attempt to demonstrate both the short- and long-term safety and efficacy of percutaneous vertebroplasty
.
MATERIALS AND METHODS: The first 1000 compression fractures treated by vertebroplasty at our institution were identified from a comprehensive prospectively acquired vertebroplasty data base. Statistical analysis was performed on the pain response and change in the Roland-Morris score at each follow-up time point. Significant procedure-related complications that occurred from the time of the procedures were also specifically extracted from the patients’ charts.

RESULTS: There was a dramatic improvement in all the evaluated parameters following percutaneous vertebroplasty. The improvement in pain, mobility, medication usage, and Roland-Morris score was noticed immediately after the procedure and persisted through the 2-year follow-up. There was a low rate of complications from the procedure, the most common being rib fractures.

Evaluation of vertebroplasty with a validated outcome measure: the Roland-Morris Disability Questionnaire.

Trout AT, Kallmes DF, Gray LA, Goodnature BA, Everson SL, Comstock BA, Jarvik JG. College of Medicine, Mayo Clinic, Rochester, MN 55905, USA.

AJNR Am J Neuroradiol. 2005 Nov-Dec;26(10):2652-7.

METHODS: Retrospective review of patients treated with vertebroplasty who completed the RDQ and 2 verbal pain scales (0-10) for pain at rest and pain with activity at baseline, 1 week, 1 month, 6 months, and 1 year post-vertebroplasty.

CONCLUSIONS: Patients who underwent vertebroplasty experienced relief of back pain and symptoms, as shown by improvement in verbal pain and RDQ scores. The RDQ correlates well with measures of pain, shows clinically significant improvement and is responsive to changes across time. More important, the RDQ provides an easily administered, well-validated, back pain-specific outcome measure that could be adopted to assess vertebroplasty outcomes.

Treatment of painful compression vertebral fractures with vertebroplasty: results and complications.

Anselmetti GC, Corgnier A, Debernardi F, Regge D. UOA di Radiologia, Istituto per la Ricerca e la Cura del Cancro, Candiolo, Turin.

Radiol Med (Torino). 2005 Sep; 110(3):262-72.

MATERIALS AND METHODS: Over an eleven-month period 49 patients underwent percutaneous vertebroplasty, of which seven were retreated, for a total of 56 operations on 108 vertebrae. The mean length of follow-up was 3.8 months.

RESULTS: One week after treatment all patients reported complete disappearance or significant alleviation of the pain. In 8 out of 49 patients (16.3%) there was a reoccurrence of pain; 7 of these patients underwent further treatment at another level with immediate pain relief. We only had one serious complication (1.7%) which involved the formation of a subcutaneous paravertebral haematoma, which was resolved in about a week. Eight patients (16.3%) developed transient pain at the site of the puncture or radiculopathy in the days following the operation. In 63 out of 108 of the treated vertebrae (58) there were small asymptomatic leakages of cement outside the vertebral body and in two asymptomatic patients (3.5%) the chest radiograph revealed a small pulmonary embolism of cement.

DISCUSSION: Our experience confirms the effectiveness of vertebroplasty in the treatment of pain caused by vertebral fractures. If the indications are respected the improvement of symptoms is often immediate, such as the return of mobility, and patient satisfaction with surgery is higher. The use of appropriate guiding systems limits the number of complications.

Percutaneous vertebroplasty compared with optimal pain medication treatment: short-term clinical outcome of patients with subacute or chronic painful osteoporotic vertebral compression fractures. The VERTOS study.

Voormolen MH, Mali WP, Lohle PN, Fransen H, Lampmann LE, van der Graaf Y, Juttmann JR,
Jansssens X, Verhaar HJ.Department of Radiology,
St Elisabeth Ziekenhuis, Tilburg

AJNR Am J Neuroradiol. 2007 Mar;28(3):555-60.

PURPOSE: To prospectively assess the short-term clinical outcome of patients with subacute or chronic painful osteoporotic vertebral compression fractures (VCF) treated with percutaneous vertebroplasty (PV) compared with optimal pain medication (OPM).

METHODS: Randomization of patients in 2 groups: treatment by PV or OPM. After 2 weeks, patients from the OPM arm could change therapy to PV.

CONCLUSION: Pain relief and improvement of mobility, function, and stature after PV is immediate and significantly better in the short term compared with OPM treatment.

Treatment of chronic symptomatic vertebral compression fractures with percutaneous vertebroplasty.

Brown DB, Gilula LA, Sehgal M, Shimony JS.

AJR Am J Roentgenol. 2004 Feb;182(2):319-22.

OBJECTIVE: Most fractures treated with percutaneous vertebroplasty are subacute and less than 1 year old. We report our experience treating chronic vertebral fractures with vertebroplasty.

CONCLUSION: Most patients with fractures more than 1 year old will experience clinical benefit from vertebroplasty. Complete relief of pain is more likely when less mature fractures are treated.

Level II evidence currently supports use of vertebroplasty. : Vertebroplasty alleviates pain from vertebral compression fractures that result from osteoporosis, hemangiomas, malignancies, and vertebral osteonecrosis.
Vertebroplasty has provided substantial pain relief in 60% to 100% of patients; has decreased analgesic use in 34% to 91% of patients; and has improved physical mobility in 29% to 100% of patients.

Complications in Vertebroplasty

unusual Presentation of Infected Vertebroplasty with Delayed Cement Dislodgment in an Immunocompromised Patient: Case Report and Review of Literature.

Lin WC, Lee CH, Chen SH, Lui CC.

Cardiovasc Intervent Radiol. 2007 Dec 13

Complications of vertebroplasty, such as infection or anterior cement extrusion, are rare. Herein, we report an unusual presentation in an immunocompromised patient with an insidious infection of the disk. This infection resulted in dislodgment of the cement inferiorly and a compression fracture of the adjacent vertebra 6 months after vertebroplasty. We discuss the significance of this case and compare it with 7 others found in the literature.

J Vasc Interv Radiol. 2007 Oct; 18(10): 1333-4.

Percutaneous vertebroplasty causing an increase in retropulsion of bone fragments. Kallmes DF.

Local metastases along the tract of needle: a rare complication of vertebroplasty in treating spinal metastases.

Chen YJ, Chang GC, Chen WH, Hsu HC, Lee TS.

Spine. 2007 Oct 1; 32(21):E615-8.

OBJECTIVE: We report local metastases along the needle tract as a rare complication of percutaneous vertebroplasty in treating spinal metastases in a lung cancer patient. SUMMARY OF BACKGROUND DATA: The true incidence of tumor implantation along the needle tract may be underestimated as many patients die before the metastases become clinically significant.

METHODS: A 76-year-old man diagnosed with adenocarcinoma of lung underwent percutaneous vertebroplasty at L1 and L3 vertebral levels due to painful spinal metastases. His condition worsened 3 months later, however, with recurrent back pain and weakness of both legs.

CONCLUSION: However, this may be a potential complication of vertebroplasty in treating spinal metastases as improvement in cancer treatments occurs with subsequent longer survival times.

Aortic aneurysm complicated with pyogenic spondylitis following vertebroplasty.

Kwak HJ, Lee JK, Kim YS, Moon KS, Joo SP, Kim JH, Kim SH, Chang WC.

J Clin Neurosci. 2008 Jan; 15(1):89-93. Epub 2007 Sep 19

However, infectious complications can be serious. We present a patient in whom pyogenic spondylitis developed 3 months after vertebroplasty. During the debridement, profuse bleeding was encountered from injury to the aorta and the patient was managed with primary closure. Two months after the initial surgery, an aortic aneurysm was detected. A wide resection of all infected tissue, including the bony lesion and aortic aneurysm was performed, and the descending thoracic aorta was replaced with a vascular graft. A titanium mesh cage filled with bone graft was employed for anterior reconstruction. Our patient illustrates that a life-threatening aortic aneurysm can indeed occur as an infectious complication of this minimally invasive procedure due to the proximity of the aorta to the thoracolumbar vertebra.

J Bone Joint Surg Am. 2007 Aug; 89(8):1827-31.

Acute paraplegia after vertebroplasty caused by epidural hemorrhage. A case report.Birkenmaier C, Seitz S, Wegener B, Glaser C, Ruge MI, von Liebe A, von SchulzePellengahr C.Department of Orthopedic Surgery, Grosshadern Medical Center, University of Munich, Marchioninistrasse 15, 81377 Munich, Germany.

Pulmonary cement embolism after percutaneous vertebroplasty: a rare and nonthrombotic cause of pulmonary embolism.

Bonardel G, Pouit B, Gontier E, Dutertre G, Mantzarides M, Goasguen O, Foehrenbach H.

Clin Nucl Med. 2007 Aug; 32(8):603-6.

We present the case of a patient with pulmonary cement embolism after percutaneous vertebroplasty. Because such patients may be completely asymptomatic, but may also present with acute and severe, cardiovascular instability, clinicians and nuclear physicians should be aware that pulmonary embolism of polymethylmethacrylate may occur after percutaneous vertebroplasty.

Delayed presentation of pulmonary polymethylme-thacrylate emboli after percutaneous vertebroplasty.

Abdul-Jalil Y, Bartels J, Alberti O, Becker R.

Spine. 2007 Sep 15; 32(20):E589-93.

STUDY DESIGN: Literature review concerning pulmonary embolism of polymethylmethacrylate (PMMA) material following percutaneous vertebroplasty and a report on 2 new cases.

OBJECTIVE: To inform clinicians about delayed clinical manifestation of pulmonary embolism of polymethylmethacrylate material after percutaneous vertebroplasty, pathophysiology, precautions, and therapeutic management of this complication.

CONCLUSION: The risk of pulmonary embolism of PMMA might be underestimated. We propose routine chest radiograph following every vertebroplasty, in order to detect pulmonary PMMA embolism and thereby prevent serious delayed cardiopulmonary failures.

An intraatrial thrombus and pulmonary thromboembolism as a late complication of percutaneous vertebroplasty.

Lim KJ, Yoon SZ, Jeon YS, Bahk JH, Kim CS, Lee JH, Ha JW.

Anesth Analg. 2007 Apr;104(4):924-6.

We report a patient who presented with dyspnea and edema five years after percutaneous vertebroplasty and underwent open-heart surgery. This case demonstrates an intraatrial thrombus and pulmonary thromboembolism caused by venous leakage of polymethylmethacrylate as a late complication of the procedure.

Padovani B, Kasriel O, Brunner P, Peretti-Viton P.Department of Radiology, Hôpital Pasteur, Nice, France.

AJNR Am J Neuroradiol. 1999 Mar;20(3):375-7.

This rare complication occurred because perivertebral venous migration was not recognized during vertebroplasty. Adequate preparation of cement and biplane fluoroscopy are recommended for vertebroplasty.

Pulmonary cement embolism: a complication of percutaneous vertebroplasty.

Duran C, Sirvanci M, Aydoðan M, Ozturk E, Ozturk C, Akman C.

Acta Radiol. 2007 Oct; 48(8):854-9.

PURPOSE: To determine the frequency of pulmonary cement embolism after percutaneous vertebroplasty.

MATERIAL AND METHODS: Between 2002 and 2006, 128 percutaneous vertebroplasties were performed in 73 patients (56 women and 17 men) in our institution. Postprocedural chest radiographs were obtained for all patients and assessed for the presence of pulmonary cement emboli.

RESULTS: Pulmonary cement embolism was detected on chest radiographs and confirmed with chest computed tomography (CT) in four patients treated with percutaneous vertebroplasty for osteoporotic collapse and one patient treated for multiple myeloma. The imaging finding of pulmonary cement embolism was solitary or multiple fine radiodense lines with occasional branching patterns. The frequency of pulmonary cement embolism was 6.8%.

CONCLUSION: An incidence of pulmonary cement embolism of 6.8% during PV was found. Close clinical follow-up, postprocedural chest radiographs, and chest CT scans, if necessary, are important for the detection of pulmonary cement embolism at an early stage.

Pulmonary embolism of polymethyl methacrylate during percutaneous vertebroplasty and kyphoplasty.

Choe DH, Marom EM, Ahrar K, Truong MT,
Madewell JE.

AJR Am J Roentgenol. 2004 Oct;183(4):1097-102.

Department of Radiology, Box 57, Division of Diagnostic Imaging, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030,

USA.OBJECTIVE: The purpose of this study was to determine the frequency, radiographic findings, and clinical significance of a pulmonary embolism of cement occurring during percutaneous vertebroplasty or kyphoplasty as detected on conventional chest radiography.

RESULTS: The emboli of cement were noted radiographically in three (4.6%) of 65 procedures performed in our institution. All patients with cement emboli had multiple myeloma. The chest radiographic findings were multiple radiographically dense opacities with a tubular and branching shape that were scattered sporadically or distributed diffusely throughout the lungs. All patients with cement pulmonary embolism remained asymptomatic. A correlation of embolism of cement to lungs was found with paravertebral venous cement leak (p < 0.001) but not with the number of vertebral bodies treated (p = 0.185) or with the type of procedure performed-kyphoplasty versus vertebroplasty (p = 0.98).

CONCLUSION: Pulmonary embolism of cement is seen in 4.6% of patients after percutaneous vertebroplasty or kyphoplasty. The characteristic radiographic findings should be recognized by radiologists.

Aortic embolism of cement: a rare complication of lumbar percutaneous vertebroplasty.

Amoretti N, Hovorka I, Marcy PY, Grimaud A, Brunner P, Bruneton JN.

Skeletal Radiol. 2007 Jul; 36(7):685-7. Epub 2007 Mar 30.

This rare complication occurred because the collateral arterial supplies to the breast metastasis and the retrograde migration of cement during the vertebroplasty were not recognized. Proper techniques can minimize the risk of arterial embolism caused by cement during the procedure.

Cement embolization into the vena cava and pulmonal arteries after vertebroplasty: interdisciplinary management.

Baumann A, Tauss J, Baumann G, Tomka M, Hessinger M, Tiesenhausen K.

Eur J Vasc Endovasc Surg. 2006 May; 31(5):558-61. Epub 2005 Dec 22.

Department of Vascular Surgery, University Hospital Graz, Graz, Austria. PURPOSE: To report interdisciplinary management in a case of cement embolization into the inferior vena cava and peripheral pulmonary arteries after percutaneous vertebroplasty. CASE REPORT: A 50-year-old female patient with an osteoporotic compression fracture of the second lumbar vertebra underwent percutaneous

Vertebroplasty with polymethylmetaacrylate. Thereafter, CT scanning revealed small asymptomatic cement emboli in peripheral pulmonary arteries, along with hook-shaped cement fragment in the inferior vena cava. Due to the risk that the large cement fragment could migrate to the pulmonary arteries and cause serious complications, they were retrieved from the inferior vena cava by an endovascular technique and extracted through a surgical groin incision. The patient received anticoagulant treatment for 3 months and is free of complaints after 1 year.

CONCLUSION: This case shows that this rare complication following vertebroplasty can be successfully managed with an interdisciplinary approach.

Renal cement embolism during percutaneous vertebroplasty.

Chung SE, Lee SH, Kim TH, Yoo KH, Jo BJ.

Eur Spine J. 2006 Oct; 15 Suppl 5:590-4. Epub 2005 Dec 14.

Department of Diagnostic Radiology, Wooridul Spine Hospital, Seoul, Republic of Percutaneous vertebroplasty (PVP) is an effective treatment for lesions of the vertebral body that involves a percutaneous injection of polymethylmethacrylate (PMMA). Although PVP is considered to be minimally invasive, complications can occur during the procedure. We encountered a renal embolism of PMMA in a 57-year-old man that occurred during PVP. This rare case of PMMA leakage occurred outside of the anterior cortical fracture site of the L1 vertebral body, and multiple tubular bone cements migrated to the course of the renal vessels via the valveless collateral venous network surrounding the L1 body. Although the authors could not explain the exact cause of the renal cement embolism, we believe that physicians should be aware of the fracture pattern, anatomy of the vertebral venous system and careful fluoroscopic monitoring to minimize the risks during the PVP.

FAT EMBOLISM

Fatal fat embolism after vertebroplasty: identification of the high-risk patient.

Syed MI, Jan S, Patel NA, Shaikh A, Marsh RA,
Stewart RV.

AJNR Am J Neuroradiol. 2006 Feb; 27(2):343-5.

Department of Radiology, Mercy Medical Center, Springfield, Ohio 45501-1308, USA.We report a rare complication of autopsy-proven fat and bone marrow embolization following percutaneous vertebroplasty in a patient who had no evidence of cement leakage. Cement injection was done during one patient encounter, covering 3 vertebral levels by using a unipedicular approach. Patients may have complications even without polymethylmethacrylate leakage.

Infected vertebroplasty due to uncommon bacteria solved surgically: a rare and threatening life complication of a common procedure: report of a case and a review of the literature.

Alfonso Olmos M, Silva González A, Duart Clemente J, Villas Tomé C.

Spine. 2006 Sep 15; 31(20):E770-3.

STUDY DESIGN: Case report.

OBJECTIVE: The aim of this work is to describe a case of infected vertebroplasty due to uncommon bacteria solved surgically with 2 years of follow-up and to discuss 6 other cases found in literature.

RESULTS: After 2 years of follow-up, the patient was free of pain, without signs of infection, and a correct fusion was achieved.

CONCLUSION: When facing an infected vertebroplasty, initial conservative treatment with needle biopsy culture and antibiotic administration are a rational option to start. If this treatment fails, surgical debridement is then indicated in order to remove the infected tissue and the acrylic cement and to stabilize the spine. Although this can be an effective treatment, it could be a difficult and hazardous surgical procedure.

Infected vertebroplasty requiring 360 degrees spinal reconstruction: long-term

J Neurosurg Spine. 2006 Jul; 5(1):86-9.

Follow-up review. Report of two cases.

Mummaneni PV, Walker DH, Mizuno J, Rodts GE.

Emory Spine Center, Emory University, Atlanta, Georgia 30329, USA. Transpedicular vertebroplasty has been established as a safe and effective treatment of thoracic and lumbar compression fractures. Complications are rare, and infectious complications requiring surgical management have only been reported once in the literature. The authors present two cases of infectious complications requiring surgical management. They emphasize that systemic infection is a contraindication to the performance of vertebroplasty. The serious nature of these infections, their surgical management, and strategies for avoiding them are discussed.

Intradural cement leakage: a devastatingly rare complication of vertebroplasty.

Chen YJ, Tan TS, Chen WH, Chen CC, Lee TS.

Spine. 2006 May 20;31(12):E379-82.

STUDY DESIGN: The aim of this case report is to examine the devastating complication that may follow vertebroplasty.

METHODS: A 90-year-old woman with a T12 and L1 osteoporotic compression fracture underwent percutaneous vertebroplasty using polymethyl methacrylate at local hospital. A literature search was performed to assess complications of vertebroplasty.RESULTS: She was transferred to our hospital due to abdominal pain. Physical examination revealed distended abdomen with local tenderness and weakness of both legs (muscle power: Grade 2). Plain radiograph of abdomen showed ileus and intradural cement leakage. Conservative treatment with nasogastric decompression was done, and her abdominal pain subsided 1 week later.

CONCLUSIONS: The needle tip should not cross the medial border of the pedicle on the anteroposterior view before it has crossed the posterior cortex of the vertebral body on the lateral view. Good quality of image monitoring and clear visualization of cement should be helpful to prevent complications.

Reported complications of this procedure were uncommon. They included damage to neural or other structures by needle misplacement or migration of cement. One study observed cement leakage in up to 27% of patients. However, this event was often without sequelae and required further intervention in only 1% of patients in that study.
It is important to note that in skilled and experienced hands with optimal image guidance vertebroplasty has been demonstrated to be a safe and effective procedure. Proper case selection and planning is important.

Intra Discal Leakage /Intraforaminal Leakage

Combined extraforaminal and intradiscal cement leakage following percutaneous vertebroplasty.

Chen JK, Lee HM, Shih JT, Hung ST.Department of Orthopaedic Surgery, Armed Forces Taoyuan General Hospital,Taoyuan, Taiwan, Republic of China.

Spine. 2007 May 20;32(12):E358-62.

STUDY DESIGN: A case report and review of the literature are presented.

METHODS: A 78-year-old woman with L2 and L5 osteoporotic compression fractures received vertebroplasty. Two weeks after surgery, the patient presented severe low back pain radiating to the right thigh, with associated weakness and numbness in the right thigh and lower leg. Roentgenographic images revealed cement leakage into the right extraforamen of L2-L3 as well as leakage into L4-L5 disc with acute adjacent compression fracture of L4.

CONCLUSION: Although considered a minimally invasive procedure, percutaneous

vertebroplasty with polymethylmethacrylate is not risk free. Intractable neurologic complications can occur if it is not performed by experienced physicians under appropriate indications and cautionary safeguards.

Vertebroplasty: cement leakage into the disc increases the risk of new fracture of adjacent vertebral body.

Lin EP, Ekholm S, Hiwatashi A, Westesson PL.

AJNR Am J Neuroradiol. 2004 Feb;25(2):175-80.

BACKGROUND AND PURPOSE: Patients successfully treated with vertebroplasty often return with new pain caused by a new vertebral body fracture. The new fractures often are adjacent to the vertebral bodies that were initially treated. In our clinical work, we have observed that cement leakage into the disk increases the risk of new fracture of the adjacent vertebral body. This study analyzed the risk of new fractures of adjacent vertebral bodies in relationship to cement leakage into the disk.

RESULTS: Fourteen patients developed new fractures during the follow-up period. In 10 patients, the new fractures were associated with cementleakage into the disk, whereas four patients had new fractures that were not associated with cement leakage into the disk. This difference was statistically significant (P =.018). A detailed analysis showed that 58% of vertebral bodies adjacent to a disk with cement leakage fractured during the follow-up period compared with 12% of vertebral bodies adjacent to a disk without cement leakage (P <.0005).

CONCLUSION: Leakage of cement into the disk during vertebroplasty increases the risk of a new fracture of adjacent vertebral bodies.

The risk of new osteoporotic vertebral compression fractures in the year after percutaneous vertebroplasty.

Voormolen MH, Lohle PN, Juttmann JR, van der Graaf Y, Fransen H, Lampmann LE.

J Vasc Interv Radiol. 2006 Jan; 17(1):71-6.

PURPOSE: To prospectively assess the incidence, location, and possible causative mechanisms of new vertebral compression fractures (VCFs) in 66 symptomatic patients with osteoporotic VCFs treated with percutaneous vertebroplasty (PV) and to study the relation between new VCFs and back pain symptoms.

RESULTS: Sixteen of 66 patients had 26 new VCFs during 1 year of follow-up after PV. Most new VCFs occurred within 3 months of PV, half of new VCFs appeared in levels adjacent to treated levels, and half of the new VCFs were symptomatic. The presence of more than two preexisting VCFs was the only independent risk factor for the development of a new VCF.

CONCLUSIONS: New VCFs occurred after PV in 24% of patients. Half of new VCFs occurred in levels adjacent to treated levels and half were symptomatic. The presence of more than two preexisting VCFs was the only independent risk factor for the development of a new VCF.

l Leakage of cement into the disk during vertebroplasty increases the risk of a new fracture of adjacent vertebral bodies.
l Although considered a minimally invasive procedure, percutaneous vertebroplasty with polymethylmethacrylate is not risk free. Intractable neurologic complications can occur if it is not performed by experienced physicians under appropriate indications and cautionary safeguards.

Vertebroplasty In Hemangioma

Comprehensive management of symptomatic and aggressive vertebral hemangiomas.

Acosta FL Jr, Sanai N, Chi JH, Dowd CF, Chin C, Tihan T, Chou D, Weinstein PR, Ames CP.

Neurosurg Clin N Am. 2008 Jan;19(1): 17-29.

Conservative surgical strategies are appropriate for most symptomatic hemangiomas causing cord compression without instability or deformity. Even so, complete intralesional spondylectomy following embolization of aggressive vertebral hemangiomas with circumferential vertebral involvement can be safely accomplished. Such a spondylectomy can also prevent recurrence of hemangiomas.Transarterial embolization without decompression is an effective treatment for painful intraosseous hemangiomas. Vertebroplasty is useful for improving pain symptoms, especially when vertebral body compression fracture has occurred in patients without neurological deficit, but is less effective in providing long-term pain relief.

Current treatment strategies and outcomes in the management of symptomatic vertebral hemangiomas

Acosta FL Jr, Dowd CF, Chin C, Tihan T, Ames CP, Weinstein PR.

Neurosurgery. 2006 Feb; 58(2):287-95; discussion 287-95.

OBJECTIVE: We analyzed the outcome of patients with symptomatic vertebral hemangiomas treated at University of California, San Francisco, over a 20 year period. Treatment included transarterial embolization, embolization followed by surgical decompression or vertebral reconstruction with arthrodesis, and percutaneous vertebroplasty alone.

CONCLUSION: Transarterial embolization followed by laminectomy is a safe and effective procedure for the treatment of cord compression by vertebral hemangioma causing stenosis without instability or deformity. Vertebroplasty preceded by embolization and followed by reconstruction can be used to treat cord compression from extraosseous tumor extension. Transarterial embolization without decompression is an effective treatment for painful intraosseous hemangiomas.

Treatment of vertebral hemangioma with percutaneous vertebroplasty

Yang XJ, Wu ZX, Zhao JF, Zhang YP, Song L, He HW, Lin X.

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2004 Dec; 26(6):643-6.

OBJECTIVE: To investigate the efficacy of percutaneous vertebroplasty in the treatment of vertebral hemangioma.

METHODS: Seven patients with vertebral hemangiomas were treated by percutaneous vertebroplasty, including one case of cervical, three cases of thoracic, and three cases of lumbar hemangiomas.

RESULTS: Good results were achieved in all the seven cases. Pain was completely relieved in 5 cases and partially relieved in 2 cases. Symptom was also recovered in 2 patients with radiculopathy. No recurrence was found after 1-9 months of postoperative follow-up.

CONCLUSION: Treatment of vertebral hemangioma with percutaneous vertebroplasty is safe and effective with minimal invasion.

Vertebroplasty in the treatment of back pain.

Muto M, Muto E, Izzo R, Diano AA, Lavanga A, Di Furia

Radiol Med (Torino). 2005 Mar; 109(3):208-19.

PURPOSE: The aim of this study is to show the utility of vertebroplasty in the treatment of some types of back pain. Vertebroplasty is a venous embolisation of the vertebral body performed under computed tomography (CT) or fluoroscopy guidance with transpedicular, anterolateral, intercostovertebral or posterolateral approach with acrylic cement.
MATERIALS AND METHODS: We report our experience in 85 patients suffering from low back and thoracic pain and treated with percutaneous vertebroplasty owing to osteoporotic vertebral compression fractures, vertebral haemangiomas or secondary lytic lesions of the spine. The amount of cement injected ranged from 4 ml (thoracic level) up to 12 ml (lumbar level).

RESULTS: The results were better for osteoporotic cases (95%) and patients with vertebral haemangioma (90%) than with metastatic lesions (77%), with improvement within24-72 hours after the treatment.

DISCUSSION AND CONCLUSIONS: Since the first case of vertebroplasty was used in vertebral haemangioma, the possibility of using this technique in other pathological conditions such as metastatic lesions and osteoporotic compression fractures has been clear. MR has a key role in the selection of patients while bone scan and CT can be useful in selected cases. Absolute controindication is local or systemic infection while relative controindications are epidural.

Cement vertebroplasty combined with ethanol injection in the treatment of vertebral hemangioma.

Chen L, Zhang CL, Tang TS.

Chin Med J (Engl). 2007 Jul 5; 120(13): 1136-9.

BACKGROUND: A number of methods have been used in the treatment of symptomatic and aggressive vertebral hemangioma, but none of them is optimal. Vertebral hemangioma treated with cement vertebroplasty or ethanol injection alone showed relatively good results despite their limitations.

RESULTS: The average score of back pain significantly decreased from 6.5 before operation to 1.7 one month after operation. No severe complications occurred during and after operation. During the period of follow-up, symptoms were not deteriorated. At the end of follow-up, neither radiographic sign of aggressive destruction nor collapse of the involved vertebra was observed. Significant improvement in the 12 patients was demonstrated on 7 of 8 SF-36 Health Scale except for mental health.

CONCLUSIONS: Cement vertebroplasty combined with ethanol injection as a safe and effective technique is an alternative to the treatment of patients with vertebral hemangioma.

Vertebroplasty preceded by embolization and followed by reconstruction can be used to treat cord compression from extraosseous tumor extension. Transarterial embolization without decompression is an effective treatment for painful intraosseous hemangiomas. Vertebroplasty is useful for improving pain symptoms, especially when vertebral body compression fracture has occurred in patients without neurological deficit.
Treatment of vertebral hemangioma with percutaneous vertebroplasty is safe and effective with minimal invasion.
Cement vertebroplasty combined with ethanol injection as a safe and effective technique is an alternative to the treatment of patients with vertebral hemangioma.

Vertebroplasty in Sclerotic Lesions

Osteoblastic and mixed spinal metastases: evaluation of the analgesic efficacy of percutaneous vertebroplasty.

Calmels V, Vallée JN, Rose M, Chiras J.

AJNR Am J Neuroradiol. 2007 Mar;28(3):570-4.

PURPOSE: To determine the analgesic efficacy of percutaneous vertebroplasty in treating osteoblastic and mixed spinal metastases.

RESULTS: The analgesic efficacy rate was 86% at 1 month and 92% at 6 months. In mostcases, it was stable. It was correlated with vertebral filling quality (Fisher test, P = .0932 at 1 month follow-up) but neither with filling volume (Mann-Whitney test, P = .143 at 1 month) nor with the vertebral structure, pure blastic or mixed (Fisher test, P = .784 at 1 month). There were 5 filling failures (4.7%) whose occurrence was correlated with the pure blastic structure of the vertebra (Mann-Whitney test, P = .033). Local clinical complications were observed in 5 cases (8.5%): 1 transitory radiculalgia (1.7%), 2 durable radiculalgias (3.4%), 1 cauda equina syndrome (1.7%), and 1 hemothorax (1.7%). General clinical complications were 2 pulmonary embolisms (3.4%).

CONCLUSION: Vertebroplasty for osteoblastic and mixed metastases allows, with a well-trained operator, a satisfactory anesthesia with acceptable clinical complication rates.

Percutaneous vertebroplasty in the treatment of blastic vertebral column metastasis from breast cancer.

Murphy KJ, Nwankwo IJ, Gailloud P.

J Vasc Interv Radiol. 2007 Feb;18(2):321-3.

Vertebroplasty for osteoblastic and mixed metastases allows, with a well-trained operator, a satisfactory pain relief with acceptable clinical complication rates.

Number of Vertebrae to treat in one session

Osteoporotic compression fractures: outcomes after single-versus multiple-level percutaneous vertebroplasty.

Singh AK, Pilgram TK, Gilula LA.

Radiology. 2006 Jan; 238(1):211-20.

MATERIALS AND METHODS: One hundred seventy-three patients (mean age at treatment, 73.8 years +/- 11.9 [standard deviation]) with 422 symptomatic osteoporotic VCFs underwent 204 treatment sessions for over 4 years. Pain immediately before and after PV was measured by using a visual analogue scale (VAS). Pain degree, activity level, and analgesic use were assessed at 2 weeks and 1, 3, 6, 12, and 24 Data were analyzed by using a combination of paired t tests, analysis of variance, contingency tables, and chi2 tests.

RESULTS: Findings of 172 PV treatment sessions for 149 patients (mean age at treatment, 73.4 years +/- 12), 110 (74%) of whom were women, were assessed; 32 treatment cases were lost to follow-up or lost owing to death. A single fracture level was treated at 65 sessions; two fracture levels, at 52 sessions; and three or more fracture levels, at 55 sessions. The mean VAS pain score decreased significantly (P < .001), from 76 +/- 21 before to 19 +/- 27 immediately after PV. Of the outcomes reported at 24 months, 82% (64 of 78 treatment sessions) were marked to complete resolution of the initial pain, 51% were complete cessation of analgesic use, and 51% were increased activity levels. These results did not differ greatly over time or when stratified into groups according to the number of fracture levels treated.

CONCLUSION: PV performed at a single fracture level and that performed at multiple fracture levels were equally effective in facilitating long-term pain relief, increased activity level, and decreased analgesic use in patients with osteoporotic VCFs.

Effect on partial pressure of oxygen in arterial blood in percutaneous vertebroplasty.

Uemura A, Numaguchi Y, Matsusako M, Kobayashi N, Saida Y, Rahman M.

AJNR Am J Neuroradiol. 2007 Mar;28(3):567-9.

BACKGROUND AND PURPOSE: The purpose of this study is to estimate the change in partial pressure of oxygen (PaO2) during percutaneous vertebroplasty and also to examine the factors related to the change in PaO2.

MATERIALS AND METHODS: The difference between preprocedural and postprocedural data of PaO2 was correlated with patients’ age, number of treated vertebral bodies, presence of cement leakage, and presence of malignant neoplasm for each patient.

CONCLUSION: PaO2 decreases during percutaneous vertebroplasty, and there is a correlation between the number of treated vertebral bodies and decrease in PaO2.

Quantity of Bone Cement to be used

The effects of cement volume on clinical outcomes of percutaneous vertebroplasty.

Kaufmann TJ, Trout AT, Kallmes DF.Department of Radiology, Mayo Clinic, Rochester, MN, USA.

AJNR Am J Neuroradiol. 2006 Oct; 27(9):1933-7.

BACKGROUND AND PURPOSE: There exists significant variability in the volume of polymethylmethacrylate cement injected during percutaneous vertebroplasty. Larger cement volumes injected may be associated with better clinical outcomes, but larger volumes may also be associated with greater risk of complications related to cement leakage. We describe an analysis of the association between clinical and procedural variables, including cement volume injected, and the clinical outcomes of patients treated with single-level vertebroplasty.

RESULTS: There was no significant association between the volume of cement injected and the clinical outcomes of postprocedure pain (P = .159-.871) and medication use (P = .223-.875).

CONCLUSION: Vertebroplasty operators need not feel compelled to achieve particular cement volumes injected in the pursuit of better clinical outcomes but should strive to achieve the maximal safe filling of individual vertebral bodies.

Kyphoplasty and Vertebroplasty

Significantly reduced radiation exposure to operators during kyphoplasty and vertebroplasty procedures: methods and techniques.

Ortiz AO, Natarajan V, Gregorius DR, Pollack S.

AJNR Am J Neuroradiol. 2006 May;27(5):989-94.

BACKGROUND AND PURPOSE: Vertebroplasty and kyphoplasty can be associated with significant radiation exposure to the operator. We compared the exposure levels to an operator performing vertebral fracture augmentation with vertebroplasty and kyphoplasty, to assess a cement injection and a monitoring technique designed to reduce this exposure.

Comparison of vertebroplasty and balloon kyphoplasty for treatment of vertebral compression fractures: a meta-analysis of the literature.

Eck JC, Nachtigall D, Humphreys SC, Hodges SD.

Spine J. 2007 May 29

STUDY DESIGN: A meta-analysis of the literature on effectiveness of pain control and risk of complications after vertebroplasty versus balloon kyphoplasty. Outcomes measures include visual analog scale and complications.

RESULTS: A total of 1,036 abstracts were identified. Of these, 168 studies met the inclusion criteria. Mean pre- and postoperative VAS scores for vertebroplasty were 8.36 and 2.68, respectively, with a mean change of 5.68 (p<.001). The mean pre- and postoperative VAS scores for kyphoplasty were 8.06 and 3.46, respectively, with a mean change of 4.60 (p<.001). There was statistically greater improvement found with vertebroplasty versus kyphoplasty (p<.001). The risk of new fracture was 17.9% with vertebroplasty versus 14.1% with kyphoplasty (p<.01). The risk of cement leak was 19.7% with vertebroplasty versus 7.0% with kyphoplasty (p<.001).

CONCLUSIONS: Both vertebroplasty and kyphoplasty provided significant improvement in VAS pain scores. Vertebroplasty had a significantly greater improvement in pain scores but also had statistically greater risk of cement leakage and new fracture.

Neurosurgery. 2007 Mar 15 [Epub ahead of print]

Balloon Kyphoplasty In Severe Osteoporotic Compression Fracture: Is It A Contraindication?

Kim HS, Ju CI, Kim SW, Lee SM, Shin H.

OBJECTIVE: Severe vertebral body collapse is considered by most authors as a contraindication to vertebroplasty because of technical difficulties. Moreover,balloon kyphoplasty is significantly difficult to perform in cases with severe compression fractures. The purpose of this study is to determine the efficacy of kyphoplasty after the combination of postural reduction and intraoperative correction of kyphotic angle for reexpansion and stabilization of severely collapsed osteoporotic compression fracture.

METHODS: Twenty-four patients underwent balloon kyphoplasty after preoperative postural reduction using a soft roll at the involved vertebra and intraoperative correction of kyphotic angle using chest and pelvic bolsters in the severely collapsed vertebrae of greater than two-thirds loss of their original heights. Imaging and clinical features were analyzed, including involved vertebra level, vertebral height, injected cement volume, clinical outcome, and complications.
RESULTS: The mean Cobb angle was 17.0 +/- 8.10 degrees and was corrected to 10.5 +/- 9.0 degrees. Kyphotic angle improved significantly from 11.8 +/- 6.1 degrees before surgery to 4.4 +/- 4.7 degrees after surgery. Anterior and middle vertebral height increased significantly. The fraction of vertebral body height increased from 25 to 50% and 40 to 57% in the anterior and middle portions, respectively. The mean pain score (visual analog scale) before kyphoplasty was 8.3, which changed to 3.1 after the procedure. Cement leakage to the adjacent disc (five cases) and paravertebral soft tissues (four cases) developed without major complications.

CONCLUSION: This new method of balloon kyphoplasty after postural reduction and intraoperative correction of kyphotic angle is safe and effective for treating severe osteoporotic compression fracture. We propose that severely collapsed vertebrae that are able to reexpand by postural reduction and the correction of kyphotic angle is not a contraindication to balloon kyphoplasty.

Percutaneous vertebroplasty and kyphoplasty for painful vertebral body fractures in cancer patients.

Fourney DR, Schomer DF, Nader R, Chlan-Fourney J, Suki D, Ahrar K, Rhines LD, Gokaslan ZL.

J Neurosurg. 2003 Jan; 98(1 Suppl):21-30.

OBJECT: The current North American experience with minimally invasive vertebro-and kyphoplasty is largely limited to the treatment of benign osteoporotic compression fractures. The objective of this study was to assess the safety and efficacy of these procedures for painful vertebral body (VB) fractures in cancer patients.

METHODS: The authors reviewed a consecutive group of cancer patients (21 with myeloma and 35 with other primary malignancies) undergoing vertebro- and kyphoplasty at their institution. Ninety-seven (65 vertebro- and 32 kyphoplasty) procedures were performed in 56 patients during 58 treatment sessions. The mean patient age was 62 years (+/- 13 years [standard deviation]) and the median duration of symptoms was 3.2 months. All patients suffered intractable spinal pain secondary to VB fractures. Patients noted marked or complete pain relief after 49 procedures (84%), and no change after five procedures (9%); early postoperative Visual Analog Scale (VAS) pain scores were unavailable in four patients (7%). No patient was worse after treatment. Reductions in VAS pain scores remained significant up to 1 year (p = 0.02, Wilcoxon signed-rank test). Analgesic consumption was reduced at 1 month (p = 0.03, Wilcoxon signed-rank test). Median follow-up length was 4.5 months (range 1 day-19.7 months).

Asymptomatic cement leakage occurred during vertebroplasty at six (9.2%) of 65 levels; no cement extravasation was seen during kyphoplasty. There were no deaths or complications related to the procedures. The mean percentage of restored VB height by kyphoplasty was 42 +/- 21%.

CONCLUSIONS: Percutaneous vertebro- and kyphoplasty provided significant pain relief in a high percentage of patients,and this appeared durable over time. The absence of cement leakage-related complications may reflect the use of 1) high-viscosity cement; 2) kyphoplasty in selected cases; and 3) relatively small volume injection. Precise indications for these techniques are evolving; however, they are safe and feasible in well-selected patients with refractory spinal pain due to myeloma bone disease or metastases.

Vertebroplasty versus kyphoplasty: biomechanical behavior under repetitive loading conditions.

Kim MJ, Lindsey DP, Hannibal M, Alamin TF.

Spine. 2006 Aug 15; 31(18):2079-84.

Height was restored with kyphoplasty, but the vertebral bodies showed significant height loss during cyclic loading. Vertebroplasty specimens had higher compression stiffness and smaller height reduction.

CONCLUSIONS: Under repetitive loading conditions, fractured vertebral bodies treated with kyphoplasty were initially taller, but because of a progressive loss of height during loading, the resulting constructs were shorter after 100,000 cycles than those treated with vertebroplasty.

Both vertebroplasty and kyphoplasty provided significant improvement in VAS pain scores. Vertebroplasty had a significantly greater improvement in pain scores but also had statistically greater risk of cement leakage and new fracture.
Severely collapsed vertebrae that are able to reexpand by postural reduction and the correction of kyphotic angle is not a contraindication to balloon kyphoplasty.

Management of painful skeletal Metastasis: RFA / Embolisation / Cementoplasty

Management of painful skeletal metastasis causing pain due to direct tumor involvement is a relenting task which needs a multi speciality involvement. As with other pain syndromes pharmacological treatment is the first line. Surgical decompression, denervation may be required in a few cases. Image guided therapy has provided a minimally invasive approach to these cases. Various options that may be available include embolisation, ablation (thermal / chemical) and cementoplasty. Chemotherapy and pharmacological analgesia may also be used as an adjuvant.

Ablative therapy for metastasis

Alcohol Ablation

Injection of alcohol is widely used in tumor management and pain treatment (neurolysis). Tumor invasion of bone, from either a primary or a meta-static lesion, is the most common cause of pain in cancer patients. Usually, the pain is controlled by high doses of opiate and by radiotherapy and/or chemotherapy. The aim of Alcoholization of bone metastasis is to treat cancer patients with excruciating and poorly controlled pain.

Possible mechanisms that may cause pain from bone metastases include the following:

• Stimulation of nerve endings in the endosteum by chemical agents released from the destroyed bone tissue such as prostaglandins, bradykinin, substance P, or histamine
• Stretching of periosteum by increasing the size of the tumor,
• Fractures,
• Tumor growth into surrounding nerves and tissues.

Stimulation of nerve endings in the endosteum by chemical agents released from the destroyed bone tissue is probably the main cause of bone pain from small metastases; as metastases enlarge, stretching of the periosteum additionally contributes to the pain.

Percutaneous alcoholization of bone metastasis is well suited in patients with extremely painful osteolytic bone metastases when conventional anticancer therapy is ineffective and high doses of opiates are necessary to control pain, and when rapid pain relief is necessary (radiation or chemotherapy usually require a 2- to 4-week delay).
The major contraindication is the risk of ethanol diffusing into vital structures and vascular structures (particularly with hypervascular lesions)

Technique

The procedure is performed under neuroleptanalgesia or general anesthesia to palliate the painful alcohol injection. After tumor location on contiguous pre- and post-contrast CT scans, the optimal puncture site and angle are defined. Contrast-enhanced CT is performed to determine the necrotic part of the tumor. Following local anesthesia (lidocane 1%), a 22-gauge needle is placed in the tumor. Initially contrast medium (iohexol 25%) diluted with lidocaine is injected into the lesion. Intratumoral instillation of lidocaine is performed to reduce the pain provoked by the injection of alcohol. The distribution of contrast media within the tumor is imaged by CT and predicts the diffusion of ethanol in the lesion. If there is diffusion of contrast medium beyond the tumor boundaries, particularly when contiguous neurologic structures are reached or if there is vascular leak, the needle is repositioned. Depending on tumor size, 3-30 ml of 96% ethanol is instilled into the tumor. In large tumors, alcohol is selectively instilled into regions considered to be responsible for pain, usually the periphery of the metastases and osteolytic areas. After injec-tion of 2-3 ml of alcohol, the distribution in the tumor is again evaluated by CT. The ethanol is visualized by the dilution of contrast media and by hypodense areas. If the ethanol is accidentally injected in contact with neural structures or other vital structures, the alcohol must be immediately diluted with the injection of an isotonic solution. If the distribution of alcohol is uneven within the tumor (particularly in large metastases), the needle is repositioned in regions of poor diffusion and the injection is repeated.

Outcome

Alcohol ablation has shown to be a good pain relieving technique particularly in the early post procedure phase. 60 to 80 percent patients have been to shown to have pain relief in various studies. One of the major advantages of the injection of alcohol into bone metastasis is the rapid relief of pain occurring within 24-48 h. Duration of pain relief ranges from 2 months to one year. Alcohol injection must be done with caution in hyper vascular metastasis (renal cell carcinoma and thyroid cancer).

Thermal Ablation

Indications

Percutaneous ablation of bone metastasis with radio-frequency or laser can be used in the same indications as alcohol ablation. Radiofrequency and laser are able to produce a much more predictable lesion than alcohol. However, alcohol ablation is a cost effective technique. Radiofrequency and laser thermocoagulation are thus reserved for tumor and pain management when alcohol injection is contraindicated. The radiofrequency ablation technique is able to produce larger lesions than interstitial laser photocoagulation using bar tip fibers. Radiofrequency is more suitable in regions where a predictable size and well-shaped coagulation is preferred. Thermocoagulation is contraindicated if the lesion is too close to neurological structures. In addition, radiofrequency cannot be used in bone tumors consolidated with osteosynthesis.

Technique

Radiofrequency ablation technique is widely used in liver tumors. An electrode with continuous saline infusion to increase the coagulation size. The infused electrode of 18-16 gauges is inserted inside the tumor and a power of 50 Watts is used over 10 min with continuous infusion of saline. For large lesions (>4 cm), the procedure should be repeated after modification of the position of the needle electrode. CT is used for the guidance of the needle electrode. Magnetic resonance imaging (MRI) can be used for guiding the needle insertion and for thermal monitoring during ablation.

Outcome

The thermocoagulation size inside bone with a single energy delivery is about 35 mm in diameter. The ablation is monitored 1 week later with MRI/CT. The procedure is repeated if ablation is incomplete. Large bone metastases require multiple applications. For lesions larger than 4 cm, two to three applications are necessary. The procedure can be repeated every week.

During the first few hours after the procedure, pain should be controlled by analgesics. Fever usually occurs in particular after a large necrosis. The septic risk is reduced by strict asepsis. Neurological complications can be avoided by sound anatomical knowledge of the treated region and precise CT control.

The main advantage of thermal ablation is the ability to create a well-controlled focal thermal injury with minimal morbidity and mortality to date. Radiofrequency is particularly useful as a tumor therapy, while alcoholization is preferred in palliative bone metastases pain management because of its simplicity and low cost.

The size of the thermal injury created by a single radiofrequency ablation is larger than that created by a single laser ablation; hence, there is less chance of treatment failure in large tumors.

Cementoplasty in Metastasis

Its role is to consolidate weight-bearing bone and to treat pain. Bone packing with acrylic cement is a procedure aimed at preventing pathological fractures and pain in patients with vertebral body lesions and acetabular metastasis.

Indications

Percutaneous injection of acrylic cement has been proposed in symptomatic vertebral hemangioma, painful vertebral body and acetabular tumors (particularly metastasis and myeloma), and severely painful osteoporosis with loss of height and/or with compression fractures of the vertebral body.

In cancer patients, cementoplasty is used particularly in the symptomatic treatment of osteolytic bone metastasis and myeloma. As it is only aimed at treating pain and consolidating weight-bearing bone, other specific tumor therapy should be carried out in conjunction for tumor management when appropriate.

The use of acrylic cement is reserved for weight-bearing bone because of its consolidation effect. In the other locations, pain can be treated with alcohol or thermoablation techniques.

The absolute contraindications are hemorrhagic diathesis and infection. Patients with more than five, or diffuse metastases are not indicated for cementoplasty. Lesions with epidural extension require careful injection to prevent epidural overflow

Technique

Acetabular cementoplasty is done in a similar way as vertebroplasty. Firstly, lesion localization and selection of the pathway are carried out using CT prior to the procedure. The 10-gauge needle is then positioned in the metastasis under CT guidance or fluoroscopy and the cement is injected under fluoroscopy control to avoid leakage into the articulation or into the soft tissues. Depending on tumor size, between 2 and 8 ml of acrylic cement are injected. The injection is stopped if the acrylic cement begins to leak. Sometimes two needles are necessary for good filling of the bone.

The injection of cement is carefully controlled with strict lateral fluoroscopy for the spine and oblique/anteroposterior for the acetabular lesions. The injection of acrylic cement is stopped immediately whenever a leak is observed. In the majority of cases, the injection of the cement is painful and the patient needs conscious sedation during this phase of the procedure.

After acetabular filling, the stylet of the needle is re-inserted and the needle is then removed before the cement begins to set. Approximately 6-7 min after mixing, the methylmethac-rylate begins to harden.

Outcome

Percutaneous injection of methylmethacrylate or ethanol may provide marked upto (60-70 percent patients require less analgesic) pain relief or bone strengthening in patients with malignant acetabular osteolysis who are unable to tolerate surgery. Injection of methylmethacrylate is usually indicated when osteolysis involves the weight-bearing bone. In non-weight-bearing bones, ethanol injection is preferred.

Ethanol and methylmethacrylate injections may be performed together if both weight-bearing and non-weight-bearing bones are involved or extensive soft-tissue involvement is present. Moreover, these injections may be performed prior to radiation therapy, which complements their action due to similar but delayed effects on pain, or after unsuccessful pain relief by radiation therapy, or in cases of local recurrence.

Conclusion

Pain management in cancer patients is an important and difficult task. Multiple techniques are available with pharmacological therapy, neurostimulatory techniques, neurosurgical procedures, interventional radiology, or a combination of these, always complemented with psychotherapy. It is essential to study the mechanism of the pain to select the optimal therapy or, more frequently, combination of therapies. Reduction of pain without systemic side effects can be achieved in advanced stages of cancer with precise percutaneous CT-guided techniques.

Pain Relief & Quality of LifeImprovement with RFA & Cementaplasty

Efficacy of percutaneous cementoplasty for bone metastasis from hepatocellular carcinoma.

Kodama H, Aikata H, Uka K, Takaki S, Mori N, Waki K, Jeong SC, Kawakami Y, Shirakawa H, Takahashi S, Toyota N, Ito K, Chayama K.

Oncology. 2007; 72(5-6):285-92. Epub 2008 Jan 11.

METHODS: Cementoplasty was performed for 22 metastatic bone tumors in 13 patients. All patients had intractable pain and were diagnosed as metastatic bone tumor from HCC. The ostyneedle was inserted in the center of the site of bone metastasis under CT guidance. VAS score, Tokuhashi score and Frankel score were used for assessment of the efficacy of cementoplasty. We also assessed the response to treatment, adverse events and prognosis.

RESULTS: Only the VAS score, but not Tokuhashi and Frankel scores, improved after cementoplasty. Cementoplasty for painful bone metastasis provided relief of severe pain but did not improve prognosis, neurological function or survival. Eleven of 13 (85%) patients showed CR or PR and the mean pain-free period was 5 months, including a 10-month pain-free period in one case. No major complications were encountered.

CONCLUSIONS: Percutaneous cementoplasty can provide pain relief and improvement of quality of life, though without survival benefits, for HCC patients with painful bone metastasis.

Percutaneous cementoplasty in multiple myeloma: a valuable adjunct for pain control and ambulation maintenance.

Tran Thang NN, Abdo G, Martin JB, Seium-Neberay Y, Yilmaz H, Verbist MC, Rufenacht D, Sappino AP, Dietrich

Support Care Cancer. 2007 Oct 25 [Epub ahead of print]

GOALS OF WORK: Bone pain and functional impairment are major concerns for multiple myeloma (MM) patients. The goal of this study was to better define the role of percutaneous cementoplasty (PC) in improving their quality of life.

MATERIALS AND METHODS: This retrospective analysis included 28 consecutive heavily pretreated MM patients managed at our institution between 1996 and 2002. They underwent a total of 34 PC procedures for the treatment of 117 vertebrae and 2 iliac sites and were evaluated at 1 month.

MAIN RESULTS: Significant pain reduction of >50% was obtained after 83% of the procedures, with a mean visual analogous score decreasing from 7.48/10 to 2.1/10 (p < 0.001). It resulted in a complete interruption of opiate analgesic consumption after 59.3% of the procedures, with a mean decrease of 70.4% in the opiate dose. Functional impairment was evaluated with the Eastern Cooperative Oncology Group (ECOG) performance status scale, with mean scores improving from 1.9 to 0.86 after the procedures (p = 0.001). There was no major complication.

CONCLUSION: PC is a safe, feasible, and efficient approach for the treatment of bone pain and disability in MM patients.

Combined bipolar radiofrequency and cementoplasty of bone metastases

Kastler B, Jacamon M, Aubry S, Barral FG, Hadjidekov G, Sarliève P, Saguet O, Lerais JM, Cadel G, Kovacs R, Boulahdour H, Pereira P.

J Radiol. 2007 Sep;88(9 Pt 2):1242-7.

The authors present here this very effective new technique which is complementary to classical pain management techniques.

Percutaneous cementoplasty of lytic metastasis in left acetabulum.

Harris K, Pugash R, David E, Yee A, Sinclair E, Myers J, Chow E; on behalf of the Bone Metastases Site Group.

Curr Oncol. 2007 Feb;14(1):4-8.

Minimally invasive procedures such as percutaneous cementoplasty can provide immediate pain relief and can restore mechanical stability for patients with bone metastases who are not candidates for surgery or who show resistance to radiotherapy or analgesic treatment. In that percutaneous cementoplasty provides immediate and long-term pain relief with few complications. We recommend that percutaneous cementoplasty be used as an additional tool for palliative treatment of patients with bone metastases.

Radiofrequency ablation therapy combined with cementoplasty for painful bone metastases: initial experience.

Toyota N, Naito A, Kakizawa H, Hieda M, Hirai N, Tachikake T, Kimura T, Fukuda H, Ito K.

Cardiovasc Intervent Radiol. 2005 Sep-Oct;28(5):578-83.

The purpose of this study was to assess the efficacy and safety of percutaneous radiofrequency (RF) ablation therapy combined with cementoplasty under computed tomography and fluoroscopic guidance for painful bone metastases. Seventeen adult patients with 23 painful bone metastases underwent RF ablation therapy combined with cementoplasty during a 2-year period. The mean tumor size was 52 x 40 x 59 mm. Initial pain relief, reduction of analgesics, duration of pain relief, recurrence rate of pain, survival rate, and complications were analyzed.

The technical success rate was 100%. Initial pain relief was achieved in 100% of patients (n=17). The mean VAS scores dropped from 63 to 24 (p<0.001) (n=8). Analgesic reduction was achieved in 41% (7 out of 17 patients). The mean duration of pain relief was 7.3 months (median: 6 months). Pain recurred in three patients (17.6%) from 2 weeks to 3 months. Eight patients died and 8 patients are still alive (a patient was lost to follow-up). The one-year survival rate was 40% (observation period: 1—30 months). No major complications occurred, but one patient treated with this combined therapy broke his right femur 2 days later. There was transient local pain in most cases, and a hematoma in the psoas muscle (n=1) and a hematoma at the puncture site (n=1) occurred as minor complications. Percutaneous RF ablation therapy combined with cementoplasty for painful bone metastases is effective and safe, in particular, for bulky tumors extending to extraosseous regions. A comparison with cementoplasty or RF ablation alone and their long-term efficacies is needed.

Percutaneous CT-guided cementoplasty for stabilization of a femoral neck lesion.

Chang SW, Murphy KP.

J Vasc Interv Radiol. 2005 Jun;16(6):889-90.

Pelvic osteoplasty in osteolytic metastases: technical approach under fluoroscopic guidance and early clinical results.

Kelekis A, Lovblad KO, Mehdizade A, Somon T, Yilmaz H, Wetzel SG, Seium Y, Dietrich PY, Rufenacht DA, Martin JB.

J Vasc Interv Radiol. 2005 Jan;16(1):81-8.

PURPOSE: To describe a new fluoroscopically guided technique for osteoplasty (or cementoplasty) of the superior and inferior pubic rami and ischial tuberosities and to provide information about the access routes and initial results on pain management after this technique.

MATERIALS AND METHODS: Twenty-three lytic metastases of the superior and inferior pubic rami and ischial tuberosities were treated in 14 consecutive patients. Percutaneous access of the bones was performed under fluoroscopy. All patients had pain refractory to radiation and narcotic therapy and were unsuitable candidates for surgery according to multidisciplinary consensus.

RESULTS: Technical success was achieved in all cases. Clinically, effective pain relief was obtained in 92% of patients. One intraarticular asymptomatic minor complication and one major complication resulting from leakage near the pudendal radiofrequency ablation.

CONCLUSION: Pelvic osteoplasty appears to be a safe and highly effective palliative therapy for painful osteolytic malignant bone metastases.

Combined radiofrequency thermal ablation and percutaneous cementoplasty treatment of a pathologic fracture.

Schaefer O, Lohrmann C, Herling M, Uhrmeister P, Langer M.

J Vasc Interv Radiol. 2002 Oct;13(10):1047-50.

Skeletal metastases commonly occur in patients with cancer and treatment is necessary to alleviate pain and prevent complications, such as mobility deficiencies and pathologic fractures. The authors present a patient with a stage
IV malignant melanoma and a pathologic fracture of the left tibial plateau treated with radiofrequency heat ablation and percutaneous cementoplasty for defect filling and stabilization. The authors believe that this approach may be an alternative to the standard treatments in palliative-care situations.

Percutaneous cementoplasty for pelvic bone metastasis.

Marcy PY, Palussière J, Descamps B, Magné N, Bondiau PY, Ciais C, Bruneton JN.

Support Care Cancer. 2000 Nov;8(6): 500-3.

The aim of this retrospective study was to prove the effectiveness of percutaneous cementoplasty in pelvic bone metastases. We studied the data entered in a multicenter prospective database on 18 cancer patients (average age 58 years) who underwent percutaneous computed tomography (CT) or fluoroscopy-guided cementoplasty from September 1996 to September 1998. The metastatic sites were: acetabulum (n = 12), iliac bone (n = 2), and sacrum (n = 4). Indications were pain recurrence (n = 9) or no relief (n = 3) after radiotherapy, and 6 procedures were performed before radiation. Mean follow-up was 4.6 months, ranging from 11 days up to 24 months. Improvement in pain and walking was obtained in 81.8% cases, and it was generally maintained, except in 1 patient who experienced pain again at day 15 because of an acetabular fracture. Percutaneous cementoplasty is a safe and efficient technique, and is mandatory when radiotherapy fails or when rapid resolution of pain is requested.

PMMA cementoplasty in symptomatic metastatic lesions of the S1 vertebral body.

Dehdashti AR, Martin JB, Jean B, Rüfenacht DA.

Cardiovasc Intervent Radiol. 2000 May-Jun;23(3):235-7.

We describe a lateral transiliac direct puncture approach to the S1 vertebral body for polymethylmethacrylate (PMMA) cementoplasty of painful metastatic lesions. This approach was performed using a 15-cm-long trocar needle with 3-mm outer diameter, introduced under general anesthesia and fluoroscopic control. A lateral projection was used to center the needle just in front of the spinal canal and subjacent to the superior plate of the S1 vertebral body. Needle progression was controlled using anteroposterior and lateral fluoroscopic projections alternately with a needle course parallel to an axial plane, avoiding conflict with the S1 foramen. After needle tip placement in the center of the S1 vertebral body, diluted PMMA with a setting time of 8 min was delivered.Ipsilateral lesions of the lateral sacral compartment were filled with the same needle by stepwise withdrawal and continuous PMMA injection.

Percutaneous Osteoplasty as a Treatment for Painful Malignant Bone Lesions of the Pelvis and Femur

Johannes Hierholzer, MD, Gianni Anselmetti, MD, Heiko Fuchs, MD, Claude Depriester, MD, Karin Koch, MD, and Dirk Pappert MD

J Vasc Interv Radiol 2003; 14:773–777

The purposes of this report are to describe percutaneous osteoplasty as a highly effective minimally invasive procedure to treat painful malignant bone lesions of the pelvis, ilium, and femur and to discuss the relevant literature. Five patients with histologically proven metastases to the pelvis, ilium, or femur were treated by percutaneous injection of liquid bone cement as an attempt to control severe bone pain. After percutaneous osteoplasty, all five patients experienced immediate and substantial pain relief and did not require pain medication for the duration of follow-up. No clinically significant complications occurred. Whereas percutaneous osteoplasty of the spine (vertebroplasty) is well-described and widely accepted to treat pain caused by benign or malignant vertebral body diseases, osteoplasty of bones outside the spine is less known. The immediate good clinical results observed in our small patient group should encourage more widespread application of this palliative treatment.

Percutaneous RFA and / or cementoplasty is safe and highly effective palliative therapy for painful osteolytic malignant bone Metastages.

Image guided Nerve Blocks

Nerve Blocks involve the intentional destruction of the nerves or nerves to interrupt nociceptive pathways by injecting alcohol. It is essential to inform the patient of the details, the benefits, and any side effects that might occur with the block technique.

Absolute contraindications

1. Abnormal blood coagulation profile

2. Infection at the site of injection

3. Allergy to relevant drugs

Other known complications are

1. Systemic toxic reactions to local anesthetic due to an excessive dose and/or accidental intravenous injection of the drug. Repeated attempts to aspirate the syringe during injection should be made to ascertain that the bevel of the needle is not in a blood vessel. Prior to injection of local anesthetic and/or ethanol near vessels, 2 ml of contrast medium should be injected as a test. If the contrast medium is not seen at the intended site of injection on the CT scan, thereby implying dispersal or contrast medium intravascularly (or even intrathecally), the procedure should be discontinued.

2. The accidental injection of local anesthetics into the subarachnoid space can occur during paravertebrs-sympathetic blocks or stellate ganglion block. A total spinal anesthesia can result. Treatment of this complication consists of immediate artificial ventilation and support of the circulation by intravasculzr fluids and vasopressors. To prevent such complications, precise CT control is mandatory with centrist medium test injection to confirm the exact position of the needle tip before any drug instillation.

Neurolytic Block of Spinal Nerve

Neurolytic block achieved by injecting 3-5 ml of 96 percent ethanol into or adjacent to one or more nerve trunks might be necessary in patients with severe excruciating pain who are not amenable to narcotics.

After neurolytic block of spinal nerves, pain relief lasts for only a few months, after which chemical neuropathy consequent to the injection of a neurolytic agent produces severe pain. Neurolytic block of somatic nerves should only be used in patients with severe terminal cancer pain not amenable to any other procedure.

Neurolytic Block of the Celiac Plexus and Splanchnic Nerves

Indications

Celiac plexus block is used to obviate or, drastically reduce, the excruciating epigastric and generalized abdominal pain caused by cancer of the pancreas, stomach, gallbladder, or other upper abdominal viscera

In tumors involving the lower third of the mediastinum, it is necessary to block the splanchnic nerves which contribute an important sensory nerve supply to the lower third of the intrathoracic part and the abdominal portion of the esophagus. block and splanchnic nerve block is preferred to celiac block in cases with large infiltration and invasion of periaortic space. The splanchnic nerve block requires a smaller volume of alcohol

Technique

Celiac Plexus Block

1. Anterior Approach

The patient is placed in a supine position on the CT table. At the level of T12, the celiac and superior mes-enteric arteries are localized after intravenous bolus injection of the contrast medium. Precise localization of the celiac plexus is obtained from these vascular structures which represent the most constant landmarks. A 22-gauge needle is inserted by an anterior approach to reach the pre-aortic retroperitoneal area. After CT scan confirmation of the needle tip position immediately lateral to the celiac artery and in front of the anterior aspect of the aorta, 2 ml of diluted contrast medium are injected to predict the diffusion of ethanol. After the injection of 10 ml of 1% lidocaine to palliate the painful alcohol injection, neurolysis is achieved with 25 ml of 50% ethanol

2. Posterior Approach

The patient is placed in a prone position. After intravenous bolus injection of contrast medium, the celiac and superior mesenteric arteries are localized. The 22-gauge needle is positioned under precise CT guidance near the celiac artery. A transaortic approach pathway could be used. After CT confirmation of needle tip position, the procedure described previously is performed. A bilateral block is often necessary with the posterior approach technique

Splanchnic Nerve Block

Under CT guidance, a 22-gauge needle is inserted into the retro crural space at the level of T11-T12 by a posterior percutaneous approach. The needle tip is located just lateral to the anterolateral surface of the vertebra where the three thoracic splanchnic nerves are located in close proximity to one another. After injection of 2ml of bupivacaine diluted with contrast medium confirming the location of the needle tip, 10 ml of ethanol (96%) are injected on both sides. A bilateral block is often essential for relief of upper abdominal pain

Outcome and Complications

With the use of celiac plexus or splanchnic nerve block, between 70% and 85% of patients with severe abdominal cancer pain obtained pain relief lasting from 1 month up to 1 year. The most frequent complication with celiac plexus block is orthostatic arterial hypotension

In splanchnic nerve block, complications like orthostatic arterial hypotension are unusual because the procedure is less likely to involve the lumbar sympathetic chain than with celiac plexus block. Pneumothorax, intrathecal, and intravascular injection can be avoided under precise CT guidance

References:

1. EUS-Guided Celiac Plexus Block (CPB) for Chronic Pancreatitis Pain: A Randomized Trial of 1 Versus 2 Injections Julia K. Leblanc, John M. Dewitt, Michelle Symms, Lee Mchenry, Stuart Sherman and Thomas F. Imperiale Gastrointestinal Endoscopy Volume 65, Issue 5, April 2007

Introduction:

EUS-CPB is performed by injecting steroids and bupivacaine into one or both sides of the celiac ganglia region. Whether a single or dual injection method is superior for patients with chronic pancreatitis is not known. Aim: To compare the clinical effectiveness and safety of EUS-CPB performed with one or two injections of steroids and bupivacaine into the celiac ganglion region in patients with chronic pancreatitis.

Methods:

Consecutive subjects with chronic pancreatitis documented by EUS criteria and pain requiring narcotics were randomized to receive steroids and bupivacaine into one or two sites (total dose of 80 mg of triamcinolone) in the celiac ganglia region. Subjects were blinded to assignment. Pre-procedure pain was assessed on a 10 point Likert scale. The degree of chronic pancreatitis (mild, moderate, severe) by EUS criteria was recorded. Follow up phone calls were made at 24 hours and weekly thereafter. Response was defined as a subjective report of pain relief and a decrease in pain scores. Telephone assessors were not blinded to assignment and recorded complications, pain relief, and use of pain medications.

Results:

Of 51 subjects (31 women: median age 43 years; range 20 to 75), 41 (80%) had a prior ER visit for pain control (median 2 ER visits, range 1-20). 27 (53%) subjects had pain relief of a median 7 days (range 1-28) duration post-procedure. Severity of chronic pancreatitis (mild, moderate, or severe) did not influence response to EUS-CPB in the 1 (p = .89) or 2 injection(p = .50) groups. There were no complications. Conclusions: In patients with chronic pancreatitis there is no difference in relief of pain with one-sided compared to two-sided EUS-CPB with 80 mg (total) triamcinolone and bupivacaine. Two injections may be beneficial in a patient that had a prior EUS-CPB. Severity of chronic pancreatitis did not affect the response to EUS-CPB.One-sided and two-sided injections were both safe.

2.A comparison of two invasive techniques in the management of intractable pain due to inoperable pancreatic cancer: neurolytic celiac plexus block and videothoracoscopic splanchnicectomy : European Journal of Surgical Oncology: 2005;31: 768-773 .T. Stefaniaka, A. Basinskib, A. Vingerhoetsc, W. Makarewicza, S. Connord, L. Kaskaa, A. Staneka, B. Kwiecinskae, A.J. Lachinskia and Z. Sledzinskia aDepartment of General, Endocrine and Transplant Surgery, Medical University of Gdansk, Poland.

Background and aims

Pancreatic cancer is characterized by a constant deterioration in quality of life, excruciating pain and progressive cachexia. The aim of this study was to compare the effectiveness of two invasive methods of pain treatment in these patients: neurolytic coeliac plexus block (NCPB) and videothoracoscopic splanchnicectomy (VSPL) to a conservatively treated control group concerning pain, quality of life and opiates’ consumption.

Patients and methods

Fifty nine patients suffering from pain due to inoperable pancreatic cancer were treated invasively with NCPB (N=35) or VSPL (N=24) in two non-randomised, prospective, case-controlled protocols. Intensity of pain (VAS-pain), quality of life (FACIT and QLQ C30) and opioid intake were compared between the groups and to a control group of patients treated conservatively before the procedure and after 2 and 8 weeks of follow-up. The analysis was performed retrospectively using meta-analysis statistics.

Results

Both methods of invasive pain treatment resulted in significant reduction of pain (VSPL effect size=11.27, NCPB effect size=7.29) and fatigue (effect sizes, respectively, 1.23 and 3.37). NCPB improved also significantly physical, emotional and social well-being (effect sizes, respectively, 2.37, 4.13 and 7.51) which was not observed after VSPL. No influence on ailments characteristic for the disease was demonstrated. Mean daily opioid consumption was significantly decreased after both procedures. There was no perioperative mortality and no major morbidity.

Conclusion: Both NCPB and VSPL provide significant reduction of pain and improvement of quality of life in inoperable pancreatic cancer patients. They present rather similar efficacy, but lower invasiveness of NCPB, in combination with its more positive effect on quality of life, pre-disposes it as being the preferred method.

Safely & Efficacy

Efficacy of coeliac plexus and splanchnic nerve blockades in body and tail located pancreatic cancer pain.

N. Suleyman Ozyalc_ýna, Gul Koknel Talu ,
Hakan C_ amlýca, Serdar Erdine

European Journal of Pain 8 (2004)

Palliative treatment, pain therapy and quality of life (QOL) are very important in pancreatic cancer patients. We evaluated the pain relieving efficacy, side effects and effects on QOL of neurolytic coeliac plexus blockade (NCPB) and splanchnic nerves neurolyticblockade (SNB) in body and tail located pancreatic cancer.The study protocol was approved by the local ethics committee. Patients were randomly divided into two groups. Coeliac group;GC, N ¼ 19 were treated with coeliac plexus blockade, whereas the patients in splanchnic group; GS, N ¼ 20 were treated withbilateral splanchnic nerve blockade. The VAS values, opioid consumption and QOL (Patient satisfaction scale¼PSS, performancestatus scale¼PS) were evaluated prior to the procedure and at 2 weeks intervals after the procedure with the survival rates.The demographic features were found to be similar. The VAS differences (difference of every control_s value with baseline value)in GS were significantly higher than the VAS differences in GC on every control meaning that VAS values in GS decreased morethan the VAS values in GC. GS patients were found to decrease the opioid consumption significantly more than GC till the 6thcontrol. GS patients had significant improvement in PS values at the first control. The mean survival rate was found to be significantly lower in GC. Two patients had severe pain during injection in GC and 5 patients had intractable diarrhoea in GC.Comparing the ease, pain relieving efficacy, QOL-effects of the methods, splanchnic nerve blocks may be an alternative to coeliacplexus blockade in patients with advanced body and tail located pancreatic cancer.

Neurolytic Celiac Plexus Block: A Better Alternative to Opioid Treatment in Upper Abdominal Malignancies: An Indian Experience.

P.N. Jain, S.V. Shrikahnde, Sheila N. Myatra, R. Sareen, Journal of Pain and palliative care pharmacotherapy.2005;19: 15-20
ABSTRACT. The majority of patients with advanced upper abdominal malignancies suffer from moderate to severe pain due to unavailability of morphine in developing world. This study was undertaken to evaluate the role of neurolytic celiac plexus block on pain and quality of life in this patient subpopulation. One hundred consecutive patients receiving opioids for their pain relief were divided in two groups. Groups I (control) patients received oral morphine and NSAID and groups II (study) patients underwent neurolytic celiac plexus block (NCPB) to compare their effects on pain relief,morphine consumption, quality of life (QOL), Karnofsky and performance scores up to one months. NCPB provided statistically significant better pain relief and reduced morphine consumption at one month (P= 0.000). Superior Karnofsky and performance scores also favored NCPB group ( P =0.000); however the difference in overall QOL was not statistically significant ( P=0.24). Patients in oral morphine group had more side effects (94% vs. 58%) as compared to NCPB (P = 0.000). NCPB is an effective tool to reduce opioid requirement and the drug-related adverse effects. It is a rewarding technique, especially when morphine availability and its easy accessibility to the deserving patient is poor.

Effect of Neurolytic Celiac Plexus Block Guided by Computerized Tomography on Pancreatic Cancer Pain.

Zhang CL, Zhang TJ, Guo YN, Yang LQ, He MW, Shi JZ, Ni JX. Dig Dis Sci. 2007 Aug 4.

The efficacy of neurolytic coeliac plexus block (NCPB) guided by computerized tomography (CT) was compared with pharmacological therapy in the treatment of pain due to pancreatic cancer. The study involved 56 patients who were placed randomly in either a NCPB group and pharmacological therapy group. At day 1, 7, and 14, the visual analogue scale (VAS) pain scores of the NCPB group were significantly lower than those of the pharmacological therapy group (P < 0.01), with values of 1.3 +/- 0.8 versus 4.1 +/- 0.9, 1.7 +/- 1.1 versus 3.1 +/- 1.1, and 2.0 +/- 1.1 versus 2.9 +/- 0.6, respectively. However, the differences in the improvement of quality of life (QOL) between two groups were not statistically significant. Moreover, the dose of opioid was significantly lower in the patients of group 1 than those of group 2, while the complications related to NCPB were transient. We therefore conclude that CT-guided NCPB with alcohol is an effective and safe modality in the management of intractable pancreatic cancer pain

Efficacy of stellate ganglion blockade for the management of type 1 complex regional pain syndrome.

Ackerman WE, Zhang JM. South Med J . 2006;99;1084-8
Pain Medicine Consultants PA, Little Rock, AR, USA.

INTRODUCTION: The purpose of this study was to examine the efficacy of stellate ganglion blockade (SGB) in patients with complex regional pain syndromes (CRPS I) of their hands.

METHODS: After IRB approval and patient informed consent, 25 subjects, with a clinical diagnosis of CRPS I of one hand as defined by the International Association for the Study of Pain (IASP) criteria, had three SGB’s performed at weekly intervals. Laser Doppler fluxmetric hand perfusion studies were performed on the normal and CRPS I hands pre- and post-SGB therapy. No patient was included in this study if they used tobacco products or any medication or substance that could affect sympathetic function. The appropriate parametric and nonparametric data analyses were performed and a p value <0.05 was used to reject the null hypothesis.

RESULTS: Symptom onset of CRPS I until the initiation of SGB therapy ranged between 3 to 34 weeks. Following the SGB series, patient pain relief was as follows: group I, 10/25 (40%) had complete symptom relief; group II, 9/25 (36%) had partial relief and group III, 6/25 (24%) had no relief. The duration of symptoms until SGB therapy was: group I, 4.6 +/- 1.8 weeks, group II, 11.9 +/- 1.6 weeks and group III, 35.8 +/- 27 weeks. Compared with the normal control hand, the skin perfusion in the CRPS I affected hand was greater in group I and decreased in groups II and III.

DISCUSSION: The results of our study demonstrate that an inverse relationship exists between hand perfusion and the duration of symptoms of CRPS I. On the other hand, a positive correlation exists between SGB efficacy and how soon SGB therapy is initiated. Duration of symptoms greater than 16 weeks before the initial SGB and/or a decrease in skin perfusion of 22% between the normal and affected hands adversely affects the efficacy of SGB therapy.

Nerve Blocks uncler Imaging Guidance is more precise, safe and effective.

Section IV
Role of Interventional Radiology in Thrombosis Management in Oncology

Contributors:
Chapter 1 – Dr. Seema Kembhavi
Chapter 2 – Dr. Krantikumar Rathod
Dr. Bhavesh Popat
Chapter 3 – Surgeon Cdr. Dr. Rochan Pant
Chapter 4 – Dr. Sunanda Anand

Deep Vein Thrombosis:Overview

Deep vein thrombosis ( DVT ) is a common complication occurring in patients affected with malignancy. The sequelae of DVT include pulmonary embolism, recurrent venous thrombosis and post thrombotic syndromes. The strategies for diagnosis and treatment have evolved in last 10 years and the evidence for the same is described in this review.

Major risk factors for venous thromboembolism

Acute provoking factors

• Hospitalisation
• Surgery
• Trauma or fracture of lower limbs or pelvis
• Immobilisation (includes plaster cast)
• Long haul travel
• Recently commenced oestrogen therapy (eg, within previous 2 weeks)
• Intravascular device (eg, venous catheter)
  
  Chronic predisposing factors
  
  Inherited
• Natural anticoagulant deficiency*
• Factor V Leiden
• Prothrombin G20210A mutation
  
  Inherited or acquired
• High plasma homocysteine
• High plasma coagulation factor VIII, IX, XI
  
  Acquired
• Age
• Obesity
• Cancer (chemotherapy)
• Leg paralysis
• Oestrogen therapy
• Pregnancy or puerperium
• Major medical illness†
• Previous venous thromboembolism
  
  * * Protein C, Protein S, Antithrombin III deficiency.
  
  † Chronic cardiorespiratory disease, inflammatory bowel disease, nephrotic syndrome, myeloproliferative disorders.
  One half to two thirds of all episodes are provoked by an acute trigger such as recent hospitalization, trauma or surgery. 1 Amongst surgical patients, the risk is highest for hip and knee surgery or major abdominal surgery and patients remains at risk for about 3 months.
  
  The remaining incidents are unprovoked and occur in patients who have chronic risk factors. In about 25 % of patients, underlying predisposition cannot be identified by clinical evaluation or laboratory testing. 1
  
  1. Diagnosis
  
  2A. Clinical prediction:
  
  It is known that only one fourth of the patients presenting with signs and symptoms of DVT have thrombosis confirmed by diagnostic testing, hence clinical diagnosis in unreliable.
  
  However, a model has been developed to classify patients into high, moderate and low probability of DVT .
  
  Assessing the pretest probability of a first episode of deep venous thrombosis2

There is a low pretest probability if the score is 0, moderate if 1–2, and high if 3. A recent modification has allowed this model to be applied to patients with previous deep venous thrombosis.3
The reproducibility of this model has been demonstrated by over 14 studies.4

2B. Laboratory testing:

The plasma levels of D-dimer (degradation product of cross linked fibrin) are high in more than 80% of patients with DVT. 5 Apart from venous thromboembolism, the levels are elevated in patients with malignancy, infection, recent surgery, trauma and pregnancy. Hence it has limited utility and a negative test is of more value in lowering the likelihood of DVT.

2C. Imaging tests:

i. Ultrasonography and Doppler:

Ultrasonography is a reliable, non-invasive and widely available diagnostic imaging test which is most commonly called upon.

The inability to completely compress the vein lumen is the hallmark of thrombosis. Doppler can be used to document lack of flow and perform additional tests like distal augmentation and valsalva maneuver.

The sensitivity and specificity of US for symptomatic proximal (common femoral to formation of popliteal ) DVT is more than 95 %, while for DVT in calf veins, the sensitivity drops to 70%. Hence imaging of calf veins is not done at many centers.

20-30 % of thrombi restricted to calf veins eventually extend into the proximal veins. A repeat US after 1 week is recommended if D-Dimer test is positive.

ii. Venography

It is gold standard test, but hardly performed in routine clinical practice, because it is invasive, involves contrast injection and is labour intensive.

iii. CT and MR venograms

Recent advances in CT (multi-detector CT) have significantly reduced the scan time, improving temporal resolution and is also capable of producing excellent multiplanar reformats. This enables visualization of the entire lower limb venous system.

2. Treatment

Anticoagulation is the therapy for DVT. The evidence based decisions in support of DVT treatment are narrated below.

A list of contra-indications of anticoagulation has been provided below, before we proceed to the choice of therapy.

Absolute contraindications

Active bleeding

Relative contraindications

Recent bleeding

Gastrointestinal bleeding within 2 weeks

(eg, bleeding peptic ulcer)

Intracranial bleeding within 3 months

Recent major trauma

Bleeding diathesis

Coagulation defect

Severe thrombocytopenia; inherited or acquired

platelet function defect

Uncontrolled hypertension

Endocarditis

Risk factors for anticoagulation-associated haemorrhagehaemorrhage

Increasing age

Alcoholism

Cognitive impairment

Chronic corticosteroid use

Liver disease

Peptic ulcer disease

Polymorphisms for the gene encoding the hepatic microsomal

enzyme CYP2CP and mutations of Ala-10 in the factor IX propeptide

3A. Choice of anti-coagulant: LMWH vs. unfractionated heparin

17 systemic reviews comparing the efficacy and safety of LMWH to unfractionated heparin were studied. Evidence is ample that LMWH is superior for the treatment of DVT, particularly in reducing the mortality and risk of major bleeding during the initial therapy.8
Additional trials are needed to examine the efficacy of LMWH for treatment of pulmonary embolism, but review of existing trials indicate that LMWH is atleast as effective as unfractionated heparin for these patients.8

3B. Indoor vs. outdoor treatment

There are four randomized trials and 9 cohort studies comparing outcomes of patients with DVT treated with LMWH at home to that with unfractionated heparin in the hospital. Five additional studies compared the costs and outcomes of patients receiving LMWH at home vs. hospital.

While outcomes did not differ between groups, equivalency cannot be definitively claimed. It is important to note that not all presenting patients were enrolled in these trials and in observational studies, sicker patients are more likely to be treated as inpatients, potentially confounding the results. Still, it is likely that LMWH at home is at least as safe as inpatient treatment for DVT, in appropriately chosen patients if required support services are in place. Little evidence exists regarding outpatient treatment of pulmonary embolism.8

3C. Use of vena cava filters to prevent pulmonary embolism.

A single randomized trial 11 and one population-based study 12 addressing vena-caval interruption were identified. 107 case series reporting the outcomes of patients receiving vena cava filters were also reviewed. 8
The randomized trial compares the efficacy of filter placement in conjunction with anticoagulation ( which is not the case when filters are usually placed) while the observational study gives no treatment details. Moreover, the data on recently available retrievable filters is limited to case series.

The available studies suggest that vena caval filters may be only modestly efficacious in reducing the recurrence of pulmonary emboli and do not affect the mortality. 8

3D Efficacy of compression stocking for post thrombotic syndrome

Three RCTs have examined the efficacy of compression stockings.13-15

The two trials ( 13 & 15) that enrolled patients early showed reduction in incidence of post-thrombotic syndrome in patients using stockings (either over the counter or custom fit). 8

3E. Optimal duration of Vitamin K antagonist

Extended duration conventional-intensity oral anticoagulation may be optimal treatment for patients with unprovoked VTE (Venous thrombotic embolism) or following a second episode of VTE while level 2 evidence indicates that patients with a provoked episode of VTE may be well served with just 3 months of anticoagulation.8

References:

1. Heit JA, O’Fallon WM, Petterson TM, et al. Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study.
Arch Intern Med 2002; 162: 1245-1248.

2. Wells PS, Anderson DR, Bormanis J, et al. Value of assessment of pretest probability of deep-vein thrombosis in clinical management.
Lancet 1997; 350: 1795-1798.

3. Wells PS, Anderson DR, Rodger M, et al. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis.
N Engl J Med 2003; 349: 1227-1235.

4. Wells PS, Owen C, Doucette S, et al. Does this patient have deep vein thrombosis?
JAMA 2006;295:199-207.

5. Fancher T, White R, Kravitz R. Combined use of rapid D-dimer testing and estimation of clinical probability in the diagnosis of deep vein thrombosis: systematic review.
BMJ 2004; 329: 821-828.

6. Fraser JD, Anderson DR. Deep venous thrombosis: recent advances and optimal investigation with US.
Radiology 1999; 211: 9-24.

7. Hirsh J, Lee AY. How we diagnose and treat deep vein thrombosis.
Blood 2002; 93: 3102-3110.

8. Jodi B. Segal, Michael B. Streiff, Lawrence V. Hofmann, Katherine Thornton, Eric B. Bass. Management of Venous Thromboembolism: A Systematic Review for a Practice Guideline Outpatient
Ann Intern Med. 2007;146: 211-222.

9. Elsharawy M, Elzayat E. Early results of thrombolysis vs anticoagulation in iliofemoral venous thrombosis. A randomised clinical trial.
Eur J Vasc Endovasc Surg. 2002;24:209-14.

10. Suresh Vedantham, C. J. Grassi, Hector Ferral, N. H. Patel, P.E. Thorpe, V. P. Antonacci, et al. Reporting Standards for Endovascular Treatment of Lower Extremity Deep Vein Thrombosis
J Vasc Interv Radiol 2006; 17:417–434

11. Decousus H, Leizorovicz A, Parent F, Page Y, Tardy B, Girard P, et al. A clinical trial of vena caval filters in the prevention of pulmonary embolism in patients with proximal deep-vein thrombosis. Pre´vention du Risque d’Embolie Pulmonaire par Interruption Cave Study Group.
N Engl J Med. 1998;338:409-

12. White RH, Zhou H, Kim J, Romano PS. A population-based study of the effectiveness of inferior vena cava filter use among patients with venous thromboembolism.
Arch Intern Med. 2000;160:2033-41.

13. Brandjes DP, Bu¨ller HR, Heijboer H, Huisman MV, de Rijk M, Jagt H, et al. Randomised trial of effect of compression stockings in patients with symptomatic proximal-vein thrombosis.
Lancet. 1997;349:759-62.

14. Ginsberg JS, Hirsh J, Julian J, Vander LaandeVries M, Magier D, Mac- Kinnon B, et al. Prevention and treatment of postphlebitic syndrome: results of a 3-part study.
Arch Intern Med. 2001;161:2105-9.

15. Prandoni P, Lensing AW, Prins MH, Frulla M, Marchiori A, Bernardi E, et al. Below-knee elastic compression stockings to prevent the post-thrombotic syndrome: a randomized, controlled trial.
Ann Intern Med. 2004;141:249-56.

Interventional Management of Deep Vein Thrombosis

The clinical spectrum of venous thromboembolic disease is a serious and potentially life threatening situation in clinical practice.
Even though anticoagulation is the accepted gold standard for treatment of VTE,aggressive interventional management is increasingly being used in selected patients.
This review briefly outlines the current guidelines for patient selection for interventional management of deep vein thrombosis.

Goals of interventional therapies:

1. Rapid reduction of thrombus load to restore venous outflow.This improves pain and disability.

2. Prevention of Pulmonary embolism

3. Limb salvage

4. Prevention of post thrombotic syndrome.

Endovascular treatment options:

1. Catheter directed thrombolysis

2. Percutaneous mechanical thrombectomy

3. Pharmacomechanical thrombolysis

Balloon angioplasty and stent placement can also be used as adjunctive modalities.

Patient Selection

Patient selection should include a careful and multidisciplinary assessment of the likely success, relative benefits and possible complications from the aggressive and costlier therapeutic protocols.

The assessment should also include the life expectancy of patients.This is particularly important in patients with advanced malignancy.

Indications:

1. Phlegmasia cerulea dolens:DVT leading to extensive limb edema and cyanosis.Patients are prone to develop arterial insuffiency from compartment syndrome and are at a high risk of limb loss or death.

2. Acute or subacute IVC thrombosis

3. Acute ilio-femoral DVT

Contraindications:

Thrombolysis is contraindicated in patients who have hemorrhagic disorder, an anatomical lesion that is prone to bleeding, or an absolute contraindication to anticoagulant therapy.

Pre-procedure work-up:

A baseline hematocrit, platelet count, INR, PTT and creatinine levels should be obtained.This is helpful for monitoring efficacy and detecting complications.

A preprocedure fibrinogen level is also obtained to serve as a baseline for later comparison.

Procedural details:

1. Venous access: Ultrasoud guidance should be used almost as a rule.This minimizes the number of needle passes and inadvertent puncture of adjacent arteries.The venous access should be selected to cover the entire thrombosed vein and may antegrade as well as retrograde punctures.

2. Diagnostic venography: The extent of DVT is documented with a venogram.This is also a reference standard to assess and report the recanalization following thrombolysis.

3. Thrombolysis protocol:The thrombolytic drug is delivered into the thrombus through a multi-side hole infusion catheter system. Urokinase (120,000 to 180,000 units/hour) or tissue plasminogen activator (0.5 to 1.0 mg/hour) may be used for thrombolysis.

Monitoring the efficacy of thrombolysis:

Improvement in the pain score and edema are the earliest clinical signs of response to thrombolysis.

Repeat venography at 6-8 hour intervals is performed to document the clearance of thrombus.Adjunctive modalities like balloon maceration can be used to increase the efficacy of thrombolysis.

Monitoring for complications:

Fibrinogen levels may not be helpful since patients can develop hemorrhagic complications in the presence of normal fibrinogen levels.

Marked pericatheter oozing, sentinel bleeds and elevated PTT levels are important markers for impending hemorrhagic complications.

When to discontinue thrombolysis?

1. Documentation of complete venous recanalization.

2. Failure to achieve lysis after significant dose of thrombolytic has been administered or after 72 hours of thrombolysis.

3. Development of hemorrhagic complication.

Reference:

Quality Improvement Guidelines for the Treatment of Lower Extremity Deep Vein Thrombosis with Use of Endovascular Thrombus Removal
Suresh Vedantham et al J Vasc Interv Radiol. March 2006.

Safety and Efficacy of Venous Thrombolysis

Catheter-directed thrombolysis for lower extremity deep venous thrombosis: report of a national multicenter registry.

Mewissen MW, Seabrook GR, Meissner MH, Cynamon J, Labropoulos N, Haughton SH.

Radiology. 1999 Apr;211(1):39-49.

PURPOSE: To evaluate catheter-directed thrombolysis for treatment of symptomatic lower extremity deep venous thrombosis (DVT).

MATERIALS AND METHODS: From a registry of patients (n = 473) with symptomatic lower limb DVT, results of 312 urokinase infusions in 303 limbs of 287 patients (137 male and 150 female patients; mean age, 47.5 years) were analyzed. DVT symptoms were acute (< or = 10 days) in 188 (66%) patients, chronic (> 10 days) in 45 (16%), and acute and chronic in 54 (19%). A history of DVT existed in 90 (31%). Lysis grades were calculated by using venographic results.
RESULTS: Iliofemoral DVT (n = 221 [71%]) and femoral-popliteal DVT (n = 79 [25%]) were treated with urokinase infusions (mean, 7.8 million i.u.) for a mean of 53.4 hours. After thrombolysis, 99 iliac and five femoral vein lesions were treated with stents. Grade III (complete) lysis was achieved in 96 (31%) infusions; grade II (50%-99% lysis), in 162 (52%); and grade I (< 50% lysis), in 54 (17%). For acute thrombosis, grade III lysis occurred in 34% of cases of acute and in 19% of cases of chronic DVT (P < .01). Major bleeding complications occurred in 54 (11%) patients, most often at the puncture site. Six patients (1%) developed pulmonary emboli. Two deaths (< 1%) were attributed to pulmonary embolism and intracranial hemorrhage. At 1 year, the primary patency rate was 60%. Lysis grade was predictive of 1-year patency rate (grade III, 79%; grade II, 58%; grade I, 32%; P < .001).

CONCLUSION: Catheter-directed thrombolysis is safe and effective. These data can guide patient selection for this therapeutic technique.

Early Results of Thrombolysis vs Anticoagulation in Iliofemoral Venous Thrombosis. A Randomised Clinical Trial

M. Elsharawyaf1, E. Elzayatb

Eur J Vasc Endovasc Surg. 2002;24:209–214

Objective: catheter directed thrombolysis has been advocated for complete and rapid dissolution of iliofemoral deep venothrombosis (DVT). The aim of our study is to compare, in a randomised trial, local thrombolysis and anticoagulation with anticoagulation alone in patients with iliofemoral DVT.

Methods: a consecutive series of 35 eligible patients, were randomised to either catheter directed thrombolysis followed by anticoagulation or to anticoagulation alone. Clot lysis and deep venous reflux were assessed with ultrasound duplex and plethysmography after 6 months.

Results: complete data were available in the 18 and 17 patients randomised to thrombolysis and anticoagulation, respectively. At 6 months, patency rate was better in cases treated with thrombolysis [13/18 (72%) vs 2/17 (12%), p < 0.001]. Venous reflux was higher in-patients treated with anticoagulant [7 patients (41%) vs 2 (11%), p = 0.04].

Conclusion: in the short-term patients treated with catheter directed thrombolysis obtained better patency and competence than those treated with standard anticoagulation.

Catheter-directed thrombolysis for iliofemoral deep venous thrombosis improves health-related quality of life

Anthony J. Comerota, MD, Richard C. Throm, BA, Susan D. Mathias, MPH, Signe Haughton, BA, Mark Mewissen, MD

J Vasc Surg 2000;32: 130-7.

Purpose: Treatment designed to eliminate thrombus in patients with iliofemoral deep venous thrombosis (DVT) is theoretically attractive; however, its benefits, compared with those of anticoagulation, have not been definitively demonstrated. Although not previously analyzed, an effective measure of treatment success is likely to be the assessment of health-related quality of life (HRQOL). This study evaluated whether catheter-directed thrombolysis for iliofemoral DVT is associated with improved HRQOL, compared with standard anticoagulation, and whether HRQOL outcome in the thrombolysis group is related to lytic success. Methods: An 80-item self-administered HRQOL questionnaire was developed. It contained the Health Utilities Index, Short Form-12, and disease-targeted scales, including health distress, stigma, health interference, physical functioning, and symptoms (eg, leg swelling, pain, ulcers). The HRQOL questionnaire was confirmed to be reliable and valid by means of psychometric testing. Questionnaires were administered to 98 retrospectively identified patients who had had iliofemoral DVT treated at least 6 months earlier. Sixty-eight patients who were identified through a DVT registry were treated with catheter-directed thrombolysis with urokinase (UK), and 30 patients who were identified by means of a medical record review were treated with anticoagulation alone. The treatment decision was made by the attending physician, and all patients were candidates for both thrombolysis and anticoagulation. Results: Most patients were women (61%), white (95%), married (65%), and had a mean interval since initial DVT of 16 months. The group treated with UK was younger (53 ± 17 years) than the group treated with heparin (61 ± 6 years; P = .039). After treatment, patients treated with UK reported better overall physical functioning (P = .046), less stigma (P = .033), less health distress (P = .022), and fewer post-thrombotic symptoms (P = .006), compared with the patients treated with anticoagulation alone. Within the UK group, phlebographically successful lysis correlated with improved HRQOL (P = .038). Patients classified as lytic failures had similar outcomes to patients treated with heparin. Conclusion: Patients with iliofemoral DVT treated with catheter-directed thrombolysis have better functioning and well-being, compared with patients treated with anticoagulation alone. Successful lysis was directly correlated with improved HRQOL, with patients who were classified as lytic failures having similar outcomes to patients treated with heparin. These data support the need for a future randomized trial, which should include an HRQOL measure as part of the outcome analysis.

Pharmacomechanical Thrombolysis and Early Stent Placement for Iliofemoral Deep Vein Thrombosis

Suresh Vedantham, MD, Thomas M. Vesely, MD, Gregorio A. Sicard, MD, Daniel Brown, MD, Brian Rubin, MD, Luis A. Sanchez, MD,
Naveen Parti, MD, Daniel Picus, MD

Vasc Interv Radiol. 2004;15:565–574

PURPOSE

To evaluate an approach to the treatment of iliofemoral deep vein thrombosis (DVT) that included pharmacomechanical catheter-directed thrombolysis with reteplase and the Helix mechanical thrombectomy device, followed by early stent placement.

MATERIALS AND METHODS

During 3-year period, 23 symptomatic limbs in 18 patients with iliofemoral DVT were treated with reteplase catheter-directed thrombolysis. After an initial infusion of 8 to 16 hours, any residual acute thrombus over a long segment (> 10 cm) was treated by maceration with use of the Helix thrombectomy device. Residual short-segment (< 10 cm) iliac vein thrombus and/or stenosis were treated with stent placement. Technical success, clinical success, complications, thrombolytic infusion time, total thrombolytic agent dose, fibrinogen level changes, and late limb status were retrospectively analyzed.

RESULTS

Technical success was achieved in 23 of 23 limbs (100%). Clinical success was achieved in 22 of 23 limbs (96%). Complete or partial thrombolysis was observed in 19 of 23 limbs (83%). Major bleeding was observed in one patient (6%) and necessitated blood transfusion. Mean per-limb thrombolytic infusion time and total dose were 19.6 hours ± 8.1 and 13.8 U ± 5.3 reteplase, respectively. Mean serum fibrinogen nadir and percentage drop in serum fibrinogen were 282 mg/dL ± 167 and 47% ± 24%, respectively. Late (mean, 19.8 ± 11.6 months) modified Venous Disability Scores were 0 (none) for six limbs, 1 (mild) for 10 limbs, 2 (moderate) for two limbs, and 3 (severe) for no limbs.

CONCLUSIONS In a preliminary experience, pharmacomechanical catheter-directed iliofemoral DVT thrombolysis with early stent placement was safe and effective.

Catheter directed thrombolysis is a safe and effective therapeutic procedure for carefully selected patients with acute DVT.

Use of Ivc Filter During Thrombolysis

Long-term outcomes of catheter directed thrombolysis for lower extremity deep venous thrombosis without prophylactic inferior vena cava filter placement.

Protack CD, Bakken AM, Patel N, Saad WE, Waldman DL, Davies MG.

J Vasc Surg. 2007 May;45(5):992-7; discussion 997.

BACKGROUND: While the predominant treatment of lower extremity deep venous thrombosis (DVT) remains systemic anticoagulation, there is a growing consensus that more aggressive percutaneous catheter directed thrombolysis (CDT) carries both short-term and long-term benefits. There remains controversy as to whether an inferior vena cava (IVC) filter is always required during CDT.

OBJECTIVE: To define the short- and long-term outcomes of CDT with and without prophylactic IVC filter placement for lower extremity DVT.

METHODS: A database of patients treated by CDT from 1996 to 2006 was compiled. Results were standardized to current Society for Vascular Surgery criteria. Average follow-up was 2.1 years, range of 1-8 years. Kaplan-Meier survival analyses were performed to assess time-dependent outcomes. Factor analyses were performed using a Cox proportional hazard model for time dependent variables. Data are presented as mean +/- SD where appropriate.

RESULTS: Sixty-nine patients (39% male, average age 48 +/- 17 years) underwent CDT: (27 received pharmacological thrombolysis, 12 received mechanical thrombolysis, and 30 received mechanical and pharmacological thrombolysis). Fourteen patients (20%) had IVC filter placement prior to or during CDT. Twenty-one had a hypercoagulable state. Technical success with grade III lysis of clot burden was achieved in 63%. Fifty-one patients required an adjuvant stent. Overall, 90-day all-cause mortality was 4% and peri-procedural morbidity was 4%. No patients developed a pulmonary embolus (PE) during therapy. By Kaplan-Meier analysis 83%, 83%, and 75% of patients were free of recurrent DVT at 1, 2, and 3 years, respectively. Hypercoagulability was associated with DVT recurrence by Cox proportional hazards analysis. No analyzed factor was predictive of PE.

CONCLUSION: Catheter directed thrombolysis without universal prophylactic IVC filter placement is safe and effective in treating acute DVT. Pulmonary embolization did not occur during CDT. Selective rather than routine IVC filter placement is a safe and appropriate approach.

Routine use of IVC filter is not necessary in patients undergoing DVT thrombolysis.It may be reserved for patients with limited cardio-pulmonary reserve.

Endovascular Management of Pulmonary Embolism

Interventional Radiology : Therapy of Pulmonary Embolism

The presence of malignancy has been estimated to increase the relative risk of deep vein thrombosis to 5times, with a high risk of recurrence (>10%). [1]. The reported prevalence is 40% to 80% for calf vein thrombosis and 10% to 20% for proximal vein thrombosis, compared with prevalences of 10% to 20% and 2% to 4%, respectively, in patients without malignancy [2]. At least 50 % of autopsies reveal venous thromboembolism in cancer victims (3.) The extensive use of long term indwelling catheters has also contributed. (4)

The Clinical manifestations of pulmonary embolism (PE) are varied, and a high index of suspicion is necessary to decrease the high rate of underdiagnosis.(5). In a study of patients clinically suspected to have PE, the presentation included hemoptysis or pleuritic pain (44%), uncomplicated dyspnoea (36%) and circulatory collapse (8%). 14% of patients presented with tachypnoea, tachycardia, or hypoxia with or without signs and symptoms of DVT. (6.) The incidence of asymptomatic pulmonary embolism is high, and a recent study based on MDCT of 403 patients not suspected of having pulmonary emboli revealed emboli in 4% of the patients. (7..)

The diagnosis of pulmonary embolism is based on a combination of clinical, laboratory and imaging findings. The current modality of choice is multidetector CT (MDCT) angiography (8.)

The standard management for PE is antithrombotic therapy, with low molecular weight heparin (LMWH), unfractionated heparin (UFH) and oral anticoagulation being employed as required. Anticoagulation does not address the immediate pathophysiological consequences of pulmonary embolism. In cases where the clinical manifestations are mild, anticoagulation suffices. Many cases present with varying degree of cardio-respiratory compromise, and some require immediate correction of the pulmonary arterial occlusion for patient survival.

Intervention in patients with pulmonary embolism is indicated in patients who have low potential for survival without aggressive management. Findings suggesting a need for urgent intervention include:

– Arterial Hypotension (< 90mm of Hg systolic/ fall of > 40 mm of Hg)

– Cardiogenic shock with hypoperfusion and hypoxia

– Circulatory collapse with need for resuscitation

– Echocardiography showing RV overload and/ or pulmonary hypertension (Controversial)

– Widened arterial- alveolar O2 gradient ( > 50 mm of Hg)

– Clinically severe PE with contraindication to anticoagulation or thrombolysis

– Precapillary Pulmonary Hypertension ( > 20 mm of Hg) (9.)

Patients with established haemodynamic compromise are obvious candidates for lytic therapy. However, the presence of circulatory collapse and need for pressor agents indicates a poor prognosis. Thus there has been an effort to find the subgroup of patients with early indicators of poor prognosis who are likely to benefit from an early institution of thrombolytic therapy. A subgroup of patients with RV dilatation has been considered as a high risk group deserving of intervention. Echocardiography (10)and CT based (11.) studies have shown that right ventricular dysfunction and dilatation are good predictors of increased mortality in patients with acute pulmonary embolism. For this reason, this group of patients are looked at with interest for the institution of aggressive revascularization therapy. The available evidence is small and not high grade, as there are few trials comparing conservative management and thrombolysis in patients with submassive pulmonary embolism. Available RCTs compare intravenous systemic thrombolysis with conventional anticoagulation (heparin, LMWHand there is no significant difference n outcomes in terms of survival, or recurrence of pulmonary embolism though the lysis groups have demonstrated a better recanalisation with reduced pulmonary hypertension (12). Metaanalysis of 9 trials with varied prospective designs and protocols ( n= 478, 1973- 1995) showed no advantage in hemodynamically stable patients who underwent thrombolysis as compared with anticoagulation alone. [13]

Possible approaches to achieving haemodynamic correction in massive PE incude:

– Surgical Thromboembolectomy

– Systemic Lytic Therapy

– Percutaneous therapy:

Systemic Thrombolysis:

Systemic thrombolysis has been a recommended intervention in patients with massive PE (14). IT is simple and has the advantage of allowing very early initiation of therapy. However, almost 30 % of patients with PE are not eligible for systemic thrombolysis due to various contraindications such as recent surgery, or advanced cancer etc. (15). Furthermore, the complication rates in patients undergoing systemic thrombolysis are not negligible, with 22 % major bleeding and 9% intracranial haemorrhage rates in the International Cooperative Pulmonary Embolism Registry (16). Patients ineligible for systemic thrombolysis are therefore candidates for other approaches.

Surgical Embolectomy:

Surgical embolectomy involves a sternotomy, arteriotomy of the pulmonary artery and embolectomy in a patient with severe haemodynamic compromise. Not surprisingly, it carries a high morbidity and mortality. In hospital mortality for this procedure is roughly 30 % (17).

Percutaneous Therapy:

The percutaneous therapies involve transvenous access to the pulmonary arterial tree (transjugular or transfemoral) and removal of the obstruction to pulmonary blood flow. This reverses the pathophysiologic changes of PE and restores haemodynamic stability. The possible procedures include:

o Thromboaspiration

o Catheter Directed Thrombolysis

o Catheter Thrombectomy

o Pharmachomechanical Thrombectomy

o Balloon angioplasty and stent placement

Thromboaspiration uses a large bore catheter to suck out the thrombus that is not adherent to the vessel wall and thereby restores flow. This procedure is simple but success is not assured as only soft non adherent clot is likely to be aspirated.
Catheter directed thrombolysis (CDT) is carried out with the intra-thrombic placement of a catheter with thrombolytics being injected locally at a much higher concentration. Adjunctive mechanical disruption of the thrombus also allows better contact of the thrombolytic agent with the obstructive thrombus. The higher effectiveness of catheter directed thrombolysis stems from the higher concentration achieved in the local site and lower requirements of total amount of drug. This has the effect of reducing the systemic complications. 94% of cases showed rapid lysis of clot with use of CDT with rTPA.(18.) Recommended protocols for thrombolysis are given in Table 1.

Catheter Thrombectomy is an alternative approach to achieving haemodynamic stabilization in massive pulmonary embolism. Various mechanical devices are available for breaking up and removing the occluding thrombus. These devices use either a mechanical action to break up a thrombus or create a low pressure zone to aspirate the thrombus and break it up. The devices can be combined with thrombolytic therapy for more effective results. A list of available devices that have been deployed in this role is given in Table 1.

Most of these were originally developed for use in thrombosed dialysis access grafts and thus are not ideal for use in the pulmonary vasculature. Out of these devices, only the Greenfield device and the Aspirex catheter are specifically designed for use in pulmonary vasculature. Significant disadvantages of the use of these devices includes blood loss ( due to haemolysis and aspiration) and haemodilution in some devices using a water jet. These devices are expensive . Few of the more commonly used devices are described below and summarized in table 2.

Greenfield Embolectomy Catheter: This is a 10 F (approx 3.3 mm)device which is inserted via the Internal Jugular Vein (IJV) or Common Femoral Vein (CFV) and uses suction to aspirate the thrombus into the catheter. The catheter and thrombus are then removed as a unit through the surgical venotomy. This is a device specifically designed for pulmonary embolectomy. It has been in use for more than 3 decades and reported success rates are high. (19, 20,21)

Amplatz Thrombectomy Device :

This catheter uses a mechanical system of thrombus extraction. A rapidly moving impeller housed in a metal casing at the tip of a catheter is used to create a low pressure area that sucks in the thrombus which is broken up into very small particles by the impeller. These particles then exit the device through side ports. The device causes certain amount of haemolysis, and haemoptysis can occur. (22).

Aspirex :

This catheter was specifically designed for pulmonary arteries and uses a high speed rotating coil to create a negative suction and macerate the aspirated clots. (23) . This device has been reported not to cause distal embolisation or haemolysis. A cohort study is being carried out to assess the usefulness of this device.

Hydrodynamic thrombectomy catheter devices:

These devices use a high velocity jet of water to create a negative suction and break up clots. These are mostly designed for smaller vessels and are of limited effectiveness in large calibre in pulmonary arteries. The devices differ in design details and costs. Isolated case reports exist for the use of the devices in pulmonary embolism. Reported complications include haemoptysis and perivascular haeorrhage. (24).

Examples include the Oasis, Hydrolyser and the Angiojet Xpeedior .

Rotatable Pigtail and other simple mechanical fragmentation devices :

The rotatable pigtail catheter is a simple 5 F angiographic catheter modified with a hole in the side wall that allows the passage of a guidewire through and through the pigtail so that it can be rotated around this central axis. This device is rotated in contact with the thrombus to fragment it.

Other such devices used for breaking up the thrombus include a variety of basic angiographic catheters, guidewires and snares such as Dormia baskets.Similar results can be achieved by mechanical balloon angioplasty. However, there is a risk of distal macroembolisation causing worsening. These procedures are usually used in combination with thrombolysis. 94% of patients showed clinical improvement in a series of 59 cases (25).

Angioplasty and Stent Placement has been used for achieving restitution of pulmonary flow. Isolated case reports exist of balloon angioplasty with or without emergency stent placement across a central occluding thrombus in cases where all else failed. (26, 27,28)

This procedure carries the risk of worsening the haemodynamic compromise due to distal macroembolisation into a previously unaffected branch. Since most reports dealing with the use of balloon angioplasty and stent placement also had concurrent thrombolysis being used, the effectiveness of these procedures as a stand -alone is difficult to assess.

Combination of two or more of these procedures has been employed in desperate situations with many reports of clinical success. (29.,30.) The most commonly used combination is that of Pharmacomechanical Thrombectomy which uses simultaneous thrombolysis and mechanical clot breakage to accelerate the restablishment of pulmonary perfusion. Concurrent use of inhaled vasodilator has also been reported to be of benefit, presumably by relieving the associated spasm in the pulmonary artries(31.). Locoregional therapies have also been combined with systemic therapies, including local pharmacomechanical and systemic thrombolysis (32).

Thrombolysis in Pulmonary Embolism

Available Evidence:

– There is no level I evidence for percutaneous management of PE as there are no large randomized trials or non randomized trials comparing invasive therapies with heparin or systemic thrombolysis. In view of the nature of illness in the patients who have been subjected to these therapies, it is perhaps impossible to obtain this level of evidence.

– The only available randomized data is for systemic (intravenous) thrombolysis. There is limited evidence to suggest that thrombolysis is of benefit in patients with submassive pulmonary embolism The Cocharane analysis (33) concluded that there was insufficient evidence to establish a definite role for thrombolysis in all cases of PE and more trials were needed.

Recommendations:

– Patients with massive PE benefit from thrombolysis. (Level 3b, Grade B)

– Patinets with sub-massive PE may benefit from thrombolysis (Level 2a, Grade B)

– Patients in whom systemic thrombolysis is contraindicated should be offered percutaneous thrombectomy or other loco-regional therapy including low-dose catheter directed thrombolysis depending on availability and expertise. (Level 2b, Grade C)

To summarize, interventional therapies aimed at removing pulmonary artery occlusion should be used in patients with evidence of haemodynamic compromise. Various techniques may be used, at times in combination, and adequate expertise and experience in the use of the various devices and techniques is necessary for better outcome.

References

1. Bates SM, Ginsberg JS. Treatment of Deep-Vein Thrombosis N Engl J Med 2004;351:268-77

2 Clagett GP. Prevention of postoperative venous thromboembolism: an update. Am J Surg;168:515–22

3 Thompson CM, Rodgers RL. Analysis of the autopsy records of 157 cases of carcinoma of the pancreas with particular reference to the incidence of thromboembolism. Am J Med Sci 1952; 223: 469–476

4. Verso M, Agnelli G. Venous thromboembolism associated with long term use of central venous catheters in cancer patients. J Clin Oncol 2003; 21: 3665–3675.

5. Stein PD, Henry JW. Prevalence of acute pulmonary embolism among patients in a general hospital and at autopsy. Chest 1995;108:978–981

6. Paul D. Stein et al Clinical Characteristics of Patients with Acute Pulmonary Embolism: Data from PIOPED II. Am J Med. 2007 October ; 120(10): 871–879

7. Gladish GW, Choe DH, Marom EM, Sabloff BS, Broemeling LD, Munden RF. Incidental pulmonary emboli in oncology patients: prevalence, CT evaluation, and natural history. Radiology. 2006 Jul;240(1):246-55

8. Stein PD, Kayali F, Olson RE. Trends in the use of diagnostic imaging in patients hospitalized with acute pulmonary embolism. Am J Cardiol 2004;93:1316–1317

9. Konstantinides S, Geibel A, Olschewski M, et al. Association between thrombolytic treatment and the prognosis of hemodynamically stable patients with major pulmonary embolism: results of a multicenter registry. Circulation 1997; 96:882– 888

10. Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet. 1999;353:1386-9

11. U. Joseph Schoepf, MD*; Nils Kucher, MD*; Florian Kipfmueller, BS; Rene Quiroz, MD, MPH; Philip Costello, MD; Samuel Z. Goldhaber, MD. Right Ventricular Enlargement on Chest Computed Tomography: A Predictor of Early Death in Acute Pulmonary Embolism. Circulation. 2004;110:3276-3280

12 Konstantinides S, Geibel A, Heusel G, Heinrich F, Kasper W. Heparin plus alteplase compared with heparin alone in patients with submassive pulmonary embolism. N Engl J Med. 2002;347:1143-1150

13. Thabut, G, Thabut D, Myers RP, Bernard-Chabert B, Marrash-Chahla R, Mal H, Fournier M. Thrombolytic Therapy of Pulmonary Embolism A Meta-Analysis. J Am Coll Cardiol 2002;40:1660 –7.

14. Task Force on Pulmonary Embolism, European Society of Cardiology. Guidelines on diagnosis and management of acute pulmonary embolism. Eur Heart J 2000; 21:1301–1336

15. Kasper W, Konstantinides S, Geibel A, et al. Management strategies and determinants of outcome in acute major pulmonary embolism: results of a multicenter registry. J Am Coll Cardiol 1997; 30:1165–1171

16. Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 1999; 353:1386–1389

17. Stein PD, Alnas M, Beemath A, et al. Outcome of pulmonary embolectomy. Am J Cardiol 2007; 99:421–423

18. Goldhaber SZ, Markis JE, Meyrovitz MF, et al. Acute pulmonary embolism treated with tissue plasminogen activator. Lancet 1986: 886–889

19. Greenfield LJ, Bruce TA, Nichols NB. Transvenous pulmonary embolectomy by catheter device. Ann Surg 1971; 174: 881–886,

20 Greenfield LJ, Zocco J. Intraluminal management of acute massive pulmonary thromboembolism. J Thorac Cardiovasc Surg 1979; 77:402–410
21 Greenfield LJ, Proctor MC, Williams DM, et al. Long-term experience with transvenous catheter pulmonary embolectomy. J Vasc Surg 1993; 18:450–457

22 Uflacker R, Strange C, Vujic I. Massive pulmonary embolism: preliminary results of treatment with the Amplatz thrombectomy device. J Vasc Interv Radiol 1996; 7:519–528

23 Kucher N, Windecker S, Banz Y, et al. Percutaneous catheter thrombectomy device for acute pulmonary embolism. Radiology 2005; 236:852–858

24 Fava M, LoyolaS, Huete I. Massive Pulmonary Embolism: Treatment with the Hydrolyser Thrombectomy Catheter. JVIR 2000; 11:1159–1164

25 De Gregorio MA, Gimeno MJ, Mainar A, Herrera M, Tobio R, Alfonso R, Medrano J, Fava M. Mechanical and enzymatic thrombolysis for massive pulmonary embolism. J Vasc Interv Radiol. 2002 Feb;13(2 Pt 1):163-9

26 Handa K, Sasaki Y Kiyonaga A, et al. Acute pulmonary thromboembolism treated successfully by balloon angioplasty: a case report. Angiology 1988; 8:775–778

27 Haskal ZJ, Soulen MC, Huetti EA, et al. Life-threatening pulmonary emboli and cor pulmonale: treatment with Radiology 1994; 191:473–475

28 Koizumi J, Kusano S, Akima T, et al. Emergent Z stent placement for treatment of cor pulmonale due to pulmonary emboli after failed lytic treatment: technical considerations. Cardiovasc Intervent Radiol 1998; 21:254–255

29 Fava M, Loyola S, Bertoni H, Dougnac A. Massive pulmonary embolism: percutaneous mechanical thrombectomy during cardiopulmonary resuscitation. J Vasc Interv Radiol 2005;16:119–123

30 Sharafuddin MJ, Hicks ME. Current status of percutaneous mechanical thrombectomy. J Vasc Interv Radiol 1998;9:15–31
31 Faintuch S, Lang EV, Cohen RI, Pinto DS. Inhaled nitric oxide as an adjunct to suction thrombectomy for pulmonary embolism. J Vasc Interv Radiol. 2004 Nov;15(11):1311-5

32 Tajima H, Murata S, Kumazaki T, Nakazawa K, Abe Y, Komada Y, Niggemann P, Takayama M, Tanaka K, Takano T. Hybrid treatment of acute massive pulmonary thromboembolism: mechanical fragmentation with a modified rotating pigtail catheter, local fibrinolytic therapy, and clot aspiration followed by systemic fibrinolytic therapy. AJR Am J Roentgenol. 2004 Sep;183(3):589-95

33 http://www.cochrane.org/reviews/en/ab004437.html

Venous Strokes in Malignancy

Systemic venous thrombosis is commonly noted in malignant cases. More cases of CVT in malignancy are being reported with the advent of magnetic resonance imaging. Cerebrovascular symptoms of CVT may be masquerading that of metastasis and sometimes both may be coexist.

Causes of CVT in Malignancy

Malignancy is a procoagulant state. CVT is commonly associated with advanced malignancy. Aseptic CVT diagnosed in elderly patients, underlying /occult malignancy should be suspected. The risk factors are same for cerebral as for systemic thrombosis.(2)

Common causes of cerebral venous thrombosis are:-

1. Changes in the vessel walls (phlebitis or phlebopathy) e.g., malignant infiltration, Thrombosis is accelerated due to infiltration of vessel walls(2)
2. Venous stenosis with malignant infiltration.(3)
3. Generation of abnormal coagulant factors. (4)
4. Paraneoplastic manifestation(5)
5. Antineoplastic chemotherapy causing endothelium toxicity(6)
6. Radiotherapy(7)
7. Bone marrow transplantation(8)
8. Associated procoagulant state :APLA, Factor V Leiden(9)
9. Neurosurgical removal of tumours with concomitant removal of adherent cortical veins.(10)

CVT is a continuing process of disequilibrium between prothrombotic and thrombolytic mechanisms. Most of the cancers can lead to cerebral thrombosis. Hypercoaguable states are reported most commonly with acute lymphoblastic leukemia, chronic myeloproliferative disorders, lung adenocarcinoma, phaeochromocytoma, ca Breast, Prostate cancer, Pancreatic adenocarcinoma noted for its migratory phlebitis, colorectal ca, ca Cervix etc.(11-16).Venous stenosis has been seen with intravascular lymphomatiosis with infiltration of cortical veins with malignant lymphoma cells causing cortical veins stenosis predisposing to cortical vein thrombosis. (2)

Malignancy predisposes to thrombosis by different mechanism. Platelets are activated, the thrombin activity increases, and the fibrinolytic function declines in cancer patients which leads to an increased incidence of spontaneous and catheter related thrombosis. Some tumors secrete procoagulants and in few cases the antineoplastic chemotherapy /hormonal therapy may lead to complex hypercoaguable states leading to thrombosis.(4)

Occasionally CVT may present as a paraneoplastic manifestation. This has been reported with phaeochromcytoma and is again believed to be due to procoagulants secreted by the tumor. It has also been reported with pancreatic cancer with liver metastasis which was associated with superior sagital sinus thrombosis (5)

Venous thrombosis is more frequent in patients treated for acute lymphoblastic leukemia (ALL) than other malignancies. The reported incidence varies from 1% to 36%, depending on the chemotherapy protocol. The risk is thought to arise from increased thrombin generation combined with reduced thrombin inhibitory capacity due to depletion of circulating anti-thrombin III by asparaginase. Central nervous system thrombosis involving the cerebral venous sinuses is a unique feature of asparaginase and is reported to occur in 1-3% of patients. (18) Acenocumarol and hormaonal blockade with flutamide, leoprolerin acetate may lead to thrombosis .Cisplatinum, methrotexate, 5-fluro-uracil , methylprediniosolone has been found to be associated with venous thrombosis.(19) GnRH agonist may inhibit the fibrinolytic system by decreasing t-pa levels used in the management of rectal cancers.(20) Allogenic bone marrow transplant in management of ALL has also been reported to cause venous thrombosis.(8) Radiotherapy has been found to increase risk of carotid atherosclerosis.(7)

There may be associated prothrombotic states like the normal population which predisposes to thrombosis. L asparganase by reducing antithrombin III and protein S has been reported leading to secondary hypercoagubility.(4,6). The heterozygous prothrombin G20210A variant was found together with acquired activated protein C resistance and a reduced activated partial thromboplastin time.(21)

Solid intracranial tumors eg meningioma may led to abnormal cortical vein anastomosis on the wall of tumor which might be damaged or blocked during neurosurgical removal leading to venous infarcts.(10)

Clinical Features & Pathophysiology

The clinical features of venous strokes follow the similar course of events. The most common symptom is headache 75%, followed by papilloedema 49%, focal neurological deficit 34%, seizures 37%, altered sensorium 30%, dysphasia 12%, multiple cranial nerve palsies 12%, cerebellar incoordination 3%,nystagmus 2%, hearing loss 2% and bilateral
signs 3% patients are like other cases .(22,23).These clinical features are commonly confused with intracranial metastasis as they may present with similar symptoms.

Cerebral venous thrombosis refers to complete or partial occlusion of either the main sinus/sinuses or the feeding cortical veins leading to secondary vasogenic edema, developing due to disruption of the blood brain barrier and engorgement of the brain interstitium with blood, and cytotoxic edema resulting from localized ischemia and damage to intracellular ion channels eventually leading to neuronal swelling, is a characteristic of cerebral venous involvement. A major sinus block leads to intracranial hypertension whereas the deep cortical occlusion would cause localized edema, venous infarction and petechial hemorrhages which may merge to form big haematomas.(22,23)

Diagnostic Modalities:

Neuroimaging is the mainstay for diagnosis. CT scan, MR venogram and DSA all have been used for the diagnosis .CT brain may give you direct or indirect evidence of cerebral thrombosis. The diagnostic investigation of choice is MRI and MRV. Contrast MR Venogram is highly sensitive diagnostic modality to pick up suspected cases. The most frequently involved sinus in these cases is Superior sagital thrombosis; however multiple sinus involvement is not uncommon. ( Images 1to5). (24-25)

A study reported with 20 cases of venous stroke reported, 9 had hematologic malignancies and 11 had solid tumors. The median interval from cancer diagnosis to presentation was 4 months for hematological and 20 months for Solid tumors. Multiple sinuses were affected in 8 of 19 patients. Disorders of coagulation were the most frequent etiology in patients with hematological malignancies; compression or invasion of the cerebral sinus from dural/ metastasis was the main cause in those with solid tumors. Treatment was directed at the underlying cause. Ten of 20 patients improved clinically and 3 of 6 patients improved radiologically on treatment. (26)

Anticoagulation & Thrombolysis

Anticoagulation is the mainstay of treatment in venous stroke in malignancy. Treatment with Low molecular wt heparin overlapped with warfarin is reported to be beneficial. Low molecular wt heparin is found to be superior to unfractionated heparin in the management. . Enoxaparin was safely administered to a series of seven patients for thrombotic complications in children undergoing cancer chemotherapy. Cancer patients not undergoing treatment and without a history of venous thrombosis does not, as a general rule, require prophylaxis. However in cases with high risk mainstay of primary prevention is low molecular weight heparin. The duration of prophylaxis should usually last for the period of treatment, except in the case of pelvic or cerebral radiotherapy where it is continued for 4-12 months beyond the treatment period:

Another study reports Dural sinus thrombosis developed in with acute lymphoblastic leukemia during induction treatment with vincristine sulfate, prednisone, and asparaginase. The cause is presumed to be secondary to hypercoagulability due to asparaginase-induced antithrombin III deficiency. The patients who received anticoagulation therapy recovered completely. Only two of the six reported patients without heparinization survived.(27,28)

A study with comprehensive search for studies of anticoagulation in cancer patients including January 2007: (Cochrane Central Register of Controlled Trials.) had similar results. Randomized clinical trials comparing LMWH, unfractionated heparin, and fondaparinux in patients with cancer .Using a standardized data form Meta-analysis of 11 studies showed a statistically significant mortality reduction in patients treated with LMWH compared with those treated with unfractionated heparin. (29)

Clinical trials have suggested a clinically relevant effect of low-molecular-weight heparin (LMWH), as compared with unfractionated heparin, on the survival of cancer patients with deep vein thrombosis. Similarly, the impact of warfarin on the survival of cancer patients with thromboembolic disorders was demonstrated. Studies demonstrated a significant role for LMWH, warfarin, anti-VIIa, and LMWH- on the regulation of angiogenesis, tumor growth and tumor metastasis. Thus, modulation of tissue factor/VIIa the noncoagulant activities by LMWH, warfarin, anti-VIIa, may be a useful therapeutic method for the inhibition of angiogenesis associated with human tumor growth and metastasis.(28)

Catastrophic intracranial dural and deep cerebral venous thrombosis may be treated by using a multimodality endovascular approach .Not much data is available for the use of thrombolytic therapy in cerebral cases unlike the systemic thrombosis. A series of 6 patients in which one had an underlying malignancy treated with endovascular thrombolysis along with mechanical devices reported improvement .All patients underwent diagnostic cerebral angiograms followed by transvenous catheterization and selective sinus and deep venous micro catheterization. Urokinase was delivered at the proximal aspect of the thrombus in dosages of 200,000 to 1,000,000 IU. Radiological studies obtained 24 hours after thrombolysis reconfirmed sinus/vein patency in all patients. All patients’ symptoms and neurological deficits improved, and no procedural complications ensued .Patients with both dural and deep cerebral venous thrombosis often have a variable clinical course and an unpredictable neurological outcome. The current intervention strategies for cerebral venous sinus thrombosis involve multimodality treatment using anticoagulation, thrombolysis by different routes, mechanical thrombectomy and surgical treatments for raised intracranial pressure and clot removal. The evidence base for this approach is slowly being built up as awareness of these techniques increases. Although conflicting opinions exist over safety and outcomes, the future looks optimistic for the treatment of this disorder. Further study is needed before evidence based treatment recommendations can be made. Endovascular therapy is warranted in symptomatic patients early in the disease course, prior to morbid and potentially fatal neurological deterioration.

Data from the peripheral venous system thrombosis clearly shows that interventional techniques improves outcome without any significant increase in complications. Regarding interventional treatment, catheter-directed thrombolysis can be applied to dissolve thrombus in selected patients with symptomatic occlusion and no contraindications to therapy. Acute occlusion of the pelvic veins and the inferior vena cava, often due to extension from the femoropopliteal system, represents a major risk for pulmonary embolism. Apart from catheter-directed thrombolysis, mechanical thrombectomy has proven to be a quick and safe treatment modality by enabling the recanalization of thrombotic occlusions in conjunction with minimal invasiveness and low bleeding risk. Mechanical thrombectomy devices should only be used in conjunction with a temporary cava filter. Catheter-directed thrombolysis is known to improve lysis rates. Together with balloon angioplasty good results have been obtained. If stenosis remains after thrombolysis and angioplasty and/or stent placement should follow. A short thrombosis can be treated with balloon angioplasty alone, whereas an extensive thrombosis requires a combination of mechanical devices and/or thrombolytic agents with adjunctive balloon angioplasty (30, 31, 32)

Malignancy is a prothrombotic state for CVT. It is a poor predictor of outcome in patients with cerebral venous thrombosis. Anticoagulation is the standard and mainstay for treatment of patients with cerebral venous sinus thrombosis. The duration of management is not specified. Prophylaxis with heparin is generally not recommended in cancer patients. Patients who are unresponsive to standard therapy may or are presenting with poor prognostic signs should be treated with endovascular therapy. (33).

Further study is needed and data is expected from dedicated oncology centers where these cases will be maximum before evidence based treatment recommendations can be made.

1) Ribes MF. Des recherches faites sur la phlebite Revue MedicalFrancais et Etrangere er Journal de clinique del ’Hotel Dieuet de la Charite de Paris 1825; 3: 5 (cited in 24).

2) Rogers LR Cerebrovascular complications in patients with cancer Semin Neurol, 24(4): 453-60 2004

3) Amagasaki K , Yamazaki H , Ohmori K , Koizumi H , Hashizume K , Sasaguchi N Malignant intravascular lymphomatosis associated with venous stenosis. Case report. J Neurosurg, 90(2): 355-8 1999

4) Abudoureyimu S , Zhang HL , Aizezi R , Jin W , Upur H Changes of prethrombotic state indexes in patients with malignant cancer Zhong Nan Da Xue Xue Bao Yi Xue Ban, 32(6): 973-7 2007

5) Astudillo L, Lacroix-Triki M, Cousin F, Chevreau C A rarely diagnosed paraneoplastic syndrome: cerebral venous thrombosis Rev Med Interne. 2007 Oct; 28(10):716-7

6) Ho CL , Chen CY , Chen YC , Chao TY Cerebral dural sinus thrombosis in acute lymphoblastic leukemia. Ann Hematol, 79(2): 90-4 2000

7) Vázquez E , Lucaya J , Castellote A , Piqueras J , Sainz P , Olivé T , Sánchez-Toledo J , Ortega JJ Neuroimaging in pediatric leukemia and lymphoma: differential diagnosis Radiographics, 22(6): 1411-28 2002

8) Peniket AJ , Miszkiel K , Patterson K , Goldstone AH , Mackinnon S , Hall-Craggs MA MR angiographic diagnosis of cerebral venous sinus thrombosis following allogeneic bone marrow transplantation Bone Marrow Transplant, 25(7): 791-5 2000

9) Ideguchi H, Ohno S, Ueda A, Ishigatsubo Y Catastrophic antiphospholipid syndrome associated with malignancies (case report and review of literature.Lupus. 2007; 16(1):59-64.

10) Kiya K , Satoh H , Mizoue T , Kinoshita Y Postoperative cortical venous infarction in tumours firmly adherent to the cortex. J Clin Neurosci, 8 Suppl 1(): 109-13 2001

11) Hasselbalch HC , Mourits-Andersen HT , Jensen BA , Jensen MK , Nielsen OJ Acute thrombotic complication at the debute of the Philadelphia chromosome-negative myeloproliferative syndrome.Ugeskr Laeger, 163(18): 2478-81 2001

12) LÃpez-Peláez MF , Millán JM , de Vergas J Fatal cerebral venous sinus thrombosis as major complication of metastatic cervical mass: computed tomography and magnetic resonance findings.J Laryngol Otol, 114(10): 798-801 2000

13) Mazzoleni S , Putti MC , Simioni P , Sainati L , Tormene D , Manara R , Carli M Early cerebral sinovenous thrombosis in a child with acute lymphoblastic leukemia carrying the prothrombin G20210A variant: a case report and review of the literature Blood Coagul Fibrinolysis, 16(1): 43-9 2005

14) TÃth L , Szakáll S , Káposzta Z , Udvardy M Cerebral deep vein thrombosis associated with rectal cancer Orv Hetil, 141(46): 2493-6 2000

15) Hotton KM , Khorsand M , Hank JA , Albertini M , Kim KM , Wilding G , Salamat MS , Larson M , Sondel P , Schiller JH A phase Ib/II trial of granulocyte-macrophage-colony stimulating factor and interleukin-2 for renal cell carcinoma patients with pulmonary metastases: a case of fatal central nervous system thrombosis Cancer, 88(8): 1892-901 2000

16) Schnittger C , Kolbe H , Fedorowski A , Heidenreich F Neurocutaneous melanoblastosis associated with cerebral sinus venous thrombosis. J Neurol, 246(3): 218-20, 1999

17) Payne JH, Vora AJ Thrombosis and Acute lymphoblastic leukemia. Br J Haematol. 2007 Aug; 138(4):430-45. Lockman LA, Mastri A, Priest JR, et al. Dural venous thrombosis in acute lymphoblastic leukemia. Pediatrics. 1980; 66: 943–947.

18) Payne JH, Vora AJ. Thrombosis in lymphoblastic leukem Br J Hematol 2007 Aug; 138(4):430-45.

19) El Amrani, Aidi S, Amarenco P.Cerebral ischemic events and anti-cancer therapy.Rev neurol (Paris). 159(4) 371-380,2003

20) Agirbasli M , Baykan OA , Tekin A , Sengor F, Cincin AA , Demir M , Vaughan DE .Short term effects of GnRH agonists on plasma fibrinolytic balance in patients with advanced prostate cancer J Thromb Thrombolysis, (): 0 2008

21) Reuner KH, Ruf A, Grau A, et al. Prothrombin gene G20210A transition is a risk factor for cerebral venous thrombosis. Stroke. 1998; 29: 1765–1769.

22) Stam, J. Thrombosis of the Cerebral Veins and Sinuses. N Engl J Med 2005; 352: 1791-98.

23) Prakash C, Bansal BC. Cerebral venous thrombosis. J Indian Acad Clin Med 2000;5:55-61.

24) Raizer and DeAngelis Cerebral sinus thrombosis diagnosed by MRI and MR venography in cancer patients Neurology.2000; 54: 1222-1226

25) Cerebral sinus thrombosis diagnosed by MRI and MR venography in cancer patients Rodas et al. Neurology.2000; 55: 903

26) Jeffrey J. Raizer, MD and Lisa M. DeAngelis, MD Cerebral sinus thrombosis diagnosed by MRI and MR venography in cancer patients Neurology 2000;54:1222-1226

27) Stine KC, Saylors RL, Saccente CS, Becton DL.Treatment of deep vein thrombosis with enoxaparin in pediatric cancer patients receiving chemotherapy.Clin Appl Thromb Hemost. 2007 Apr; 13(2):161-5.

28) Shaker A Mousa Anti-thrombotics in thrombosis and cancer. Future Oncology Jun 2005, Vol. 1, No. 3, Pages 395-403

29) Akl E , Rohilla S , Barba M , Sperati F , Terrenato I , Muti P , SchÃnemann H Anticoagulation for the intial treatment of venous thromboembolism in patients with cancer.Cochrane Database Syst Rev, (1): CD006649 2008

30) Simon A , Bode U , Lieber K , Beutel K , Fleischhack G Review and update of the use of urokinase in theprevention and management of CVAD-related complications in pediatric oncology patients.Am J Infect Control, 36(1): 54-8 2008

31) Mahanty HD , Posselt AM , Lipshutz GS , Schneider DB , Freise CE Catheter-directed therapy for DVT after pancreas transpl. Clin Transplant, 21(6): 748-54 2007

32) Philips MF , Bagley LJ , Sinson GP , Raps EC , Galetta SL , Zager EL , Hurst RW Endovascular thrombolysis for symptomatic cerebral venous thrombosis .J Neurosurg, 90(1): 65-71 1999

33) Breteau G , Mounier-Vehier F , Godefroy O , Gauvrit JY , Mackowiak-Cordoliani MA , Leys D Cerebral venous thrombosis 3-year clinical outcome in 55 consecutive patients J Neurol, 250(1): 29-35 2003

SECTION V
Role of Functional Imaging in Interventional Radiology

Contributors:
Dr. V. Rangarajan
Dr. Anshu Rajnish
Dr. Nilendu Purandare
Dr. Sneha Shah

PET-CT IN RADIO-FREQUENCY ABLATION

Surgical resection is the treatment of choice in patients with colorectal liver metastases. The 5-year survival rate after resection of colorectal liver metastases ranges between 25% and 40%, with a median survival time between 28 and 46 months.1-6. (Suffix)

Local ablative techniques such as cryosurgery ablation (CSA) and radiofrequency ablation (RFA) have been used for the treatment of colorectal liver metastases.7-11

Positron emission tomography (PET) with fluorine-18-deoxyglucose (FDG) is an imaging modality that allows direct evaluation of cellular glucose metabolism. Being a functional imaging modality, FDG-PET is of added value in differentiating between residual tumor, recurrent disease, and postoperative treatment changes.The potential role of FDG-PET in measuring the efficacy of local tumor ablation as well as the added value of FDG-PET in the detection of tumor recurrence during follow-up has been studied. This study by Langenhoff et al 12 showed that FDG-PET performed early after treatment by differentiating post treatment changes from residual or recurrent malignant tumor can provide additional information about the efficacy of local tumor ablation. This study also provides evidence that FDG-PET has an added value in the detection of tumor recurrence during follow-up. FDG-PET reveals hepatic recurrences in or outside the treated area as well as extra hepatic recurrences earlier than conventional follow-up, ie, CT scan and CEA (carcinoma embryonic antigen) measurement.

However limited data is available about the value of using FDG PET in humans during the hours after RFA. Veit et al. 13 retrospectively evaluated 15 liver metastases in 11 patients who had undergone FDG PET within 2 days after RFA.They have reported a false positive inflammatory rim of uptake around the ablated lesion which can mask residual tumor tissue.
Khandani et al 14 addressed this issue in a prospective study which showed that 18F-FDG PET can be used to evaluate the RFA site for macroscopic residual tumor within hours after ablation, a scan which they have termed “early PET.” Their hypothesis was that false-positive findings related to inflammation would not be observed at a very
early time point so that any residual focal uptake would likely be gross residual tumor.

Assessment of extent of ablation with FDG PET would allow a second RFA procedure to be performed early when its efficacy is likely to be higher.

Thus there is robust evidence available for this new potential application of PET & it certainly warrants further prospective studies in that direction.

FDG-PET reveals hepatic recurrances in or outside the treated area as well as extrahepatic recurrances earlier than conventional follow up i.e. CT Scan & CEA measurement.

PET-CT In Directing Biopsies

Image guided biopsies have been the back bone of establishing diagnosis as well as for detecting recurrences in oncology. Computed tomography (CT scan) & ultrasound (USG) are the imaging modalities which are more commonly used for this purpose, whereas MRI & fluoroscopy are seldomly used to guide biopsies. Positron emission tomography (PET) imaging using FDG due to its ability to highlight viable portions of the tumor can be used to direct biopsies.
PET can be effectively used to direct bone biopsies to confirm metastatic involvement & provides incremental improvement to diagnostic yield over bone scintigraphy15.

In cases of large masses biopsy can be performed under CT guidance targeting the most FDG avid portion of the tumor. This will be very useful for histological tumor grading as biopsy would be obtained from the most metabolically active region of the tumor. This was studied by Hain et al in a prospective study of 20 patients in which they showed that the biopsy site suggested by FDG PET scan finding was representative of the most malignant site on histology16 .Thus PET appears to be a very useful tool to direct the site of biopsy in soft tissue masses with a clinical suspicion of sarcoma in addition to providing incremental value over CT scan & bone scintigraphy in directing interventions.

References

1. Fong Y, Cohen AM, Fortner JG, et al: Liver resection for colorectal metastases. J Clin Oncol 15:938-946, 1997.

2. Doci R, Gennari L, Bignami P, et al: One hundred patients with hepatic metastases from colorectal cancer treated by resection: Analysis of prognostic determinants. Br J Surg 78:797-801, 1991

3. Rosen CB, Nagorney DM, Taswell HF, et al: Perioperative blood transfusion and determinants of survival after liver resection for metastatic colorectal carcinoma. Ann Surg 216:493-504, 1992

4. Gayowski TJ, Iwatsuki S, Madariaga JR, et al: Experience in hepatic resection for metastatic colorectal cancer: Analysis of clinical and pathologic risk factors. Surgery 116:703-710, 1994

5. Scheele J, Stangl R, Altendorf-Hofmann A: Hepatic metastases from colorectal carcinoma: Impact of surgical resection on the natural history. Br J Surg 77:1241-1246, 1990

6. Wanebo HJ, Chu QD, Vezeridis MP, et al: Patient selection for hepatic resection of colorectal metastases. Arch Surg 131:322-329, 1996

7. Seifert JK, Junginger T, Morris DL: A collective review of the world literature on hepatic cryotherapy. J R Coll Surg Edinb 43:141-154, 1998

8. Bilchik AJ, Wood TF, Allegra DP: Radiofrequency ablation of unresectable hepatic malignancies: Lessons learned. Oncologist 6:24-33, 2001

9. Wood TF, Rose DM, Chung M, et al: Radiofrequency ablation of 231 unresectable hepatic tumors: Indications, limitations, and complications. Ann Surg Oncol 7:593-600, 2000

10. Ruers TJ, Jager GJ, Wobbes T: Cryosurgery for colorectal liver metastases. Semin Oncol 27:120-125, 2000 (suppl 10)

11. Elias D, Cavalcanti A, Sabourin JC, et al: Resection of liver metastases from colorectal cancer: The real impact of the surgical margin.Eur J Surg Cancer 24:174-179, 1998

12. Langenhoff BS, Oyen WJ, Jager GJ, et al. Efficacy of fluorine-18-deoxyglucose positron emission tomography in detecting tumor recurrence after local ablative therapy for liver metastases: a prospective study. J Clin Oncol 2002; 20:4453–4458

13 Veit P, Antoch G, Stergar H, Bockisch A, Forsting M, Kuehl H. Detection of residual tumor after radiofrequency ablation of liver metastasis with dualmodality PET/CT: initial results. Eur Radiol 2006;16:80–87

14 Amir H. Khandani,Benjamin F. Calvo,Bert H. O’Neil,Jennifer Jorgenson,Matthew A. Mauro.A Pilot Study of Early 18F-FDGPET to Evaluate the Effectiveness of Radiofrequency Ablation of Liver Metastases. AJR 2007; 189:1199–1202.

15 Pezeshk P,Sadow CA,Winalski CS et al.Usefulness of 18 F-FDG PET-Directed skeletal biopsy for metastatic neoplasm.Acad Radiol 2006;13:1011-1015.

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Single Photon Computerized Emission Tomography (Spect) Study of Brain Perfusion –
Role in Balloon Test Occlusion

Occlusion of internal carotid artery is often necessary to treat tumors invading internal carotid artery, ulcerative carotid artery, and aneurysm. The balloon occlusion test of the internal carotid artery has been used to predict whether the patient will be able to tolerate temporary or permanent occlusion of ICA.While this can be achieved by various studies including Xenon 133 studies, Perfusion CT, MRI etc. SPECT- Single Photon Emission Computerized Tomography study with Brain perfusion agents like 99mTc ECD or 99mTc HMPAO is easy and useful.

Principle: The SPECT agents mentioned above are lipophilic agents that cross the blood brain barrier and once it is within the parenchyma, undergoes a PH shift and gets fixed. It cannot leave or move back through the blood brain barrier and hence is fixed. The tracer uptake and distribution seen therefore is a reflection of the status of the regional blood flow at the time of injection. Since the tracer is injected approximately at the last third of the occlusion period, the SPECT is a true representation of the status of the regional blood flow and indirectly the metabolism.

Technique:

A baseline SPECT scan is done with 20mCi 99mTc ECD at least a day before the balloon occlusion study.
On the day of the test occlusion, 20-30mCi 99mTc ECD is injected under regulatory guidelines, approximately 15 minutes after the beginning of balloon occlusion. Post study, a SPECT study is done after the patient is stable within 12 -24 hours.
Both the studies – baseline and post occlusion studies are compared and are assessed qualitatively and quantitatively.

References

1. Balloon occlusion test of the internal carotid artery: correlation with stump pressure and 99mTc-HMPAO SPECT.

Kato K, Tomura N, Takahashi S, Sakuma I, Sasaki K, Kitani H, Watarai J

Acta Radiol. 2006 Dec;47(10):1073-8.

2. Spect measurements of regional cerebral perfusion and carbon dioxide reactivity: correlation with cerebral collaterals in internal carotid artery occlusive disease de Boorder MJ, van der Grond J, van Dongen AJ, Klijn CJ, Jaap Kappelle L, Van Rijk PP, Hendrikse J.

J Neurol. 2006 Oct;253(10):1285-91.

3. Comparison of technetium Tc 99m hexamethylpro-pyleneamine oxime single-photon emission tomograph with stump pressure during the balloon occlusion test of the internal carotid artery.

Tomura N, Omachi K, Takahashi S, Sakuma I, Otani T, Watarai J, Ishikawa K, Kinouchi H, Mizo

AJNR Am J Neuroradiol. 2005 Sep;26(8):1937-42

4. The magnetic resonance Matas test: Feasibility and comparison with the conventional intraarterial balloon test occlusion with SPECT perfusion imaging

Hori M, Okubo T, Aoki S, Ishigame K, Araki T, Nukui H.

J Magn Reson Imaging. 2005 Jun;21(6):709-14

5. Elective stenting for symptomatic middle cerebral artery stenosis presenting as transient ischaemic deficits or stroke attacks: short term arteriographical and clinical outcome.

Kim JK, Ahn JY, Lee BH, Chung YS, Chung SS, Kim OJ, Kim WC, Joo JY

J Neurol Neurosurg Psychiatry. 2004 Jun;75(6):847-51

6. Evaluating brain tolerability to carotid artery occlusion.

Zhong J, Ding M, Mao Q, Wang B, Fu H

Neurol Res. 2003 Jan;25(1):99-103

7. Correlative assessment of hemodynamic parameters obtained with T2*-weighted perfusion MR imaging and SPECT in symptomatic carotid artery occlusion

Kim JH, Lee SJ, Shin T, Kang KH, Choi PY, Kim JH, Gong JC, Choi NC, Lim BH.

AJNR Am J Neuroradiol. 2000 Sep;21(8):1450-6