Gilles Mentha

Effect of Surgical Margin Status on Survival and Site of Recurrence After Hepatic Resection for Colorectal Metastases

Objective:To evaluate the influence of surgical margin status on survival and site of recurrence in patients treated with hepatic resection for colorectal metastases. Methods:Using a multicenter database, 557 patients who underwent hepatic resection for colorectal metastases were identified. Demographics, operative data, pathologic margin status, site of recurrence (margin, other intrahepatic site, extrahepatic), and long-term survival data were collected and analyzed. Results:On final pathologic analysis, margin status was positive in 45 patients, and negative by 1 to 4 mm in 129, 5 to 9 mm in 85, and ≥1 cm in 298. At a median follow-up of 29 months, the 1-, 3-, and 5-year actuarial survival rates were 97%, 74%, and 58%; median survival was 74 months. Tumor size ≥5 cm, >3 tumor nodules, and carcinoembryonic antigen level >200 ng/mL predicted poor survival (all P < 0.05). Median survival was 49 months in patients with positive margins and not yet reached in patients with negative margins (P = 0.01). After hepatic resection, 225 (40.4%) patients had recurrence: 21 at the surgical margin, 56 at another intrahepatic site, 82 at an extrahepatic site, and 66 at both intrahepatic and extrahepatic sites. Patients with negative margins of 1 to 4 mm, 5 to 9 mm, and ≥1 cm had similar overall recurrence rates (P > 0.05). Patients with positive margins were more likely to have surgical margin recurrence (P = 0.003). Adverse preoperative biologic factors including tumor number greater than 3 (P = 0.01) and a preoperative CEA level greater than 200 ng/mL (P = 0.04) were associated with an increased risk of positive surgical margin. Conclusions:A positive margin after resection of hepatic colorectal metastases is associated with adverse biologic factors and increased risk of surgical-margin recurrence. The width of a negative surgical margin does not affect survival, recurrence risk, or site of recurrence. A predicted margin of <1 cm after resection of hepatic colorectal metastases should not be used as an exclusion criterion for resection.

Hepatocyte steatosis is a cytopathic effect of hepatitis C virus genotype 3.

BACKGROUND/AIMS Patients infected with the hepatitis C virus (HCV) often have liver steatosis, suggesting the possibility of a viral cytopathic effect. The aim of this study was to correlate the occurrence and severity of liver steatosis with HCV RNA type, level and sequence of the core-encoding region. METHODS We scored the liver steatosis in 101 HCV-infected individuals carefully selected to exclude other risk factors of a fatty liver. Results were compared with HCV RNA genotype and level in serum and liver. In selected patients, we assessed the effect of antiviral therapy on steatosis and the relationship between nucleocapsid sequence heterogeneity and fat infiltration. RESULTS Steatosis was found in 41 (40.6%) patients, irrespective of sex, age or route of infection. HCV genotype 3 was associated with higher steatosis scores than other genotypes. A significant correlation between steatosis score and titer of intrahepatic HCV RNA was found in patients infected with genotype 3, but not in those infected with genotype 1. In selected patients, response to alpha-interferon was associated with the disappearance of steatosis. Analysis of the nucleocapsid of 14 HCV isolates failed to identify a sequence specifically associated with the development of steatosis. CONCLUSIONS We provide virological and clinical evidence that the steatosis of the liver is the morphological expression of a viral cytopathic effect in patients infected with HCV genotype 3. At variance with published evidence from experimental models, the HCV nucleocapsid protein does not seem to fully explain the lipid accumulation in these patients.

Rates and patterns of recurrence following curative intent surgery for colorectal liver metastasis: An international multi-institutional analysis of 1669 patients

Objective(s):To investigate rates and patterns of recurrence in patients following curative intent surgery for colorectal liver metastasis. Background:Outcomes following surgical management of colorectal liver metastasis have largely focused on overall survival. Contemporary data on rates and patterns of recurrence following surgery for colorectal liver metastasis are limited. Methods:One thousand six hundred sixty-nine patients treated with surgery (resection ± radiofrequency ablation [RFA]) for colorectal liver metastasis between 1982 and 2008 were identified from an international multi-institutional database. Clinicopathologic data, recurrence patterns, and recurrence-free survival (RFS) were analyzed. Results:At the time of the initial liver-directed surgery, surgical treatment was resection only (90.2%), resection plus RFA (8.0%), or RFA alone (1.8%). While 5-year overall survival was 47.3%, 947 (56.7%) patients recurred with a median RFS time of 16.3 months. First recurrence site was intrahepatic only (43.2%), extrahepatic only (35.8%), intra- and extrahepatic (21.0%). There was no difference in RFS based on site of recurrence (intrahepatic: 16.9 months; extrahepatic: 16.6 months; intra- and extrahepatic: 16.2 month; P > 0.05). Receipt of adjuvant chemotherapy was associated with overall recurrence risk (hazard ratio [HR] = 0.56), while history of RFA (HR = 2.39, P = 0.001) and R1 margin status (HR = 1.36) were predictive of intrahepatic recurrence. Pattern of recurrence and RFS remained similar following repeat surgery for recurrent disease. Conclusions:While 5-year survival following surgery for colorectal liver metastasis approaches 50%, over one-half of patients develop recurrence within 2 years. The pattern of failure is distributed relatively equally among intrahepatic, extrahepatic, and intra- plus extrahepatic sites. Patients undergoing repeat surgery for recurrent metastasis have similar patterns of recurrence and RFS time.

Budd-Chiari syndrome: a review by an expert panel

Harry L.A. Janssen*, Juan-Carlos Garcia-Pagan, Elwyn Elias, Gilles Mentha, Antoine Hadengue, Dominique-Charles Valla, for the European Group for the Study of Vascular Disorders of the Liver Department of Gastroenterology and Hepatology, University Hospital Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, Barcelona, Spain Liver Unit, Queen Eilzabeth Hospital, Birmingham, UK Division of Hepatology and Transplantation Unit, University Hospital of Geneva, Geneva, Switzerland Service d’Hepatologie, Hopital Beaujon, Clichy, France

Hepatic Resection for Noncolorectal Nonendocrine Liver Metastases: Analysis of 1452 Patients and Development of a Prognostic Model

Objective:To determine the utility of hepatic resection (HR) in the treatment of patients with noncolorectal nonendocrine liver metastases (NCNELM). Summary Background Data:The place of HR in the treatment of NCNELM remains controversial, primarily due to the limitations of previously published reports and the heterogeneity of primary tumor sites and histologies. Methods:A multivariate risk model was developed by analyzing prognostic factors and long-term outcomes in 1452 patients with NCNELM treated with HR at 41 centers from 1983 to 2004. Results:Hepatic metastases were solitary in 56% and unilateral in 71% (mean diameter, 50.5 mm). Extrahepatic metastases were present in 22%. The most common primary sites were breast (32%), gastrointestinal (16%), and urologic (14%). The most common histologies were adenocarcinoma (60%), GIST/sarcoma (13.5%), and melanoma (13%). R0 resection was achieved in 83% of patients with a 60-day mortality rate of 2.3% and a major complication rate of 21.5%. Tumor recurred in 67% of patients (liver, 24%; extrahepatic, 18%; both, 25%). Overall and disease-free survivals at 5 years were 36% and 21% and at 10 years were 23% and 15%, respectively. In multivariate analysis, factors associated with poor prognosis were patient age >60 years, nonbreast origin, melanoma or squamous histology, disease-free interval <12 months, extrahepatic metastases, R2 resection, and major hepatectomy (all P ≤ 0.02). A prognostic model based on these factors effectively stratified patients into low-risk (0–3 points, 46% 5-year survival), mid-risk (4–6 points, 33% 5-year survival), and high-risk (>6 points, <10% 5-year survival) groups (P = 0.0001). Discussion:HR for NCNELM is safe and effective, with outcomes mainly dependent on primary tumor site and histology. For individual patients, a statistical model based on key prognostic factors could validate the indication for hepatic resection by predicting long-term survivals.

Intrahepatic Cholangiocarcinoma: An International Multi-Institutional Analysis of Prognostic Factors and Lymph Node Assessment

PURPOSE To identify factors associated with outcome after surgical management of intrahepatic cholangiocarcinoma (ICC) and examine the impact of lymph node (LN) assessment on survival. PATIENTS AND METHODS From an international multi-institutional database, 449 patients who underwent surgery for ICC between 1973 and 2010 were identified. Clinical and pathologic data were evaluated using uni- and multivariate analyses. RESULTS Median tumor size was 6.5 cm. Most patients had a solitary tumor (73%) and no vascular invasion (69%). Median survival was 27 months, and 5-year survival was 31%. Factors associated with adverse prognosis included positive margin status (hazard ratio [HR], 2.20; P < .001), multiple lesions (HR, 1.80; P = .001), and vascular invasion (HR, 1.59; P = .015). Tumor size was not a prognostic factor (HR, 1.03; P = .23). Patients were stratified using the American Joint Committee on Cancer/International Union Against Cancer T1, T2a, and T2b categories (seventh edition) in a discrete step-wise fashion (P < .001). Lymphadenectomy was performed in 248 patients (55%); 74 of these (30%) had LN metastasis. LN metastasis was associated with worse outcome (median survival: N0, 30 months v N1, 24 months; P = .03). Although patients with no LN metastasis were able to be stratified by tumor number and vascular invasion (N0; P < .001), among patients with N1 disease, multiple tumors and vascular invasion, either alone or together, failed to discriminate patients into discrete prognostic groups (P = .34). CONCLUSION Although tumor size provides no prognostic information, tumor number, vascular invasion, and LN metastasis were associated with survival. N1 status adversely affected overall survival and also influenced the relative effect of tumor number and vascular invasion on prognosis. Lymphadenectomy should be strongly considered for ICC, because up to 30% of patients will have LN metastasis.

Neoadjuvant chemotherapy and resection of advanced synchronous liver metastases before treatment of the colorectal primary

In many patients with advanced synchronous liver metastases from colorectal tumours, the metastases progress during treatment of the primary, precluding curative treatment. The authors have investigated a management strategy that involves high‐impact chemotherapy first, resection of liver metastases second and finally removal of the primary tumour in patients with adverse prognostic factors.

OncoSurge: A Strategy for Improving Resectability With Curative Intent in Metastatic Colorectal Cancer

PURPOSE Most patients with colorectal liver metastases present to general surgeons and oncologists without a specialist interest in their management. Since treatment strategy is frequently dependent on the response to earlier treatments, our aim was to create a therapeutic decision model identifying appropriate procedure sequences. METHODS We used the RAND Corporation/University of California, Los Angeles Appropriateness Method (RAM) assessing strategies of resection, local ablation and chemotherapy. After a comprehensive literature review, an expert panel rated appropriateness of each treatment option for a total of 1,872 ratings decisions in 252 cases. A decision model was constructed, consensus measured and results validated using 48 virtual cases, and 34 real cases with known outcomes. RESULTS Consensus was achieved with overall agreement rates of 93.4 to 99.1%. Absolute resection contraindications included unresectable extrahepatic disease, more than 70% liver involvement, liver failure, and being surgically unfit. Factors not influencing treatment strategy were age, primary tumor stage, timing of metastases detection, past blood transfusion, liver resection type, pre-resection carcinoembryonic antigen (CEA), and previous hepatectomy. Immediate resection was appropriate with adequate radiologically-defined resection margins and no portal adenopathy; other factors included presence of < or = 4 or > 4 metastases and unilobar or bilobar involvement. Resection was appropriate postchemotherapy, independent of tumor response in the case of < or = 4 metastases and unilobar liver involvement. Resection was appropriate only for > 4 metastases or bilobar liver involvement, after tumor shrinkage with chemotherapy. When possible, resection was preferred to local ablation. CONCLUSION The results were incorporated into a decision matrix, creating a computer program (OncoSurge). This model identifies individual patient resectability, recommending optimal treatment strategies. It may also be used for medical education.

Sinusoidal obstruction syndrome and nodular regenerative hyperplasia are frequent oxaliplatin-associated liver lesions and partially prevented by bevacizumab in patients with hepatic colorectal metastasis

Rubbia‐Brandt L, Lauwers G Y, Wang H, Majno P E, Tanabe K, Zhu A X, Brezault C, Soubrane O, Abdalla E K, Vauthey J‐N, Mentha G & Terris B
(2010) Histopathology56, 430–439
Sinusoidal obstruction syndrome and nodular regenerative hyperplasia are frequent oxaliplatin‐associated liver lesions and partially prevented by bevacizumab in patients with hepatic colorectal metastasis

Living donor liver transplantation for early hepatocellular carcinoma: a life expectancy and cost-effectiveness perspective

Cadaveric liver transplantation (CLT) is an excellent treatment for early hepatocellular carcinoma (HCC). Its use, however, is limited by the shortage of grafts, with up to 30% of patients developing contraindications to the procedure while waiting for a donor. Living donor liver transplantation (LDLT) has emerged as an alternative to overcome this limitation. We compared the consequences of LDLT versus CLT using a Markov model balancing the gains and losses in life expectancy among donors and recipients. For a 60-year-old recipient with a 70% 5-year survival after transplantation, a 4% monthly drop-out rate, and a donor with 1% mortality, LDLT became more effective than CLT after 3.5 months on the waiting list. These results varied with the probability of developing contraindications to transplantation, the survival after transplantation, and the donors mortality. For a 12-month delay saved on the waiting list, the gain in survival provided by LDLT compared with CLT ranged between 0 and 2.8 life years depending on survival after transplantation, time spent on the waiting list, and drop-out rate. LDLT was cost-effective (less than