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Background: HCC are known to have satellite nodules and microvascular invasions requiring sufficient margins. An alpha-fetoprotein (AFP) level >100 ng/mL is associated with worse pathological features in HCC. In practice, large resection margins, particularly >1 cm, are infrequently retrieved on the specimens., Methods: 397 patients from 5 centres were included from 2012 to 2017. The primary endpoint was time-to-recurrence in relation to AFP level (> or <100 ng/ml) as well as surgical margins (> or <1 cm). The secondary endpoint was overall survival (OS)., Results: The median follow-up was 25 months. In Low AFP group, median time to recurrence (TTR) for patients with margins <1 cm was 36 months and for patients with margins ≥1 cm was 34 months (p = 0.756), and overall survival (OS) was not significantly different according to margins (p = 0.079). In High-AFP group, patients with margins <1 cm had a higher recurrence rate than patients with margins ≥1 cm (p = 0.016): median TTR for patients with margins <1 cm was 8 months whereas it was not reached for patients with margins ≥1 cm. Patients with margins <1 cm had a significantly worse OS compared to the patients with margins ≥1 cm (p = 0.043)., Conclusion: Preoperative AFP level may help determine margins to effectively treat high AFP tumours. For low-AFP tumours, margins didn't have an impact on TTR or OS., (Copyright © 2021 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Introduction: Major hepatectomy (MH) is often needed in the curative management of intrahepatic cholangiocarcinoma (IHCC) and colorectal liver metastases (CRLM). While similar outcomes could be expected after MH for IHCC and CRLM, outcomes seem worse after MH for IHCC. A better understanding of such differences might help improving perioperative outcomes but comprehensive analysis are lacking., Methods: All patients undergoing curative intent MH for IHCC or CRLM from 2003 to 2009 were included from two dedicated multi-institutional datasets. Preoperative management and short-term outcomes after MH were first compared. Independent predictors of postoperative mortality and morbidity were identified., Results: Among 827 patients, 333 and 494 patients underwent MH for IHCC and CRLM, respectively. Preoperative portal vein embolization was more frequently performed in the CRLM group (p < 0.001). MH in the IHCC group required more extended resection (p < 0.001). Postoperative mortality and severe morbidity rates were significantly higher in the IHCC group (7.2% vs. 1.2% and 29.7% vs. 11.1%, p < 0.001, respectively). Main causes for mortality were postoperative liver failure and deep surgical site infection. MH for IHCC was an independent risk factor for mortality (p < 0.001) and severe morbidity (p < 0.001). After propensity score matching (212 patients in each group), the aforementioned differences regarding outcomes remained statistically significant., Conclusion: This study suggests that IHCC patients are inherently more at risk after MH as compared to CRLM patients. Considering that postoperative liver failure was the most frequent cause of death, preoperative planning might have been inadequate in the setting of IHCC while more complex/extended resections should be expected., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background & Aims: Selection criteria for hepatectomy in patients with cirrhosis are controversial. In this study we aimed to build prognostic models of symptomatic post-hepatectomy liver failure (PHLF) in patients with cirrhosis., Methods: This was a cohort study of patients with histologically proven cirrhosis undergoing hepatectomy in 6 French tertiary care hepato-biliary-pancreatic centres. The primary endpoint was symptomatic (grade B or C) PHLF, according to the International Study Group of Liver Surgery's definition. Twenty-six preoperative and 5 intraoperative variables were considered. An ordered ordinal logistic regression model with proportional odds ratio was used with 3 classes: O/A (No PHLF or grade A PHLF), B (grade B PHLF) and C (grade C PHLF)., Results: Of the 343 patients included, the main indication was hepatocellular carcinoma (88%). Laparoscopic liver resection was performed in 112 patients. Three-month mortality was 5.25%. The observed grades of PHLF were: 0/A: 61%, B: 28%, C: 11%. Based on the results of univariate analyses, 3 preoperative variables (platelet count, liver remnant volume ratio and intent-to-treat laparoscopy) were retained in a preoperative model and 2 intraoperative variables (per protocol laparoscopy and intraoperative blood loss) were added to the latter in a postoperative model. The preoperative model estimated the probabilities of PHLF grades with acceptable discrimination (area under the receiver-operating characteristic curve [AUC] 0.73, B/C vs. 0/A; AUC 0.75, C vs. 0/A/B) and the performance of the postoperative model was even better (AUC 0.77, B/C vs. 0/A; AUC 0.81, C vs. 0/A/B; p <0.001)., Conclusions: By accurately predicting the risk of symptomatic PHLF in patients with cirrhosis, the preoperative model should be useful at the selection stage. Prediction can be adjusted at the end of surgery by also considering blood loss and conversion to laparotomy in a postoperative model, which might influence postoperative management., Lay Summary: In patients with liver cirrhosis, the risk of a hepatectomy is difficult to appreciate. We propose a statistical tool to estimate this risk, preoperatively and immediately after surgery, using readily available parameters and on online calculator. This model could help to improve the selection of patients with the best risk-benefit profiles for hepatectomy., (Copyright © 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Introduction: Epidemiological data is lacking on primary Budd-Chiari syndrome (BCS) in France., Methods: Two approaches were used: (1) A nationwide survey in specialized liver units for French adults. (2) A query of the French database of discharge diagnoses screening to identify incident cases in adults. BCS associated with cancer, alcoholic/viral cirrhosis, or occurring after liver transplantation were classified as secondary., Results: Approach (1) 178 primary BCS were identified (prevalence 4.04 per million inhabitants (pmi)), of which 30 were incident (incidence 0.68 pmi). Mean age was 40 ± 14 yrs. Risk factors included myeloproliferative neoplasms (MPN) (48%), oral contraceptives (35%) and factor V Leiden (16%). None were identified in 21% of patients, ≥2 risk factors in 25%. BMI was higher in the group without any risk factor (25.7 kg/m 2 vs 23.7 kg/m 2 , p < 0.001). Approach (2) 110 incident primary BCS were admitted to French hospitals (incidence 2.17 pmi). MPN was less common (30%) and inflammatory local factors predominated (39%)., Conclusion: The entity of primary BCS as recorded in French liver units is 3 times less common than the entity recorded as nonmalignant hepatic vein obstruction in the hospital discharge database. The former entity is mostly related to MPN whereas the latter with abdominal inflammatory diseases., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: The impact of intraoperative blood transfusion (IBT) on outcomes following intrahepatic cholangiocarcinoma (IHCC) resection remains to be ascertained., Methods: All consecutive IHCC resected were analyzed. A first cohort (n = 569) was used for investigating short-term outcomes (morbidity and mortality). A second cohort (n = 522) excluding patients dead within 90 days of surgery was analyzed for exploring overall survival (OS) and disease free survival (DFS). Patients who received IBT were compared to those who did not, after using a propensity score matching (PSM) method., Results: Among 569 patients, 90-day morbidity and mortality rates were 47% (n = 269) and 8% (n = 47). After PSM, 208 patients were matched. There was an association between IBT and increased overall morbidity and severe morbidity (p = 0.010). However, IBT did not impact 90-day mortality rate (p > 0.999). Regarding long-term outcomes analysis in the second cohort (n = 522), 5-year OS and DFS rates were 39% and 25%. Using PSM, 196 patients were matched and no association between IBT and OS or DFS was found (p = 0.333 and p = 0.491)., Conclusions: IBT is associated with an increased risk of morbidity but does not impact on long-term outcomes. Need for IBT should be considered as a surrogate of advanced disease requiring complex resection. Still, restricted transfusion policy should remain advocated for IHCC resection., (Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Information on the incidence, management, and prognosis of hepatocellular carcinoma (HCC) is derived from population samples, regional data, or registries. Comprehensive national evaluations within a given country are lacking. This study aimed to investigate regional variations in HCC care within France., Methods: This observational study analysed data from French administrative databases for more than 30,000 patients with HCC diagnosed between 2009 and 2012, and followed-up until 2013. The incidence of HCC, access to surgery, and survival, at both the national level and two geographical levels (the 21 French regions and 95 French departments into which France is divided administratively), were determined. The influence on outcome of the structure of the hospital where HCC was first managed was assessed., Results: At the national level, the median survival was 9.4months and only 22.8% of patients had curative treatment. There were marked variations between regions and departments in incidence, access to curative treatment (range 1.3-28.8% and 8.1-32.3% respectively), and in median survival (range 5.7-12.1 and 4.3-16.5months respectively). The administrative type and annual HCC-caseload of the hospital where patients were first admitted also had an independent influence on treatment and survival., Conclusion: Despite full insurance coverage for all citizens, national measures to reduce inequities in the management of cancer patients, standardised recommendations for HCC surveillance and management, the percentage of patients undergoing curative treatment and their survival may vary four-fold depending on their postcode. The hospital in which patients are first managed has a clear influence on accessibility to both good care and survival., Lay Summary: Population-based studies have highlighted large and sometimes unexpected differences between countries in the survival of patients with malignancy. As these differences are considered to indicate the overall effectiveness of health systems, in addition to the incidence of the cancer or quality of registration, variations within a given country should be minimal. However, similar to between countries differences, this study shows differences within the same country in the incidence, curative treatment rate, and survival of patients with HCC. Evidence that access to care and survival varies within a country can strengthen the impetus for government and clinicians to address these disparities., (Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Laparoscopic left lateral sectionectomy (LLS) has now become standard practice. However, published series are small and retrospective. The aim was to compare at a national level the use and short-term outcome of laparoscopic and open LLS., Methods: National hospital discharge databases were screened to identify all adult patients who had undergone elective LLS in France between 2007 and 2012. Outcome measurements included blood transfusion, severe morbidity, mortality and length of hospital stay. The independent influence of the laparoscopic approach on these outcomes was tested overall and after stratifying for the indication (benign condition, primary malignancy, liver metastasis)., Results: Over the 6-year study period, 2198 patients underwent LLS, accounting for 6.9% of all elective liver resections. Some 28.5% of LLS procedures were performed laparoscopically. Among hospitals in which LLS was carried out, 33.2% of procedures were done laparoscopically (median 2 laparoscopic LLS resections per year). The laparoscopic approach was independently associated with a shorter length of hospital stay irrespective of the indication, and a lower transfusion rate in patients with benign condition or primary malignancy., Conclusion: LLS is seldom performed and the laparoscopic approach has not been adopted widely. The potential benefit of laparoscopic LLS varies according to the indication., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Hepatocellular adenoma (HCA) is a benign hepatic lesion that may be complicated by bleeding and malignant transformation. The aim of the present study is to report on large series of liver resections for HCA and assess the incidence of hemorrhage and malignant transformation., Methods: A retrospective cross-sectional study, from 27 European high-volume HPB units., Results: 573 patients were analyzed. The female: male gender ratio was 8:2, mean age: 37 ± 10 years. Of the 84 (14%) patients whose initial presentation was hemorrhagic shock (Hemorrhagic HCAs), hemostatic intervention was urgently required in 25 (30%) patients. No patients died after intervention. Tumor size was >5 cm in 74% in hemorrhagic HCAs and 64% in non-hemorrhagic HCAs (p < 0.001). In non-hemorrhagic HCAs (n = 489), 5% presented with malignant transformation. Male status and tumor size >10 cm were the two predictive factors. Liver resections included major hepatectomy in 25% and a laparoscopic approach in 37% of the patients. In non-hemorrhagic HCAs, there was no mortality and major complications occurred in 9% of patients., Discussion: Liver resection for HCA is safe. Presentation with hemorrhage was associated with larger tumor size. In males with a HCA >10 cm, a HCC should be suspected. In such situation, a preoperative biopsy is preferable and an oncological liver resection should be considered., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Supra-mesocolic surgery (SMS) is complicated in patients with portal vein cavernoma (PC) and portal decompression is recommended. The aim of this study was to report a large single centre of SMS in patients with PC without portal decompression., Methods: Between 2006 and 2013, all patients who met inclusion criteria were analyzed retrospectively. The primary endpoint was the feasibility rate, surgical and postoperative outcome. The secondary endpoints were the long-term outcome of patients who underwent biliary bypass for cholangitis. Risk factors for complications were studied., Results: Thirty patients underwent 51 procedures. Pancreatitis was the main etiology of PC (19/30) and biliary obstruction was mainly related to the underlying disease and not to portal cholangiopathy (12/14). All planned procedures were successfully completed. Fourteen patients underwent biliary bypass. Median blood loss (250 ml), transfusion (n = 7), mortality (n = 0), overall morbidity (n = 12) and the median hospital stay (10 days). Good long-term control of cholangitis was achieved in the 9 patients alive with available follow-up. Significant risk factors for complications were a previous abdominal wall scar, previous intra-abdominal surgical field and liver fibrosis., Conclusion: SMS can be safely performed in patients with PC. In patients with risk factors for complications, portal decompression should be discussed., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) was recently developed to induce rapid hypertrophy and reduce post-hepatectomy liver failure in patients with insufficient remnant liver volume (RLV). However, mortality rates >12% have been reported. This study aimed to analyze the perioperative course of ALPPS and to identify factors associated with morbi-mortality., Methods: Between April 2011 and September 2013, 62 patients operated in 9 Franco-Belgian hepatobiliary centres underwent ALPPS for colorectal metastases (N = 50) or primary tumors, following chemotherapy (N = 50) and/or portal vein embolization (PVE; N = 9)., Results: Most patients had right (N = 31) or right extended hepatectomy (N = 25) (median RLV/body weight ratio of 0.54% [0.21-0.77%]). RLV increased by 48.6% [-15.3 to 192%] 7.8 ± 4.5 days after stage1, but the hypertrophy decelerated beyond 7 days. Stage2 was cancelled in 3 patients (4.8%) for insufficient hypertrophy, portal vein thrombosis or death and delayed to ≥9 days in 32 (54.2%). Overall, 25 patients (40.3%) had major complication(s) and 8 (12.9%) died. Fourteen patients (22.6%) had post-stage1 complication of whom 5 (35.7%) died after stage2. Factors associated with major morbi-mortality were obesity, post-stage1 biliary fistula or ascites, and infected and/or bilious peritoneal fluid at stage2. The latter was the only predictor of Clavien ≥3 by multivariate analysis (OR: 4.9; 95% CI: 1.227-19.97; p = 0.025). PVE did not impact the morbi-mortality rates but prevented major cytolysis that was associated with poor outcome., Conclusions: The inter-stages course was crucial in determining ALPPS outcome. The factors of high morbi-mortality rates associated with ALPPS are linked to the technique complexity., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Perioperative bleeding is a predictor of morbidity following liver resection. The transfusion-related score (TRS), which is derived from five variables (cirrhosis, preoperative haemoglobin level, tumour size, vena cava exposure and associated extraliver surgical procedure), has been proposed to predict the likelihood of transfusion in liver resection., Objective: The purpose of this observational study was to evaluate the external validity of the TRS., Methods: In a retrospective, monocentre, observational cohort study of patients undergoing elective liver resection surgery, data for transfused and non-transfused patients were compared by univariate analysis. The TRS was calculated for each patient. The frequency of transfusion was calculated for each score level. The accuracy of the TRS was evaluated using the area under the receiver operator characteristic curve (AUC)., Results: A total of 205 patients submitted to liver resection were included. Of these, 48 (23.4%) patients received a blood transfusion. There was no significant difference between transfused and non-transfused patients in age, American Society of Anesthesiologists (ASA) score or cirrhosis. The AUC for the TRS was 0.68 (95% confidence interval 0.59-0.77). Among TRS items, only vena cava exposure and associated surgical procedures were significantly associated with risk for transfusion., Conclusions: In the present population, the TRS appeared to serve as a weak predictor of perioperative transfusion. This study confirms that the external validity of the transfusion predictive score should be subject to further investigation before it can be implemented in clinical use., (© 2014 International Hepato-Pancreato-Biliary Association.)

Background: Liver resection is considered to offer the only hope of cure for patients with liver malignancy. However, there are concerns about its safety, particularly in view of the increasing efficacy of less invasive strategies. No systematic review of prognostic research in liver resections has yet been performed., Methods: A systematic search identified articles published between 1999 and 2012 that performed a risk prediction analysis in patients undergoing liver resection. Studies were included if an outcome occurring within 90 days of surgery was identified, multivariable analysis performed and regression coefficients provided. The main endpoints were the outcomes and predictors chosen by the investigators, their definition, the performance and validity of the models, and the quality of the study as assessed using the QUIPS (quality in prognosis studies) tool., Results: A total of 91 studies were included. Eleven were prospective, but only two of these were registered. Twenty-eight endpoints were identified. These focused on postoperative morbidity or mortality, but many were redundant or ill defined and other relevant patient-reported outcomes were lacking. Predictors were not standardized, were poorly defined and overlapped. Only nine studies assessed the performance of their models and seven made an internal or temporal validation, but none reported an external validation or impact analysis. The median QUIPS score was 34 out of 50, indicating a high risk for bias., Conclusion: Prognostic research in liver resection is still at the developmental stage., (© 2014 International Hepato-Pancreato-Biliary Association.)

Introduction: As mortality and morbidity after a curative resection remains high, it is essential to identify pre-operative factors associated with an early death after a major resection., Methods: Between 1998 and 2008, we selected a population of 331 patients having undergone a major hepatectomy including segment I with a lymphadenectomy and a common bile duct resection for a proven hilar cholangiocarcinoma in 21 tertiary centres. The study's objective was to identify pre-operative predictors of early death (<12 months) after a resection., Results: The study cohort consisted of 221 men and 110 women, with a median age of 61 years (range: 24-85). The post-operative mortality and morbidity rates were 8.2% and 61%, respectively. The 1-, 3- and 5-year overall survival rates were 85%, 64% and 53%, respectively. The median tumour size was 23 mm on pathology, ranging from 8 to 40. A tumour size >30 mm [odds ratio (OR) 2.471 (95% confidence interval (CI) 1.136-7.339), P = 0.001] and major post-operative complication [OR 3.369 (95% CI 1.038-10.938), P = 0.004] were independently associated with death <12 months in a multivariate analysis., Conclusion: The present analysis of a series of 331 patients with hilar cholangiocarcinoma showed that tumour size >30 mm was independently associated with death <12 months., (© 2014 International Hepato-Pancreato-Biliary Association.)

Introduction: A left lateral section is the first choice for a laparoscopic anatomic liver resection. The objective of this case-control study was to assess the surgical outcome after a laparoscopic left lateral resection for benign liver lesions compared with the open approach., Methods: From January 2004 to April 2011, 31 laparoscopic left lateral resections were matched with 31 open left lateral resections by selection based on pathology of the lesion, size of the lesion, American Society of Anesthesiologists (ASA) grade, body mass index (BMI), age and gender of the patient., Results: Duration of the operation (laparoscopic: 182 ± 71 versus open: 244 ± 105 min; P = 0.04), blood loss (223 ± 281 versus 455 ± 593 ml; P = 0.03), duration of hospital stay (4.1 ± 1.7 versus 8.1 ± 4.4 days; P < 0.001) and total cost of hospitalization (7475 ± 2679 versus 11504 ± 7776 Euros; P < 0.001) were significantly lower in the laparoscopic group., Conclusions: This matched case-control study demonstrated procedural safety, excellent post-operative outcomes and economic benefits for a laparoscopic liver resection. A laparoscopic left lateral liver sectionectomy is recommended as a gold standard for benign liver lesions., (© 2013 International Hepato-Pancreato-Biliary Association.)

Aims: To assess the accuracy of pathology reports on gallbladder specimens from patients operated on for incidental gallbladder carcinoma., Methods: Demographic data, details on pathological reports including gross and microscopic features section were recorded in 100 selected patients with incidental gallbladder carcinoma diagnosed from 2004 to 2007., Results: Pathology reports had a conventional format in 93% of cases, without any standardization. Turnaround time ranged from 1 to 35 days. Frozen sections were performed in 20% of cases. The reports failed to give information on prognostic histological factors: exact tumour site (missing in 55% of cases), depth of tumour infiltration within the gallbladder wall (missing in 10%), surgical margins (missing in 40% for the cystic duct margin), tumour differentiation (missing in 28%), vascular invasion (missing in 52%) and perineural invasion (missing in 51%). Lymph node status could be assessed in 44% of cases. Distances between the tumour and the cystic duct and circumferential margins were not specified in 68% and 84% of cases. Only 29% of the reports clearly stated the pTNM stage in the conclusion section. The pT stage with margin status and tumour site was only mentioned in 30% of the reports., Conclusion: Pathology reports on gallbladder carcinoma from participating centres frequently lacked important information on key prognostic histological factors., (Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Objectives: Recent improvements in surgical technique have extended the indications for liver resection. The aims of this study were to assess whether this extension is associated with a changing patient profile and to evaluate how this potential shift has influenced mortality after liver resection in order to define standard expectations for hepatectomy., Methods: The characteristics and postoperative outcomes of all patients undergoing elective hepatectomy from 2000 to 2009 were reviewed retrospectively. Multivariate analysis was conducted to determine the factors associated with mortality in the subgroup of patients with malignant disease., Results: Among the 2012 patients in whom hepatectomies were performed, the percentage of patients operated for malignancy increased from 66.4% in 2000 to 82.3% in 2009 (P < 0.001). These patients experienced higher mortality (4.5% versus 0.7%; P < 0.001), were significantly older, and displayed greater comorbidity and underlying parenchymal disease compared with those with benign lesions. Mortality over the entire study period was 3.5% and was fairly stable, dropping from 3.8% in 2000 to 3.1% in 2009 (P = 0.686). On multivariate analysis, age of >60 years, an American Society of Anesthesiologists score of ≥3, major resection, vascular procedure, severe fibrosis (F3-F4) and steatosis of >30% were associated with increased mortality in patients with malignant disease., Conclusions: The profile of patients undergoing liver resection has changed and now includes more high-risk patients with diseased parenchyma undergoing major hepatectomy for malignancy. This change in patient profile is responsible for the stability in mortality rates over the years., (© 2013 International Hepato-Pancreato-Biliary Association.)

Background & Aims: To assess the accuracy of pathology reports in patients operated on for hilar cholangiocarcinoma., Methods: Pathology reports for 263 patients operated on in 22 tertiary hepatobiliary centers were reviewed. The report format, turnaround time, tissue specimens, intraoperative consultations, macroscopic and microscopic descriptions, and conclusions were assessed., Results: Surgeons provided pathologists with pertinent clinical and imaging data in only 14% of cases and gave information on specimen orientation in only 24% of cases. The reports frequently failed to give information on prognostic histological factors: tumor differentiation (missing in 27% of cases), vascular invasion (45%), tumor thickness (99%), and infiltration of the bile duct surgical margins (4%). Distances between the tumor and the vessel margin, liver margin and the periductal soft tissue circumferential margin were not specified in 87%, 79%, and 89% of cases, respectively. Only 21% of the reports gave the pTNM stage in the conclusion section. A lack of information prevented retrospective pTNM staging in 48% of cases. Three percent of the reports had discrepancies in their conclusion section., Conclusions: Our French, nationwide study revealed that pathology reports on hilar cholangiocarcinoma frequently lack important information on the main prognostic histological factors and pTNM staging. We recommend the use of a standardized pathology report in this context., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: An increasing proportion of patients with hepatocellular carcinoma are older than 75 years. Previous studies suggested that ageing does not adversely impact survival but they have the drawback of being retrospective and spanning a prolonged period of time., Goals: Evaluate management and prognosis of hepatocellular carcinoma in elderly., Patients and Methods: A multidisciplinary oncology meeting prospectively evaluated all patients with hepatocellular carcinoma. Management were standardised according to European and American guidelines. Forty patients older than 75 years were matched with younger patients for tumour extension and liver function. Both groups were compared for the type of treatment and survival., Results: Male/female ratio was 1.2 as compared to 7 in controls. Cirrhosis was related mostly to hepatitis C virus in elderly, and equally to hepatitis C or B virus and alcohol in controls. Curative treatments were recommended in 55% of elderly and 75% of controls. Treatment actually performed was curative in 25% in elderly as compared to 63% in controls. Median survival (30 months) was identical in both groups., Conclusion: Despite more restricted access to curative treatments, survival of elderly patients with hepatocellular carcinoma is comparable to that of younger patients., (Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: Jaundice is frequent in patients with gallbladder cancer (GBC) and indicates advanced disease and, according to some teams, precludes routine operative exploration. The present study was designed to re-assess the prognostic value of jaundice in patients with GBC., Methods: Patients with GBC operated from 1998 to 2008 were included in a retrospective multicenter study (AFC). The main outcome measured was the prognostic value of jaundice in patients with GBC focusing on morbidity, mortality and survival., Results: A total of 110 of 429 patients with GBC presented with jaundice, with a median age of 66 years (range: 31-88). The resectability rate was 45% (n=50) and the postoperative mortality and morbidity rates were 16% and 62%, respectively; 71% had R0 resection and 46% had lymph node involvement. Overall 1- and 3-year survivals of the 110 jaundiced patients were 41% and 15%, respectively. For the 50 resected patients, 1- and 3-year survivals were 48% and 19%, respectively (real 5-year survivors n=4) which were significantly higher than that of the 60 non-resected patients (31%, 0%, p=0.001). Among the resected jaundiced patients, T-stage, N and M status were found to have a significant impact on survival. R0 resection did not increase the overall survival in all resected patients, but R0 increased median survival in the subgroup of N0 patients (20 months versus 6 months, p=0.01)., Conclusion: This series confirms that jaundice is a poor prognostic factor. However, the presence of jaundice does not preclude resection, especially in highly selected patients (N0)., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background/aims: Hepatic cholangiocarcinomas are tumors with poor prognosis and with increasing incidence worldwide. The aim of the study was to compare morphological features and protein profiles of hilar and peripheral cholangiocarcinomas., Methods: Clinicopathological data were collected from 111 cholangiocarcinomas (59 peripheral and 52 hilar). Protein expression, assessed on tissue samples using tissue microarray and protein array technologies, was compared between both types of tumors and with extrahepatic cholangiocarcinoma and hepatocholangiocarcinoma., Results: Hilar cholangiocarcinomas were smaller in size (mean: 2.7 vs. 8 cm, p<0.001), were more often well differentiated adenocarcinomas (65% vs. 36% well differentiated, p<0.01) and carried out stronger perineural invasion (83% vs. 42%, p<0.001) than peripheral cholangiocarcinomas. Regarding protein expression, hilar cholangiocarcinomas more often expressed MUC5AC (62% vs. 22%, p<0.0001), Akt2 (54% vs. 27%, p<0.001), CK8 (98% vs. 81%, p<0.005) and annexin II (92% vs. 66%, p<0.001). Interestingly, VEGF A expression was more frequently encountered in peripheral cholangiocarcinoma (69% vs. 25%, p<0.0001) and correlated with increased vascular density. Using protein array antibody, we identified filamin A as significantly overexpressed (>2-fold) in peripheral cholangiocarcinomas., Conclusions: Our results show that hilar and peripheral cholangiocarcinomas display specific protein profiles, especially regarding VEGF expression. This suggests a potential benefit for anti-angiogenic therapies in peripheral hepatic CCs.

Scope: Cholangiocarcinoma, or biliary tract tumors, are rare tumors for which survival is short, as diagnosis is often made at an advanced stage. Indeed, diagnosis remains difficult, since symptoms are often unspecific and appear at latest stages. This article presents an update of recent data and therapeutic options., Current Situation and Salient Points: Several etiologic factors have been identified, but for most patients, none of these factors can be found. Prognosis is often poor, and remains difficult to establish because of the lack of sufficient large-scale studies looking at the impact on preexisting tumor characteristics on overall survival. Surgery remains when possible the gold standard. When tumor removal is impossible, due to a local extension, the appropriate care of patients remains to be defined. Chemotherapy has been proposed with evidence of objective response but limited data on its ability to prolong overall survival and to enhance quality of life. Active chemotherapies appear to be made from combination of an antimetabolite, such as 5-fluorouracile or gemcitabine, and a platinum drug., Perspectives: In the near future, indications of chemotherapy could be enlarged and targeted therapy might also be used, since several molecules have been tested in preclinical studies, and be offered to patients in clinical trials.

The spleen plays a central role in the pathophysiology of several potentially severe diseases such as inherited red cell membrane disorders, hemolytic anemias, and malaria. Research on these diseases is hampered by ethical constraints that limit human spleen tissue explorations. We identified a surgical situation--left splenopancreatectomy for benign pancreas tumors--allowing spleen retrieval at no risk for patients. Ex vivo perfusion of retrieved intact spleens for 4 to 6 hours maintained a preserved parenchymal structure, vascular flow, and metabolic activity. Function preservation was assessed by testing the ability of isolated-perfused spleens to retain Plasmodium falciparum-infected erythrocytes preexposed to the antimalarial drug artesunate (Art-iRBCs). More than 95% of Art-iRBCs were cleared from the perfusate in 2 hours. At each transit through isolated-perfused spleens, parasite remnants were removed from 0.2% to 0.23% of Art-iRBCs, a proportion consistent with the 0.02% to 1% pitting rate previously established in artesunate-treated patients. Histologic analysis showed that more than 90% of Art-iRBCs were retained and processed in the red pulp, providing the first direct evidence of a zone-dependent parasite clearance by the human spleen. Human-specific physiologic or pathophysiologic mechanisms involving clearing or processing functions of the spleen can now be experimentally explored in a human tissue context.

Background/aims: Because of a potential risk of needle tract seeding, the use of ultrasound (US)-guided biopsy for the diagnosis of hepatocellular carcinoma (HCC) is controversial. This study was aimed at determining the usefulness, accuracy and safety of this technique as well as the incidence of needle tract seeding., Methods: From 1986 to 1996, 137 patients who underwent resection or transplantation for suspected HCC had US-guided biopsy before surgery. The analysis of the resected liver was compared to the results of biopsy. Patients were assessed with a mean follow up of 38 months., Results: The diagnosis of HCC was established by biopsy in 122 patients (89%). Thirteen of the 15 patients with negative biopsy were shown to have HCC after surgery. The remaining two patients had non-malignant nodules. Sensitivity and accuracy of US-guided biopsy were 90 and 91%, respectively. Accuracy was significantly influenced by the location of the nodule but not by its size. Needle tract seeding occurred in two patients (1.6%)., Conclusions: In this series, the incidence of needle tract seeding was less than 2% and no recurrence was observed after local excision. This risk should be balanced with the risk of deciding an aggressive treatment in a patient without malignancy. Patients with negative biopsy should undergo a second biopsy and/or repeated investigations by imaging techniques.

Background/aims: Most hepatocellular carcinomas are still discovered at an advanced stage and are left untreated as large hepatocellular carcinomas are contraindications to liver transplantation and percutaneous ethanol injection and are usually considered as poor indications for liver resection. The aim of this study was to reassess the results of surgery in these patients., Methods: Between 1984 and 1996, 256 patients underwent resection of biopsy-proven, non-fibrolamellar hepatocellular carcinoma. Of these, 121 had a tumour diameter of less than 5 cm (small hepatocellular carcinomas) and 94 a tumour diameter of more than 8 cm (large hepatocellular carcinomas). The short- and long-term outcome of patients with small and large hepatocellular carcinomas were compared., Results: The in-hospital mortality rate following resection of small and large hepatocellular carcinomas was comparable (11.5 vs. 10.6%), even after stratifying for the presence and severity of an underlying liver disease. In patients with a chronic liver disease, large hepatocellular carcinomas were associated with a greater risk of death and recurrence during the first 2 operative years. In the long term, however (3-5 years), survival and disease-free survival following resection of small and large hepatocellular carcinomas were comparable (34 vs. 31% and 25 vs. 21% at 5 years). Similarly, treatment of and survival after the onset of recurrence were not influenced by the size of the initial tumour., Conclusions: Patients with large hepatocellular carcinomas should not be abandoned and should be considered for liver resection as this treatment may be associated with an in-hospital mortality rate and a long-term survival comparable to that observed after resection of small hepatocellular carcinomas.

Background/aims: After liver transplantation for autoimmune hepatitis, the long-term results and the incidence of recurrence of primary disease are unknown., Methods: In this retrospective study we reviewed the clinical course of 25 patients transplanted for autoimmune hepatitis and followed for a mean of 5.3 years (2-8.5 years)., Results: The actuarial 5-year patient and graft survival rates were 91% (+/-6%) and 83% (+/-8%). The actuarial 1-year rate of acute rejection was 50% (+/-10.2%), which was comparable to that of patients transplanted for primary biliary cirrhosis and primary sclerosing cholangitis. Autoantibodies persisted in 77% of patients, at a lower titer than before liver transplantation. Ten patients were excluded from the study of autoimmune hepatitis recurrence, one because of an early postoperative death and nine because of hepatitis C virus infection acquired before or after liver transplantation. In the remaining 15 patients, who were free of hepatitis C virus infection, 5-year patient and graft survivals were 100% and 87%, respectively. Despite triple immunosuppressive therapy, three patients (20%) developed chronic hepatitis with histological and serological features of autoimmune hepatitis in the absence of any other identifiable cause. The disease was severe in two patients, leading to graft failure and asymptomatic in another, despite marked histological abnormalities. In one of these three patients, autoimmune hepatitis recurred on the second liver graft as well., Conclusions: Patients undergoing liver transplantation for autoimmune hepatitis have an excellent survival rate although severe primary disease may recur, suggesting the need for stronger post-operative immunosuppressive therapy.

Background/aims: Orthotopic liver transplantation is currently considered as the treatment of choice for primary biliary cirrhosis in the terminal stage and, as for other autoimmune liver disease, the risk of recurrence of the disease within the graft has been raised. There is, however, some discrepancy about the risk of recurrence based on pathological analysis. In addition, pathological recurrence of primary biliary cirrhosis within the graft is not always associated with a rise in the serological markers of the disease. In order to clarify this situation, we have monitored antimitochondrial antibodies before and after transplantation., Methods: Antimitochondrial antibodies were detected by indirect immunofluorescence (variation in antibody titers) and the antimitochondrial antibodies-2 by western blotting (variation in the number of peptides recognized in 16 primary biliary cirrhosis patients followed for at least 4 years after transplantation., Results: Antimitochondrial antibody titers had normalized 1 year after transplantation in seven patients, declined in seven others and remained unchanged in two. Over the 4 years of follow up, four patients demonstrated a subsequent increase in antimitochondrial antibody titers. Western blot analysis demonstrated the loss of one or more bands in seven patients during the first operative year after transplantation and in three other patients thereafter; in six patients the western blotting profile remained identical to that obtained before transplantation. The important changes generally occurred during the first year post-transplantation, without significant changes thereafter, except for three patients who demonstrated a secondary reappearance of the initially lost band. Disappearance of all bands was never observed. There was no concordance between the normalization of antimitochondrial antibody titers (indirect immunofluorescence) and the reduction in the number of peptides recognized (western blotting). Serum bilirubin and alkaline phosphatase levels had normalized by 1 year after transplantation, and remained normal thereafter. Routine liver biopsies performed on a yearly basis did not disclose any pattern suggestive of primary biliary cirrhosis recurrence., Conclusions: Antimitochondrial antibody titers decreased in primary biliary cirrhosis patients after liver transplantation, although antimitochondrial antibodies-2 never disappeared as assessed by western blotting. In the present study these features were not associated with biochemical or histological (correction of histoclogical) evidence of primary biliary cirrhosis recurrence.