European experience of 573 liver resections for hepatocellular adenoma: a cross-sectional study by the AFC-HCA-2013 study group.

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.

Todani Type II Congenital Bile Duct Cyst: European Multicenter Study of the French Surgical Association and Literature Review.

OBJECTIVE: The purpose of the study was to analyze clinical presentation, surgical management, and long-term outcome of patients suffering from biliary diverticulum, namely Todani type II congenital bile duct cyst (BDC). BACKGROUND: The disease incidence ranges between 0.8% and 5% of all reported BDC cases with a lack of information about clinical presentation, management, and outcome. METHODS: A multicenter European retrospective study was conducted by the French Surgical Association. The patients' medical records were included in a Web site database. Diagnostic imaging studies, operative and pathology reports underwent central revision. RESULTS: Among 350 patients with congenital BDC, 19 type II were identified (5.4%), 17 in adults (89.5%) and 2 in children. The biliary diverticulum was located at the upper, middle, and lower part of the extrahepatic biliary tree in 11, 4, and 4 patients (58%, 21%, and 21%, respectively). Complicated presentation occurred in 6 patients (31.6%), including one case of synchronous carcinoma. Surgical techniques included diverticulum excision in all patients. Associated resection of the extrahepatic biliary tree was required in 11 cases (58%) and could be predicted by the presence of complicated clinical presentation. There was no mortality. Long-term outcome was excellent in 89.5% of patients (median follow-uptime: 52 months). CONCLUSIONS: According to the present largest Western series of Todani type II BDC, the type of clinical presentation rather than BDC location, was able to guide the extent of biliary resection. Excellent long-term outcome can be achieved in expert centers.

Nodular Regenerative Hyperplasia in Patients Undergoing Liver Resection for Colorectal Metastases After Chemotherapy: Risk Factors, Preoperative Assessment and Clinical Impact.

BACKGROUND: Nodular regenerative hyperplasia (NRH) is a severe form of chemotherapy-related liver injury (CALI) that may worsen the short-term outcome of liver resection (LR) for colorectal metastases (CRLM). The present study aimed to clarify the incidence, risk factors, preoperative assessment, and clinical impact of NRH. METHODS: Overall, 406 patients undergoing 478 LRs for CRLM after chemotherapy between 2000 and 2012 were studied. All resection specimens were reviewed. After Gomori staining, NRH was graded according to the Wanless score. RESULTS: NRH was diagnosed in 87 (18.2 %) patients, grades 2-3 in 14 (2.9 %) patients. At multivariate analysis, the prevalence of NRH was increased after oxaliplatin administration (21.4 vs. 8.4 %; p = 0.003), and reduced by the addition of bevacizumab (11.7 vs. 19.8 %; p = 0.020). Two parameters predicted the presence of NRH: the APRI score (AST to platelet ratio index: 25.5 % if >0.36 vs. 9.8 % if ≤0.36; p = 0.004), and the platelet count (63.6 % if <100 × 10(3)/mm(3) vs. 25.3 % if 100-200 × 10(3)/mm(3) vs. 11.9 % if >200 × 10(3)/mm(3); p = 0.032). Ninety-day mortality and liver failure rates were 0.6 and 3.6 %. NRH was an independent predictor of postoperative liver failure (9.2 % if present vs. 2.3 % if not present; p = 0.021). In patients with grades 2-3 NRH, the rate of liver failure was 14.3 %, 25.0 % after major hepatectomy. No other forms of CALI impacted short-term outcomes. CONCLUSIONS: NRH was the most relevant form of CALI, increasing the risk of postoperative liver failure. Oxaliplatin increased the incidence of NRH, while bevacizumab decreased it. The APRI score and platelet count were useful tools for predicting NRH.

Rectal outcomes after a liver-first treatment of patients with stage IV rectal cancer.

BACKGROUND: The treatment of patients with metastatic rectal cancer remains controversial. We developed a reverse strategy, the liver-first approach, to optimize the chance of a curative resection. The aim of this study was to assess rectal outcomes after reverse treatment of patients with metastatic rectal cancer. METHODS: From May 2000 to November 2013, a total of 34 consecutive selected patients with histology-proven adenocarcinoma of the rectum and liver metastases were prospectively entered into a dedicated computerized database. All patients were treated via our reverse strategy. Rectal and overall survival outcomes were analyzed. RESULTS: Most patients presented with advanced disease (median Fong clinical risk score of 3; range 2-5). One patient failed to complete the whole treatment (3%). Rectal surgery was performed after a median of 3.9 months (range 0.4-17.8 months). A total of 73.3% patients received preoperative radiotherapy. Perioperative mortality and morbidity rates were 0 and 27.3% after rectal surgery. Severe complications were reported in two patients (6.1%): one anastomotic leak and one systemic inflammatory response syndrome. The median hospital stay was 11 days (range 5-23 days). Complete local pathological response was observed in three patients (9.1%). The median number of lymph nodes collected was 14. The R0 rate was 93.9%. There was no positive circumferential margin. After a mean follow-up of 36 months after rectal surgery, 5-year overall survival was 52.5%. Five patients experienced pelvic recurrence. CONCLUSIONS: In our cohort of selected patients with stage IV rectal cancer, the reverse strategy was not only safe and effective, but also oncologically promising, with a low morbidity rate and high long-term survival.

Is Hepatic Resection for Large or Multifocal Intrahepatic Cholangiocarcinoma Justified? Results from a Multi-Institutional Collaboration.

BACKGROUND: The role of surgical resection for patients with large or multifocal intrahepatic cholangiocarcinoma (ICC) remains unclear. This study evaluated the long-term outcome of patients who underwent hepatic resection for large (≥7 cm) or multifocal (≥2) ICC. METHODS: Between 1990 and 2013, 557 patients who underwent liver resection for ICC were identified from a multi-institutional database. Clinicopathologic characteristics, operative details, and long-term survival data were evaluated. RESULTS: Of the 557 patients, 215 (38.6 %) had a small, solitary ICC (group A) and 342 (61.4 %) had a large or multifocal ICC (group B). The patients in group B underwent an extended hepatectomy more frequently (16.9 vs. 30.4 %; P < 0.001). At the final pathology exam, the patients in group B were more likely to show evidence of vascular invasion (22.5 vs. 38.5 %), direct invasion of contiguous organs (6.5 vs. 12.9 %), and nodal metastasis (13.3 vs. 21.0 %) (all P < 0.05). Interestingly, the incidences of postoperative complications (39.3 vs. 46.8 %) and hospital mortality (1.1 vs. 3.7 %) were similar between the two groups (both P > 0.05). The group A patients had better rates for 5-year overall survival (OS) (30.5 vs. 18.7 %; P < 0.05) and disease-free survival (DFS) (22.6 vs. 8.2 %; P < 0.05) than the group B patients. For the patients in group B, the factors associated with a worse OS included more than three tumor nodules [hazard ratio (HR), 1.56], nodal metastasis (HR, 1.47), and poor differentiation (HR, 1.48). CONCLUSIONS: Liver resection can be performed safely for patients with large or multifocal ICC. The long-term outcome for these patients can be stratified on the basis of a prognostic score that includes tumor number, nodal metastasis, and poor differentiation.

Anatomy of the liver: an outline with three levels of complexity--a further step towards tailored territorial liver resections.

The vascular anatomy of the liver can be described at three different levels of complexity according to the use that the description has to serve. The first--conventional--level corresponds to the traditional 8-segments scheme of Couinaud and serves as a common language between clinicians from different specialties to describe the location of focal hepatic lesions. The second--surgical--level, to be applied to anatomical liver resections and transplantations, takes into account the real branching of the major portal pedicles and of the hepatic veins. Radiological and surgical techniques exist nowadays to make full use of this anatomy, but this requires accepting that the Couinaud scheme is a simplification, and looking at the vascular architecture with an unprejudiced eye. The third--academic--level of complexity concerns the anatomist, and the need to offer a systematization that resolves the apparent contradictions between anatomical literature, radiological imaging, and surgical practice. Based on the real number of second-order portal branches that, although variable averages 20, we submit a system called the "1-2-20 concept", and suggest that it fits best the number of actual--as opposed to idealized--anatomical liver segments.

Accurate computed tomography-based portal pressure assessment in patients with hepatocellular carcinoma.

BACKGROUND & AIMS: Liver resection is generally restricted to patients without clinically significant portal hypertension (Hepatic Venous Pressure Gradient - HVPG - ⩽10mmHg) and several teams perform transjugular HVPG measurements as part of the pre-operative work-up. The present study investigates whether a non-invasive Computed Tomography (CT)-based assessment could be as accurate as the invasive transjugular measurement. METHODS: A cohort of patients with hepatocellular carcinoma (HCC) treated by resection (n=36) or transplantation (n=39) was selected (mean age: 61±9.2years, male/female ratio: 4/1). Pre-operative CTs were read by two independent investigators, and potential CT-based HVPG predictors were compared to the transjugular HVPG measurements. A validation was conducted on another cohort of 70 non-surgical patients. RESULTS: The invasive HVPG values were significantly correlated to liver/spleen volume ratio, spleen volume, platelet count, and peri-hepatic ascites (p<0.001), which all showed high inter-observer agreements (intra-class correlation coefficients ⩾0.927, Kappa ⩾0.945). The presence of a HVPG >10mmHg was best predicted by the liver/spleen volume ratio (AUC: 0.883 [0.805-0.960]) and the peri-hepatic ascites (p<0.001). These two variables were combined into an accurate model for predicting HVPG >10mmHg (AUC: 0.911 [0.847-0.975]), with sensitivity, specificity, and positive and negative predictive values of 92%, 79%, 91%, and 81%. The model was also accurate in the validation cohort with an AUC of 0.820 [0.719-0.921]. The computed formula was: CONCLUSIONS: The proposed CT-based model showed a high accuracy in the prediction of HVPG and, if further confirmed by prospective validation, could replace the invasive transjugular assessment in patients not requiring a biopsy of the non-tumoral liver.

Pre-retrieval reperfusion decreases cancer recurrence after rat ischemic liver graft transplantation.

BACKGROUND & AIMS: Liver transplantation from marginal donors is associated with ischemia/reperfusion (I/R) lesions, which may increase the risk of post-transplant hepatocellular carcinoma (HCC) recurrence. Graft reperfusion prior to retrieval (as for extracorporeal membrane oxygenation--ECMO) can prevent I/R lesions. The impact of I/R on the risk of cancer recurrence was assessed on a syngeneic Fischer-rat liver transplantation model. METHODS: HCC cells were injected into the vena porta of all recipients at the end of an orthotopic liver transplantation (OLT). Control donors were standard heart-beating, ischemic ones (ISC), underwent 10 min or 30 min inflow liver clamping prior to retrieval, and ischemic/reperfused (ISC/R) donors underwent 2h liver reperfusion after the clamping. RESULTS: I/R lesions were confirmed in the ISC group, with the presence of endothelial and hepatocyte injury, and increased liver function tests. These lesions were in part reversed by the 2h reperfusion in the ISC/R group. HCC growth was higher in the 10 min and 30 min ISC recipients (p = 0.018 and 0.004 vs. control, as assessed by MRI difference between weeks one and two), and was prevented in the ISC/Rs (p = 0.04 and 0.01 vs. ISC). These observations were associated with a stronger pro-inflammatory cytokine profile in the ISC recipients only, and the expression of hypoxia and HCC growth-enhancer genes, including Hmox1, Hif1a and Serpine1. CONCLUSIONS: This experiment suggests that ischemia/reperfusion lesions lead to an increased risk of post-transplant HCC recurrence and growth. This observation can be reversed by graft reperfusion prior to retrieval.

Validation of a dropout assessment model of candidates with/without hepatocellular carcinoma on a common liver transplant waiting list.

The model of end-stage liver disease (MELD) score is often used for liver graft allocation, and patients with hepatocellular carcinoma (HCC) receive exception points (22 in the US). A better model is desirable for patients with HCC as they tend to have a privileged access to transplantation, without taking HCC characteristics into account. A new simpler model designed from a training set of US patients (n = 49 026) was tested on two validation sets (US and UK patient cohorts with, respectively, n = 20 475 and n = 1781). The risk of dropout was between 3.2 and 7.8% at 3 months in patients with HCC, and was captured into a score, including HCC size, HCC number, AFP, and MELD (-37.8 +1.9*MELD+5.9 if HCC Nb ≥ 2 + 5.9 if AFP > 400 + 21.2 if HCC size > 1 cm). This new model could be validated on external US and UK liver candidate cohorts. It provides a dynamic and more accurate assessment of dropout than the use of exception MELD (C-indices of 66.2-73.7% vs. 52.7-56.6%). In addition, the model shows a similar distribution as MELD for patients with non-HCC, and both scores could be used in parallel for the management of waiting-list patients with and without HCC.

Risk factors for early and late biliary complications in pediatric liver transplantation.

BC are a common source of morbidity after pediatric LT. Knowledge about risk factors may help to reduce their incidence. Retrospective analysis of BC in 116 pediatric patients (123 LT) (single institution, 05/1990-12/2011, medium follow-up 7.9 yr). One-, five-, and 10-yr survival was 91.1%, no patient died of BC. Prevalence and risk factors for anastomotic and intrahepatic BC were examined. There were 29 BC in 123 LT (23.6%), with three main categories: 10 (8.1%) primary anastomotic strictures, eight (6.5%) anastomotic leaks, and three (2.4%) intrahepatic strictures. Significant risk factors for anastomotic leaks were total operation time (increase 1.26-fold) and early HAT (<30 days post-LT; increase 5.87-fold). Risk factor for primary anastomotic stricture was duct-to-duct choledochal anastomosis (increase 5.96-fold when compared to biliary-enteric anastomosis). Risk factors for intrahepatic strictures were donor age >48 yr (increase 1.09-fold) and MELD score >30 (increase 1.2-fold). To avoid morbidity from anastomotic BC in pediatric LT, the preferred biliary anastomosis appears to be biliary-enteric. Operation time should be kept to a minimum, and HAT must by all means be prevented. Children with a high MELD score or receiving livers from older donors are at increased risk for intrahepatic strictures.

The role of hepatic ischemia-reperfusion injury and liver parenchymal quality on cancer recurrence.

Hepatic ischemia/reperfusion (I/R) injury is a common clinical challenge. Despite accumulating evidence regarding its mechanisms and potential therapeutic approaches, hepatic I/R is still a leading cause of organ dysfunction, morbidity, and resource utilization, especially in those patients with underlying parenchymal abnormalities. In the oncological setting, there are growing concerns regarding the deleterious impact of I/R injury on the risk of post-surgical tumor recurrence. This review aims at giving the last updates regarding the role of hepatic I/R and liver parenchymal quality injury in the setting of oncological liver surgery, using a "bench-to-bedside" approach. Relevant medical literature was identified by searching PubMed and hand scanning of the reference lists of articles considered for inclusion. Numerous preclinical models have depicted the impact of I/R injury and hepatic parenchymal quality (steatosis, age) on increased cancer growth in the injured liver. Putative pathophysiological mechanisms linking I/R injury and liver cancer recurrence include an increased implantation of circulating cancer cells in the ischemic liver and the upregulation of proliferation and angiogenic factors following the ischemic insult. Although limited, there is growing clinical evidence that I/R injury and liver quality are associated with the risk of post-surgical cancer recurrence. In conclusion, on top of its harmful early impact on organ function, I/R injury is linked to increased tumor growth. Therapeutic strategies tackling I/R injury could not only improve post-surgical organ function, but also allow a reduction in the risk of cancer recurrence.

Identifying risk factors for central pontine and extrapontine myelinolysis after liver transplantation: a case-control study.

BACKGROUND: Central pontine and extrapontine myelinolysis (CPEPM) is a rare but potentially fatal complication after orthotopic liver transplantation (OLT). The aim of this study was to identify risk factors for development of CPEPM after OLT and to assess patient outcome. METHODS: We reviewed the clinical data of 1,378 patients who underwent OLT between 1987 and 2009 in Geneva, Switzerland and Edmonton, Canada. Nineteen patients (1.4 %) developed CPEPM. We compared their characteristics with control patients, matched by age, gender, date of OLT, and MELD score. RESULTS: The 19 patients with CPEPM (7F, mean age 52.1 ± 2 years) had a mean MELD score of 26 ± 2.2. Before OLT, patients who develop CPEPM presented more frequently low (<130 mmol/l; p < 0.04) and very low (<125 mmol/l; p < 0.009) sodium than controls. In patients developing CPEPM, the number of platelet units and fresh frozen plasma transfused during surgery was higher (p = 0.05 and 0.047), hemorrhagic complications were more frequent after OLT (p = 0.049), and variations of sodium before and after OLT were higher (p = 0.023). The association of >2 of these conditions were strongly associated with CPEPM (p = 0.00015). Mortality at 1 year of patients developing CPEPM was higher (63 vs. 13 %, p < 0.0001). CONCLUSIONS: High MELD score patients undergoing OLT, receiving massive perfusions of Na-rich products, experiencing surgery-related hemorrhagic complication and important fluctuations of Na are at risk of developing CPEPM. Therefore careful monitoring of natremia in the perioperative period and use of water-free perfusion in case of massive blood-products transfusion are critical points of this patient management.

Complete pathological response (ypT0N0M0) after preoperative chemotherapy alone for stage IV rectal cancer.

BACKGROUND: Complete pathological response occurs in 10-20% of patients with rectal cancer who are treated with neoadjuvant chemoradiation therapy prior to pelvic surgery. The possibility that complete pathological response of rectal cancer can also occur with neoadjuvant chemotherapy alone (without radiation) is an intriguing hypothesis. CASE PRESENTATION: A 66-year old man presented an adenocarcinoma of the rectum with nine liver metastases (T3N1M1). He was included in a reverse treatment, aiming at first downsizing the liver metastases by chemotherapy, and subsequently performing the liver surgery prior to the rectum resection. The neoadjuvant chemotherapy consisted in a combination of oxaliplatin, 5-FU, irinotecan, leucovorin and bevacizumab (OCFL-B). After a right portal embolization, an extended right liver lobectomy was performed. On the final histopathological analysis, all lesions were fibrotic, devoid of any viable cancer cells. One month after liver surgery, the rectoscopic examination showed a near-total response of the primary rectal adenocarcinoma, which convinced the colorectal surgeon to perform the low anterior resection without preoperative radiation therapy. Macroscopically, a fibrous scar was observed at the level of the previously documented tumour, and the histological examination of the surgical specimen did not reveal any malignant cells in the rectal wall as well as in the mesorectum. All 15 resected lymph nodes were free of tumour, and the final tumour stage was ypT0N0M0. Clinical outcome was excellent, and the patient is currently alive 5 years after the first surgery without evidence of recurrence. CONCLUSION: The presented patient with stage IV rectal cancer and liver metastases was in a unique situation linked to its inclusion in a reversed treatment and the use of neoadjuvant chemotherapy alone. The observed achievement of a complete pathological response after chemotherapy should promote the design of prospective randomized studies to evaluate the benefits of chemotherapy alone in patients with stages II-III rectal adenocarcinoma (without metastasis).

Initial cholecystectomy vs sequential common duct endoscopic assessment and subsequent cholecystectomy for suspected gallstone migration: a randomized clinical trial.

IMPORTANCE: The optimal management of treatment for patients at intermediate risk of a common duct stone (including increased liver function tests but bilirubin <4 mg/dL and no cholangitis) is a matter of debate. Many stones migrate spontaneously into the duodenum, making preoperative common duct investigations unnecessary. OBJECTIVE: To compare strategies of cholecystectomy first vs a sequential endoscopic common duct assessment and cholecystectomy for the management of patients with an intermediate risk of a common duct stone. The main objective was to reduce the length of stay and the secondary objectives were to reduce the number of common duct investigations, morbidity, and costs. DESIGN, SETTING, AND PARTICIPANTS: Interventional, randomized clinical trial with 2 parallel groups performed between June 2011 and February 2013, with a patient follow-up of 6 months. The trial comprised a random sample of 100 adult patients admitted to Geneva University Hospital, Geneva, Switzerland, for acute gallstone-related conditions with an intermediate risk of a common duct stone. Fifty patients were randomized to each group. INTERVENTIONS: Cholecystectomy first with intraoperative cholangiogram for the study group and endoscopic common duct assessment and clearance followed by cholecystectomy for the control group. MAIN OUTCOMES AND MEASURES: Length of initial hospital stay (primary end point), number of common duct investigations and morbidity and mortality within 6 months after initial admission, and quality of life at 1 and 6 months after discharge (EQ-5D-5L [EuroQol Group, 5-level] questionnaire). RESULTS: Patients who underwent cholecystectomy as a first step had a significantly shorter length of hospital stay (median, 5 days [interquartile range {IQR}, 1-8] vs median, 8 days [IQR, 6-12]; P < .001), with fewer common duct investigations (25 vs 71; P < .001), no significant difference in morbidity or quality of life. CONCLUSIONS AND RELEVANCE: Among patients at intermediate risk of a common duct stone, initial cholecystectomy compared with sequential common duct endoscopy assessment and subsequent surgery resulted in a shorter length of stay without increased morbidity. If these findings are confirmed, initial cholecystectomy with intraoperative cholangiogram may be a preferred approach. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01492790.

Systematic review and meta-analysis of fibrin sealants for patients undergoing pancreatic resection.

INTRODUCTION: Post-operative pancreatic fistula (POPF) is a common complication after partial pancreatic resection, and is associated with increased rates of sepsis, mortality and costs. The role of fibrin sealants in decreasing the risk of POPF remains debatable. The aim of this study was to evaluate the literature regarding the effectiveness of fibrin sealants in pancreatic surgery. METHODS: A comprehensive database search was conducted. Only randomized controlled trials comparing fibrin sealants with standard care were included. A meta-analysis regarding POPF, intra-abdominal collections, post-operative haemorrhage, pancreatitis and wound infections was performed according to the recommendations of the Cochrane collaboration. RESULTS: Seven studies were included, accounting for 897 patients. Compared with controls, patients receiving fibrin sealants had a pooled odds ratio (OR) of developing a POPF of 0.83 [95% confidence interval (CI): 0.6-1.14], P = 0.245. There was a trend towards a reduction in post-operative haemorrhage (OR = 0.43 (95%CI: 0.18-1.0), P = 0.05) and intra-abdominal collections (OR = 0.52 (95%CI: 0.25-1.06), P = 0.073) in those patients receiving fibrin sealants. No difference was observed in terms of mortality, wound infections, re-interventions or hospital stay. CONCLUSION: On the basis of these results, fibrin sealants cannot be recommended for routine clinical use in the setting of pancreatic resection.

Operative management of colorectal liver metastases.

In this review, the authors describe the management of patients with colorectal liver metastases in the era of effective chemotherapies and advanced interventional radiology. They give special attention to the surgical procedures that decrease the operative mortality and morbidity and produce clear margins. They discuss the best timing for chemotherapy, resection of the primary tumor, and resection of the liver metastases in an effort to improve long-term survival. The use of preoperative portal vein embolization, two-stage hepatectomy for bilobar synchronous liver metastases, and the liver-first strategy have allowed for treatment of patients with advanced disease with a curative intent, and to obtain 5-year overall survival of 30 to 60% despite poor prognostic factors and a cure (no recurrence at 10 years) in more than 20% of patients. These rates would have been unimaginable only two decades ago.

Liver resection for colorectal metastases after chemotherapy: impact of chemotherapy-related liver injuries, pathological tumor response, and micrometastases on long-term survival.

OBJECTIVES: We analyzed the impact of chemotherapy-related liver injuries (CALI), pathological tumor regression grade (TRG), and micrometastases on long-term prognosis in patients undergoing liver resection for colorectal metastases after preoperative chemotherapy. BACKGROUND: CALI worsen the short-term outcomes of liver resection, but their impact on long-term prognosis is unknown. Recently, a prognostic role of TRG has been suggested. Micrometastases (microscopic vascular or biliary invasion) are reduced by preoperative chemotherapy, but their impact on survival is unclear. METHODS: Patients undergoing liver resection for colorectal metastases between 1998 and 2011 and treated with oxaliplatin and/or irinotecan-based preoperative chemotherapy were eligible for the study. Patients with operative mortality or incomplete resection (R2) were excluded. All specimens were reviewed to assess CALI, TRG, and micrometastases. RESULTS: A total of 323 patients were included. Grade 2-3 sinusoidal obstruction syndrome (SOS) was present in 124 patients (38.4%), grade 2-3 steatosis in 73 (22.6%), and steatohepatitis in 30 (9.3%). Among all patients, 22.9% had TRG 1-2 (major response), whereas 55.7% had TRG 4-5 (no response). Microvascular invasion was detected in 37.8% of patients and microscopic biliary infiltration in 5.6%.The higher the SOS grade the lower the pathological response: TRG 1-2 occurred in 16.9% of patients with grade 2-3 SOS versus 26.6% of patients with grade 0-1 SOS (P = 0.032).After a median follow-up of 36.9 months, 5-year survival was 38.6%. CALI did not negatively impact survival. Multivariate analysis showed that grade 2-3 steatosis was associated with better survival than grade 0-1 steatosis (5-year survival rate of 52.5% vs 35.2%, P = 0.002). TRG better than the percentage of viable cells stratified patient prognosis: 5-year survival rate of 60.4% in TRG 1-2, 40.2% in TRG 3, and 29.8% in TRG 4-5 (P = 0.0001). Microscopic vascular and biliary invasion negatively impacted outcome (5-year survival rate of 23.3% vs 45.7% if absent, P = 0.017; 0% vs 42.3%, P = 0.032, respectively). CONCLUSIONS: TRG was confirmed to be a crucial prognostic determinant. CALI do not negatively impact long-term prognosis, but the tumor response is reduced in patients with grade 2-3 SOS. Steatosis was found to have a protective effect on survival. Micrometastases significantly impacted prognosis assessment.

Surgical management of congenital intrahepatic bile duct dilatation, Caroli's disease and syndrome: long-term results of the French Association of Surgery Multicenter Study.

OBJECTIVE: To assess clinical presentation and long-term results of surgical management of congenital intrahepatic bile duct dilatation (IHBDD) (Caroli disease and syndrome) in a multicenter setting. BACKGROUND: Congenital IHBDD predisposes to biliary stasis, resulting in intrahepatic lithiasis, septic complications, and cholangiocarcinoma. Although liver resection (LR) is considered to be the treatment of choice for unilobar disease extent into the liver, the management of bilobar disease and/or associated congenital hepatic fibrosis remains challenging. METHODS: From 1978 to 2011, a total of 155 patients (median age: 55.7 years) were enrolled from 26 centers. Bilobar disease, Caroli syndrome, liver atrophy, and intrahepatic stones were encountered in 31.0%, 19.4%, 27.7%, and 48.4% of patients, respectively. A complete resection of congenital intrahepatic bile ducts was achieved in 90.5% of the 148 patients who underwent surgery. RESULTS: Postoperative mortality was nil after anatomical LR (n = 111) and 10.7% after liver transplantation (LT) (n = 28). Grade 3 or higher postoperative morbidity occurred in 15.3% of patients after LR and 39.3% after LT. After a median follow-up of 35 months, the 5-year overall survival rate was 88.5% (88.7% after LT), and the Mayo Clinic score was considered as excellent or good in 86.0% of patients. The 1-year survival rate was 33.3% for the 8 patients (5.2%) who presented with coexistent cholangiocarcinoma. CONCLUSIONS: LR for unilobar and LT for diffuse bilobar congenital IHBDD complicated with cholangitis and/or portal hypertension achieved excellent long-term patient outcomes and survival. Because of the bad prognosis of cholangiocarcinoma and the sizeable morbidity-mortality after LT, timely indication for surgical treatment is of major importance.

A model for dropout assessment of candidates with or without hepatocellular carcinoma on a common liver transplant waiting list.

UNLABELLED: In many countries, the allocation of liver grafts is based on the Model of End-stage Liver Disease (MELD) score and the use of exception points for patients with hepatocellular carcinoma (HCC). With this strategy, HCC patients have easier access to transplantation than non-HCC ones. In addition, this system does not allow for a dynamic assessment, which would be required to picture the current use of local tumor treatment. This study was based on the Scientific Registry of Transplant Recipients and included 5,498 adult candidates of a liver transplantation for HCC and 43,528 for non-HCC diagnoses. A proportional hazard competitive risk model was used. The risk of dropout of HCC patients was independently predicted by MELD score, HCC size, HCC number, and alpha-fetoprotein. When combined in a model with age and diagnosis, these factors allowed for the extrapolation of the risk of dropout. Because this model and MELD did not share compatible scales, a correlation between both models was computed according to the predicted risk of dropout, and drop-out equivalent MELD (deMELD) points were calculated. CONCLUSION: The proposed model, with the allocation of deMELD, has the potential to allow for a dynamic and combined comparison of opportunities to receive a graft for HCC and non-HCC patients on a common waiting list.

The impact of wait list body mass index changes on the outcome after liver transplantation.

Obesity is associated with poor health outcomes in the general population, but the evidence surrounding the effect of body mass index (BMI) on postliver transplantation survival is contradictory. The aim of this study was to assess the impact of wait list BMI and BMI changes on the outcomes after liver transplantation. Using the Scientific Registry of Transplant Recipients, we compared survival among different BMI categories and examined the impact of wait list BMI changes on post-transplantation mortality for patients undergoing liver transplantation. Cox proportional hazards multivariate regression was carried out to adjust for confounding factors. Among 38 194 recipients, underweight patients had a poorer survival compared with normal weight (HR = 1.3, 95% CI: 1.13-1.49). Conversely, overweight and mildly obese men experienced better survival rates compared with their lean counterparts (HR = 0.9, 95% CI: 0.84-0.96, and HR = 0.86, 95% CI: 0.79-0.93 respectively). Female patients gaining weight over 18.5 kg/m(2) while on the wait list showed improving outcomes (HR = 0.46, (95% CI: 0.28-0.76)) compared with those remaining underweight. This study supports the harmful impact of underweight on postliver transplant survival, and highlights the need for a specific monitoring and management of candidates with BMIs close to 18.5 kg/m(2) . Obesity does not constitute an absolute contraindication to liver transplantation.