D. Castaing

New paradigms in post-hepatectomy liver failure.

IntroductionLiver failure after hepatectomy remains the most feared postoperative complication. Many risk factors are already known, related to patient’s comorbidities, underlying liver disease, received treatments and type of resection. Preoperative assessment of functional liver reserve must be a priority for the surgeon.MethodsPhysiopathology of post-hepatectomy liver failure is not comparable to fulminant liver failure. Liver regeneration is an early phenomenon whose cellular mechanisms are beginning to be elucidated and allowing most of the time to quickly recover a functional organ. In some cases, microscopic and macroscopic disorganization appears. The hepatocyte hyperproliferation and the asynchronism between hepatocytes and non-hepatocyte cells mitosis probably play a major role in this pathogenesis.ResultsMany peri- or intra-operative techniques try to prevent the occurrence of this potentially lethal complication, but a better understanding of involved mechanisms might help to completely avoid it, or even to extend the possibilities of resection.ConclusionFuture prevention and management may include pharmacological slowing of proliferation, drug or physical modulation of portal flow to reduce shear–stress, stem cells or immortalized hepatocytes injection, and liver bioreactors. Everything must be done to avoid the need for transplantation, which remains today the most efficient treatment of liver failure.

Does pathological response after transarterial chemoembolization for hepatocellular carcinoma in cirrhotic patients with cirrhosis predict outcome after liver resection or transplantation

BACKGROUND & AIMSnTo investigate the prognostic significance of pathologic response (PR) after transarterial chemoembolization (TACE) in cirrhotic patients resected or transplanted for hepatocellular carcinoma (HCC), and to identify predictors of complete pathologic response (CPR).nnnMETHODSnBetween 1990 and 2010, 373 consecutive cirrhotic patients with HCC were treated by TACE followed by either liver resection (LR:184 patients) or liver transplantation (LT:189 patients). The PR was evaluated as the mean percentage of non-viable tumor area within each tumor. CPR was defined as the absence of any viable tumor area in all the present nodules.nnnRESULTSnA total of 59 (32%) and 37 (20%) patients had CPR after LR and LT, respectively. Five-year overall survival (OS) was higher in patients with CPR compared to those without, after LR (58% vs. 34%; p=0.0006) and tends to be higher after LT (84% vs. 65%; p=0.09). The 5-year recurrence-free survival (RFS) rates were significantly higher in both groups (24% vs. 13% after LR; p=0.008 and 94% vs. 73% after LT, p=0.007). A cut-off value of >90% necrosis emerged as an impacting factor on patient survival after LR or LT. On multivariate analysis stratified on the type of procedure (LR or LT), PR >90% remained an independent factor of better OS and RFS. Independent factors associated with CPR were: a maximal tumor size <30 mm (RR 2.17 [1.27-3.74]), a single tumor (RR 6.08 [3.29-12.07]), and an preoperative AFP<100 ng/ml (see results section) (RR 3.99 [1.63-11.98]). The probability to achieve a CPR ranged from 2% in the absence of any factors to 48% in the presence of all factors.nnnCONCLUSIONnIn cirrhotic patients with HCC, a complete or nearly complete PR improves long-term survival after LR and LT independently of other pathological factors. This underlines the importance of neoadjuvant treatment to obtain a significant decrease of active tumor load.

Is unexpected peritoneal carcinomatosis still a contraindication for resection of colorectal liver metastases?: Combined resection of colorectal liver metastases with peritoneal deposits discovered intra-operatively

AIMSnThe discovery of unexpected peritoneal carcinomatosis (PC) at the time of hepatectomy for colorectal liver metastases (CLM) is usually considered a contraindication for continuing resection. The first aim of this study was to assess the long-term outcome of patients operated for CLM, and who presented unexpected PC during laparotomy. The second aim was to identify preoperative predictors of PC.nnnMETHODSnAll patients at a single center between 1985 and 2010 who had unexpected PC, discovered during planed resection of CLM, and negative preoperative imaging for PC were selected. Clinicopathological data were retrospectively analyzed to assess survival outcomes and to identify predictors of unexpected PC.nnnRESULTSnOut of the 1340 operated patients for CLM, 42 (3%) had unexpected PC. Only patients (nxa0=xa030; 71%) who had PC limited to two abdominal regions (Median peritoneal cancer index (PCI): 2 (1-6)) were resected. Twelve patients were not resected due to the extent of peritoneal disease. The overall survival of the 30 patients resected for CLM who had limited PC was 18% at 5 years (median: 42 months). On multivariate analysis, a previous history of PC, a pT4 stage and bilobar CLM were independent predictors of unexpected PC.nnnCONCLUSIONnUnexpected PC should not be a contraindication for resection provided that the PCI is low and complete resection of all peritoneal and hepatic lesions can be achieved. Previous history of PC, a pT4 primary tumor and bilobar CLM are associated with increased risk of unexpected PC.

Surgical anatomy of the biliary tract

An intimate knowledge of the morphological, functional, and real anatomy is a prerequisite for obtaining optimal results in the complex surgery of extra and intrahepatic cholangiocarcinoma. A complete presentation of the surgical anatomy of the bile ducts includes study of the liver, hepatic surface, margins, and scissures. The frequent variations from the normal anatomy are described and an overview of the blood supply and lymphatics of the biliary tract is presented.

A Decision Analysis Model Identifies the Interval of Efficacy for Transarterial Chemoembolization (TACE) in Cirrhotic Patients with Hepatocellular Carcinoma Awaiting Liver Transplantation

IntroductionFor liver transplant candidates with hepatocellular carcinoma (HCC), the ability of neoadjuvant transarterial chemoembolization (TACE) to improve outcomes remains unproven. The objective of our study was to determine if there was a specific time interval where neoadjuvant TACE would decrease the number of HCC patients removed from the pretransplant waitlist.Materials and MethodsA decision model was developed to simulate a randomized trial of neoadjuvant treatment with TACE vs. no TACE in 600 virtual patients with HCC and cirrhosis. Transition probabilities for TACE morbidity (1u2009±u20091%), TACE response rates (30u2009±u200920%), and disease progression (7u2009±u20097% per month) were assigned by systematic review of the literature (18 reports). Sensitivity analyses were performed to determine time thresholds where TACE would decrease the number of delisted patients.ResultsTACE treatment had statistical benefit at waitlist time breakpoints of 4 and 9xa0months (Pu2009<u20090.05). When waitlist times were less than 4xa0months, waitlist attrition was similar (20% vs. 34%, Pu2009=u20090.08). When waitlist times exceed 9xa0months, waitlist dropout rates re-equilibrated (33% vs. 46%, Pu2009=u20090.06). Review of the current literature determined that only those studies reporting on patients with waitlist times between 4 and 9xa0months found a benefit to neoadjuvant TACE.ConclusionsThis analysis indicates that the benefit of neoadjuvant TACE may be limited to those patients transplanted from 4 to 9xa0months from first TACE. These data may help transplant programs to tailor TACE treatments based on predicted waitlist times to achieve optimal resource utilization and improved organ allocation efficiency.

Could post-liver transplantation course be helpful for the diagnosis of so called cryptogenic cirrhosis?

Abstract:u2002 Cryptogenic cirrhosis (CC) is diagnosed in 5–30% of cirrhotic patients overall and 7% of patients who undergo liver transplantation for cirrhosis. In our series of patients transplanted for CC, pre‐transplant clinical and histological data and the post‐transplant course were reexamined in an attempt to identify the aetiology. Among the 881 patients transplanted in our centre between 1987 and 2000, 28 patients with a median age of 46u2003yr (range: 18–69) at transplantation were initially classified as having CC. Two patients were excluded because of intense ischaemic lesions caused by chemoembolization prevented histological analysis of the native liver (nu2003=u20031) and because of cryptic HBV infection (nu2003=u20031). Among the remaining 26 patients, four groups were individualized: (i) patients with chronic inflammatory liver disease with autoimmune features (nu2003=u200314, 54%); (ii) patients with features suggestive of non‐alcoholic fatty liver disease (nu2003=u20033, 11.5%); (iii); patients with incomplete septal cirrhosis (ISC) and vascular liver disease (nu2003=u20033), and (iv) patients with unresolved CC (nu2003=u20036, 23%). In the autoimmune liver disease group, the median International Autoimmune Hepatitis score was 12.5 (range: 11–19) after reevaluation and review of the post‐transplantation course was helpful to confirm the diagnosis with the occurrence of active graft hepatitis in nine patients, with autoantibodies in five patients. The vascular group was characterized by lesions of obliterative portal venopathy and ISC in all native livers. Diagnosis of NAFLD was based on the clinical background of obesity and/or type 2 diabetes and the presence of steatosis or steatohepatitis in native livers and graft biopsies. A definite aetiological diagnosis can be achieved in the majority of patients initially diagnosed with CC. Autoimmune liver disease emerged as the main aetiology (14 of 26 patients, 54%) and frequently recurred on the grafted liver (nine cases). In all cases a precise diagnosis is obviously of practical interest for better management of post‐transplant survey and treatment.

Drop-out between the two liver resections of two-stage hepatectomy. Patient selection or loss of chance?

BACKGROUNDnTwo-stage hepatectomy (TSH) is the present standard for multiple bilobar colorectal liver metastases (CLM), but 25-35% of patients fail to complete the scheduled procedure (drop-out). To elucidate if drop-out of TSH is a patient selection (as usually considered) or a loss of chance.nnnMETHODSnAll the consecutive patients scheduled for a TSH at the Paul Brousse Hospital between 2000 and 2012 were considered. TSH patients were matched 1:1 with patients receiving a one-stage ultrasound-guided hepatectomy (OSH) at the Humanitas Research Hospital in the same period. Matching criteria were: primary tumor N status; timing of CLM diagnosis; CLM number and distribution into the liver.nnnRESULTSnSixty-three pairs of patients were analyzed. Demographic and tumor characteristics were similar (median 7 CLM), except for more chemotherapy lines and adjuvant chemotherapy in TSH. Drop-out rate of TSH was 38.1% (0% of OSH). The two groups had similar R0 resection rate (19.0% OSH vs. 15.9% TSH). OSH and completed TSH had similar five-year survival (from CLM diagnosis 49.8% vs. 49.7%, from liver resection 36.1% vs. 44.3%), superior to drop-out (10% three-year survival, pxa0<xa00.001). OSH and completed TSH had similar recurrence-free survival (at three years 21.7% vs. 20.5%) and recurrence sites. The completion of resection (drop-out vs. OSH/completed TSH) was the only independent prognostic factor (pxa0=xa00.003).nnnCONCLUSIONSnDrop-out of TSH could be a loss of chance rather than a criteria for patient selection. Unselected OSH patients had the same outcomes of selected patients who completed TSH. A complete resection is the main determinant of prognosis.

Resection of non resectable liver metastases after chemotherapy: Prognostic factors and long term results

3550 Background: Chemotherapy allows an increased number of patients with primarily non resectable colorectal liver metastases (CRLM) to be further resected after tumor downstaging. However the benefit of this rescue surgery is still debated and prognostic factors of outcome are lacking Methods: From February 1988 to December 2000, 1400 consecutive patients with CLRM were managed at a single institution. From these, 295 (21%) were primarily resected and 1105 (79%) initially non resectable were treated by systemic chemotherapy using either oxaliplatin or irinotecan regimens. Non resectable patients were routinely reexplored every 3-4 courses.Surgery was reconsidered when potentially curative after response to chemotherapy. Fifteen factors assumed to be predictive of survival were evaluated by uni- and multivariate analysis in patients secondarily resected Results: In the non resectable group, 139 good responders (13%) could be secondarily submitted to hepatic resection after an average of 10 courses of chemotherapy. CRLM were initially non resectable because too large (7%), ill-located (15%), multinodular (55%) or associated to extrahepatic tumor (22%). Operative mortality within 2 months was 0.7% (1/139). Tumor recurrence was treated by repeat hepatectomy in 50 patients (36%) and pulmonary resection in 27 (19%). After a mean follow up of 5.3±3.2 years, overall 5-year survival was 36% (disease-free : 22%) compared to 47% for primarily resected patients (p= 0.02). At multivariate analysis, 4 preoperative factors were independently associated to decreased survival : rectal primary, number of metastases ≥3, CA 19-9 level > 100 UI/L and concomitence of peritoneal or lymph nodes metastases. 5-year survival according to the presence of 0,1, 2, 3 or 4 of these factors was respectively 60%, 30-40%, 10-18% and 0-3%.nnnCONCLUSIONSnEffective chemotherapy allows 13% of patients with irresectable CRLM to be rescued by liver surgery with a hope of long term remission. Although lower than that of initially resectable patients, the overall 5-year survival is 36% for a similar risk of mortality. 4 preoperative factors are able to predict long-term survival. No significant financial relationships to disclose.

Importance of conserving middle hepatic vein distal branches for homogeneous regeneration of the left liver after right hepatectomy

BACKGROUNDnLiver regeneration enables repeat surgical procedures to achieve a potential cure in liver cancer patients. However, data regarding segmental regeneration and liver anatomy after liver resection are scarce. This study examined left liver regeneration after right hepatectomy and the impact of hepatic venous drainage on the regeneration of the paramedian sector (Couinauds segment IV).nnnMETHODSnTwenty patients in whom right hepatectomy with conservation of the middle hepatic vein (MHV) on healthy liver had been performed were analysed for segmental volumes and vascular anatomy. Volumetric analysis of left liver segments and three-dimensional MHV reconstruction were conducted using pre- and postoperative computed tomography. The volumetric proportions represented by each segment within the left liver were compared and MHV anatomy was analysed to determine its potential role in the regeneration of left liver segments.nnnRESULTSnAfter right hepatectomy, the proportion represented by segment IV within the left liver decreases by 13%, whereas the proportion represented by segments II and III increases by 15%. This heterogeneous regeneration is particularly observed in patients in whom a venous branch for segment IVb is sacrificed, leading to an altered outflow similar to that observed in MHV deprivation. The risk for venous branch deprivation in IVb is correlated to the depth of the bifurcation of the MHV in liver parenchyma.nnnCONCLUSIONSnIt is crucial to conserve the MHV in its distal part if homogeneous left liver regeneration after right hepatectomy that will allow potential repeat liver resection is to be achieved.

Outcomes of surgical shunts and transjugular intrahepatic portasystemic stent shunts for complicated portal hypertension

Transjugular intrahepatic portasystemic stent shunt (TIPSS), instead of surgical shunt, has become the standard treatment for patients with complicated portal hypertension. This study compared outcomes in patients who underwent TIPSS or surgical shunting for complicated portal hypertension.