Intensive Early Rehabilitation in the Intensive Care Unit for Liver Transplant Recipients: A Randomized Controlled Trial.

OBJECTIVE: To validate the feasibility and tolerance of an intensive rehabilitation protocol initiated during the postoperative period in an intensive care unit (ICU) in liver transplant recipients. DESIGN: Prospective randomized study. SETTING: ICU. PARTICIPANTS: Liver transplant recipients over a period of 1 year (N=40). INTERVENTIONS: The "usual treatment group" (n=20), which benefited from the usual treatment applied in the ICU (based on physician prescription for the physiotherapist, with one session a day), and the experimental group (n=20), which followed a protocol of early and intensive rehabilitation (based on a written protocol validated by physicians and an evaluation by physiotherapist, with 2 sessions a day), were compared. MAIN OUTCOME MEASURES: Our primary aims were tolerance, assessed from the number of adverse events during rehabilitation sessions, and feasibility, assessed from the number of sessions discontinued. RESULTS: The results revealed a small percentage of adverse events (1.5% in the usual treatment group vs 1.06% in the experimental group) that were considered to be of low intensity. Patients in the experimental group sat on the edge of their beds sooner (2.6 vs 9.7d; P=.048) and their intestinal transit resumed earlier (5.6 vs 3.7d; P=.015) than patients in the usual treatment group. There was no significant difference between the 2 arms regarding length of stay (LOS), despite a decrease in duration in the experimental group. CONCLUSIONS: The introduction of an intensive early rehabilitation program for liver transplant recipients was well tolerated and feasible in the ICU. We noted that the different activities proposed were introduced sooner in the experimental group. Moreover, there is a tendency to decreased LOS in the ICU for the experimental group. These results now need to be confirmed by studies on a larger scale.

Compared efficacy of preservation solutions in liver transplantation: a long-term graft outcome study from the European Liver Transplant Registry.

Between 2003 and 2012, 42 869 first liver transplantations performed in Europe with the use of either University of Wisconsin solution (UW; N = 24 562), histidine-tryptophan-ketoglutarate(HTK; N = 8696), Celsior solution (CE; N = 7756) or Institute Georges Lopez preservation solution (IGL-1; N = 1855) preserved grafts. Alternative solutions to the UW were increasingly used during the last decade. Overall, 3-year graft survival was higher with UW, IGL-1 and CE (75%, 75% and 73%, respectively), compared to the HTK (69%) (p < 0.0001). The same trend was observed with a total ischemia time (TIT) >12 h or grafts used for patients with cancer (p < 0.0001). For partial grafts, 3-year graft survival was 89% for IGL-1, 67% for UW, 68% for CE and 64% for HTK (p = 0.009). Multivariate analysis identified HTK as an independent factor of graft loss, with recipient HIV (+), donor age ≥65 years, recipient HCV (+), main disease acute hepatic failure, use of a partial liver graft, recipient age ≥60 years, no identical ABO compatibility, recipient hepatitis B surface antigen (-), TIT ≥ 12 h, male recipient and main disease other than cirrhosis. HTK appears to be an independent risk factor of graft loss. Both UW and IGL-1, and CE to a lesser extent, provides similar results for full size grafts. For partial deceased donor liver grafts, IGL-1 tends to offer the best graft outcome.

Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS): impact of the inter-stages course on morbi-mortality and implications for management.

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.

Pancreatic neuroendocrine tumor: A multivariate analysis of factors influencing survival.

BACKGROUND: The outcomes of pancreatic neuroendocrine tumors are extremely diverse, and determining the best strategy, optimal timing of therapy and the therapeutic results depend on understanding prognostic factors. We determined the clinical, radiological and histological factors associated with survival and tumor recurrence for patients with pancreatic neuroendocrine tumor. METHODS: From January 1, 1991 to December 31, 2011, 127 patients with pancreatic neuroendocrine tumor underwent pancreatectomy. The variables including clinical characteristics, surgical data and pathological findings were examined by univariate and multivariate analyses. RESULTS: There were 103 patients with non-functional tumors (81%). Sixty-four patients (50%) underwent left pancreatectomy, 51 (42%) patients underwent pancreatico-duodenectomy, 12 (9%) patients underwent enucleation and 2 patients (1%) underwent central pancreatectomy. Forty-eight patients (38%) had synchronous liver metastases. Six patients (5%) required portal vein resection, and 19 (15%) patients required enlarged "en-bloc" resection of adjacent organs. The overall morbidity and mortality rates were 48% and 2.3%, respectively. The 1-, 3- and 5-year overall survival rates were 94%, 84%, and 74%, respectively. In multivariate analyses, synchronous liver metastases (p = 0.02) and portal vein resection (p < 0.01) were independent prognostic factors of survival. CONCLUSIONS: Synchronous liver metastases and portal vein resection were found to be independent factors influencing survival.

[Giant renal angiomyolipoma with right heart failure]. / Angiomyolipome rénal géant compliqué d'insuffisance cardiaque droite.

We report the case of a 63-year-old woman presenting a 26cm right renal angiomyolipoma with intratumoral arteriovenous fistula responsible for a high-output right heart failure. A radical surgical treatment after preoperative embolization allowed rapid improvement of cardiac symptoms with an uneventful postoperative course.

Minimal portal vein stenosis is a promising preconditioning in living donor liver transplantation in porcine model.

BACKGROUND & AIMS: The main hindrance in promoting living donor liver transplantation remains the morbi-mortality risk for the donor. Considering the opposed remodeling influence of portal and hepatic artery flows, our working hypothesis was to identify a lobar portal vein stenosis capable of inducing a contralateral liver mass compensatory enlargement, without the downstream ipsilateral atrophic response. METHODS: Twenty-four pigs entered this study. Six of them were used to establish hemodynamic changes following a progressive left portal vein (LPV) stenosis, in blood flow, pressure and vessel diameter of the LPV, main portal vein and hepatic artery. Sixteen pigs were divided into 4 groups: sham operated animals, 20% LPV stenosis, 50% LPV stenosis, and 100% LPV stenosis. Daily liver biopsies were collected until post-operative day 5 to investigate liver regeneration and atrophy (Ki67, STAT3, LC3, and activated caspase 3) according to the degree of LPV stenosis. Finally, changes in liver volumetry after 20% LPVS were investigated. RESULTS: A 20% LPV stenosis led to dilatation of the hepatic artery and a subsequent four-fold increase in hepatic arterial flow. Concomitantly, liver regeneration was triggered in the non-ligated lobe and the cell proliferation peak, 5 days after surgery, was comparable to that obtained after total LPV ligation. Moreover, 20% LPV stenosis preconditioning did not induce left liver atrophy contrary to 50 and 100% LPV stenosis. CONCLUSIONS: A 20% LPV stenosis seems to be the adequate preconditioning to get the remnant liver of living donor ready to take on graft harvesting without atrophy of the future graft.

Is port-site resection necessary in the surgical management of gallbladder cancer?

INTRODUCTION: Gallbladder carcinoma is frequently discovered incidentally on pathologic examination of the specimen after laparoscopic cholecystectomy (LC) performed for presumed "benign" disease. The objective of the present study was to assess the role of excision of port-sites from the initial LC for patients with incidental gallbladder carcinoma (IGBC) in a French registry. METHODS: Data on patients with IGBC identified after LC between 1998 and 2008 were retrospectively collated in a French multicenter database. Among those patients undergoing re-operation with curative intent, patients with port-site excision (PSE) were compared with patients without PSE and analyzed for differences in recurrence patterns and survival. RESULTS: Among 218 patients with IGBC after LC (68 men, 150 women, median age 64 years), 148 underwent re-resection with curative intent; 54 patients had PSE and 94 did not. Both groups were comparable with regard to demographic data (gender, age > 70, co-morbidities), surgical procedures (major resection, lymphadenectomy, main bile duct resection) and postoperative morbidity. In the PSE group, depth of tumor invasion was T1b in six, T2 in 24, T3 in 22, and T4 in two; this was not significantly different from patients without PSE (P = 0.69). Port-site metastasis was observed in only one (2%) patient with a T3 tumor who died with peritoneal metastases 15 months after resection. PSE did not improve the overall survival (77%, 58%, 21% at 1, 3, 5 years, respectively) compared to patients with no PSE (78%, 55%, 33% at 1, 3, 5 years, respectively, P = 0.37). Eight percent of patients developed incisional hernia at the port-site after excision. CONCLUSION: In patients with IGBC, PSE was not associated with improved survival and should not be considered mandatory during definitive surgical treatment.

Pancreatectomy for adenocarcinoma in elderly patients: postoperative outcomes and long term results: a study of the French Surgical Association.

AIM: To determine the benefit of surgery for resectable pancreatic adenocarcinomas (PAs) in elderly patients. METHODS: From 2004 to 2009, 932 patients with resectable PAs underwent pancreatectomies without neoadjuvant treatment in 37 institutions. The patients were divided into three groups according to age: <70 years (control group; n = 580); 70-79 years (70s group, n = 288), and ≥ 80 years (80s group; n = 64). Preoperative, intraoperative, postoperative, and histological data were recorded to assess the postoperative course and survival. RESULTS: Preoperative or intraoperative characteristics, and the histological findings were comparable in the three groups. Postoperative mortality and morbidity rates did not differ in the three groups. Adjuvant therapies were more frequently used in younger patients than in elderly patients (p < 0.01). The overall 1-year, 3-year, and 5-year survival rates of control group/70's group/80's group were 82.2%/75.7%/75.7%, 49.9%/41.8%/31%, and 38.7%/33.2%/0%, respectively (p = 0.16). The median survival of the control, 70s, and 80s groups was 24 months, 35.3 months, and 30 months, respectively. Four independent prognostic indicators were identified by multivariate analysis: venous invasion (hazard ratio (HR) = 2.12), arterial invasion (HR = 2.96), positive lymph nodes (HR = 2.25), and adjuvant treatment (HR = 0.65). CONCLUSIONS: Fit elderly patients with resectable PAs should not be excluded from surgical resection of PA solely because of their real age. Moreover, elderly patients seem to obtain similar advantages from pancreatectomies than younger patients.

Multicentre European study of preoperative biliary drainage for hilar cholangiocarcinoma.

BACKGROUND: Indications for preoperative biliary drainage (PBD) in the context of hepatectomy for hilar malignancies are still debated. The aim of this study was to investigate current European practice regarding biliary drainage before hepatectomy for Klatskin tumours. METHODS: This was a retrospective analysis of all patients who underwent formal or extended right or left hepatectomy for hilar cholangiocarcinoma between 1997 and 2008 at 11 European teaching hospitals, and for whom details of serum bilirubin levels at admission and at the time of surgery were available. PBD was performed at the physicians' discretion. The primary outcome was 90-day mortality. Secondary outcomes were morbidity and cause of death. The association of PBD and of preoperative serum bilirubin levels with postoperative mortality was assessed by logistic regression, in the entire population as well as separately in the right- and left-sided hepatectomy groups, and was adjusted for confounding factors. RESULTS: A total of 366 patients were enrolled; PBD was performed in 180 patients. The overall mortality rate was 10·7 per cent and was higher after right- than left-sided hepatectomy (14·7 versus 6·6 per cent; adjusted odds ratio (OR) 3·16, 95 per cent confidence interval 1·50 to 6·65; P = 0·001). PBD did not affect overall postoperative mortality, but was associated with a decreased mortality rate after right hepatectomy (adjusted OR 0·29, 0·11 to 0·77; P = 0·013) and an increased mortality rate after left hepatectomy (adjusted OR 4·06, 1·01 to 16·30; P = 0·035). A preoperative serum bilirubin level greater than 50 µmol/l was also associated with increased mortality, but only after right hepatectomy (adjusted OR 7·02, 1·73 to 28·52; P = 0·002). CONCLUSION: PBD does not affect overall mortality in jaundiced patients with hilar cholangiocarcinoma, but there may be a difference between patients undergoing right-sided versus left-sided hepatectomy.

Prognostic value of jaundice in patients with gallbladder cancer by the AFC-GBC-2009 study group.

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).

Liver transplantation in a patient treated by sorafenib for hepatocellular carcinoma.

Sorafenib is a multikinase inhibitor currently used in the palliative treatment of advanced hepatocellular carcinoma. In patients with small hepatocellular carcinoma, sorafenib could be suggested as neoadjuvant therapy to control tumor growth during waiting time for liver transplantation. However, up to now, safety of liver transplantation in patients undergoing sorafenib treatment is not known. Herein, we report a case of successful liver transplantation in a patient treated by sorafenib for hepatocellular carcinoma. In this patient, liver transplantation was performed safely and histological examination of explanted liver evidenced complete necrosis of the largest tumor nodule.

[Abdominal cystic tumor revealing lymphangioleiomyomatosis]. / Tumeurs kystiques rétropéritonéales compliquées révélatrices d'une lymphangioléiomyomatose.

We report the case of a 39 year-old woman with many years of intermittent abdominal pain who was found to have cystic masses evocative of cystic lymphangioma involving the posterior mediastinal and retroperitoneum. Worsening abdominal pain led to a recommendation for laparoscopic unroofing and decompression of the cysts. During the postoperative period, hemorrhagic shock required reintervention with excision of the tumoral mass. Pathologic examination revealed lymphangioleiomyomatosis (LAM). On the 15th postoperative day, the patient developed a chylopneumothorax which required prolonged chest tube drainage. The presence of multiple polycystic lesions in the pulmonary parenchyma supported the diagnosis of diffuse LAM with primary extrapulmonary presentation. This diagnosis should be considered preoperatively since it modifies the treatment: a complete excision of the cystic lesions seems to be necessary in order to prevent bleeding and lymphatic extravasation.

[Radical surgery in intrahepatic cholangiocarcinoma]. / Chirurgie radicale des cholangiocarcinomes périphériques.

The aim of this retrospective study was to evaluate the results of surgical treatment of intrahepatic cholangiocarcinoma treated by the same team. Between 1988 and 2005, 75 patients underwent surgery for intrahepatic cholangiocarcinoma. There were 53 resections including three additional interventions for recurrence. Twenty-seven exploratory laparotomies showed non resectable tumors and two were followed by a liver transplantation at the beginning of the study. Major hepatectomy was performed in 85% of resections while hepatectic resection was extended to an adjacent organ in 40%. A lymphadenectomy was performed in 32 cases. Mortality was 7.8% (two massive pulmonary embolisms, one mutiple organ failure after transplantation and one post-operative peritonitis). Global morbidity was 47%. Resectability was 66%. In case of surgical resection, the median survival rate was 18 months versus 4 months without resection (p<0.001). Actuarial survival rates at 1 year, 3 years and 5 years were 69, 31 and 27% respectively. Positive nodes decreased the survival rate (13 months versus 20 months, p=0.01). A positive margin (R1 or R2 resection) did not significantly decrease the survival rate (18 months versus 15 months). In conclusion, intrahepatic cholangiocarcinoma is a tumor that often requires a major or an extended hepatectomy. Complete resection is an acceptable and reasonable goal, whatever the patient's age. This radical surgical approach can prolong survival. Palliative surgery is not an option if incomplete resection is predicted.

Ileal patch duodenoplasty after right colectomy extended to the duodenal wall.

After radical resection of cancer of the right colonic flexure, a parietal defect can be created in case of duodenal invasion. In this paper the authors describe an "easy and safe" duodenoplasty surgical technique using an ileal patch.

Aggressive multimodal therapy of sporadic malignant insulinoma can improve survival: a retrospective 35-year study of 12 patients.

AIM: Sporadic malignant insulinoma (SMI) is a rare disease, and the consequent paucity of data in the literature and the development of aggressive treatments for liver metastases have led us to retrospectively analyze a series of 12 cases of SMI. METHODS: Every patient presenting with SMI, according to the WHO 2004 histopathology criteria, between 1970 and June 2005 in Marseille was included in the study. Patients with multiple endocrine neoplasia type 1 (MEN-1) and tumours of uncertain malignant potential were excluded. RESULTS: The ratio of male/female was 4/8, and mean age at diagnosis was 52.5 years. A 48-h fasting test in 10 patients was conclusive in nine, after a mean duration of 12 h 45 min. SMI size ranged from 7-120 mm (mean 30.3mm). Six patients had liver metastases and one had isolated lymph-node invasion. Surgery was performed in 12 patients. Five persisting diseases (mean follow-up of 1.8 years) required other treatments (chemoembolization, radiofrequency thermoablation [RFTA], liver transplantation); one patient relapsed 8.5 years after surgery; six were still in complete remission (mean follow-up of 5.8 years), and one patient had died by the time of the 24-month follow-up. CONCLUSION: Aggressive sequential multimodal therapy can prolong the survival of patients with SMI even in the presence of liver metastases.

Predictors of long-term survival after liver transplantation for metastatic endocrine tumors: an 85-case French multicentric report.

Liver transplantation (LTx) for metastatic endocrine tumors (MET) remains controversial due to the lack of clear selection criteria. From 1989 to 2005, 85 patients underwent LTx for MET. The primary tumor was located in the pancreas or duodenum in 40 cases, digestive tract in 26 and bronchial tree in five. In the remaining 14 cases, primary location was undetermined at the time of LTx. Hepatomegaly (explanted liver > or =120% of estimated standard liver volume) was observed in 53 patients (62%). Extrahepatic resection was performed concomitantly with LTx in 34 patients (40%), including upper abdominal exenteration (UAE) in seven. Postoperative in-hospital mortality was 14%. Overall 5-year survival was 47%. Independent factors of poor prognosis according to multivariate analysis included UAE (relative risk (RR): 3.72), primary tumor in duodenum or pancreas (RR: 2.94) and hepatomegaly (RR: 2.63). After exclusion of cases involving concomitant UAE, the other two factors were combined into a risk model. Five-year survival rate was 12% for the 23 patients presenting both unfavorable prognostic factors versus 68% for the 55 patients presenting one or neither factor (p < 10(-7)). LTx can benefit selected patients with nonresectable MET. Patients presenting duodeno-pancreatic MET in association with hepatomegaly are poor indications for LTx.

Prognostic factors after resection for hepatocellular carcinoma in nonfibrotic or moderately fibrotic liver. A 116-case European series.

The purpose of this study was to identify factors influencing prognosis after resection for hepatocellular carcinoma in the noncirrhotic liver and to measure the impact of moderate fibrosis on presentation and prognosis. A series of 116 primary procedures were performed for hepatocellular carcinoma in the noncirrhotic liver. These cases accounted for 42% of hepatic resections performed for hepatocellular carcinoma during the study period (1987-2005). Seventy-seven cases (58%) occurred in patients with nonfibrotic livers (Metavir score F0). The mean age was 61 years. The sex ratio was 3.5, with a female predominance before 50 years. Hepatitis B virus (HBV) or hepatitis C virus infection was found in 30% of patients. Symptoms were present in 64% of cases. Elevated serum alpha fetoprotein levels were observed in 44% of cases. Procedures involved minor hepatectomy in 40 cases, major hepatectomy in 72 cases, and transplantation in 4 cases. Postoperative mortality was 6% and morbidity was 31%. Complete resection was achieved in 90% of cases. The tumor was isolated in 72% of cases. The mean tumor diameter was 10.6 cm. Vascular invasion was observed in 48% of cases. Hepatocellular carcinoma in the nonfibrotic liver was associated with younger age and female sex, but there was no difference with other hepatocellular carcinoma with regard to histological or prognostic features. With a median follow-up of 79 months, overall survival was 40% for a median of 41 months. Multivariate analysis identified incomplete resection, vascular invasion, and HBV infection as independent factors of poor prognosis. In case of recurrence, repeat resection was feasible in 30% of cases with 69% survival at 5 years. Although hepatocellular carcinoma in the noncirrhotic liver is generally diagnosed at an advanced stage, its resectability remains high. As a result, hepatocellular carcinoma in the noncirrhotic liver accounts for a large proportion of cases in surgical series and has a better prognosis than hepatocellular carcinoma in the cirrhotic liver. Vascular invasion, incomplete resection, and HBV infection are independent factors of poor prognosis.