Jean-Christophe Weber

A Two-Stage Hepatectomy Procedure Combined With Portal Vein Embolization to Achieve Curative Resection for Initially Unresectable Multiple and Bilobar Colorectal Liver Metastases

Objective:To assess outcome after a 2-stage hepatectomy procedure (TSHP) combined with portal vein embolization (PVE) in the treatment of patients with unresectable multiple and bilobar colorectal liver metastases (MBCLM). Background:Patients with MBCLM are often considered for palliative chemotherapy only, due to too small future remnant liver (FRL). Recently, right hepatectomy with simultaneous left liver wedge resections after previous right PVE has been reported in a curative intent. However, the growth of metastatic nodules in FRL after PVE can be more rapid than that of the nontumoral remnant hepatic parenchyma. Therefore, metastases located in the FRL should be ideally resected before PVE. Then, a right (or extended right) hepatectomy can be safely performed during a second-stage hepatectomy. Therefore, we analyzed our experience with the use of TSHP combined with PVE in treatment of MBCLM. Patients and Methods:Between December 1996 and April 2003, 33 patients with unresectable MBCLM were selected for a TSHP. A right or an extended right hepatectomy was planned after treatment of left FRL metastases to achieve a curative resection. The first-stage hepatectomy consisted in a clearance of the left hemiliver by resection or radiofrequency destruction of metastases of the left FRL. Subsequently, a right PVE was performed to induce atrophy of the right hemiliver and hypertrophy of the left hemiliver. Finally, a second-stage hepatectomy was planned to resect the right liver metastases. Results:There was no operative mortality. Post-PVE morbidity was 18.1%; postoperative morbidity was 15.1% and 56.0% after first- and second-stage hepatectomy, respectively. TSHP could be achieved in 25 of 33 patients (75.7%). The 1- and 3-year survival rates were 70.0% and 54.4%, respectively, in the 25 patients in whom the TSHP was completed. Conclusions:In selected patients with initially unresectable MBCLM, a TSHP combined with PVE can be achieved safely with long-term survival similar to that observed in patients with initially resectable liver metastases.

Is pancreaticoduodenectomy with mesentericoportal venous resection safe and worthwhile

BACKGROUND Whether or not superior mesentericoportal venous resection (SM-PVR) associated with pancreaticoduodenectomy (PD) is safe and worthwhile has not been fully confirmed. The aim of the present study was to investigate results of this surgical procedure performed for pancreatic head and periampullary neoplasms. METHODS As a first analysis, postoperative morbidity and mortality after PD with (n = 31) or without SM-PVR (n = 119) were investigated in 150 patients with pancreatic head and periampullary neoplasms. As a second analysis, rates of margin-negative resection and survival after SM-PVR (n = 21) and without SM-PVR (n = 66) were compared in 87 patients with pancreatic ductal adenocarcinoma of the pancreatic head. In these patients undergoing SM-PVR (n = 21), survival rate was investigated in patients who did (n = 13) and did not (n = 8) undergo a margin-negative resection. RESULTS In the first analysis, duration of surgery and volume of blood transfused perioperatively were higher in patients undergoing SM-PVR. However, mortality, morbidity rates, and mean hospital stay did not differ between patients who did undergo SM-PVR (31 patients, 3.2%, 48.4%, and 22.2 days, respectively) and who did not (119 patients, 2.5%, 47.1%, 25.9 days, respectively). No postoperative death occurred in the recent part of the present study, since 1994, in patients undergoing SM-PVR. In the second analysis of pancreatic ductal adenocarcinoma, rates of margin-negative resection and 2-year survival did not significantly differ between patients who did and did not undergo SM-PVR (62% and 22%, respectively, versus 73% and 24%). In patients undergoing SM-PVR, survival rate was significantly higher for patients undergoing a margin-negative resection (n = 13) than for patients undergoing a macroscopic or microscopic margin-positive resection (n = 8, 2-year survival = 57.1% versus 0%, P <0.05). CONCLUSION PD combined with SM-PVR can be performed safely. This surgical procedure is followed by a promising survival rate and can be recommended in order to obtain a margin-negative resection; however, candidates for SM-PVR should be carefully selected.

Significance of hepatic pedicle lymph node involvement in patients with colorectal liver metastases: A prospective study

BackgroundWe investigated whether hepatic pepticle lymph node (HP-LN) involvement is a more significant prognostic factor and whether HP-LN dissection could be efficient in patients with positive HP-LN involvement.MethodsFrom 1988 to 1998, HP-LN dissection was prospectively performed in 160 patients undergoing hepatectomy for colorectal liver metastases. Survival of patients with HP-LN involvement limited to the hepatoduodenal ligament and retropancreatic portion (area 1) was compared with that of patients with HP-LN involvement spreading over the common hepatic artery and celiac axis (area 2).ResultsHP-LN involvement was detected in 17 patients. The survival rate was significantly lower in patients with HP-LN involvement. HP-LN involvement was the most significant prognostic factor. Survival was significantly higher in patients with HP-LN involvement limited to area 1 than in those with HP-LN involvement spreading over area 2.ConclusionsHP-LN involvement was the most significant prognostic indicator in patients with colorectal liver metastases. Positive LNs of area 1 should no longer be considered an absolute contraindication to liver resection, but in case of area 2 lymph node involvement, liver resection does not seem justified.

Salivary gland lymphomas in patients with Sjögren's syndrome may frequently develop from rheumatoid factor B cells.

OBJECTIVE Patients with Sjögrens syndrome (SS) have an increased risk of developing monoclonal B cell non-Hodgkins lymphomas (MNHL), which frequently occur in the salivary glands (SG). The transition from the benign lymphocyte infiltrate of the gland that characterizes SS to MNHL is not well understood. Previous sequence analyses of the expressed variable (V) region genes have supported the theory that the surface Ig (sIg) plays an important role in the initial expansion of nonmalignant B cell clones and in lymphomagenesis. However, the antigenic specificities of these B cells were unknown. We describe the specificities of the Ig expressed by 2 cases of MNHL that developed in the SG of 2 patients with SS. METHODS The expressed V genes were amplified by polymerase chain reaction from biopsy specimens, sequenced, and subcloned into eukaryotic expression vectors. The constructs were transfected into P3X63-Ag8.653 cells to obtain 2 monoclonal cell lines, each secreting 1 of the sIg expressed by the MNHL. These IgM were tested by enzyme-linked immunosorbent assay and immunofluorescence against a panel of antigens potentially implicated in SS. RESULTS Our main finding was that the Ig products of the neoplastic B cells were rheumatoid factors (RF). Contrary to expectations, they did not react with nuclear or cytoplasmic antigens, double-stranded DNA, self antigens commonly bound by natural autoantibodies, or SG tissue. CONCLUSION Previous analyses of V gene use have provided indirect evidence that SG MNHL may frequently express RF. We demonstrate that this hypothesis is true in the 2 patients we studied. Large-scale studies will be needed to establish the exact frequency of RF specificity among SS-associated MNHL.

Hepatic Metastases of Gastroenteropancreatic Neuroendocrine Tumors: Safe Hepatic Surgery

Abstract. Liver metastases of neuroendocrine tumors are usually slow-growing, and cytoreductive hepatectomy can help reduce the effects of endocrinopathies and increase life expectancy and symptom-free survival. However, it has yet to be fully investigated how hepatectomy for metastatic neuroendocrine tumors can be performed safely. Here we report the results of 13 patients with neuroendocrine liver metastases operated on in our institution and those of a French multicentric study that included 131 patients. Preoperative patient selection and appropriate surgical technique, sometimes combined with preoperative portal embolization and local tumor destruction (radiofrequency and cryotherapy), may increase the resectability and the safety of the procedure. The mortality rate after hepatectomy was 0% (2.3% in the French study); the 3- and 6-year survival rates were 91% and 68%, respectively, in our institution (the mean survival time was 66 months in the French multicentric survey). Significant prolonged survival with complete palliation of symptoms can be obtained after liver metastases resection with low mortality.

First and repeat resection of colorectal liver metastases in elderly patients.

Objective:The objective of this study was to evaluate the short- and long-term outcome after first and repeat resection in patients older than 70 years. Summary Background Data:Liver resection is the best treatment for colorectal liver metastases and is currently increasingly performed in elderly patients. The benefit of resection for these patients needs to be evaluated. Methods:Between 1990 and 2000, 56 first and 16 repeat liver resections were performed in 61 patients older than 70 years. Patients were identified from a prospective database and records were reviewed retrospectively. Results:First and repeat liver resection resulted, respectively, in a 0% and 7% postoperative mortality rate and a 41% and 38% complication rate, respectively. Median survival after first resection of 53 patients with R0 resection was 33 months, and the 5-year survival rate was 22%. Factors associated with poor long-term survival in multivariate analysis were extrahepatic disease, high carcinoembryonic antigen level over 200 ng/mL, and the presence of 3 or more liver metastases. Patients without these risk factors showed a median survival of 42 months and a 5-year survival rate of 36%. Repeat liver resection resulted in a median survival of 17 months and in a 3-year survival rate of 25%. Conclusion:First and repeat liver resection for colorectal liver metastases can be performed safely in patients older than 70 years. A 5-year survival rate similar to those of younger patients can be expected after first liver resection for patients without the presence of risk factors.

Surgical Resection of Hepatocellular Carcinoma. Post-operative Outcome and Long-term Results in Europe: An Overview

A multicenter retrospective review of 1467 patients treated by liver resection (LR) for hepatocellular carcinoma (HCC) in Europe over a 13‐year period showed a mean mortality rate of 10.6%, which was correlated with the extent of LR, the etiology of cirrhosis and the study period with an improvement during the last years. Improved 5‐year overall survival (20–51%) and disease‐free survival (20–33%) reached similar rates in cirrhotic than in non‐cirrhotic patients. Overall results were similar to those reported in Asian series as far as patients and tumor characteristics were comparable. (Liver Transpl 2004;10:S58–S63.)

Surgical repair after bile duct and vascular injuries during laparoscopic cholecystectomy: when and how?

Abstract. Recent collective reviews have outlined when and how surgeons should treat patients with bile duct injuries after laparoscopic cholecystectomy (LC). However, little is described about other injuries combined with bile duct injuries, for example, hepatic arterial injury and secondary biliary cirrhosis. Fifteen patients with bile duct injuries following LC were referred and surgically treated from 1990 to 1998 in our institution. We report how patients with hepatic arterial injury combined with bile duct injuries during LC were treated. The present study also reports unusual complicated situations: one patient with biliary cirrhosis referred 4 years after LC, another treated with internal biliary metallic stent referred 2.5 years after LC, and another with isolated right hepatic ductal injury. Short- and long-term surgical outcomes after biliary repair were compared between simply referred patients and those with complicated history. Patients who were referred several years after LC and who were referred after primary hepaticojejunostomy were included with patients with complicated history (n= 4, group B), and the other patients were included with patients with simple history (n= 11, group A). Simultaneous right hepatic arterial occlusion was observed in 3 of these 15 patients, and arterial reconstruction was performed in 2 of the 3 patients in addition to biliary reconstruction. No postoperative complication occurred in these three patients. The patient with isolated injury of the right hepatic duct and the other with biliary cirrhosis were successfully treated with hepaticojejunostomy. The other patient treated with biliary stent underwent hepaticojejunostomy but a second operation was required because of later stenosis. Mean hospital stay was significantly longer in group B (30.3 ± 6.9 days) than in group A (18.5 ± 2.5 days, p< 0.05). Rehospitalization was more frequent in group B than in group A (p < 0.01). However, long-term outcome was successful in both groups. The present results showed that arterial reconstruction should be performed when the distal right hepatic artery can be exposed and reconstructed, and suggested that patients with bile duct injuries during LC should be immediately referred to surgical institutions in which surgeons have adequate experience of bile duct repair and hepatic arterial reconstruction.

Is a proliferation index of cancer cells a reliable prognostic factor after hepatectomy in patients with colorectal liver metastases

BACKGROUND In spite of many reports focusing on prognostic factors after hepatectomy in patients with colorectal liver metastases, few studies have investigated pathological factors, eg, fibrous pseudocapsulation, growth pattern at the tumor margin, and proliferation activity of cancer cells, other than histological type and surgical margin. The aim of the present study was to investigate whether absence of pseudocapsulation, infiltrative growth pattern of metastases, and higher proliferation of cancer cells shown by Ki-67 immunohistochemical reactivity were associated with poorer survival after hepatectomy among patients with colorectal liver metastases. METHODS Between 1988 and 1998, 221 patients underwent hepatic resection of colorectal metastases with curative intent in our institution. Pathology analyses were focused on pseudocapsulation of liver metastases, growth pattern at the tumor edge, and Ki-67 labelling index (Ki-67 LI) of cancer cell nuclei. Univariate analyses of survival and of disease-free survival were performed for several clinicopathological factors, and multivariate analyses of survival and disease-free survival were also performed. RESULTS The univariate survival analyses showed that pseudocapsulation, growth pattern, and Ki-67 LI were significant prognostic factors, besides synchronous versus metachronous occurrence of metastases, carcinoembryonic antigen level before hepatectomy, and number of metastases. A multivariate analysis showed that Ki-67 labeling index was the most reliable prognostic factor of survival. In addition, Ki-67 LI and microscopic growth pattern were multivariately predictive factors of disease-free survival. CONCLUSIONS This large single-institution study showed that investigation of cancer cell proliferation and pathologic characteristics of the tumor margin are major prognostic factors.

Modern management of non-chemotherapy drug-induced agranulocytosis: a monocentric cohort study of 90 cases and review of the literature

BACKGROUND: The present study reports a monocentric experience of 90 drug-induced agranulocytosis cases and discusses their management, in particular the role of hematopoietic growth factors. METHODS: Data from 90 patients with drug-induced agranulocytosis who met the criteria of the IAAAS group and of Bénichou and Solal-Celigny [Nouv Rev Fr Hematol 1993; 33: 257.] were retrospectively reviewed. All cases were extracted from a cohort study of the Hopitaux Universitaires de Strasbourg, France. Data were specifically analyzed with regard to the use of hematopoietic growth factors (in 42 patients). RESULTS: Mean patient age was 63 (range 17-95) years and the sex ratio (M/F) was 0.39. An underlying disease was present in 37% of the patients. Antibiotics (25%), antithyroid drugs (23%), and antiaggregative platelet agents (16%) were the most frequent causative drugs. Main clinical features included isolated fever (41%), septicemia or septic shock (31%), and pneumonia (10%). Mean neutrophil count was 0.13 (range 0-0.46)x10(9)/l. Outcome was favorable in 98% of patients. The mean durations of hematological recovery (neutrophil count over 1.5x10(9)/l), antibiotic therapy, and hospitalization was 8.5 (range 2-21) days, 9.2 (range 2-21) days, and 10.5 (range 3-23) days, respectively. All patients were treated with broad-spectrum antibiotics and 42 patients with hematopoietic growth factors. In these 42 patients, the mean durations for hematological recovery, antibiotic therapy, and hospitalization were significantly reduced at: 6.3 (range 2-16) days, 7.1 (range 2-16) days, and 9.1 (range 3-23) days, respectively (all P<0.05). CONCLUSIONS: The present study shows that new causative drugs are emerging (antibiotics, antithyroid, and antiaggregative platelet agents), that drug-induced agranulocytosis remains typically a serious accident with severe sepsis, and that modern management with broad spectrum antibiotics and hematopoietic growth factors may reduce the mortality.