Olivier Farges

Seven hundred forty-seven hepatectomies in the 1990s: an update to evaluate the actual risk of liver resection.

BACKGROUND Recent reports highlighting reduced mortality rates to less than 1% after hepatic resections have evaluated the management of selected patients. The current risk of liver resection in unselected patients needs to be more clearly defined to appreciate the actual risk of new indications. STUDY DESIGN From 1990 to 1997, 747 consecutive patients, including 16 operated in emergency, underwent hepatic resection. Resection was indicated for malignancy in 473 patients (63%). Major resections were performed in 333 patients (45%). An underlying liver disease, including cirrhosis (n = 239) and obstructive jaundice (n = 4), was present in 253 patients (35%). Multivariate analysis of the risk factors for postoperative mortality, morbidity, and transfusion after stratifying patients for the circumstance of the operation and the pathological changes of the remnant liver was performed. RESULTS There was no intraoperative death and the overall mortality rate was 4.4%. This rate was 25% after emergency liver resection and 3.9% after elective liver resection (p < 0.001). After elective resection, mortality was significantly higher in patients with cirrhosis (8.7%) or obstructive jaundice (21%) than in patients with a normal liver (1%; p < 0.001). Analysis of this subgroup of 478 patients with normal liver showed that the mortality rate was 0% in 220 patients operated for a benign disease and in 263 patients who underwent minor resections. All five deaths occurred in patients with a malignancy and resulted from extrahepatic complications. In patients with a malignancy, the only independent predictor of death was an associated extrahepatic procedure. The incidence of postoperative complications was 22% and was influenced by the American Society of Anaesthesiology (ASA) score, extent of resection, presence of a steatosis, and an associated extrahepatic procedure. The incidence of major complications was 8% and of reoperation 3%. Perioperative blood transfusion was required in 112 of 478 (23%) and was not associated with increased mortality. CONCLUSIONS The 1% basic risk of elective liver resection on normal liver suggests that indications of resection for malignancy could be extended, unless an associated extrahepatic procedure is needed. Because of this low basic risk, future studies evaluating resection on normal liver should not consider in-hospital mortality as the only end point.

Original scientific articleSeven hundred forty-seven hepatectomies in the 1990s: an update to evaluate the actual risk of liver resection1

BACKGROUND Recent reports highlighting reduced mortality rates to less than 1% after hepatic resections have evaluated the management of selected patients. The current risk of liver resection in unselected patients needs to be more clearly defined to appreciate the actual risk of new indications. STUDY DESIGN From 1990 to 1997, 747 consecutive patients, including 16 operated in emergency, underwent hepatic resection. Resection was indicated for malignancy in 473 patients (63%). Major resections were performed in 333 patients (45%). An underlying liver disease, including cirrhosis (n = 239) and obstructive jaundice (n = 4), was present in 253 patients (35%). Multivariate analysis of the risk factors for postoperative mortality, morbidity, and transfusion after stratifying patients for the circumstance of the operation and the pathological changes of the remnant liver was performed. RESULTS There was no intraoperative death and the overall mortality rate was 4.4%. This rate was 25% after emergency liver resection and 3.9% after elective liver resection (p < 0.001). After elective resection, mortality was significantly higher in patients with cirrhosis (8.7%) or obstructive jaundice (21%) than in patients with a normal liver (1%; p < 0.001). Analysis of this subgroup of 478 patients with normal liver showed that the mortality rate was 0% in 220 patients operated for a benign disease and in 263 patients who underwent minor resections. All five deaths occurred in patients with a malignancy and resulted from extrahepatic complications. In patients with a malignancy, the only independent predictor of death was an associated extrahepatic procedure. The incidence of postoperative complications was 22% and was influenced by the American Society of Anaesthesiology (ASA) score, extent of resection, presence of a steatosis, and an associated extrahepatic procedure. The incidence of major complications was 8% and of reoperation 3%. Perioperative blood transfusion was required in 112 of 478 (23%) and was not associated with increased mortality. CONCLUSIONS The 1% basic risk of elective liver resection on normal liver suggests that indications of resection for malignancy could be extended, unless an associated extrahepatic procedure is needed. Because of this low basic risk, future studies evaluating resection on normal liver should not consider in-hospital mortality as the only end point.

The “50-50 Criteria” on Postoperative Day 5: An Accurate Predictor of Liver Failure and Death After Hepatectomy

Objective:To standardize the definition of postoperative liver failure (PLF) for prediction of early mortality after hepatectomy. Summary Background Data:The definition of PLF is not standardized, making the comparison of innovations in surgical techniques and the timely use of specific therapeutic interventions complex. Methods:Between 1998 and 2002, 775 elective liver resections, including 69% for malignancies and 60% major resections, were included in a prospective database. The nontumorous liver was abnormal in 43% with steatosis >30% in 14%, noncirrhotic fibrosis in 43%, and cirrhosis in 12%. The impact of prothrombin time (PT) <50% and serum bilirubin (SB) >50 &mgr;mol/L on postoperative days (POD) 1, 3, 5, and 7 was analyzed. Results:The lowest PT level was observed on postoperative day (POD) 1, while the peak of SB was observed on POD 3. These 2 variables tended to return to preoperative values by POD 5. The median interval between hepatectomy and postoperative death was 15 days (range, 5–39 days). Postoperative mortality significantly increased in patients with PT <50% and SB >50 &mgr;ml/L. The conjunction of PT <50% and SB >50 &mgr;mol/L on POD 5 was a strong predictive factor of mortality. In patients with significant morbidity, this “50-50 criteria” was met 3 to 8 days before clinical evidence of complications. Conclusions:The association of PT <50% and SB >50 &mgr;ml/L on POD 5 (the 50-50 criteria) was a simple, early, and accurate predictor of more than 50% mortality rate after hepatectomy. This criteria could be identified early enough, before clinical evidence of complications, for specific interventions to be applied in due time.

Intrahepatic recurrence after resection of hepatocellular carcinoma complicating cirrhosis.

To determine whether a careful evaluation of tumor extension by preoperative computed tomography scan after intra-arterial injection of ultrafluid lipiodol and by intraoperative ultrasound examination reduced the recurrence rate of hepatocellular carcinoma after resection, a series of 47 cirrhotic patients with a single tumor operated on from 1984 was studied. Alphafetoprotein level was less than 100 ng/mL in 26 patients (55%), size of the tumor was less than 5 cm in 28 patients (59%), and capsule was present in 30 patients (63%). The resection was performed with free margin measuring 1 cm or more. The overall cumulative survival rates at 3 and 5 years were 35% and 17%, respectively. Intrahepatic recurrence was observed in 28 patients (60%), located less than 2 cm from the resection margin in only four patients. The cumulative intrahepatic recurrence rate at 3 years was 81% and was significantly higher in patients with tumor 5≥ 5 cm and in patients with preoperative alphafetoprotein level of 5≥ 100 ng/mL. In this series the cumulative intrahepatic recurrence rate at 5 years was 100%. This high recurrence rate after resection, even with careful evaluation of tumor extension, indicates that liver transplantation might be envisaged for the treatment of cirrhotic patients with resectable hepatocellular carcinoma.

Portal Vein Embolization Before Right Hepatectomy: Prospective Clinical Trial

ObjectiveTo assess the impact of liver hypertrophy of the future liver remnant volume (FLR) induced by preoperative portal vein embolization (PVE) on the immediate postoperative complications after a standardized major liver resection. Summary Background DataPVE is usually indicated when FLR is estimated to be too small for major liver resection. However, few data exist regarding the exact quantification of sufficient minimal functional hepatic volume required to avoid postoperative complications in both patients with or without chronic liver disease. MethodsAll consecutive patients in whom an elective right hepatectomy was feasible and who fulfilled the inclusion and exclusion criteria between 1998 and 2000 were assigned to have alternatively either immediate surgery or surgery after PVE. Among 55 patients (25 liver metastases, 2 cholangiocarcinoma, and 28 hepatocellular carcinoma), 28 underwent right hepatectomy after PVE and 27 underwent immediate surgery. Twenty-eight patients had chronic liver disease. FLR and estimated rate of functional future liver remnant (%FFLR) volumes were assessed by computed tomography. ResultsThe mean increase of FLR and %FFLR 4 to 8 weeks after PVE were respectively 44 ± 19% and 16 ± 7% for patients with normal liver and 35 ± 28% and 9 ± 3% for those with chronic liver disease. All patients with normal liver and 86% with chronic liver disease experienced hypertrophy after PVE. The postoperative course of patients with normal liver who underwent PVE before right hepatectomy was similar to those with immediate surgery. In contrast, PVE in patients with chronic liver disease significantly decreased the incidence of postoperative complications as well as the intensive care unit stay and total hospital stay after right hepatectomy. ConclusionsBefore elective right hepatectomy, the hypertrophy of FLR induced by PVE had no beneficial effect on the postoperative course in patients with normal liver. In contrast, in patients with chronic liver disease, the hypertrophy of the FLR induced by PVE decreased significantly the rate of postoperative complications.

CONTINUOUS VERSUS INTERMITTENT PORTAL TRIAD CLAMPING FOR LIVER RESECTION: A CONTROLLED STUDY

OBJECTIVE The authors compared the intra- and postoperative course of patients undergoing liver resections under continuous pedicular clamping (CPC) or intermittent pedicular clamping (IPC). SUMMARY BACKGROUND DATA Reduced blood loss during liver resection is achieved by pedicular clamping. There is controversy about the benefits of IPC over CPC in humans in terms of hepatocellular injury and blood loss control in normal and abnormal liver parenchyma. METHODS Eighty-six patients undergoing liver resections were included in a prospective randomized study comparing the intra- and postoperative course under CPC (n = 42) or IPC (n = 44) with periods of 15 minutes of clamping and 5 minutes of unclamping. The data were further analyzed according to the presence (steatosis >20% and chronic liver disease) or absence of abnormal liver parenchyma. RESULTS The two groups of patients were similar in terms of age, sex, nature of the liver tumors, results of preoperative assessment, proportion of patients undergoing major or minor hepatectomy, and nature of nontumorous liver parenchyma. Intraoperative blood loss during liver transsection was significantly higher in the IPC group. In the CPC group, postoperative liver enzymes and serum bilirubin levels were significantly higher in the subgroup of patients with abnormal liver parenchyma. Major postoperative deterioration of liver function occurred in four patients with abnormal liver parenchyma, with two postoperative deaths. All of them were in the CPC group. CONCLUSIONS This clinical controlled study clearly demonstrated the better parenchymal tolerance to IPC over CPC, especially in patients with abnormal liver parenchyma.

Resection Prior to Liver Transplantation for Hepatocellular Carcinoma

Objective: To evaluate the feasibility and postoperative course of liver transplantation (LT) in cirrhotic patients who underwent liver resection prior to LT for HCC. Summary Background Data: Although LT provides longer survival than liver resection for treatment of small HCCs, donor shortage and long LT wait time may argue against LT. The feasibility and survival following LT after hepatic resection have not been previously examined. Methods: Between 1991 and 2001, among 107 patients who underwent LT for HCC, 88 met Mazzaferos criteria upon pathologic analysis of the explant. Of these, 70 underwent primary liver transplantation (PLT) and 18 liver resection prior to secondary liver transplantation (SLT) for recurrence (n = 11), deterioration of liver function (n = 4), or high risk for recurrence (n = 3). Perioperative and postoperative factors and long-term survival were compared. Results: Comparison of PLT and SLT groups at the time of LT revealed similar median age (53 vs. 55 years), sex, and etiology of liver disease (alcohol/viral B/C/other). In the SLT group, the mean time between liver resection and listing for LT was 20 months (range 1–84 months). Overall time on LT waiting list of the two groups was similar (3 vs. 5 months). Pathologic analysis after LT revealed similar tumor size (2.2 vs. 2.3 cm) and number (1.6 vs. 1.7). Perioperative and postoperative courses were not different in terms of operative time (551 vs. 530 minutes), blood loss (1191 vs. 1282 mL), transfusion (3 vs. 2 units), ICU (9 vs. 10 days) or hospital stay (32 vs. 31 days), morbidity (51% vs. 56%) or 30-day mortality (5.7% vs. 5.6%). During a median follow-up of 32 months (3 to 158 months), 3 patients recurred after PLT and one after SLT. After transplantation, 3- and 5-year overall survivals were not different between groups (82 vs. 82% and 59 vs. 61%). Conclusions: In selected patients, liver resection prior to transplantation does not increase the morbidity or impair long-term survival following LT. Therefore, liver resection prior to transplantation can be integrated in the treatment strategy for HCC.

Risk of major liver resection in patients with underlying chronic liver disease: a reappraisal.

OBJECTIVE To explore the relation of patient age, status of liver parenchyma, presence of markers of active hepatitis, and blood loss to subsequent death and complications in patients undergoing a similar major hepatectomy for the same disease using a standardized technique. SUMMARY BACKGROUND DATA Major liver resection carries a high risk of postoperative liver failure in patients with chronic liver disease. However, this underlying liver disease may comprise a wide range of pathologic changes that have, in the past, not been well defined. METHODS The nontumorous liver of 55 patients undergoing a right hepatectomy for hepatocellular carcinoma was classified according to a semiquantitative grading of fibrosis. The authors analyzed the influence of this pathologic feature and of other preoperative variables on the risk of postoperative death and complications. RESULTS Serum bilirubin and prothrombin time increased on postoperative day 1, and their speed of recovery was influenced by the severity of fibrosis. Incidence of death from liver failure was 32% in patients with grade 4 fibrosis (cirrhosis) and 0% in patients with grade 0 to 3 fibrosis. The preoperative serum aspartate transaminase (ASAT) level ranged from 68 to 207 IU/l in patients with cirrhosis who died, compared with 20 to 62 in patients with cirrhosis who survived. CONCLUSION A major liver resection such as a right hepatectomy may be safely performed in patients with underlying liver disease, provided no additional risk factors are present. Patients with a preoperative increase in ASAT should undergo a liver biopsy to rule out the presence of grade 4 fibrosis, which should contraindicate this resection.

Obesity and diabetes as a risk factor for hepatocellular carcinoma

Ten percent of patients who undergo resection for hepatocellular carcinoma (HCC) associated with chronic liver disease have no detectable cause for this underlying liver disease. Recent studies have shown that patients with cryptogenic chronic liver disease frequently have risk factors for nonalcoholic fatty liver disease (NAFLD). This study examines the incidence of risk factors for NAFLD in patients with chronic liver disease who underwent resection for HCC. Among 210 patients with chronic liver disease who underwent resection for HCC, 18 (8.6%) had no identifiable cause for the underlying liver disease. These patients were assessed for obesity, diabetes mellitus, and histological features of the tumor and the adjacent liver parenchyma. Comparisons were made with matched patients with alcohol‐ and chronic‐viral‐hepatitis‐related HCC. The prevalence of obesity (50% vs. 17% vs. 14%), diabetes (56% vs. 17% vs. 11%), aspartate aminotransferase / alanine aminotransferase ratio < 1 (50% vs. 19% vs. 17%), and steatosis > 20% (61% vs. 17% vs. 19%) was significantly higher in patients with cryptogenic liver disease than in patients with alcohol abuse and chronic viral hepatitis (P < 0.0001 for each). Well‐differentiated tumors were significantly more common in patients with cryptogenic liver disease (89% vs. 64% in patients with alcohol‐related HCC vs. 55% in patients with chronic viral hepatitis‐related HCC, P < 0.0001).

Is there a role of preservation of the spleen in distal pancreatectomy

BACKGROUND The spleen may be preserved during distal pancreatectomy (DP) for benign disease. The aim of this retrospective study was to compare the postoperative course of DP with or without splenectomy. STUDY DESIGN From June 1992 to June 1997, 40 adult patients without chronic pancreatitis underwent elective DP for benign lesions. Fifteen underwent spleen-preserving DP (Conservative Group) and 25 DP with splenectomy (Splenectomy Group). In spleen-preserving DP, we attempted to preserve the splenic artery and vein. RESULTS Spleen-preserving DP was successfully performed in all 15 cases. Patient groups were comparable for clinical features, indication for DP, and surgical procedure. There were no postoperative deaths. The overall incidence of pancreatic fistula was 23%, but was significantly higher in the Conservative Group (40%) than in the Splenectomy Group (12%; p < 0.05). Subphrenic abscesses were more frequently observed in the Conservative Group than in the Splenectomy Group (p < 0.05). The mean duration of postoperative hospital stay was 19 days (range 6 to 46 days) in the Conservative Group and 12.5 days (range 7 to 45 days) in the Splenectomy Group (p < 0.05). At the end of mean followup of 30 months (range 8 to 40 months), no severe postsplenectomy sepsis was observed in the Splenectomy Group. CONCLUSIONS In our experience, DP with splenectomy has a lower morbidity rate and we consider it to be the best procedure for benign pancreatic disease.