Trends in indications, complications and outcomes for venous resection during pancreatoduodenectomy.

BACKGROUND: Pancreatoduodenectomy with superior mesenteric-portal vein resection has become a common procedure in pancreatic surgery. The aim of this study was to compare standard pancreatoduodenectomy with pancreatoduodenectomy plus venous resection at a high-volume centre, and to examine trends in management and outcome over a decade for the latter procedure. METHODS: This retrospective observational study included all patients undergoing pancreatoduodenectomy with or without venous resection at Oslo University Hospital between January 2006 and December 2015. Trends were evaluated by assessing preoperative clinical and radiological characteristics, as well as perioperative outcomes in three time intervals (early, intermediate and late). RESULTS: A total of 784 patients had a pancreatoduodenectomy, of whom 127 (16·2 per cent) underwent venous resection. Venous resection resulted in a longer operating time (median 422 versus 312 min; P = 0·001) and greater estimated blood loss (EBL) (median 700 versus 500 ml; P = 0·004) than standard pancreatoduodenectomy. The rate of severe complications was significantly higher for pancreatoduodenectomy with venous resection (37·0 versus 26·3 per cent; P = 0·014). The overall burden of complications, evaluated using the Comprehensive Complication Index (CCI), did not differ (median score 8·7 versus 8·7; P = 0·175). Trends in venous resection over time showed a significant reduction in EBL (median 1050 versus 375 ml; P = 0·001) and duration of hospital stay (median 14 versus 9 days; P = 0·011) between the early and late periods. However, despite an improvement in the intermediate period, severe complication rates returned to baseline in the late period (18 of 43 versus 9 of 42 versus 20 of 42 patients in early, intermediate and late periods respectively; P = 0·032), as did CCI scores (median 20·9 versus 0 versus 20·9; P = 0·041). CONCLUSION: Despite an initial improvement in severe complications for venous resection during pancreatoduodenectomy, this was not maintained over time. Every fourth patient with venous resection needed relaparotomy, most frequently for bleeding.

Resection margin involvement and tumour origin in pancreatic head cancer.

BACKGROUND: Assessment of the origin of adenocarcinoma in pancreatoduodenectomy specimens (pancreatic, ampullary or biliary) and resection margin status is not performed in a consistent manner in different centres. The aim of this review was to identify the impact of such variations on patient outcome. METHODS: A systematic literature search for articles on pancreatic, ampullary, distal bile duct and periampullary cancer was performed, with special attention to data on resection margin status, pathological examination and outcome. RESULTS: The frequent reclassification of tumour origin following slide review, and the wide variation in published incidence of pancreatic (33-89 per cent), ampullary (5-42 per cent) and distal bile duct (5-38 per cent) cancers indicate that the histopathological distinction between the three cancer groups is less accurate than generally believed. Recent studies have shown that the wide range of rates of microscopic margin involvement (R1) in pancreatoduodenectomy specimens (18-85, 0-27 and 0-72 per cent respectively for pancreatic, ampullary and distal bile duct cancers) is mainly caused by differences in pathological assessment rather than surgical practice and patient selection. As a consequence of the existing inconsistency in reporting of these data items, the clinical significance of microscopic margin involvement in each of the three cancer groups remains unclear. CONCLUSION: Inaccurate and inconsistent distinction between pancreatic, ampullary and distal bile duct cancer, combined with inaccuracies in resection margin assessment, results in obfuscation of key clinicopathological data. Specimen dissection technique plays a key role in the quality of the assessment of both tumour origin and margin status. Unless the pathological examination is meticulous and standardized, comparison of results between centres and observations in multicentre trials will remain of limited value.

Hepatic radiofrequency ablation using perfusion electrodes in a pig model: effect of the Pringle manoeuvre.

AIM: To assess the influence of the Pringle manoeuvre on volume and geometry of coagulations close to the portal vein using an impedance-controlled radiofrequency ablation system with perfusion electrodes. METHODS: Twelve pigs were randomly assigned to a control group (n = 6) and a group where the Pringle manoeuvre was applied during ablation (n = 6). One coagulation was made in each animal close to the portal vein. All animals were sacrificed 4 days after ablation, and the livers were removed for gross and histopathologic analysis. RESULTS: Effective coagulation volume in the Pringle group (10.8 +/- 5.0 cm(3)) was significantly increased (p = 0.03) compared to the control group (4.1 +/- 4.1 cm(3)). The efficacy ratio, defined as the effective coagulation volume divided by the coagulation volume, was not significantly different in the Pringle group (0.47 +/- 0.27) compared to the control group (0.33 +/- 0.22). The geometrical centre of the effective coagulation volume did not correspond to the position of the ablation electrode. Thermal damage of the gallbladder was found in three animals, all belonging to the Pringle group. CONCLUSIONS: The Pringle manoeuvre was associated with increased effective coagulation volume, but did not significantly influence the predictability of coagulation volume or geometry.

Effects of butyrate on epidermal growth factor receptor binding, morphology, and DNA synthesis in cultured rat hepatocytes.

We have examined the effect of butyrate on morphology, DNA synthesis, and epidermal growth factor (EGF) receptor binding in primary cultures of rat hepatocytes. Butyrate added 2 h after plating retarded the flattening and maintained the polyhedral shape of the hepatocytes in culture. Both insulin- and EGF-stimulated DNA syntheses were slightly stimulated by butyrate at 1 mM but strongly inhibited at 5 mM. EGF receptor binding was also strongly affected by butyrate treatment of the hepatocytes. The freshly isolated hepatocytes (prior to plating) and the early-stage cultures (2 h) exhibited two classes of surface EGF receptors with high and low affinity (Kd approximately 0.05 and approximately 0.7 nM, respectively). With increasing time in culture there was a decrease in the total EGF receptor number and a corresponding reduction in the capacity for receptor-mediated EGF internalization. The high-affinity receptor class was more strongly reduced than the low-affinity class and was almost absent after 40 h in culture. Butyrate dose-dependently counteracted the decrease in the number of surface EGF receptors during culturing and preserved the high-affinity binding component. Thus, after 40 h, the cells cultured in the presence of butyrate (5 mM) had an approximately 50% elevation in the total number of receptors and the capacity to endocytose EGF compared to control cells, whereas the binding at low ligand concentration (0.02 nM) was increased 4-fold. The results suggest that butyrate, in addition to affecting morphology and DNA synthesis, also has marked effects on the hepatocyte EGF receptor status.

n-butyrate and dexamethasone synergistically modulate the surface expression of epidermal growth factor receptors in cultured rat hepatocytes.

n-Butyrate was previously found to increase the epidermal growth factor (EGF) receptor binding in primary cultures of rat hepatocytes. We show here that butyrate and dexamethasone synergistically modulate the surface expression of the EGF receptors. The butyrate-induced enhancement of high-affinity EGF binding was only slight in the absence of glucocorticoid, but was strongly and dose-dependently amplified by dexamethasone. Butyrate counteracted the inhibition by insulin of the dexamethasone-induced increase in EGF binding. The results indicate that the glucocorticoid has a permissive effect on a butyrate-sensitive process that determines the surface expression of the high-affinity class of EGF receptors.

p53 accumulation confers prognostic information in resectable adenocarcinomas with ductal but not with intestinal differentiation in the pancreatic head.

The aim of the study was to examine the relation between p53 protein accumulation, clinicopathological variables and prognosis in resectable adenocarcinomas of the pancreatic head. The clinical records and tissue specimens of 82 consecutive patients resected for adenocarcinomas located in the head of the pancreas were reviewed retrospectively. Formalin-fixed and paraffin-embedded specimens from each tumour were stained with the monoclonal antibody DO7, and the nuclear p53 positivity within each tumour was assessed. Histopathological reclassification showed that 60 tumours exhibited ductal differentiation and 22 tumours intestinal differentiation. Twenty-five percent (15/60) of the ductal tumours and 50% (11/22) of the intestinal tumours were positive for p53 accumulation. p53 immunoreactivity was significantly correlated to a worse prognosis in the tumours of ductal differentiation, with median survival 0.76 years for p53 positive and 1.44 years for p53 negative patients. The p53 positivity of tumours with intestinal differentiation showed no such correlation. No correlation was found between p53 accumulation and other known prognostic factors in either the ductal or the intestinal type of tumours. Our results indicate that the tumour biology of ductal adenocarcinomas differs significantly from that of adenocarcinomas of the intestinal type located in the pancreatic head, and that p53 accumulation confers a worse prognosis only of ductal tumours. Subclassification of these tumours based on type of differentiation is therefore suggested since periampullary tumours include ductally as well as intestinally differentiated adenocarcinomas.

Erroneous diagnosis of pancreatic cancer after radiotherapy of testicular cancer.

BACKGROUND: After radiotherapy with or without chemotherapy radiation-induced normal tissue alteration may mimic cancer and may cause major morbidity. RESULTS: Two patients irradiated for seminoma, in one case combined with cisplatin-based chemotherapy, developed clinical symptoms and radiological signs comparable to pancreatic cancer (stenosis of the ductus choledochus). The non-malignant diagnosis was finally established by revision of the histological specimen (case 1) and per-operatively (case 2). In both patients by-pass operations for biliary tract stenosis resulted in excellent palliation. CONCLUSION: Radiation-induced fibrosis within the upper retroperitoneal space is an important differential diagnosis versus pancreatic cancer in patients with prior radiotherapy for seminoma. Diagnosis based only on clinical and radiological findings may lead to incorrect patient information and registration errors in Cancer Registries.

Regulation of hepatocyte epidermal growth factor receptors by n-butyrate and dimethyl sulfoxide: sensitivity to modulation by the tumor promoter TPA.

n-Butyrate and dimethyl sulfoxide (DMSO) are known to promote differentiated characteristics in certain cells, including hepatocytes. We have previously reported that butyrate up-regulates the surface expression of hepatocyte epidermal growth factor (EGF) receptors and preserves a high-affinity receptor subpopulation. In the present study, culturing of hepatocytes with DMSO dose-dependently (0.5-2%) increased EGF binding and maintained a high-affinity binding component which was otherwise down-regulated during culturing. Although butyrate was more effective than DMSO in most experiments, the two agents caused qualitatively the same alteration in hepatocyte EGF receptor status. The high-affinity component of the EGF binding present in cells treated with butyrate or DMSO was reduced by treatment (10 nM-1 microM, 1 h) with the phorbol ester tumor promoter TPA, an activator of protein kinase C. Butyrate- or DMSO-treated hepatocytes were more susceptible to this response to TPA than were untreated hepatocytes. The present data indicate that in hepatocytes both butyrate and DMSO preserve a high-affinity EGF receptor subpopulation which is otherwise down-regulated during hepatocyte culture, and that this effect particularly comprises receptors that are sensitive to modulation by the tumor promoter TPA.

The regulation of cyclic AMP levels in cultured MH1C1 rat hepatoma cells and in solid tumours derived from MH1C1 cell inoculates.

Several studies have found high cAMP content in hepatomas in vivo, while hepatoma cells in vitro have very low levels. To explore this discrepancy and the regulation of cAMP in hepatomas, we have examined the cell line MH1C1 from Morris hepatoma 7795. These cells in culture contained low intracellular cAMP concentrations (approximately 0.5 pmol/mg protein at confluency), and were unresponsive to glucagon and prostaglandins (PG) E1 and E2. In contrast, solid hepatomas in rats developed from inoculates of MH1C1 had a 40-fold higher basal cAMP concentration and were stimulated by PGE1 and PGE2. Fibroblasts cultured from these tumours also contained high cAMP levels and responded strongly to PGE1. This may suggest that the difference in cAMP regulation between hepatomas in vivo and hepatoma cells in vitro results from the presence of other cells in the solid tumour rather than from selection of low-cAMP cells during the cloning procedure. Low-Km and intermediate-Km cAMP phosphodiesterase activity was high in MH1C1, compared to normal hepatocytes. This might contribute to the low cAMP level. The ability of MH1C1 to form cAMP was not defective, as the level could be increased more than 200-fold by beta-adrenergic activation in the presence of the phosphodiesterase inhibitor methylisobutylxanthine.

Validation of estimated 3D temperature maps during hepatic cryo surgery.

A simple model for estimating temperature distribution within the frozen region during cryo ablation was tested for accuracy. Freezing experiments were conducted in both ex vivo and in vivo porcine livers. Temperature was measured during freezing using a fiber-optic temperature sensor. Three-dimensional MR images were obtained at the end of each freezing cycle. From the MR image volumes, three-dimensional temperature maps were calculated numerically using a simplified bio-heat model. Estimated temperatures were compared to measured temperatures. The median difference between measured and estimated temperature was 3.03 degrees C. The median distance from a sensor element to the closest point on a isotherm surface with the corresponding estimated temperature was 0.70 mm. The accuracy of this model is acceptable. Temperature maps as outlined here may be used for monitoring of cryotherapy in order to increase clinical effectiveness.

A comparative study of the short-term outcome following open and laparoscopic liver resection of colorectal metastases.

BACKGROUND: Laparoscopic resection of liver tumors is feasible, but few studies have compared short-term outcome of the laparoscopic approach to that of a conventional technique. METHODS: Eighteen tumor resections performed during 14 procedures (14 patients) by conventional surgery were compared to 21 similar resections performed laparoscopically during 15 procedures (13 patients). All patients had colorectal liver metastases. RESULTS: No perioperative mortality occurred. Surgical time, peroperative bleeding and blood transfusion requirement were similar in the two groups. The resection margin was involved by tumor tissue in one specimen laparoscopically resected and in two specimens conventionally resected (p = 0.58). Patients operated laparoscopically remained in hospital for median 4 days, while patients operated conventionally stayed median 8.5 days (p <0.001). Patients operated laparoscopically required less opioid medication than patients having conventional surgery (median 1 vs 5 days; p = 0.001). CONCLUSIONS: Short-term outcome of laparoscopic liver resection compares to that of conventional surgery, with the additional benefits derived from minimal invasive therapy.

Laparoscopic resection of the pancreas: a feasibility study of the short-term outcome.

BACKGROUND: Laparoscopic resection is not an established treatment for tumors of the pancreas. We report our preliminary experience with this innovative approach to pancreatic disease. METHODS: Thirty two patients with pancreatic disease were included in the study on an intention-to-treat basis. The preoperative indications for surgery were as follows: neuroendocrine tumors ( n=13), unspecified tumors ( n=11), cysts ( n=2), idiopathic thrombocytopenic purpura with ectopic spleen ( n=2), annular pancreas ( n=1), trauma ( n=1), aneurysm of the splenic artery ( n=1), and adenocarcinoma ( n=1). RESULTS: Enucleations ( n=7) and distal pancreatectomy with ( n=12) and without splenectomy ( n=5) were performed. Three patients underwent laparoscopic exploration only. Four procedures (13%) were converted to an open technique. One resection was converted to a hand-assisted procedure. The mortality rate for patients undergoing laparoscopic resection was 8.3% (two of 24). Complications occurred after resection in nine of 24 procedures (38%). The median hospital stay was 5.5 days (range, 2-22). Postoperatively, opioid medication was given for a median of 2 days (range, 0-13). CONCLUSION: Resection of the pancreas can be performed safely via the laparoscopic approach with all the potential benefits to the patients of minimally invasive surgery.

Liver tumors and minimally invasive surgery: a feasibility study.

Laparoscopic liver resection has not yet been established, although recent reports document that liver resection can be performed safely by the laparoscopic approach. Other interventional procedures like cryoablation have also been introduced in treatment of liver metastases. In this report 11 liver resections performed laparoscopically in eight patients are presented. Six patients had colorectal metastases, one a metastases from a malignant melanoma, and one patient had focal nodular hyperplasia. Two patients received synchronous cryoablation of remaining liver metastases. During follow up, two patients received percutaneous cryoablation of liver recurrences monitored by an open configuration magnetic resonance scanner. All except one of the tumors we attempted to remove had free resection margins (re-resection of new metastasis). No complications occurred except an atelectasis of the left lower pulmonary lobe in one patient. Median postoperative hospital stay was 3 days, and median postoperative opioid-dependent days was 1. The report demonstrates that minimally invasive techniques may safely be combined in hepatic intervention, and that the advantages of minimally invasive surgery, such as reduced hospital stay and less patient discomfort, also applies to liver resections.

Reclassification of tumour origin in resected periampullary adenocarcinomas reveals underestimation of distal bile duct cancer.

BACKGROUND: Primary adenocarcinomas removed by pancreatoduodenectomy originate from the duodenum (DC), ampulla (AC), distal bile duct (DBC), or pancreas (PC). Pathobiology, staging, survival, and adjuvant chemotherapy vary among these cancers. The proximity of the structures of possible origin renders it difficult to obtain a correct diagnosis, which might lead to inconsistencies in reported data and inappropriate adjuvant treatment. METHODS: Records of 207 patients undergoing pancreatoduodenectomy (1998-2009) for periampullary adenocarcinoma were reviewed. Routine histopathology reports of tumour origin performed by multiple pathologists were independently re-evaluated based on predetermined criteria by two experienced pancreatic pathologists. RESULTS: Slide review changed the diagnosis in 55 (27%) patients. After reclassification, final distribution was 29 (14%) DC, 52 (25%) AC, 57 (28%) DBC, and 69 (33%) PC. The diagnosis was revised in 4 (14%) DC, 7 (17%) AC, 30 (53%) DBC and 14 (19%) PC. The underestimation of DBC during routine histopathology was caused by misinterpretation of DBC either PC or AC. Misclassification of PC was mainly due to erroneous diagnosis of AC. Reassignment of tumour origin caused no significant changes in survival within cancer type, but resulted in a significant difference in survival between DBC and PC (p = 0.004). CONCLUSION: Specialist slide review resulted in reassignment of tumour origin in 27% of periampullary adenocarcinomas. Distal bile duct cancer was found to be most frequently misdiagnosed (53%). Correct diagnosis of tumour origin is crucial for data quality, appropriate adjuvant therapy, and patient inclusion in clinical trials.

Kinetics of epidermal growth factor binding and processing in isolated intact rat hepatocytes. Dynamic externalization of receptors during ligand internalization.

The kinetics of binding and processing of epidermal growth factor (EGF) was studied in freshly isolated rat hepatocytes. After isolation the hepatocytes had a nonhomogeneous population of surface EGF receptors consisting of approximately 9000 high-affinity sites (Kd 21 pM) and 165,000 low-affinity sites (Kd 0.62 nM). Incubation at 37 degrees C (45 min) increased the number of surface receptors per cell to about 260,000. This increase was selective for the low-affinity receptors and was cycloheximide-sensitive. During 5 h of incubation at 37 degrees C the hepatocytes internalized 6-7-times more EGF molecules than the number of cell surface receptors, based on clearance measurements. The uptake was unaffected by cycloheximide. Concomitant estimation, using acid/salt elution, of surface-bound EGF and internalized EGF showed that the number of internalized EGF molecules exceeded the decrease in surface-binding 6 times. The ratio between internalized EGF and the decrease in surface binding was temperature-dependent, being reduced to a one-to-one stoichiometry at 10 degrees C. After down-regulation (approximately equal to 75%) induced by 5 nM unlabeled EGF the surface EGF receptors did not recover during subsequent incubation (2 h) at 37 degrees C. However, the remaining surface receptors internalized EGF in ninefold excess of their number. The large discrepancy between internalization capacity and cell surface binding capacity was also found in the presence of cycloheximide. The results support the idea that internalized EGF receptors are partly replaced by externalization of preformed intracellular receptors during EGF uptake in isolated hepatocytes, involving recycling of a small population of EGF receptors and/or recruitment of unexposed, pre-existing receptors.

Rapid constitutive internalization and externalization of epidermal growth factor receptors in isolated rat hepatocytes. Monensin inhibits receptor externalization and reduces the capacity for continued endocytosis of epidermal growth factor.

It was previously demonstrated that freshly isolated rat hepatocytes can internalize severalfold more epidermal growth factor (EGF) molecules than the number of surface EGF receptors, suggesting extensive reutilization of receptors during endocytosis (Gladhaug, I. P. & Christoffersen, T. (1987) Eur. J. Biochem. 164, 267-275). The present report attempts to explore the pathways involved in the externalization of EGF receptors. Incubation of hepatocytes at 37 degrees C in the absence of ligand increased the surface receptor pool by 50-100% within 45 min. Pretreatment with monensin inhibited the turnover of the surface EGF receptor pool by 50-60% within 10 min and blocked the temperature-dependent externalization of receptors. Cycloheximide caused a slower attenuation of the surface receptor pool, whereas tunicamycin and chloroquine did not significantly affect the exchange of receptor pools. Monensin reduced the surface receptor pool and the endocytic uptake in corresponding proportions, without affecting the internalization of prebound EGF. Endocytic uptake was unaffected by chloroquine and slightly reduced by cycloheximide. The internalization of unoccupied receptors and the endocytosis of prebound EGF followed similar kinetics (t1/2 approximately 5 min), suggesting that unoccupied receptors are internalized at a rate comparable to that of occupied receptors. The results suggest that there is a rapid turnover of the surface pool of EGF receptors with constitutive internalization of unoccupied surface receptors and externalization of internal receptors. This is consistent with, but does not prove, a true recycling of the EGF receptors in the hepatocytes. The monensin-sensitive externalization pathway determines the capacity for continued endocytosis of EGF.

Amiloride inhibits constitutive internalization and increases the surface number of epidermal growth factor receptors in intact rat hepatocytes.

In previous experiments the surface expression of epidermal growth factor (EGF) receptors in freshly isolated rat hepatocytes varied temperature- and time-dependently and was depleted by monensin and cycloheximide in a way suggesting that a subpopulation of these receptors are subject to constitutive cycling (Gladhaug and Christoffersen; 1988). We here report the finding that pretreatment of the hepatocytes with amiloride exerts marked effects on cellular EGF receptor movements. After 2 h incubation with 1 mM amiloride, the receptor level was approximately 270,000 sites/cell surface vs. 140,000 in the untreated cell, with no change in receptor affinity. Amiloride thus stabilized the surface EGF receptor pool at an elevated level. In cells pretreated with amiloride for 60 min, the relative endocytosis decreased from about 2.6 EGF molecules internalized per receptor during 15 min endocytosis in untreated cells to about 1.5 molecules/receptor in amiloride-treated cells. These results suggest that amiloride causes an accumulation of EGF receptors at the hepatocyte surface due to inhibition of constitutive receptor internalization. In addition, it was found that in amiloride-treated hepatocytes the phorbol ester TPA strongly inhibited high-affinity EGF binding without affecting the total surface receptor number. In control cells, TPA did not consistently affect binding. Pretreatment with amiloride prevented surface EGF receptor depletion induced by cycloheximide and puromycin, but it did not significantly inhibit surface receptor depletion caused by monensin. Although the underlying mechanism of the amiloride effect on intracellular receptor trafficking is not clear, the results provide further evidence for a continuous, ligand-independent EGF receptor cycling pathway in hepatocytes.

Regulation of surface expression of high-affinity receptors for epidermal growth factor (EGF) in hepatocytes by hormones, differentiating agents, and phorbol ester.

Freshly isolated adult rat hepatocytes exhibit a nonhomogeneous population of epidermal growth factor (EGF) receptors with about 10,000 high-affinity binding sites (Kd 20 pM) and about 200,000 low-affinity sites (Kd 600 pM) per cell. With culturing as primary monolayers under conditions where the cells show a marked increase in the sensitivity to the growth-stimulatory effect of EGF, a gradual reduction in the number of EGF receptors and an almost complete loss of high-affinity EGF receptors is seen. Insulin, which promotes growth of hepatocytes in concert with EGF, enhances the down-regulation of these high-affinity receptors. The differentiating (and growth-inhibitory) agent n-butyrate counteracts this down-regulation and preserves the high-affinity receptors. This effect of butyrate is synergistic with the glucocorticoid agent dexamethasone. Another differentiating agent, dimethylsulfoxide (DMSO), also counteracts the down-regulation of high-affinity EGF receptors. Moreover, the tumor promoter, tetradecanoylphorbol acetate (TPA), down-regulates the EGF receptor. This effect is particularly evident when studying the high-affinity receptors up-regulated by prior treatment with butyrate plus dexamethasone. Taken together these results provide strong support for the notion that an inverse relationship exists between expression of high-affinity EGF binding and responsiveness to growth activation by EGF.

[Liver resection--indications and results]. / Leverreseksjon--indikasjoner og resultater.

BACKGROUND: Liver resection is an established treatment for malignancies like colorectal metastases and hepatocellular carcinoma. MATERIAL AND METHODS: Indications and outcomes of liver resection at the National Hospital, Oslo, Norway was studied retrospectively in 226 patients operated between 1977 and 1999. RESULTS: The main indication for surgery was colorectal metastases (n = 137). The frequency of liver resection for colorectal malignancies was < 1 per 100,000 patients per year in the hospital's catchment area. Other indications included hepatocellular carcinoma (n = 30), benign tumours like hemangioma (n = 14), and various primary and secondary malignant tumours. Reoperation due to postoperative complications was performed in 13 patients (6%). Total perioperative mortality defined as death before hospital discharge or within 30 days after discharge, was 3% (7/226). No perioperative deaths occurred among the 159 patients operated after 1987. Five year survival for patients operated for colorectal metastases and hepatocellular carcinoma were 29% and 24%, respectively. INTERPRETATION: The main indication for liver resection is colorectal metastases. Liver resection is a safe operation with potential curation for selected patients.