Øystein Mathisen

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.

Hepatic resection for colorectal metastases: Can preoperative scoring predict patient outcome?

A retrospective study was performed to define patient selection, safety, and efficacy of hepatic resection for colorectal metastases. The recently proposed preoperative clinical risk score (CRS) for selection of patients for surgery was also assessed. In all, 146 consecutive hepatic resections in 137 patients operated in the period between 1977 and 1999 were studied. Of these patients, 113 were classified into five CRS groups. Perioperative mortality was 1.4% (2 patients; no death in 120 patients operated after 1985) and morbidity was 38%. Five-year actuarial survival (perioperative mortality included) was 29% (median 37 months), and actual 5-year survival was 25% (17/69 patients). Patients operated after 1995 lived longer than those operated before 1995. Multiple regression analyses identified preoperative carcinoembryonic antigen CEA<100 µg/L, nodal status at resection of primary tumor, and RO vs. R1/R2 resection as prognostic parameters. CRS grouping had prognostic importance. The relative risk (hazard rate) of tumor recurrence in patients with CRS 3–4 was 2.1, compared to that of patients with CRS 0–2. Five-year actuarial survival in the two groups was 12% and 40%, respectively. Fourteen of 15 long-term survivors (τ;5 years) classified by the CRS system had CRS of 2 or less. Resection for colorectal liver metastases is safe, and long-term survival rates are acceptable. CRS predicts patient outcome, but the clinical role in patient selection will have to be defined in prospective studies.ResumeUne étude rétrospective a été réalisée pour définir la sélection des patients, la sûreté et l’efficacité de la résection hépatique pour métastases d’origine colorectale. Le score préopératoire «Clinical Risk Score» (CRS), proposé récemment pour la sélection des patients candidats à la chirurgie, a été évalué chez 146 patients consécutifs ayant eu une résection hépatique entre 1977 et 1999; 113 de ces patients ont été classés en cinq groupes selon le CRS. La mortalité périopératoire a été de 1.4% (2 patients; aucune mortalité parmi 120 patients opérés après 1985) et la morbidité, de 38%. La survie actuarielle à 5 ans (mortalité périopératoire incluse) a été de 29% (médiane de 37 mois) et la survie actuelle à 5 ans a été de 25% (17/69 patients). Les patients opérés après 1995 ont survécu plus longtemps que ceux opérés avant 1995. L’analyse par régression multiple a identifié comme facteurs pronostiques, le taux d’ACE inférieur à 100 ng/1, l’état ganglionnaire au moment de la résection tumorale primitive et une résection R0 vs. une résection R1/R2. Le risque relatif de récidive chez les patients CRS 3–4 a été de 2.1 comparé à celui des patients CRS 0–2. La survie actuarielle à 5 ans a été, respectivement, de 12% et de 40%. Quatorze des 15 survivants à long terme (τ; 5 ans), classés par le système CRS, avaient un score de 2 ou moins. La résection des métastases colorectales est sure et la survie à long terme, acceptable. Le score CRS prédit l’évolution mais son rôle clinique dans la sélection des patients reste à être défini par des études prospectives.ResumenPara seleccionar de manera eficaz y segura a los pacientes subsidiarios de resección hepática por padecer metástasis en hígado de un cáncer colorrectal, se realiza un estudio retrospectivo, en el que se valoró la clasificación reciente de Riesgo Clínico (CRS). Se estudiaron 146 resecciones hepáticas en 137 pacientes intervenidos entre 1977 y 1999. 113 de estos pacientes se clasificaron en alguno de los cinco grupos de la CRS. La mortalidad perioperatoria fue del 1.4% (2 pacientes; no se registró mortalidad alguna en los 120 pacientes intervenidos después del año 1985) y la morbilidad del 38%. La supervivencia actuarial a los 5 años (incluyendo la mortalidad perioperatoria) fue del 29% (media 37 meses) y la supervivencia actual a los 5 años fue del 25% (17/69 pacientes). Los enfermos intervenidos después de 1995 vivieron más tiempo que los operados con anterioridad. Los análisis de regresión múltiple señalaron como parámetros pronósticos: CEA preoperatorio menor de 100 ng/1, grado de afectación ganglionar en la resección del tumor primario y resección R0 vs R1/R2. La clasificación CRS tiene importancia pronóstica. El riesgo relativo de recidiva tumoral en pacientes de los grupos CRS 3–4 fue 2.1 en relación con la de los grupos CRS 0–2. La supervivencia actuarial a los 5 años fue respectivamente del 12% y 40%. 14 de los 15 supervivientes a largo plazo (τ;5 años) clasificados con el sistema CRS pertenecían a los grupos CRS 2 ó menores. El sistema CRS permite pronosticar los resultados, pero el papel del estudio clínico en la selección de los pacientes ha de definirse mejor en próximos estudios prospectivos.

Resectable adenocarcinomas in the pancreatic head: the retroperitoneal resection margin is an independent prognostic factor

BackgroundThe retroperitoneal margin is frequently microscopically tumour positive in non-curative periampullary adenocarcinoma resections. This margin should be evaluated by serial perpendicular sectioning. The aim of the study was to determine whether retroperitoneal margin involvement independently predicts survival after pancreaticoduodenectomy within a framework of standardized assessment of the resected specimens.Methods114 consecutive macroscopically margin-free periampullary adenocarcinomas were examined according to a prospective standardized protocol for histopathologic evaluation. The retroperitoneal margin was assessed by serial perpendicular sectioning. The periampullary cancer origin (pancreas, ampulla, distal bile duct or duodenum) was registered prospectively and reevaluated retrospectively. Associations between histopathologic factors were evaluated by Chi-square test, Fishers exact test, Kruskal-Wallis test, and Mann-Whitney test, as appropriate. Survival curves were calculated by the Kaplan-Meier method and compared using the log-rank test. Associations between histopathologic factors and survival were also evaluated by unadjusted and adjusted Cox regression analysis, including stepwise variable selection, in order to identify factors that independently predict a poor prognosis after periampullary adenocarcinoma resections.ResultsMicroscopic resection margin involvement (R1 resection) was present in 40 tumours, of which 32 involved the retroperitoneal margin. Involvement of the retroperitoneal margin independently predicted a poor prognosis (p = 0.010; HR 1.89; CI 1.16–3.08) after presumed curative (R0 and R1) resection. In microscopically curative (R0) resections (n = 74), pancreatic tumour origin was the only factor that independently predicted a poor prognosis (p < 0.001; HR 4.71 for pancreatic versus ampullary; CI 2.13–10.4).ConclusionSerial perpendicular sectioning of the retroperitoneal resection margin demonstrates that tumour involvement of this margin independently predicts survival after pancreaticoduodenectomy for adenocarcinoma. Periampullary tumour origin is the only histopathologic factor that independently predicts survival in microscopically curative (R0) resections.

Laparoscopic liver resection for malignant and benign lesions: ten-year Norwegian single-center experience.

BACKGROUND The introduction of laparoscopic liver resection has been challenging because new and safe surgical techniques have had to be developed, and skepticism remains about the use of laparoscopy for malignant neoplasms. We present herein a large-volume single-center experience with laparoscopic liver resection. DESIGN Retrospective study. SETTING Rikshospitalet University Hospital. PATIENTS One hundred thirty-nine patients who underwent 177 laparoscopic liver resections in 149 procedures from August 18, 1998, through October 14, 2008. One hundred thirteen patients had malignant lesions, of whom 96 had colorectal metastases. INTERVENTION Laparoscopic liver resection for malignant and benign lesions. MAIN OUTCOME MEASURES Perioperative and oncologic outcomes and survival. RESULTS Five procedures (3.4%) were converted to laparotomy and 1 (0.7%) to laparoscopic radiofrequency ablation. The remaining 143 procedures were completed laparoscopically, during which 177 liver resections were undertaken, including 131 nonanatomic and 46 anatomic resections. The median operative time and blood loss were 164 (50-488) minutes and 350 (<50-4000) mL, respectively. There were 10 intraoperative (6.7%) and 18 postoperative (12.6%) complications. One patient (0.7%) died. The median postoperative stay and opioid requirement were 3 (1-42) and 1 (0-11) days, respectively. Tumor-free resection margins determined by histopathologic evaluation were achieved in 140 of 149 malignant specimens (94.0%). The 5-year actuarial survival for patients undergoing procedures for colorectal metastases was 46%. CONCLUSIONS In experienced hands, laparoscopic liver resection is a favorable alternative to open resection. Perioperative morbidity and mortality and long-term survival after laparoscopic resection of colorectal metastases appear to be comparable to those after open resections.

Laparoscopic resection of colorectal liver metastases: surgical and long-term oncologic outcome.

Objective: To analyze the immediate and long-term outcome after laparoscopic resection of colorectal liver metastases and difference between observed and predicted [Fongs and Basingstoke Predictive Index (BPI) scores] survivals. Background: Laparoscopic liver resection has been reported safe and feasible and improves postoperative course. The oncologic outcomes after resection of colorectal metastases are poorly reported. Methods: Between August 1998 and January 2010, 122 patients underwent laparoscopic resection for colorectal liver metastases during 135 procedures at Rikshospitalet. Patients undergoing surgery between August 1998 and June 2009 were included in research analysis. The patients had median Fongs and BPIs scores of 2 (0–5) and 7 (0–23), respectively. Mainstream analysis of hospital data was done on intent-to-treat basis. Intraoperative incidents and postoperative complications were analyzed according to the Satava and Clavien-Dindo classifications. Median follow-up was 24 (0–100) months. Results: One hundred fifty-one liver resections were performed in 107 patients during 118 procedures: 117 nonanatomic and 34 anatomic liver resections. There were 5 conversions to laparotomy (4.2%). The resection margin was free of tumor tissue in 141 (93.4%) of 151 specimens, and the distance between the resection margin and tumor tissue was median 6 (0–40) mm. Intraoperative incidents occurred in 14 cases (11.9%), including 5 (4.2%), 8 (6.8%), and 1 (0.8%) cases of grades I, II, and III, respectively. Postoperative complications were observed in 16 cases (14.3%), including 2, 3, 7, 3, 0, and 1 cases of grades I, II, IIIa, IIIb, IV, and V, respectively. During follow-up, 21 patients received repeat liver resection of recurrences (11 by laparoscopy and 10 by laparotomy). The 5-year overall survival rates were 51% as laparoscopically completed cases and 47% as intent-to-treat. The observed actuarial survival values exceeded the values expected by Fongs and BPIs score, with 10.2% and 6.7% as laparoscopically completed cases and with 3.8% and 2.4% as intent-to-treat, respectively. Conclusions: Laparoscopic resection is a favorable alternative to open liver resection for patients with colorectal liver metastases. The observed actuarial survival values after laparoscopic resection surpass the values expected by major scoring systems.

Liver transplantation for nonresectable liver metastases from colorectal cancer.

Objective:The objective of this pilot study was to investigate the potential for long-term overall survival (OS) after liver transplantation for colorectal liver metastases (CLMs). Background:Patients with nonresectable CLMs have poor prognosis, and few survive beyond 5 years. CLMs are currently considered an absolute contraindication for liver transplantation, although liver transplantation for primary and some secondary liver malignancies shows excellent outcome in selected patients. Before 1995, several liver transplantations for CLMs were performed, but outcome was poor (5-year survival rate: 18%) and liver transplantation for CLMs was abandoned. Since then, the survival rate after liver transplantation in general has improved by almost 30%. On the basis of this, a 5-year survival rate of about 50% after liver transplantation for CLMs could be anticipated. Methods:In a prospective pilot study, liver transplantation for nonresectable CLMs was performed (n = 21). Main inclusion criteria were liver-only CLMs, excised primary tumors, and at least 6 weeks of chemotherapy. Results:Kaplan-Meier estimates of the OS rate at 1, 3, and 5 years were 95%, 68%, and 60%, respectively. Metastatic recurrence of disease was common (mainly pulmonary). However, a significant proportion of the recurrences were accessible for surgery, and at follow-up (after median of 27 months; range, 8–60), 33% had no evidence of disease. Hepatic tumor load before liver transplantation, time from primary surgery to liver transplantation, and progressive disease on chemotherapy were identified as significant prognostic factors. Conclusions:OS exceeds by far reported outcome for chemotherapy, which is the only treatment option available for this patient group. Furthermore, OS is comparable with liver resection for resectable CLMs and survival after repeat liver transplantation for nonmalignant diseases. Selection strategies based on prognostic factors may further improve the outcome (ClinicalTrials.gov: NCT01311453).

DNA sequence profiles of the colorectal cancer critical gene set KRAS-BRAF-PIK3CA-PTEN-TP53 related to age at disease onset.

The incidence of colorectal cancer (CRC) increases with age and early onset indicates an increased likelihood for genetic predisposition for this disease. The somatic genetics of tumor development in relation to patient age remains mostly unknown. We have examined the mutation status of five known cancer critical genes in relation to age at diagnosis, and compared the genomic complexity of tumors from young patients without known CRC syndromes with those from elderly patients. Among 181 CRC patients, stratified by microsatellite instability status, DNA sequence changes were identified in KRAS (32%), BRAF (16%), PIK3CA (4%), PTEN (14%) and TP53 (51%). In patients younger than 50 years (n = 45), PIK3CA mutations were not observed and TP53 mutations were more frequent than in the older age groups. The total gene mutation index was lowest in tumors from the youngest patients. In contrast, the genome complexity, assessed as copy number aberrations, was highest in tumors from the youngest patients. A comparable number of tumors from young (<50 years) and old patients (>70 years) was quadruple negative for the four predictive gene markers (KRAS-BRAF-PIK3CA-PTEN); however, 16% of young versus only 1% of the old patients had tumor mutations in PTEN/PIK3CA exclusively. This implies that mutation testing for prediction of EGFR treatment response may be restricted to KRAS and BRAF in elderly (>70 years) patients. Distinct genetic differences found in tumors from young and elderly patients, whom are comparable for known clinical and pathological variables, indicate that young patients have a different genetic risk profile for CRC development than older patients.

Single-centre experience of laparoscopic pancreatic surgery†

Laparoscopic resection is regarded as safe and feasible in selected patients with benign pancreatic tumours. Few data exist on laparoscopic surgery for malignant lesions and larger neoplasms in unselected patients.

Laparoscopic resection of exocrine carcinoma in central and distal pancreas results in a high rate of radical resections and long postoperative survival

BACKGROUND The role of laparoscopic resection in patients with pancreatic cancer remains to be clarified, because previous reports have not clearly defined oncologic outcomes. The objective of the present study was to investigate this question with the rate of R0 resection and long-term survival as endpoints. METHODS This retrospective observational study included prospectively collected data from 40 patients operated laparoscopically with curative intent for exocrine pancreatic malignancies identified among 250 consecutive patients undergoing laparoscopic pancreatic operations since 1997. All 40 patients had histologically verified exocrine pancreatic carcinoma. RESULTS Ten patients (25%) with typical ductal adenocarcinoma of the pancreas were deemed nonresectable by laparoscopic staging. Laparoscopic distal pancreatectomy was performed in 29 patients; 8 resections were combined with resections of adjacent organs and 1 removal of a malignant intraductal papillary mucinous neoplasm what appeared to be ectopic pancreatic tissue. In 1 patient, the resection was completed by hand-assisted technique, and 1 procedure was converted to open resection. Postoperative morbidity was 23% (n = 7). The median hospital stay was 5 days (range, 1-30). The rate of R0 resections was 93%. Postoperative 3-year survivals rates were 36% for the entire cohort (n = 30) and 30% in typical ductal adenocarcinoma (n = 21). CONCLUSION Laparoscopic distal pancreatectomy for exocrine pancreatic carcinoma is comparable with outcomes after open surgery and supports the concept that laparoscopic distal pancreatectomy is a safe, oncologic procedure.