Owe Lundberg

Survival after laparoscopic surgery versus open surgery for colon cancer : long-term outcome of a randomised clinical trial

BACKGROUND Laparoscopic surgery for colon cancer has been proven safe, but debate continues over whether the available long-term survival data justify implementation of laparoscopic techniques in surgery for colon cancer. The aim of the COlon cancer Laparoscopic or Open Resection (COLOR) trial was to compare 3-year disease-free survival and overall survival after laparoscopic and open resection of solitary colon cancer. METHODS Between March 7, 1997, and March 6, 2003, patients recruited from 29 European hospitals with a solitary cancer of the right or left colon and a body-mass index up to 30 kg/m(2) were randomly assigned to either laparoscopic or open surgery as curative treatment in this non-inferiority randomised trial. Disease-free survival at 3 years after surgery was the primary outcome, with a prespecified non-inferiority boundary at 7% difference between groups. Secondary outcomes were short-term morbidity and mortality, number of positive resection margins, local recurrence, port-site or wound-site recurrence, and blood loss during surgery. Neither patients nor health-care providers were blinded to patient groupings. Analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00387842. FINDINGS During the recruitment period, 1248 patients were randomly assigned to either open surgery (n=621) or laparoscopic surgery (n=627). 172 were excluded after randomisation, mainly because of the presence of distant metastases or benign disease, leaving 1076 patients eligible for analysis (542 assigned open surgery and 534 assigned laparoscopic surgery). Median follow-up was 53 months (range 0.03-60). Positive resection margins, number of lymph nodes removed, and morbidity and mortality were similar in both groups. The combined 3-year disease-free survival for all stages was 74.2% (95% CI 70.4-78.0) in the laparoscopic group and 76.2% (72.6-79.8) in the open-surgery group (p=0.70 by log-rank test); the difference in disease-free survival after 3 years was 2.0% (95% CI -3.2 to 7.2). The hazard ratio (HR) for disease-free survival (open vs laparoscopic surgery) was 0.92 (95% CI 0.74-1.15). The combined 3-year overall survival for all stages was 81.8% (78.4-85.1) in the laparoscopic group and 84.2% (81.1-87.3) in the open-surgery group (p=0.45 by log-rank test); the difference in overall survival after 3 years was 2.4% (95% CI -2.1 to 7.0; HR 0.95 [0.74-1.22]). INTERPRETATION Our trial could not rule out a difference in disease-free survival at 3 years in favour of open colectomy because the upper limit of the 95% CI for the difference just exceeded the predetermined non-inferiority boundary of 7%. However, the difference in disease-free survival between groups was small and, we believe, clinically acceptable, justifying the implementation of laparoscopic surgery into daily practice. Further studies should address whether laparoscopic surgery is superior to open surgery in this setting.

Port Site Metastases from Gallbladder Cancer after Laparoscopic Cholecystectomy. Results of a Swedish Survey and Review of Published Reports

OBJECTIVE To investigate the incidence of port site metastases from unsuspected gallbladder cancer after laparoscopic cholecystectomy. DESIGN Retrospective national multicentre study, 1991-94. SETTING All 8 university and 24 central hospital, Sweden. SUBJECTS AND INTERVENTIONS All 32 hospitals were interviewed by means of a written questionnaire. The registers of all Swedish Oncological Centres and the registers of the National Board of Health and Welfare were checked for reported cases of gallbladder cancer and surgical classification codes for cholecystectomy. To detect laparoscopic interventions incorrectly registered as open operations, all cholecystectomies registered as open were matched against the Swedish Registry of Laparoscopic Cholecystectomy for the years 1991-93 and all patients records for 1994 were scrutinised. RESULTS Replies were obtained from 30/32 clinics (94%) and 11976 laparoscopic cholecystectomies were done. Of 447 patients with verified gallbladder carcinoma 270 had their gallbladders removed, 55 (20%) laparoscopically. 9 of these (16%) developed port site metastases and 6 died from their disease at a median of 18 months (range 5-22). Two patients are alive, 54 and 45 months after cholecystectomy. One patient has been lost to follow-up. CONCLUSIONS Port site metastases from gallbladder cancer may be more common than previously thought. A laparoscopic procedure should not be done if cancer of the gallbladder is suspected.

Expertise-based randomized clinical trial of laparoscopic versus small-incision open cholecystectomy

Several randomized clinical trials have compared laparoscopic cholecystectomy (LC) and small‐incision open cholecystectomy (SIOC). Most have had wide exclusion criteria and none was expertise‐based. The aim of this expertise‐based randomized trial was to compare healthcare costs, quality of life (QoL), pain and clinical outcomes after LC and SIOC.

Port site metastases after laparoscopic cholecystectomy.

The true incidence of abdominal wall metastases after open or laparoscopic operations is unknown. The large number of reports of patients with port site metastases may represent publication bias, but there is a suspicion that recurrence of the tumour in the abdominal incision is more common after laparoscopic operations. The aetiology of port site metastases is not known but in cases of gallbladder cancer the laparoscopic handling of the tumour, perforation of the gallbladder, and extraction of the malignant specimen may be risk factors for the spread of malignant cells. These risk factors are not equally applicable in laparoscopic colorectal cancer operations in which the incidence of port site metastases seems to be lower. In addition, several other factors are probably involved in the development of such metastases, including the creation of pneumoperitoneum and the use of different gases. Laparoscopic cholecystectomy is contraindicated when gallbladder cancer is known or suspected preoperatively. When signs of malignancy are encountered during a laparoscopic operation it should be converted to an open procedure. If a gallbladder cancer is diagnosed after a completed laparoscopic operation a careful clinical follow up is indicated and if signs of recurrent malignancy develop in the port sites they should be excised, particularly as port site metastases may be the only manifestation of recurrent disease.

Effect of pneumoperitoneum induced by carbon dioxide and air on tumor load in a rat model.

Laparoscopic surgery for malignant disease is highly controversial mainly due to the large number of abdominal wall metastases being reported. Previous experimental studies have particularly studied CO2 pneumoperitoneum and its effect on tumor development. The purpose of this study was to compare CO2- and air-induced pneumoperitoneum with regard to intraperitoneal tumor growth. Altogether 39 rats were injected intraperitoneally with 105 colonic tumor cells and randomly allocated into three groups: 13 rats had a pneumoperitoneum created with CO2, 13 with air, and 13 served as controls. Tumor development was determined semiquantitatively by a peritoneal cancer index scale after 12 days. CO2 and air pneumoperitoneum equally increased intraperitoneal tumor growth compared to controls. Pneumoperitoneum induced by CO2 and air seems to increase tumor load, but the mechanisms are not established. This finding supports the hypothesis that insufflation not only by causing tumor cell movements but in fact pneumoperitoneum per se and the used gas are involved in the development of abdominal wall metastases after laparoscopic surgery.

Pneumoperitoneum impairs blood flow and augments tumor growth in the abdominal wall

Background: Despite several clinical and experimental studies, the mechanisms behind the development of port site metastases in laparoscopic surgery have remained largely unknown. The current study was designed to investigate the effect of pneumoperitoneum on blood flow in the abdominal wall and its possible effects on tumor growth at this site.Methods: A total of 40 Wistar Fu rats had a laser Doppler probe placed on their left rectus muscle and a suspension of 50,000 adenocarcinoma cells was injected into their right rectus muscle. The experimental group (n = 20) was insufflated with air at 10 mmHg for 45 min while abdominal blood flow was registered before and during insufflation and after exsufflation. The control group (n = 20) was not insufflated but the blood flow was recorded in the same manner. After 9 days, all animals were killed and the occurrence of tumor was observed. The tumors were analyzed with respect to weight and volume. Results: The insufflation caused an 82% reduction in blood flow in the experimental group (p < 0.001). No reduction in blood flow was registered in the control group. Tumor nodules developed significantly more often in the insufflated group (20/20) compared to the controls (14/20) (p = 0.016). Tumor weight (p = 0.003) and volume (p < 0.001) were significantly increased in the insufflated group. Conclusions: Pneumoperitoneum seems to enhance tumor growth. It also causes a significant reduction in blood flow in the abdominal wall, which may contribute to the increased susceptibility of tumor take.