Josep M. Piqué

Laparoscopy-assisted colectomy versus open colectomy for treatment of non-metastatic colon cancer: a randomised trial

BACKGROUND Although early reports on laparoscopy-assisted colectomy (LAC) in patients with colon cancer suggested that it reduces perioperative morbidity, its influence on long-term results is unknown. Our study aimed to compare efficacy of LAC and open colectomy (OC) for treatment of non-metastatic colon cancer in terms of tumour recurrence and survival. METHODS From November, 1993, to July, 1998, all patients with adenocarcinoma of the colon were assessed for entry in this randomised trial. Adjuvant therapy and postoperative follow-up were the same in both groups. The main endpoint was cancer-related survival. Data were analysed according to the intention-to-treat principle. FINDINGS 219 patients took part in the study (111 LAC group, 108 OC group). Patients in the LAC group recovered faster than those in the OC group, with shorter peristalsis-detection (p=0.001) and oral-intake times (p=0.001), and shorter hospital stays (p=0.005). Morbidity was lower in the LAC group (p=0.001), although LAC did not influence perioperative mortality. Probability of cancer-related survival was higher in the LAC group (p=0.02). The Cox model showed that LAC was independently associated with reduced risk of tumour relapse (hazard ratio 0.39, 95% CI 0.19-0.82), death from any cause (0.48, 0.23-1.01), and death from a cancer-related cause (0.38, 0.16-0.91) compared with OC. This superiority of LAC was due to differences in patients with stage III tumours (p=0.04, p=0.02, and p=0.006, respectively). INTERPRETATION LAC is more effective than OC for treatment of colon cancer in terms of morbidity, hospital stay, tumour recurrence, and cancer-related survival.

The Long-term Results of a Randomized Clinical Trial of Laparoscopy-assisted Versus Open Surgery for Colon Cancer

Objective:The aim of this study was to compare the long-term outcome of laparoscopy-assisted colectomy (LAC) and open colectomy (OC) for nonmetastatic colon cancer. Methods:From November 1993 to July 1998 all patients with adenocarcinoma of the colon were assessed for entry in this single center, clinically randomized trial. Adjuvant therapy and postoperative follow-up were similar in both groups. The primary endpoint was cancer-related survival and secondary endpoints were probability of overall survival and probability of being free of recurrence. Data were analyzed according the intention-to-treat principle. Results:Two hundred and nineteen patients entered the study (111 LAC group and 108 OC group). The median follow-up was 95 months (range, 77–133). There was a tendency of higher cancer-related survival (P = 0.07, NS) and overall survival (P = 0.06, NS) for the LAC group. Probability of cancer-related survival was higher in the LAC group (P = 0.02) when compared with OC. The regression analysis showed that LAC was independently associated with a reduced risk of tumor relapse (hazard ratio 0.47, 95% CI 0.23–0.94), death from a cancer-related cause (0.44, 0.21–0.92) and death from any cause (0.59, 0.35–0.98). Conclusions:LAC is more effective than OC in the treatment of colon cancer.

Short-term outcome analysis of a randomized study comparing laparoscopic vs open colectomy for colon cancer

The authors examined the impact of the laparoscopic approach on the early outcome of resected colon carcinomas. The role of laparoscopic techniques in the treatment of colon carcinomas is questionable. Previous studies have suggested technical feasibility of surgical resections of these cancers by laparoscopic means and have implied a benefit to laparoscopic technique for patients undergoing colorectal resections. A prospective, randomized study was conducted comparing laparoscopic assisted colectomy (LAC) open colectomy (OC) for colon cancer. We present the preliminary results in relation to the short-term outcome and judge the feasibility of the laparoscopic procedure to as a way of performing accurate oncologic resection and staging. Benefit has been demonstrated with LAC in this setting. Passing flatus, oral intake, and discharge from hospital occurred earlier in LAC- than OC-treated patients The mean operative time was significantly longer in the LAC group than in the OC group. The overall morbidity was significantly lower in the LAC group. No significant differences were observed between both groups in the number of lymph nodes removed or the pathological stage following the Astler-Coller modification of the Dukes classification. The laparoscopic approach improves the short-term outcome of segmental colectomies for colon cancer. However, the further follow-up of these patients will allow us to answer in the near future whether or not the LAC may influence the long-term outcome.

Modulation of the Hyperdynamic Circulation of Cirrhotic Rats by Nitric Oxide Inhibition

The effects of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide (NO) biosynthesis on the splanchnic and systemic circulation, were investigated in rats with cirrhosis induced by carbon tetrachloride. Portal hypertension in these rats was accompanied by decreased arterial blood pressure and peripheral vascular resistance as well as by splanchnic vasodilation with increased portal venous inflow and decreased splanchnic resistance. Intravenous bolus administration of L-NMMA (25 mg/kg) significantly increased systemic blood pressure and decreased cardiac output. L-NMMA also significantly increased systemic and splanchnic vascular resistance; whereas blood flow to the stomach, small intestine, colon, pancreas, mesentery, spleen, and kidney was decreased significantly. L-NMMA did not alter the portal pressure or portosystemic shunting in these cirrhotic rats, yet portal vascular resistance increased, suggesting effects on the intrahepatic and collateral circulation. Pretreatment with L-arginine (300 mg/kg) prevented the hemodynamic changes induced by L-NMMA. These findings support the concept that local excess formation of NO contributes to changes in splanchnic circulation associated with portal hypertension in cirrhosis.

The vasodilator role of endogenous nitric oxide in the rat gastric microcirculation.

The role of endogenous nitric oxide (NO) in the gastric microcirculation of the anaesthetised rat was investigated using the selective inhibitor of NO synthesis, NG-monomethyl-L-arginine (L-NMMA). L-NMMA (12.5-50 mg kg-1 i.v.) induced a dose-dependent increase in systemic arterial blood pressure (BP) and fall in resting gastric mucosal blood flow (MBF), as estimated by hydrogen-gas clearance. The effects of L-NMMA on BP and MBF were abolished by concurrent administration of L-arginine. The enantiomer D-NMMA had no effect on resting BP or MBF. These findings indicate that endogenous NO, derived from L-arginine, plays a local vasodilator role in the gastric mucosal microvasculature.

Effects of inhibiting nitric oxide biosynthesis on the systemic and splanchnic circulation of rats with portal hypertension.

1 The effects of inhibiting endogenous nitric oxide (NO) synthesis with NG‐monomethyl‐l‐arginine (l‐NMMA) on the systemic and splanchnic circulation have been investigated in rats with experimental chronic portal hypertension, anaesthetized with ketamine. 2 Portal hypertension was induced by partial portal vein ligation, 2 weeks prior to study. This procedure induced a reduction in systemic arterial blood pressure (MAP), an increase in cardiac output as measured by radiolabelled microspheres, a reduction in peripheral and splanchnic vascular resistance and an increased portal venous inflow (PVI) and portal pressure, as compared to control non‐ligated rats. 3 l‐NMAA (6.25 and 50 mg kg−1, i.v.) dose‐dependently increased MAP, reduced cardiac output and PVI, and increased peripheral and splanchnic vascular resistance. With l‐NMMA (50 mg kg−1), PVI and the vascular resistances returned to values comparable to those determined in control non‐ligated anaesthetized rats under resting conditions. 4 Porto‐collateral resistance was also increased by these doses of l‐NMMA, whereas portal pressure was unchanged. The increase in renal blood flow and decrease in renal vascular resistance also seen in portal‐hypertensive rats was reversed by l‐NMMA (50 mg kg−1). 5 These effects of l‐NMMA (50 mg kg−1) were inhibited by prior administration of l‐arginine (300 mg kg−1, i.v.). 6 These findings indicate that the chronic hyperdynamic circulatory characteristics following portal vein stenosis can be attenuated by l‐NMMA. Thus, the excessive formation of endogenous NO may be implicated in the pathogenesis of the haemodynamic disturbances and splanchnic vasodilatation associated with chronic portal hypertension.

Propranolol in prevention of recurrent bleeding from severe portal hypertensive gastropathy in cirrhosis

The two main causes of gastrointestinal bleeding in cirrhosis are oesophageal varices and portal hypertensive gastropathy (PHG). Rebleeding from varices can be prevented by beta-blockers, but it is not clear whether these drugs effectively reduce rebleeding from PHG. 54 cirrhotic patients with acute or chronic bleeding from severe PHG took part in a randomised, controlled trial to investigate the efficacy of propranolol in prevention of rebleeding from PHG. 26 patients were randomised to receive propranolol daily at a dose that reduced the resting heart rate by 25% or to 55 bpm (20-160 mg twice daily), throughout mean follow-up of 21 (SD 11) months. 28 untreated controls were followed-up, with the same examinations, for 18 (13) months. The actuarial percentages of patients free of rebleeding from PHG were significantly higher in the propranolol-treated patients than in the untreated controls at 12 months (65% vs 38%; p less than 0.05) and at 30 months of follow-up (52% vs 7%; p less than 0.05). Propranolol-treated patients had fewer episodes of acute bleeding than controls (0.010 [0.004] vs 0.120 [0.040] per patient per month). Multivariate analysis showed that absence of propranolol treatment was the only predictive variable for rebleeding. Actuarial survival was slightly higher in the propranolol group than in the controls, but the difference was not significant. Thus, long-term propranolol treatment significantly reduces the frequency of rebleeding from severe PHG, and may improve the prognosis of cirrhotic patients with this disorder.

Postoperative Surveillance in Patients With Colorectal Cancer Who Have Undergone Curative Resection: A Prospective, Multicenter, Randomized, Controlled Trial

PURPOSE Although systematic postoperative surveillance of patients with colorectal cancer has been demonstrated to improve survival, it remains unknown whether a more intensive strategy provides any significant advantage. This prospective, multicenter, randomized, controlled trial was aimed at comparing the efficacy of two different surveillance strategies in terms of both survival and recurrence resectability. PATIENTS AND METHODS Patients with stage II or III colorectal cancer were allocated randomly to either a simple surveillance strategy including clinical evaluation and serum carcinoembryonic antigen monitoring, or an intensive strategy in which abdominal computed tomography or ultrasonography, chest radiograph, and colonoscopy were added. RESULTS A total of 259 patients were included: 132 were observed according to the simple strategy and 127 were observed according to the intensive strategy. Both groups were similar with respect to baseline characteristics and rate and type of tumor recurrence. After a median follow-up of 48 months, there was no difference in the probability of overall survival in the whole series (hazard ratio [HR] = 0.87; 95% CI, 0.49 to 1.54; P = .62). However, the intensive strategy was associated with higher overall survival in patients with stage II tumors (HR = 0.34; 95% CI, 0.12 to 0.98; P = .045) and in those with rectal lesions (HR = 0.09; 95% CI, 0.01 to 0.81; P = .03), mainly due to higher rate of resectability for recurrent tumors. Colonoscopy was responsible for the detection of the highest proportion (44%) of resectable tumor recurrence in the intensive arm. CONCLUSION A more intensive surveillance strategy improves the prognosis of patients with stage II colorectal cancer or those with rectal tumors. Inclusion of regular performance of colonoscopy seems justified up to the fifth year of follow-up, at least.

Port site metastases and recurrence after laparoscopic colectomy. A randomized trial

AbstractBackground: This study was performed to prospectively assess the impact of the laparoscopic approach to the patterns of port site metastases (PSM) and recurrence rate (RR) of resected colon carcinomas as compared with conventional colectomies. Methods: All patients were included in a prospective randomized trial comparing laparoscopic-assisted colectomy (LAC) versus open colectomy (OC) for colon cancer. The randomization was stratified for localization of the lesion. Patients with metastasic disease at the time of the surgery were excluded. Follow-up in the outpatient clinic was done every 3 months for a minimum of 12 months. Endpoints for the study were metastasis at port site and laparotomy incision as well as recurrence rate. Results: Of 91 segmental colectomies performed from November 1993 to January 1996, there were 44 LAC and 47 OC. Patient data were similar in both groups (age, sex, Dukes stage, type of operation). Mean follow-up was 21.4 months, with a range of 13 to 41 months. There were no wounds or PSM in those series. RR was similar for both groups. For LAC, it was five of 31 (16.1%); for OC, it was six of 40 (15%). Conclusions: The laparoscopic approach has a recurrence rate similar to that for open procedures for colon cancer. However, additional follow-up of these patients is needed before we can determine whether or not the laparoscopic approach influences overall survival.

Effects of Long-term Sulindac Therapy on Colonic Polyposis

Excerpt Sulindac treatment has been reported to induce marked reductions in the number and size of adenomatous polyps in the rectal segment after subtotal colectomy (1). These findings were not con...