Phase 1 trial of intraperitoneal paclitaxel in combination with intravenous cisplatin and oral capecitabine in patients with advanced gastric cancer and peritoneal metastases (IPGP study).

AIMS: Gastric cancer with peritoneal involvement has a poor prognosis. Intraperitoneal (IP) paclitaxel has shown promising results in these patients. However, this approach has only been studied in the Asian population, and in combination with S-1. We investigated the maximum tolerated dose of IP paclitaxel, with a standard chemotherapy combination, in the Australian population. METHODS: The study of the population included metastatic human epidermal growth factor receptor 2 (HER2) negative gastric adenocarcinoma with peritoneal involvement. Treatment included six 21-day cycles of cisplatin (80 mg/m2 IV, day 1) plus capecitabine (1000 mg/m2 PO BD, days 1-14) plus IP paclitaxel (days 1 and 8). IP paclitaxel doses for cohort 1-3 were 10, 20, and 30 mg/m2 , respectively, in a 3 + 3 standard dose-escalation design. RESULTS: Fifteen patients were enrolled of which 6 were female and the median age was 63. Two patients developed dose-limiting toxicities. No grade 4/5 toxicities were recorded. The maximum tolerated dose was not reached. Therefore, as defined by the study protocol, the recommended phase-2 dose for IP paclitaxel was determined to be 30 mg/m2 . The 12-month survival rate was 46.7%, and the median survival was 11.5 months (interquartile range [IQR]: 15.3-6.9). CONCLUSIONS: IP paclitaxel is safe in combination with cisplatin and capecitabine and the recommended phase-2 dose is 30 mg/m2 .

Anterior 90° partial vs Nissen fundoplication--5 year follow-up of a single-centre randomised trial.

INTRODUCTION: Nissen fundoplication can be followed by side effects, and this has driven modifications, including partial fundoplications. We previously reported early outcomes from a randomised trial of Nissen vs anterior 90° partial fundoplication. This paper reports 5-year follow-up outcomes to determine whether anterior 90° fundoplication achieves a satisfactory longer-term outcome. METHODS: From February 1999 to August 2003, 79 patients were randomised to Nissen vs anterior 90° fundoplication. Patients were followed yearly using a standardized clinical questionnaire which included symptom scores to assess heartburn, dysphagia, other post-fundoplication side effects and overall satisfaction with the outcome. Five-year clinical outcomes were analysed. RESULTS: Seventy-four patients were available for follow-up at 5 years. There were no significant differences for heartburn or satisfaction, although more patients used antisecretory medication after anterior 90° fundoplication (29.7 vs 8.1 %). Dysphagia was greater after Nissen fundoplication when measured by an analogue score for solid food and a composite dysphagia score. Symptoms of bloating were more common following Nissen fundoplication (80.0 vs 32.4 %), and less patients could eat a normal diet (78.4 vs 94.6 %). Re-operation was undertaken in four patients after Nissen fundoplication (dysphagia, three; hiatus hernia, one) vs three after anterior 90° fundoplication (recurrent reflux, three). CONCLUSIONS: At 5 years, anterior 90° partial fundoplication was associated with less side effects, offset by greater use of antisecretory medication. Reflux symptoms and overall satisfaction were similar to Nissen fundoplication. Laparoscopic anterior 90° partial fundoplication is an effective treatment for gastro-esophageal reflux.

Laparoscopic cardiomyotomy for achalasia: clinical outcomes beyond 5 years.

BACKGROUND: Laparoscopic cardiomyotomy is the most common surgical procedure for the treatment of achalasia, although few reports describe long-term surgical outcomes. METHODS: The outcomes for 155 patients who underwent a laparoscopic cardiomyotomy with anterior partial fundoplication more than 5 years ago (July 1992 to May 2004) were determined. Patients were followed prospectively at yearly time points using a structured questionnaire which evaluated symptoms of dysphagia, reflux, side-effects, and overall satisfaction with the clinical outcome. RESULTS: Clinical data were available for 125 patients. Thirteen patients died within 5 years of surgery, four were unable to complete the questionnaire, and one developed esophageal squamous cell carcinoma. Nine patients were lost to follow-up, and three would not answer the questionnaire (92.2% late follow-up). Postoperative dysphagia, odynophagia, chest pain, and heartburn was significantly improved at 1 year, 5 years, and late (5+ years) follow-up, with outcomes stable beyond 12 months. Seventy-seven percent of patients reported a good or excellent result (minimal or no symptoms) at 5 years and 73% at late follow-up. At late follow-up, 90% considered they had made the correct decision to undergo surgery. CONCLUSIONS: At minimum 5 years follow-up, laparoscopic cardiomyotomy for achalasia achieves effective and durable relief of symptoms, and most patients are satisfied with the outcome.