Irofulven as first line therapy in recurrent or metastatic gastric cancer: a phase II multicenter study by the Cancer Therapeutics Research Group (CTRG).

BACKGROUND: The purpose of this study was to evaluate the tolerability and efficacy of irofulven, a DNA interacting acylfulvene analog, as first line therapy for patients with recurrent or metastatic gastric cancer. PATIENTS AND METHODS: Twenty-three patients with recurrent or metastatic gastric cancer received irofulven at a dose of 0.45 mg/kg administered intravenously over 30-min infusion (up to a maximum of 50 mg), on days 1 and 8, every 3 weeks. RESULTS: The median number of cycles delivered per patient was 2 (range 1-6). Two patients (9%) had >or= 1-week delay in administration of subsequent cycle of chemotherapy. For the day 8 chemotherapy, dose reductions were required in seven patients (30%); dose omitting occurred in five patients (22%). Grade 3/4 anemia and neutropenia occurred in 22 and 17% of patients, respectively. There was no grade 4 thrombocytopenia and no neutropenic fever was observed. Of the 20 evaluable patients, there were no responses observed, 3 patients had stable disease after 2 cycles of treatment which was not confirmed by a further assessment. Median overall survival was 6.05 months (95% CI 4.55-9.39). CONCLUSIONS: Irofulven was tolerated at the dose of 0.45 mg/kg on days 1 and 8, every 3 weeks but showed no evidence of antitumor activity in patients with advanced gastric cancer.

Can visual distraction decrease the dose of patient-controlled sedation required during colonoscopy? A prospective randomized controlled trial.

BACKGROUND AND STUDY AIMS: We previously demonstrated that audio distraction using relaxation music could lead to a decrease in the dose of sedative medication required and improve patient satisfaction during colonoscopy. This prospective randomized controlled trial was designed to test the hypotheses that visual distraction may also decrease the requirement for sedatives and that audio and visual distraction may have additive beneficial effects when used in combination. PATIENTS AND METHODS: 165 consecutive patients who underwent elective colonoscopy were randomly allocated into three groups to receive different modes of sedation: group 1 received visual distraction and patient-controlled sedation (PCS); group 2 received audiovisual distraction and PCS; group 3 received PCS alone. A mixture of propofol and alfentanil, delivered by a Graseby 3300 PCA pump, was used for PCS in these groups. Each bolus of PCS delivered 4.8 mg propofol and 12 micro g alfentanil. Measured outcomes included the dose of PCS used, complications, recovery time, pain score, satisfaction score, and willingness to use the same mode of sedation if the procedure were to be repeated. RESULTS: Eight patients were excluded after randomization. The mean+/-SD dose of propofol used in group 2 (0.81 mg/kg +/- 0.49) was significantly less than the dose used in group 1 (1.17 mg/kg +/- 0.81) and that used in group 3 (1.18 mg/kg +/- 0.60) ( P < 0.01, one-way analysis of variance). The mean +/- SD pain score was also lower in group 2 (5.1 +/- 2.5), compared with the pain scores in group 1 (6.2 +/- 2.2) and group 3 (7.0 +/- 2.4) ( P < 0.01, one-way analysis of variance). The mean +/- SD satisfaction score was higher in groups 1 (8.2 +/- 2.4)) and 2 (8.4 +/- 2.4), compared with the score in group 3 (6.1 +/- 2.9) ( P < 0.01, one-way analysis of variance). A majority of patients in groups 1 (73 %) and 2 (85 %) said that they would be willing to use the same mode of sedation again, compared with only 53 % in group 3 ( P < 0.01, chi-squared test). CONCLUSIONS: Visual distraction alone did not decrease the dose of sedative medication required for colonoscopy. When audio distraction was added, both the dose of sedative medication required and the pain score decreased significantly. Both visual and audiovisual distraction might improve patients' acceptance of colonoscopy.

The clinical efficacy of neoadjuvant chemotherapy in squamous esophageal cancer: a prospective nonrandomized study of pulse and continuous-infusion regimens with Cisplatin and 5-Fluorouracil.

BACKGROUND: We evaluated cisplatin and 5-fluorouracil as preoperative adjuvant chemotherapy for patients with locally advanced squamous esophageal cancer and compared two different infusion regimens. The outcomes were also compared with those of our historical control patients treated by surgery alone. METHODS: From 1991 to 1997, 83 consecutive esophageal cancer patients underwent surgical exploration after completion of two cycles of cisplatin and 5-fluorouracil chemotherapy regimens, either in pulse or in continuous infusion cycles. Outcomes were compared with those of 76 historical control patients. Both groups were comparable in demographic characteristics and tumor stages. The resection rates, operative morbidity, mortality, and survival rates were compared. RESULTS: Partial response was achieved in 50% of patients who received chemotherapy. There was no chemotherapy-related mortality. The resection, morbidity, and mortality rates and median survival between the surgery-alone group and the chemotherapy group were 71.1% vs. 82%, 51% vs. 55%, and 4% vs. 10.8%, 12.0 vs. 13.5 months, respectively (P >.05). There was also no statistically significant difference between the two regimens. CONCLUSIONS: Preoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil infusion, in pulse or continuous regimens, followed by surgery for squamous esophageal cancer patients had no added benefit in the overall survival.

Effect of intravenous omeprazole on recurrent bleeding after endoscopic treatment of bleeding peptic ulcers.

BACKGROUND: After endoscopic treatment of bleeding peptic ulcers, bleeding recurs in 15 to 20 percent of patients. METHODS: We assessed whether the use of a high dose of a proton-pump inhibitor would reduce the frequency of recurrent bleeding after endoscopic treatment of bleeding peptic ulcers. Patients with actively bleeding ulcers or ulcers with nonbleeding visible vessels were treated with an epinephrine injection followed by thermocoagulation. After hemostasis had been achieved, they were randomly assigned in a double-blind fashion to receive omeprazole (given as a bolus intravenous injection of 80 mg followed by an infusion of 8 mg per hour for 72 hours) or placebo. After the infusion, all patients were given 20 mg of omeprazole orally per day for eight weeks. The primary end point was recurrent bleeding within 30 days after endoscopy. RESULTS: We enrolled 240 patients, 120 in each group. Bleeding recurred within 30 days in 8 patients (6.7 percent) in the omeprazole group, as compared with 27 (22.5 percent) in the placebo group (hazard ratio, 3.9; 95 percent confidence interval, 1.7 to 9.0). Most episodes of recurrent bleeding occurred during the first three days, which made up the infusion period (5 in the omeprazole group and 24 in the placebo group, P<0.001). Three patients in the omeprazole group and nine in the placebo group underwent surgery (P=0.14). Five patients (4.2 percent) in the omeprazole group and 12 (10 percent) in the placebo group died within 30 days after endoscopy (P=0.13). CONCLUSIONS: After endoscopic treatment of bleeding peptic ulcers, a high-dose infusion of omeprazole substantially reduces the risk of recurrent bleeding.

Evaluation of a selective transport medium for gastric biopsy specimens to be cultured for Helicobacter pylori.

Since the means of culturing Helicobacter pylori may not be available in some laboratories, prolonging the survival of this organism during transportation is a major concern in terms of improving detection rates. A selective transport medium was evaluated for the preservation of H. pylori from 254 gastric biopsy specimens collected from a rural area in China where culturing is not feasible. Gastric biopsy specimens were inoculated in sterile broth consisting of brain heart infusion (BHI) broth, horse serum, and yeast extract supplemented with vancomycin, amphotericin B, and nalidixic acid (VAN). Of the 254 biopsy specimens, 238 were identified by histology to have H. pylori infection. Total rates of recovery of H. pylori from the H. pylori-positive gastric biopsy specimens stored in the BHI-VAN broth ranged from 76 to 46% after storage of specimens for 5 to 9 days. In conclusion, the selective medium is useful for prolonging the survival of H. pylori in gastric biopsy specimens for which immediate culture is not feasible.

Randomised comparison between adrenaline injection alone and adrenaline injection plus heat probe treatment for actively bleeding ulcers.

OBJECTIVE: To compare endoscopic adrenaline injection alone and adrenaline injection plus heat probe for the treatment of actively bleeding peptic ulcers. DESIGN: Randomised prospective study of patients admitted with actively bleeding peptic ulcers. SETTING: One university hospital. SUBJECTS: 276 patients with actively bleeding ulcers detected by endoscopy within 24 hours of admission: 136 patients were randomised to endoscopic adrenaline injection alone and 140 to adrenaline injection plus heat probe treatment. MAIN OUTCOME MEASURES: Initial endoscopic haemostasis; clinical rebleeding; requirement for operation; requirement for blood transfusion; hospital stay, ulcer healing at four weeks; and mortality in hospital. RESULTS: Initial haemostasis was achieved in 131/134 patients (98%) who received adrenaline injection alone and 135/136 patients (99%) who received additional heat probe treatment (P = 0.33). Outcome as measured by clinical rebleeding (12 v 5), requirement for emergency operation (14 v 8), blood transfusion (2 v 3 units), hospital stay (4 v 4 days), ulcer healing at four weeks (79.1% v 74%), and in hospital mortality (7 v 8) were not significantly different in the two groups. In the subgroup of patients with spurting haemorrhage 8/27 (29.6%; 14.5% to 50.3%) patients from the adrenaline injection alone group and 2/31 (6.5%; 1.1% to 22.9%) patients from the dual treatment group required operative intervention. The relative risk of this was lower in the dual treatment group (0.17; 0.03 to 0.87). Hospital stay was significantly shorter in the dual treatment group than the adrenaline injection alone group (4 v 6 days, P = 0.01). CONCLUSION: The addition of heat probe treatment after endoscopic adrenaline injection confers an advantage in ulcers with spurting haemorrhage.

Mesh hernioplasty using a stapler.

BACKGROUND: The recent development of laparoscopic hernioplasty has evoked extensive re-examination of the safety and effectiveness of using synthetic mesh materials in hernia surgery. We have investigated the efficacy of anterior stapling mesh repair in the treatment of inguinal hernia. METHODS: From July 1993 to June 1994, a modified open mesh hernioplasty using staples for anchorage has been performed in 127 patients. RESULTS: The mean age of patients was 61.4 +/- 13.0 years. Over 90% of them were operated on under local anaesthesia. The operation time ranged from 30 to 95 min with a median of 39 min. Only sixteen patients (12.6%) required postoperative parenteral analgesics and the median time for resuming daily activities was 7 days. Apart from two patients with reactionary haemorrhage, there was no other significant complication observed. Only one recurrence was encountered over the 26-month median follow-up period. CONCLUSIONS: We conclude that the modified mesh hernia repair with a stapling device is a feasible, inexpensive and safe procedure that is well tolerated under local anaesthesia by most patients.