Tat Kuen Choi

Chemotherapy for advanced hepatocellular carcinoma Adriamycin versus quadruple chemotherapy

In a prospective clinical trial, 39 patients with advanced hepatocellular carcinoma were randomized to receive either Adriamycin (20 patients) or a combination of 5‐fluorouracil, methotrexate, cyclophosphamide, and vincristine (19 patients). Five patients receiving Adriamycin and none receiving quadruple chemotherapy responded (P < 0.05 in favor of Adriamycin). A further 25 patients were treated with Adriamycin, making a total of 45. The overall objective response rate was 24% (11 patients), with 3 complete remissions and 8 partial remissions. The median survival for Adriamycin‐treated patients (13.0 weeks for the first 20 patients and 14.4 weeks for all patients) was longer than those treated by quadruple chemotherapy (6.5 weeks). The difference, however, was not significant by the Wilcoxan test as modified by Gehan. Patients with positive HbsAg had a significantly higher chance of having a response, while serum alpha‐fetoprotein levels did not correlate with response.

Sucralfate Overcomes Adverse Effect of Cigarette Smoking on Duodenal Ulcer Healing and Prolongs Subsequent Remission

A unicenter, single-blind, randomized study was conducted on 283 patients with active duodenal ulcer to compare possible factors that may affect healing and relapse in patients treated with a potent antisecretory agent, cimetidine, or a site-protective and cytoprotective agent, sucralfate. The endoscopic healing rates at 4 wk were 76% and 79%, respectively, and cross-over treatment of the failures for a further 4 wk resulted in 68% healing with cimetidine and 69% healing with sucralfate, both differences being not statistically different. Unlike cimetidine, healing by sucralfate was unaffected by cigarette smoking, reluctance to give up smoking, habitual use of alcohol, high maximal acid output, and large ulcer diameter. In particular, the healing rate of smokers treated with sucralfate (82%) was significantly greater than that of smokers treated with cimetidine (63%). Duodenal bulb deformity significantly affected healing in both groups, and was the only offsetting factor identifiable for sucralfate out of 46 factors examined. Of the patients with healed ulcers, 238 participated in a 24-mo follow-up study consisting of interviews at 2-mo intervals and endoscopy at 4-mo intervals or whenever symptoms recurred. The cumulative relapse rate was significantly (p less than 0.007) greater in patients healed with cimetidine than with sucralfate, 50% relapse occurring at 6 and 12 mo, respectively. In both, the cumulative relapse rate was significantly greater in cigarette smokers than in nonsmokers, but smokers and nonsmokers treated with cimetidine relapsed (50% at 4 and 8 mo, respectively) faster than the corresponding smokers and nonsmokers treated with sucralfate (50% at 8 and 18 mo, respectively). Furthermore, in cimetidine- but not sucralfate-healed patients, early ulcer relapse (within 6 mo) was associated with short duration of illness, short remission period, long symptomatic spell, and reluctance to give up smoking. We conclude that smoking adversely affects duodenal ulcer healing by cimetidine and hastens subsequent relapse, and that sucralfate overcomes the adverse effect of smoking on healing as encountered with cimetidine, and results in a subsequent remission period double that of cimetidine.

Prostaglandin E1 (Misoprostol) overcomes the adverse effect of chronic cigarette smoking on duodenal ulcer healing

Chronic cigarette smoking adversely affects duodenal ulcer healing despite treatment by potent gastric acid-reducing agents. Prostaglandins of the E series possess antisecretory and cytoprotective properties and theoretically offer advantages over existing therapeutic agents. A double-blind randomized study was performed to compare complete duodenal ulcer healing as assessed by endoscopies every two weeks for up to 12 weeks. Two hundred twenty-nine patients were randomized to receive misoprostol, an orally stable synthetic derivative of prostaglandin E1, in 200-μg or 300-μg qid dosages, or placebo. Life-table analysis showed that (1) both regimens of misoprostol were significantly more effective than placebo, achieving healing rates of 61% and 71%, respectively, at four weeks, and (2) cigarette smoking significantly impaired healing by placebo but not by misoprostol. In fact, the time-healing curves of smokers and nonsmokers on the higher dose of misoprostol completely overlapped. Furthermore, delayed treatment and large ulcer diameter adversely affected healing by misoprostol in smokers, whereas in nonsmokers, high basal and maximal acid output were unfavorable. Misoprostol is recommended for the treatment of duodenal ulcer, particularly in chronic smokers early in a given period of symptoms.

Bronchoscopy and carcinoma of the esophagus I: Findings of bronchoscopy in carcinoma of the esophagus

Tracheobronchial involvement frequently occurs in patients with carcinoma of the esophagus. A study of the results of 525 bronchoscopies performed on patients with carcinoma of the esophagus who were evaluated for surgery revealed that abnormalities were found in 33.9 percent. The incidence was highest for those with cervical and upper-third thoracic tumors; however, a significant number of lower-third thoracic and abdominal tumors also showed abnormalities (12.5 and 5 percent, respectively). The incidence was also higher with large tumors, but again, a significant number of apparently small tumors also showed abnormalities. The abnormalities could be broadly classified into two groups: those showing only impingement and those showing actual invasion. Further studies are needed to determine whether the tumors with impingement are resectable.

Effect of sucralfate and cimetidine on duodenal ulcer-associated antral gastritis and Campylobacter pylori☆

The course of gastritis and Campylobacter pylori was studied in a single-blind randomized trial comparing cimetidine 200 mg three times a day and 400 mg at night and sucralfate 1 g four times a day orally for four weeks in 140 patients with proved duodenal ulcer. At least two antral biopsies were performed during endoscopy before entry and at the end of four weeks. The activity and the degree of chronic inflammation, as assessed histologically by the degree of infiltration of, respectively, polymorphs and chronic inflammatory cells, were graded blindly by two pathologists as nil, mild, moderate, or severe. The density of C. pylori, as assessed after Warthin-Starry stain, was similarly graded. Ulcer-healing rates were comparable in the cimetidine (73.2 percent) and sucralfate (79.7 percent) groups. Improvement of the activity of gastritis occurred significantly (p less than 0.05) more frequently in the sucralfate (33.3 percent) than in the cimetidine group (18.3 percent), and remained so (p less than 0.05) when only patients with healed ulcer were compared. The density of C. pylori decreased significantly in the sucralfate group after treatment (p less than 0.01) but not in the cimetidine group. The 12-month ulcer relapse rates were significantly (p less than 0.05) lower by life-table analysis in patients healed with sucralfate than in those healed with cimetidine and were unaffected by either the density of Campylobacter in either group or the improvement of the gastritis. It is concluded that sucralfate improves duodenal ulcer-associated antral gastritis and decreases the density of C. pylori, and that factors other than bacterial density and antral gastritis may be responsible for the advantage of sucralfate over cimetidine in ulcer relapse.

Bronchoscopy and carcinoma of the esophagus II: carcinoma of the esophagus with tracheobronchial involvement

Involvement of the tracheobronchial tree, as observed through the bronchoscope, was in the form of impingement or invasion. Bronchoscopy was performed on 525 patients with carcinoma of the esophagus. Impingement was found in 91 patients and invasion in 87 patients. Forty-eight of the 63 patients with impingement and 7 of the 51 patients with invasion were found to have resectable tumors. Bypass operations were performed on the rest of the patients. The operative mortality was high for both bypass and resection procedures. The median survival for bypassed patients and resected patients were 4 months and 9 months, respectively. Four resected patients survived 3 years or more, 2 of whom had no evidence of recurrence. Most patients with impingement have resectable tumors and long-term survival is possible if the tumor can be resected.

Chronic Antral Gastritis in Duodenal Ulcer: Natural History and Treatment With Prostaglandin E1

The natural history of chronic antral gastritis in relation to the healing of duodenal ulcer and its response to treatment, if any, are unknown. We performed a double-blind controlled trial using an oral prostaglandin E1, misoprostol, in 229 patients with active duodenal ulcer randomized to receive placebo (n = 76), misoprostol 200 micrograms (n = 77), or misoprostol 300 micrograms (n = 76), q.i.d. orally. Healing of duodenal ulcer was assessed biweekly up to 12 wk by endoscopy, during which procedures at least two antral and two fundal biopsy specimens were taken. The activity and the degree of chronic inflammation of gastritis, as assessed histologically by the infiltration of polymorphs and chronic inflammatory cells, respectively, was graded blindly by two pathologists as nil, mild, moderate, or severe. Before treatment, 99% of patients had chronic antral gastritis and 1.5% had chronic fundal gastritis. In the placebo group, healed duodenal ulcer was associated with significantly (p less than 0.01, life table analysis) higher incidence of improvement of the activity of the antral gastritis (nil or mild as endpoint) than unhealed ulcer (30% vs. 4% at week 8). Irrespective of whether duodenal ulcer was healed or unhealed, significantly (p less than 0.01) more patients on misoprostol (50% at week 8) showed improvement (nil or mild as endpoint) than the placebo group. The degree of chronic inflammation of the antral gastritis showed similar significant changes in favor of misoprostol. Smoking and alcohol intake had no significant effect on the improvement of chronic antral gastritis. In conclusion, healing of duodenal ulcer was associated with improvement of the activity of chronic antral gastritis, which, as shown for the first time, could be further enhanced by a therapeutic agent--prostaglandin E1.

Regional chemotherapy through a saphenous vein graft for the treatment of head and neck cancers

Regional chemotherapy was given through a vein grafted between the common carotid and external carotid arteries to 20 patients who had a variety of advanced head and neck cancers. The objective response rate was 73.6%, which included 36.8% complete response. The median duration of response was more than 10 months. The toxicity was mild and well tolerated. The complication rate associated with the procedure was low. This form of regional chemotherapy has significant advantages over the conventional form that uses drugs given through the retrograde temporal artery because the catheter‐related complications are eliminated, the perfusion of the tumor can be maintained consistently, and, consequently, the response rate is high and the duration of response is increased.

Survival after surgery for advanced carcinoma of the stomach other than the cardia

The survival of 103 patients operated on for advanced carcinoma of the stomach other than the cardia was assessed. The median duration of survival for patients subjected to palliative partial gastrectomy, total gastrectomy, gastrojejunostomy, and biopsy only was 24, 22, 11, and 10 weeks, respectively. All of these patients had definite residual tumor. In the 27 patients with preoperative signs of incurable tumor, the high operative mortality rate (19 percent), the low rate of resectability (26 percent), and the short duration of survival in the patients who had resection (median 11 weeks) combined lead to the conclusion that exploration for the possibility of resection is not worthwhile.

Surgery during acute pancreatitis: Observations in 50 patients

Surgery was performed during the acute phase of illness in 50 of 348 patients with acute pancreatitis. The operative mortality was 40 percent. Analysis of the indications for operation, the operative findings, and the mortality rate revealed that the suspected complications for which operation was planned were not always borne out by the operative findings. In addition, the deterioration of patients while being treated conservatively, or the presence of severe acute pancreatitis preoperatively, were not predictive of the finding of hemorrhagic or necrotizing pancreatitis at operation. In a significant proportion of patients with severe pancreatitis, the diagnosis of pancreatitis was first made at laparotomy. More use should be made of the newer investigative methods to better identify any complications which may have occurred and the necessity for operative intervention.