Robert J. Keehn

Preoperative radiation and surgery for cancer of the rectum: veterans administration surgical oncology group trial II

In a prospective randomized trial, 361 male patients with histologically proven adenocarcinoma of the rectum, judged preoperatively to require abdominoperineal resection (APR), were treated by surgery alone or were given 3,150 rads of preoperative radiotherapy. Surgical resection was done on 320 patients, 262 having “curative” APR. Only moderate symptoms from radiotherapy were noted and postoperative complications and 30‐day mortality were similar in both groups. Five‐year survival for curative APR was the same in both groups (50% for both treated and control patients). The incidence of positive lymph nodes in the resected specimens was 35% in treated and 41% in controls. In the first preoperative radiotherapy trial conducted by the group, 5‐year survival in patients undergoing “curative” APR was 47% in treated versus 34% in control groups. Additionally, the difference in positive lymph nodes in the resected specimens was substantially greater in the first trial (26% in treated versus 44% in controls). Cancer 58:352–359, 1986.

Efficacy of prolonged intermittent therapy with combined 5‐FU and methyl‐CCNU following resection for gastric carcinoma. A veterans administration surgical oncology group report

This prospective evaluation of 5‐fluorouracil (5‐FU) and methyl‐CCNU administered in combination to patients with surgery for histologically proved gastric adenocarcinoma is based upon 312 patients randomized between August 1974 and May 1980. Patients were stratified into three categories of resectability, (1) complete, (2) proven incomplete, and (3) nonresectable, prior to random treatment assignment to surgery alone or surgery followed by adjuvant chemotherapy. Drug therapy consisted of discrete 5‐day courses administered at 7‐week intervals. Toxic reactions were reported in association with 42% of the courses. Treatment was suspended or discontinued in 6% of the courses because of hematologic toxicity. Treated patients with curative resections experienced a more favorable survival than did controls, but the early advantage was lost by the end of the second follow‐up year. However, no statistically significant improvements in survival or reductions in risks of recurrence were observed. Similar proportions of treated and control deaths were attributable to residual or recurrent disease.

Factors influencing survival after resection in cancer of the colon and rectum

Investigators from twenty-one Veterans Administration Hospitals (Table I) founded the VA Surgical Cancer Chemotherapy Study Group in 1957 to investigate the effect of cancer chemotherapy as an adjuvant to operation for resectable cancer of the lung, stomach, and large bowel. A preliminary report on the use of triethylenethiophosphoramide (TSPA) as an adjuvant to surgery in cancer of the colon and rectum was published in 1964 [I]. It was based on 1,171 resections, including 929 “curative” operations, with a two year follow-up study on 426 and a forty-four month follow-up study on eighty curative cases. The purpose of this paper is to give the five year results on the use of TSPA as an adjuvant, and also to examine characteristics of the patient, the disease, the operation, and the postoperative course for their influence on recurrence and survival in this group of patienk.

Efficacy of prolonged intermittent therapy with combined 5-fluorouracil and methyl-ccnu following resection for carcinoma of the large bowel. A veterans administration surgical oncology group report

This prospective evaluation of 5‐FU and methyl‐CCNU administered in combination to patients with curative surgery for histologically proved colorectal adenocarcinoma is based upon 645 patients randomized between August 1973 and July 1979. Beyond the requirement that the resection be clinically and microscopically complete, patients were not stratified prior to random treatment assignment to surgery alone or surgery followed by adjuvant chemotherapy. Drug therapy consisted of discrete 5‐day courses administered at 7‐week intervals, start to start. Toxic reactions were reported in association with 40% of courses. In 10% of patients with hematologic toxicity, the reactions were sufficiently severe to require the suspension or discontinuation of treatment. Treated patients experienced a slightly more favorable survival than did controls. However, the advantage was seen only in the 216 patients (34% of total) with one to four positive lymph nodes in the resected specimen. Similar proportions of treated and control deaths were attributed to residual or recurrent disease. Cancer 53:1–8 1984.

Twenty-four mortality follow-up of Army veterans with disability separations for psychoneurosis in 1944

&NA; World War II Army inductees medically discharged for psychoneurosis in 1944 experienced a 20‐percent excess mortality over the period 1946‐1969, highest in the earlier years and diminishing thereafter. Some of the differential mortality, e.g., from inflammatory diseases of the CNS, may represent diagnostic error in 1944. Behavioral maladjustments, or pathological personality types coexisting with psychoneurosis, may explain the increased risk of death from alcoholism, suicide, and homicide. Although they usually existed prior to service, and most probably continued thereafter, the anxiety and emotional conflicts leading to discharge in 1944 seem not to have been associated with chronic disturbances of physiologic function sufficient to cause severe organic disease in later life. A possible exception is cerebrovascular disease, for which the discrepancy is neither large nor reinforced by similar differences in mortality from hypertension or hypertensive heart disease.

Use of 5-fluorodeoxyuridine (FUDR) as an adjuvant to the surgical management of carcinoma of the stomach

5‐Fluorodeoxyuridine was administered to 185 patients randomized to the treated group following gastric resection for carcinoma of the stomach. Two hundred twelve patients were randomized to control groups. There are no significant differences in operative mortality, complications, or 3‐year survival rates.

Factors related to survival following resection for gastric carcinoma. Analysis of 903 cases

This report is based on 903 patients with resections for gastric carcinoma between October 1957, and July 1969, entered in controlled trials of adjuvant therapy with Thio‐TEPA and FUDR. Neither Thio‐TEPA nor FUDR, as administered, prolonged survival. The extent of disease at the time of curative surgery is related to survival for the first 36 months postoperatively. Involvement of lymph nodes, resection of the esophagus, and serosal penetration are predictive of recurrence up to 36 months. There appear to be three groups of patients: 1) Cured (26%); 2) Slowly growing tumor−23% (median survival, 25 months); and 3) Rapidly growing tumor−51% (median survival, eight months). The absence of blood‐vessel invasion, lymphatic invasion, lymph‐node involvement, and serosal penetration characterize those patients in Group A.

A Controlled Study of Preoperative Irradiation in Cancer of the Sigmoid Colon and Rectum: Preliminary Report

The authors initiated a prospective controlled study to determine the clinical effect of low-dose preoperative irradiation on clinically operable patients with histologically proved adenocarcinoma of the colon or rectum. Preoperative irradiation had no demonstrable effect upon the incidence of surgical complications or upon mortality during the first three months after resection. The pathologist identified lymph nodes in 24% of the resected x-ray cases and in 38% of the controls. Lymphatic invasion and serosal penetration were also reported significantly less frequently for the irradiated. No remarkable differences were seen when survival from operation was computed for subgroups of resected cases.

Efficacy of MER immunotherapy when added to a regimen of 5-fluorouracil and methyl-CCNU following resection for carcinoma of the large bowel. A Veterans Administration Surgical Oncology Group report.

Two hundred four patients with a microscopically incomplete resection for carcinoma of the colon or rectum were accepted for study. All patients were treated with 5‐flurouracil and methyl‐CCNU beginning about the second postoperative week. Concurrent immunotherapy with the methanol extraction residue of bacillus Calmette‐Guérin (MER) was randomly assigned to 103 patients. Treatment was continued as long as acceptable to the patient, and until clinical recurrence. Toxic reactions to the drug were not increased by the addition of MER, and seldom were servere enough to require the discrimination of therapy. No evidence of improved survival was seen in treated patients. On the contrary, survival in patients who experienced severe reactions to treatment may have been impaired by MER, with the period of impairment continuing after all adjuvant therapy was stopped. Similar proportions of treated and control deaths were attributable to residual or recurrent disease.

Gastrointestinal bleeding after operation for pancreatic cancer

Gastrointestinal bleeding after surgery for cancer of the pancreas contributes significantly to patient morbidity and to patient mortality, if the bypass was performed for palliation. Bleeding after resection of the pancreatic tumor appears to be amenable to therapy, and unaltered by the addition of vagotomy at the time of surgery. Patients undergoing palliative surgery who are expected to live beyond the postoperative period may well benefit from measures to reduce the risk of gastrointestinal bleeding.