McClure L. Smith

Combination Adriamycin and radiation therapy in gynecologic cancers

Anthracyclic antibiotics, of which Adriamycin is representative, have the ability to bind to cellular DNA and thereby interfere with the X-ray repair process. When radiation survival curves of tissue cultures were studied, increased cell-killing was noted in those cultures with Adriamycin over those without the drug. The mechanism by which this occurs may be related to a reduced rate of DNA strand break rejoining, as demonstrated by use of alkaline sucrose gradient techniques. A preliminary clinical Phase I study, in which patients with advanced gynecologic malignancy were treated by simultaneous Adriamycin and X radiation, suggests that combined therapy is well-tolerated, and that such combinations may prove useful in selected patients.

Vaginal reconstruction following extensive treatment for pelvic cancer

Since 1970, 23 patients at UCLA and The City of Hope who have undergone extensive treatment for pelvic malignancy have had vaginal function successfully restored. A combination of methods, including split-thickness skin graft and the construction of an external vulvar pouch, is often necessary to obtain maximal functional results. The external vulvar pouch was very useful, although not as anatomically appealing as internal methods of reconstruction. In young patients who required an exenteration, a new technique using part of the anterior bladder fundus was developed. Preliminary experience with this method was promising. Among the gorup of 23 patients, there have been no overt failures. By combining restoration of rectal function with vaginal reconstruction, two major steps have been taken toward total rehabilitation of the patient undergoing extensive treatment for pelvic malignancy. Persistence, ingenuity, and planning by the surgeon are essential to obtain a maximum functional result for each patient.

Enteroperineal fistulae following pelvic exenteration: A 10-point program of management

Abstract Enteroperineal fistulae represent one of the most serious complications following pelvic exenteration. Thirteen patients with this complication were treated at UCLA and City of Hope hospitals since 1956. Of the first nine patients managed with a variety of methods, there was only one survivor. Because of these poor initial results, a 10-point program of management of this complication was developed. This program consisted of preoperative Hypaque small bowel X rays, a small bowel tube, hyperalimentation, prophylactic antibiotics, and early surgical intervention. Specific recommendations for surgical management included the isolation of the fistula without resection, the creation of a double-barreled mucous fistula to drain the involved segment of small bowel, and the performance of an anastomosis between more proximal ileum and ascending or transverse colon. Results in four patients so managed have been encouraging and all four patients were subsequently discharged from the hospital ambulatory.

Essential fatty acid deficiency with long-term hyperalimentation

Abstract Content of essential fatty acids was determined in the plasma lipid fractions of patients with malignancies of the female reproductive tract. A marked deficiency was identified in two such patients while on prolonged total parenteral nutrition with hypertonic glucose and casein hydrolysate, compared to a control group of ambulatory and postoperative patients. The progressive deficiency observed in one patient was completely reversed by infusions of fat emulsion over a 3-week period. These results indicate a need for inclusion of essential fatty acids with prolonged total parenteral nutrition.

Use of sigmoid colon for rectal substitution following pelvic exenteration

Abstract Pelvic exenteration with rectal substitution using a mobilized segment of sigmoid colon was carried out in 11 selected patients with advanced pelvic malignancy. Satisfactory “rectal” function was achieved in six patients, eliminating the need for permanent colostomy. Rectal substitution was made possible by preserving the rectal sphincter to which the sigmoid colon segment was anastomosed. The portion of the procedure dealing with excision of the tumor and surrounding structures was not altered in patients selected for rectal substitution. With apparent increasing success in radical pelvic surgery, including decreasing operative mortality rates, efforts to increase patient acceptance by alleviating the disfigurement and disability of a permanent colostomy would seem worthwhile.

Radioprotection of the digestive tract by intravenous infusion of vasopressin

The effect of venous infusions of vasopressin during fractionated abdominal radiation exposures was evaluated in four pairs of dogs. In each pair, the control dog was given venous infusion of saline during irradiation. The results were analyzed from clinical observation, autopsy findings, and pathological examination. It appears that venous infusion of vasopressin has a definite and reproducible effect of radioprotection on the gastrointestinal tract, the dose modifying factor (DMF) being 1.5. Radiation therapy of the gynecologic malignancies would be one major application since the radiosensitivity of the intestinal tract is often a limiting factor in delivering high doses to the tumor, and further investigations are being done to study the effects of vasopressin on the radiosensitivity of malignant tumors.