Dennis F. Devereux

New surgical approach to minimize radiation‐associated small bowel injury in patients with pelvic malignancies requiring surgery and high‐dose irradiation. A preliminary report

Complications associated with small bowel intolerance to radiation therapy at doses higher than 4500 to 5000 cGy have been the limiting factor in delivering pelvic radiation either as an adjuvant to surgery or alone in the treatment of pelvic malignancies. Despite numerous surgical, medical, and radiation therapy technical measures to minimize small bowel injury, none have been uniformly successful in eliminating this problem. With the availability of a new synthetic absorbable mesh, a pelvic sling can be placed at the time of exploration or definitive surgery aimed at suspending the small bowel out of the pelvis. Preliminary work in animal models has shown the mesh sling to be well‐tolerated and successful. Barium‐contrast simulation studies of seven patients with pelvic malignancies requiring resectional surgery and postoperative radiation therapy in whom the mesh sling was placed at the time of surgery demonstrate total exclusion of the small bowel from the pelvic radiation treatment field. All patients have been followed for at least 4 months since mesh placement, and to date no complications have occurred. It is possible that this technique of bowel exclusion will permit the delivery of larger doses of radiation therapy in patients with pelvic malignancies aiming at more effective local and regional control of cancer without increased complications from radiation‐associated small bowel injury.

New surgical method to prevent pelvic radiation enteropathy

Pelvic radiation doses exceeding 4,000–4,500 cGy are known to be associated with acute and chronic radiation enteropathy. This same radiation dose is, at the same time, only moderately effective in the elimination of microscopic malignancy, let alone gross clinical disease. Numerous medical and surgical attempts to minimize this complication have been uniformly unsuccessful. With the availability of a new synthetic, absorbable, polyglycolic acid mesh, an intestinal sling surgical procedure has been devised to exclude the small bowel from the pelvis and subsequent radiation fields. Twenty-five patients have been treated by this new technique with only one complication presenting as a fungal infection. Small-bowel barium contrast studies in 16 patients referred for postoperative radiation demonstrated 13 satisfactory exclusions of the small bowel from the translateral pelvic irradiation field. In 16 evaluable patients, three had unsatisfactory exclusion two of which were due to technical error. This has permitted high-dose (5,500–6,500 cGy) radiotherapy to the critical treatment volume without posttreatment complication. Mean follow-up time is 14.8 months. Several patients have been reexplored demonstrating complete absorption of the mesh without fibrinous adhesions or other foreign body reaction. It is concluded that this new technique of small bowel exclusion will permit the routine delivery of much higher doses of radiation in patients requiring improved local-regional control of their pelvic cancers and without morbidity from radiation-associated small bowel injury.

Tumor-associated metabolism in the rat is a unique physiologic entity

The metabolic responses associated with the tumor-bearing state, as compared to states of sepsis and prolonged starvation, were examined. Tumor-bearing rats manifested significant elevation of triglycerides, significant reduction of glucose and insulin levels, significantly increased plasma skeletal muscle proteolysis-inducing activity, and an unchanged hepatic protein synthetic activity compared to control rats. Prolonged starvation produced an adaptation characterized by significant hypoglycemia and hypoinsulinemia, reduced hepatic protein synthesis, and increased peripheral protolysis compared to controls. Septic animals had glucose, insulin, and lipid levels similar to control animals but had increased hepatic protein synthesis. Each state manifested its own unique metabolic response compared to controls. It appears that the metabolic consequences of cancer in this sarcoma rat model is different than septic and prolonged starvation states.

The specific diagnosis of hepatocellular carcinoma by scintigraphy: multiple radiotracer approach

The accuracy of scintigraphy in diagnosing hepatocellular carcinoma (HCC) at Boston City Hospital between January 1, 1978 and September 30, 1983 is retrospectively reviewed. A combined protocol using technetium‐99m sulfur colloid (TsSC), gallium (Ga), and scintiangiography (STA) was employed in order to enhance diagnostic specificity. There were 14 cases of HCC, of which 10 were proven histologically. The others were diagnosed clinically and angiographically. With one exception, all patients who had triple tracer scintigraphy showed a specific pattern of findings: (1) cold defects with TcSC; (2) Ga‐avid foci, and (3) increased vascular supply from hepatic arteries. One false‐positive study and one false‐negative study were originally reported, although in both cases, strict adherence to the three criteria above would have avoided diagnostic error. These results indicate that triple tracer scintigraphy may be an effective diagnostic test for HCC. The relative efficacy of scintigraphy, ultrasonography, and computerized tomography in diagnosing HCC is also discussed.

Alteration of Lipid Metabolism Associated with Renal Adenocarcinoma in the Wistar-Lewis Rat

Tumor bearing has been associated with a number of metabolic and biochemical alterations in man and animals. Recent studies have shown that Fischer rats bearing methylcholanthrene-induced sarcomas display elevations of plasma cholesterol and triglyceride levels. We investigated Wistar-Lewis rats bearing a transplantable, spontaneously arising renal adenocarcinoma histologically similar to human clear cell carcinoma of the kidney to determine whether similar metabolic derangements could be demonstrated. Baseline fasting levels of triglyceride and cholesterol were established in nontumor-bearing control rats. The presence of tumor implanted either subcutaneously in the flank or grown subcapsularly within the kidney resulted in a 20 to 25-fold elevation in circulating triglyceride. Following complete excision of implanted tumor, triglyceride levels returned to baseline.

Surgical treatment of low grade soft tissue sarcomas

Nineteen patients who have undergone surgical resection of low grade soft tissue sarcomas were retrospectively reviewed. Four patients received additional radiation therapy, and 15 did not. Of the 15 patients treated by surgery alone, 4 had positive margins in the original specimen; all 4 had local recurrence within a mean of 42 months. Eleven patients had negative margins. Ten have had no recurrence in a mean of 40 months. One patient had local recurrence at 36 months. Two of the four patients with positive margins were reoperated on and in achieving negative margins have remained disease-free a mean of 84 months. Three patients receiving additional postoperative radiation therapy had positive margins, and all had recurrence in a mean of 36 months. One patient with negative margins who also received radiation therapy is disease-free at 144 months. It appears that tumor-positive margins are associated with a high likelihood of local recurrence, whereas negative margins appear associated with a long disease-free interval and possible cure. Radiation therapy to positive margins did not prevent local recurrence.

Hyperlipidemia in tumor-bearing rats

Hyperlipidemia occurs in animals bearing tumors but the mechanism of its development is uncertain. We have measured triacylglycerol clearance and production rate in rats bearing a transplantable sarcoma. The plasma content of very-low-density lipoprotein triacylglycerol was increased in these tumor-bearing rats but our data excluded a primary clearance defect because the rate of triacylglycerol accumulation (mg/min) after Triton injection was equal to or greater than in normal control rats, except in cachectic rats with very large tumors. The fractional clearance of injected radioactive triacylglycerols was less in tumor-bearing rats than in controls, but the turnover (mg/min) was probably not decreased in the tumor-bearing rats because of their expanded plasma pool. Also inconsistent with a decreased turnover was our finding of a greater production of radioactive plasma triacylglycerols after injection of a tracer dose of radioactive free fatty acid, and unchanged production in Triton-treated rats. Therefore, in the fasted state, the hyperlipidemia of the tumor-bearing rats was associated with an unchanged or possibly an increased flux of hepatic triacylglycerols and a primary clearance defect was excluded. After fat-feeding, rats with tumors developed a higher post-prandial hyperlipidemia than control rats. Therefore, the clearance mechanism for the plasma triacylglycerols was close to saturation in the fasted state, and the added influx of exogenous triacylglycerols was removed less efficiently in the tumor-bearing rats.