Biomedical subjects
Publications and source records attributed to H C Hoover.
Anorectal melanoma in an uncommon tumor that has a poor prognosis. We present a case of anorectal melanoma and review the literature pertaining to prognosis and treatment. Although no controlled trials of treatment of anorectal melanoma have been done, the evidence suggests that conservative excision confers comparable survival with less morbidity than radical surgery.
There are numerous obstacles to implementing and conducting clinical trials. Patient accrual and the costs of clinical trials are difficult problems for researchers. Additional obstacles to implementing clinical trials are patient-related, physician-related, and nurse-related barriers.
Postinjury metabolism is characterized by breakdown of muscle protein as substrate for energy production and gluconeogenesis and by the resultant loss of lean body mass and weight loss. The branched chain amino acids (BCAAs) which are principally oxidized by the skeletal muscle have been implicated in recent in vitro and in vivo studies as having special anticatabolic and regulating effects in skeletal muscle. We studied the anticatabolic effects of the BCAAs in 35 patients undergoing operative injury of moderate severity. In a prospective randomized and blinded manner patients were infused for five days starting immediately after surgery with either 5% dextrose or 5% dextrose with an amino acid solution containing 22, 35 or 100% BCAAs. All patients survived and there were no major postoperative complications. Mean hospital stay was 17 days for patients receiving amino acids and 19 days for patients receiving 5% dextrose only (p = ns). All three groups receiving amino acid solutions were in nitrogen equilibrium or in a slight positive nitrogen balance, while the group receiving 5% dextrose only was in a mean negative nitrogen balance of 6.6 +/- 0.6 gN/day. The differences between the three groups receiving amino acids were slight and not significant. Weight loss was 2 +/- 0.7 kg in the 5% dextrose group, 1 +/- 0.7 kg in the 22% BCAAs group, 0.5 +/- 0.5 kg in the 35% BCAAs group and the 100% BCAAs group gained 0.4 +/- 1.8 kg. Blood chemistries in the different groups and during the study period remained within normal limits except for ammonia levels rising significantly in the 5% dextrose group and SGOT levels rising in the 22% and 35% BCAA groups. With mild variations the plasma amino acid patterns in all groups were similar to the normal pattern, even in the 100% BCAAs group receiving an unbalanced amino acid solution, suggesting the complete cessation of amino acid efflux from muscle, the muscle depending solely on the exogenous supply of BCAAs to satisfy its metabolic requirements. The results suggest that early nutritional suppport in the postoperative period will result in nitrogen equilibrium and that the infusion of the three BCAAs only in the postoperative state is as effective in preventing muscle catabolism as other more balanced amino acid solutions. In the postinjury state balanced amino acid solutions rich in BCAA may prove beneficial.
A study of warfarin anticoagulation as an adjunct to amputation of osteosarcomas was undertaken after finding dramatic results in experimental systems. Anticoagulation was started 7 days preoperatively, continued during the operation, and for up to six months postoperatively. Three of 21 (14%) non-anticoagulated control patients are alive at 5-11 years. Five of 9 (56%) of the anticoagulated patients remain alive 5-8 years. The presumed mechanism of increased survival is an inhibition of fibrin deposition around circulating tumor cells, thereby preventing their adherence to capillary endothelium to initiate metastasis formation.
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Anticoagulation with warfarin is effective in decreasing experimental metastases, presumably by preventing the fibrin coagulum demonstrated to be necessary for the lodging of tumor cells. To determine the optimal level of anticoagulation for maximal antimetastatic effect, two similar experiments were completed with a methylcholanthrene-induced sarcoma in C57Bl mice. Footpad tumors were produced by tumor cell injection and the mice were divided into four equal groups: control, and groups on 1, 2, and 3 mg. per liter of warfarin, respectively. Control and anticoagulated mice were amputated at the same interval. Three weeks after amputation, all were killed and their metastases were quantitated. Prothrombin times ranged from 10 seconds in the control to 30 seconds in the 3 mg. per liter group. In Experiment 1, there was a significant reduction of pulmonary metastases at all levels of anticoagulation. The controls showed a mean number of 7.7 metastases per mouse, as compared to 2.9 (p less than 0.002) at 1 mg. per liter, 2.1 (p less than 0.0035) at 2 mg. per liter, and 0.7 (p less than 0.002) at 3 mg. per liter. In Experiment 2, the significant effect was found only at the 3 mg. per liter dose, with those mice having 2.3 metastases per mouse as compared with 5.5 in the controls (p less than 0.0001). We conclude that full anticoagulation in the range of 2.5 to 3 times normal is required for a maximal antimetastatic effect.
Improved nitrogen sparing was demonstrated in 20 patients undergoing either head-and-neck operations or abdominal explorations, who were randomized to receive intravenously either 3 per cent amino acids or 5 per cent dextrose. Infusions were started immediately after operation and continued for a minimum of six days. In patients receiving amino acids, as compared with those receiving dextrose, mean cumulative six-day nitrogen losses were significantly lower (42 plus or minus 5 g [S.E.M.] and 74 plus or minus 7 g, respectively--P smaller 0.005), as were serum glucose and insulin levels, but beta-hydroxybutyrate, acetoacetate and blood urea nitrogen were significantly elevated. No adverse effects of the amino acid solution were observed. The presumed mechanism for improved nitrogen sparing is a decrease in serum glucose and insulin levels, allowing greater endogenous fat mobilization and utilization, thus sparing lean body mass.
Of the four major biological mechanisms of cancer spread, hematogenous dissemination is perhaps the most significant, as it usually heralds a fatal outcome for the patient. Recent experimental approaches have shown ways of altering the metastatic process and even totally inhibiting it in some animal models. It appears that these models may be applicable to certain human cancers. To prevent hematogenous metastasis formation the process must be inhibited at any one of four levels: 1) growth of the primary; 2) invasion of vessel walls; 3) release of viable tumor cells; or 4) entrapment and growth in distant organs. Judicious handling of the primary can decrease metastasis by minimizing the shedding of tumor cells. New experimental agents prevent the release of tumor cells from the primary by normalizing the blood vessels of the tumor. Warfarin, heparin, and fibrinolytic agents inhibit the entrapment of circulating tumor cells, presumably by their effect on coagulative mechanisms. A better understanding of the benefits of combined approaches to cancer using chemotherapy, irradiation, and immunotherapy, alone and as adjuncts to surgery, offers new opportunity to study methods of controlling metastatic disease.
Metastasis of metastases was demonstrated experimentally. Mice whose primary tumors were amputated after the development of pulmonary metastases were placed into parabiosis with normal syngeneic partners. Metastases were demonstrated in the nontumor-bearing partners despite their development of passive immunity. Immunizing the nontumor-bearing partner prior to joining into parabiosis was not protective against the formation of metastasis.
The first case of metastatic cystosarcoma phylloides in an adolescent is reported. This case also represents the first reported response of this tumor to chemotherapy and irradiation. This tumor showed an unusually rapid rate of cell division probably making it more susceptible to these agents. The importance of an early diagnosis and definitive excision is stressed.
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