Decision in the management of cutaneous malignant melanoma.

Eighty-five percent of the cases of cutaneous malignant melanoma can be identified during a biological stage in which they are incapable of producing metastases and can be cured by surgical excision, alone. Recognition of these cases has major impact for potentially improving survival in this neoplastic system. Once recognized, excisional biopsy of the primary melanoma enables the pathologist to accurately microstage these tumors. The role of surgery, both for the primary site and the regional lymph nodes, continues to undergo refinement as additional information regarding the biology of melanoma becomes available. Adjuvant chemotherapy and/or immunotherapy remains investigational, at present, and awaits the demonstration of its clinical value.

The surgical therapy of malignant melanomas.

Survival from malignant melanoma has been serially followed over a long period of time. A summation of this information is seen in Table 5. The steadily improving 5- and 10-yr disease-free intervals in stage I disease probably represents a combination of increased awareness of early lesions and the application of aggressive, initial surgical treatment. The ominous and essentially unchanged prognosis in stage II disease reinforces this goal. Suspicion and gross recognition of early melanoma is essential. Adequate biopsy with the appropriate classification provides the surgeon with insight into the correct therapy. This usually entails wide, three-dimensional excision and wound closure by free skin-grafting. Regional lymphadenectomy is performed whenever anatomical and microscopic conditions dictate the need. The roles of amputation, regional perfusion, and adjuvant therapy require clarification. Studies are being pursued to provide firm data concerning the value of these methods.

Fatty acid synthesis by human adipose tissue.

The effect of age and nutritional status on the synthesis of fatty acids from a variety of labeled substrates by human adipose tissue in vitro was investigated. The results of this study clearly demonstrate that, although human adipose tissue is able to oxidize glucose to CO2, its ability to incorporate glucose-carbon into long chain fatty acids is negligible. Although the utilization of acetate for the synthesis of fatty acids by adipose tissue is substantial in the presence of glucose and insulin, its physiologic significance in human under normal dietary conditions is questionable. That the capacity of human adipose tissue is limited is further supported by (1) a negligible incorporation of pyruvate-3-14C (up to 25 mM concentration in the incubation medium) into fatty acids, (2) a lack of stimulation in lipogenesis by human adipose tissue after refeeding a diet high in carbohydrate and very low in fat to a previously starved human, and (3) an extremely low activity of pyruvate carboxylase and ATP-citrate lyase in adipose tissues from humans of varying ages. The activities of other key lipogenic enzymes, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and NADP-malate dehydrogenase, are also low. These enzymes can be stimulated in human adipose tissue after a fasting-refeeding regimen. The activity of phosphoenolpyruvate carboxykinase is also very low in human adipose tissue,and it is suggested that a pathway of glyceroneogenesis may not play a significant role in human adipose tissue. In light of our results, together with previous reports, it is possible to conclude that the capacity of human adipose tissue to utilize a dietary carbohydrate for the synthesis of fatty acids is extremely low and that the liver plays a major role in the biosynthesis of endogenous fatty acids from dietary carbohydrate in the human.

The biology of human malignant melanoma. Preliminary findings in the nude mouse.

The nude mouse model was explored as a means of predicting the behavior of human cutaneous malignant melanoma. Subcutaneous implants from 20 patients were observed for external growth, microscopic appearance, and autoradiographic analyses following tritiated thymidine labeling. Normal epithelial and dermal components were maintained in the six low-risk primary implants, but none had any external growth or tumor cell preservation. Four of the five metastatic implants grew throughout the observation periods, with 30% of the counted tumor cells taking up the radioisotope. There was a slower growth rate in four of nine high-risk primary implants, with tumor cell preservation in eight. Only 6% of the counted tumor cells incorporated tritiated thymidine. This model appears to be capable of discriminating among the behavior of various forms of human malignant melanoma.

Narrowing resection margins for patients with low-risk melanoma.

Surgeons hesitate to accept lesser cancer operations for several reasons. Paramount, however, is the fear that they might jeopardize cure rates by inadvertently leaving residual tumor behind. In cutaneous melanoma, for example, wide excision of the primary tumor site, usually in combination with skin grafting, has been the standard for years. Recently, as the biologic characteristics of this neoplastic system have become better understood, a subset of patients has been identified who can be cured readily by surgical excision alone. It is in this low-risk group of patients that lesser margins of excisions have been advocated. To date, a majority of surgeons have not accepted this thesis. In an effort to study this further, one of us prospectively treated 45 patients with thin, low-risk melanomas by conservative excision of their primary tumor sites. The margins invariably were 2 cm or less, and two thirds of the patients were operated on as out-patients utilizing local anesthesia. After a mean follow-up period of 36 months, no recurrences of melanoma developed. Acceptance of this treatment appears appropriate in this subset of patients.

Optimal resection margin for cutaneous malignant melanoma.

Cutaneous malignant melanoma has traditionally been treated by "wide" local excision with a 5-cm margin of normal skin about the tumor. The rationale of wide excision for melanoma has never been clearly defined, but the procedure is known to be effective in preventing local recurrence. We studied 105 patients who had 109 primary melanomas in 1977 and related margin width of the definitive excision to the presence of satellites, to the subsequent development of local recurrence and in-transit metastases, and to survival. Survival was not dependent on margin width, and there were no incidences of local recurrence. Satellitosis and in-transit cutaneous metastasis indicate that a melanoma is capable of local recurrence; these phenomena occurred only in tumors whose thickness (Breslow) was greater than 2.0 mm. These data provide a rationale for wide excision of "thick" melanomas and support more modest local therapy for thin cutaneous melanoma.

The treatment of malignant melanoma of the skin.

This review of 117 melanomas occurring in 115 patients treated by a single surgeon suggests the appropriateness of the therapeutic decisions to be mentioned based upon tumor behavior, determined by microstaging. Local control of level II lentigo maligna melanoma was achieved, in most instances, by local excision with visibly free margins and primary closure. In most of the other instances of melanoma, adequate local control was accomplished by wide three-dimensional excision, 5 centimeter margins--closure usually required grafting. Minor amputation was performed with satisfactory results in those patients with appropriate lesions in the volar-subungual area. Regional lymphadenectomy in patients with level IV and V disease in whom the tumors drained to a single node basin revealed occult metastases in 25 per cent of the patients and, therefore, appears warranted as prophylactic treatment. Preliminary data on recurrences suggest that the frequency of the recurrence paralleled the biologic aggressiveness of the tumor, determined by microstaging in association with the presence or the absence of lymph node metastases.

Hemoccult screening in selected patients.

One hundred patients, asymptomatic relative to gastrointestinal disease, who applied for elective hernia repair were tested as outpatients for occult blood in the stool. Twenty-six had one or more positive specimens. Among this group colonic disease was found in seven, including adenocarcinoma (Dukes' stage A) in one, adenomatous polyps in three, and colonic diverticula in the remainder. The unexpectedly high false-positive rate (33%) was reduced markedly by giving a meat-free diet before stool collection. Patient compliance was excellent and the cost-benefit ratio appeared to be acceptable.

Interval cholecystectomy: an appraisal.

Interval cholecystectomy (IC), the removal of a diseased gallbladder after drainage for acute infection, is considered an appropriate procedure in suitable patients. While increased technical problems can be expected, other potentially serious complications are frequently overlooked. This review, prompted by difficulties during IC, compares multiple parameters (eg, technical difficulties, morbidity, postoperative convalescence) between this group and "routine" gallbladder operations (RC). During the period between 1970 and 1979, 224 patients with gallbladder disease were operated upon at this Veterans Administration Medical Center. Included among these were seven patients who required cholecystostomy, five of whom were treated by subsequent IC. When compared to the RC group, IC was usually done in older patients and was technically more difficult, as evidenced by longer operating times and increased operative blood loss. In addition, this group's postoperative convalescent period was significantly prolonged because of an increased rate of complications, wound infections being the most common. These were believed to be responsible for the two deaths in this group (the only deaths in the entire RC-IC group.

Screening for occult blood in selected patients. The potential for false-negatives.

Seventy-one patients presenting for elective hernia repair without gastrointestinal symptoms were screened for occult blood in their stools. All patients had stools negative for occult blood and were studied with proctosigmoidoscopy and barium enema. Polyps were found in 10% of the study population. The potential for missing polyps definitely exists if patients are selected for further studies only on the basis of tests for occult stool blood.

Nonocclusive ischemic colitis secondary to hemorrhagic shock.

A young male with a penetrating chest wound suffered modest and transitory hemorrhagic shock. Nonocclusive right-sided ischemic colonic necrosis developed secondarily. This became obvious on serial follow-up examinations, prompting exploration and curative surgical resection. This case represents ischemic colitis secondary to hemorrhagic shock following trauma. Upon review of the literature, only five other such cases have been reported. Although shock-associated ischemic colitis is well documented, it is extremely uncommon to see gangrenous changes of the bowel in young, otherwise healthy, trauma victims. Mesenteric vasospasm is believed to be the causative factor in these cases. For unknown reasons, the right colon seems to be the favored site of ischemic damage. Nonocclusive intestinal ischemia should be considered in patients who have abdominal pain after a hypotensive episode.

Hemoccult screening in selected patients. The hernia patient older than age fifty years.

Two hundred and forty patients, asymptomatic relative to gastrointestinal disease, who applied for elective hernia repair, were tested as outpatients for occult blood in the stool. Thirty-eight patients had one or more positive specimens. Significant pathologic characteristics were identified by lower gastrointestinal evaluation in 23 of these patients. One patient had an adenocarcinoma (Dukes' Stage B). Eight patients had polyps of various types, 11 patients had colonic diverticula, and three patients had anorectal disease. Patient compliance was excellent and the cost-benefit ratio appeared to be acceptable.