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Vaginal melanoma is a rare cancer usually diagnosed as a locally advanced disease. Aggressive surgical management of the primary tumor and local-regional recurrences, combined with the use of adjuvant radiation and chemotherapy, improves disease-free interval and, perhaps, survival times. Techniques of regional chemotherapy allow the delivery of high doses of chemotherapy to the tumor bed, while minimizing systemic toxicities. These treatments can be used to decrease tumor size, render bulky tumors resectable, and decrease the need for radical procedures. Additionally, they may help eradicate clinically inapparent local-regional disease and have a favorable effect on survival times. © 1993 Wiley-Liss, Inc.

Hypothesis: Treatment for melanoma that has metastasized to the supraclavicular nodes should be intensive and use a multimodality approach. Design: Retrospective analysis of clinical records. Setting: Six primary care centers, 2 of which were referral centers. Patients: Eighteen patients diagnosed as having a rare pattern of advanced melanoma metastatic to the clavicular region. Intervention: Combined radiotherapy, chemotherapy, and thorough surgical excision of the affected nodal basins. Main Outcome Measure: Length of survival from time of diagnosis and treatment to time of follow-up. Results: Median survival among the 18 patients was 28 months with a 22% survival rate at 5 years after diagnosis. Among patients who received radiotherapy to the clavicular node basin, mean length of survival was 88.7 months with a 50% 5-year survival rate compared with a mean length of survival of 33.8 months and an 8.3% 5-year survival rate in patients who did not receive radiotherapy (P

PURPOSE Patients with primary cutaneous melanoma > or = 1.5 mm in thickness are at high risk of having regional micrometastases at the time of initial surgical treatment. A phase III international study was designed to evaluate whether prophylactic isolated limb perfusion (ILP) could prevent regional recurrence and influence survival. PATIENTS AND METHODS A total of 832 assessable patients from 16 centers entered the study; 412 were randomized to wide excision (WE) only and 420 to WE plus ILP with melphalan and mild hyperthermia. Median age was 50 years, 68% of patients were female, 79% of melanomas were located on a lower limb, and 47% had a thickness > or = 3 mm. RESULTS Median follow-up duration is 6.4 years. There was a trend for a longer disease-free interval (DFI) after ILP. The difference was significant for patients who did not undergo elective lymph node dissection (ELND). The impact of ILP was clearly on the occurrence-as first site of progression - of in-transit metastases (ITM), which were reduced from 6.6% to 3.3%, and of regional lymph node (RLN) metastases, with a reduction from 16.7% to 12.6%. There was no benefit from ILP in terms of time to distant metastasis or survival. Side effects were higher after ILP, but transient in most patients. There were two amputations for limb toxicity after ILP. CONCLUSION Prophylactic ILP with melphalan cannot be recommended as an adjunct to standard surgery in high-risk primary limb melanoma.

The relationship between breast cancer and radiation treatment for cervical cancer was evaluated in an international study of 953 women who subsequently developed breast cancer and 1,806 matched controls. Radiation doses to the breast (average 0.31 Gy) and ovaries (average 32 Gy) were reconstructed for exposed subjects on the basis of their original radiotherapy records. Overall, 88% of the breast cancer cases and 89% of the controls received radiation treatment [relative risk (RR) = 0.88; 95% confidence interval (CI) = 0.7-1.2]. Among women with intact ovaries (561 cases, 1,037 controls), radiotherapy was linked to a significant 35% reduction in breast cancer risk, attributable in all likelihood to the cessation of ovarian function. Ovarian doses of 6 Gy were sufficient to reduce breast cancer risk but larger doses did not reduce risk further. This saturation-type response is probably due to the killing of a critical number of ovarian cells. Cervical cancer patients without ovaries (145 cases, 284 controls) were analyzed separately because such women are at especially low natural risk for breast cancer development. In theory, any effect of low-dose breast exposure, received incidentally during treatment for cervical cancer, should be more readily detectable. Among women without ovaries, there was a slight increase in breast cancer risk (RR = 1.07; 95% CI = 0.6-2.0), and a suggestion of a dose response with the RR being 1.0, 0.7, 1.5 and 3.1 for breast doses of 0, 0.01-0.24, 0.25-0.49 and 0.50+ Gy, respectively. However, this trend of increasing RR was not statistically significant. If low-dose radiation increases the risk of breast cancer among women over age 40 years, it appears that the risk is much lower than would be predicted from studies of younger women exposed to higher doses.

Sera from patients receiving autologous cell immunization were shown to contain antibody specific for melanoma cells by immunofluorescence, microcomplement fixation, and mixed hemadsorption. These hyperimmune specific sera were used to define antigens shed into tissue culture media from human malignant melanoma cells. When supernatants from cultured melanoma cells were passed over a Sephadex G-200 column, melanoma antigens were found in Peak 2. The active fraction was further purified by carboxymethylcellulose ion exchanger and found in the 0.4 M NaCl gradient. This fraction has been tested in four immunized patients and in one nonimmunized melanoma patient. All five patients developed lymphocytic vasculitis compatible with delayed hypersensitivity reaction. These antigens should be of benefit in studying delayed hypersensitivity in melanoma patients and as potential agents for specific immunotherapy.

The clinical records of 94 patients with regionally advanced melanoma (nodal disease or regional satellites) were reviewed to determine the value of preoperative bone and liver imaging. Of 68 bone scans obtained, none were suggestive of metastases. of 97 liver imaging studies (computed tomography, scintiscan, or sonography) in 88 patients, only two were found to have demonstrable metastases. Liver enzyme elevation was present in both of these patients. Bone and liver imaging in the absence of signs or symptoms of dissemination by history, physical examination, chest x-ray, and enzyme determination for regionally advanced melanoma appears to be of little value unless the patient is involved in a protocol study.

An antiserum to human melanoma antigens was obtained from a melanoma patient after immunization with autologous irradiated cultured melanoma cells and bacillus Calmette-Guerin. Using the microcomplement fixation assay, the antiserum, at a titer of 1/1,800, was noted to bind strongly with 7 of 10 allogeneic cultured human melanoma cells lines. However, using the indirect immunofluorescence test and serum at a much lower titer (1/8), only 3 of the 10 melanoma cell lines were positive. Using both microcomplement fixation and indirect immunofluorescence, no significant reactivity was noted in several nonmelanoma cell lines including Hela, human lung adenocarcinoma, human prostatic carcinoma, WI-38 and VA-13 cell lines. These data suggest that common melanoma membrane antigens exist on 7 of 10 cultured human melanoma cell lines as tested by microcomplement fixation and that this assay is more sensitive than immunofluorescence. These common melanoma membrane antigens may eventually be extracted, purified and used for specific immunodiagnosis and immunotherapy.

This study was designed to study the effect of different fixatives on melanoma antigens by immunofluorescence. Two postautoimmune antimelanoma sera were tested on two human malignant melanoma cell lines fixed with different fixatives by indirect immunofluorescence. Ethanol, methanol, formalin, trichloroacetic acid and acetone gave sharp membrane fluorescence. Minimal to moderate cytoplasmic fluorescence was seen with acetone but none with the others. Formalin gave the highest membrane fluorescent antibody titers at 1/512. Isopentane and isooctane yielded bright cytoplasmic fluorescence. Weak diffuse cytoplasmic fluorescence was seen with glutaraldehyde. Fluorescence was completely abrogated by paraformaldehyde. No fluorescence was seen with four nonimmunized melanoma sera and phosphate-buffered saline when used as controls. It can be concluded that different fluorescent patterns were seen on melanoma cells when different fixatives were used.

This case is presented to describe how an ellipse of skin taken with a pectoralis major musculocutaneous flap can be sewn in a spiral fashion to make a water-tight tube to replace the cervical esophagus. While this case may represent a technical triumph of the use of musculocutaneous flaps, we cannot help but feel it is a hollow victory because of the patient's addiction to cigarettes and alcohol. While constant attention and hard work have kept her alive for 16 years, with four primary cancers of the oral cavity, pharynx, and proximal esophagus, continued use of alcohol and cigarettes (Fig. 7) may well defeat our technical advances.

Malignant melanoma, a visible cutaneous lesion, innocuous and readily curable at inception, but unsightly, painful and usually fatal at advanced stages, continues to attract medical interest far ou...

Eight chimpanzees were immunized, each with a single melanoma cell line. It was found that the serum of only one of the eight chimpanzees showed immunofluorescence with four of the five melanoma cell lines at the membrane surface; but it showed no fluorescence with normal skin fibroblasts, WI-38 cells, HeLa cells, human or monkey kidney cells. With appropriate absorption studies it was found that the antiserum was specific to melanoma cell lines. Trypsinated cells showed bright patchy membrane fluorescence, whereas non-trypsinated cells showed bright full ring fluorescence. The chimpanzee's antibody was C'-fixing IgG. It was concluded that the immunized chimpanzee produced antibody to surface antigen(s) common to four of the five melanoma cell lines tested.