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The risk of developing a second cancer among white and black females with an initial cancer of the uterine cervix or corpus has been estimated based on the experience of the Charity Hospital of Louisiana Tumor Registry, a participant of the End Results Program of the National Cancer Institute. Observed second primary cancers were compared to expected numbers in order to obtain a direct estimate of risk. White females having an initial cancer of the cervix had a 5-to-6-fold excess risk of developing a subsequent cancer of the oral pharynx, lung, or bladder during the first 5 years following their initial cancer with no excess risk during subsequent years. Black females with cervical cancer had a 3.5-fold excess risk for developing oral cavity and lung cancer. There was no excess risk for developing subsequent cancer of the breast or large intestine, but a slight excess risk for developing subsequent cancer of the ano-rectum. There was a 7% excess risk among both whites and blacks with initial cancer of the corpus uteri of subsequently developing another cancer.

Objective The authors present their 35-year experience with intra-arterial chemotherapeutic regional perfusion of 1139 patients with melanomas, using an extracorporeal oxygenated circuit and heart-lung apparatus. Summary Background Data Intra-arterial chemotherapy produces improved responses in many tumors. By isolating and sustaining the area with extracorporeal oxygenated circulation, high doses can be delivered to the tumor area, limited only by local toxicity. Drug levels up to 10 times those achieved by systemic administration are obtained. Methods Techniques for hyperthermic perfusion were developed for limbs, pelvis, head, neck, and skin of the breast. Melphalan (Burroughs Wellcome, Research Triangle Park, NC) was used in 753 patients. Combinations with melphalan or other drugs were used in remaining cases at temperature of 38 to 40 C for 30 to 60 minutes. Results Chemotherapy perfusion followed by tumor excision or node dissection, was performed where indicated. The cumulative 10-year survival for patients with localized melanomas was 70%. For patients with local recurrences or satellites within 3 cm, survival was 61%. For those with regionally confined intransit tumors, survival was 30%; for those with regional node involvement, 38%; for those with intransit and nodal metastases, 16%; for those with distant metastases and perfusion—mainly to save functional limbs–survival was 7%. Multiple perfusions were performed in 158 patients with recurrent disease on 366 occasions. Patients with Indolent regionally confined melanomas were benefited by prolongation of useful life. Conclusions Safe perfusion techniques are available for most anatomic regions. Increased chemotherapeutic doses are delivered to isolated areas limited only by local toxicity. Adjunct perfusion in poor prognosis stage I cases is useful in reducing local recurrence, and intransit or lymph node metastases. Regional perfusion reduces the need for major amputation. Multiple perfusion can be useful in treating recurrent chronic melanoma.

Background: Malignant melanoma (MM) is often reported as the third most common cause of intracranial metastasis (IM) after carcinoma of the breast and lung. Most patients with advanced MM will have widespread extracranial disease, but the majority will die from intracerebral spread. Methods: A retrospective review of 117 patients with documented IM from MM over the past 25 years was undertaken. Various factors (including age, race, sex distribution, primary lesions with Clark's level, Breslow's thickness, primary sites and staging at initial presentation, diagnosis of IM and its various treatment methods, survival data, and autopsy findings) were analyzed. Prognostic indicators were clarified from this analysis as a predictor of central nervous system (CNS) metastasis. An ideal treatment plan was also analyzed in order to predict a better survival. Results: Fifty-eight percent of patients were male; 42% were female. Seventy-one percent of the primary lesions were of Clark's level IV and V, with mean Breslow's thickness of 3.5 mm. Median time interval between the initial diagnosis and development of IM was 3.5 years. Complete surgical resection of the intracranial lesion in the brain resulted in the longest mean survival of 10.3 months, whereas mean survival for the group with no treatment was only 3 weeks. Patients with primary lesions of the head and neck had the lowest mean survival of 3.3 months, whereas those whose primary sites were unknown had the longest mean survival of 7.5 months. One- and 2-year survival were 9% and 3%, respectively. All but one of the 30 patients at autopsy were found to have visceral metastasis, namely of the lung, liver, and bone. Conclusion: An aggressive search for metastasis should be undertaken in patients at high risk of developing CNS metastasis, e.g., male, head and neck primary, Clark's level IV and V, Breslow's thickness of >3 mm, and presence of visceral metastases, mainly lung. A complete surgical resection should be attempted whenever possible, with adjunctive use of whole-brain irradiation, along with systemic chemotherapy for further control of recurrence and to prolong survival.

Purpose: This study is to document the activity and acceptability for a new topical agent, A-007, in the treatment of cutaneous metastases from cancer. Patients and methods: This is a multicenter study involving 27 patients with inoperable skin lesions from histologically confirmed cancers of the breast and oral cavity, non-Hodgkin’s lymphoma, Kaposi’s sarcoma, and angiosarcoma that had failed radiotherapy or systemic treatment. A-007, as a 0.25% gel, was applied twice daily to the areas of cancer to be measured as well as applied to a healthy control area distant from the cancer areas. An untreated cancer area was also included and documented as a cancer control. Results: The overall objected response rate with A-007 was 26%, with an additional 19% minimum response/stabilization of cancer. For patients with breast cancer, hormonal status did not have an impact on response. The median duration of response was 15 weeks (with one patient having a response for 3.5 years). Toxicities observed were itching, burning, and a rash, in 6 of the 27 patients. The skin toxicities were in the cancer-treated fields; none were observed in the A-007 control areas. All irritated areas cleared while continuing treatment, and the tumor lesions in the areas of itching also improved. Conclusion: A-007, as a 0.25% gel, is confirmed as an effective palliative treatment option for cutaneous metastases from cancers. Skin reactions were minimal, tolerated, and no cessation of treatment was required.

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.

From 1957 to 1992, 1139 patients had regional perfusion alone, or combined with excisional surgery for malignant melanoma. Of these, 158 patients had multiple perfusions for recurrent disease, including 155 for limb melanoma and three for head and neck melanoma. One-hundred-and-twenty patients were perfused twice, 28 treated three times, eight treated four times, and two treated five times. At first perfusion, 39 patients were classified as disease stages I and II, 98 at stage III, and 21 at stage IV. Melphalan was used in 70% of perfusions, either alone or in combination. Nitrogen mustard was used sparingly in only a few patients. Fifty-one patients with stage III disease had the greatest number of perfusions (127). Cumulative survival from date of first perfusion at 5 and 10 years were: stage 1,68 and 36%; stage IIIA, 25 and 16%; stage IIIB, 32 and 10%; stage IIIAB, 29 and 11% and stage IV, 14 and 0%. When compared with the entire series, the percent survival was decreased by 2 to 3 times, however, 21 patients remain alive and disease-free. For stages I and II, patients are alive and disease-free from 5 to 33 years. For stage IIIA, 6 patients were alive at the last follow-up, however, the status of two are currently unknown. For stage IIIB survival times range from 8 to 106 months with two patients alive without recurrence. For stage IIIAB, two patients are alive and disease-free at 15 and 26 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Patients with advanced renal cell carcinoma, previously failed maximal treatment with standard chemo-hormonal-radiation therapies, were treated with plant lectin phytohemagglutinin (PHA)-stimulated autologous peripheral blood lymphocytes in a 10-year study with a 16-year follow up period. In a phase I-II setting, 52 patients were given subcutaneously 40-80 x 10(6) PHA-stimulated lymphocytes weekly for 3 weeks and then escalated to a maximum number of 80 x 10(9) lymphocytes over the next 9 weeks at 3 week intervals. In vitro blastogenesis under study conditions (10 micrograms/ml PHA for 72 hr) measured by [3H]thymidine uptake was optimal with lymphocyte stimulating indexes approaching 300. Lymphocytes obtained from patients with breast cancer, melanoma and renal cell carcinoma responded to PHA similarly to those from normal volunteers. All patients that responded developed erythematous reactions at the sites of injection; malaise, joint paint and chill-fever for 24-48 hr. The patients that responded the best were those with at least 1 positive reaction out of 4 skin tests (tuberculosis, yeast, dermatophytin, mumps) prior to therapy. All toxicity was transient and did not exceed Grade I based on criteria of the Southwest Oncology Group. The majority of patients developed a lymphopenia in the first 24 hr followed by a lymphocytosis 48-72 hr later. For some patients the lymphocytosis was as much as 30% atypical lymphocytes. Of 41 evaluable patients, there were 5 complete responses, 8 partial responses, 3 stable diseases, and 25 progressive disease. The overall response rate was 32% and the median survival was 2.8 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Between 1958 and 1990, 82 patients with acral lentiginous melanoma were treated by the Tulane Surgical Service with regional perfusion, excision of lesion, and lymph node dissection. The patient group comprised 27 white men, 29 white women, 18 black men, and 8 black women, with an average age of 61 years. More foot lesions than hand lesions were reported, and all the black men had foot lesions. In stage I patients, overall 5-year survival rates were 65% at 5 years and 44% at 10 years, with differences by race and gender. The black men did poorest, with a 13% 10-year survival rate. Survival rates were worse with increasing disease stage when calculated using univariate analysis. The 5-year survival rate of all patients with stage III and stage IV disease was 26%. A multivariate analysis was performed in 78 of 82 patients in whom all variables of Clark's level, age, race, stage, and sex were known. A strong relationship was observed between decreasing survival time and increasing Clark's level, with stage of marginal significance. In a multivariate analysis of patients with stage I disease, an increasing level of invasion was found to be significant, with a trend for a relationship to thickness. A trend toward decreased survival time was observed in men and blacks.

• The regional delivery of high-dose chemotherapy for malignant neoplasms of the limb with the isolated regional perfusion technique was first described in the late 1950s. Recently, the use of concomitant hemofiltration for rapid systemic drug removal permits the use of higher regional drug levels in treating patients with advanced abdominal malignant neoplasms without complete vascular isolation. Twenty-five patients successfully underwent 42 treatments of high-dose intra-arterial chemotherapy with concomitant hemofiltration at Tulane University Medical Center Hospital, New Orleans, La, from 1989 through 1990. One patient (4%) achieved a complete response. Two patients (8%) had partial responses following high-dose intra-arterial chemotherapy with concomitant hemofiltration and their residual disease was resected for cure. Seven patients (28%) achieved a partial response, 11 (44%) had stable disease, and four (16%) had progression of disease. (Arch Surg.1991;126:1390-1396)

Soft tissue sarcomas are relatively rare tumors. Each year in the U.S., there are approximately 5,500 new cases and 2,900 deaths attributed to these tumors [1,2]. Approximately 60% of these tumors develop in the extremities.

High-dose intra-arterial chemotherapy with concomitant hemofiltration (HICCH) has potential usefulness in the pre-operative or perioperative setting of treating patients with advanced intra-abdominal or intra-thoracic malignancies. Using high-dose intra-arterial chemotherapy together with concomitant hemofiltration, the effluent blood from a tumor-bearing region can be rapidly cleared of the peak chemotherapeutic drug level. This allows then the delivery of higher drug doses to a regionally confined malignancy. The use of this type of system was originally defined by Dedrick et al [1] for the treatment of patients with primary brain tumors. Aigner et al and Muchmore et al have investigated similar systems for patients with advanced intra-abdominal malignancies [2, 3]. In a group of 25 patients with advanced intra-abdominal and intra-thoracic malignancies, some have successfully undergone 40 treatments with high-dose regional chemotherapy plus concomitant hemofiltration at the Tulane Medical Center Hospital.

Thirty-one patients with subungual melanoma representing 2.6 per cent of all patients with limb melanoma were treated by isolated regional perfusion. Acral lentiginous melanoma prevalent on subungual and volar skin was the most common histologic type. The subungual lesions primarily occurred on the lower limbs (61%) and great toe (48%). At diagnosis, most patients had advanced disease; 53 per cent of stage I patients had lesions with level IV invasion or greater. The median thickness of the primary lesion was 2.35 mm. All patients were treated by isolated regional perfusion and amputation of the involved digit, as well as regional lymph-node dissection where clinically indicated. The mean survival rate for all stages at five years was 35 per cent. Patients with stage I disease had the best survival rates, 61 per cent at five years and 54 per cent at ten years; however, patients with advanced disease, stage III (M.D. Anderson classification), had only a 17 per cent survival rate at five years and 8 per cent at 10 years. Women had slightly better survival rates than men, and patients with upper-limb lesions had the better prognosis.

From 1976 to 1980, 377 randomized patients were entered in a multicentric study supported by the W.H.O. Melanoma Group. In this report, only 196 patients are considered for analysis: 31.6 % were excluded because of inadequate treatment or protocol violations. Three arms of treatment were compared: DTIC alone, DTIC plus bacillus Calmette-Guérin, and DTIC plus Corynebacterium parvum. No significant difference in terms of complete response plus partial response was detected among the three regimens. Twenty-five patients (12.7 %) responded with complete tumor regression, and 18 (9.3 %) with partial regression. Complete plus partial responses were thus achieved in 22 % of evaluable patients. Responders had a longer median survival than nonresponders. Overall median survival was 6 months. Brain metastases were detected in 17 % of the patients. Median time from the beginning of treatment to the diagnosis of CNS involvement was 4 months. There is no evidence that active aspecific immunotherapy added to DTIC increases the response rate in patients with disseminated disease. The toxic effects were acceptable, and no drug-related death was observed.

Three hundred thirty-one women with metastatic breast cancer were randomized to receive combination chemotherapy with either cyclophosphamide, Novantrone (mitoxantrone; Lederle Laboratories, Wayne, NJ), and fluorouracil (CNF) or cyclophosphamide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and fluorouracil (CAF). Patients could not have had prior chemotherapy, although adjuvant chemotherapy was acceptable. Initial doses were 500 mg/m2 of cyclophosphamide and 500 mg/m2 of fluorouracil with either 10 mg/m2 of mitoxantrone or 50 mg/m2 of doxorubicin, administered intravenously (IV) on day 1 and repeated every 3 weeks. There were no statistically significant differences in pretreatment or prior therapy characteristics between the groups. For patients assigned to the CNF and CAF groups, respectively, 25 (18%) were premenopausal, 39 (40%) were estrogen receptor (ER) negative, 39 (38%) had a disease-free interval less than 1 year, and 24 (26%) had received prior adjuvant chemotherapy. All patients were compared for response rate, duration of response, time to progression or death, time to treatment failure (TTF), and survival. None of these parameters were statistically significant favoring one regimen over the other. The response rate (complete [CR] and partial response [PR]) was 29% for the CNF group (95% confidence interval of 22% to 37%) and 37% for the CAF group (95% confidence interval of 29% to 45%). The median response duration and TTF were 171 days and 125 days for the CNF group and 254 days and 147 days for the CAF group, respectively. The median survival times for the CNF group and the CAF group were 377 and 385 days, respectively. The major dose-limiting toxicity for both regimens was leukopenia, manifested as granulocytopenia. The incidence of stomatitis/mucositis was 10% in the CNF group and 19% in the CAF group. Alopecia occurred in 49% of CNF patients (severely for 4%) and in 86% of CAF patients (severely for 39%). Nausea/vomiting occurred in 80% of CNF patients and in 81% of CAF patients; the degree of severity was also comparable. There was significantly less cardiotoxicity observed in the CNF group compared with the CAF group. Although CNF is somewhat less effective in overall response rate, survival curves are identical. CNF can be offered to patients who reject anthracycline-containing regimens because of fear of alopecia.

Metastatic involvement of the gallbladder in melanoma is rare, but constitutes the most common metastatic lesion involving this organ. Two cases of metastatic melanoma to the gallbladder with radiographic evidence of gallbladder abnormality prior to surgery are presented. These cases are compared to the nine previously reported cases of metastatic melanoma to the gallbladder with abnormal cholecystograms. All eleven cases presented with signs and symptoms compatible with cholecystitis. Nine of the eleven patients had a previous melanoma primary and most had other extrabiliary metastases. Associated cholelithiasis appeared to be only incidental. In addition, nine reported cases of "primary" biliary melanoma were reviewed. Clinical and pathologic presentations in the latter cases were similar to the former cases with metastases. Seventy-eight percent had extrabiliary sites of metastasis at some time in the course of their disease, tending to refute the impression of "primary" biliary melanoma. Melanoma in the gallbladder is much more likely to have metastasized from a regressed skin primary than to have arisen de novo. The two reported cases and the 18 cases from the literature indicate that the physician must consider gallbladder metastasis in melanoma patients presenting with symptoms compatible with cholecystitis.

The results of three Phase III studies of DTIC in 580 patients with metastatic melanoma were reviewed to evaluate the subsequent course of 26 patients who achieved a complete response (CR) to chemotherapy. The majority (17 of 26) of these patients had soft tissue metastases. Six of the 26 patients remained in CR at last report (30-259 weeks), two died of other causes while remaining free of melanoma, and 18 relapsed and died. Ninety-five percent of the 26 patients were alive at 1 year, and survival was 31.1% at 72 months. Seven of the eight patients with sustained remission received chemotherapy for at least 6 months after CR developed, whereas 10 of 18 relapsing patients were treated for less than 6 months after CR was achieved. Long-term sustained CR to chemotherapy occurs in 1% to 2% of patients treated with DTIC, and late relapse is rare in patients who remain in CR for 2 years.

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.

A prospectively randomized study of postoperative chemotherapy with dimethyl triazeno imidazole carboxamide (DTIC) was conducted by the Central Oncology Group from 1972 until 1976. Of 174 patients operated upon for melanoma and entered into the study, 87 were randomly selected to receive DTIC, four courses in 12 months, at 4.5 mg/kg/d x 10. One-hundred-sixty-five (95%) of the cases were evaluable, including 40 high risk Stage I, 96 Stage II, and 29 Stage III cases. At a median follow-up period of 2.5 years, the control group had a better median disease-free interval (40 weeks vs. 73 weeks), median survival time (103 weeks vs. 133 weeks), and percentage of patients living free of disease (28% vs. 44%) than the DTIC-treated group. While disease-free interval appeared to be improved in the 25% of patients on DTIC therapy who developed thrombocytopenia, the overall effect of postoperative DTIC therapy was apparently not beneficial (P less than 0.05).

From 1957 to 1975, 113 patients with sarcoma of the extremities have been treated with chemotherapy by regional perfusion, either alone or as an adjunct to excisional surgery. Perfusion alone in 54 patients was associated with an early response rate of 83%, but only four patients had complete regression of tumor for longer than three months. When perfusion was followed by immediate or delayed excision, better results were obtained. In 49 Stage I patients and in 24 Stage II patients, cumulative survivals of 66% and 59% were obtained at five years and 66% and 51% at 10 years. The procedure has also been useful in saving functional limbs by converting tumors to operability, and in the palliation of pain and ulceration.

Acral lentiginous melanoma (ALM) is the fourth clinicopathologic variant of malignant melanoma. It occurs on volar surfaces of hands and feet, subungual sites, and fingers or toes. It is characterized by slow lentiginous radial growth and central plaque-like thickening, heavily pigmented tumor cells, markedly thickened papillary dermis, and diffuse reticular infiltration. Lesions are unusually large and, in most cases, thick and ulcerated. There were 180 patients with acral melanoma (AM), which includes 67 in whom the specific features of ALM could be documented. One hundren sixty had primary lesions on ;the foot, and 20 occurred on the hand. There were 104 men and 76 women. There were 41 black patients and 139 whites. Five-year survivals following all modalities of therapy in 122 patients with Stage I acral melanoma is 63% for planter/palmar lesions, 58% for subungual lesions, and 27% for skin of digits. For the subgroup of Stage I patients with ALM treated by surgery and regional chemotherapy by perfusion, the five-year survival for all sites is 72% and 56% at 10 and 15 years, respectively. Survival in ALM is essentially the same as for all AM lesions.

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.

Three patients with biopsy-proven lentigo maligna were treated with topical 5-fluorouracil. Treatment consisted of twice daily application of 5% 5-fluorouracil cream for 13, 6, and 9 weeks, respectively. Two patients demonstrated presence of invasive melanoma; in one the melanoma was evident before chemotherapy, and in the other the lesion became evident after chemotherapy. In both the lentigo was treated topically and the melanoma excised locally. Posttreatment followup times through April 1, 1974 have been 42, 24, and 22 months, respectively. There has been no evidence of metastases in any patient. Topical chemotherapy with 5-fluorouracil cream appears to offer an encouraging alternative method of therapy for lentigo maligna of the face.

Common human melanoma membrane antigens have been demonstrated by immunofluorescent microscopy in cultured melanoma cells using antisera raised in humans by autoimmunization of patients with their own irradiated tumor cells mixed with adjuvant BCG. The melanoma antigens will migrate, cap, and become extruded on the cell surface when they are treated with the postimmune anti-melanoma sera. Some of these antigens are spontaneously shed into the culture media even without added antibody. Those shed antigens are stable to dialysis and lyophilization and may be isolated from a Sephadex G-200 solumn along with proteins of molecular weight 80,000–150,000 by membrane fluorescence inhibition and micro-complement fixation. Further purification of such antigens may facilitate the development of radio or enzymoimmunoassay which will permit sensitive measurement of antigens in melanoma patients.

In an effort to identify new trends in the presentation and treatment of primary hyperparathyroidism, 66 patients treated since 1975 were compared with 100 patients diagnosed and treated from 1948 to 1970. Despite widespread use of multichannel analyzers, the late patients had an insignificant increase in diagnosis while asymptomatic (18 percent versus 9 percent in the early group). Hypertension was the most common presenting complaint in patients seen since 1975, compared with renal disease in patients seen before 1970. Findings of diffuse hyperplasia were more common in the late patients (17 percent versus 3 percent in the early patients). There were no differences in rates of operative complications or persistent postoperative hypercalcemia. In the late series of patients persistent hypercalcemia after surgery for hyperplasia was due to inadequate resection of parathyroid tissue. In the adenoma patients, failure to locate the abnormal parathyroid gland was the cause of operative failure.

(1985). Clinical Science Review: Regional Perfusion for Malignant Melanoma and Soft Tissue Sarcoma: A Review. Cancer Investigation: Vol. 3, No. 2, pp. 129-143.

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.

Malignant melanoma in the American Black is an uncommon disease. Scattered reports have appeared in the literature indicating a somewhat different behavior and distribution from melanoma in the White patient. The last published report prior to the organization of the Tumor Registry at Charity Hospital of Louisiana on melanoma in the Black was in 1948 by Muelling when 28 cases were reported. From 1948 through 1974, 96 additional patients have been recorded in the Charity Hospital Registry which represents the largest reported experience in the American Literature. The average age at diagnosis is 57.8 years as opposed to 53 years for White patients observed over the same time period. The ratio by sex is essentially equal in Blacks. The disease usually presents on the palmar or plantar surfaces of the hands or feet in the Black. In the registry data 51% occurred on the lower limb, 11% on the upper limb, 6% on the trunk, 6% on the genitalia, 1% on the head or neck, 13% were of extradermal origin, and 10% had unknown primary sites. The 5-year cumulative survival for all Black patients in this series is 27%. In contrast to the poor overall survival, a 78% 5-year survival has been achieved in Stage I patients treated with perfusion, wide excision, and regional lymph node dissection.

1. 1. Tumour arylsulphatase and DOPA oxidase activities from patients with malignant melanomas were measured and correlated with the degree of pigmentation. 2. 2. Liver arylsulphatase activities from poikilothermic vertebrates were measured and correlated with the liver melanin pigment cell cycle. 3. 3. A direct relationship was suggested between liver pigment content and arylsulphatase.