Carl M. Sutherland

Chemotherapy of sarcomas of the limbs by regional perfusion.

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.

Regional chemotherapy for melanoma. A 35-year experience.

ObjectiveThe 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 DataIntra-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. MethodsTechniques 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. ResultsChemotherapy 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. ConclusionsSafe 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.

Malignant melanoma in the American Black.

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.

Prognostic evaluation of intracranial metastasis in malignant melanoma.

AbstractBackground: 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 Clarks level, Breslows 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 Clarks level IV and V, with mean Breslows 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, Clarks level IV and V, Breslows 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.

Acral lentiginous melanoma

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 lack 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 Clarks level, age, race, stage, and sex were known. A strong relationship was observed between decreasing survival time and increasing Clarks 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.

Evaluation of the worth of Corynebacterium parvum in conjunction with chemotherapy as adjuvant treatment for primary breast cancer: Eight‐year results from the national surgical adjuvant breast and bowel project B‐10

During the 1970s, information obtained from animal tumor models and from patients with a spectrum of solid tumors indicated the worth of a variety of immunostimulating agents. These findings provided a biological and clinical rationale for conducting randomized trials to evaluate the worth of those agents. Consequently, in May 1977 the National Surgical Adjuvant Breast and Bowel Project (NSABP) implemented a randomized trial to determine whether Corynebacterium parvum (C. parvum, CP) plus chemotherapy would be more effective than chemotherapy alone in prolonging the disease‐free survival (DFS) and survival (S) of patients with primary operable breast cancer and positive axillary nodes. The results of that trial through 8 years of follow‐up fail to indicate that treatment with CP used in conjunction with 1‐phenylalanine mustard (L‐PAM) plus 5‐fluorouracil (PF) results in a better DFS and S than that observed after chemotherapy alone. Use of the immunomodulator has instead resulted in a poorer, but not statistically significant, outcome. Despite adjustments made to account for any imbalance in distribution of prognostic factors between the two treatment groups and despite considering treatment compliance as a factor, the unfavorable outcome persisted. A high incidence of fever and chills was associated with the administration of CP. The administration of hydrocortisone before each CP treatment reduced the frequency of those and other systemic effects. The failure to demonstrate a benefit from CP is in keeping with the failure of other nonspecific stimulating agents to contribute to the creation of a new paradigm for the treatment of breast cancer.

Isolated hyperthermia chemotherapy perfusion for limb melanoma.

Safe techniques for regional chemotherapy of the limbs by perfusion are now available. The method is effective in obtaining regionally confined high levels of toxic drugs or chemotherapeutic agents in the isolated areas. The best responses have been observed in limb melanoma with recurrent or intransit disease. Chemotherapy by perfusion as an adjunct to surgical excision reduces the local recurrence and the regional and lymph node metastases. Our survivals for adjunctive perfusion for Stage I melanomas with Level V and lesions 5 mm thick and thicker are better than usually reported. Regional chemotherapy has had an important role in reduction of major amputations for the control of limb melanoma. Multiple chemotherapeutic limb perfusions can further extent survival in patients with recurring melanoma.

Long-term survival and prognostic factors in breast cancer patients with localized (no skin, muscle, or chest wall attachment) disease with and without positive lymph nodes†

Uncertainty exists regarding the magnitude of excess mortality from localized breast cancer at long follow‐up times (>15 years) since diagnosis and regarding the effects of race and age as prognostic factors at all follow‐up times. Long‐term survival was determined in 1141 patients (311 white, 830 black) diagnosed as having localized breast cancer with and without positive axillary lymph nodes, but without any signs of complete or incomplete skin, muscle, or chest wall attachment. Survival curves were estimated by means of actuarial methods; prognostic factors were evaluated with the Coxs regression analysis. Survival from all causes was 62%, 43%, 33%, 25%, and 18% at 5, 10, 15, 20, and 30 years, respectively. Breast cancer‐specific survival was 76%, 65%, 63%, 61%, and 59% at 5, 10, 15, 20, and 30 years, respectively. Breast cancer‐specific hazard rates exceeded those expected in the general population by 119 times, 53 times, 12 times, and 6 times at 0 to 5, 5 to 10, 10 to 20, and 20 to 25 years, respectively. Of the 395 patients enrolled after 1968 who had modified radical or radical surgery, 338 had known number of positive nodes and size of tumor. Breast cancer‐specific survival was significantly increased with: (1) a decreasing number of positive lymph nodes, 0, 1 to 3, and 4 or more (P = 0.000); (2) later year of diagnosis (1974 or before versus 1975 or later) (P = 0.000); and (3), possibly, tumor size of 7.0 cm or less (P = 0.09). When these variables were controlled, no significant association of age at diagnosis or race with breast cancer‐specific survival was found. These data suggest that the number of nodes, year of diagnosis and, possibly, tumor size are important prognostic factors for survival, but race and age are not. Also, excess mortality may exist at late intervals; however, it is small in relation to other causes.

Detection of human melanoma antigens in cell-free supernatants

Abstract 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.

Effect of Different Fixatives on the Localization of Human Melanoma Antigens by Immunofluorescence

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.