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.

Sequential methotrexate and fluorouracil for the treatment of node-negative breast cancer patients with estrogen receptor-negative tumors: eight-year results from National Surgical Adjuvant Breast and Bowel Project (NSABP) B-13 and first report of findings from NSABP B-19 comparing methotrexate and fluorouracil with conventional cyclophosphamide, methotrexate, and fluorouracil.

PURPOSE: To compare sequential methotrexate (M) and fluorouracil (F) (M-->F) with surgery (National Surgical Adjuvant Breast and Bowel Project [NSABP] B-13) and cyclophosphamide (C), M, and F with M-->F (NSABP B-19), in patients with estrogen receptor (ER)-negative tumors and negative axillary nodes. PATIENTS AND METHODS: A total of 760 patients were randomized to B-13; 1,095 patients with the same eligibility requirements were randomized to B-19. Disease-free survival (DFS), distant disease-free survival (DDFS), and survival were determined using life-table estimates. RESULTS: A significant benefit in overall DFS (74% v 59%; P < .001) was demonstrated at 8 years in all B-13 patients who received M-->F (69% v 56% [P = .006] in those or= 50 years). A survival advantage was evident in older patients (89% v 80%; P = .03). In B-19, through 5 years, an overall DFS advantage (82% v 73%; P < .001) and a borderline survival advantage (88% v 85%; P = .06) were evident with CMF. The DFS (84% v 72%; P < .001) and survival (89% v 84%; P = .04) benefits from CMF were greater in women aged F or CMF after lumpectomy and breast irradiation resulted in a low probability of ipsilateral breast tumor recurrence (IBTR). In B-13, the frequency of IBTR was 2.6% following M-->F versus 13.4% in women treated by lumpectomy; it was 0.6% following CMF in B-19. Toxicity >or= grade 3 was more frequent among CMF patients in B-19. The age-related difference in CMF benefit was not related to amount of drug received. CONCLUSION: M-->F and CMF are effective for node-negative patients with ER-negative tumors. The incidence of local-regional or distant metastases and IBTR decreased after either therapy. The benefit from either therapy was evident in all patients, but the CMF advantage was greater in those F may be used in patients with medical problems that would preclude CMF administration.

Patient characteristics, treatment, and outcome of unknown primary melanoma in the United States for the years 1981 and 1987.

The American College of Surgeons performed a patient care and evaluation study of malignant melanoma for years 1981 and 1987 to determine the presenting symptoms, methods of evaluation, clinical management, and disease outcome. Previous reports on malignant melanoma of the skin, mucous membrane, and eye have been published. This report details the findings for 58 patients with malignant melanoma of an unknown primary diagnosed in 1981 and 87 patients diagnosed in 1987. The total number of patients was relatively small in comparison to all malignant melanoma patients. These patients were younger than the skin, ocular, and mucous membrane melanoma patients. There were significantly more males than females. When the anatomical site of a pathological positive node was known, it most frequently was in the axilla. Surgery, radiation therapy, and chemotherapy were frequently used in treatment of these patients. Although the overall prognosis is poor, some patients will have long term survival, and aggressive therapy should be considered for at least some of these patients.

Patient characteristics, methods of diagnosis, and treatment of mucous membrane melanoma in the United States of America.

BACKGROUND: There is limited information regarding mucous membrane malignant melanoma. STUDY DESIGN: The American College of Surgeons performed a patient care and evaluation study of malignant melanoma for 1981 and 1987 to determine the presenting symptoms, methods of evaluation, clinical management, and disease outcome. Previous reports on malignant melanoma of the skin and ocular melanoma have been prepared. This report details the findings for 60 patients with mucous membrane melanoma diagnosed in 1981 and 97 patients diagnosed in 1987. RESULTS: The patients with mucous membrane melanoma were generally older than patients with either skin or ocular melanoma. Significantly more females than males were reported, with no significant change between study years. Proportionally, more blacks were diagnosed with this condition than in the previous studies of skin and ocular melanoma. The patients with melanoma in this study had a poor prognosis based on characteristics known to be important for skin melanoma. As for patients with skin melanoma, most patients with mucous membrane melanoma were treated with operation alone, but good results were infrequent in patients with mucous membrane melanoma. Local, regional, and systemic recurrences were significant problems and overall survival was poor. CONCLUSIONS: We need new methods of treating these patients to control the disease and improve survival rates.

Regional chemotherapy for melanoma. A 35-year experience.

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.

Multiple perfusions for 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)

Patient characteristics, methods of evaluation and treatment of ocular melanoma in the United States for the years 1981 and 1987.

The American College of Surgeons performed a patient care and evaluation study of malignant melanoma for 1981 and 1987 to determine the presenting symptoms, methods of evaluation, clinical management and resulting outcome. A previous report on malignant melanoma of the skin has been published. This report details the findings of 245 ocular melanomas in 1981 and 275 ocular melanomas in 1987. Most of the ocular melanomas were uveal. The patients with ocular melanoma were older than the patients with skin melanoma. No significant difference was found in the number of ocular instances by gender and by study year. A high percentage of non-Hispanic Caucasians were documented with this disease, and a high percentage of ocular melanomas were not classified by the standard Callender classification. A significant number of melanomas had pigmentation, and a significant number of patients had imaging studies that, in the absence of an elevated alkaline phosphatase, usually yielded negative results. Most patients were treated with enucleation, with an increase in frequency of radiation therapy from 1981 to 1987. Local and regional recurrence was not a problem, but systemic metastases occurred frequently. Type of histologic factors by the Callender classification had an influence on 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 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.

Concordant uptake of Tc-99m sestamibi and Tl-201 in unsuspected breast tumor.

An unsuspected breast tumor was discovered in a 65-year-old woman referred for evaluation of possible ischemic heart disease. Marked tumor uptake of Tl-201 and concordant but less intense uptake of Tc-99m sestamibi (Tc-99m MIBI) was observed after both planar and SPECT imaging post treadmill exercise. Although many reports in the literature document Tl-201 tumor uptake, this is much less frequently reported with Tc-99m MIBI at this time. To the authors' knowledge, Tc-99m MIBI breast tumor uptake has not been reported to date. Tc-99m MIBI might prove useful in the detection of primary and metastatic breast carcinoma, and warrants further investigation.

Patient characteristics, methods of diagnosis and treatment of melanoma in the United States.

The American College of Surgeons performed a patient care and evaluation study of melanoma for 1981 and 1987 to determine the presenting symptoms, methods of evaluation, clinical management and resulting outcome. Melanomas of the skin, eye, mucous membrane, metastases with unknown primary site and miscellaneous sites were included. Details concerning 5,004 patients from 681 hospitals in the study in 1981 and 6,900 patients from 844 hospitals in the study in 1987 were obtained--most melanomas were located in the skin; a decline in symptoms occurred at initial diagnosis; an increase in age at first diagnosis was reported; most melanomas were in Caucasian patients; slightly more melanomas occurred in men than women; more melanomas occurred in men on the head and neck and trunk, and more in the lower extremity in women; most tumors were not large in diameter; a significant shift was reported to lower levels of Clark's invasion, and a significant amount of unknowns existed in the Breslow's thickness of invasion. The large number of unknowns makes analysis difficult, but there seems to be some shift toward thinner levels of Breslow's in tumors in which it was known, from 1981 to 1987. Only a small proportion of patients in the current series was known to have node involvement or known distant metastases. An overall decline in diagnostic studies occurred between 1981 and 1987.

A new coaxial needle for pre-operative localization of breast abnormalities.

A new coaxial needle, containing a retractable anchoring wire with a helical tip, has been developed for purposes of mammographic and sonographic localization of non-palpable suspicious breast abnormalities before surgical excision. The helically shaped tip provides the needle with a number of potential advantages over other currently available localization needles. During in vitro comparisons with other needles quantitative and qualitative evidence was obtained to suggest that the new needle can be expected to have improved anchoring capability, be deflected less by tough fibrous tissue interfaces and be more visible sonographically. The anchoring wire can also be retracted and repositioned. Preliminary clinical experience with the needle was consistent with these expectations.

Granular cell tumor of the breast.

Granular cell tumors are rare tumors occasionally located in the breast. They are generally benign, but can mimic breast carcinoma thus complicating diagnosis and treatment. The etiology of these tumors remains obscure, but may be neurogenic in origin. We report a case of granular cell tumor of the breast and present a review of the topic.

Risk factors for breast cancer.

Despite the numerous risk factors for the development of breast cancer that have been investigated, only a few demonstrate a clear association with breast cancer development. Female gender and increasing age are the most important factors, followed by factors involving a woman's menstrual, reproductive, and family history. The risks related to menstruation and reproduction are probably related to the duration of estrogenic breast stimulation. The relationship of family history and breast cancer risk is unclear, but there may be a true genetic basis. The previous occurrence of breast cancer (invasive or in situ), the presence of proliferative pathological changes, especially with atypia, and the presence of other malignancies (e.g., primary ovarian and endometrial cancer) are histological risk factors for the development of new or recurrent breast cancer. Radiation exposure, the use of exogenous estrogens (both estrogen replacement therapy and oral contraceptives), diet (especially fat consumption), and alcohol intake may all play a role in cancer risk. Certain medications as well as patient demographics may also have a weak association. Cigarette smoking, caffeine consumption, and stress presently have little support for an association with breast cancer risk. It should be noted that in only one in four patients can breast cancer be accounted for by the known risk factors. This demonstrates that although presently known risk factors may help in screening for the early detection of breast carcinoma, in its possible prevention by modulation of influenceable factors, and in advising patients about their risks, these factors are merely strong associations with breast cancer incidence and not actual causations. The mechanisms of the development of breast cancer are as yet unknown.

Regional perfusion for the treatment of subungual melanoma.

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.

Isolated regional perfusion for treatment of limb melanoma in the American black.

Since 1957, 961 patients with invasive malignant melanoma of the limbs were treated by regional perfusion. Forty-eight patients were black, representing 5 per cent of all patients with regional melanoma treated during this period. Thirty-one of the 48 patients were men, and 17 were women. Only 21 of the 48 patients had stage I lesions (M.D. Anderson classification), of whom 63 per cent had level IV or greater invasion. The average depth of invasion was 3.70 mm. Of 21 patients with stage III disease, 15 came to diagnosis with an intact primary lesion in addition to regional disease, and the majority of lesions arose on a plantar site with level V invasion. Eighty per cent of the patients had acral lentiginous melanoma. All melanoma patients were treated by isolated regional perfusion with wide excision of the primary plus regional lymph node dissection for biopsy-proven regional disease. At 10 years, survival rates were 71 per cent for stage I patients and 12.5 per cent for those with stage III disease. When black patients having had acral melanoma on a plantar or palmar site were compared with white patients of a similar stage of disease, however, it was found that black patients had equivalent long-term survival rates.

Breast neoplasms: duplex sonographic imaging as an adjunct in diagnosis.

Sonographic breast imaging has been useful in the differentiation of cystic from solid masses. It has also been helpful in the characterization of palpable breast masses in the absence of corresponding abnormalities. The authors undertook a prospective study that incorporated pulsed Doppler analysis into sonographic real-time imaging of solid breast masses. Thirty-eight patients were examined. In 12 of the patients there were positive Doppler signals, while in 26 patients there were no Doppler signals. The 12 patients showing positive Doppler signals proved to have infiltrating ductal carcinoma, while the 26 patients with negative Doppler signals proved to have benign breast disorders. Pulsed Doppler analysis as a supplement to sonographic real-time imaging shows promise for the identification of breast carcinoma.

Charity Hospital experience with long-term survival and prognostic factors in patients with breast cancer with localized or regional disease.

Long-term survival, the prognostic effects of race, age, tumor size, number of positive nodes, and presence of grave signs (fixation, peau d'orange/edema, dimpling/retraction, satellite nodules, and ulceration) in this distribution of estrogen receptors (ERs) and progesterone receptors (PRs) were studied in 2480 patients (1815 blacks, 665 whites) diagnosed with localized or regional breast cancer at Charity Hospital of Louisiana at New Orleans (CHNO) from 1948 to 1985 and followed up in the CHNO Tumor Registry. Breast cancer-specific survival rates were 57%, 45%, 41%, 39%, 38%, and 35% at 5, 10, 15, 20, 25, and 30 years, respectively. Size of tumor, clinical status of nodes, and degree of fixation were important prognostic clinical factors, and number of nodes was an important pathologic factor with no additional value of the "grave signs." Size and fixation were related. Independent of size, clinical and pathologic status and fixation were related. ER was related to age and PR was related to number of nodes. The excess mortality from breast cancer at later intervals from diagnoses was small compared with mortality from other causes. Some, but not all, clinical findings were important prognostic indicators. ER and PR were related to some variables with unclear meaning.