The role of surgery in cutaneous malignant melanoma.
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Biomedical subjects
Publications and source records attributed to D G Coit.
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To examine the natural history of lymph node metastasis from sarcomas and the utility of therapeutic lymphadenectomy, clinical histories of all adult patients identified by a prospective sarcoma database for the 10-year period July 1982 to July 1991 were examined. Of the 1772 sarcoma patients, 46 (2.6%) were identified with lymph node metastasis. Median follow-up of all patients from diagnosis of lymph node metastasis was 12.9 months (range, 0 to 100 months). Median survival for nonsurvivors was 12.7 months (range, 0 to 40.7). The tumor types with the highest incidence of lymph node metastasis are angiosarcoma (5/37 total cases; 13.5%), embryonal rhabdomyosarcoma (ERMS) (12/88 total cases; 13.6%), and epithelioid sarcoma (2/12 total cases; 16.7%). Lymph node metastasis from visceral primary (p = 0.004) and malignant fibrous histiocytomas (p = 0.006) were associated with particularly poor prognosis. Thirty-one patients underwent radical, therapeutic lymphadenectomy with curative intent, whereas 15 patients had less than curative procedures, in most cases biopsy only. Patients not treated with radical lymphadenectomy had a median survival of 4.3 months (range, 1 to 32) whereas radical lymphadenectomy was associated with a 16.3 month median survival and the only long-term survivors (46% 5-year survival by Kaplan-Meier). The authors conclude that lymph node metastases from sarcoma are rare in adults, but vigilance is warranted, especially in angiosarcoma, ERMS, and epithelioid subtypes. Radical lymphadenectomy is appropriate treatment for isolated metastasis to regional lymph nodes and may provide long-term survival.
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Patterns of recurrence and outcome were determined in 403 patients with melanoma who underwent an axillary or inguinal lymphadenectomy. Recurrences developed at single sites in 291 (72%) patients, with a median survival of 11 months, and at multiple sites in 112 (28%) patients, with a median survival of 3 months. Among patients with single-site recurrence, those with nonvisceral recurrence (n = 190) had a median survival of 18.5 months compared with 6 months in those with visceral recurrence (n = 101). Recurrences were treated surgically in 240 (60%) patients, with a median survival of 15 months, and nonsurgically in 112 patients, with a median survival of 4 months. Median survival after complete resection of single-site recurrence was 19 months compared with 6 months after incomplete resection. Multivariate analysis revealed that outcome was improved by surgical treatment, single-site and nonvisceral recurrence, and primary site in an extremity. These observations support an approach of selective resection in the treatment of recurrences after lymphadenectomy.
A rare case of carcinoma arising within a gastric duplication cyst in a 72 year old woman is presented. This is the oldest patient in whom neoplastic transformation of this usually benign developmental abnormality has been reported. The clinical and pathologic features of this patient are demonstrated and reviewed in the context of prior reported cases.
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A technique for long term central venous access through the gonadal vein is described. It has been used five times in four patients with consistently satisfactory results.
Two new cases of papillary and cystic neoplasm of the pancreas are reported. One patient was a 20-year-old woman with massive unresectable liver metastases, and the other was a 15-year-old boy. To study the natural history and malignant potential of this tumor, the English literature was reviewed to obtain an additional 56 cases. Clinical characteristics include pain and a mass in most patients, although many are found incidentally. Jaundice, hemoperitoneum, nausea, and vomiting are unusual findings. Most patients are treated by wide resection with good results. These tumors appear to be indolent. However, 16% of patients had major organ or blood vessel invasion, and 7% had liver metastases at some time during the course of their disease, illustrating the malignant nature of this tumor. Long-term follow-up is necessary to evaluate the efficacy of treatment, especially in the case of locally advanced and metastatic disease.
One hundred thirty-four patients undergoing axillary or inguinal lymph node dissection were randomized to receive perioperative treatment with either cefazolin or placebo. Risk factors for wound complications (age greater than 60 years, open wound, obesity, smoking, extremity edema, diabetes, arteriosclerotic cardiovascular disease) were recorded. The rate of complications was 36% in 97 patients (72%) with any risk factor present, compared with 14% in patients with no risk factors. Complications were seen in 30% of patients: in 14% after axillary lymph node dissection, and in 64% after inguinal lymph node dissection. The risk of complications was 23% in the group administered antibiotic treatment compared with 36% in that administered placebo treatment. This trend toward fewer complications was seen only after axillary lymph node dissection, when the rate of complications was 8% in the antibiotic-treated group compared with 20% in the placebo-treated group. After inguinal lymph node dissection, the rate of complications was 69% in the antibiotic-treated group compared with 62% in the placebo-treated group.
Seventy patients with Merkel cell carcinoma were treated at Memorial Sloan-kettering Cancer Center between 1969 and 1989. The overall estimated 5-year survival rate was 64%. Factors predictive of improved survival included head and neck site and negative lymph nodes at presentation. Local recurrence was seen in 18 patients (26%) and did not correlate with patient-, tumor-, or treatment-related variables. Nine patients with local recurrence (50%) were free of disease following aggressive reoperation. Regional nodes were involved at some point during the course of the disease in forty-six patients (66%). Regional lymph node involvement was apparent within 2 years of diagnosis in 40 (87%) of 46 patients in whom it occurred. Systemic disease was nearly uniformly preceded by the appearance of nodal metastases and was uniformly fatal regardless of subsequent therapy. This suggests an orderly "cascade" pattern of spread for this tumor, in which elective regional lymph node dissection may be justified. Our recommendations for treatment include a wide excision of the primary tumor and either elective or early therapeutic regional node dissection. The role of adjuvant radiotherapy or chemotherapy remains unproven.
Approximately 60% of patients who die from melanoma have gastrointestinal (GI) metastases at autopsy, yet antemortem diagnosis is uncommon. A retrospective review was completed on 32 patients who underwent an operation at Memorial Sloan-Kettering Cancer Center between 1977 and 1987 for complications of melanoma metastatic to the stomach, small bowel, or colon. Operations were most often performed on an emergent basis, and indications included bleeding or anemia in 12, obstruction in 10, abdominal pain in 8, intestinal perforation in 1, and acute GI bleeding with obstruction in 1. GI involvement was the first sign of metastatic disease in 10 patients. Median survival after operation was 6.2 months (range: 1 to 42 months). Five patients were alive 2 years after operation, although only one remains free of disease 39 months after complete resection of a single site. Operative mortality was 3%, and 94% of patients were discharged from the hospital. Due to the low operative mortality, surgical palliation should be considered for those in whom the quality of life may be improved.
Although pathologic nodal status is a major determinant of outcome in melanoma, there is substantial prognostic heterogeneity among node-positive patients. This study was undertaken to further clarify significant variables predicting survival in patients with melanoma metastatic to axillary or groin nodes. From 1019 patients with melanoma undergoing axillary or groin dissection between 1974 and 1984, the authors identified 449 patients with histologically positive nodes. Both univariate and multivariate analyses were performed using the Kaplan-Meier product limit method and the Cox model of proportional hazard regression. The major determinant of survival was pathologic stage (PS) according to the 1983 AJCC staging system. Three hundred fifty patients (78%) were classified PS-III (one nodal group involved), with a survival of 39% at 5 years and 32% at 10 years. Factors independently predictive of a favorable outcome in these patients were nontruncal primary site (p = 0.0002), microscopic nodal involvement (p = 0.001), number of positive nodes less than three (p = 0.003), and absence of extranodal disease (p = 0.01). Ninety-nine patients (22%) were classified PS-IV, 51 with two nodal stations involved (N2), 25 with intransit disease and one nodal station involved (N2), 7 with extraregional soft tissue metastases (M1), and 16 with visceral metastases (M2). Survival for PS-IV patients was 9% at 5 and 10 years, respectively. Within PS-IV, factors independently predictive of a more favorable outcome were the absence of extranodal disease (p = 0.0001), female sex (p = 0.03), and a long interval from diagnosis to lymph node dissection (p = 0.04). These factors were incorporated into a model predicting relative risk of death from disease for both PS-III and PS-IV patients, separating patients into groups at high, intermediate, and low risk of recurrence after lymphadenectomy.
A combination of recombinant human interleukin 2 (rhIL-2) and mouse monoclonal antibody R24 (recognizing the ganglioside GD3) was evaluated in patients with metastatic melanoma in a phase I trial. rhIL-2 was given at a constant daily dose of 1 x 10(6) units/m2 i.v. over 6 h on days 1-5 and 8-12. R24 was given on days 8-12 at four dose levels (1, 3, 8, and 12 mg/m2 daily). Twenty patients were evaluable for toxicity and response, five at each dose level. The toxicity of the combination was not overlapping and generally mild. There was a rebound peripheral blood T-lymphocytosis at the end of treatment increasing with the dose of R24. The median lymphocyte count on day 12 of treatment was 3108 +/- 554/ml in patients treated at R24 doses of 8 and 12 mg/m2 versus 2239 +/- 672/ml at doses of 1 and 3 mg/m2. This evidence and other data suggested that R24 enhanced IL-2-mediated T-cell activation in vivo. Two patients demonstrated increases in R24-mediated antibody-dependent cellular cytotoxicity for GD3-expressing cells during treatment. rhIL-2 appeared to accelerate the development of human anti-mouse antibody; three patients developed human anti-mouse antibody by the fifth day of R24 treatment, earlier than observed in prior studies using R24 alone and one patient during the first week of rhIL-2 alone, prior to R24 treatment. One patient had a partial response in soft tissue sites lasting 6 months and two patients had minor responses. This clinical trial extends the previous observation that R24 enhances lymphocyte proliferation in vitro.
From 1982 to 1987, 114 patients underwent operation at Memorial Sloan-Kettering Cancer Center for soft-tissue sarcoma of the retroperitoneum. A retrospective analysis of these patients defines the biologic behavior, surgical management of primary and recurrent disease, predictive factors for outcome, and impact of multimodality therapy. Complete resection was possible in 65% of primary retroperitoneal sarcomas and strongly predicts outcome (p less than 0.001). The rate of complete resection was not altered by histologic type, size, or grade of tumor. These patients had a median survival of 60 months compared to 24 months for those undergoing partial resection and 12 months for those with unresectable tumors. Forty-nine per cent of completely resected patients have had local recurrence. This is the site of first recurrence in 75% of patients. These patients undergo reoperation when feasible. Complete resection of recurrent disease was performed in 39 of 88 (44%) operations, with a 41-month median survival time after reoperation. Tumor grade was a significant predictor of outcome (p less than 0.001). High-grade tumors (n = 65) were associated with a 20-month median survival time compared to 80 months for low-grade tumors (n = 49). Gender, histologic type, size, previous biopsy, and partial resection versus unresectable tumors did not predict outcome by univariate analysis. Adjuvant radiation therapy and chemotherapy could not be shown to have significant impact on survival. Concerted attempt at complete resection of both primary and recurrent retroperitoneal soft-tissue sarcoma is indicated.
We evaluated the importance of 14 clinical and pathologic variables as determinants of prognosis in patients with malignant melanoma and positive regional lymph nodes at axillary dissection. The records of 197 patients operated on between 1974 and 1984 were reviewed. Univariate analysis indicated as prognostically significant the number (p less than 0.001) and percentage (p less than 0.001) of positive nodes, highest nodal status (p less than 0.001), macroscopic or microscopic nodal metastases (p = 0.002), presence or absence of extranodal disease (p = 0.003), clinical stage (III versus less than III, p = 0.015), and site (considered as trunk versus other locations, p = 0.02). However, by multivariate analysis, only three variables were shown to be independent determinants of survival: percentage of positive nodes (p = 0.004), presence or absence of extranodal disease (p = 0.012), and site (trunk versus other locations, p = 0.019). Combining these three variables, subsets of patients with markedly different prognoses could be generated. It is possible to predict a favorable outcome for patients with less than 10% positive nodes, no extranodal disease, and a primary lesion at a site other than the trunk. It is also possible to recognize that the prognosis is very poor for patients with extranodal disease and truncal primary lesions, regardless of the percentage of positive lymph nodes. Finally it was verified that the prognosis is always unfavorable when the percentage of positive lymph nodes is very high.
Twenty-four patients underwent biopsy or resection of the liver for focal nodular hyperplasia (FNH) at Memorial Sloan-Kettering Cancer Center from 1978 to 1988. Twenty-two of the patients were women. The mean age was 35 years. A history of antecedent oral contraceptive or conjugated estrogen (Premarin) use was obtained in 18 of 21 women. There were two men, aged 26 and 37 years; neither gave a history of hormone use. Most of the tumors were solitary (22 of 24) and located in the left lobe of the liver (17 of 22). Fifteen of the patients had a prior or simultaneous malignant lesion and six had other benign tumors. Most of the tumors were resected with a wedge or subsegment of liver (13 of 24). Four patients underwent segmentectomy and five required lobectomy for removal of the tumors. Two patients had an intraoperative biopsy only. The patients in whom the tumor was diagnosed preoperatively underwent computed tomography and arteriography routinely. Scintigraphy of the liver with sulfur colloid was obtained in only three patients, despite its distinct potential for nonoperative diagnosis of FNH.
Overall results after operations for gastric cancer in Japan are far superior to results obtained in the US and Europe. We have reviewed the Japanese literature in an effort to determine what factors explain this difference. It appears that the survival differences are due mainly to a greater frequency of early gastric cancer in Japan; meticulous histopathologic evaluation of the surgical specimens, resulting in more accurate pathologic staging; and the presumed benefit of extended nodal dissection when it extends outside of the level of node-positive disease. Although patients with both apparent and confirmed direct adjacent organ invasion can be helped by resection of those organs, extended resections of uninvolved pancreas and spleen do not improve rate of survival beyond the benefit of improved nodal dissection. Overall, there would appear to be justification for reexamining extended nodal dissection for gastric cancer in the US. Opportunities for a meaningful national study are significant.
The extent of lymph node dissection necessary to optimize survival and minimize local recurrence in patients with melanoma of the trunk or lower extremity is not well defined. We reviewed the records of 420 patients undergoing superficial or combined superficial and deep groin dissection for melanoma. Prognosis depended on the extent of lymph node involvement rather than the extent of surgery performed. Node-positive patients undergoing elective lymph node dissection had an improved survival over those undergoing therapeutic lymph node dissection. In no subgroup of patients was more extensive lymphadenectomy associated with significant improvement in survival or alteration in pattern of recurrence. Dissection of the deep pelvic nodes in patients with melanoma appears to be of more prognostic than therapeutic value.