Does complete resection of melanoma metastatic to solid intra-abdominal organs improve survival?

BACKGROUND: Patients with distant melanoma metastases have median survivals of 4 to 8 months. Previous studies have demonstrated improved survival after complete resection of pulmonary and hollow viscus gastrointestinal metastases. We hypothesized that patients with metastatic disease to intra-abdominal solid organs might also benefit from complete surgical resection. METHODS: A prospectively acquired database identified patients treated for melanoma metastatic to the liver, pancreas, spleen, adrenal glands, or a combination of these from 1971 to 2000. The primary intervention was complete or incomplete surgical resection of intra-abdominal solid-organ metastases, and the main outcome measure was postoperative overall survival (OS). Disease-free survival (DFS) was a secondary outcome measure. RESULTS: Sixty patients underwent adrenalectomy, hepatectomy, splenectomy, or pancreatectomy. Median OS was significantly improved after complete versus incomplete resections, but median OS after complete resection was not significantly different for single-site versus synchronous multisite metastases. The 5-year survival in the group after complete resection was 24%, whereas in the incomplete resection group, there were no 5-year survivors. Median DFS after complete resection was 15 months. Of note, the 2-year DFS after complete resection was 53% for synchronous multi-site metastases versus 26% for single-site metastases. CONCLUSIONS: In highly selected patients with melanoma metastatic to intra-abdominal solid organs, aggressive attempts at complete surgical resection may improve OS. It is important that the number of metastatic sites does not seem to affect the OS after complete resection.

Dermal versus intraparenchymal lymphoscintigraphy of the breast.

BACKGROUND AND OBJECTIVE: Dermal and intraparenchymal (IP) injections of radiocolloid have been used for lymphoscintigraphic identification of the sentinel node (SN) in breast cancer. Because of our institute's extensive experience with dermal and IP lymphoscintigraphy for melanoma and breast cancer, we compared patterns of lymphatic migration after both types of injections to identify any differences in drainage patterns or SN identification. METHODS: Lymphoscintigrams (n = 31) after dermal injections in 30 patients with primary cutaneous melanoma on the breast were compared with lymphoscintigrams after IP injections in 97 consecutive patients with breast cancer. In each case, 400 microCi of filtered 99mTc-sulfur colloid was injected in four quadrants around the tumor or in the biopsy cavity. All lymphoscintigrams were reviewed for patterns of migration and SN location. RESULTS: Five of 31 (16%) dermal injections demonstrated bilateral axillary migration (n = 3) or a suprasternal SN (n = 2), neither of which was found with IP injections. Conversely, 3 of 97 (3%) IP injections demonstrated direct supraclavicular (n = 2) or costal margin (n = 1) nodes (P = .006), neither of which was found with dermal injections. Low axillary SNs were noted after 26 (84%) dermal and 93 (96%) IP injections (P = .037). The incidence of extra-axillary SNs was 26% (8 of 31) in the dermal group but only 5% (5 of 97) in the IP group (P = .0027). CONCLUSION: There is a significant difference in lymphatic drainage and SN localization between dermal and IP lymphoscintigraphy. This finding has implications for injection techniques when lymphatic mapping of the SN is undertaken to stage a breast carcinoma.

Earlier diagnosis of second primary melanoma confirms the benefits of patient education and routine postoperative follow-up.

BACKGROUND: Rising health care costs have caused providers to question the benefit of regular follow-up after treatment for patients with early stage cutaneous melanoma. The authors hypothesized that routine reassessment and careful education of these patients would facilitate earlier diagnosis of a subsequent second primary melanoma, as reflected by reduced thickness of that lesion. METHODS: A prospective melanoma data base was used to identify patients who developed a second primary melanoma after treatment for American Joint Committee on Cancer (AJCC) Stage I or II cutaneous melanoma. After excision of the initial primary melanoma, all patients underwent routine biannual follow-up for new primary lesions. Follow-up consisted of a questionnaire and a complete skin examination by a physician. In addition, patients were regularly educated regarding the increased risk of developing a second melanoma. A paired t test was used to examine AJCC stage, thickness, and level of invasion of the initial melanoma compared with the second primary melanoma. RESULTS: Of 3310 patients with AJCC Stage I or II melanoma, 114 patients (3.4%) developed a second primary melanoma. AJCC staging of both first and second melanomas was available in 82 patients (72%). When the AJCC stages of first and second melanomas were compared, 39 of 82 patients (48%) had lower stage second primary lesions, and 41 (50%) had same-stage second primary lesions. The mean tumor thickness was 1.32 +/- 1.02 mm for the initial melanoma, decreasing to 0.63 +/- 0.52 mm for the second melanoma; in fact, tumor thickness increased in only 4 of 51 patients (8%) whose records contained data for both first and second melanomas. Similarly, the level of invasion decreased in 60% of patients, remained the same in 27% of patients, and increased in only 13% of patients. By paired t test, the differences in AJCC stage, tumor thickness, and level of invasion between first and second melanomas were each highly significant (P = 0.0001). CONCLUSIONS: In this study, the second primary melanoma in patients with a prior cutaneous melanoma was significantly thinner than the initial primary lesion. This is evidence that careful follow-up and patient education allow earlier diagnosis. All patients diagnosed with cutaneous melanoma should be counseled regarding the risks of second melanoma and should undergo lifelong follow-up at biannual intervals.

Does sentinel lymphadenectomy improve staging and alter therapy in elderly women with breast cancer?

BACKGROUND: Routine axillary lymph node dissection (ALND) for elderly women with invasive breast cancer has been questioned because it rarely alters therapy yet carries a significant morbidity rate. Sentinel lymphadenectomy (SLND) improves axillary staging and alters therapy in women with T1 breast cancer, but it is not clear whether SLND alters therapy in elderly women with breast cancer. METHODS: A prospective breast cancer data base was used to identify women 70 years old and older who underwent SLND for axillary staging of invasive breast cancer between 1991 and 1998. RESULTS: There were 75 invasive breast cancers in 73 women. The mean patient age was 74.5 years (range, 70-90 years). Median tumor size was 1.4 cm (range, 0.1-6.2 cm). Of the 75 tumors, 42 (56%) had favorable primary characteristics; the remaining tumors had unfavorable characteristics. SLND was performed alone in 17 cases (23%) and was followed by completion ALND in 58 cases (77%). Positive lymph nodes were identified in 32 cases (43%); 26 (81.3%) were detected by hematoxylin and eosin stains, and 6 (18.7%) were detected by immunohistochemistry alone. Five patients (6.9%) received adjuvant chemotherapy. Seven patients (9.6%) received axillary/supraclavicular radiation for positive nodes. Ten (13.7%) of 73 patients had obvious alterations in therapy because of axillary nodal status. As a result of SLND, 3 (13.6%) of 22 patients with tumors 1.0 cm or smaller received tamoxifen, and 7 (15%) of 46 patients with tumors between 1.0 and 3.0 cm in size had changes in therapy. When patient and tumor characteristics were analyzed to determine relationships to therapeutic decision-making, nodal status was the variable most significantly associated with changes in therapy (P = .0001). CONCLUSIONS: SLND improves axillary staging in elderly women with invasive breast cancer. Results of immunohistochemistry do not alter therapy in this group of individuals (P = .6367). In patients with small primary tumors, SLND alters therapy by increasing the number of patients receiving tamoxifen. In addition, SLND affects adjuvant systemic chemotherapy and regional radiotherapy in a significant number of patients with larger tumors, particularly tumors between 1.0 and 3.0 cm.

Vaccine therapy for patients with melanoma.

Investigation into the therapeutic use of vaccines in patients with metastatic melanoma is critically important because of the lack of effective conventional modalities. The most extensively studied melanoma vaccines in clinical trials are whole-cell preparations or cell lysates that contain multiple antigens capable of stimulating an immune response. Unfortunately, in the majority of studies, immune responses to these vaccines have not translated into a survival advantage. Advances in tumor cell immunology have led to the identification of candidate tumor cell antigens that can stimulate an immune response; this, in turn, has allowed for refinements in vaccine design. However, the exact tumor antigens that should be targeted with a specific vaccine are unknown. The univalent antigen vaccines, which have greater purity, ease of manufacturing, and reproducibility compared with polyvalent vaccines, may suffer from poorer efficacy due to immunoselection and appearance of antigen-negative clones within the tumor. Novel approaches to vaccine design using gene transfection with cytokines and dendritic cells are all promising. However, the induction of immune responses does not necessarily confer a therapeutic benefit. Therefore, these elegant newer strategies need to be studied in carefully designed clinical trials so that outcomes can be compared objectively with standard therapy. If survival is improved with these vaccine approaches, their ease of administration and lack of toxicity will firmly entrench active specific vaccine immunotherapy as a standard modality in the treatment of the melanoma patient.

Increased incidence of second primary melanoma in patients with a previous cutaneous melanoma.

BACKGROUND: Patients with cutaneous melanoma reportedly have an increased risk of developing second primary melanoma; however, this increased risk has not been well characterized with respect to age and time from first melanoma. We hypothesized that, as a result of temporal variations in environmental exposure, genetic susceptibility, and impaired immune competence, the incidence of second primary melanoma varies significantly with respect to age and time. METHODS: A review of our prospective melanoma data base, containing records for 8928 patients, was undertaken to identify patients with American Joint Committee on Cancer stage I and II cutaneous melanoma, who were treated from 1971 to 1998. RESULTS: Second primary melanoma was identified in 113 (3.4%) of 3310 patients with American Joint Committee on Cancer stage I and II cutaneous melanoma. In 11 patients (0.3%), the second melanoma was identified within 2 months of the initial tumor; the remaining 102 patients had a metachronous lesion. The incidence rate of second primary melanoma was 325 per 100,000. The standardized incidence ratio, defined as the ratio of the number of observed second melanomas to the number of expected melanoma cases, was 25.6. The 5- and 10-year risk of developing a second melanoma was 2.8% and 3.6%, respectively. Both the annual risk of developing a second melanoma and the standardized incidence ratio were elevated in younger patients (ages 15-39 years) and in older patients (ages 65-79 years). CONCLUSIONS: Patients with cutaneous melanoma are at very high risk for development of second primary melanoma. This risk approximates 0.5% per year for the first 5 years of follow-up. Patients aged 15-39 and patients aged 65-79 have a particularly high incidence of second melanoma, suggesting different causes for the development of second primaries. All patients with melanoma should undergo careful surveillance for second melanomas in addition to routine screening for recurrence.

Safety and durability of single-layer, stentless, biliary-enteric anastomosis.

Biliary-enteric anastomosis has long been associated with significant complications of early bile leak, cholangitis, and late stricture formation, and controversy exists regarding which operative technique best prevents these problems. Biliary-enteric anastomosis was performed using a single-layer running 4-0 polyglactin (Vicryl) suture, without a transanastomotic stent, in 97 patients by a single surgeon over a 17-year period. Indications for operation included malignant obstruction (84.5%), benign stricture, choledocholithiasis, and choledochal cyst. The most common operation performed was a choledochoduodenostomy; the remaining operations were either Roux-en-Y choledochojejunostomy, hepaticoduodenostomy, or Roux-en-Y hepaticojejunostomy. Complications occurred in 14.1 per cent of patients; there was one perioperative death. There was only one case of anastomotic leak (1%), which resolved spontaneously within 1 week. Mean hospital stay was 8.7 days. The mean follow-up was 13.1 months in all patients. Among patients with benign disorders of the biliary tract, the mean follow-up was 21 months, during which time no patient developed an anastomotic stricture. One patient experienced postoperative cholangitis, although not as a result of anastomotic stricture. Biliary-enteric anastomosis for both benign and malignant disorders can be safely performed using a running, absorbable suture without a stent.

Choledochoduodenostomy for palliation in unresectable pancreatic cancer.

OBJECTIVE: To determine whether choledochoduodenostomy provides adequate long-term palliation of obstructive jaundice in unresectable pancreatic cancer. DESIGN: Consecutive case series. SETTING: Tertiary referral center. PATIENTS: From 1980 to 1997, 79 consecutive patients (45 men, 34 women; mean age, 67.8 years) with biopsy-proved pancreatic cancer found to be unresectable at operation. INTERVENTION: All patients had resectable disease by preoperative criteria. At exploratory laparotomy, unresectability was determined by the presence of liver or peritoneal metastases, encasement of major vascular structures by tumor, and/or celiac lymph node involvement. Choledochoduodenostomy for biliary bypass was performed in 71 (90%) of 79 patients; Roux-en-Y choledochojejunostomy was performed in the remaining 8 patients. MAIN OUTCOME MEASURES: Resolution of jaundice, duration of hospital stay, mean survival, postoperative complications, and evidence of recurrent biliary obstruction. RESULTS: All patients experienced rapid resolution of jaundice. Average hospital stay was 8.3 days. Mean survival after operation was 13.1 months (range, 2 weeks to 62 months). Postoperative mortality was 3%. There were no biliary or duodenal leaks. Four patients (6%) required hospitalization for gastrointestinal hemorrhage; however, only 1 (1%) was from peptic ulceration. No patient developed recurrent biliary obstruction. CONCLUSIONS: Choledochoduodenostomy provides rapid, long-lasting relief of jaundice, with little morbidity and a low rate of duodenal ulceration, and is the palliative operation of choice when patients are found to have unresectable disease at operation or when stenting procedures fail.

Breast cancer in pregnancy and lactation.

Although breast cancer is the most common malignancy in pregnancy, its overall incidence remains low. It appears that pregnancy and breast cancer are merely coincidental and that pregnancy does not directly contribute to the development or accelerated progression of breast cancer. The majority of studies have documented a significant delay in diagnosis secondary to physiologic changes of the breast during pregnancy and have reasoned that this is the likely explanation for the advanced stage of disease upon initial presentation. Although pregnant patients present at a later stage of breast cancer, survival stage for stage is the same when pregnant patients are compared with young nonpregnant patients with breast cancer. A suspicious breast mass in a pregnant patient should be biopsied and appropriately treated, without need for extensive preoperative staging. Therapeutic abortion should be performed only on an individual basis, namely in patients in whom necessary radiation or chemotherapy would be detrimental to the developing fetus and in whom a significant delay of this treatment would be harmful. In patients with early-stage disease, it is recommended to wait 2 years after treatment of breast cancer for subsequent pregnancy; however, in women with advanced disease, subsequent pregnancy should be discouraged.