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Introduction: Although sentinel lymph node (SLN) status is the most powerful predictor of prognosis in patients with clinically localized melanoma, a proportion of melanoma patients with histologically negative SLNs will still recur. It is hypothesized that tumor response may be altered or mediated by specific cytokines. We therefore investigated whether levels of IL-4, IL-6, IL-10, TNF-alpha, or IFN-gamma would predict disease recurrence in melanoma patients with histologically negative SLNs., Methods: This prospective cohort study involved 218 patients with clinically localized melanoma who underwent a histologically negative SLN biopsy. Preoperative plasma cytokine levels were determined by enzyme-linked immunosorbent assay on these patients, as well as on 90 healthy controls. Kaplan-Meier life tables were constructed, and Cox proportional hazards analyses were performed to assess predictors of disease-free survival (DFS)., Results: At a median follow-up of 43 months, 33 of 218 patients (15%) had suffered disease recurrence. Melanoma patients had significant elevations of IL-4, IL-6, and IL-10 compared to healthy controls; levels of IFN-gamma were less elevated in melanoma patients compared to controls. Despite this, melanoma patients with detectable IFN-gamma levels were at significantly higher risk for recurrence compared to patients with undetectable levels (5-year DFS 70% vs. 86%, P = .03). On multivariate analysis including standard melanoma prognostic factors, only tumor thickness (P = .004) and the presence of detectable IFN-gamma levels (P = .05) were significant independent prognostic factors for disease-free survival., Conclusions: Among melanoma patients with clinically localized disease who have undergone a histologically negative SLN biopsy, presence of a detectable plasma level of IFN-gamma is an independent predictor of disease recurrence. Elevated levels of IFN-gamma may identify a group of early-stage melanoma patients who are more likely to have recurrence of disease and who may benefit from adjuvant therapies, including immunotherapies.

Background: For patients with potentially resectable pancreatic cancer, the poor outcome associated with resection alone and the survival advantage demonstrated for combined-modality therapy have stimulated interest in preoperative chemoradiotherapy. The goal of this study was to analyze the effects of different preoperative chemoradiotherapy schedules, intraoperative radiation therapy, patient factors. and histopathologic variables on survival duration and patterns of treatment failure in patients who underwent pancreaticoduodenectomy for adenocarcinoma of the pancreatic head., Methods: Data on 132 consecutive patients who received preoperative chemoradiation followed by pancreaticoduodenectomy for adenocarcinoma of the pancreatic head between June 1990 and June 1999 were retrieved from a prospective pancreatic tumor database. Patients received either 45.0 or 50.4 Gy radiation at 1.8 Gy per fraction in 28 fractions or 30.0 Gy at 3.0 Gy per fraction in 10 fractions with concomitant infusional chemotherapy (5-fluorouracil, paclitaxel, or gemcitabine). If restaging studies demonstrated no evidence of disease progression, patients underwent pancreaticoduodenectomy. All patients were evaluated with serial postoperative computed tomography scans to document first sites of tumor recurrence., Results: The overall median survival from the time of tissue diagnosis was 21 months (range 19-26, 95%CI). At last follow-up, 41 patients (31%) were alive with no clinical or radiographic evidence of disease. The survival duration was superior for women (P = .04) and for patients with no evidence of lymph node metastasis (P = .03). There was no difference in survival duration associated with patient age, dose of preoperative radiation therapy, the delivery of intraoperative radiotherapy, tumor grade, tumor size, retroperitoneal margin status, or the histologic grade of chemoradiation treatment effect., Conclusion: This analysis supports prior studies which suggest that the survival duration of patients with potentially resectable pancreatic cancer is maximized by the combination of chemoradiation and pancreaticoduodenectomy. Furthermore, there was no difference in survival duration between patients who received the less toxic rapid-fractionation chemoradiotherapy schedule (30 Gy, 2 weeks) and those who received standard-fractionation chemoradiotherapy (50.4 Gy, 5.5 weeks). Short-course rapid-fractionation preoperative chemoradiotherapy combined with pancreaticoduodenectomy, when performed on accurately staged patients, maximizes survival duration and is associated with a low incidence of local tumor recurrence.

Background: When implemented in several common surgical procedures, clinical pathways have been reported to reduce costs and resource utilization, while maintaining or improving patient care. However, there is little data to support their use in more complex surgery. The objective of this study was to determine the effects of clinical pathway implementation in patients undergoing elective pancreaticoduodenectomy (PD) on cost and resource utilization., Methods: Outcome data from before and after the development of a clinical pathway were analyzed. The clinical pathway standardized the preoperative outpatient care, critical care, and postoperative floor care of patients who underwent PD. An independent department determined total costs for each patient, which included all hospital and physician costs, in a blinded review. Outcomes that were examined included perioperative mortality, postoperative morbidity, length of stay, readmissions, and postoperative clinic visits., Results: From January, 1996 to December, 1998, 148 consecutive patients underwent PD or total pancreatectomy; 68 before pathway development (PrePath) and 80 after pathway implementation (PostPath). There were no significant differences in patient demographics, comorbid conditions, underlying diagnosis, or use of neoadjuvant therapy between the two groups. Mean total costs were significantly reduced in PostPath patients compared with PrePath patients ($36,627 vs. $47,515; P = .003). Similarly, mean length of hospital stay was also significantly reduced in PostPath patients (13.5 vs. 16.4 days; P = .001). The total cost differences could not be attributed solely to differences in room and board costs. Cost and length-of-stay differences remained when outliers were excluded from the analysis. Despite these findings, there were no significant differences between PrePath and PostPath patients in terms of perioperative mortality (3% vs. 1%), readmissions within 1 month of discharge (15% vs. 11%), or mean number of clinic visits within 90 days of discharge (3.3 vs. 3.4 visits)., Conclusions: The establishment of a clinical pathway for PD patients dramatically reduced costs and resource utilization without any apparent detrimental effect on quality of patient care. These findings support the implementation of clinical pathways for PD patients, as well as investigation into pathway care for other complex surgical procedures.

Background: Although previous studies have demonstrated that truncal site is associated with an adverse prognosis, explanations for such risk are lacking. In addition, the number of nodal basins as well as the number of lymph nodes containing regional metastases are important prognostic factors in these patients. Because the lymphatic drainage pattern of truncal melanoma often includes more than one basin, we designed a study to evaluate (1) whether patients with multiple nodal basin drainage (MNBD) were at an increased risk of lymph node metastases identified by sentinel lymph node (SLN) biopsy, and (2) whether the histological status of an individual basin reliably predicted the status of the other draining basins in patients with MNBD., Methods: The records of 295 consecutive truncal melanoma patients who were managed primarily with intraoperative lymphatic mapping and SLN biopsy, between 1991 and 1997, were reviewed. All patients underwent preoperative lymphoscintigraphy, which established the number and location of draining nodal basins. Univariate and multivariate analyses of relevant clinicopathological factors were performed to assess which factors may predict the presence of a pathologically positive SLN., Results: At least one SLN was identified in 281 patients. MNBD was present in 86 (31%) patients, and a pathologically positive SLN was found in 56 (20%) patients. By multivariate analysis, the presence of MNBD (relative risk = 1.9; P = .03), tumor thickness (P = .007), and tumor ulceration (relative risk = 2.4; P = .01) were significant independent risk factors for the presence of at least one pathologically positive SLN. SLN pathology in one basin did not predict the histology of other basins in 19 (22%) of 86 patients with MNBD., Conclusions: MNBD is independently associated with an increased risk of nodal metastases in truncal melanoma patients. Because the histological status of an individual basin did not reliably predict the status of the other draining basins in patients with MNBD, it is important to adequately identify and completely assess all nodal basins at risk, as defined by lymphoscintigraphy, in truncal melanoma patients.

Background: Regional nodal basin control is an important goal of lymphadenectomy in the management of melanoma patients with nodal disease. The purpose of this study was to determine if previous sentinel lymph node (SLN) biopsy compromises the ultimate regional nodal control achieved by subsequent therapeutic lymph node dissection in melanoma patients with microscopic lymph node metastases., Methods: A surgical melanoma database and hospital records were reviewed for 602 patients with primary cutaneous melanoma who underwent successful lymphatic mapping and SLN biopsy between 1991 and 1997., Results: A total of 105 (17%) of 602 patients had histologically positive SLNs and were offered therapeutic lymphadenectomy; 101 (96%) underwent this procedure. Thirty-six patients (36%) developed recurrent melanoma at one or more sites. The median follow-up period was 30 months. Recurrence in the previously dissected nodal basin was observed in 10 patients (10%); none had recurrence at only that site. Nodal basin disease appeared after local/in-transit (n = 6) or distant (n = 1) failure in seven patients and, as a component of the first site of failure, simultaneously with local/in-transit (n = 2) or distant (n = 1) recurrence in three patients., Conclusions: Nodal basin failure after lymphadenectomy in patients who underwent previous biopsy of a histologically positive SLN is primarily a function of aggressive locoregional disease rather than of contamination from previous surgery. Because regional nodal control was comparable with that in other series, we conclude that SLN biopsy with selective lymphadenectomy does not compromise regional nodal basin control.

Background: Historically, patients with thick (> or =4 mm) primary melanoma have not been considered candidates for elective lymph node dissection, because their risk for occult distant disease is significant. Sentinel lymph node (SLN) biopsy offers an alternative approach to assess disease in the regional nodal basin, but no studies have specifically addressed the role for this technique in patients with thick melanoma. Although adjuvant therapy benefits patients who develop nodal metastases, data that supports its routine use in all patients with thick melanoma is both limited and controversial. This study was performed to determine whether pathological status of the SLN is an important risk factor in this heterogeneous group and, thus, provides a rationale for SLN biopsy., Methods: The records of 131 patients with primary cutaneous melanoma whose primary tumors were at least 4 mm thick and who underwent lymphatic mapping and SLN biopsy were reviewed. Several known prognostic factors, i.e., tumor thickness, ulceration, Clark level, location, sex, as well as SLN pathological status were analyzed with respect to disease-free and overall survival., Results: Lymphatic mapping and SLN biopsy was successful in 126 (96%) of 131 patients who underwent the procedure. In 49 patients (39%), the SLN biopsy was positive by conventional histology, although it was negative in 77 patients (61%). The median follow-up was 3 years. Although presence of ulceration and SLN status were independent prognostic factors with respect to disease-free and overall survival, SLN status was the most powerful predictor of overall survival by univariate and multivariate analyses., Conclusions: Lymphatic mapping and SLN biopsy is a highly accurate method of staging lymph node basins at risk for regional metastases in patients with thick melanoma and identifies those patients who may benefit from earlier lymphadenectomy as well as patients with a more favorable prognosis. Pathological status of the SLN in these patients with clinically negative nodes is the most important prognostic factor for survival and is essential to establish stratification criteria for future adjuvant trials in this high-risk group.

Background: Randomized trials have demonstrated the efficacy of 1- and 2-cm excision margins for thin and intermediate-thickness melanomas, respectively. The optimal margin of excision for thick melanomas is still unknown, however. We evaluated whether the margins used for intermediate-thickness melanomas can be applied safely to thicker lesions., Methods: The charts of 278 patients with thick primary melanomas treated between 1985 and 1996 were retrospectively reviewed. Patients with distant metastases at presentation or with follow-up less than 6 months were excluded. Median follow-up was 27 months. Known melanoma prognostic factors and excision margins were evaluated for their impact on local recurrence (LR), disease-free survival (DFS), and overall survival (OS)., Results: Median tumor thickness was 6.0 mm, and 57% were ulcerated. At presentation, 201 patients (72%) were node negative and 77 (28%) were node positive (palpable or occult). The 5-year OS and DFS rates were 55% and 30%, respectively. The LR rate for all patients was 12%. Although nodal status, thickness, and ulceration were significantly associated with OS by multivariate analysis, neither LR nor excisional margin (<2 cm vs. >2 cm) significantly affected DFS or OS in these patients., Conclusions: Because margins of excision greater than 2 cm do not improve LR, DFS, or OS compared to a margin of 2 cm or less, a 2-cm margin of excision is adequate for patients with thick melanoma. Because nodal status is a significant prognostic factor in these patients, staging by sentinel node biopsy should be considered in patients with thick melanomas and clinically negative nodal basins to allow proper entry and stratification in adjuvant therapy trials.