Jeffrey D. Wagner

Prospective Study of Fluorodeoxyglucose–Positron Emission Tomography Imaging of Lymph Node Basins in Melanoma Patients Undergoing Sentinel Node Biopsy

PURPOSE To prospectively compare positron emission tomography (PET) imaging of regional lymph node basins to sentinel node biopsy (SNB) in patients with American Joint Committee on Cancer (AJCC) stage I, II, and III melanoma localized to the skin. METHODS Patients with cutaneous melanoma with Breslows depth greater than 1 mm (AJCC T2-4N0M0) or localized regional cutaneous recurrence (TxN2bM0) underwent whole-body imaging of glucose metabolism with fluorodeoxyglucose (FDG) PET followed by SNB. PET scans were interpreted in a blinded fashion and compared with histologic analyses of SNB specimens and clinical follow-up examination. Nodal tumor volumes were estimated. RESULTS Eighty-nine lymph node basins were evaluated by FDG-PET and SNB in 70 assessable patients. Eighteen patients (25.7%) had lymph node metastases at the time of FDG-PET imaging: 17 proved by SNB (24.3%) and one by follow-up examination (1.4%). Median tumor volume in positive sentinel node basins was 4.3 mm3 (range, 0.07 to 523 mm3). Sensitivity of SNB for detection of occult regional lymph node metastases was 94.4%, specificity was 100%, positive predictive value (PPV) was 100%, and negative predictive value (NPV) was 98.6%. Sensitivity of FDG-PET was 16.7%, specificity was 95.8%, PPV was 50%, and NPV was 81.9%. At a median follow-up duration of 16.6 months, seven patients (10%) developed recurrent disease. PET predicted one recurrence (14.3%) in a node basin missed by SNB. CONCLUSION FDG-PET is an insensitive indicator of occult regional lymph node metastases in patients with melanoma because of the minute tumor volumes in this population. FDG-PET does not have a primary role for staging regional nodes in patients with clinically localized melanoma.

Inefficacy of F‐18 fluorodeoxy‐D‐glucose‐positron emission tomography scans for initial evaluation in early‐stage cutaneous melanoma

The purpose of the current study was to determine the sensitivity and specificity of initial F‐18 fluorodeoxy‐D‐glucose‐positron emission tomography (FDG‐PET) scanning for detection of occult lymph node and distant metastases in patients with early‐stage cutaneous melanoma.

The Prognostic Importance of Sentinel Lymph Node Biopsy in Thin Melanoma

BackgroundSentinel lymph node biopsy (SLNB) is prognostically useful in patients with cutaneous melanoma with Breslow thickness >1 mm. The objective of this study was to determine whether sentinel node histology has similar prognostic importance in patients with thin melanomas (≤1 mm).MethodsThis was a retrospective study of patients who underwent SLNB for clinically localized melanoma at Indiana University Medical Center between 1994 and 2003. SLNB results and traditional melanoma prognostic indicators were studied in univariate log-rank tests.ResultsOne hundred eighty-four patients with melanomas ≤1 mm thick underwent SLNB. SLNB was tumor positive in 12 patients (6.5%). Univariate analysis of SLNB results revealed that Breslow thickness, Clark level of invasion, and mitotic index were associated with SLNB status. Tumor positivity was observed at different rates in tumor thickness subsets: <.75 mm, 2.3%; and .75 to 1.0 mm, 10.2% (P = .0372). Disease-free survival and overall survival were significantly associated with SLNB results in melanomas ≤1 mm (log-rank test: P < .0001 and P = .0125, respectively) at a median follow-up of 26.3 months.ConclusionsSLNB histology in melanomas ≤1.0 mm deep is a significant predictor of outcome. SLNB should be considered for selected patients with melanomas .75 to 1.0 mm.

Current therapy of cutaneous melanoma.

Melanoma is a growing public health problem. Optimal care of the melanoma patient is multidisciplinary, but plastic surgeons and other surgical specialties play a central role in the management of these patients. Although surgery remains the mainstay of therapy for melanoma, several recent clinical studies have helped to clarify the biology of the disease and have changed the patterns of care for patients with melanoma. The advent of lymphatic mapping for interrogation of regional lymph nodes and interferon as the first effective postsurgical adjuvant therapy have had a major impact on the care of melanoma in the United States and elsewhere. This article will review the current clinical approach and therapy for cutaneous melanoma. The diagnosis, prognostic variables, staging evaluation, current surgical and medical treatment, and follow-up guidelines for patients with all stages of melanoma are reviewed. Recent studies, controversies, and directions of future investigational therapies will be discussed.

Initial assessment of positron emission tomography for detection of nonpalpable regional lymphatic metastases in melanoma.

The purpose of this pilot study is to determine the feasibility of position emission tomography with fluorodeoxyglucose (FDG‐PET) for detection of nonpalpable regional lymph node metastases in patients with melanoma.

Patterns of initial recurrence and prognosis after sentinel lymph node biopsy and selective lymphadenectomy for melanoma.

&NA; The histologic status of the sentinel lymph node is a highly significant prognostic factor for patients with clinically localized cutaneous melanoma. The patterns of initial treatment failure of patients with positive sentinel lymph node biopsy versus those with negative results have not been well described. The purpose of this study was to determine the relative prognostic importance of sentinel lymph node status and to compare patterns of initial treatment failure and prognosis of node‐positive versus nodenegative cutaneous melanoma patients staged by sentinel lymph node biopsy and selective lymphadenectomy. The authors reviewed the pertinent demographic and surgical data in a consecutive series of patients with cutaneous melanoma who underwent sentinel lymph node staging of nonpalpable regional nodes. Sentinel lymph node biopsy was performed using a combination of blue dye and radiolocalization. Patients with positive biopsy results underwent selective lymphadenectomy, whereas those with negative results were observed. Site(s) and date(s) of initial recurrence and death were determined, and diseasefree and overall survival probabilities were compared between positive and negative groups using the log‐rank test and multivariable Cox regression analysis. Between February of 1994 and August of 2000, 408 patients with melanoma underwent sentinel lymph node biopsy to stage 518 regional lymph node basins. Mean Breslow tumor thickness was 2.27 mm (range, 0.2 to 14.0 mm). Eighty‐five patients (20.8 percent) had at least one histologically positive sentinel lymph node, and selective lymphadenectomy yielded additional positive lymph nodes in 18 of 84 patients (21.4 percent). Recurrences were noted in 70 patients (17 percent) at a median follow‐up period of 31.4 months. Recurrences were more frequent in patients with positive biopsy results (36.5 percent) than in those with negative results (12.1 percent, p < 0.0001). Distant sites of initial recurrence were more likely in the positive group than in the negative group (71 percent versus 49 percent of recurrences, respectively; p = 0.06). The false‐negative rate for sentinel lymph node staging was 4.5 percent and overall accuracy was 99 percent compared with clinical follow‐up. Disease‐free and overall survival correlated significantly with tumor thickness, ulceration, sentinel lymph node status, and the number of tumor‐positive lymph nodes (two‐sided p < 0.0001 for all comparisons). Multivariable analysis revealed that sentinel lymph node status (p = 0.003), tumor thickness (p = 0.016), ulceration (p = 0.006), and age (p = 0.003) were significant independent predictors of survival for the entire group. Tumor thickness and ulceration were significant predictors of recurrence and survival in sentinel node‐negative patients but not in sentinel node‐positive patients. Sentinel lymph node histology is possibly the most important negative predictor of early recurrence and survival in patients with American Joint Committee on Cancer stage I and II melanoma. The number of positive lymph nodes provides additional prognostic information. Although sentinel node‐negative patients are a prognostically favorable group, various combinations of local and regional recurrences comprise the most common pattern of initial relapse after a negative sentinel lymph node biopsy result. (Plast. Reconstr. Surg. 112: 486, 2003.)

Sentinel lymph node biopsy for melanoma: experience with 234 consecutive procedures.

Sentinel lymph node biopsy is increasingly used to identify occult metastases in regional lymph nodes of patients with melanoma. Selection of patients for sentinel lymph node biopsy and subsequent lymphadenectomy is an area of debate. The purpose of this study was to describe a large clinical series of these biopsies for cutaneous melanoma and to identify patients most likely to gain useful clinical information from sentinel lymph node biopsy. The Indiana University Melanoma Program computerized database was queried to identify all patients who underwent this procedure for clinically localized cutaneous melanoma. It was performed using preoperative technetium Tc 99m lymphoscintigraphy and isosulfan blue dye. Pertinent demographic, surgical, and histopathologic data were recorded. Univariate and multivariate logistic regression and classification table analyses were performed to identify clinical variables associated with sentinel node and nonsentinel node positivity. In total, 234 biopsy procedures were performed to stage 291 nonpalpable regional lymph node basins. Mean Breslow’s thickness was 2.30 mm (2.08 mm for negative sentinel lymph node biopsy, 3.18 mm for positive). The mean number of sentinel nodes removed was 2.17 nodes per basin (range, 1 to 8). Forty-seven of 234 melanomas (20.1 percent) and 50 of 291 basins (17.2 percent) had a positive biopsy. Positivity correlated with AJCC tumor stage: T1, 3.6 percent; T2, 8.1 percent; T3, 27.4 percent; T4, 44 percent. By univariate logistic regression, Breslow’s thickness (p = 0.003, continuous variable), ulceration (p = 0.003), mitotic index ≥ 6 mitoses per high power field (p = 0.008), and Clark’s level (p = 0.04) were significantly associated with sentinel lymph node biopsy result. By multivariate analysis, only Breslow’s thickness (p = 0.02), tumor ulceration (p = 0.02), and mitotic index (p = 0.02) were significant predictors of biopsy positivity. Classification table analysis showed the Breslow cutpoint of 1.2 mm to be the most efficient cutpoint for sentinel lymph node biopsy result (p = 0.0004). Completion lymphadenectomy was performed in 46 sentinel node-positive patients; 12 (26.1 percent) had at least one additional positive nonsentinel node. Nonsentinel node positivity was marginally associated with the presence of multiple positive sentinel nodes (p = 0.07). At mean follow-up of 13.8 months, four of 241 sentinel node-negative basins demonstrated same-basin recurrence (1.7 percent). Sentinel lymph node biopsy is highly reliable in experienced hands but is a low-yield procedure in most thin melanomas. Patients with melanomas thicker than 1.2 mm or with ulcerated or high mitotic index lesions are most likely to have occult lymph node metastases by sentinel lymph node biopsy. Completion therapeutic lymphadenectomy is recommended after positive biopsy because it is difficult to predict the presence of positive nonsentinel nodes.

Lymphoscintigraphy with sentinel lymph node biopsy in cutaneous merkel cell carcinoma

Merkel cell carcinoma (MCC) is a rare cutaneous malignancy characterized by an aggressive clinical behavior with high rates of locoregional and systemic recurrence. Regional disease and distant metastases are associated with poor prognosis. Despite a predisposition of MCC to spread via the lymphatics, prophylactic lymph node dissection in the absence of clinically apparent lymph node involvement is controversial. The value of lymphoscintigraphy in cutaneous melanoma is established in lesions with ambiguous lymphatic drainage patterns. When used with sentinel lymph node biopsy (SLNB), it can identify subjects with occult regional node metastasis. The authors present 2 patients with MCC who underwent regional node staging with lymphoscintigraphy-directed SLNB. Both patients had sentinel nodes that were positive for metastatic disease. In patients with MCC, minimally invasive regional node staging SLNB may be useful in limiting the sequelae of routine lymphadenectomies. Whether early identification and treatment of patients with occult regional node disease can influence survival in MCC is not known.

Metopic Synostosis: Evaluation of Aesthetic Results

Analysis of intermediate- and long-term results of surgical treatment of metopic synostosis is lacking. We therefore retrospectively studied 23 patients with metopic synostosis (14 males, 9 females) who have been followed from 3 months to 8.1 years (mean 42.5 months) after operation. Age at first operation ranged from 2 to 56 months (mean 8.2 months), with 15 patients operated on before 6 months and 8 after 7 months. Fronto-orbital remodeling and calvarial vault reshaping with floating forehead techniques were carried out in all patients. Stabilization of bony segments was accomplished with microplates and screws in 7 patients (30 percent), wires in 15 (65 percent), and absorbable sutures in 1. Complications included minor wound dehiscence (n = 1), seizures (n = 1), and increased intracranial pressure (n = 1). Postoperative photographic documentation of surgical results was avaiable in 17 of the 23 patients. Aesthetic outcome in these 17 patients was graded (I = none or minor contour irregularities; II = moderate; and III = severe) by one of the authors (Cohen) and by a lay panel (n = 3) according to the degree of residual cranio-orbital deformity. Judged by the surgeon, grade I results were present in 53 percent, grade II in 35 percent, and grade III in 12 percent. To date, total reoperation (reoperative fronto-orbital remodeling and calvarial vault reshaping) was necessary in 2 patients (9 percent), one of whom had signs of increased intracranial pressure 3 years after the original craniofacial procedure, while partial reoperation (temporal cranioplasty) was carried out (n = 2) or recommended (n = 3) in another 5 patients. When outcomes were analyzed critically, aesthetic results appeared to be superior in the group stabilized with plates and screws, although follow-up times were shorter (mean 14.6 months) than for patients undergoing fronto-orbital remodeling with wire osteosynthesis (mean 54.5 months). Serial postoperative photographs, which were available in 10 patients, showed that forehead deformities worsened over time in 1 patient but were stable in the remaining 9.

Clinical utility of open lung biopsy for undiagnosed pulmonary infiltrates

Open lung biopsy (OLB) is often performed as the definitive diagnostic procedure in patients with undiagnosed pulmonary infiltrates, but controversy exists as to the clinical utility of this practice. A retrospective review of 50 consecutive patients who underwent OLB for undiagnosed pulmonary infiltrates was done to assess the diagnostic value as well as the frequency with which these results affected therapy and mortality. Histologic tissue diagnoses were obtained in all patients. Specific pathologic diagnoses were obtained in 56% of patients, nonspecific in 44%. Lobar or lateralized infiltrates were more likely to yield a specific diagnosis (87%) than diffuse, bilateral infiltrates (42%). Thirty-four patients (68%) had previously had a nondiagnostic transbronchial biopsy; 58% of these patients had a specific diagnosis established by OLB. Twelve patients (24%) were in acute respiratory failure at the time of OLB; this group had a 50% mortality rate as compared with only 2.6% for patients not in acute respiratory failure (p less than 0.01). Therapy was altered (new specific or nonspecific treatment initiated or therapy withdrawn) in 78% of patients undergoing OLB. Thirty-day in-hospital survival was significantly higher in patients for whom either specific or nonspecific therapy was indicated and initiated versus those in whom no therapy was initiated or all therapy was withdrawn (mortality: 5.5% versus 35.7%; p = 0.01). Mortality was not related to the presence of immunosuppression or to the finding of a specific diagnosis. The overall mortality rate of 14% in this series compares favorably with mortality rates found in similar series, reflecting differences in patient populations and possibly the timing of intervention. OLB remains a clinically valuable diagnostic tool in selected patients.