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Background The usefulness of sentinel lymph node biopsy (SLNB) in staging cutaneous melanoma has been proven. Therefore, different tracers have been used to identify the sentinel lymph nodes (SLNs). The use of isotopic tracers together with radioactivity detectors allowed a much more precise and direct approach to the SLNs. However, not all centres have access to a Nuclear Medicine department hindering sentinel lymph node detection (SLND) and consequently, other markers such as ferromagnetic tracers have been evaluated looking for the same advantages and effectiveness as isotopic tracers. Ferromagnetic tracers have proven their usefulness in other cancer entities such as breast, prostate and thyroid cancer. The objective was to assess the detection and concordance rates between isotopic and ferromagnetic techniques for SLNB in cutaneous melanoma. Method Isotopic SLNB technique and ferromagnetic tracer were compared for cutaneous melanoma in a non-inferiority multicentre prospective study carried out in six Spanish hospitals. Results A total of 60 patients were recruited and 133 lymph nodes removed. The detection rate was slightly higher with ferromagnetic tracer in head-neck and trunk melanomas, and with isotopic tracer in limbs. The patients' and nodes' concordance rates between both techniques for ex vivo samples were 95% and 86% for head-neck and trunk tumours and 97% and 93% for limbs tumours, respectively. The concordance rates for involved nodes were 100% and 88.2% for patients and nodes, respectively. Conclusion The intraoperative detection and biopsy of SLN in cutaneous melanoma using a ferromagnetic was a reliable alternative method to the isotopic technique in cutaneous melanomas.

The therapeutic value of sentinel lymph node biopsy (SLNB) in thin melanoma remains controversial. The aim of this study is to determine the role of SLNB in the survival of thin melanomas (≤1 mm). A multicenter retrospective observational study was designed. A propensity score matching was performed to compare patients who underwent SLNB vs. observation. A multivariate Cox regression was used. A total of 1438 patients were matched by propensity score. There were no significant differences in melanoma-specific survival (MSS) between the SLNB and observation groups. Predictors of MSS in the multivariate model were age, tumor thickness, ulceration, and interferon treatment. Results were similar for disease-free survival and overall survival. The 5- and 10-year MSS rates for SLN-negative and -positive patients were 98.5% vs. 77.3% (p < 0.001) and 97.3% vs. 68.7% (p < 0.001), respectively. SLNB does not improve MSS in patients with thin melanoma. It also had no impact on DSF or OS. However, a considerable difference in MSS, DFS, and OS between SLN-positive and -negative patients exists, confirming its value as a prognostic procedure and therefore we recommend discussing the option of SLNB with patients.

The clinical value of sentinel lymph node (SLN) biopsy in thick melanoma patients (Breslow >4 mm) has not been sufficiently studied. The aim of the study is to evaluate whether SLN biopsy increases survival in patients with thick cutaneous melanoma, and, as a secondary objective, to investigate correlations between survival and lymph node status. We included 1211 consecutive patients with thick melanomas (>4 mm) registered in the participating hospitals' melanoma databases between 1997 and 2015. Median follow-up was 40 months. Of these patients, 752 were matched into pairs by propensity scores based on sex, age, tumor location, histologic features of melanoma, year of diagnosis, hospital, and adjuvant interferon therapy. The SLN biopsy vs. observation was associated with better DFS (adjusted hazard ratio [AHR], 0.74; 95% confidence interval [CI] 0.61-0.90); P = .002) and OS (AHR, 0.75; 95% CI, 0.60-0.94; P = .013) but not MSS (AHR, 0.84; 95% CI, 0.65-1.08; P = .165). SLN-negative patients had better 5- and 10-year MSS compared to SLN-positive patients (65.4% vs. 51.9% and 48.3% vs 38.8%; p=0.01, respectively). As a conclusion, SLN biopsy was associated with better DFS but not MSS in thick melanoma patients after adjustment for classic prognostic factors. SLN biopsy is useful for stratifying these patients into different prognostic groups. This article is protected by copyright. All rights reserved.

Acral melanoma (AM) is associated with a poor prognosis in part because of delayed diagnosis, but probably also because of other intrinsic characteristics of location. The aim of this study was to review the specific characteristics and outcome of AM in Caucasians. This was a cross-sectional retrospective clinical-pathological study of 274 patients identified with AM in the database of a referral unit in Europe from 1986 to 2010. The mean age of the patients was 56.6 (SD 17.7) years. 269 cases could be histologically classified and included in the study. In all, 222 (82.5%) were located on feet. According to melanoma subtype, 165 (61.3%) were acral lentiginous melanoma (ALM), 84 (31.2%) were superficial spreading melanoma (SSM), and 20 (7.5%) were nodular melanoma (NM). SSM patients were characterized by female predominance (77.4%), younger age, and classic melanoma-risk phenotype (fair skin and multiple nevi). Among the 198 invasive cases with a mean follow-up of 56.2 months, the mean (SD) Breslow's thickness was 3.1 (3.6) mm, being 1.4 (1.4) mm in SSM, 3.5 (4.1) mm in ALM and 4.9 (2.9) mm in NM (P

Introduction: Sentinel lymph node (SLN) biopsy is useful for the prognostic stratification of patients with thick melanoma. Identifying which variables are associated with SLN involvement and establishing risk in different subgroups of patients could be useful for guiding the indication of SLN biopsy. The value of complete lymph node dissection (CLND) in patients with a positive SLN biopsy is currently under debate. Materials and methods: To identify factors associated with SLN involvement in thick melanoma we performed a multicentric retrospective cohort study involving 660 patients with thick melanoma who had undergone SLN biopsy. To analyze the role of CLND in thick melanoma patients with a positive SLN biopsy, we built a multivariate Cox proportional hazards model for melanoma-specific survival (MSS) and disease-free survival (DFS) and compared 217 patients who had undergone CLND with 44 who had not. Results: The logistic regression analysis showed that age, histologic subtype, ulceration, microscopic satellitosis, and lymphovascular invasion were associated with nodal disease. The CHAID (Chi-squared Automatic Interaction Detection) decision tree showed ulceration to be the most important predictor of lymphatic involvement. For nonulcerated melanomas, the histologic subtype lentigo maligna melanoma was associated with a low rate of SLN involvement (4.3%). No significant differences were observed for DFS and MSS between the CLND performed and not-performed groups. Nodal status on CLND was associated with differences in DFS and MSS rates. Conclusion: We identified subgroups of thick melanoma patients with a low likelihood of SLN involvement. CLND does not offer survival benefit, but provides prognostic information. (C) 2019 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Background There is no international consensus on optimal follow-up schedules and which supplementary tests should be used after resection of a primary melanoma. Objective We sought to analyze the performance of the follow-up components and identify procedures that detect melanoma metastasis earlier. Methods This was a prospective cohort from 290 consecutive patients given a diagnosis of stage IIB, IIC, and III melanoma. Patients were followed up with an intensive protocol based on imaging studies (computed tomography of the chest, abdomen, and pelvis, and brain magnetic resonance imaging), periodic laboratory tests, regular physical examinations, and patient self-examinations. Results A total of 2382 clinical examinations and 3069 imaging tests were performed. The patients completed 899.8 person-years of follow-up, with a median of 2.5 years. In all, 115 recurrences in 290 patients were recorded, of which computed tomography detected 48.3%; brain magnetic resonance imaging, 7.6%; laboratory test, 2.5%; physician, 23.7%; and patient, 17.8%. Limitations Patients with stage III melanoma were not systematically classified into subgroups and overall survival was not evaluated. Conclusion We observed that this intensive monitoring is appropriate for early detection of recurrence in stage IIB, IIC, and III melanoma. Prompt diagnosis of metastasis and the recent development of new therapeutic targets may improve overall survival.

Isolated perfusion is a treatment option when metastases are located on a limb and they are too numerous or when they recur too frequently for excision, even in the presence of distant metastases. Isolated limb perfusion enables treatment of an entire extremity with drugs without exposing the rest of the body to the medication. In the isolated limb, drug concentrations of up to 20 times the level that would be tolerated in the rest of the body may be reached. Perfusion provides the opportunity to treat not only the lesions that are evident but also occult lesions that could become evident later. Continuous monitoring can detect systemic leakage at an early stage. This is needed in situations when systemic leakage is known to occur and when tumor necrosis factor is administered. The detection of systemic leakage was classically performed by measurement of radiotracer concentrations in blood samples from the perfusate and systemic circulation. Radioguided monitoring of potential systemic leakage has been accomplished by using a precordial scintillation detector, a handheld gamma ray probe, or a mobile small field-of-view gamma camera in the operating room.

Summary Background Histological features such as Breslow thickness, ulceration and mitosis are the main criteria to guide sentinel lymph node biopsy (SLNB) in melanoma. Dermoscopy may add complementary information to these criteria. Objectives To evaluate the correlation between dermoscopy structures and SLNB positivity. Methods Retrospective analysis of 123 consecutive melanomas with Breslow thickness > 0·75 mm, SLNB performed during follow-up and dermoscopic images. Results Men were more likely to have a positive SLNB. The presence of ulceration and blotch and the absence of a pigmented network in dermoscopy correlated with positive SLNB. Histological ulceration also correlated with positive SLNB. A dermoscopy SCORE predicted SLN status with a sensitivity of 96·3% and a specificity of 30·2%. When sex and Breslow thickness were added (SCOREBRESEX), the sensitivity remained at 96·3% but the specificity increased to 52·1%. This study is limited by the number of patients and was performed in only one institution. Conclusions Dermoscopy allowed a more precise prediction of SLN status. If a combined SCOREBRESEX was used to select patients for SLNB, 41·5% of procedures might be avoided.

Introduction and objectives Electrochemotherapy is indicated for the treatment of unresectable cutaneous and subcutaneous tumors. The technique involves the synergistic use of electroporation of cell membranes to increase the cytotoxicity of anticancer drugs delivered to the tumor cells. The aim of this study was to analyze the clinical effectiveness and safety of electrochemotherapy in the treatment of unresectable locoregional recurrent or metastatic melanomas. Material and methods We studied 31 patients treated between January 2007 and December 2012. The European Standard Operating Procedures of Electrochemotherapy (ESOPE) were applied in all cases. Treatment response was analyzed as overall patient response (mean response based on results for all lesions treated in a given patient). Results Response was classified as partial in 49% of patients and complete in 23%. At 1 year, the level of response achieved had been maintained in 17 patients. Disease progression was observed in 28% of the series. Immediate local complications (pain, swelling, erythema) were mild and resolved within 48 hours in most cases. Eight patients developed subsequent local complications, such as ulcers and secondary infections associated with necrosis of the lesions. These complications were brought under control with topical treatments. Conclusions Electrochemotherapy is a very effective, safe, and efficient treatment for advanced locoregional disease in patients with unresectable melanoma lesions.

Localization of sentinel lymph nodes can be challenging if they are in difficult anatomic locations or near high radiotracer activity. The purpose of this study was to assess the value of intraoperative real-time imaging using a portable gamma-camera in conjunction with a conventional gamma-counting probe when it is difficult to localize the sentinel node.After (99m)Tc-nanocolloid injection, patients with various malignancies underwent presurgical lymphoscintigraphy followed by surgery (usually the next day). We evaluated 20 patients who required sentinel lymph node biopsy and in whom the location or other characteristics of the sentinel node would make intraoperative retrieval difficult. During surgery, the sentinel node was localized using a portable gamma-camera together with a hand-held gamma-probe. A (153)Gd pointer or (125)I seed was used to better depict the sentinel node location in real time.Using only a conventional hand-held gamma-probe, surgeons were able to definitively localize the sentinel node in 15 of 20 patients. Intraoperatively, the portable gamma-camera showed uptake by the definite sentinel node in 19 of 20 patients and helped to precisely localize the node with the hand-held gamma-probe in 4 patients. In 1 of these patients, the sentinel node was metastatic.The combination of a standard hand-held gamma-probe and real-time imaging provided by a portable gamma-camera offers a high intraoperative detection rate in patients with difficult sentinel node localization as assessed by presurgical lymphoscintigraphy.

Background: The treatment of malignant melanoma or sarcomas on a limb using extremity perfusion with tumour necrosis factor (TNF-alpha) and melphalan can result in a high degree of systemic toxicity if there is any leakage from the isolated blood territory of the limb into the systemic vascular territory. Leakage is currently controlled by using radiotracers and heavy external probes in a procedure that requires continuous manual calculations. The aim of this work was to develop a light, easily transportable system to monitor limb perfusion leakage by controlling systemic blood pool radioactivity with a portable gamma camera adapted for intraoperative use as an external probe, and to initiate its application in the treatment of MM patients. Methods: A special collimator was built for maximal sensitivity. Software for acquisition and data processing in real time was developed. After testing the adequacy of the system, it was used to monitor limb perfusion leakage in 16 patients with malignant melanoma to be treated with perfusion of TNF-alpha and melphalan. Results: The field of view of the detector system was 13.8 cm, which is appropriate for the monitoring, since the area to be controlled was the precordial zone. The sensitivity of the system was 257 cps/MBq. When the percentage of leakage reaches 10% the associated absolute error is +/- 1%. After a mean follow-up period of 12 months, no patients have shown any significant or lasting side-effects. Partial or complete remission of lesions was seen in 9 out of 16 patients (56%) after HILP with TNF-alpha and melphalan. Conclusion: The detector system together with specially developed software provides a suitable automatic continuous monitoring system of any leakage that may occur during limb perfusion. This technique has been successfully implemented in patients for whom perfusion with TNF-alpha and melphalan has been indicated.

Summary Objective. To determine the prognostic value of detecting tyrosinase transcripts in melanoma sentinel lymph nodes (SLNs). Methods. Reverse transcription (RT) PCR for tyrosinase mRNA was performed on negative SLNs of 76 patients with melanoma. Results. Tyrosinase mRNA was found in 39 patients (51.3%). After a median follow-up period of 51 months, significant differences were found in overall survival (OS) but not in disease-free survival (DFS). The 5-year OS and DFS rates were 97.2% and 80%, respectively, for RT-PCR tyrosinase-negative (TN) patients vs. 78.67% and 66.24% for RT-PCR tyrosinase-positive (TP) patients (P = 0.019 and P = 0.38, respectively). Of four progressing patients in the TN group, three relapsed with subcutaneous, soft-tissue or lymph-node metastases, while seven out of nine progressing patients in the TP group relapsed at visceral sites. Conclusions. No significant differences in DFS were found by RT-PCR tyrosinase expression analysis at melanoma SLNs. Significant differences in OS could be related to a different pattern of relapse and must be confirmed after a longer follow-up time.

Contains fulltext : 57915.pdf (Publisher’s version ) (Closed access) Malignant melanoma (MM) early lymph node (LN) metastasis usually appears first in the sentinel LN (SLN). Breslow thickness is the main factor considered in the selection of patients to be submitted to SLN biopsy. The present study aimed to describe other independent prognostic factors useful in SLN candidate selection. During one year, 94 MM patients (90 primary cutaneous MM with Breslow thickness > or = 0.76 mm, and four cutaneous relapses), were submitted to SLN biopsy in the Melanoma Unit at the Hospital Clinic, Barcelona, Spain. The prognostic factors studied were: Breslow thickness, Clark's level of invasion, mitotic rate, cellular type (small, epithelioid, fusocellular, sarcomatoid), vertical growth phase, regression > 50%, severe vascularization, infiltrate (lymphocytic, plasmocytic), ulceration, neurotropism, intravascular/intraneural invasion, protein p16 expression and recurrence. Nineteen SLN (20.2%) were positive and 75 (79.8%) negative. No positive SLN occurred in MM with Breslow thickness < or = 1.0 mm. Breslow thickness > or = 2 mm (P = 0.005), severe vascularization (P = 0.005), small cell (P = 0.000) and ulceration (P = 0.005) were significant prognostic factors by univariate analysis. Small cell (P = 0.008) and ulceration (P = 0.05) were also significant prognostic factors in a multivariate analysis. The probability of finding a positive SLN for small cell was 56.9% [95% confidence interval (CI), 26.8-82.6%]. The probability of positive SLN for ulceration was 35.5% (95% CI, 14.2-64.7%). For small cell and ulceration together the probability increased to 86.3% (95% CI, 54.3-97.1%). The results of this study corroborated ulceration as a prognostic factor for SLN candidate selection and for the first time we have described small cell melanoma morphology as a significant factor associated with positive SLN.

The sentinel lymph node (SLN) is the first node in a nodal basin to receive the direct lymphatic flow from a malignant melanoma. However, in some patients, lymphoscintigraphic study reveals the presence of lymphatic nodes in the area between the primary melanoma and the regional basin. These nodes are called "in-transit nodes" or "interval nodes" and, by definition, are also SLNs. The purpose of this study was to determine the incidence and location of in-transit SLNs in patients with malignant melanoma and to assess whether it is really necessary to harvest them. The evaluation involved 600 consecutive malignant melanoma patients. Lymphoscintigraphy was performed on the day before surgery following intradermal injection of 74-111 MBq of (99m)Tc-nanocolloid in four doses around the primary melanoma or the biopsy scar. Dynamic and static images were obtained and revealed SLNs in 599 out of 600 patients. The SLN was intraoperatively identified with the aid of patent blue dye and a hand-held gamma probe. Lymphoscintigraphy showed in-transit SLNs in 59/599 patients (9.8%). During surgery, all these in-transit SLNs were harvested, with those in the popliteal and epitrochlear regions being the most difficult to identify and excise. Metastatic cell deposits were subsequently identified in ten (16.9%) of these in-transit SLNs. In conclusion, lymphoscintigraphy has a key role in the identification of in-transit SLNs. Although the incidence of these nodes is relatively low in malignant melanoma patients, such SLNs present metastatic deposits in a significant percentage of cases and therefore the identification of in-transit SLNs in these patients is really necessary.

Unresectable metastatic melanoma has no elective treatment. Neither chemotherapy, intravenous IL-2 nor biochemotherapy clearly improves the overall survival. Recent assays with therapeutic vaccines have been recently yielded promising results. Here, we describe the application, clinical tolerance and antitumoural activity of a heterologous polyvalent melanoma whole cell vaccine in patients with metastatic melanoma. Twenty-eight AJCC stage III/IV melanoma patients with progressive unresectable metastatic disease were treated with our heterologous polyvalent melanoma whole cell vaccine between July 1, 1998 and July 1, 2002. All patients had already been unsuccessfully treated with high doses of IFN-alpha2 and/or polychemotherapy and/or biochemotherapy and/or perfusion of extremities, or could not receive other treatments due to their age or underlying illness. Twenty-three were assessable. The vaccine was constituted by 10 melanoma cell lines, derived from primary, lymph node and metastatic melanomas. Prior to intradermal inoculation, the cells were irradiated and mixed with BCG, and 50% were treated with DNFB. After a median follow-up of 19 months, 26% of patients responded: 3 CR (18, 16+, and 26+ months), 2 PR (8 and 22 months) and 1 MR (36+ months). The median survival of the whole group was 20.2 months. None of the 28 patients initially included in the study presented significant toxicity. This vaccination program had specific antitumoural activity in advanced metastatic melanoma patients and was well tolerated. The clinical responses and the median survival of our group of patients, together with the low toxicity of our polyvalent vaccine, suggest that this approach could be applied to earlier metastatic melanoma patients.

Scintigraphic identification of the sentinel lymph node is achievable in nearly all patients with malignant melanoma. However, in a very small number of cases the sentinel node fails to be detected, and sometimes recurrence appears during follow-up in patients who had previously tested negative for metastatic disease. The purpose of this study was to review our experience in order to isolate the reasons for erroneous sentinel lymph node identification. The evaluation involved 435 consecutive malignant melanoma patients with AJCC stages I and II (clinically negative nodes) and Breslow thickness >0.76 mm. Lymphoscintigraphy was performed the day before surgery by intradermal administration of technetium-99m labelled nanocolloid. Dynamic and static images were obtained. The sentinel node was intraoperatively identified with the aid of patent blue dye and a hand-held gamma probe. After removal, routine histopathological examination with haematoxylin-eosin (H-E) and immunohistochemistry with S 100 and HMB45 (IHC) were performed. In those patients who developed regional recurrences during follow-up, sentinel nodes were further evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR). Lymphoscintigraphy visualised at least one sentinel node in 434 out of 435 patients (99.8%). Uptake in in-transit sentinel lymph nodes was observed in 32 patients (7.4%). During surgery, localisation and removal of sentinel nodes was successful in 430/435 patients (98.8%). A total of 790 sentinel lymph nodes were harvested, with a mean of 1.8 per patient. Routine histopathological examination with H-E or IHC revealed metastatic disease in 72 patients (16.8%). During a mean follow-up of 26 months, seven of those patients with a negative sentinel node developed regional lymph node metastases. In five of them RT-PCR was positive for micrometastases within the sentinel node. In conclusion, erroneous sentinel lymph node identification can be due to changes in the surgical team, difficult lymph node location or absence of a thorough histological study. Nevertheless, it is not possible to explain completely why, in a very small percentage of cases, the sentinel node is erroneously identified.

To assess the usefulness of lymphoscintigraphy and intraoperative gamma probe in the detection of sentinel lymph nodes.Prospective open study.University hospital, Spain.40 patients with malignant melanoma (24 stage I/II, 16 stage III).The day before operation a lymphoscintigram with 99mTc-nanocolloid was taken and the first lymph node identified was considered to be the sentinel node. A hand-held gamma probe was used for intraoperative mapping.Identification of the sentinel node.Sentinel nodes were identified in 39/40 patients (98%). In 24 patients with stage I/II disease, 34 sentinel nodes were found (6 invaded and 28 clear of melanoma). A total number of 161 regional lymph nodes were harvested, none of them invaded by melanoma. In 16 patients with stage III disease, 22 sentinel nodes were located (14 invaded and 8 clear of melanoma). A total of 89 regional lymph nodes were excised in patients with invaded sentinel nodes (44 of which were invaded and 45 clear of disease). 41 lymph nodes were excised from patients with clear sentinel nodes, and all were also clear of melanoma.We conclude that this is a useful technique for the selection of patients with melanoma who may require lymphadenectomy.

7514 Background: Detection of micro metastases in SLNs in MM pts is an important prognostic factor. When SLNs are involved survival is reduced in 40%, nevertheless, prediction of outcome is impreci...

Introduction: In patients with primary cutaneous melanoma, there is generally a delay between excisional biopsy of the primary tumour and sentinel-node biopsy. The objective of this study is to analyse the prognostic implications of this delay. Patients and method: This was an observational, retrospective, cohort study in four tertiary referral hospitals. A total of 1963 patients were included. The factor of interest was the interval between the date of the excisional biopsy of the primary melanoma and the date of the sentinel-node biopsy (delay time) in the prognosis. The primary outcome was melanoma-specific survival and disease-free survival. Results: A delay time of 40 days or less (hazard ratio (HR), 1.7; confidence interval (CI), 1.2-2.5) increased Breslow thickness (Breslow ⩾2 mm, HR, >3.7; CI, 1.4-10.7), ulceration (HR, 1.6; CI, 1.1-2.3), sentinel-node metastasis (HR, 2.9; CI, 1.9-4.2), and primary melanoma localised in the head or neck were independently associated with worse melanoma-specific survival (all P