Survival following surgical treatment for anorectal melanoma seems similar for local excision and extensive resection regardless of nodal involvement.

BACKGROUND: Anorectal melanoma is a rare malignancy with a dismal prognosis. The purpose of this study was to investigate whether the survival per stage is influenced by the surgical approaches (local excision or extensive resection), to assess prognostic factors of survival, and to answer the question whether the practiced surgical approaches changed over time. METHODS: Dutch cancer registry organizations (IKNL and PALGA) were queried for all patients with a diagnosis of anorectal melanoma (1989-2019). Patients with disseminated disease at diagnosis were excluded. Survival outcomes were compared for the two surgical approaches stratified by stage (clinical node negative (cN0) and clinical node positive (cN+)) and date of diagnosis. RESULTS: A total of 103 patients were included in this study. In both cN0 and cN+ patients the surgical strategy did not significantly influence survival (cN0: 21.7% 5-year survival, median 25 months for local excision versus 13.7% 5-year survival, median 17 months for extensive resection (p = 0.228), cN+: 11.1% 5-year survival for local excision, median 17 months versus 8.7% 5-year survival, median 14 months for extensive resection (p = 0.741)). Stage and date of diagnosis showed to be prognostic factors of survival. The ratio between the two surgical approaches was unchanged over three decades. CONCLUSIONS: Extensive resection does not seem to improve survival in both cN0 and cN+ anorectal melanoma patients compared to local excision. However in the past three decades no shift towards local excision has been found. cN+ stage and an older date of diagnosis are predictors for worse survival.

The association between active tumor volume, total lesion glycolysis and levels of S-100B and LDH in stage IV melanoma patients.

INTRODUCTION: The Standardized Uptake Value (SUV) in single lesions on 18F-FDG PET/CT scans and serum S-100B concentrations are inversely associated with disease-free survival in stage IV melanoma. The aim of this study was to assess the association between biomarkers (S-100B, LDH) and the PET-derived metrics SUVmean/max, metabolic active tumor volume (MATV), and total lesion glycolysis (TLG) in stage IV melanoma in order to understand what these biomarkers reflect and their possible utility for follow-up. METHODS: In 52 stage IV patients the association between PET-derived metrics and the biomarkers S-100B and LDH was assessed and the impact on survival analyzed. RESULTS: S-100B was elevated (>0.15 µg/l) in 37 patients (71%), LDH in 11 (21%). There was a correlation between S-100B and LDH (R2 = 0.19). S-100B was correlated to both MATV (R2 = 0.375) and TLG (R2 = 0.352), but LDH was not. Higher MATV and TLG levels were found in patients with elevated S-100B (p < 0.001) and also in patients with elevated LDH (>250 U/l) (p < 0.001). There was no association between the biomarkers and SUVmean/max. Survival analysis indicated that LDH was the only predictor of melanoma-specific survival. CONCLUSION: In newly diagnosed stage IV melanoma patients S-100B correlates with 18F-FDG PET/CT derived MATV and TLG in contrast to LDH, is more often elevated than LDH (71% vs. 21%) and seems to be a better predictor of disease load and disease progression. However, elevated LDH is the only predictor for survival. The biomarkers, S-100B and LDH appear to describe different aspects of the extent of metastatic disease and of tumornecrosis.

A prediction tool incorporating the biomarker S-100B for patient selection for completion lymph node dissection in stage III melanoma.

INTRODUCTION: Completion lymph node dissection (CLND) in sentinel node (SN)-positive melanoma patients is accompanied with morbidity, while about 80% yield no additional metastases in non-sentinel nodes (NSNs). A prediction tool for NSN involvement could be of assistance in patient selection for CLND. This study investigated which parameters predict NSN-positivity, and whether the biomarker S-100B improves the accuracy of a prediction model. METHODS: Recorded clinicopathologic factors were tested for their association with NSN-positivity in 110 SN-positive patients who underwent CLND. A prediction model was developed with multivariable logistic regression, incorporating all predictive factors. Five models were compared for their predictive power by calculating the Area Under the Curve (AUC). A weighted risk score, 'S-100B Non-Sentinel Node Risk Score' (SN-SNORS), was derived for the model with the highest AUC. Besides, a nomogram was developed as visual representation. RESULTS: NSN-positivity was present in 24 (21.8%) patients. Sex, ulceration, number of harvested SNs, number of positive SNs, and S-100B value were independently associated with NSN-positivity. The AUC for the model including all these factors was 0.78 (95%CI 0.69-0.88). SN-SNORS was the sum of scores for the five parameters. Scores of ≤9.5, 10-11.5, and ≥12 were associated with low (0%), intermediate (21.0%) and high (43.2%) risk of NSN involvement. CONCLUSIONS: A prediction tool based on five parameters, including the biomarker S-100B, showed accurate risk stratification for NSN-involvement in SN-positive melanoma patients. If validated in future studies, this tool could help to identify patients with low risk for NSN-involvement.

Laparoscopic anterior versus endoscopic posterior approach for adrenalectomy: a shift to a new golden standard?

PURPOSE: There has been an increased utilization of the posterior retroperitoneal approach (PRA) for adrenalectomy alongside the "classic" laparoscopic transabdominal technique (LTA). The aim of this study was to compare both procedures based on outcome variables at various ranges of tumor size. METHODS: A retrospective analysis was performed on 204 laparoscopic transabdominal (UMC Groningen) and 57 retroperitoneal (UMC Utrecht) adrenalectomies between 1998 and 2013. We applied a univariate and multivariate regression analysis. Mann-Whitney and chi-squared tests were used to compare outcome variables between both approaches. RESULTS: Both mean operation time and median blood loss were significantly lower in the PRA group with 102.1 (SD 33.5) vs. 173.3 (SD 59.1) minutes (p < 0.001) and 0 (0-200) vs. 50 (0-1000) milliliters (p < 0.001), respectively. The shorter operation time in PRA was independent of tumor size. Complication rates were higher in the LTA (19.1%) compared to PRA (8.8%). There was no significant difference in recovery time between both approaches. CONCLUSIONS: Application of the PRA decreases operation time, blood loss, and complication rates compared to LTA. This might encourage institutions that use the LTA to start using PRA in patients with adrenal tumors, independent of tumor size.

The predictive power of serum S-100B for non-sentinel node positivity in melanoma patients.

BACKGROUND: Completion lymph node dissection (CLND) in sentinel node (SN) positive melanoma patients leads to substantial morbidity and costs, while only approximately 20% have a metastasis in non-sentinel nodes (NSNs). The aim of this study was to investigate if the biomarkers S-100B and Lactate Dehydrogenase (LDH) are associated with NSN positivity, to identify patients in whom CLND could safely be omitted. METHODS: All SN positive patients who underwent CLND at the University Medical Centre Groningen between January 2004 and January 2015 were analysed. Patient and tumor characteristics, and serum S-100B and LDH values measured the day before CLND were statistically tested for their association with NSN positivity. RESULTS: NSN positivity was found in 20.6% of the 107 patients undergoing CLND. Univariate analysis revealed male gender (p = 0.02), melanoma of the lower extremity (p = 0.05), Breslow thickness (p = 0.004), ulceration (p = 0.04), proportion of involved SNs (p = 0.045) and S-100B value (p = 0.01) to be associated with NSN positivity. LDH level was not significantly associated with positive NSNs (p = 0.39). In multivariable analysis, S-100B showed to have the strongest association with NSN positivity, within its reference interval of 0.20 µg/l (p = 0.02, odds ratio 5.71, 95% confidence interval 1.37-23.87). CONCLUSION: In this study, the preoperatively measured S-100B value is the strongest predictor for NSN positivity in patients planned for CLND. Fluctuations of the S-100B level within the reference interval might give important clues about residual tumor load. Although further validation will be needed, this new closer look of S-100B could be of value in patient selection for CLND in the future.

Deep lymph node metastases in the groin significantly affects prognosis, particularly in sentinel node-positive melanoma patients.

BACKGROUND: In order to define patients eligible for only a superficial groin dissection or a combined superficial and deep groin dissection, this study aimed to determine the incidence of deep lymph node metastases (LNM) in patients with melanoma metastasized to the groin, to identify patient and melanoma factors that predict deep nodal involvement, and to analyze the impact of deep nodal involvement on survival and recurrence. METHODS: Patients who underwent a combined superficial (inguinal) and deep (iliac and obturator) complete (CLND) or therapeutic lymph node dissection (TLND) of the groin between 1994 and 2012 were analyzed. RESULTS: QueryDeep LNM were found in 8 of 62 CLND patients (13 %) and in 21 of 67 TLND patients (31 %). More than three superficial LNM was the only independent predictor for deep LNM in both CLND and TLND patients. The 5-year melanoma-specific survival (MSS) for CLND and TLND patients with deep LNM was 14.3 and 16.6 %, respectively, and was significantly worse (hazard ratio [HR] 3.39, 95 % CI 1.34-8.58, p = 0.010; and HR 2.01, 95 % CI 1.04-3.88, p = 0.039) compared with CLND and TLND patients without deep LNM (5-year MSS: 54.1 and 37.2 %, respectively). Distant recurrence was significantly associated with deep LNM in CLND patients (p = 0.032). CONCLUSIONS: The present study showed that LNM in the deep area of the groin are fairly common in both CLND and TLND patients and significantly affect prognosis, especially in CLND patients. The number of superficial LNM is the only factor that was found to predict a finding of deep nodal metastases.

Cutaneous melanoma: medical specialists' opinions on follow-up and sentinel lymph node biopsy.

BACKGROUND: The purpose, frequency and content of follow-up (FU) visits have been widely debated for all common malignancies, including melanoma. The aim was to gain insight into Dutch medical specialists' opinions on melanoma FU and to assess their views on sentinel lymph node biopsy (SLNB). METHODS: All members of the Dutch Society of Surgical Oncology and the Dutch Society of Dermatology and Venereology were invited to complete a web-based questionnaire, consisting of 25 questions addressing the following topics: 1) respondent characteristics, 2) knowledge of national melanoma guideline, 3) opinions on melanoma FU, and 4) view on the significance of SLNB. RESULTS: A total of 378 respondents (response = 37%) started the survey, including 173 surgeons (46%) and 205 dermatologists (54%). Of these, 97% and 92% agreed that the purpose of FU is detection of local recurrence and second primary, respectively. Concerning frequency of FU in the first 10 years after diagnosis, 42% preferred a less frequent FU than indicated by the current guideline, while 4% preferred more frequent FU. Overall, twenty-five percent agreed that the standard diagnostics of cutaneous melanoma should include a SLNB, the percentage was highest amongst surgical residents (44%). CONCLUSION: The majority of specialists consider melanoma FU to be primarily an instrument to detect recurrences and secondary primaries. The frequency of FU, as prescribed by the current guideline, could be reduced according to 42%. The importance of SLNB seems to be insufficiently addressed in the Dutch guideline and by Dutch medical specialists despite its role in the AJCC staging system.

S-100B: a stronger prognostic biomarker than LDH in stage IIIB-C melanoma.

BACKGROUND: In melanoma patients with nodal macrometastases, the distinction between good and poor prognosis is based on the presence of primary melanoma ulceration or metastatic involvement of 4 or more lymph nodes in the 7th edition of the American Joint Committee on Cancer (AJCC) classification. We hypothesized that biomarkers would increase the accurateness of staging in these patients. The aim was to assess and compare the prognostic impact of biomarkers S-100B and LDH and to determine the best timing of their measurement in stage IIIB-C melanoma. METHODS: A total of 119 patients underwent therapeutic lymph node dissection (TLND) for nodal macrometastases with serum S-100B and LDH level measurements preoperatively. In 75 of them, S-100B and LDH were also measured on postoperative days 1 and 2. S-100B and LDH levels on days 0, 1, and 2 were compared for their association with disease-free survival (DFS) and disease-specific survival (DSS). RESULTS: At a median follow-up of 17 (range 1-89) months, S-100B levels at all time points were associated with DFS. In multivariable analysis, preoperative S-100B and S-100B measured on day 2 showed the strongest association with DFS (hazard ratio [HR] 2.55, P = 0.007 and HR 3.80, P = 0.01). For DSS, the preoperative S-100B level was the strongest independent predictor (HR 2.81, P = 0.01). LDH measurements showed a significant association with DSS in univariate analysis only when measured preoperatively (HR 2.46, P = 0.01). In multivariable analysis, LDH measurement was not associated with melanoma prognosis. CONCLUSIONS: The S-100B level measured preoperatively is, in contrast to LDH, one of the most important independent predictors of melanoma prognosis in patients undergoing TLND for nodal macrometastases.

Stage IV melanoma: completely resectable patients are scarce.

BACKGROUND: In melanoma, about 1 in 5 patients develops distant metastases and suffers a very poor prognosis. Common treatment options comprise surgery, systemic medical therapy, and radiotherapy, depending on the number, the location, and the resectability of distant metastases. Previous studies suggested that surgery should be the first choice of treatment whenever complete surgical removal is feasible. However, the proportion of patients that are candidates for this approach is not clear. The aim of the present study was to evaluate the extent of disease and resectability in melanoma patients presenting with stage IV disease at our institute. METHODS: All melanoma patients diagnosed with stage IV between January 2011 and August 2012 were assessed for extent and resectability of their disease. RESULTS: About half of 70 assessed patients had 7 or more metastases at diagnosis, whereas 13 patients had only 1 metastasis. The vast majority (n = 55, 78.6 %) was ineligible for complete surgical resection. Six patients did receive complete surgery as initial stage IV treatment and in 9 patients incomplete surgery was performed. Widespread disease (n = 44) and unresectable metastasis (n = 11) were the most common reasons for refraining from complete surgery. CONCLUSION: The results of the present study show that only a small proportion of patients diagnosed with stage IV melanoma are candidates for complete surgical resection with curative intent in our institution.

Early mobilization after ilio-inguinal lymph node dissection for melanoma does not increase the wound complication rate.

AIM: Ilio-inguinal lymph node dissection for stage III melanoma is accompanied by a substantial amount of wound complications. Our treatment protocols changed in time in terms of postoperative bed rest prescriptions, being in chronological order Group A: 10 days with a Bohler Braun splint, Group B: 10 days without splint, and Group C: 5 days without splint. The aim of this study was to evaluate the effect of bed rest prescriptions on wound complications. METHODS: For this study, we included all patients who underwent ilio-inguinal dissection for stage III melanoma in the period 1989-2011. Both univariate and multivariable analysis were performed to identify factors that were associated with occurrence of wound complications defined as wound infection, wound necrosis, and seroma. RESULTS: Of the 204 patients analyzed, 99 suffered one or more wound complications: 51 wound infection, 29 wound necrosis, and 39 seroma. A wound complication occurred in 26 out of 64, 51 out of 89, and 22 out of 51 patients for Group A, B, and C, respectively. Univariate analysis showed age >55 (p = 0.001) and presence of comorbidity (p = 0.002) to be associated with higher incidence of wound complications. The 5 day bed rest protocol used in group C did not significantly increase the incidence of wound complications (ref = Group A: OR = 1.18; 95%CI = 0.52-2.68, p = 0.698). CONCLUSION: Early mobilization did not significantly increase the overall wound complication rate after ilio-inguinal lymph node dissection for melanoma. Age >55 and comorbidity were risk factors in univariate analysis.

Assessment of a new scoring system for predicting non-sentinel node positivity in sentinel node-positive melanoma patients.

BACKGROUND: When completion lymph node dissection (CLND) is performed in sentinel node (SN)-positive melanoma patients, a positive non-sentinel node (NSN) is found in approximately 20% of them. Recently, Murali et al. proposed a new scoring system (non-sentinel node risk score, N-SNORE) to predict the risk of NSN positivity in SN-positive patients. The objectives of the current study were to identify factors predicting NSN positivity and to assess the validity of the N-SNORE in an independent patient cohort. METHODS: All SN-positive patients who underwent CLND at a single institution between 1995 and 2010 were analyzed. Characteristics of the patient, primary melanoma, and SN(s) were tested for association with NSN positivity. Missing values were reconstructed using multiple imputation to enable multivariable analysis. RESULTS: CLND revealed positive NSNs in 30 (23%) of 130 SN-positive patients. Primary melanoma regression (p = 0.03) was independently associated with NSN positivity. After adjustment because of missing data on perinodal lymphatic invasion, N-SNORE proved to be a significant stratification model in our patient cohort (p = 0.003): 5.9% NSN positivity in the very low risk category and 75.0% NSN positivity in the very high risk category. CONCLUSIONS: Presence of regression in the primary melanoma was independently associated with a higher risk of NSN positivity. The slightly modified N-SNORE scoring system provided useful stratification of the risk for NSN positivity. However, lack of perinodal lymphatic invasion data may have reduced its predictive value.

Therapeutic lymph node dissection in melanoma: different prognosis for different macrometastasis sites?

BACKGROUND: The prognostic significance of primary tumor location, especially the poor prognosis for melanomas in the scalp and neck region, is well established. However, the prognosis for different sites of nodal macrometastasis has never been studied. This study investigated the prognostic value of the location of macrometastasis in terms of recurrence and survival rates after therapeutic lymph node dissection (TLND). METHODS: All consecutive FDG-PET-staged melanoma patients with palpable and cytologically proven lymph node metastases operated at our clinic between 2003 and 2011 were included. Disease-free survival and disease-specific survival (DSS) were compared for nodal metastases in the groin, axilla, and neck regions by multivariable analysis. RESULTS: A total of 149 patients underwent TLND; there were 70 groin (47 %), 57 axillary (38 %), and 22 neck (15 %) dissections. During a median follow-up of 18 (range 1-98) months, 102 patients (68 %) developed recurrent disease. Distant recurrence was the first sign of progressive disease in 78, 76, and 55 % of the groin, axilla, and neck groups, respectively (p = 0.26). Low involved/total lymph nodes (L/N) ratio (p < 0.001) and absence of extranodal growth pattern (p = 0.05) were independent predictors of a longer disease-free survival. For DSS, neck site of nodal metastasis (p = 0.02) and low L/N ratio (p < 0.001) were independent predictors of long survival. The estimated 5-year DSS for the groin, axilla, and neck sites was 28, 34, and 66 %, respectively. CONCLUSIONS: There seems significantly longer DSS after TLND for nodal macrometastases in the neck compared to axillary and groin sites, although larger series should confirm this finding.