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BackgroundSince the introduction of minimally invasive surgery, surgeons appear to be experiencing more occupational musculoskeletal injuries. The aim of this study is to investigate the current frequency and effects of occupational musculoskeletal injuries on work absence.MethodsAn online questionnaire was conducted among all surgeons affiliated to the Dutch Society for Endoscopic Surgery, Gastrointestinal Surgery, and Surgical Oncology. In addition, this survey was conducted among surgeons, gynaecologists, and urologists of one cluster of training hospitals in the Netherlands.ResultsThere were 127 respondents. Fifty-six surgeons currently suffer from musculoskeletal complaints, and 30 have previously suffered from musculoskeletal complaints with no current complaints. Frequently reported localizations were the neck (39.5 %), the erector spinae muscle (34.9 %), and the right deltoid muscle (18.6 %). Most of the musculoskeletal complaints were present while operating (41.8 %). Currently, 37.5 % uses medication and/or therapy to reduce complaints. Of surgeons with past complaints, 26.7 % required work leave and 40.0 % made intraoperative adjustments. More surgeons with a medical history of musculoskeletal complaints have current complaints (OR 6.1, 95 % CI 1.9–19.6). There were no significant differences between surgeons of different operating techniques in localizations and frequency of complaints, or work leave.ConclusionsDespite previous various ergonomic recommendations in the operating room, the current study demonstrated that musculoskeletal complaints and subsequent work absence are still present among surgeons, especially among surgeons with a positive medical history for musculoskeletal complaints. Even sick leave was necessary to fully recover. There were no significant differences in reported complaints between surgeons of different operating techniques. Almost half of the respondents with complaints made intraoperative ergonomic adjustments to prevent future complaints. The latter would be interesting for future research.

Background The Clinicopathological and Gene Expression Profile (CP-GEP) model was developed to accurately identify patients with T1-T3 primary cutaneous melanoma at low risk for nodal metastasis. Objectives To validate the CP-GEP model in an independent Dutch cohort of patients with melanoma. Methods Patients (aged ≥ 18 years) with primary cutaneous melanoma who underwent sentinel lymph node biopsy (SLNB) between 2007 and 2017 at the Erasmus Medical Centre Cancer Institute were eligible. The CP-GEP model combines clinicopathological features (age and Breslow thickness) with the expression of eight target genes involved in melanoma metastasis (ITGB3, PLAT, SERPINE2, GDF15, TGFBR1, LOXL4, CXCL8 and MLANA). Using the pathology result of SLNB as the gold standard, performance measures of the CP-GEP model were calculated, resulting in CP-GEP high risk or low risk for nodal metastasis. Results In total, 210 patients were included in the study. Most patients presented with T2 (n = 94, 45%) or T3 (n = 70, 33%) melanoma. Of all patients, 27% (n = 56) had a positive SLNB, with nodal metastasis in 0%, 30%, 54% and 16% of patients with T1, T2, T3 and T4 melanoma, respectively. Overall, the CP-GEP model had a negative predictive value (NPV) of 90Á5% [95% confidence interval (CI) 77Á9-96.2], with an NPV of 100% (95% CI 72Á2-100) in T1, 89Á3% (95% CI 72Á8-96Á3) in T2 and 75Á0% (95% CI 30Á1-95Á4) in T3 melanomas. The CP-GEP indicated high risk in all T4 melanomas. Conclusions The CP-GEP model is a noninvasive and validated tool that accurately identified patients with primary cutaneous melanoma at low risk for nodal metastasis. In this validation cohort, the CP-GEP model has shown the potential to reduce SLNB procedures in patients with melanoma.What is already known about this topic?• The majority (70-85%) of patients with cutaneous melanoma who undergo a sentinel lymph node biopsy (SLNB) procedure have no metastasis in the SLN.• To identify patients at low risk for nodal metastasis, the Clinicopathological and Gene Expression Profile (CP-GEP) model was developed (n = 754 patients, US cohort).• The CP-GEP model combines age, Breslow thickness and the expression of eight target genes involved in melanoma metastasis, and has the potential to reduce SLNB procedures in patients with T1-T3 cutaneous melanoma.

Background The introduction of programmed cell death protein 1 (PD-1) blockers (i.e. nivolumab and pembrolizumab) has significantly improved the prognosis of patients with advanced melanoma. However, the long treatment duration (i.e. two years or longer) has a high impact on patients and healthcare systems in terms of (severe) toxicity, health-related quality of life (HRQoL), resource use, and healthcare costs. While durable tumour responses have been observed and PD-1 blockade is discontinued on an individual basis, no consensus has been reached on the optimal treatment duration. The objective of the Safe Stop trial is to evaluate whether early discontinuation of first-line PD-1 blockade is safe in patients with advanced and metastatic melanoma who achieve a radiological response. Methods The Safe Stop trial is a nationwide, multicentre, prospective, single-arm, interventional study in the Netherlands. A total of 200 patients with advanced and metastatic cutaneous melanoma and a confirmed complete response (CR) or partial response (PR) according to response evaluation criteria in solid tumours (RECIST) v1.1 will be included to early discontinue first-line monotherapy with nivolumab or pembrolizumab. The primary objective is the rate of ongoing responses at 24 months after discontinuation of PD-1 blockade. Secondary objectives include best overall and duration of response, need and outcome of rechallenge with PD-1 blockade, and changes in (serious) adverse events and HRQoL. The impact of treatment discontinuation on healthcare resource use, productivity losses, and hours of informal care will also be assessed. Results will be compared to those from patients with CR or PR who completed 24 months of treatment with PD-1 blockade and had an ongoing response at treatment discontinuation. It is hypothesised that it is safe to early stop first-line nivolumab or pembrolizumab at confirmed tumour response while improving HRQoL and reducing costs. Discussion From a patient, healthcare, and economic perspective, shorter treatment duration is preferred and overtreatment should be prevented. If early discontinuation of first-line PD-1 blockade appears to be safe, early discontinuation of PD-1 blockade may be implemented as the standard of care in a selected group of patients. Trial registration The Safe Stop trial has been registered in the Netherlands Trial Register (NTR), Trial NL7293 (old NTR ID: 7502), https://www.trialregister.nl/trial/7293. Date of registration September 30, 2018.

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