BACKGROUND Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. METHODS In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis. RESULTS Immediate completion lymph-node dissection was not associated with increased melanoma-specific survival among 1934 patients with data that could be evaluated in an intention-to-treat analysis or among 1755 patients in the per-protocol analysis. In the per-protocol analysis, the mean (±SE) 3-year rate of melanoma-specific survival was similar in the dissection group and the observation group (86±1.3% and 86±1.2%, respectively; P=0.42 by the log-rank test) at a median follow-up of 43 months. The rate of disease-free survival was slightly higher in the dissection group than in the observation group (68±1.7% and 63±1.7%, respectively; P=0.05 by the log-rank test) at 3 years, based on an increased rate of disease control in the regional nodes at 3 years (92±1.0% vs. 77±1.5%; P<0.001 by the log-rank test); these results must be interpreted with caution. Nonsentinel-node metastases, identified in 11.5% of the patients in the dissection group, were a strong, independent prognostic factor for recurrence (hazard ratio, 1.78; P=0.005). Lymphedema was observed in 24.1% of the patients in the dissection group and in 6.3% of those in the observation group. CONCLUSIONS Immediate completion lymph-node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma-specific survival among patients with melanoma and sentinel-node metastases. (Funded by the National Cancer Institute and others; MSLT-II ClinicalTrials.gov number, NCT00297895.)

Inhibitory receptors mediate CD8 T-cell hyporesponsiveness against cancer and infectious diseases. PD-1 and CTLA-4 have been extensively studied, and blocking antibodies have already shown clinical benefit for cancer patients. Only little is known on extended co-expression of inhibitory receptors and their ligands. Here we analyzed the expression of eight inhibitory receptors by tumor-antigen specific CD8 T-cells. We found that the majority of effector T-cells simultaneously expressed four or more of the inhibitory receptors BTLA, TIM-3, LAG-3, KRLG-1, 2B4, CD160, PD-1 and CTLA-4. There were major differences depending on antigen-specificity, differentiation and anatomical localization of T-cells. On the other hand, naive T-cells were only single or double positive for BTLA and TIM-3. Extended co-expression is likely relevant for effector T-cells, as we found expression of multiple ligands in metastatic lesions of melanoma patients. Together, our data suggest that naive T-cells are primarily regulated by BTLA and TIM-3, whereas effector cells interact via larger numbers of inhibitory receptors. Blocking multiple inhibitory receptors simultaneously or sequentially may improve T-cell based therapies, but further studies are necessary to clarify the role of each receptor-ligand pair.

Reaction‐based sensing: A fluorescent probe for the detection of hydrogen sulfide was prepared and evaluated on the basis of H2S‐mediated benzodithiolone formation. The probe showed good selectivity and sensitivity for hydrogen sulfide.

Recurrent laryngeal nerve (RLN) injury is a feared complication after thyroid and parathyroid surgery. It induces important postoperative morbidity. The present study aimed to assess the incidence of transient/permanent postoperative RLN injuries after thyroid and parathyroid surgery in the present cohort, to observe the timing of recovery, and to identify risk factors for permanent RLN injury after thyroidectomy.All consecutive patients operated on at our institution for thyroid and parathyroid pathologies from 2005 to 2013 were reviewed for vocal cord paresis. Vocal cord paresis was defined based on postoperative fiberoptic laryngoscopy. Demographics, intraoperative details, and postoperative outcomes were collected. Treatment types were assessed, and recovery times collected. Patients with vocal cord paresis on preoperative fiberoptic laryngoscopy were excluded from the analysis.The cohort included 451 thyroidectomies (756 nerves at risk) and 197 parathyroidectomies (276 nerves at risk). There were 63 postoperative vocal cord pareses after thyroidectomy and 13 after parathyroidectomy. Sixty-nine were transient (10.6%) and 7 permanent (1.1%). The main performed treatment was speech therapy in 51% (39/76) of the patients. Median recovery time after transient injuries was 8 weeks. In the group with vocal cord paresis, risk factors for permanent injuries after thyroidectomy were previous thyroidectomy and intraoperative RLN injury on univariate analysis. On multivariate analysis, only intraoperative RLN injury remained significant.Most of the patients with transient postoperative RLN injury recovered normal vocal cord mobility within 6 months. The most common performed treatment was in this cohort speech therapy. Permanent RLN injuries remained rare (1.1%).

Identifying cancer biomarkers is of great interest for patient prognosis and monitoring. However, tumor-associated factors are diluted in blood and challenging to detect. Broggi et al. show that lymphatic exudate, accessible at the time of lymphadenectomy, is highly enriched in tumor-associated factors and therefore a promising source for biomarker discovery.