Marc H.W.A. Wijnen

Pediatric patients with high-risk neuroblastoma have poor survival rates and urgently need more effective treatment options with less side effects. Since novel and improved immunotherapies may fill this need, we dissect the immunoregulatory interactions in neuroblastoma by single-cell RNA-sequencing of 24 tumors (10 pre- and 14 post-chemotherapy, including 5 pairs) to identify strategies for optimizing immunotherapy efficacy. Neuroblastomas are infiltrated by natural killer (NK), T and B cells, and immunosuppressive myeloid populations. NK cells show reduced cytotoxicity and T cells have a dysfunctional profile. Interaction analysis reveals a vast immunoregulatory network and identifies NECTIN2-TIGIT as a crucial immune checkpoint. Combined blockade of TIGIT and PD-L1 significantly reduces neuroblastoma growth, with complete responses (CR) in vivo. Moreover, addition of TIGIT+PD-L1 blockade to standard relapse treatment in a chemotherapy-resistant Th-ALKF1174L/MYCN 129/SvJ syngeneic model induces CR. In conclusion, our integrative analysis provides promising targets and a rationale for immunotherapeutic combination strategies.

BACKGROUND: A thyroglossal duct cyst is the most common form of congenital anomaly in the neck. Surgical removal is very effective. However, in some cases, a cyst recurs. The purpose of this study was to identify factors that predispose to recurrence of a thyroglossal duct cyst. METHODS: A retrospective study was conducted of consecutive patients who underwent surgical resection for histologically confirmed thyroglossal duct cysts between 1998 and 2013 in a tertiary referral center. RESULTS: Two hundred seven patients were included. The overall recurrence rate was 9.7%. The most important factor predicting recurrence was the type of resection: recurrence rate was 5.3% after the Sistrunk procedure, and 55.6% after plain excision (p < .001). The only other factor that was significantly associated with chance of recurrence was postoperative infection. CONCLUSION: The Sistrunk procedure is the treatment of choice for thyroglossal duct cysts because it yields low recurrence and morbidity. Postoperative infections, rather than preoperative infections, are associated with recurrence.

PURPOSE: The aim of this study was to investigate the possible deleterious effect of the lateral intersecting margins (so-called dog ears) on anastomotic disruption after experimentally performed double-stapled anastomoses. METHODS: Two groups of double-stapled side-to-end anastomoses were performed using pig small intestines. Group A consisted of 35 circular anastomoses and Group B of 32 double-stapled anastomoses with a bilateral dog ear. In both groups bursting pressures were tested using a water-filled, pressure-controlled automatic pumping system (Hamou Endomat), and special attention was paid to the location(s) in the anastomoses were the disruption(s) occurred. RESULTS: In Group A bursting pressures were significantly higher than in Group B (median pressure, 90 vs. 60 mmHg; P < 0.001, Mann-Whitney U test). Remarkably, in Group B in 13 cases (42 percent) the first disruption occurred at the corner of a dog ear. CONCLUSIONS: We conclude that the lateral intersections of double-stapled anastomoses are a structural weak spot and that the currently most often applied double-stapled anastomosis is a less effective type of anastomosis than a complete circular one. Resolving this technical problem might help to reduce the number of anastomotic disruptions after low anterior resections.