PURPOSE: This trial evaluates the addition of the PD-L1 antibody atezolizumab (ATZ) to standard-of-care fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) as a perioperative treatment for patients with resectable esophagogastric adenocarcinoma (EGA). METHODS: DANTE started as multicenter, randomized phase II trial, which was subsequently converted to a phase III trial. Here, we present the results of the phase II proportion, focusing on surgical pathology and safety outcomes on an exploratory basis. Patients with resectable EGA (≥cT2 or cN+) were assigned to either four preoperative and postoperative cycles of FLOT combined with ATZ, followed by eight cycles of ATZ maintenance (arm A) or FLOT alone (arm B). RESULTS: Two hundred ninety-five patients were randomly assigned (A, 146; B, 149) with balanced baseline characteristics between arms. Twenty-three patients (8%) had tumors with microsatellite instability (MSI), and 58% patients had tumors with a PD-L1 combined positive score (CPS) of ≥1. Surgical morbidity (A, 45%; B, 42%) and 60-day mortality (A, 3%; B, 2%) were comparable between arms. Downstaging favored arm A versus arm B (ypT0, 23% v 15% [one-sided P = .044]; ypT0-T2, 61% v 48% [one-sided P = .015]; ypN0, 68% v 54% [one-sided P = .012]). Histopathologic complete regression rates (pathologic complete response or TRG1a) were higher after FLOT plus ATZ (A, 24%; B, 15%; one-sided P = .032), and the difference was more pronounced in the PD-L1 CPS ≥10 (A, 33%; B, 12%) and MSI (A, 63%; B, 27%) subpopulations. Complete margin-free (R0) resection rates were relatively high in both arms (A, 96%; B, 95%). The incidence and severity of adverse events were similar in both groups. CONCLUSION: Within the limitations of the exploratory nature of the data, the addition of ATZ to perioperative FLOT is safe and improved postoperative stage and histopathologic regression.

Obesity has become a major health problem in the industrialized world. Immune regulation plays an important role in adipose tissue homeostasis; however, the initial events that shift the balance from a noninflammatory homeostatic environment toward inflammation leading to obesity are poorly understood. Here, we report a role for the costimulatory molecule programmed death-ligand 1 (PD-L1) in the limitation of diet-induced obesity. Functional ablation of PD-L1 on dendritic cells (DCs) using conditional knockout mice increased weight gain and metabolic syndrome during diet-induced obesity, whereas PD-L1 expression on type 2 innate lymphoid cells (ILC2s), T cells, and macrophages was dispensable for obesity control. Using in vitro cocultures, DCs interacted with T cells and ILC2s via the PD-L1:PD-1 axis to inhibit T helper type 1 proliferation and promote type 2 polarization, respectively. A role for PD-L1 in adipose tissue regulation was also shown in humans, with a positive correlation between PD-L1 expression in visceral fat of people with obesity and elevated body weight. Thus, we define a mechanism of adipose tissue homeostasis controlled by the expression of PD-L1 by DCs, which may be a clinically relevant finding with regard to immune-related adverse events during immune checkpoint inhibitor therapy.

Background: Although addition of adjuvant chemotherapy is the current standard, the prognosis of pancreatic cancers still remains poor. The NEPAFOX trial evaluated perioperative treatment with FOLFIRINOX in resectable pancreatic cancer. Patients and Methods: This multicenter phase II trial randomized patients with resectable or borderline resectable pancreatic cancer without metastases into arm (A,) upfront surgery plus adjuvant gemcitabine, or arm (B,) perioperative FOLFIRINOX. The primary endpoint was overall survival (OS). Results: Owing to poor accrual, recruitment was prematurely stopped after randomization of 40 of the planned 126 patients (A: 21, B: 19). Overall, approximately three-quarters were classified as primarily resectable (A: 16, B: 15), and the remaining patients were classified as borderline resectable (A: 5, B: 4). Of the 12 evaluable patients, 3 achieved partial response under neoadjuvant FOLFIRINOX. Of the 21 patients in arm A and 19 patients in arm B, 17 and 7 underwent curative surgery, and R0-resection was achieved in 77% and 71%, respectively. Perioperative morbidity occurred in 72% in arm A and 46% in arm B, whereas non-surgical toxicity was comparable in both arms. Median RFS/PFS was almost doubled in arm B (14.1 months) compared with arm A (8.4 months) in the population with surgical resection, whereas median OS was comparable between both arms. Conclusions: Although the analysis was only descriptive owing to small patient numbers, no safety issues regarding surgical complications were observed in the perioperative FOLFIRINOX arm. Thus, considering the small number of patients, perioperative treatment approach appears feasible and potentially effective in well-selected cohorts of patients. In pancreatic cancer, patient selection before initiation of neoadjuvant therapy appears to be critical.

Portomesenteric vein thrombosis (PMVT) is a rare post-operative complication of bariatric procedures, occurring in between 0.3% and 1% of cases. A structured questionnaire consisting of 27 items was available online to members of the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) to investigate the occurrence of PMVT. A total of 89 bariatric surgeons from 61 countries participated. Twenty-six (29.21%) reported at least one case of PMVT (46.15% males; 53.84% females). The surgery most associated with PMVT occurrence was sleeve gastrectomy (84.6%), followed by Roux-en-Y gastric bypass (RYGB) (7.69%), and laparoscopic adjustable gastric banding (LAGB) (7.69%). The time gap between surgery and PMVT was 19.28 ± 8.72 days. The predominant symptom was abdominal pain in 96.15% of patients, followed by fever in 26.9%. Complete occlusion of the portal vein was reported in 34.6% of cases, with involvement of the portal system in 69%, extension to the superior mesenteric district in 23%, and extension to the splenic vein in two patients (7.7%). Our survey, which is the largest regarding PMVT to date, revealed a diffuse lack of standardization in the choice, duration, and dosing of prophylaxis regimens as well as treatment modalities, reflecting the literature gap on the topic.

Introduction: Standard-of-care gastroesophageal reflux disease (GERD) procedures are associated with adverse events (AEs) (i.e., dysphagia, gas-bloating). RefluxStop has been developed to circumvent these outcomes. This study presents the results of 28 patients managed with RefluxStop in Germany. Methods: Between July 2021 and November 2023, 28 patients with GERD underwent RefluxStop surgery, a novel laparoscopic antireflux procedure. Retrospective chart analysis with patient-informed consent was conducted to determine clinical outcomes, such as GERD Health-Related Quality of Life (GERD-HRQL) score, proton pump inhibitors (PPI) use, symptomatology, patient satisfaction, and perioperative AEs. Results: Baseline characteristics ( n = 28): age 47 ± 13.1 years; 67.9% female; body mass index (BMI) 27.3 ± 4.1 kg/m ² ; 93% PPI use for 5.6 ± 2.7 years; and hiatal hernia in 100% of cases of mean (standard deviation [SD]) size 3.4 (0.8) cm, whereof 35.7% were large hiatal hernia (4–6 cm). At a mean (SD) follow-up of 14.1 (4.7) months, patients experienced 88.6% improvement in median (IQR) total GERD-HRQL score from a baseline of 35 (7.7) to 4 (4.2) at follow-up ( P < .05). Preoperative dysphagia (35.7%) resolved completely in all patients ( P < .001). The mean (SD) GERD-HRQL heartburn subdomain decreased by 90.6% from a baseline of 18.1 (6.1) to 1.7 (1.2) at follow-up and all patients (100%) had scores <5. Similarly, the mean (SD) regurgitation subdomain decreased from a baseline of 13.2 (4.7) to 2 (1.6) at follow-up and all patients (100%) had scores <5. Patient satisfaction was achieved in 96.4% of patients with no PPI use required in 93% of patients ( P < .001); only one patient required PPIs for persistent GERD symptoms. No cases of reoperation or esophageal dilatation were performed. Minor intraoperative AEs occurred in seven patients (i.e., neck emphysema). Conclusion: RefluxStop provides excellent safety and effectiveness outcomes for GERD treatment. Dysphagia completely resolved (0%) with 88.6% improvement in median GERD-HRQL score and satisfaction achieved in 96.4% of patients. These promising results reproduced the outcomes noted in the RefluxStop CE trial in real-world settings.