The ICOS pathway has been implicated in the development and functions of regulatory T (Treg) cells, including those producing IL-10. Treg cell-derived IL-10 is indispensable for the establishment and maintenance of intestinal immune homeostasis. We examined the possible involvement of the ICOS pathway in the accumulation of murine colonic Foxp3-and/or IL-10expressing cells. We show that ICOS deficiency does not impair induction of IL-10 by intestinal CD4 T cells but, instead, triggers substantial reductions in gut-resident and peripherally derived Foxp3 + Treg cells. ICOS deficiency is associated with reduced demethylation of Foxp3 CNS2 and enhanced loss of Foxp3. This instability significantly limits the ability of ICOS-deficient Treg cells to reverse ongoing inflammation. Collectively, our results identify a novel role for ICOS costimulation in imprinting the functional stability of Foxp3 that is required for the retention of full Treg cell function in the periphery.

Surgery is often used for large or symptomatic brain metastases but is associated with risk of developing leptomeningeal dissemination. Emerging data suggest that fractionated stereotactic radiation therapy (FSRT) is an effective management strategy in large brain metastases. We sought to retrospectively compare leptomeningeal disease (LMD) and local control (LC) rates for patients treated with surgical resection followed by radiosurgery (S þ SRS) versus FSRT alone. Methods and Materials:We identified all patients with a brain metastasis !3 cm in diameter treated from 2004 to 2017 with S þ SRS or FSRT alone (25 or 30 Gy in 5 fractions) who had follow-up imaging. LMD was defined as focal or diffuse leptomeningeal enhancement that was >5 mm from the index metastasis. Categorical baseline characteristics were compared with the c 2 test. LMD and LC rates were evaluated by the Kaplan-Meier (KM) method, with the log-rank test used to compare subgroups.Results: A total of 125 patients were identified, including 82 and 43 in the S þ SRS and FSRT alone groups, respectively. Median pretreatment Graded Prognostic Assessment in the S þ SRS and FSRT groups was 2.5 and 1.5, respectively (P < .001). Median follow-up was 7 months. The KM estimate of 12-month LMD rate in the S þ SRS and FSRT groups was 45% and 19%, respectively (P Z .048). The KM estimate of 12-month local control in the S þ SRS and FSRT groups was 70% and 69%, respectively (P Z .753). The 12-month KM estimate of grade !3 toxicity was 1.4% in S þ SRS group versus 6.3% in the FSRT alone group (P Z .248). After adjusting for graded prognostic assessment (GPA), no overall survival difference was observed between groups (P Z .257).Conclusions: Surgery is appropriate for certain brain metastases, but S þ SRS may increase LMD risk compared with FSRT alone. Because S þ SRS and FSRT seem to have similar LC, FSRT may be a viable alternative to S þ SRS in select patients with large brain metastases.Sources of support: This research did not receive any funding from agencies in the public, commercial, or not-for-profit sectors. Disclosures: J.B.F., R.A.P., and C.D.W. have unrelated contracts, personal fees, and grants with Varian Medical Systems. J.M.M. has disclosures unrelated to this project. The authors report no specific conflicts of interest concerning the findings specified in this article.

PurposeTo assess the long‐term stability of the anchored radiofrequency transponders and compare displacement rates with other commercially available lung fiducial markers. We also sought to describe late toxicity attributable to fiducial implantation or migration.Materials and methodsThe transponder cohort was comprised of 17 patients at our institution who enrolled in a multisite prospective clinical trial and underwent bronchoscopic implantation of three anchored transponders into small (2–2.5 mm) airways. We generated a comparison cohort of 34 patients by selecting patients from our institutional lung SBRT database and matching 2:1 based on the lobe containing tumor and proximity to the bronchial tree. Assessment of migration was performed by rigidly registering the most recent follow‐up CT scan to the simulation scan, and assessing whether the relative geometry of the fiducial markers had changed by more than 5 mm. Toxicity outcomes of interest were hemoptysis and pneumothorax.ResultsThe median follow‐up of patients in the transponder cohort was 25.3 months and the median follow‐up in the comparison cohort was 21.7 months. When assessing the most recent CT, all fiducial markers were within 5 mm of their position at CT simulation in 11 (65%) patients in the transponder group as compared to 23 (68%) in the comparison group (P = 0.28). One case of hemoptysis was identified in the transponder cohort, and bronchoscopy confirmed bleeding from recurrent tumor; no cases of hemoptysis were noted in the comparison cohort. No case of pneumothorax was noted in either group.ConclusionNo significant difference in the rates of fiducial marker retention and migration were noted when comparing patients who had anchored transponders placed into small airways and a 2:1 matched cohort of patients who had other commercially available lung fiducial markers placed. In both groups, no late or chronic toxicity appeared to be related to the implanted fiducial markers.

Background and study aims: Obesity prevalence continues to rise in the United States with Roux-en-Y gastric bypass (RYGB) surgery being one of the most common bariatric procedures. With this trend, more patients with altered upper gastrointestinal (UGI) anatomy have required endoscopic intervention including direct percutaneous endoscopic jejunostomy (DPEJ) placement. We aim to assess the safety and success rates of DPEJ in RYGB patients. Patients and Methods: All patients at a tertiary care referral center who underwent DPEJ during an 8-year period were queried from a prospectively maintained registry of all enteroscopy procedures. Duplicate cases and altered upper UGI anatomy subtypes other than RYGB were excluded. The final cohort consisted of 2 groups: RYGB vs native anatomy (NA). Demographic, procedural, readmission, follow-up, and complication data were recorded. Comparative analysis was performed. Results: Seventy-two patients were included where 28 had RYGB and 44 had NA. Both groups had similar baseline and pre-procedure data. Procedure success rate was 89% in RYGB patients and 98% in NA patients (p=0.13). There were no intraprocedural complications. Early and late postprocedural complication rates were similar between the groups (both 4% vs 7%). Average follow-up time in the RYGB and NA groups were 12.97 ± 9.35 and 13.44 ± 9.21 months respectively. Although readmission rates at one-month and six-month were higher in the NA versus the RYGB group (21% vs 7% and 25% vs 15%), these differences were not significant. Conclusion: DPEJ can be successful and safely placed in RYGB patients with no significant difference in procedure success, complication, or readmission rates when compared to control.

BACKGROUND Obscure gastrointestinal (GI) bleeding is defined as persistent bleeding despite negative evaluation with both esophagogastroduodenoscopy and colonoscopy and can be secondary to small intestinal pathology. Standard endoscopy as well as push endoscopy can be a challenge in those with altered anatomy given inaccessible areas as well as perforation risk. Single and double balloon enteroscopy can be warranted in this patient population in instances of obscure GI bleed. AIM To assess the safety and diagnostic efficacy of balloon enteroscopy for obscure GI bleeding in patients with surgically altered anatomy. METHODS A search was conducted through PubMed, MEDLINE, Google Scholar, Scopus, and Embase with the key words “enteroscopy,” “obscure bleeding,” and “altered anatomy,” to identify relevant articles in English with no restricted time frame. A search within the Reference Citation Analysis database was conducted to ensure inclusion of the latest high impact articles. Study types included in the review were prospective and retrospective reviews, case series, and case reports. The reference lists of these papers were also reviewed to find further papers that were applicable. The authors extracted the data from the studies that fit inclusion criteria. Data of interest included type of study, type of procedure, and type of altered anatomy, as well as the number of patients with any diagnostic or therapeutic intervention. Data was also recorded on procedure tolerance and complications. The data was analyzed with descriptive statistics. RESULTS Our literature search yielded 14 studies that were included. There were 68 procedures performed with 61 unique patients subjected to these procedures. Forty-four (65%) of the procedures were double balloon, 21 (31%) were single balloon, and 3 (4%) were classified as through the scope balloon assisted. The most common altered anatomy types included Gastric Bypass Roux-en-Y, Pylorus Sparing Whipple, Orthotopic Liver Transplantation with Roux-en-Y, and Gastrojejunostomy Roux-en-Y. The procedures were successfully performed in each patient. There were 5 (7%) procedures that were complicated by perforation. Amongst the available data, the diagnostic yield was 48/59 (81%) and a therapeutic yield of 39/59 (66%). One patient was recommended surgical revision of their altered anatomy following enteroscopy. CONCLUSION Balloon enteroscopy is a useful diagnostic modality in investigating obscure GI bleeding within those with surgically altered anatomy; however, precautions must be taken as this population may have increased perforation risk.