Anne Berger

The human spleen is a major reservoir for long-lived vaccinia virus–specific memory B cells

The fact that you can vaccinate a child at 5 years of age and find lymphoid B cells and antibodies specific for this vaccination 70 years later remains an immunologic enigma. It has never been determined how these long-lived memory B cells are maintained and whether they are protected by storage in a special niche. We report that, whereas blood and spleen compartments present similar frequencies of IgG(+) cells, antismallpox memory B cells are specifically enriched in the spleen where they account for 0.24% of all IgG(+) cells (ie, 10-20 million cells) more than 30 years after vaccination. They represent, in contrast, only 0.07% of circulating IgG(+) B cells in blood (ie, 50-100,000 cells). An analysis of patients either splenectomized or rituximab-treated confirmed that the spleen is a major reservoir for long-lived memory B cells. No significant correlation was observed between the abundance of these cells in blood and serum titers of antivaccinia virus antibodies in this study, including in the contrasted cases of B cell-depleting treatments. Altogether, these data provide evidence that in humans, the two arms of B-cell memory--long-lived memory B cells and plasma cells--have specific anatomic distributions--spleen and bone marrow--and homeostatic regulation.

Enteropathy associated T cell lymphoma in celiac disease: A large retrospective study

Abstract Introduction Prognosis of enteropathy-associated T cell lymphoma is poor but predictors of survival remain ill-defined. How clinical presentation, pathological features and therapies influence outcome was evaluated in 37 thoroughly characterized patients with celiac disease and T-cell lymphoma. Patients and methods Medical files were studied retrospectively. Lymphoma and intestinal mucosa were analysed by histopathology, multiplex PCR and intestinal intraepithelial lymphocytes phenotyping. Survival and prognostic factors were analysed using Kaplan–Meier curves with Logrank test and Cox Model. Results Lymphoma complicated non clonal enteropathy, celiac disease (n =15) and type I refractory celiac disease (n =2) in 17 patients and clonal type II refractory celiac disease in 20 patients. Twenty-five patients underwent surgery with resection of the main tumour mass in 22 cases. In univariate analysis, non clonal celiac disease, serum albumin level>21.6g/L at diagnosis, chemotherapy and surgical resection predicted good survival (p =0.0007, p <0.0001, p <0.0001, p <0.0001, respectively). In multivariate analysis, serum albumin level>21.6g/L, chemotherapy and reductive surgery were all significantly associated with increased survival (p <0.002, p <0.03, p <0.03, respectively). Conclusions Our study underlines the prognostic value of celiac disease type in patients with T-cell lymphoma, and suggests that a combination of nutritional, chemotherapy and reductive surgery may improve survival.

Role of intraoperative enteroscopy in the management of obscure gastointestinal bleeding at the time of video-capsule endoscopy

BACKGROUND This study aimed at evaluating the role of intraoperative enteroscopy (IOE) for the management of obscure gastrointestinal (GI) bleeding in patients who had been preoperatively explored by video-capsule endoscopy (VCE). METHODS Eighteen patients who underwent IOE for obscure GI bleeding were prospectively recorded between November 2000 and January 2007. The bleeding site was preoperatively localized by VCE in the small bowel in 15 patients, but the origin of bleeding remained unknown in 3 patients. RESULTS In the 3 patients with negative VCE, IOE was normal, but intraoperative conventional endoscopy identified gastric (n = 1) and colonic (n = 2) lesions. Among the 15 patients with VCE positive for small-bowel lesions, laparotomy and IOE yielded localization and treatment (surgical n = 11 and endoscopic n = 2) guidance for 13 of 15 (87%) lesions. At median 19-month follow-up, 3 bleeding recurrences (3 of 15 [20%]) were recorded, resulting in a 73% therapeutic efficacy of IOE. CONCLUSIONS IOE remains useful for the management of obscure GI bleeding when preoperative VCE is positive for small-bowel lesions that are not reachable by nonoperative enteroscopy. When VCE is negative, new conventional endoscopy should be proposed instead of IOE.

Intraoperative Enteroscopy: Is There Still a Role?

Intraoperative enteroscopy (IOE) to explore obscure gastrointestinal bleeding is now rarely indicated. IOE allows complete small bowel exploration in 57% to 100% of cases, finds a bleeding source in 80% of cases, allows the recurrence-free management of gastrointestinal bleeding in 76% of cases, but carries a high morbidity and mortality. IOE only remains indicated to guide the intraoperative treatment of preoperatively identified small bowel lesions when nonoperative treatments are unavailable and/or when intraoperative localization by external examination is impossible.

Is Mini-Gastric Bypass a Rational Approach for Type-2 Diabetes?

Purpose of ReviewMorbid obesity and type-2 diabetes mellitus (T2DM) are both major public health problems. Bariatric surgery is a proven and effective treatment for these conditions; laparoscopic Roux-en-Y gastric bypass (RYGB) is currently the gold-standard treatment. One-anastomosis gastric bypass (OAGB) is described as a simpler, safer, and non-inferior alternative to RYGB to treat morbid obesity. Concerning T2DM, experts of the OAGB procedure report promising metabolic results with good long-term remission of T2DM; however, heterogeneity within the literature prompted us to analyze this issue.Recent FindingsOAGB has gained popularity given its safety and long-term efficacy. Concerning the effect of OAGB for the treatment of T2DM, most reports involve non-controlled single-arm studies with heterogeneous methodologies and a few randomized controlled trials. However, this available literature supports the efficacy of OAGB for remission of T2DM in obese and non-obese patients. Two years after OAGB, the T2DM remission and improvement rate increased from 67 to 100%. The results were improved and stable in the long term. The 5-year T2DM remission rate increased from 82 to 84.4%. OAGB is non-inferior compared with RYGB and even superior to other accepted bariatric procedures, such as sleeve gastrectomy and adjustable gastric banding.SummaryOAGB is an efficient, safe, simple, and reversible procedure to treat T2DM. The literature reveals interesting results for T2DM remission in non-obese patients. High-level comparative studies are required to support these data.

Deep Learning and Radiomics predict complete response after neo-adjuvant chemoradiation for locally advanced rectal cancer

Treatment of locally advanced rectal cancer involves chemoradiation, followed by total mesorectum excision. Complete response after chemoradiation is an accurate surrogate for long-term local control. Predicting complete response from pre-treatment features could represent a major step towards conservative treatment. Patients with a T2-4 N0-1 rectal adenocarcinoma treated between June 2010 and October 2016 with neo-adjuvant chemoradiation from three academic institutions were included. All clinical and treatment data was integrated in our clinical data warehouse, from which we extracted the features. Radiomics features were extracted from the tumor volume from the treatment planning CT Scan. A Deep Neural Network (DNN) was created to predict complete response, as a methodological proof-of-principle. The results were compared to a baseline Linear Regression model using only the TNM stage as a predictor and a second model created with Support Vector Machine on the same features used in the DNN. Ninety-five patients were included in the final analysis. There were 49 males (52%) and 46 females (48%). Median tumour size was 48 mm (15–130). Twenty-two patients (23%) had pathologic complete response after chemoradiation. One thousand six hundred eighty-three radiomics features were extracted. The DNN predicted complete response with an 80% accuracy, which was better than the Linear Regression model (69.5%) and the SVM model (71.58%). Our model correctly predicted complete response after neo-adjuvant rectal chemoradiotherapy in 80% of the patients of this multicenter cohort. Our results may help to identify patients who would benefit from a conservative treatment, rather than a radical resection.

TNFR2/BIRC3-TRAF1 signaling pathway as a novel NK cell immune checkpoint in cancer

ABSTRACT Natural Killer (NK) cells control metastatic dissemination of murine tumors and are an important prognostic factor in several human malignancies. However, tumor cells hijack many of the NK cell functional features compromising their tumoricidal activity. Here, we show a deleterious role of the TNFα/TNFR2/BIRC3/TRAF1 signaling cascade in NK cells from the tumor microenvironment (TME). TNFα induces BIRC3/cIAP2 transcripts and reduces NKp46/NCR1 transcription and surface expression on NK cells, promoting metastases dissemination in mice and poor prognosis in GIST patients. NKp30 engagement, by promoting the release of TNFα, also contributes to BIRC3 upregulation, and more so in patients expressing predominantly NKp30C isoforms. These findings reveal that in the absence of IL-12 or a Th1-geared TME, TNFα can be considered as a negative regulatory cytokine for innate effectors.

Necrotizing pancreatitis complicated by oesophageal haemorrhage

Bleeding is a rare complication of pancreatic pseudocyst. We describe an exceptional case of necrotizing pseudocyst with mediastinal extension providing cataclysmic oesophageal haemorrhage. The patient was successfully treated by adequate endoscopic, radiological and surgical management.