Role of the fatty pancreatic infiltration in pancreatic oncogenesis.

Although pancreatic precancerous lesions are known to be related to obesity and fatty pancreatic infiltration, the mechanisms remain unclear. We assessed the role of fatty infiltration in the process of pancreatic oncogenesis and obesity. A combined transcriptomic, lipidomic and pathological approach was used to explore neoplastic transformations. Intralobular (ILF) and extralobular (ELF) lipidomic profiles were analyzed to search for lipids associated with pancreatic intraepithelial neoplasia (PanINs) and obesity; the effect of ILF and ELF on acinar tissue and the histopathological aspects of pancreatic parenchyma changes in obese (OB) and non-obese patients. This study showed that the lipid composition of ILF was different from that of ELF. ILF was related to obesity and ELF-specific lipids were correlated to PanINs. Acinar cells were shown to have different phenotypes depending on the presence and proximity to ILF in OB patients. Several lipid metabolic pathways, oxidative stress and inflammatory pathways were upregulated in acinar tissue during ILF infiltration in OB patients. Early acinar transformations, called acinar nodules (AN) were linked to obesity but not ELF or ILF suggesting that they are the first reversible precancerous pancreatic lesions to occur in OB patients. On the other hand, the number of PanINs was higher in OB patients and was positively correlated to ILF and ELF scores as well as to fibrosis. Our study suggests that two types of fat infiltration must be distinguished, ELF and ILF. ILF plays a major role in acinar modifications and the development of precancerous lesions associated with obesity, while ELF may play a role in the progression of PDAC.

Lymphoma In Patients With Inflammatory Bowel Disease: A Multicenter Collaborative Study Between Getaid And Lysa.

BACKGROUND: IBD is associated with an increased risk of developing lymphoma. Although recent data clarifies lymphoma epidemiology in IBD patients, clinical and pathological characteristics of lymphoma occurring in IBD remain ill-known. METHODS: Patients with IBD and lymphoma were retrospectively identified in the framework of a national collaborative study including the Groupe d'Étude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID) and the Lymphoma Study Association (LYSA). We characterized clinical and prognostic features for the 3 most frequent lymphoma subtypes occurring in IBD. We performed a multicentric case-control study. Controls (lymphoma de novo) were matched (5:1) to cases on gender, age at diagnosis, lymphoma subtype, year of diagnosis, IPI/FLIPI indexes. Overall survival (OS) and progression free survival were compared between cases and controls. RESULTS: 133 IBD patients with lymphoma were included (males = 62.4 %, median age at lymphoma diagnosis = 49 years in males ; 42 in females). Most had Crohn's disease (73.7 %) and were exposed to thiopurines (59.4 %). The most frequent lymphoma subtypes were diffuse large B cell lymphoma (DLBCL, 45.1 %), Hodgkin lymphoma (HL, 18.8 %), and follicular lymphoma (FL, 10.5 %). When matched with 365 controls, prognosis was improved in IBD patients with DLBCL compared to controls (p = 0.0064, hazard ratio = 0.36) or similar (HL and FL). CONCLUSION: Lymphomas occurring in IBD patients do not seem to have a worse outcome than in patients without IBD. Due to the scarcity of this situation, those patients should be managed in expert centers.

Acid Reflux Is Common in Patients With Gastroesophageal Reflux Disease After One-Anastomosis Gastric Bypass.

INTRODUCTION: Patients with one-anastomosis gastric bypass (OAGB) can develop gastroesophageal reflux disease (GERD). The nature of this GERD (acid or biliary) remains unclear. OBJECTIVE: To assess the nature of GERD via impedance pH testing in patients presenting with reflux post OAGB. METHODS: Retrospective analysis of a prospectively collected database of 43 patients with OAGB backgrounds who developed postoperative GERD and were investigated with impedance pH monitoring between 2006 and 2019. RESULTS: Mean age was 52.48 ± 9 years. Mean body mass index (BMI) prior to OAGB was 46.82 kg/m2. None of these patients had clinical GERD before surgery. The median time interval between surgery and investigation with 24-h impedance pH monitoring was 64 (56) months. The mean BMI at the time of investigations was 32.67 ± 6.9 kg/m2. The type of reflux was acid in 13 (30.2%), non-acid (biliary) in 12 (27.9%), and mixed (acid and biliary) in 5 (11.6%) patients. However, it remained not confirmed in 13 (30.2%). Median DeMeester score was 48.95 (27.67) in patients with acid, 2.8 (7.4) in patients with biliary, and 28.7 (5.6) in patients with mixed reflux. Median percent of time spent with pH < 4 was 9.65 (8) in patients with acid, 0.6 (1.75) in patients with biliary, and 7.7 (3.9) in patients with mixed reflux. CONCLUSION: Acid reflux seems to be as common as bile reflux in patients presenting with GERD after OAGB. In case of revisional surgery for severe GERD post OAGB, 24-h impedance pH monitoring could be essential to determine the surgical procedure of choice.

A Scoring System to Determine Patients' Risk of Colectomy Within 1 Year After Hospital Admission for Acute Severe Ulcerative Colitis.

BACKGROUND & AIMS: There is consensus on the criteria used to define acute severe ulcerative colitis (ASUC) and on patient management, but it has been a challenge to identify patients at risk for colectomy based on data collected at hospital admission. We aimed to develop a system to determine patients' risk of colectomy within 1 y of hospital admission for ASUC based on clinical, biomarker, and endoscopy data. METHODS: We performed a retrospective analysis of consecutive patients with ASUC treated with corticosteroids, ciclosporin, or tumor necrosis factor (TNF) antagonists and admitted to 2 hospitals in France from 2002 through 2017. Patients were followed until colectomy or loss of follow up. A total of 270 patients with ASUC were included in the final analysis, with a median follow-up time of 30 months (derivation cohort). Independent risk factors identified by Cox multivariate analysis were used to develop a system to identify patients at risk for colectomy 1 y after ASUC. We developed a scoring system based on these 4 factors (1 point for each item) to identify high-risk (score 3 or 4) vs low-risk (score 0) patients. We validated this system using data from an independent cohort of 185 patients with ASUC treated from 2006 through 2017 at 2 centers in France. RESULTS: In the derivation cohort, the cumulative risk of colectomy was 12.3% (95% CI, 8.6-16.8). Based on multivariate analysis, previous treatment with TNF antagonists or thiopurines (hazard ratio [HR], 3.86; 95% CI, 1.82-8.18), Clostridioides difficile infection (HR, 3.73; 95% CI, 1.11-12.55), serum level of C-reactive protein above 30 mg/L (HR, 3.06; 95% CI, 1.11-8.43), and serum level of albumin below 30 g/L (HR, 2.67; 95% CI, 1.20-5.92) were associated with increased risk of colectomy. In the derivation cohort, the cumulative risks of colectomy within 1 y in patients with scores of 0, 1, 2, 3, or 4 were 0.0%, 9.4% (95% CI, 4.3%-16.7%), 10.6% (95% CI, 5.6%-17.4%), 51.2% (95% CI, 26.6%-71.3%), and 100%. Negative predictive values ranged from 87% (95% CI, 82%-91%) to 92% (95% CI, 88%-95.0%). Findings from the validation cohort were consistent with findings from the derivation cohort. CONCLUSIONS: We developed a scoring system to identify patients at low-risk vs high-risk for colectomy within 1 y of hospitalization for ASUC, based on previous treatment with TNF antagonists or thiopurines, C difficile infection, and serum levels of CRP and albumin. The system was validated in an external cohort.

Clinical Outcomes of Submicroscopic Infections and Correlates of Protection of VAR2CSA Antibodies in a Longitudinal Study of Pregnant Women in Colombia.

Malaria in pregnancy can cause serious adverse outcomes for the mother and the fetus. However, little is known about the effects of submicroscopic infections (SMIs) in pregnancy, particularly in areas where Plasmodium falciparum and Plasmodium vivax cocirculate. A cohort of 187 pregnant women living in Puerto Libertador in northwest Colombia was followed longitudinally from recruitment to delivery. Malaria was diagnosed by microscopy, reverse transcription-quantitative PCR (RT-qPCR), and placental histopathology. Gestational age, hemoglobin concentration, VAR2CSA-specific IgG levels, and adhesion-blocking antibodies were measured during pregnancy. Statistical analyses were performed to evaluate the impact of SMIs on birth weight and other delivery outcomes. Twenty-five percent of women (45/180) were positive for SMIs during pregnancy. Forty-seven percent of infections (21/45) were caused by P. falciparum, 33% were caused by P. vivax, and 20% were caused by mixed Plasmodium spp. Mixed infections of P. falciparum and P. vivax were associated with lower gestational age at delivery (P = 0.0033), while other outcomes were normal. Over 60% of women had antibodies to VAR2CSA, and there was no difference in antibody levels between those with and without SMIs. The anti-adhesion function of these antibodies was associated with protection from SMI-related anemia at delivery (P = 0.0086). SMIs occur frequently during pregnancy, and while mixed infections of both P. falciparum and P. vivax were not associated with a decrease in birth weight, they were associated with significant risk of preterm birth. We propose that the lack of adverse delivery outcomes is due to functional VAR2CSA antibodies that can protect pregnant women from SMI-related anemia.

Chronic Mesenteric Ischemia: A Rare Cause of Chronic Abdominal Pain.

BACKGROUND: Chronic mesenteric ischemia is a rare disease with nonspecific clinical symptoms, such as chronic postprandial abdominal pain and weight loss. Diagnostic modalities and revascularization techniques have evolved during the past 20 years. The significance of stenosis in a single splanchnic vessel remains unclear. Our aims were to assess the outcomes of 2 revascularization techniques and report on the diagnostic modalities of splanchnic vessel stenoses. METHODS: The demographic data, medical history, technical characteristics, and outcomes of the revascularization procedures were recorded for all of the patients admitted for endovascular revascularization or open surgical revascularization of the splanchnic vessels as treatment for chronic mesenteric ischemia in our tertiary referral center since 2000. RESULTS: Fifty-four patients were included in this study: 43 received endovascular revascularization, and 11 had open surgical revascularization. The symptoms were abdominal pain, weight loss, and diarrhea in 98%, 53%, and 25% of the cases, respectively. Computed tomography angiography was the key diagnostic tool for 60% of the patients. A single-vessel stenosis was found in one-third of the patients. Endovascular and open revascularization had similar early and late outcomes, and no 30-day mortality was observed. However, we did observe higher morbidity in the open revascularization group (73% vs 19%, P <.03). CONCLUSIONS: Chronic mesenteric ischemia may be diagnosed in the presence of a splanchnic syndrome and stenosis of a single splanchnic vessel, typically assessed using computed tomography angiography. In selected patients, endovascular revascularization had similar efficacy as, and lower complication rates than open revascularization.