Marginal Ulcer Incidence and the Population of Gastrin Producing G cells Retained in the Gastric Pouch after Roux-en-Y Gastric Bypass: Is There a Relationship?

INTRODUCTION: Marginal ulcers are the most prevalent endoscopic abnormality after RYGB. The etiology is still poorly understood; however, an increase in acid secretion has been strongly implicated as a causal agent. Although gastrin is the greatest stimulant of acid secretion, to date, the presence of gastrin producing G cells retained in the gastric pouch, related to the occurrence of marginal ulcers, has not been evaluated. OBJECTIVE: Evaluate the density of G cells and parietal cells in the gastric pouch of RYGB patients with a diagnosis of marginal ulcer on the post-op EGD. METHOD: We retrospectively evaluated 1104 gastric bypasses performed between 2010 and 2020. Patients with marginal ulcer who met the inclusion criteria and controls were selected from this same population. Endoscopic gastric pouch biopsies were evaluated using immunohistochemical study and HE staining to assess G cell and parietal cell density. RESULTS: In total, 572 (51.8%) of the patients performed endoscopic follow-up after RYGB. The incidence of marginal ulcer was 23/572 (4%), and 3 patients required revision surgery due to a recalcitrant ulcer. The mean time for ulcer identification was 24.3 months (2-62). G cell count per high-power field (× 400) was statistically higher in the ulcer group (p < 0.05). There was no statistical difference in parietal cell density between groups (p 0.251). CONCLUSION: Patients with a marginal ulcer after gastric bypass present a higher density of gastrin-producing G cells retained in the gastric pouch.

Kinin B1 receptor deficiency protects mice fed by cafeteria diet from abnormal glucose homeostasis.

The kallikrein-kinin system has been implicated in body weight and glucose homeostasis. Their major effectors act by binding to the kinin B2 and B1 receptors. It was assessed the role of the kinin B1 receptor in weight and glucose homeostasis in B1 receptor knockout mice (B1RKO) subjected to a cafeteria diet (CAF). Wild-type (WT) and B1RKO male mice (C57BL/6 background; 8 weeks old) were fed a standard diet (SD) or CAF for 14 weeks, ad libitum, and four groups were formed: WT-SD; B1RKO-SD; WT-CAF; B1RKO-CAF. Body weight and food intake were assessed weekly. It was performed glucose tolerance (GTT) and insulin tolerance tests (ITT), and HOMA-IR, HOMA-ß and HOMA-ß* 1/HOMA-IR were calculated. Islets from WT and B1RKO were isolated in order to measure the insulin secretion. Western blot was used to assess the hepatic AKT phosphorylation and qPCR to assess gene expression. CAF induced a higher body mass gain in B1RKO compared to WT mice. CAF diet increased epididymal fat depot mass, hepatic fat infiltration and hepatic AKT phosphorylation in both genotypes. However, B1RKO mice presented lower glycemic response during GTT when fed with CAF, and a lower glucose decrease in the ITT. This higher resistance was overcomed with higher insulin secretion when stimulated by high glucose, resulting in higher glucose uptake in the GTT when submitted to CAF, despite lower insulin sensitivity. Islets from B1RKO delivered 4 times more insulin in 3-month-old mice than islets from WT. The higher insulin disposition index and high insulin delivery of B1RKO can explain the decreased glucose excursion during GTT. In conclusion, CAF increased the ß-cell function in B1RKO mice, compensated by the diet-induced insulin resistance and resulting in a healthier glycemic response despite the higher weight gain.

Transient Elastography in HIV Infected Patients with Liver Steatosis Identifies a High-Risk Group for Non-Alcoholic Steatohepatitis.

OBJECTIVE: The study aimed to assess the role of TE in HIV-infected patients with NAFLD. METHODS: HIV-infected patients undergoing ART were enrolled between August 2016 and February 2017, following the inclusion criteria: ≥18 years with undetectable HIV viral load. Exclusion criteria included pregnancy, alcohol intake ≥20g/day and co-infection with hepatitis B or C. Patients underwent an abdominal US to diagnose liver steatosis. Significant fibrosis (≥F2) was considered when APRI>1.0, FIB4>3 and liver stiffness ≥7.1kPa. Subjects with TE ≥7.1kPa were prescribed a liver biopsy and the NAFLD Scoring System ≥3 was considered as a diagnosis of NASH. The poisson regression model was used to identify factors associated with liver steatosis. RESULTS: 98 patients were included. The mean age of the subjects was 49±11 years and 53 (54.1%) were males. Liver steatosis was diagnosed in 31 patients (31.6%) and was independently associated with male sex (PR= 2.18) and higher BMI (PR=1.08). Among the 31 patients with NAFLD, 26 showed results for TE, APRI and FIB4. The prevalence of significant fibrosis assessed by TE, APRI and FIB4 was 26.9%, 6.4% and 3.2%, respectively. Seven patients (26.9%) had a TE result ≥7.1kPa, which was associated with higher triglyceride levels, FIB4 score and CAP values. Liver biopsy was perfomed on six of those with TE ≥7.1kPa and NASH was found in 5 (83.3%) and liver fibrosis without NASH in one. CONCLUSION: NAFLD prevalence in HIV-infected patients is higher than the general population. TE ≥7.1kPa was not able to diagnose significant fibrosis but accurately detect a subgroup of patients at a high risk for NASH among HIV monoinfected individuals with steatosis.

Hepatic steatosis among people living with HIV in Southern Brazil: prevalence and risk factors.

Chronic liver disease is an important cause of morbidity and mortality among people living with human immunodeficiency virus (HIV) and is frequently related to non-alcoholic fatty liver disease (NAFLD). The objective is to estimate the prevalence and risk factors of hepatic steatosis among consecutive patients with stable HIV infection on antiretroviral therapy (ART). Also, the use of transient elastography (TE) as a mean to identify a subgroup at risk for non-alcoholic steatohepatitis (NASH) and/or liver fibrosis. HIV infected patients were enrolled between August2016 and February2017. Inclusion criteria: ≥18 years with undetectable HIV viral load. Exclusion criteria: pregnancy; alcohol intake ≥20 g/day and co-infection B or C viruses. Patients underwent ultrasound (US) to diagnose liver steatosis. Significant fibrosis (≥F2) was estimated if at least one of the following were present: APRI > 1.0, FIB4 > 3 and/or liver stiffness ≥7.1kPa. Subjects with TE ≥ 7.1kPa were proposed a liver biopsy and NAFLD Scoring System (NAS) ≥ 3 was considered as diagnosis of NASH. A total of 98 patients were included. Liver steatosis was diagnosed in 31 patients (31.6%) and was independently associated with male gender, BMI, ALT and total bilirubin levels. The prevalence of significant fibrosis assessed by TE, APRI and FIB4 was 26.9%, 6.4% and 3.2%, respectively. Seven patients had a TE result ≥7.1kPa. NASH was found in 5 (83.3%). Among HIV infected patients undergoing ART, almost one third have NAFLD. Neither TE, APRI or FIB4 were able to act as surrogates for significant liver fibrosis. Nevertheless, TE ≥ 7.1kPa was able to accurately select a subgroup of patients at risk for NASH.

Hypothermia is better than ischemic preconditioning for preventing early hepatic ischemia/reperfusion in rats.

BACKGROUND: Topical hypothermia (TH) and ischemic preconditioning (IPC) are used to decrease I/R injury. The efficacy of isolated or combined use of TH and IPC in the liver regarding inflammation and cytoprotection in early ischemia/reperfusion (I/R) injury needs to be evaluated. MATERIAL AND METHODS: Wistar rats underwent 70% liver ischemia for 90 min followed by 120 min of reperfusion. Livers of animals allocated in the sham, normothermic ischemia (NI), IPC, TH, and TH+IPC groups were collected for molecular analyses by ELISA and Western blot, aiming to compare proinflammatory, anti-inflammatory, and antioxidant profiles. RESULTS: Compared with NI, TH presented decreased tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and IL-12 concentrations and increased IL-10 levels. TH animals displayed lower inducible nitric oxide synthase (iNOS) and higher endothelial nitric oxide synthase (eNOS) expressions. NAD(P)H-quinone oxidoreductase-1(NQO1) expression was also lower with TH. Isolated IPC and NI were similar regarding all these markers. TH+IPC was associated with decreased IL-12 concentration and reduced iNOS and NQO1 expressions, similarly to isolated TH. Expression of Kelch-like ECH-associated protein (Keap)-1 was increased and expression of nuclear and cytosolic nuclear erythroid 2-related factor 2 (Nrf2) was decreased with TH+IPC vs. NI. CONCLUSION: TH was the most effective method of protection against early I/R injury. Isolated IPC entailed triggering of second-line antioxidant defense enzymes. Combined TH+IPC seemed to confer no additional advantage over isolated TH in relation to the inflammatory process, but had the advantage of completely avoid second-line antioxidant defense enzymes.

Management of Severe Gastrointestinal Tuberculosis with Injectable Antituberculous Drugs.

Abdominal tuberculosis (TB) is generally responsive to medical treatment, and early diagnosis and management can prevent unnecessary surgical intervention. However, intravenous therapy is needed for severe forms of tuberculosis with extensive gastrointestinal involvement. The authors report an immunocompetent patient with gastrointestinal TB who was successfully managed with a combination of surgical intervention and anti-TB medications, and discuss the importance of injectable anti-TB medications in the management of severe gastrointestinal TB. The present case report provides a model for assessment and intervention in severe forms of gastrointestinal TB.

Spatial distribution of cancer stem cells in head and neck squamous cell carcinomas.

BACKGROUND: CD44 and aldehyde dehydrogenase 1 (ALDH1) are considered putative markers of highly tumorigenic cells (i.e., cancer stem-like cells) in head and neck squamous cell carcinomas. This small subset of cells is believed to be the primary responsible for tumor initiation and progression. The objectives of this study were (i) to evaluate the patterns of CD44 and ALDH1 expression in the tumor center and in the invasive front, as well as in adjacent non-tumor epithelium, and (ii) to correlate these findings with clinical parameters. MATERIALS AND METHODS: The sample comprised 44 patients with primary head and neck squamous cell carcinomas. Hematoxylin and eosin (HE) staining was used for histopathological tumor grading and for morphological analysis of adjacent non-tumor epithelium. Semiquantitative analysis was performed in histological sections immunostained for CD44 and ALDH1. RESULTS: ALDH1 immunostaining in the invasive front showed positive association with tumor size, regional metastasis, tumor histopathological grading, and disease progression. Moreover, expression of this marker in both tumor invasive front and adjacent non-tumor epithelium was related with more aggressive tumors. CD44 immunostaining was heterogeneous in all areas evaluated and did not show association with clinical data. CONCLUSION: Collectively, these data suggest that ALDH1 immunostaining in the invasive front and in adjacent non-tumor epithelium may help identify tumors with a more aggressive behavior, potentially contributing to improving treatment customization and the monitoring of patients with head and neck cancer.

In vivo toxicological evaluation of polymeric nanocapsules after intradermal administration.

Polymeric nanocarriers have shown great promise as delivery systems. An alternative strategy has been to explore new delivery routes, such as intradermal (i.d.), that can be used for vaccines and patch-based drug delivery. Despite their many advantages, there are few toxicity studies, especially in vivo. We report a safety assessment of biodegradable poly(ɛ-caprolactone) lipid-core nanocapsules (LNC) with a mean size of 245±10nm following single and repeated intradermal injections to Wistar rats. Suspensions were prepared by interfacial deposition of polymer. The animals (n=6/group) received a single-dose of saline solution (1.2ml/kg) or LNC (7.2×10(12)LNC/kg), or repeated-doses of two controls, saline solution or Tween 80 (0.9ml/kg), or three different concentrations of LNC (1.8, 3.6, and 5.4×10(12)LNC/kg) for 28 consecutive days. Clinical and physiological signs and mortality were observed. Samples of urine, blood, and tissue were used to perform toxicological evaluation. There were no clinical signs of toxicity or mortality, but there was a slight decrease in the relative body weights in the Tween 80-treated group (p<0.01) after repeated administration. No histopathological alterations were observed in tissues or significant changes in blood and urinary biomarkers for tissue damage. Mild alterations in white blood cells count with increases in granulocytes in the Tween-80 group (p<0.05) were found. Genotoxicity was evaluated through the comet assay, and no statistical difference was observed among the groups. Therefore, we conclude that, under the conditions of these experiments, biodegradable LNC did not present appreciable toxicity after 28 consecutive days of intradermal administration and is promising for its future application in vaccines and patch-based devices for enhancing the delivery of drugs.

Endoscopic augmentation of the esophagogastric junction with polymethylmethacrylate: durability, safety, and efficacy after 6 months in mini-pigs.

BACKGROUND AND AIMS: Endoscopic augmentation of the esophagogastric junction (EGJ) with polymethylmethacrylate (PMMA) has been reported in an experimental short-term study. We assessed whether endoscopic augmentation of the EGJ with PMMA is durable, safe, and efficacious after 6 months in mini-pigs. METHODS: Ten mini-pigs were studied under anesthesia. After a pilot study in two animals, eight mini-pigs underwent lower esophageal sphincter (LES) manometry and gastrostomy with measurement of gastric yield volume (GYV) and gastric yield pressure (GYP). Endoscopic implantation of PMMA was performed aiming for the submucosa of the EGJ. Six months later, LES manometry and GYV and GYP measurements were repeated and animals were sacrificed, followed by microscopic analyses of the EGJ. RESULTS: Out of 32 implants (four per animal), 29 (91%) were identified as submucosal nodules postmortem. PMMA deposits were found at microscopic analysis in all animals and located as follows [mean (range)]: submucosa 61.5% (37.5-91%), muscularis propria 21.5% (0-58%), mucosa 11% (0-25%), and subserosa 6% (0-17%). Neither esophageal perforation nor death was observed. A significant increase in GYV (1,404 versus 905 ml; p = 0.02) and a borderline increase in GYP (8.1 versus 6.5 mmHg; p = 0.057) were detected 6 months later. CONCLUSIONS: Endoscopic augmentation of the esophagogastric junction with PMMA was durable and had no complications after 6 months. However, the occurrence of implants in the subserosa requires technical refinement before use in clinical trials.

Small cell carcinoma of the esophagus: clinicopathological and immunohistochemical findings in four cases

O carcinoma de pequenas células do esôfago é uma neoplasia incomum. Säo relatados os achados clínico-patológicos e imuno-histoquímicos de quatro casos. Disfagia foi a apresentaçäo clínica mais freqüente. Um dos pacientes foi tratado com cirurgia; os outros três näo receberam nenhum tipo de tratamento. Histologicamente, três eram tumores do tipo "oat-cell" com áreas de célula do tipo intermediário. O tipo combinado näo foi observado. A imunohistoquímica demonstrou positividade para enolase neuronal específica e para cromogranina em todos os quatro casos. Um caso era um carcinoma primário duplo, um deles do tipo escamoso e o outro do tipo pequenas células