Dietary intervention reverses molecular markers of hepatocellular senescence in the GAN diet-induced obese and biopsy-confirmed mouse model of NASH BMC Gastroenterology -
Mathias Flensted-Jensen, Denise Oró, Emma A. Rørbeck, Chen Zhang, Martin Rønn Madsen, Andreas Nygaard Madsen, Jenny Norlin, Michael Feigh, Steen Larsen, Henrik H. Hansen
Abstract
Background
Hepatocellular senescence may be a causal factor in the development and progression of non-alcoholic steatohepatitis (NASH). The most effective currently available treatment for NASH is lifestyle intervention, including dietary modification. This study aimed to evaluate the effects of dietary intervention on hallmarks of NASH and molecular signatures of hepatocellular senescence in the Gubra-Amylin NASH (GAN) diet-induced obese (DIO) and biopsy-confirmed mouse model of NASH.
Methods
GAN DIO-NASH mice with liver biopsy-confirmed NASH and fibrosis received dietary intervention by switching to chow feeding (chow reversal) for 8, 16 or 24 weeks. Untreated GAN DIO-NASH mice and chow-fed C57BL/6J mice served as controls. Pre-to-post liver biopsy histology was performed for within-subject evaluation of NAFLD Activity Score and fibrosis stage. Terminal endpoints included blood/liver biochemistry, quantitative liver histology, mitochondrial respiration and RNA sequencing.
Results
Chow-reversal promoted substantial benefits on metabolic outcomes and liver histology, as demonstrated by robust weight loss, complete resolution of hepatomegaly, hypercholesterolemia, elevated transaminase levels and hepatic steatosis in addition to attenuation of inflammatory markers. Notably, all DIO-NASH mice demonstrated ≥ 2 point significant improvement in NAFLD Activity Score following dietary intervention. While not improving fibrosis stage, chow-reversal reduced quantitative fibrosis markers (PSR, collagen 1a1, α-SMA), concurrent with improved liver mitochondrial respiration, complete reversal of p21 overexpression, lowered γ-H2AX levels and widespread suppression of gene expression markers of hepatocellular senescence.
Conclusions
Dietary intervention (chow reversal) substantially improves metabolic, biochemical and histological hallmarks of NASH and fibrosis in GAN DIO-NASH mice. These benefits were reflected by progressive clearance of senescent hepatocellular cells, making the model suitable for profiling potential senotherapeutics in preclinical drug discovery for NASH.
A potential anatomic subtype of short bowel syndrome: a matched case-control study BMC Gastroenterology - Tập 16 - Trang 1-8 - 2016
Wencheng Kong, Jian Wang, Rongchao Ying, Yousheng Li, Huicheng Jin, Qi Mao, Danhua Yao, Mingxiao Guo
Fundamental researches suggest that ileum presents greater adaptive potential than the jejunum. However, few studies estimate the association between ileum and adaptive potential in human. To discover the association, we conducted this matched case-control study. A 1:2 pair-matched, case-control study was conducted from January 1, 2001 to January 1, 2015 in Intestinal Rehabilition and Transplant Center. The case group was ileum predominated (IP) group and the control group was jejunum predominated (JP) group. Demographic data, medical history and progression of each patient were collected. There were 24 IP cases and 48 JP controls in this study. The cumulative probabilities of parenteral nutrition (PN) weaning in IP group were higher than that in JP group. The Bristol stool scale scores of IP group were lower than that of JP group at third month. The Cox proportional hazards regression model confirmed that IP had a higher odds of PN weaning (OR = 2.69; 95 % CI: 1.27, 5.70, p = 0.01) as compared with JP group. The conditional logistic regression with 1:2 matching also confirmed IP group had a higher odds (OR = 4.84; 95 % CI: 2.02, 11.56, p <0.01). Our results indicated that ileum presents greater adaptive potential than the jejunum in nutrition and fluid absorption. And a potential anatomic subtype of short bowel syndrome was proposed. Further research need to be conducted to more fully understand the adaptive potential of ileum besides nutrition and fluid absorption.
Applicability of a short/rapid 13C-urea breath test for Helicobacter pylori: retrospective multicenter chart review study BMC Gastroenterology - Tập 12 - Trang 1-5 - 2012
Hemda Schmilovitz-Weiss, Vered Sehayek-Shabat, Rami Eliakim, Eitan Skapa, Yona Avni, Haim Shirin
Carbon labeled urea breath tests usually entail a two point sampling with a 20 to 30-minute gap. Our aim was to evaluate the duration of time needed for diagnosing Helicobacter pylori by the BreathID® System. This is a retrospective multicenter chart review study. Test location, date, delta over baseline, and duration of the entire test were recorded. Consecutively 13C urea breath tests results were extracted from the files over a nine year period. Of the 12,791 tests results, 35.1% were positively diagnosed and only 0.1% were inconclusive. A statistically significant difference in prevalence among the countries was found: Germany showing the lowest, 13.3%, and Israel the highest, 44.1%. Significant differences were found in time to diagnosis: a positive diagnosis had the shortest and an inconclusive result had the longest. Overall test duration averaged 15.1 minutes in Germany versus approximately 13 minutes in other countries. Diagnosis was achieved after approximately 9 minutes in Israel, Italy and Switzerland, but after 10 on average in the others. The mean delta over baseline value for a negative diagnosis was 1.03 ± 0.86, (range, 0.9 - 5), versus 20.2 ± 18.9, (range, 5.1 - 159.4) for a positive one. The BreathID® System used in diagnosing Helicobacter pylori can safely shorten test duration on average of 10-13 minutes without any loss of sensitivity or specificity and with no test lasting more than 21 minutes.
The galactose elimination capacity and mortality in 781 Danish patients with newly-diagnosed liver cirrhosis: a cohort study BMC Gastroenterology - Tập 9 - Trang 1-6 - 2009
Peter Jepsen, Hendrik Vilstrup, Peter Ott, Susanne Keiding, Per K Andersen, Niels Tygstrup
Despite its biologic plausibility, the association between liver function and mortality of patients with chronic liver disease is not well supported by data. Therefore, we examined whether the galactose elimination capacity (GEC), a physiological measure of the total metabolic capacity of the liver, was associated with mortality in a large cohort of patients with newly-diagnosed cirrhosis. By combining data from a GEC database with data from healthcare registries we identified cirrhosis patients with a GEC test at the time of cirrhosis diagnosis in 1992–2005. We divided the patients into 10 equal-sized groups according to GEC and calculated all-cause mortality as well as cirrhosis-related and not cirrhosis-related mortality for each group. Cox regression was used to adjust the association between GEC and all-cause mortality for confounding by age, gender and comorbidity, measured by the Charlson comorbidity index. We included 781 patients, and 454 (58%) of them died during 2,617 years of follow-up. Among the 75% of patients with a decreased GEC (<1.75 mmol/min), GEC was a strong predictor of 30-day, 1-year, and 5-year mortality, and this could not be explained by confounding (crude hazard ratio for a 0.5 mmol/min GEC increase = 0.74, 95% CI 0.59–0.92; adjusted hazard ratio = 0.64, 95% CI 0.51–0.81). Further analyses showed that the association between GEC and mortality was identical for patients with alcoholic or non-alcoholic cirrhosis etiology, that it also existed among patients with comorbidity, and that GEC was only a predictor of cirrhosis-related mortality. Among the 25% of patients with a GEC in the normal range (≥ 1.75 mmol/min), GEC was only weakly associated with mortality (crude hazard ratio = 0.79, 95% CI 0.59–1.05; adjusted hazard ratio = 0.80, 95% CI 0.60–1.08). Among patients with newly-diagnosed cirrhosis and a decreased GEC, the GEC was a strong predictor of short- and long-term all-cause and cirrhosis-related mortality. These findings support the expectation that loss of liver function increases mortality.
Stercoral colitis complicated with ischemic colitis: a double-edge sword BMC Gastroenterology - Tập 17 - Trang 1-6 - 2017
Maliha Naseer, Jenil Gandhi, Noor Chams, Zain Kulairi
Stercoral colitis is a rare inflammatory process involving the colonic wall secondary to fecal impaction with high morbidity and mortality; especially if complicated with ischemic colitis, stercoral ulcer formation and subsequent perforation. There are several case reports published on abdominal perforation resulting from stercoral colitis. However, stercoral colitis complicated by ischemic colitis is rare. The purpose of this case report is to describe the potential challenges in the diagnosis and management of stercoral colitis with ischemic colitis. An 87 years old male with history of chronic constipation presents with severe abdominal pain to the emergency department. The patient was hemodynamically stable. On physical examination, the abdomen was mildly distended with moderate tenderness. Lab work was significant for leukocytosis and lactic acidosis. Abdominal CT scan revealed large amount of retained stool in the colon, bowel wall thickening and infiltration of peri-colonic fat, which were suggestive for stercoral colitis. Patient was started on IV fluids and antibiotics. He was given an enema, followed by laxative and manual disimpaction of stool. Colonoscopy was performed and biopsies were obtained. Tissue biopsy was significant for focal active colitis with regenerative glandular changes and neural hyperplasia. Elevated lactic acid level secondary to ischemia of the bowel wall with CT scan findings aid in establishing the diagnosis of stercoral colitis complicated with ischemic colitis. Urgent treatment with laxatives and fecal disimpaction is indicated to prevent perforation and peritonitis.
Clinical characteristics, CT signs, and pathological findings of Pyrrolizidine alkaloids-induced sinusoidal obstructive syndrome: a retrospective study BMC Gastroenterology - Tập 20 Số 1 - 2020
Fang Liu, Xinxin Rong, Hui Guo, Dong Xu, Chang Liu, Lingling Meng, Xiaoqian Yang, Tingting Guo, Xuefeng Kan, Yuhu Song
Abstract
Background
One major etiology of hepatic sinusoidal obstruction syndrome (HSOS) in China is the intake of pyrrolizidine alkaloids (PAs). Since PAs-induced HSOS is a rare disease that has not been clearly characterized until now, the aim of this study was to investigate clinical characteristics, CT features, and pathological findings of PA-induced HSOS.
Methods
This retrospective cohort study included 116 patients with PAs-induced HSOS and 68 patients with Budd-Chiari syndrome from Jan 2006 to Sep 2016. We collected medical records of the patients, and reviewed image features of CT, and analyzed pathological findings.
Results
Common clinical manifestations of PAs-induced HSOS were abdominal distention (98.26%), ascites (100%), jaundice (52.94%), abdominal pain (36.36%). Abnormal liver function was observed in most of PAs-induced HSOS. On CT scan, common findings included: ascites, hepatomegaly, the thickening of gallbladder wall, pleural effusion, patchy liver enhancement, and heterogeneous hypoattenuation. Most of the patients had a low ascitic total protein (< 25 g/L) and a high SAAG (≥ 11.0 g/L). In acute stage, pathologic features were massive sinusoidal dilatation, sinusoidal congestion, the extravasation of erythrocytes, hepatocellular necrosis, the accumulation of macrophages, the deposition of hemosiderin. In subacute stage, complete loss of pericentral hepatocytes, sinusoidal dilatation, the deposition of pigment granules were observed.
Conclusions
The PAs-induced HSOS patients displayed distinct clinical characteristics, imaging features, and pathological findings, which provided some evidences for the diagnosis of PAs-induced HSOS.
Trial registration
ChiCTR-DRD-17010709.
Central lymph node metastasis is predictive of survival in advanced gastric cancer patients treated with D2 lymphadenectomy BMC Gastroenterology - Tập 21 - Trang 1-8 - 2021
Huiwen Lu, Bochao Zhao, Rui Huang, Yimeng Sun, Zirui Zhu, Huimian Xu, Baojun Huang
The number of positive lymph nodes, which was defined as “N stage”, is mostly used to predict the survival of D2-resected gastric cancer patients, not the location. A “central lymph node” (CnLN) was defined by Ikoma et al., included common hepatic, celiac and proximal splenic artery LNs. CnLNs located in the extraperigastric area are included in the D2 LN station for gastric cancer. We speculate that CnLNs can be regarded as a predictor of survival. Eligible advanced gastric cancer patients who underwent curative resection and D2 lymph node dissection between 2004 and 2012 at our institution were identified. The frequency of CnLN metastases and risk factors affecting DFS were examined. Survival differences were assessed by log-rank tests and Kaplan–Meier curves. The study identified 1178 patients who underwent curative surgery or D2 or more extensive lymphadenectomy. A total of 342 patients had been proven to have CnLN metastasis. Larger tumor size (P < 0.001), more frequent lymphatic vessel invasion (P < 0.001), signet ring cell histology (P = 0.014), and more advanced pathological T stage (P = 0.013) were significantly related to CnLNs metastasis. The patients with CnLN metastasis had a poor prognosis (HR for DFS of 1.366, 95%CI = 1.138–1.640, P = 0.001). For the pN2/3 patients, CnLN metastasis was associated with shorter 5-year DFS (for pN2 patients: 25.9% vs 39.3%, P = 0.017; for pN3 patients: 11.5% vs 23.4%, P = 0.005). Gastric cancer patients with CnLN metastasis who underwent D2 resection had a poor prognosis. With the same N stage, the patients with positive CnLNs had shorter survival. CnLNs metastasis could be a supplement to N stage and a predictor of survival in gastric cancer patients. Large sample, multicenter, randomized clinical trials are still needed in the future.
Production of ERCP training model using a 3D printing technique (with video) BMC Gastroenterology - Tập 20 - Trang 1-9 - 2020
Chang-Il Kwon, Yeonsun Shin, Jaeok Hong, Minje Im, Guk Bae Kim, Dong Hee Koh, Tae Jun Song, Won Suk Park, Jong Jin Hyun, Seok Jeong
ERCP training models are very different in terms of anatomical differences, ethical issues, storage problems, realistic tactile sensation, durability and portability. There is no easy way to select an optimized model for ERCP training. If the ERCP training model could be made as a soft silicone model using 3D printing technique, it would have numerous advantages over the models presented so far. The purpose of this study was to develop an optimized ERCP training model using a 3D printing technique and to try to find ways for implementing various practical techniques. All organ parts of this model were fabricated using silicone molding techniques with 3D printing. Especially, various anatomy of the ampulla of Vater and common bile duct (CBD) were creatively designed for different diagnostic and therapeutic procedures. In order to manufacture each of the designed organ parts with silicone, a negative part had to be newly designed to produce the molder. The negative molders were 3D printed and then injection molding was applied to obtain organ parts in silicone material. The eight different types of ampulla and CBD were repeatedly utilized and replaced to the main system as a module-type. ERCP training silicone model using 3D technique was semi-permanently used to repeat various ERCP procedures. All ERCP procedures using this model could be observed by real-time fluoroscopic examination as well as endoscopic examination simultaneously. Using different ampulla and CBD modules, basic biliary cannulation, difficult cannulation, stone extraction, mechanical lithotripsy, metal stent insertion, plastic stent insertion, and balloon dilation were successfully and repeatedly achieved. Endoscopic sphincterotomy was also performed on a specialized ampulla using a Vienna sausage. After repeat procedures and trainings, all parts of organs including the ampulla and CBD modules were not markedly damaged or deformed. We made a specialized ERCP training silicon model with 3D printing technique. This model is durable, relatively cheap and easy to make, and thus allows the users to perform various specialized ERCP techniques, which increases its chances of being a good ERCP training model.
