Risks and benefits of TIPS in HCC and other liver malignancies: a literature review

Abstract Background Transjugular intrahepatic portosystemic shunt (TIPS) is a well-validated treatment option for clinically significant portal hypertension (CSPH) in the context of liver cirrhosis. Its high efficacy and safety in the management of treatment-refractory ascites and variceal bleeding have been extensively proven. Contraindications for TIPS include severe right heart failure, hepatic encephalopathy, and sepsis. However, the role of liver malignancy in TIPS is debatable. Mostly, primary liver malignancies such as hepatocellular carcinoma (HCC) emerge from advanced liver diseases. Coexisting portal hypertension in HCC often results in limited treatment options and a poor prognosis. Summary Previous studies have shown that TIPS implantation in patients with HCC is technically feasible and is usually not associated with major adverse events. Furthermore, TIPS may help in bridging the time to liver transplantation in early HCC and allow for locoregional treatment in advanced HCC. However, several studies suggest that seeding tumour cells to the lungs by TIPS placement might worsen the prognosis. Conclusions TIPS placement in patients with coexisting liver malignancy remains a case-by-case decision, and there is no profound evidence allowing general recommendations. This review aims to provide a state-of-the-art overview of the potential risks and benefits of TIPS placement in patients with liver malignancies

Gastrointestinal Bleeding Diagnosed by Capsule Endoscopy – A Change towards More Patients with Bleeding-related Drugs

Background: Video capsule endoscopy (VCE) is the standard procedure for a work-up of a suspected bleeding source after negative gastroscopy and colonoscopy. Popularity of this procedure increased in the last decade. In this work we aimed to identify the changes in patient characteristics and how those changes influence bleeding related findings. In particular the assumed higher risk of gastrointestinal bleeding of the new oral anticoagulants (nOAC) compared to phenprocoumon was of interest. Methods: Consecutive VCE examinations performed at our center from January 2004 to March 2018 were identified retrospectively. Baseline characteristics of the patients, VCE results and treatment that was initiated were analyzed. Results: 560 VCE were included in the analysis. The rate of VCE per month increased from 2.3/month in the period of January 2004 – December 2012 up to 5.0/month in January 2013 – March 2018. Accompanied by this increase the examined patients suffered from significantly more comorbidities (72 vs. 82%, p 0.001) and used a higher number of bleeding-related drugs (47 vs. 66%, p <0.001), especially nOACs. Age above 65 and bleeding-related drugs were significantly associated with angiodysplasias found on VCE examinations. NOACs and phenprocoumon showed no difference in their correlation to angiodysplasias. Conclusion: This single center retrospective analysis revealed a steep increase in VCE examinations over the last years with an increase in the prevalence of comorbidities and the use of bleeding-related drugs. Interestingly, use of both nOACs and phenprocoumon did not result in a significant higher rate of angiodysplasias in the VCE

GDNF protects enteric glia from apoptosis: evidence for an autocrine loop

Abstract Background Enteric glia cells (EGC) play an important role in the maintenance of intestinal mucosa integrity. During the course of acute Crohn's disease (CD), mucosal EGC progressively undergo apoptosis, though the mechanisms are largely unknown. We investigated the role of Glial-derived neurotrophic factor (GDNF) in the regulation of EGC apoptosis. Methods GDNF expression and EGC apoptosis were determined by immunofluorescence using specimen from CD patients. In primary rat EGC cultures, GDNF receptors were assessed by western blot and indirect immunofluorescence microscopy. Apoptosis in cultured EGC was induced by TNF-α and IFN-γ, and the influence of GDNF on apoptosis was measured upon addition of GDNF or neutralizing anti-GDNF antibody. Results Increased GDNF expression and Caspase 3/7 activities were detected in in specimen of CD patients but not in healthy controls. Moreover, inactivation of GDNF sensitized in EGC cell to IFN-γ/TNF-α induced apoptosis. Conclusions This study proposes the existence of an autocrine anti-apoptotic loop in EGC cells which is operative in Crohn's disease and dependent of GDNF. Alterations in this novel EGC self-protecting mechanism could lead to a higher susceptibility towards apoptosis and thus contribute to disruption of the mucosal integrity and severity of inflammation in CD.</p

Hsp72 Overexpression Accelerates the Recovery from Caerulein-Induced Pancreatitis

<div><h3>Background and Aims</h3><p>Heat shock protein (Hsp) 72 is a molecular chaperone which is upregulated in response to a variety of stress situations and has a general cytoprotective function. Increased Hsp72 levels were implicated in protection from acute pancreatitis; a hypothesis which was not tested in a transgenic mouse model yet.</p> <h3>Methods</h3><p>To analyze the role of Hsp72 during acute pancreatitis, well-characterized transgenic animals overexpressing rat Hsp72 (Hsp72 mice) under the control of the ß-actin promoter were subjected to caerulein- and L-arginine-induced acute pancreatitis. The severity of experimental pancreatitis was determined via serum lipase levels, morphometric evaluation and quantification of pancreatic edema/inflammation.</p> <h3>Results</h3><p>Hsp72 mice displayed ∼100-times Hsp72 overexpression, but no changes in the remaining chaperones. Robust Hsp72 signal was observed in pancreatic acini, but not in islets or ductal cells. In both models, elevated Hsp72 did not protect from development of acute pancreatitis and the pancreatitis-associated lung injury, but accelerated recovery from caerulein-induced tissue injury (lower lipase levels, edema, inflammation and necrosis 36 h after caerulein administration). The observed protective function of Hsp72 in caerulein-induced pancreatitis is likely due to an attenuated NF-κB signalling.</p> <h3>Conclusions</h3><p>Hsp72 overexpression accelerates the recovery from acute pancreatitis and may represent a potential treatment strategy.</p> </div

Histological scoring confirms the accelerated recovery of Hsp72 mice from caerulein - induced pancreatitis.

<p>(A–C) Animals subjected to caerulein for 6, 12, 36 and 96 hours as well as untreated animals were histologically evaluated with respect to their tissue edema (A), extent of necrosis (B) as well as leucocyte infiltration (C). Note that 36 hours after caerulein-injection, Hsp72 mice (black bars) display significantly lower values in all three assessed parameters than their non-transgenic littermates (grey bars). D) Serum lipase levels were measured in Hsp72 (black bars) and nontransgenic (grey bars) mice and visualized as mean ± SEM values from at least 4 mice per group/time point. Note that 36 hours after caerulein injection, Hsp72 mice display significantly lower lipase levels than the nontransgenic animals. *P< 0.05.</p

Hsp72 mice show abundant Hsp72 overexpression in exocrine pancreas.

<p>Pancreatic tissues from nontransgenic (A,B) and Hsp72 mice (C,D) were analyzed by in situ hybridization using rat Hsp72 sense (A,C) and antisense probes (B,D). Note, the prominent Hsp72 signal in exocrine, but not endocrine pancreas of transgenic animals (D), while the nontransgenic mice and sense probes did not exhibit any labelling. Scale bars 200 µm (A–D).</p

PCR Primers (5′–3′) for Genotyping and Real-Time qRT-PCR.

<p>PCR Primers (5′–3′) for Genotyping and Real-Time qRT-PCR.</p

Hsp72 mice display an accelerated recovery from acute pancreatitis.

<p>Representative pancreatic tissue sections from non-transgenic (A,B,E,F,I,J,M,N,Q,R) and Hsp72 mice (C,D,G,H,K,L,O,P,S,T) were stained with hematoxylin and eosin. Animals were analyzed 6 h (E–H), 12 h (I–L), 36 h (M–P) and 96 h (Q–T) after first caerulein injection and were compared with untreated controls (A–D). Note that 36 hours after first caerulein injection, Hsp72, but not non-transgenic animals displayed an almost complete histological recovery (M–P). Scale bars 1 mm (A,C,E,G,I,K,M,O,Q,S) and 200 µm (B,D,F,H,J,L,N,P,R,T).</p

Hsp72 overexpression does not protect from L-arginine-induced acute pancreatitis.

<p>(A) Pancreatic tissue sections from nontransgenic (a, c) and Hsp72 mice (b, d) were stained with haematoxylin and eosin prior to (a,b) and after treatment with L-arginine (c, d). Scale bars (a–d), 100 µm. (B) Morphometric analysis of histological sections reveals the extent of edema, necrosis and leukocyte infiltration in nontransgenic (grey bars) and Hsp72 animals (black bars) injected with L-arginine (C) Serum lipase levels and pancreatic water content (D) determine the extent of pancreatic/acinar injury in Hsp72 (black bars) and nontransgenic mice (grey bars) subjected to L-arginine. The data are presented as mean ± SEM. At least 5 mice were used per group/time point.</p