Comparison of endoscopic ultrasound-guided choledochoduodenostomy and endoscopic retrograde cholangiopancreatography in first-line biliary drainage for malignant distal bile duct obstruction: A multicenter randomized controlled trial

Introduction:In patients with malignant distal bile duct obstruction and normal gastrointestinal anatomy, endoscopic ultrasound-guided choledochoduodenostomy (EUS-CDS) is indicated when endoscopic retrograde cholangiopancreatography (ERCP) fails. The ERCP drainage route passes through the tumor, whereas the EUS-CDS route does not. Therefore, EUS-CDS is expected to have a longer stent patency than ERCP. However, for first-line biliary drainage, it remains unclear whether EUS-CDS or ERCP is superior in terms of stent patency. To reduce the frequency of highly adverse events (AEs) such as bile peritonitis or stent migration following EUS-CDS, we developed an antimigration metal stent with a thin delivery system for tract dilatation. This study is designed to assess whether EUS-CDS with this novel stent is superior to ERCP with a traditional metal stent in terms of stent patency when the two techniques are used for first-line drainage of malignant distal biliary obstruction.Methods/design:This study is a multicenter single-blinded randomized controlled trial (RCT) involving 95 patients in four tertiary centers. Patients with malignant distal biliary obstruction that is unresectable or presents a very high surgical risk and who pass the inclusion and exclusion criteria will be randomized to EUS-CDS or ERCP in a 1:1 proportion. The primary endpoint is the stent patency rate 180 days after stent insertion. Secondary outcomes include the rates of technical success, clinical success, technical success in cases not requiring fistulous-tract dilation (only EUS-CDS group), procedure-related AEs, re-intervention success, patients receiving post-drainage chemotherapy, procedure time, and overall survival time.Discussion:If EUS-CDS is superior to ERCP in terms of stent patency and safety for the first-line drainage of malignant distal biliary obstruction, it is expected that the first-line drainage method will be changed from ERCP to EUS-CDS, and that interruption of chemotherapy due to stent dysfunction can be avoided.Trial registration:University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR), ID: UMIN000041343. Registered on August 6, 2020. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000047201Version number: 1.2, December 7, 2020.     

The use of a biventricular assist device for postcardiotomy profound biventricular failure

A 58-year-old woman who could not be weaned from cardiopulmonary bypass was treated with a biventricular assist device (BVAD) using a centrifugal pump for the left side and a pneumatic pulsatile pump for the right side. At the initiation of the BVAD support, predominant right ventricular failure was recognized and therefore weaning was begun from the left side. The left ventricular assist device was discontinued after 87 h and the patient was finally weaned from the right ventricular assist device after 205 h. Despite the complete recovery of cardiac function, the patient developed renal failure followed by an intractable infection and died of multiple organ failure on the 59th postoperative day (POD).     

Correlation of ratio of serum pepsinogen I and II with prevalence of gastric cancer and adenoma in Japanese subjects

Objective: Gastric cancer (GC) and adenoma (GA) are reported to be related to atrophic gastritis, in which the serum pepsinogen (PG) I level and the PGI/PGII ratio (I/II ratio) are reduced. To verify that the finding of a low PG level increases the risk for GC and GA, we investigated the correlation between low PG levels and the prevalence of GC and GA in individuals.
Methods: The 2,039 subjects (734 Japanese men, mean age 68.5 yr, and 1,305 women, mean age 66.7 yr), selected from among 10,996 local residents who underwent health check-ups based on reductions in their serum PG levels, underwent upper gastrointestinal endoscopy.
Results: Gastrointestinal endoscopy detected 21 GCs and 15 GAs. The prevalence of GC was higher than that in the residents without low serum PG. The percentage of early stage of GC (90%) was significantly higher than that of GC detected in unscreened residents (56.9%). The prevalence of GC in men was closely and significantly correlated with the I/II ratio (  r = 0.935  ,   p = 0.0063  ), whereas there was less correlation with age (  r = 0.842  ,   p = 0.0734  ). The prevalence of GA was also closely and significantly correlated with the I/II ratio in men (  r = 0.881  ,   p = 0.0203  ), but not with age (  r = 0.163  ,   p = 0.7928  ). In women the prevalence of GC (r 5 0.744,   p = 0.090  ) and GA (  r = 0.678  ,   p = 0.1392  ) did not correlate as strongly with the I/II ratio, although the highest prevalence was seen in the group with the lowest I/II ratio.
Conclusion: Our study verified that a low I/II ratio signifies a high risk for GC and GA and that measuring serum PG levels can be used as a screening method for GC and GA.     

Progression of Renal Dysfunction in Patients with Cardiovascular Disease

It has been established that patients with chronic kidney disease (CKD) suffer from frequent cardiovascular events. On the other hand, recent studies suggest that renal damage tends to worsen in patients with cardiovascular diseases (CVD). Although the mechanisms for the cardiorenal association are unclear, the presence of arteriosclerotic risk factors common to both CVD and CKD is important. In arteriosclerosis, vascular derangement progresses not only in the heart but also in the kidney. In addition, heart failure, cardiac catheterization and hesitation of medical treatments due to renal dysfunction may explain the progression of renal damage. Therefore, the goal of treatments is a total control of arteriosclerotic risk factors. Medication should be selected among agents with protective effects on both heart and kidney. It is important to always consider the presence of CKD for the treatment of the cardiovascular disease and strictly control the risk factors.Key Words: CKD, angiotensin II, aldosterone, ARB, hypertension.     

Primary hepatic presentation of Hodgkin's lymphoma: A case report

Hodgkin's lymphoma (HL) is in general a lymph node‐based disease. Hepatic involvement usually occurs in the advanced disease. Primary and prominent manifestation of the disease in the liver is extremely rare. We report magnetic resonance imaging leading to diagnosis in a rare case of liver involvement as the first sign of HL.     

Shape of Barrett's epithelium is associated with prevalence of erosive esophagitis

AIM:To test the hypothesis that the shape and length of Barrett‘s epithelium are associated with prevalence of erosive esophagitis.METHODS:A total study population comprised 869 patients who underwent endoscopy during a health checkup at our hospital.The presence and extent of Barrett‘s epithelium were diagnosed based on the Prague C & M Criteria.We originally classified cases of Barrett‘s epithelium into two types based on its shape,namely,flamelike and lotus-like Barrett‘s epithelium,and into two groups b...     

Notch-Hes1 pathway is required for the development of IL-17-producing γδ T cells

Unlike conventional T cells, which are exported from the thymus as naive cells and acquire effector functions upon antigen encounter in the periphery, a subset of γδ T cells differentiates into effectors that produce IL-17 within the fetal thymus. We demonstrate here that intrathymic development of the naturally occurring IL-17-producing γδ T cells is independent of STAT3 and partly dependent on RORγt. Comparative gene-expression analysis identified Hes1, one of the basic helix-loop-helix proteins involved in Notch signaling, as a factor specifically expressed in IL-17-producing γδ T cells. Hes1 is critically involved in the development of IL-17-producing γδ T cells, as evidenced by their severe decrease in the thymi of Hes1-deficient fetal mice. Delta-like 4 (Dll4)-expressing stromal cells support the development of IL-17-producing γδ T cells in vitro. In addition, conditional Hes1 ablation in peripheral γδ T cells decreases their IL-17 production but not their IFN-γ production. These results reveal a unique differentiation pathway of IL-17-producing γδ T cells.     

Cellular mechanism for herbal medicine Junchoto to facilitate intestinal Cl<Superscript>−</Superscript>/water secretion that involves cAMP-dependent activation of CFTR

Constipation is a common symptom frequently compromising the quality of daily life. Several mechanistically different drugs have been used to mitigate constipation, including Japanese herbal (Kampo) medicines. However, the mechanisms of their actions are often not well understood. Here we aimed to investigate the molecular mechanisms underlying the effects of Junchoto (JCT), a Kampo medicine empirically prescribed for chronic constipation. Cl^? channel activity was measured by the patch-clamp method in human cystic fibrosis transmembrane conductance regulator (CFTR)-expressing HEK293T cells and human intestinal Caco-2 cells. cAMP was measured by a luciferase-based assay. Cell volume change was measured by a particle-sizing and particle-counting analyzer and video-microscopic measurement. In both CFTR-expressing HEK293T and Caco-2 cells, JCT dose-dependently induced whole-cell currents showing typical biophysical and pharmacological features of CFTR. Robust expression of CFTR was confirmed by RT-PCR and Western blotting in Caco-2 cells. Luciferase-based measurement revealed that JCT increases intracellular cAMP levels. Administration of the adenylate cyclase inhibitor SQ22536 or CFTR inhibitor-172, or treatment with small interfering RNAs (siRNA) targeting CFTR, abolished JCT-induced whole-cell currents, suggesting that elevated intracellular cAMP by JCT causes activation of CFTR in Caco-2 cells. Finally, blockade of CFTR activity by CFTR inhibitor-172 or siRNA-knockdown of CFTR or application of SQ22536 markedly reduced the degree of cell volume decrease induced by JCT. JCT can induce a Cl^? efflux through the CFTR channel to promote water secretion, and this effect is likely mediated by increased cAMP production.     

Effect of sumatriptan on gastric emptying: a crossover study using the BreathID system

AIM:To determine the effect of oral sumatriptan on gastric emptying using a continuous 13 C breath test(BreathID system).METHODS:Ten healthy male volunteers participated in this randomized,2-way crossover study.The subjects fasted overnight and were randomly assigned to receive a test meal(200 kcal/200 mL) 30 min after pre-medication with sumatriptan 50 mg(sumatriptan condition),or the test meal alone(control condition).Gastric emptying was monitored for 4 h after administration of the test meal by the 13 C-acetic acid breath test performed continually using the BreathID system.Then,using Oridion Research Software(β version),the time taken for emptying of 50% of the labeled meal(T 1/2) similar to the scintigraphy lag time for 10% emptying of the labeled meal(T lag),the gastric emptying coefficient(GEC),and the regression-estimated constants(β and κ) were calculated.The statistical significance of any differences in the parameters were analyzed using Wilcoxon’s signed-rank test.RESULTS:In the sumatriptan condition,significant differences compared with the control condition were found in T 1/2 [median 131.84 min(range,103.13-168.70) vs 120.27 min(89.61-138.25);P = 0.0016],T lag [median 80.085 min(59.23-125.89) vs 61.11 min(39.86-87.05);P = 0.0125],and β [median 2.3374(1.6407-3.8209) vs 2.0847(1.4755-2.9269);P = 0.0284].There were no significant differences in the GEC or κ between the 2 conditions.CONCLUSION:This study showed that oral sumatriptan significantly delayed gastric emptying of a liquid meal.     

The periodontal pathogen aggregatibacter actinomycetemcomitans deteriorates ventricular remodeling after myocardial infarction in mice

Chronic inflammation plays a fundamental role in coronary heart disease (CHD). Periodontal disease is a common infectious disease and is a potential source of systemic inflammation. However, the effect of periodontal infection on CHD has not yet been proven. The purpose of this study was to determine the effect of periodontopathic bacteria on experimental myocardial infarction (MI). We implanted a chamber into the subcutaneous tissue of each male mouse. Aggregatibacter actinomycetemcomitans (A.a. n = 8), which is a major periodontal pathogen, or PBS (n = 6) was injected into the chamber. Then, MI was induced by permanent ligation of the left anterior descending coronary artery. To exclude the nonspecific effect of the pathogen, we injected A.a. into the mice without MI (n = 4). The plasma level of anti-A.a. antibody was statistically higher in A.a.-infected mice than in vehicle control mice. Seven days after the myocardial ischemia, the A.a.-positive MI hearts showed a larger infarct size and length than the A.a.-negative MI mice. The A.a.-positive MI hearts showed more MOMA-2 positive myocardial infiltrating cells compared to the A.a.-negative MI mice. The injection of A.a. into the mice without MI did not affect their hearts. We concluded that a periodontal pathogen infection might deteriorate ventricular remodeling after MI through inflammatory cell infiltration.