Lidocaine‐Propitocain Cream,a Eutectic Mixture of Local Anesthetics,Effectively Relieves Pain Associated With Vascular Access Intervention Therapy in Patients Undergoing Hemodialysis: A Placebo‐Controlled,Double‐Blind,Crossover Study

Vascular access intervention therapy (VAIVT) is necessary to maintain vascular access in patients undergoing hemodialysis. VAIVT‐associated vasodilatation is painful. However, few reports have focused on effective pain relief at the time of VAIVT. The present study was performed to determine whether lidocaine‐propitocain cream, a eutectic mixture of local anesthetics (EMLA), effectively reduces VAIVT‐associated pain in patients undergoing hemodialysis. This placebo‐controlled, double‐blind, crossover study was conducted in a single center. Among 210 patients who underwent a total of 437 VAIVT procedures from August 2017 to June 2018, 30 patients were randomly allocated to either the EMLA–placebo arm or placebo–EMLA arm at the time of VAIVT. EMLA application significantly reduced the visual analog scale score compared with placebo (47.0 ± 21.1 vs. 68.6 ± 20.7 mm, respectively; P < 0.05). EMLA is a safe and effective treatment for relief of VAIVT‐associated pain in patients undergoing hemodialysis.     

Pulse-wave velocity,the ankle-brachial index,and the visceral fat area are highly associated with colorectal adenoma

Background

Although both colorectal neoplasms and atherosclerosis may be induced by visceral fat accumulation, no association between these factors has yet been elucidated.

Methods

Among Japanese participants in our colonoscopic screening and annual surveillance programs, asymptomatic subjects were investigated. Visceral fat area was measured by computed tomography, and the ankle-brachial index and pulse-wave velocity (markers of systemic atherosclerosis) were also estimated. Colorectal findings during screening were investigated in association with these parameters.

Results

Nine hundred and seven subjects (males: 71.9%; mean age: 57.3 ± 8.7 years) were enrolled. Colorectal adenomas were identified during colorectal screening of 407 subjects (44.9%). The prevalence of all colorectal adenoma and advanced neoplasia increased with an elevated pulse-wave velocity from 32.2% (advanced neoplasia, 2.6) to 62.1% (8.4%) in higher quartiles (p < 0.001 and p = 0.003). The risk of advanced neoplasia was higher in subjects with an abnormal ankle-brachial index (33% vs. 4.6%, p < 0.001). Upon multivariate analysis, visceral fat area and pulse-wave velocity were associated with all adenoma, and the ankle-brachial index with advanced neoplasia.

Conclusions

The risk of colorectal adenoma was strongly associated with visceral fat area and markers of atherosclerosis. Colorectal adenoma and atherosclerosis may share a common pathogenesis and the same populations are at high-risk.     

Influence of PD‐L1 cross‐linking on cell death in PD‐L1‐expressing cell lines and bovine lymphocytes

Programmed death‐ligand 1 (PD‐L1) blockade is accepted as a novel strategy for the reactivation of exhausted T cells that express programmed death‐1 (PD‐1). However, the mechanism of PD‐L1‐mediated inhibitory signalling after PD‐L1 cross‐linking by anti‐PD‐L1 monoclonal antibody (mAb) or PD‐1–immunogloblin fusion protein (PD‐1‐Ig) is still unknown, although it may induce cell death of PD‐L1⁺ cells required for regular immune reactions. In this study, PD‐1‐Ig or anti‐PD‐L1 mAb treatment was tested in cell lines that expressed PD‐L1 and bovine lymphocytes to investigate whether the treatment induces immune reactivation or PD‐L1‐mediated cell death. PD‐L1 cross‐linking by PD‐1‐Ig or anti‐PD‐L1 mAb primarily increased the number of dead cells in PD‐L1^high cells, but not in PD‐L1^low cells; these cells were prepared from Cos‐7 cells in which bovine PD‐L1 expression was induced by transfection. The PD‐L1‐mediated cell death also occurred in Cos‐7 and HeLa cells transfected with vectors only encoding the extracellular region of PD‐L1. In bovine lymphocytes, the anti‐PD‐L1 mAb treatment up‐regulated interferon‐γ (IFN‐γ) production, whereas PD‐1‐Ig treatment decreased this cytokine production and cell proliferation. The IFN‐γ production in B‐cell‐depleted peripheral blood mononuclear cells was not reduced by PD‐1‐Ig treatment and the percentages of dead cells in PD‐L1⁺ B cells were increased by PD‐1‐Ig treatment, indicating that PD‐1‐Ig‐induced immunosuppression in bovine lymphocytes could be caused by PD‐L1‐mediated B‐cell death. This study provides novel information for the understanding of signalling through PD‐L1.     

Diurnal variation of carbohydrate insulin ratio in adult type 1 diabetic patients treated with continuous subcutaneous insulin infusion

To estimate the carbohydrate‐to‐insulin ratio (CIR), a formula dividing a constant, usually 300–500, by the total daily dose (TDD) of insulin, is widely utilized. An appropriate CIR varies for each meal of the day, however. Here, we investigate diurnal variation of CIR in hospitalized Japanese type 1 diabetic patients treated with continuous subcutaneous insulin infusion. After optimization of the insulin dose, TDD and total basal insulin dose (TBD) were 34.9 ± 10.2 and 9.3 ± 2.8 units, respectively, with a percentage of TBD to TDD of 27.3 ± 6.0%. The products of CIR and TDD at breakfast, lunch and dinner were 311 ± 63, 530 ± 161, and 396 ± 63, respectively, suggesting that in the formula estimating CIR using TDD, the constant should vary for each meal of the day, and that 300, 500, and 400 are appropriate for breakfast, lunch, and dinner, respectively.     

Association between autoimmune pancreatitis and malignancy

Chronic inflammatory diseases are often associated with malignancy, and this phenomenon occurs even in the field of gastroenterology. For example, chronic pancreatitis has been reported to be highly associated with the occurrence of pancreatic cancer. However, the association between autoimmune pancreatitis (AIP) and pancreatic cancer is still an unsolved problem. As AIP is associated with immunoglobulin G4-related disease, which causes a variety of inflammatory and fibrotic lesions, the association between AIP and total malignancies is also a matter of interest. Here, we discuss the association between AIP and malignancy. As for the association between AIP and pancreatic cancer, there is no conclusive evidence, although several reports have suggested that the relative risk of pancreatic cancer is high in AIP. Concerning the association between AIP and total malignancies, there are two reports from Japan. Neither report supported the idea that chronic inflammation in AIP caused the increased risk of total malignancies. However, one report proposed the possibility that AIP might develop as a paraneoplastic syndrome in some patients because many cancers occurred within 1 year of AIP diagnosis, and thereby concluded that patients with AIP were at high risk of having various cancers. The paraneoplastic syndrome hypothesis should be tested in future studies.     

Questionnaire-Based Survey Conducted in 2011 concerning Endoscopic Management of Barrett's Esophagus in East Asian Countries

Background/Aims: Endoscopic definitions and management of Barrett's esophagus vary widely among countries. To examine the current situation regarding diagnosis, epidemiology, management and treatment of Barrett's esophagus in East Asian countries using a questionnaire-based survey. Methods: Representative members of the Committee of the International Gastrointestinal Consensus Symposium developed and sent a questionnaire to major institutions in China, South Korea, Japan, Thailand, Indonesia, and the Philippines. Results: A total of 56 institutions in the 6 countries participated in the survey. We found that the presence of specialized columnar metaplasia is considered to be important for diagnosing Barrett's esophagus in East Asian countries except for Japan. C&M criteria have not been well accepted in East Asia. The palisade vessels are mainly used as a landmark for the esophagogastric junction in Japan. The prevalence of long segment Barrett's esophagus is extremely low in East Asia, while the prevalence of short segment Barrett's esophagus is very high only in Japan, likely due to different diagnostic criteria. Conclusion: Among East Asian countries, we found both similarities and differences regarding diagnosis and management of Barrett's esophagus. The findings in the present survey are helpful to understand the current situation of Barrett's esophagus in East Asian countries.