Evaluation of the Validity of Endoscopic Transpapillary Gallbladder Drainage for Acute Cholecystitis Based on the Tokyo Guidelines 2018.

GOALS: We evaluated the validity of endoscopic transpapillary gallbladder drainage (ETGBD) as a bridging therapy prior to elective Lap-C for the patients with acute cholecystitis (AC). BACKGROUND: The Tokyo Guidelines 2018 recommend early laparoscopic cholecystectomy (Lap-C) for patients with AC, however, some patients require the preoperative drainage because of inadequate for early Lap-C du to background and comorbidities. STUDY: We performed a retrospective cohort analysis using data from our hospital records from 2018-2021. In total, 71 cases of 61 patients with AC underwent ETGBD. RESULTS: The technical success rate was 85.9%. Patients in the failure group had more complicated branching of the cystic duct. The length of time until feeding was started and until WBC levels normalized, and the length of hospital stay were significantly shorter in the success group. The median waiting period for surgery was 39 days in the ETGBD success cases. The median operating time, amount of bleeding, and length of postoperative hospital stay were 134 min, 83.2g, and 4 days, respectively. In patients who underwent Lap-C, the waiting period for surgery and the operating time were similar between the ETGBD success and failure groups. However, the temporary discharge period after drainage and the length of postoperative hospital stay were significantly longer in the patients with ETGBD failure. CONCLUSIONS: Our study revealed that ETGBD has equivalent efficacy prior to elective Lap-C despite some challenges that lower its success rate. Preoperativ ETGBD can improve patient quality of life by eliminating the need for a drainage tube.

Hemorrhoids as a risk factor for colorectal adenomas on colonoscopy.

Background and study aims Colorectal premalignant polyps and hemorrhoids are important findings in colonoscopy; however, the association between them is unclear. Therefore, we investigated the association between the presence and severity of hemorrhoids and the detection of precancerous colorectal polyps on colonoscopy. Patients and methods This retrospective, single-center, cross-sectional study enrolled patients who underwent colonoscopy at Toyoshima Endoscopy Clinic between May 2017 and October 2020. The association between hemorrhoids and other outcomes (patient age, sex, withdrawal time for colonoscopy, expert endoscopist, number of adenomas per colonoscopy, detection rates of adenoma, advanced neoplasia, clinically significant serrated polyp, and sessile serrated lesion) was assessed using a binomial logistic regression model. Results A total of 12,408 patients were enrolled in this study. Hemorrhoids were identified in 1,863 patients. Univariable analysis showed that patients with hemorrhoids were older (61.0 vs. 52.5 years, P  < 0.001), had a higher number of adenomas per colonoscopy (1.16 vs. 0.756, P  < 0.001) than those without hemorrhoids. Multivariable analyses also demonstrated that hemorrhoids were associated with a higher number of adenomas per colonoscopy (odds ratio [OR]: 1.061; P  = 0.002), regardless of patient age, sex, and expert endoscopist. Among patients with hemorrhoids, severe hemorrhoids with a mucosal elevation ≥ 10 mm were associated with a higher number of adenomas per colonoscopy than mild hemorrhoids (OR: 1.112, P  = 0.044), regardless of patient age, sex, and expert endoscopist. Conclusions Hemorrhoids, especially severe ones, are associated with a high number of adenomas. Complete colonoscopy should be performed in patients with hemorrhoids.

Annual change of respiratory functions in adult patients with asthma: the potential of antiasthma treatments for many years to repair irreversible changes of the airway.

BACKGROUND: Little is known regarding annual changes of respiratory functions among patients with asthma after asthma symptoms enter remission. OBJECTIVE: Annual changes of respiratory function and influence of patient characteristics and treatment variables on these changes were assessed in patients with adult asthma. METHODS: Respiratory function (pre- and postbronchodilator forced expiratory volume in one second [FEV1] and reversibility by short-acting ß2-agonist) and their changes were retrospectively investigated and relationships between these changes, after symptomatic remission, and patient characteristics and treatments were analyzed in adult outpatients with asthma who had undergone spirometry (including a reversibility test) ≥5 times in >5 years. RESULTS: In patients ≥40 years old, or with disease duration ≥10 years or receiving treatment for severe asthma (steps 4-5, high-dose inhaled glucocorticosteroids, or addition of other medications), both pre- and postbronchodilator FEV1 values were significantly lower (p < .05). Mean annual change of prebronchodilator FEV1 (Δpre-FEV1), annual change of postbronchodilator FEV1 (Δpost-FEV1), and annual change of reversibility (Δ reversibility) were -13.8 ± 59.7 ml/year, -25.9 ± 51.0 ml/year, and -0.56% ± 1.89%/year, respectively. Multivariate analysis after stepwise selection for variables in patient characteristics or treatments showed that disease duration ≥10 years contributed to annual improvement of respiratory functions (Δpre-FEV1: odds ratio [OR] 1.57, 95% confidence interval [CI] 1.01-2.46; Δpost-FEV1: OR 2.13, 95% CI 1.25-3.66), treatment with long-acting ß2-agonists (LABAs) contributed to annual improvement of respiratory function (Δpre-FEV1: OR 2.05, 95% CI 1.23-3.16; Δpost-FEV1: OR 1.78, 95% CI 1.11-2.87), and poor compliance contributed to annual worsening of respiratory functions (Δpre-FEV1: OR 0.43, 95% CI 0.24-0.76; Δpost-FEV1: OR 0.39, 95% CI 0.22-0.70). In addition, duration of disease ≥10 years and severe treatment (steps 4-5) from the beginning contributed to decreasing Δreversibility (OR 0.55, 95% CI 0.34-0.87 and OR 0.50, 95% CI 0.29-0.83, respectively). CONCLUSIONS: Long-term treatments for asthma are expected to normalize respiratory dysfunction, which cannot be repaired in the short term. Treatment with LABAs and patient compliance may be the most important factors associated with annual improvement of respiratory functions.

Cytochrome P450 1A1 (CYP1A1) inhibitor alpha-naphthoflavone interferes with UDP-glucuronosyltransferase (UGT) activity in intact but not in permeabilized hepatic microsomes from 3-methylcholanthrene-treated rats: possible involvement of UGT-P450 interactions.

The effects of cytochrome P450 (P450, CYP) ligands and permeabilization of microsomes on 3-hydroxybenzo(a)pyrene [3-OH-B(a)P] glucuronidation mediated by rat hepatic microsomes were studied. While the UDP-glucuronosyltransferase (UGT) activity with non-permeabilized microsomes from 3-methylcholanthrene (MC)-treated rats was markedly reduced by alpha-naphthoflavone (NF), this inhibitor had hardly any effect when permeabilized microsomes were used in which the inhibitor was expected to have easy access to UGT. Kinetic analysis indicated that the inhibitory effect of alpha-NF is competitive. These results suggest that a UGT isoform(s) involved in 3-OH-B(a)P glucuronidation is interfered by a CYP1A inhibitor via a mechanism dependent on the intact nature of microsomal membranes in MC-treated rats. It is likely that P450 functions as a substrate transporter for some isoforms of UGT via possible interactions between UGT and P450.

Activation of microsomal epoxide hydrolase by interaction with cytochromes P450: kinetic analysis of the association and substrate-specific activation of epoxide hydrolase function.

The kinetics of the association between cytochrome P450 (P450) and microsomal epoxide hydrolase (mEH) was studied by means of resonant mirror based on the principle of surface plasmon resonance. The dissociation equilibrium constants (K(D)) for the affinity of P450 enzymes for mEH were estimated by resonant mirror using an optical biosensor cell covalently bound to rat mEH. Comparable K(D) values were obtained for CYP1A1 and 2B1, and these were greater by one order of magnitude than that for the CYP2C11. To clarify the influences of P450 enzymes on the catalytic activity of mEH, the hydrolyzing activity for styrene oxide and benzo(a)pyrene-7,8-oxide [B(a)P-oxide] was analyzed in the presence or absence of P450s. Styrene oxide hydrolysis was activated by all P450s including the CYP1A, 2B, 2C, and 3A subfamilies. In agreement with the association affinity determined by resonant mirror, CYP2C11 tends to have enhanced activity for styrene oxide hydrolysis. On the other hand, B(a)P-oxide hydrolysis was enhanced by only CYP2C11 while CYP1A1 and CYP2B1 had no effect. These results suggest that (1) many P450 enzymes associate nonspecifically with mEH, (2) the CYP2C11 plays a greater role in the association/activation of mEH and (3) the P450-mediated activation of mEH depends upon the substrate of mEH.