Risk Factors for Adverse Events in Patients with Chronic Constipation Following Lubiprostone Administration.

INTRODUCTION: Lubiprostone is an effective treatment of chronic constipation (CC). However, as with other stimulant or osmotic laxatives, adverse events (AEs) can make it difficult to continue treatment. This article investigates AE risk factors associated with lubiprostone. METHODS: We retrospectively analyzed all 1,338 Japanese patients with CC treated at our hospital from October 2013 to July 2017. All patients were diagnosed with constipation as defined by the Roma III criteria. Enrolled patients received lubiprostone orally (24 or 48 µg daily), after which we investigated the incidence of AEs. The causative factors for diarrhea and nausea, the most common AEs, were examined by the backward logistic regression model. RESULTS: Two hundred eight (15.5%) experienced at least 1 AE. No serious AEs were associated with the study drug. The AEs reported by >1% of patients overall were diarrhea (6.1%) and nausea (4.2%). We performed a multivariate logistic regression using a backward variable selection method to investigate AE risk factors. Factors associated with higher incidence of diarrhea were patient age of 65 years or more (odds ratio: [95% confidence interval]; p value) (2.09: [1.05-4.16]; 0.035). Factors associated with greater likelihood of nausea included female gender (1.99: [1.10-3.61]; 0.023), and the chief complaint was a patient complaining of abdominal pain and fullness (2.07: [1.01-4.22]; 0.046). CONCLUSIONS: Understanding AE risk factors can help avoid unnecessary AEs and promote more effective treatment.

Propensity score matching analysis: incidence and risk factors for "stardust" gastric mucosa, a novel gastric finding potentially induced by vonoprazan.

BACKGROUND: Vonoprazan, a potassium-competitive acid blocker, is used for acid-related diseases. Occasionally, small white protrusions called "stardust" gastric mucosa have been detected in the stomachs of some patients taking vonoprazan. AIMS: To determine the incidence of, and risk factors for, stardust gastric mucosa potentially induced by vonoprazan METHODS: In this study, we enrolled 19 503 patients who underwent endoscopy at our hospital between 2016 and 2019. Using propensity score matching, we retrospectively compared patients who received and did not receive vonoprazan. The two groups were matched for age, sex, history of proton pump inhibitor use, and atrophic gastritis. RESULTS: After 1:1 propensity score matching, each group comprised 2516 patients. Stardust gastric mucosa was detected significantly more often in the stomachs of patients receiving vonoprazan than those who had not received vonoprazan (4.9% vs 0.2%, P < 0.001). Its location was 70.7% in the upper third of the stomach, 29.3% in the middle third and none in the lower third. Histologically, this lesion had a mucus pool within a dilated duct surrounded by flattened glandular epithelium. The cumulative incidence rate of stardust gastric mucosa at 1, 2 and 3 years was 4.6%, 16.5% and 26.2%, respectively. The factors independently associated with the presence of stardust gastric mucosa were >205 days of vonoprazan oral intake (odds ratio [OR]: 6.99, 95% confidence interval [CI]: 4.60-10.88) and female sex (OR: 1.75, 95% CI: 1.20-2.58). CONCLUSIONS: Stardust gastric mucosa appeared more frequently in the stomachs of patients taking vonoprazan.

Real-World Comparison of Elobixibat and Lubiprostone Treatment in Patients with Chronic Constipation: A Propensity Score-Matched Analysis.

INTRODUCTION: Elobixibat is a new laxative, but its efficacy and adverse events (AEs) are insufficiently examined compared with those of other laxatives. Hence, by propensity score (PS) matching, we compared the effects and AEs between elobixibat and lubiprostone. METHODS: We retrospectively analyzed 1,887 Japanese patients with chronic constipation (CC) treated at our hospital between October 2013 and April 2020. Enrolled patients were divided into three treatment groups, namely, elobixibat (10 mg daily) (E10 group, n = 293), lubiprostone (24 µg daily) (L24 group, n = 772), and lubiprostone (48 µg daily) (L48 group, n = 822), as their first treatment. We then investigated the changes on the weekly average number of spontaneous bowel movements, stool consistency scores (SCSs), and AEs starting from the baseline until the end of the 2-week treatment. To adjust for patients' background, we performed one-to-one nearest neighbor matching without replacement between elobixibat- and lubiprostone-treated patients according to the individual estimated PSs. RESULTS: After treatment, for SCSs, both the L24 and L48 groups significantly improved compared with the E10 group (p < 0.05), but their stools were soft (Bristol Stool Form Scale: 4.8). Notably, the E10 group had less frequent AEs than the L24 group (26 [9.0%] vs. 43 [14.8%], p = 0.03). Particularly, nausea was significantly less in the E10 group than that in the L48 group (2 [0.7%] vs. 7 [2.4%], p = 0.01). CONCLUSION: Elobixibat is a beneficial drug for patients with mildly symptomatic CC and is safe to use, given its few AEs.

A rare case of pyogenic granuloma of the jejunum causing gastrointestinal bleeding.

Pyogenic granulomas (PG) are lobular capillary hemangiomas mostly found in the mucous membranes of the skin and oral cavity, and rarely occur in the gastrointestinal tract. Here we describe a case of an 84-year-old patient with alcoholic cirrhosis who presented with persistent melena and progressive anemia. Endoscopy showed esophageal varices and he underwent endoscopic variceal ligation (EVL) with transient resolution of anemia. However, due to worsening anemia, he underwent capsule endoscopy that revealed a bleeding tumor in the small intestine. We performed double-balloon endoscopy and found a 7-mm polyp with a white coat located in the jejunum and resected it at a later date. Histological characteristics led to the diagnosis of PG, and the patient's melena and anemia subsequently improved.

Cellulose nanofiber dispersion as a new submucosal injection material for endoscopic treatment: preliminary experimental study.

Background and aims Although various solutions have been tested for submucosal injections during endoscopic treatment, the ideal solution has not been established. We investigated the suitability of a cellulose nanofiber (CNF) dispersion with high viscosity and thixotropy as a potential submucosal injection material for endoscopic treatment. Methods We evaluated the catheter injectability and mucosa-elevating capacity of CNF dispersion compared with sodium hyaluronate (SH) solution, which has been reported to be a promising submucosal injection solution. The catheter injectability of CNF dispersion was examined under conditions equivalent to those used clinically in endoscopic treatment. The mucosa-elevating capacity of CNF dispersion was examined in porcine stomachs. Results There was no significant difference between the catheter injectability of 0.4 % CNF dispersion and 0.4 % SH solutions; however, 0.4 % CNF dispersion maintained significantly higher and longer elevation of the submucosal layer than 0.4 % SH solution. A clear separation of the mucosal layer from the underlying muscle layer was achieved by injecting 0.4 % CNF dispersion. Conclusion This preliminary study suggests that CNF dispersion could be an ideal submucosal injection material for endoscopic treatment because of its unique high thixotropy index.

Impact on prognosis of rebiopsy in advanced non-small cell lung cancer patients after epidermal growth factor receptor-tyrosine kinase inhibitor treatment: a systematic review.

BACKGROUND: Osimertinib, the third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has become the standard treatment in cases where rebiopsy reveals T790M mutation after the first-line EGFR-TKI treatment. However, the prognosis of patients after rebiopsy, the most important outcome for cancer patients, has not been described sufficiently. This systematic review aimed to clarify whether rebiopsy contributes to improved prognosis in the first- or second-generation EGFR-TKI refractory patients. METHODS: Using free word and control terms related to "non-small cell lung cancer" and "rebiopsy," we searched studies from Medical Literature Analysis and Retrieval System Online via PubMed, Embase, Cochrane Central Register of Controlled Trials, and World Health Organization International Clinical Trials Registry Platform. We included cohort studies and case reports written in English and judged whether each study answers our research questions. RESULTS: Of the 144 studies included, only one reported the prognosis of patients with/without rebiopsy showing that in EGFR-TKI refractory non-small cell lung cancer patients, the post-progression survival (PPS) was significantly longer in patients who received rebiopsy and treatment based on a resistant mechanism (median PPS 24.2 months) than those who received rebiopsy and salvage regimen (median PPS 15.2 months, p = 0.002) and who did not receive rebiopsy (median PPS 9.7 months, p < 0.001). Most of the other studies reported the detection rate of T790M mutation or rebiopsy procedure. CONCLUSIONS: Only a few previous studies have investigated the effectiveness of rebiopsy. Hence, further study is needed to determine the prognosis or adverse events of rebiopsy.

[A case report of suspected Stauffer syndrome presenting with fever, extensive inflammation, and abnormal liver function tests].

A man was referred to our hospital because of malaise and abnormal liver function tests. He had had a kidney removed for early renal cell carcinoma. We performed ultrasonography, CT scan, and liver biopsy, all of which were normal. However, FDG-PET revealed abnormal, diffuse uptake in the bone. A bone biopsy showed abnormal clear cells resembling renal cell carcinoma. Because there was no other primary origin, this histopathological finding led to the diagnosis of bone metastasis of renal cell carcinoma, and the abnormal liver function test was thus inferred to be due to Stauffer syndrome.

[CT enterography with polyethylene glycol electrolyte solution for diagnosis of Crohn's disease].

This study aimed to assess the diagnostic usefulness of CT enterography (CTE) in Crohn's disease in Japanese patients. A total of 32 cases with bowel symptoms underwent CT enterography with polyethylene glycol electrolyte solution as oral contrast medium, among which 18 were clinically diagnosed as Crohn's disease and 14 were not: ulcerative colitis 1, Beçhet disease 1, simple ulcer 1, inflammatory bowel disease without definite diagnosis 5 and bowel symptoms of unknown origin 6. The incidence of bowel wall thickening, mural hyperenhancement, "the comb sign", mesenteric lymph nodes swelling, and stenosis were significantly higher in Crohn's disease than in other disease. Moreover, uneven bowel wall thickening and unilateral mural hyperenhancement on CTE were characteristic features of Crohn's disease, which our original quantitative evaluation with imaging analysis could support. Consequently, CTE is useful in Japanese patients with Crohn's disease.

[A case of jejunal adenocarcinoma with serum DUPAN-2 elevation].

A 50-year-old woman was admitted to our hospital because of abdominal pain and vomiting. Ileus with ulcerated jejunal tumor was diagnosed and biopsy revealed adenocarcinoma. Because her serum level of DUPAN-2 was high, she was examined by PET scan, which revealed that she had a left ovarian mass in addition to the jejunal tumor. Surgical resection was performed: both tumors were adenocarcinoma, but the ovarian tumor was considered to be metastatic clinically and histologically. Immunostaining for DUPAN-2 was positive in the both tumors. The serum level of DUPAN-2 returned to normal after the surgery, and has been within normal limits for about 3 years without any additional therapy. This case shows a possible relation between small bowel adenocarcinoma and DUPAN-2.

Organ-specific profiles of genetic changes in cancers caused by activation-induced cytidine deaminase expression.

Various molecular changes characterizing organ-specific carcinogenesis have been identified in human tumors; however, the molecular mechanisms of the genomic changes specific for each cancer are not well defined. A transgenic (Tg) mouse model with constitutive expression of the nucleotide-editing enzyme, activation-induced cytidine deaminase (AID), develops tumors in various organs as a result of the mutagenic activities of AID. This phenotypic character of AID Tg mice allowed us to analyze the organ-specific genetic changes in tumor-related genes commonly triggered by AID-mediated mutagenesis. Among the 80 AID Tg mice analyzed, 11 mice developed hepatocellular carcinomas, and 7 developed lung cancers. In addition, 1 developed the gastric cancer and 3 developed gastric adenomas. Organ-specific preferences for nucleotide changes were observed in some of the tumor-related genes in each epithelial tissue of the AID Tg mice. Of note, the c-myc and K-ras genes were the preferential targets of the mutagenic activity of AID in lung and stomach cancers, respectively, whereas mutations in the p53 and beta-catenin genes were commonly observed in all 3 organs. Quantitative RT-PCR analyses revealed that alpha-fetoprotein, insulin-like growth factor-2 and cyclin D1 genes were specifically upregulated in HCC, whereas upregulation of the matrix metalloproteinase-7 gene was more marked in lung cancer. Our findings suggest that AID, a DNA mutator that plays a critical role linking inflammation to human cancers, might be involved in the generation of organ-specific genetic diversity in oncogenic pathways during cancer development.

Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium.

Infection with Helicobacter pylori (H. pylori) is a risk factor for the development of gastric cancer. Here we show that infection of gastric epithelial cells with 'cag' pathogenicity island (cagPAI)-positive H. pylori induced aberrant expression of activation-induced cytidine deaminase (AID), a member of the cytidine-deaminase family that acts as a DNA- and RNA-editing enzyme, via the IkappaB kinase-dependent nuclear factor-kappaB activation pathway. H. pylori-mediated upregulation of AID resulted in the accumulation of nucleotide alterations in the TP53 tumor suppressor gene in gastric cells in vitro. Our findings provide evidence that aberrant AID expression caused by H. pylori infection might be a mechanism of mutation accumulation in the gastric mucosa during H. pylori-associated gastric carcinogenesis.