Medical treatment selection and outcomes for hospitalized patients with severe ulcerative colitis as defined by the Japanese criteria.

BACKGROUND: Hospitalization for ulcerative colitis (UC) is potentially life-threatening. Severe disease in the Japanese criteria which modifies the Truelove-Witts' criteria might encompass more fulminant cases than the definition for acute severe UC. However, few studies have investigated the predictive factors for clinical remission (CR) after medical treatments for severe hospitalized patients by Japanese criteria. METHODS: Medical treatment selection, CR rates, and factors contributing to CR on day 14 were assessed in severe patients by Japanese criteria. We also investigated whether the reduction rate in patient-reported outcome 2 (PRO2) on day 3 could predict short-term prognosis. RESULTS: Eighty-five severe hospitalized patients were selected. Corticosteroids, tacrolimus, and infliximab were mainly selected as first-line treatments (76/85; 89.4%). The CR rates on day 14 were 26.8%, 21.4%, and 33.3% in patients receiving corticosteroids, tacrolimus, and infliximab, respectively. Extensive disease (odds ratio [OR] 0.022; 95% confidence interval [CI] 0.002-0.198), higher PRO2 (OR 0.306; 95% CI 0.144-0.821), and higher reduction rate in PRO2 on day 3 (OR 1.047; 95% CI 1.019-1.075) were independent factors predicting CR on day 14. If the cutoff value for the reduction rate in PRO2 on day 3 was 18.3%, sensitivity was 0.714 and specificity was 0.731 to predict CR on day 14. A higher reduction rate in PRO2 on day 3 (OR 0.922; 95% CI 0.853-0.995) was a negative factor to predict surgery within 28 days. CONCLUSIONS: Tacrolimus and infliximab in addition to corticosteroids were used as first-line treatment in severe hospitalized patients. PRO2 on day 3 is a useful marker for switching to second-line therapy or colectomy.

Linked-color imaging with or without artificial intelligence for adenoma detection: a randomized trial.

BACKGROUND: Adenoma detection rate (ADR) is an important indicator of colonoscopy quality and colorectal cancer incidence. Both linked-color imaging (LCI) with artificial intelligence (LCA) and LCI alone increase adenoma detection during colonoscopy, although it remains unclear whether one modality is superior. This study compared ADR between LCA and LCI alone, including according to endoscopists' experience (experts and trainees) and polyp size. METHODS: Patients undergoing colonoscopy for positive fecal immunochemical tests, follow-up of colon polyps, and abdominal symptoms at a single institution were randomly assigned to the LCA or LCI group. ADR, adenoma per colonoscopy (APC), cecal intubation time, withdrawal time, number of adenomas per location, and adenoma size were compared. RESULTS: The LCA (n=400) and LCI (n=400) groups showed comparable cecal intubation and withdrawal times. The LCA group showed a significantly higher ADR (58.8% vs. 43.5%; P<0.001) and mean (95%CI) APC (1.31 [1.15 to 1.47] vs. 0.94 [0.80 to 1.07]; P<0.001), particularly in the ascending colon (0.30 [0.24 to 0.36] vs. 0.20 [0.15 to 0.25]; P=0.02). Total number of nonpolypoid-type adenomas was also significantly higher in the LCA group (0.15 [0.09 to 0.20] vs. 0.08 [0.05 to 0.10]; P=0.02). Small polyps (≤5, 6-9mm) were detected significantly more frequently in the LCA group (0.75 [0.64 to 0.86] vs. 0.48 [0.40 to 0.57], P<0.001 and 0.34 [0.26 to 0.41] vs. 0.24 [0.18 to 0.29], P=0.04, respectively). In both groups, ADR was not significantly different between experts and trainees. CONCLUSIONS: LCA was significantly superior to LCI alone in terms of ADR.

Nintedanib-associated enterocolitis with intractable diarrhea: a case report.

Revised idiopathic pulmonary fibrosis treatment guidelines were published in 2015, and nintedanib was conditionally recommended. Although diarrhea is reported to be a common major adverse event associated with nintedanib, there have been few reports on detailed endoscopic findings of nintedanib-associated enterocolitis. A 74-year-old woman was diagnosed with idiopathic pulmonary fibrosis 4 years ago in May. She was started on nintedanib (300 mg). Three months later, hepatic dysfunction was observed; therefore, the drug was temporarily discontinued and then resumed at a dose reduction of 200 mg. Five months later, the patient developed diarrhea, and the dose was reduced to 150 mg. However, no effect was noted; hence, colonoscopy was performed. Various inflammatory lesions, such as erythema and erosions, were observed continuously at the rectum, which resembled ulcerative colitis. No improvement was observed 2 months after follow-up colonoscopy, and nintedanib-related enterocolitis was suspected. The dose was further reduced to 100 mg. Since the endoscopic findings of nintedanib-associated enterocolitis are similar to those of ulcerative colitis, it is critical to consider patients with diarrhea who are taking nintedanib as having associated enterocolitis and attempt to reduce or discontinue the drug if diarrhea does not improve with antidiarrheal agents.

Real-world efficacy and safety of advanced therapies in hospitalized patients with ulcerative colitis.

BACKGROUND: This multicenter observational cohort study aimed to evaluate the utilization and short-term efficacy of advanced therapy (AT) in hospitalized patients with acute severe ulcerative colitis (ASUC). METHODS: In total, 221 patients with ASUC were enrolled between August 2020 and July 2021. The primary endpoint was clinical remission (CR, defined as a patient-reported outcome score < 2 with no blood in the stool) rate on Day 7 and 14 in hospitalized patients who received corticosteroids (CS) and AT. RESULTS: Among patients with ASUC, 120 and 101 patients received CS or any AT as first-line treatment, respectively. The CR rates on Day 7 and 14 were 22.5% and 35.0%, respectively, in hospitalized patients who received CS as first-line treatment. Most patients who used ATs had CS-dependent or frequent recurrences. Eight different ATs (apheresis, tacrolimus, infliximab, golimumab, tofacitinib, vedolizumab, ustekinumab, and cyclosporine) were used as first-line treatment in patients with ASUC, and the CR rates on Day 7 and 14 were 16.8% and 29.7%, respectively. Twenty-five patients received the second ATs after hospitalizations, and the CR rates on Day 7 and 14 were 0% and 12%, respectively. The CR rates on Day 14 were significantly higher in patients who changed to AT than in those whose dose of CS increased (34.0% vs 10.7%, p = 0.020) among patients who had already used CS before hospitalization. CONCLUSION: Most first-use ATs were effective for patients with ASUC, while second-use ATs might have had limited benefits in inducing CR. These findings may contribute to considerations for the management of hospitalized patients.

Duodenal gastric-type neoplasm with uncertain malignant potential in a lipoma.

The pathologic diagnosis of duodenal tumors is a developing field; however, its overview remains unclear. We describe a rare case of a duodenal gastric-type neoplasm in a 50-year-old woman. She visited her primary care doctor with complaints of upper abdominal pain, tarry stools, and shortness of breath on exertion. She was admitted owing to a stalked polyp with erosion and hemorrhage in the descending part of the duodenum. Endoscopic mucosal resection (EMR) was performed on the polyp. Histologically, the resected polyp was a lipomatous lesion in the submucosal layer, composed of mature adipose tissues. Scattered irregular lobules of Brunner's gland-like structures with well-preserved construction but mildly enlarged nuclei and occasional conspicuous nucleoli of the constituent cells were observed. The resection margin was negative. EMR findings of the duodenal polyp showed a gastric epithelial tumor within a lipoma, a rare histological type that has not been reported previously. This tumor may be classified as a "neoplasm with uncertain malignant potential" in a lipoma, an intermediate category between adenoma and invasive adenocarcinoma. There is no consensus on treatment, and careful follow-up is recommended. This is the first report of a duodenal gastric-type neoplasm with uncertain malignant potential in a lipoma.

Combined effects of granulocyte and monocyte adsorption apheresis and corticosteroids on ulcerative colitis.

Several new treatments for ulcerative colitis have been developed recently. The depletion of leukocytes by granulocyte and monocyte adsorption apheresis (GMA) was developed and adapted for patients with ulcerative colitis with rare adverse events. We investigated whether treatment with GMA and prednisolone (GMA + PSL) is more effective than PSL alone for patients with moderate to severe ulcerative colitis. Forty-seven patients with moderate to severe ulcerative colitis were retrospectively analyzed. Among the 47 patients, 27 received PSL, while 20 received GMA + PSL. The clinical activity of ulcerative colitis was evaluated using the Lichtiger clinical activity index (CAI) and serum levels of C-reactive protein. Mayo endoscopic score (MES) was used to examine endoscopic activity. The clinical remission rate was significantly higher in the GMA + PSL group than in the PSL group (65% vs 29.6%, p = 0.0206). The mucosal healing rate was also significantly higher in the GMA + PSL group than in the PSL group (60% vs 26%, p = 0.0343). The combination of GMA and steroids may be more effective than steroids alone for inducing clinical remission and mucosal healing in patients with moderate to severe ulcerative colitis.

Positive zinc intake and a Japanese diet rich in n-3 fatty acids induces clinical remission in patients with mild active ulcerative colitis: a randomized interventional pilot study.

Zinc intake has reduced hospitalizations in patients with ulcerative colitis (UC), highlighting the need to maintain blood zinc levels. This prospective study investigated whether the promotion of zinc intake and a Japanese diet (high in n-3 fatty acids) could induce clinical remission in patients with mild active UC. Patients with mild active UC were randomly assigned to either (1) continue an unrestricted diet or (2) receive nutritional guidance promoting zinc intake and a Japanese diet. The primary endpoint was clinical remission at 24 weeks. Secondary endpoints were the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) scores, Clinical Activity Index (CAI), Geboes Histopathology Score (GHS), and biomarkers, including zinc levels, measured at 12 and 24 weeks. Nutritional assessments were performed using the Food Frequency Questionnaire. The CAI, UCEIS, and GHS scores were significantly lower in the intervention group than in the control group, with a significantly higher proportion of patients achieving clinical remission. Furthermore, the intervention group exhibited weight gain and significantly increased blood zinc levels. The combination of promoting dietary zinc intake and a Japanese diet rich in n-3 fatty acids can induce clinical remission in patients with mild active UC.

AdvanCE, a capsule endoscope delivery device, is effective in investigating a waterfall stomach.

AdvanCE is a useful device in patients who cannot swallow capsule endoscopes, or when these remain in the patient's stomach without passing into the duodenum. A net or snare may be used to guide the capsule endoscope into the duodenum when the capsule endoscope becomes stuck in the stomach, but it may be difficult to guide the capsule into the duodenum in some cases, particularly in those of waterfall stomach. In such cases, AdvanCE is found to be an effective guidance tool.

Transgenerational impacts of oral probiotic administration in pregnant mice on offspring gut immune cells and colitis susceptibility.

BACKGROUND AND AIM: The study of the impact of environmental factors during pregnancy on fetal development has so far been focused primarily on those negatively affecting human health; however, little is known about the effects of probiotic treatment during pregnancy on inflammatory bowel diseases (IBD). In this study, we investigated whether oral administration of heat-killed probiotics isolated from fermented foods decreased the vulnerability of offspring to IBD. METHODS: Probiotics were administered to the pregnant mice until the birth of pups, after which the parent mice were maintained with autoclaved water. Partial pups were evaluated for dextran sodium sulfate-induced colitis. The influence of CD11c+ CD103+ dendritic cells (DCs) and regulatory T cells (Tregs) in mesenteric lymph nodes of parent mice and their pups was analyzed. RESULTS: Oral administration of heat-killed probiotics to pregnant dams significantly decreased inflammation induced by dextran sodium sulfate in pups. Probiotic treatment increased the number of CD103+ DCs, and the expression of ß8-integrin in CD103+ DCs and Tregs in mesenteric lymph nodes, not only in dams themselves but also in their offspring. CONCLUSIONS: Oral administration of probiotics during gestation induced transgenerational immunomodulatory effects on the gut-associated immune system and resilience to experimental colitis in the offspring. Our results suggest that consumption of fermented foods during pregnancy can be effective in preventing inflammatory diseases such as IBD beyond generation.

Endo-wing versus transparent hood-assisted colonoscopy for colorectal adenoma detection: A randomized controlled trial.

BACKGROUND AND AIM: This study aimed to compare the mean number of adenomas in patients undergoing Endo-wing-assisted colonoscopy (EAC) and transparent hood-assisted colonoscopy (TAC). METHODS: Patients undergoing colonoscopy for positive fecal immunochemical tests, colon polyp surveillance, and evaluation of abdominal symptoms at a single institution were randomly assigned to the EAC or TAC group. The mean number of adenomas per patient, adenoma detection rate, cecal intubation time, withdrawal time, mean number of adenomas per location, and adenoma size were compared. RESULTS: Overall, 800 patients were enrolled. The EAC and TAC groups comprised 372 and 393 patients, respectively. The groups did not significantly differ with respect to cecal intubation and withdrawal times. The mean number of adenomas per patient was significantly higher in the EAC group (1.13 vs 0.90, P = 0.04), particularly in the sigmoid colon (0.54 [201/372] vs 0.38 [149/393], P = 0.04). The adenoma detection rates were 48.1% and 45.0% in the EAC and TAC groups, respectively, albeit without significant difference between the two groups (P = 0.393). The total number of sessile-type adenomas (0.73 [270/372] vs 0.47 [183/393], P < 0.0001) and small polyps (≤ 5 mm) (0.53 [198/372] vs 0.41 [159/393], P = 0.016) was significantly higher in the EAC group. CONCLUSION: Endo-wing-assisted colonoscopy is significantly superior to TAC in terms of the mean number of adenomas per patient.

Novel probiotic yeast from Miso promotes regulatory dendritic cell IL-10 production and attenuates DSS-induced colitis in mice.

BACKGROUND: Yeasts are a type of fungi thought to have probiotic functions. In this study, we isolated a novel probiotic yeast (Zygosaccharomyces sapae strain I-6) from Miso (a traditional Japanese fermented food). We examined its effects on phenotypic changes in intestinal dendritic cells (DCs), and evaluated its anti-inflammatory effects in dextran sulfate sodium (DSS)-induced colitis. METHODS: A single colony was selected from homogenized Miso, based on its ability to produce interleukin (IL)-10 in CD11c+ bone marrow DCs (BMDCs) in vitro. The anti-inflammatory effects of strain I-6 on CD11c+ BMDCs and CD11c+ CD103+ DCs were analyzed in mouse mesenteric lymph nodes in vitro and in a DSS mouse model. RESULTS: The IL-10 concentrations in the co-culture BMDC supernatants treated with I-6 were dramatically higher than in those treated with Saccharomyces cerevisiae (Sc). IL-10 production is mediated by both TLR2 and Dectin-1. ß-Glucan extracted from I-6 also induced higher levels of IL-10 production in BMDCs than ß-glucan from Sc. The number of mesenteric lymph node CD11c+ CD103+ DCs was significantly increased by I-6 administration, compared with Sc administration. Strain I-6 showed strong anti-inflammatory effects on DSS-induced colitis compared to Sc. Moreover, the adoptive transfer of I-6-treated BMDCs showed anti-inflammatory effects on DSS-induced colitis in mice without oral administration of I-6 cells. CONCLUSIONS: Strain I-6 induced phenotypic changes in intestinal CD11c+ DCs characterized by high IL-10 production and exerted strong anti-inflammatory effects on DSS-induced colitis. Traditional Japanese fermented foods may be a valuable source of probiotic yeasts for effective IBD therapy and treatment.

Linked color imaging versus white light imaging colonoscopy for colorectal adenoma detection: A randomized controlled trial.

BACKGROUND AND AIM: The adenoma detection rate is an important indicator of colonoscopy quality and colorectal cancer incidence. We compared the adenoma detection rates between white light imaging (WLI) and linked color imaging (LCI) colonoscopy. METHODS: Patients undergoing colonoscopy for positive fecal immunochemical tests, follow-up of colon polyps, and abdominal symptoms at three institutions were randomly assigned to the LCI or WLI groups. Mean adenoma number per patient (including based on endoscopists' experience), adenoma detection rate, cecal intubation time, withdrawal time, mean adenoma number per location, and adenoma size were compared. RESULTS: The LCI and WLI groups comprised 494 and 501 patients, respectively. No significant differences in the cecal intubation rate (LCI vs WLI: 99.5% vs 99.4%), cecal intubation time, and withdrawal time were noted between groups. The mean adenoma number per patient was significantly higher in the LCI group than in the WLI group (1.07 vs 0.88, P = 0.04), particularly in the descending [0.12 (58/494) vs 0.07 (35/501), P = 0.01] and sigmoid colon [0.41 (201/494) vs 0.30 (149/501), P ≤ 0.001]. However, the adenoma detection rate was 47.1% in the LCI group and 46.9% in the WLI group, with no significant difference (P = 0.93). The total number of sessile-type adenomas was significantly higher in the LCI group than in the WLI group (346/494 vs 278/501, P = 0.04). As for polyp size, small polyps (≤ 5 mm) were detected at a significantly higher rate in the LCI group (271/494 vs 336/501, P = 0.04). CONCLUSION: Linked color imaging is significantly superior to WLI in terms of mean adenoma number per patient.

Rituximab-induced Ileocolitis in a Patient with Gastric MALToma: A Case Report and Literature Review.

Rituximab (RTX) is effective for treating cancer, but reports of RTX-associated enterocolitis are limited. We herein report the case of a 65-year-old man who developed RTX-induced ileocolitis. He was diagnosed with gastric mucosa-associated lymphoid tissue lymphoma (MALToma) and treated with RTX. He complained of bloody diarrhea after RTX. Mucosal inflammation on colonoscopy indicated RTX-induced ileocolitis. He was treated with corticosteroids, and his symptoms improved. We reviewed the RTX-associated gastrointestinal adverse events and classified the features into ulcerative colitis, Crohn's disease, microscopic colitis, and ileocolitis. To our knowledge, this is the first case of a Japanese patient who developed RTX-induced ileocolitis.

Detection of early stage gastric cancers in screening laser endoscopy using linked color imaging for patients with atrophic gastritis.

BACKGROUND AND AIMS: Laser endoscopy involves blue laser imaging in bright mode (BLI-bright). Linked color imaging (LCI) is superior to white light imaging (WLI) for detecting gastric cancers. This study aimed to detect gastric cancers on screening endoscopy using not only WLI but also BLI-bright and LCI in patients with atrophic gastritis. PATIENTS AND METHODS: A total of 500 patients with atrophic gastritis undergoing screening esophagogastroduodenoscopy were included. The gastric lumen was observed in the WLI mode, followed by the LCI and BLI-bright modes. When gastric neoplasms were suspected, the mode was changed to WLI, and we sprayed indigo carmine. Finally, biopsy specimens were taken for those lesions and pathological diagnosis was made. We compared the size, morphology, and color of gastric neoplasms found by the first WLI mode and those detected by only the LCI mode or BLI-bright mode. RESULTS: We detected 16 gastric neoplasms (3.2%), of which 13 were early gastric cancers (EGCs) and three were gastric adenomas. Ten EGCs and two gastric adenomas (75%) were detected by the first WLI mode; three EGCs and one gastric adenoma (25%) were missed by the first WLI mode and were detected by the LCI mode or BLI-bright mode. All were less than 1 cm in diameter and were reddish. Mean diameter of the lesions was significantly less for LCI-detected or BLI-bright-detected lesions than for WLI-detected lesions (7.8 vs 21.2 mm). CONCLUSIONS: Laser endoscopy is useful for detecting EGCs by LCI for patients with atrophic gastritis.

Chronic Enteropathy Associated with SLCO2A1 with Pachydermoperiostosis.

A 49-year-old man complained of chronic palpitation and shortness of breath, which had recently become exacerbated. A blood examination indicated severe refractory anemia and hypoproteinemia. Physical examinations revealed anemia, a systolic murmur, and spoon nails. Multiple nonspecific ileal ulcers were observed. A pathological examination indicated a small granuloma with CD68-positive histiocytes. He had a deeply wrinkled forehead, chiseled face, and clubbed fingers. Radiography revealed periostosis of the fingers and long bones in the limb. He was diagnosed with pachydermoperiostosis. SLCO2A1 demonstrated a c.1807C>T homo-mutation. He was also diagnosed with SLCO2A1-associated chronic enteropathy and thus was treated with 5-aminosalicylic acid, which temporarily improved the ileal ulcers, anemia, and hypoalbuminemia.

Randomized control trial of adenoma detection rate in Endocuff-assisted colonoscopy versus transparent hood-assisted colonoscopy.

BACKGROUND AND AIM: Transparent hood-assisted colonoscopy (TAC) has been reported to improve the cecal insertion rate and adenoma detection rate (ADR). An endoscopic cap (Endocuff) with two rows of soft wings was recently developed to improve ADR, by flattening the mucosal folds during withdrawal. This randomized prospective control study aimed to compare ADR between Endocuff-assisted colonoscopy (EAC) and TAC. METHODS: A total of 513 patients undergoing colon adenoma screening were included. EAC was performed in 256 patients and TAC in 260 patients. Cecal intubation rate, cecal intubation time, ADR, and mean adenoma number per patient (MAP) were investigated in both groups (clinical trial registration: UMIN000016278). RESULTS: We excluded six patients in the EAC group and two patients in the TAC group because of colonic stenosis due to colonic adenocarcinomas. Finally, 250 patients (151 men/99 women, median age 62.1 years) were assigned to EAC and 258 patients (165 men/93 women, median age 64.3 years) were assigned to TAC. There were no significant differences in cecal intubation rate, intubation time, withdrawal time, and cleanliness score between groups. The ADR was 50.8% in EAC and 52.7% in TAC, with no significant difference (P = 0.666). The MAP was 1.35 in EAC and 1.20 in TAC, with no significant difference (P = 0.126). However, The MAP of diminutive adenomas (< 5 mm) tended to be higher in EAC than in TAC (P = 0.077). There was no significant difference in MAP in each segment between groups. CONCLUSIONS: Endocuff-assisted colonoscopy might be equivalent to TAC in cecal intubation time, ADR, and MAP.