Remission Factors for Ustekinumab Treatment of Ulcerative Colitis: A Multicenter Retrospective Study of Real-World Data in Japan.

Ustekinumab (UST) is an anti-IL-12/23p40 monoclonal antibody used to treat inflammatory bowel disease. The aim of this retrospective, multicenter study was to investigate the effectiveness of UST administration in achieving remission in patients with ulcerative colitis (UC) and to determine patient characteristics that influence its effectiveness. Of 88 UC patients who received UST from March 2020 to August 2023, 47 with traceable data and for whom 56 weeks had elapsed since the start of treatment received UST to induce remission. The remission rates at 8 weeks were 66% overall, 73.7% for Bio Naïve (never used biologics/JAK inhibitors), and 60.7% for Bio Failure (used biologics/JAK inhibitors) groups. Remission rates at 56 weeks were 70.2% overall, 73.7% for Bio Naïve, and 67.9% for Bio Failure groups. Ustekinumab showed good mid-to-long-term results in the induction of remission of UC in both Bio Naïve and Bio Failure groups. The group showing remission at 8 weeks had a significantly higher non-relapse or continuation rate (proportion of patients with no worsened symptoms necessitating surgery/drug change) at 56 weeks. Predictive factors for achieving remission after UST in UC were female gender, low body mass index, and low lymphocyte-to-monocyte ratio. Thus, UST is effective for moderate-to-severe UC.

Recent steroid use and the relapse risk in ulcerative colitis patients with endoscopic healing.

BACKGROUND: Endoscopic healing (EH) is a therapeutic target in ulcerative colitis (UC). However, even patients who have achieved EH relapse frequently. AIMS: To investigate the association between recent steroid use and relapse risk in UC patients with EH. METHODS: This multi-centre cohort study included 1212 UC patients with confirmed EH (Mayo endoscopic subscore ≤1). We excluded patients with current systemic steroid use or history of advanced therapy. We divided patients into a recent steroid group (last systemic steroid use within 1 year; n = 59) and a non-recent or steroid-naïve group (n = 1153). We followed the patients for 2 years to evaluate relapse, defined as induction of systemic steroids or advanced therapy. We used logistic regression to estimate the odds ratio (OR) of relapse. RESULTS: Relapse occurred in 28.8% of the recent steroid group and 5.6% of the non-recent/steroid-naïve group (multi-variable-adjusted OR 5.53 [95% CI 2.85-10.7]). The risk of relapse decreased with time since the last steroid use: 28.8% for less than 1 year after steroid therapy, 22.9% for 1 year, 16.0% for 2 years and 7.9% beyond 3 years, approaching 4.0% in steroid-naïve patients. (ptrend <0.001). CONCLUSIONS: Even for patients with UC who achieved EH, the risk of relapse remains high following recent steroid therapy. Physicians need to consider the duration since last steroid use to stratify the relapse risk in UC patients with EH.

The Impact of Partial Splenic Embolization on Portal Hypertensive Gastropathy in Cirrhotic Patients with Portal Hypertension.

This study investigated the impact of partial splenic embolization (PSE) on portal hypertensive gastropathy (PHG). We retrospectively analyzed endoscopic findings and the portal venous system of 31 cirrhotic patients with PHG. The improved group was defined as the amelioration of PHG findings using the McCormack classification. Child-Pugh scores of the improved group (18 of 31 patients) were significantly lower compared with those of the non-improved group (p = 0.018). The changes in the diameters of the portal trunk and those of the spleno-portal junction and spleen hilum in the splenic vein of the improved group were significantly larger than those of the non-improved group (p = 0.007, p = 0.025, and p = 0.003, respectively). The changes in the diameters of the portal vein and splenic hilum of the splenic vein showed significant correlations with Child-Pugh score (r = 0.386, p = 0.039; r = 0.510, p = 0.004). In a multivariate analysis of baseline factors related to the improved group, Child-Pugh grade A was significantly associated with the improvement of PHG (odds ratio 6.875, p = 0.033). PSE could be useful for PHG, especially in patients with Child-Pugh grade A, at least in the short term.

Endobronchial Watanabe Spigot Placement for Hepatic Abscess and Bronchobiliary Fistula Following Radiofrequency Ablation for Hepatocellular Carcinoma.

A bronchobiliary fistula (BBF) is an uncommon but severe complication after radiofrequency ablation (RFA). However, the definitive salvage methods are controversial. We herein report a patient with hepatocellular carcinoma with hepatic abscess and BBF following RFA. We also review previous reports of BBF after RFA. The patient was a man in his 70s who underwent RFA for recurrent hepatocellular carcinoma in the subphrenic area. Despite percutaneous transhepatic abscess drainage, bilioptysis persisted. Finally, the BBF was occluded with an endobronchial Watanabe spigot under fiber-optic bronchoscopy. Placing an endobronchial Watanabe spigot should be considered as a salvage therapy for refractory BBF following RFA.

Impact of Cabozantinib Exposure on Proteinuria and Muscle Toxicity in Patients with Unresectable Hepatocellular Carcinoma.

This prospective study investigated the impact of cabozantinib exposure on proteinuria and muscle toxicity, in a cohort of 14 Japanese patients with unresectable hepatocellular carcinoma (uHCC). We measured the trough concentration of cabozantinib (Ctrough) weekly for 6 weeks after starting treatment. Although the initial dose was less than 60 mg in most cases, dose interruption occurred in 79%, primarily because of proteinuria and/or malaise. The median and coefficient of variation of maximum Ctrough at 7−42 d were 929.0 ng/mL and 59.2%, respectively. The urinary protein-to-creatinine ratio (UPCR), serum creatine kinase, and serum aldolase values were all significantly elevated following treatment. Moreover, maximum changes in serum creatine kinase and aldolase were significantly associated with maximum Ctrough (r = 0.736, p < 0.01; r = 0.798, p < 0.001; respectively). Receiver operating characteristic (ROC) curve analysis showed that changes in serum creatine kinase ≥70.5 U/L and aldolase ≥6.1 U/L from baseline relatively accurately predicted inclusion in the high-maximum Ctrough (≥929.0 ng/mL) group, with an area under the ROC of 0.929 and 0.833, respectively. Measurement of serum creatine kinase and aldolase may increase the clinical usefulness of cabozantinib treatment for uHCC and help alleviate difficulties with dose adjustments.

Early Clinical Remission Is a Predictor of Long-Term Remission with the Use of Vedolizumab for Ulcerative Colitis.

Vedolizumab (VDZ) is an α4ß7 integrin-antibody used to manage refractory ulcerative colitis (UC). This retrospective multicenter study aimed to identify predictors of efficacy or the time points when evaluation of VDZ therapy for UC would be most useful. We compiled data on 87 patients with moderate to severe active UC that was treated with VDZ. Overall clinical remission (CR) rates at 6 weeks and 52 weeks after VDZ administration were 44.4% (bio-naïve 44.2%, bio-failure 44.8%) and 52.8% (bio-naïve 53.5%, bio-failure 51.7%) respectively. Also, 83.3% (bio-naïve 81.3%, bio-failure 85.7%) of patients achieved mucosal healing at week 52. Among patients with a CR at week 52, 73.3% had a CR at week 6. In contrast, of patients who discontinued VDZ, 82.4% had not reached a CR at week 6. Our study demonstrated that VDZ was effective in a large percentage of UC patients, with a high mucosal healing rate even after prior biological exposures. This suggests that VDZ can be a treatment option even in bio-failure cases. Additionally, it was considered that early CR can predict long-term remission and that week 6 can be a helpful evaluation point for treatment decisions when using VDZ for UC.

Plasmablastic Lymphoma of the Small Intestine in an HIV- and EBV-negative Patient.

Plasmablastic lymphoma (PBL) is a rare aggressive B-cell lymphoproliferative disorder that is strongly associated with immunodeficiency, most often with human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) infection, and that mainly occurs in the oral cavity. Although some clinical features can lead to a diagnosis, PBL in an extraoral site is difficult to suspect clinically in a patient who is HIV negative. The small intestine as a site of PBL has also been described very rarely. We herein present a rare case of PBL of the small intestine in an 85-year-old HIV- and EBV-negative male.

Usefulness of flexible spectral imaging color enhancement for the detection and diagnosis of small intestinal lesions found by capsule endoscopy.

OBJECTIVE: Capsule endoscopy (CE) is an established technique for the detection and diagnosis of obscure gastrointestinal bleeding (OGIB). Flexible spectral imaging color enhancement (FICE) is a software feature of RAPID 6.5. This study assessed the value of FICE for accurate identification of red lesions during CE. METHODS: We randomly selected 10 patients who underwent CE for OGIB at Juntendo University. The CE images were read by five endoscopists. Small bowel videos, which were recorded by regular CE devices (PillCam SB2, Given Imaging), were evaluated on RAPID 6.5. We standardized the reading condition to a dual view, at a speed of 20 frames/s in manual mode. This interpreted FICE-CE images obtained at settings 1-3. Both conventional and FICE images were read at random. We defined a conventional image as standard and investigated the potential of FICE in detecting small intestinal lesions by the Steel-Dwass test. RESULTS: We considered that conventional images represented baseline (100). On this basis, detection rates for FICE images were as follows: FICE1 = 266.4 ± 33.1 (p < 0.0001); FICE2 = 255.4 ± 25.6 (p < 0.0001); and FICE3 = 117.0 ± 12.3 (p = 0.9447). Detection rates using FICE1 and FICE2 images were significantly higher than conventional CE images. FICE1 and FICE2 were more useful in detecting erosions than conventional CE (p < 0.0001) and FICE3 (p < 0.0001). CONCLUSIONS: FICE-CE has a high level of visibility by transparentizing bile or enhancing the color difference associated with reddish mucosa. We found that FICE-CE images were useful in the diagnosing of small intestinal lesions.

Abnormality of autophagic function and cathepsin expression in the liver from patients with non-alcoholic fatty liver disease.

AIM: Recent evidences indicate that hepatic steatosis suppresses autophagic proteolysis. The present study evaluated the correlation between autophagic function and cathepsin expression in the liver from patients with non-alcoholic fatty liver disease (NAFLD). METHODS: Liver biopsy specimens were obtained from patients with chronic liver diseases (chronic hepatitis C [CHC; n = 20], chronic hepatitis B [CHB; n = 16], primary biliary cirrhosis [PBC; n = 23], NAFLD [n = 22] and control [n = 14]). The number of autophagic vesicles in hepatocytes was counted by using transmission electron microscopy. Expression of cathepsin B, D, L and p62 in the liver section was analyzed by immunohistochemical staining. The histological severity of NAFLD is assessed by NAFLD activity score (NAS). RESULTS: The number of autophagic vesicles in hepatocytes was significantly increased in both CHC and NAFLD groups, but not CHB and PBC, more than control. Although hepatocytes with aggregation of p62 were observed in less than 15% of CHC, p62 aggregation was detected in approximately 65% of NAFLD. Cathepsin B, D and L expression was significantly suppressed in the liver from NAFLD patients. Suppression of cathepsin B, D and L expression was not observed in CHB, CHC and PBC. In NAFLD patients, p62 aggregation was correlated with serum alanine aminotransferase value and inflammatory activity by NAS. CONCLUSION: These results indicate that a decrease in hepatic cathepsin expression in NAFLD is associated with autophagic dysfunction. Hepatic inflammation correlates with autophagic dysfunction in NAFLD. These findings indicate that the suppression of autophagic proteolysis by hepatic steatosis is involved in the pathogenesis of NAFLD.

Multiple carcinoid tumors of the small intestine preoperatively diagnosed by double-balloon endoscopy.

BACKGROUND: Multiple carcinoid tumors of the small intestine are rare and are very difficult to detect preoperatively. CASE REPORT: A 75-year-old woman in whom the bleeding focus could not be found by upper and lower endoscopy and abdominal CT was admitted for evaluation of anemia. We examined the patient with total double-balloon endoscopy (DBE) and located multiple submucosal tumors. The multiple carcinoid tumors were resected successfully under laparoscopy. CONCLUSIONS: We report a case of a successful laparoscopic operation for multiple carcinoid tumors in the small intestine without intraoperative endoscopy. Total digestive tract observation using DBE is very useful for laparoscopic operation for multiple tumors in the small intestine.

The relationship between physical activity level and completion rate of small bowel examination in patients undergoing capsule endoscopy.

OBJECTIVE: Capsule endoscopy (CE) allows direct examination of the small bowel in a safe, noninvasive and well-tolerated manner. Nonetheless, experience indicates failure to reach the cecum in 20-30% of patients within the 8 hour battery life. Attempts to improve the completion rate (CR) as defined by reaching the cecum have been unsuccessful. This study was to investigate the relationship between patients' physical activity and CR. METHODS: Between January 2009 and January 2010, 76 patients (44 men, 32 women; median age 64.5 yr) underwent CE for the diagnosis of small intestinal disorders. Indications for CE were obscure gastrointestinal bleeding/anemia (62 cases), others (14 cases). Patients were divided into an outpatient group (n=23), mild bed rest group (n=35) and strict bed rest group (n=18). RESULTS: For all patients, the average gastric transit time was 65.5 minutes, small bowel transit time was 301.4 minutes and the CR was 86.8%. However, the CR was 100% (23/23) in the outpatient group, an 85.7% (30/35) in the mild bed rest group, and 72.2% (13/18) in the strict bed rest group. The CR increased with physical activity of patients by Cochran-Armitage Trend Test (p=0.009). In multivariate logistic regression analyses, low physical activity was a significant risk factor for failure to reach the cecum during CE examination; adjusted OR: 3.39, 95% CI: 1.01-11.42 (p=0.048). CONCLUSION: Our observations suggested that increasing physical activity would increase the likelihood of a complete bowel examination by CE. Further, for CE, inconvenient bowel preparations like the use of polyethylene glycol may be avoided.

Reactive lymphoid hyperplasia of the liver associated with primary biliary cirrhosis.

BACKGROUND: Although reactive lymphoid hyperplasia (RLH) can be found in various organs, including the gastrointestinal tract, orbit, lung, and skin, its occurrence in the liver is rare. CASE REPORT: We report the case of a 47-year-old RLH woman who was identified with RLH of the liver during clinical follow- up of primary biliary cirrhosis. The mass, found incidentally during a medical examination, appeared on ultrasonogram as a hypoechoic mass in the 7th segment of the liver. Further analyses using composed tomography, magnetic resonance imaging, and angiography suggested malignancy, and we performed lateral segmentectomy of the liver. Histologically, the tumor was composed of lymphoid follicles with germinal centers that expressed kappa and lambda light-chain B-cell markers at equal frequency, and no IgH gene rearrangements were detected in Southern blots. Based on these results, we identified the lesion as RLH. CONCLUSIONS: We suggest that this diagnosis be taken into consideration in other cases involving a space-occupying liver mass associated with autoimmune disease.