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Background and Aims: Familial mediterranean fever (FMF), an autoinflammatory disease, is characterized by periodic fever and serositis. An MEFV gene mutation has been identified as the cause of FMF. Recently, patients with MEFV gene mutations and chronic gastrointestinal mucosal inflammation mimicking inflammatory bowel disease (IBD) have been reported. In this retrospective study, we analyzed the clinical characteristics of patients with IBD unclassified (IBDU) with MEFV gene mutations. Methods: MEFV gene analysis was performed on 8 patients with IBDU among 710 patients with IBD who had been treated at Kyorin University Hospital from April 2016 to December 2018. Clinical manifestations, endoscopic findings, and serological markers were also analyzed. Results: The average of the 8 patients with IBDU (3 men, 5 women) was 32.7 ± 6.4 years (range 26–76 years). Their symptoms comprised diarrhea (n = 8, 100%), hematochezia (n = 3, 37.5%), abdominal pain (n = 3, 37.5%), high fever (n = 2, 16.5%), and other periodic symptoms (n = 2, 16.5%). MEFV gene mutation was confirmed in 4/8 of these patients. Colonoscopy showed various mucosal lesions, rectal sparing, right side dominant colitis, pseudopolyposis, and granular protrusions. Colchicine was administered to 5 of the 8 patients (4 with and 1 without MEFV mutation) who were resistant to conventional treatment for ulcerative colitis. Clinical and endoscopic improvement was observed in all of 5 patients treated with colchicine. Conclusions: Some patients diagnosed as having IBDU have enterocolitis related to MEFV gene mutation and respond to colchicine therapy.

Background Fecal biomarkers are considered to be useful surrogate markers for endoscopic activity. Given the mechanisms of fecal biomarkers, we hypothesized that the extent of ulcerative colitis (UC; pancolitis, left-sided colitis, and proctitis) could affect the usefulness of fecal biomarkers for assessing endoscopic and clinical disease activity; however, few studies have evaluated the utility of fecal biomarkers in the disease extent of UC. Methods Fecal calprotectin, a fecal immunochemical test for hemoglobin, and fecal lactoferrin were used as fecal biomarkers. UC patients, who underwent colonoscopy within 30 days of the fecal biomarker test, participated in this observational study. Clinical and endoscopic disease activity was assessed using the Lichtiger Index and Mayo endoscopic subscore (MES), respectively. Results A total of 162 colonoscopies were performed on 133 UC patients. A correlation analysis between each biomarker and the MES for each disease-extent subgroup showed a decreased correlation in the proctitis compared with the other groups. With the exception of proctitis, it was possible to distinguish between MES 0 and MES ≥ 1 with high area-under-the-curve values for fecal calprotectin and fecal lactoferrin. The fecal immunochemical test for hemoglobin was superior at discriminating MES 0 for proctitis. Conclusions For the practical application of fecal biomarkers for UC patients, it is necessary to consider disease extent before use. In particular, patients with proctitis exhibit a low correlation between stool biomarkers and endoscopic findings. The usefulness of these biomarkers for endoscopic remission is reduced, except for the fecal immunochemical test for hemoglobin.

Background and Aim Vedolizumab is a humanized monoclonal antibody that selectively inhibits the migration of gut‐homing memory T cells into the intestinal submucosa by antagonizing the interaction of α4β7 integrin with MAdCAM‐1. Vedolizumab is employed for ulcerative colitis with moderate to severe activity; however, predictors of its clinical efficacy have not been established in real‐world clinical practice. We investigated the clinical characteristics predicting vedolizumab efficacy. Methods This was a single‐center, retrospective, observational study that enrolled patients with ulcerative colitis at Kyorin University Hospital. Fifty‐two consecutive patients who started vedolizumab induction therapy and were tracked for minimum 14 weeks between August 2018 and February 2021 were included. Clinical and endoscopic disease activities were scored at baseline and at weeks 2, 6, and 14 with the Lichtiger index and at baseline and week 24 with the Mayo endoscopic subscore, respectively. Clinical remission, clinical response, and endoscopic remission were defined as Lichtiger index of ≤3, Lichtiger index of ≤10 with a reduction of minimum 3 points from baseline, and Mayo endoscopic subscore of ≤1, respectively. Results In these cases, clinical response/remission rates at weeks 2, 6, and 14 were 26.9%/15.3%, 50.0%/46.3%, and 57.6%/50.0%, respectively. The endoscopic remission rate at week 24 was 60%. The clinical response at week 6 was significantly associated with endoscopic remission at week 24 after starting vedolizumab. Conclusions In vedolizumab treatment for ulcerative colitis, the clinical response at week 6 can be a predictor for endoscopic remission at week 24. Clinical response of vedolizumab at week 6 predicted endoscopic remission at week 24 in ulcerative colitis with moderate to severe activity.

A 19-year-old man with a history of Peutz-Jeghers syndrome (PJS) and two previous partial small bowel resections because of intussusception presented with lower abdominal pain. Computed tomography (CT) showed concentric multilayer and cord-like structures in the transverse colon. Colo-colonic intussusception was suspected and he was hospitalized. After two therapeutic enemas were unsuccessful, a colonoscopy was performed. The intussusception was reduced and a 40-mm transverse colon polyp with a thick stalk was resected. After the procedure, his abdominal pain was relieved and he was discharged on the sixth hospital day. This case and several previous reports suggest that PJS polyps with tumor diameter exceeding 30 mm and location in the transverse or sigmoid colon can cause intussusception. Endoscopic treatment should be considered for these lesions.

We retrospectively evaluated the impact of therapeutic modifications of atezolizumab (Atezo) plus bevacizumab (Bev) therapy (Atezo/Bev), including the interruption or discontinuation of both Atezo and Bev, and the reduction or discontinuation of Bev, on the outcome of patients with unresectable hepatocellular carcinoma (uHCC) (median observation period: 9.40 months). One hundred uHCC from five hospitals were included. Therapeutic modifications without discontinuation of both Atezo and Bev (n = 46) were associated with favorable overall survival (median not reached; hazard ratio (HR): 0.23) and time to progression (median: 10.00 months; HR: 0.23) with no therapeutic modification defined as the reference. In contrast, the discontinuation of both Atezo and Bev without other therapeutic modifications (n = 20) was associated with unfavorable overall survival (median: 9.63 months; HR: 2.72) and time to progression (median: 2.53 months; HR: 2.78). Patients with modified albumin–bilirubin grade 2b liver function (n = 43) or immune-related adverse events (irAEs) (n = 31) discontinued both Atezo and Bev without other therapeutic modifications more frequently (30.2% and 35.5%, respectively) than those with modified albumin–bilirubin grade 1 (10.2%) and without irAEs (13.0%). Patients with objective response (n = 48) experienced irAEs more frequently (n = 21) than those without (n = 10) (p = 0.027). Avoiding the discontinuation of both Atezo and Bev without other therapeutic modifications may be the optimal management of uHCC.

Although anemia is one of the signs of colorectal cancer, the relationships between histological findings and hematological findings other than hemoglobin level have not been adequately investigated. We investigated the relationship between hematological findings, serum iron, and histological findings in 358 patients (207 men and 157 women) with colorectal cancer. Their mean (+/-SD) ages were 64.3 +/- 12.4 and 63.8 +/- 13.3 years. A hemoglobin level of less than 10 g/dl was the criterion for anemia, and 20.8% of the men and 25.8% of the women met this criterion. Univariate analysis showed that carcinoma of the cecum, ascending colon, and transverse colon; large-size carcinoma, invasion beyond the proper muscle layer; positive lymph node metastasis: and clinical stage (Dukes' B, C, and D) were factors associated with high incidence of anemia. Histological type did not affect the hematological findings. Multivariate analysis showed that age, tumor site, and tumor size were significant factors related to anemia. Depth of invasion, the presence or absence of lymph node metastasis, and Dukes' classification were not significant factors. In the presence of these factors, mean corpuscular volume and mean corpuscular hemoglobin concentration values were low, and red blood cells were microcytic and hypochromic. The incidence of a low serum iron level was about twice the frequency of a hemoglobin level of less than 10 g/dl. The results of the multivariate analysis showed that none of the factors were significantly related to iron deficiency.

Background. Intraoperative radiation therapy (IORT) has been performed to prevent local recurrence of rectal cancer only when positive margins are suspected. To further reduce local recurrence, we attempted to develop a new IORT irradiation method in which electron beam irradiation is administered as uniformly as possible to the intrapelvic dissection surfaces. Methods. Low anterior resection and abdominoperineal resection were performed in one male and one female cadaver. Electron beam irradiation was administered by four different methods, and absorbed doses were measured at 15 sites within the pelvis. We also attempted to measure absorbed doses at nine sites within the pelvis in 14 patients treated with IORT. Results. The cadaver study revealed low absorbed doses in the lateral walls of the pelvis when a single irradiation was delivered from the anterior. When the lateral walls of the pelvis were irradiated twice, once each time on the right and left, the absorbed doses were low in the central pelvis and presacrum. Relatively high absorbed doses were achieved in all of these areas by a technique that combined these two methods. Adequate absorbed doses were not achieved by a single irradiation administered from the perineum. Conclusion. This study suggests that electron beam irradiation administered three times to the dissected surfaces in the pelvis after resection of rectal cancer (i.e., to the central pelvis and presacrum from the anterior, and to the left and right lateral walls of the pelvis) is the most suitable method for achieving adequate absorbed doses.[PUBLICATION ABSTRACT]

We evaluated a new dose-intensive schedule for oral UFT (tegafur and uracil in a molar ratio of 1:4) administered for 5 consecutive days followed by 2 drug-free days (weekly-5-method), in comparison with conventional daily administration (weekly-7 method), in Yoshida-sarcoma-bearing rats. The single dose of 20 mg/kg of UFT for rats corresponds to the human single dose when converted to dose per unit of body-surface area. The drug was administered 3 times a day for the weekly-5 method and twice a day for the weekly-7 method. A 7-day period was considered 1 course. The total doses per course were almost the same in both methods. Antitumor efficacy and survival effect were evaluated after 3 courses. Body weight changes and food consumption were also measured as indices of toxicity. The plasma pharmacokinetics were analyzed by simulating dosage patterns. Significant tumor-growth inhibition was seen with both the weekly-5 and the weekly-7 methods as compared to the control. Moreover, the weekly-5 method showed higher tumor-growth inhibition and a better survival effect than the weekly-7 method. These results appear to be related to the duration of plasma concentrations of 5-FU being maintained above a certain concentration for a longer time with the weekly-5 method. Food consumption with the weekly-5 method recovered to the control level after the drug-free period, and body weight gain was also favorable. The results of this study suggest that the dose-intensive method of administering UFT orally for the weekly-5 method is a useful dosage schedule. Thus, this dosage schedule is recommended for use in clinical trials.[PUBLICATION ABSTRACT]