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Background Nonalcoholic fatty liver disease, which is highly associated with obesity, includes nonalcoholic steatohepatitis. Lipopolysaccharides from the intestine would induce inflammation in the liver in nonalcoholic fatty liver disease. This study aimed to examine the role of the bilio-pancreatic limb in the effect of duodenal–jejunal bypass on nonalcoholic steatohepatitis, with respect to the gut–liver axis, using a rat model. Methods Nonalcoholic steatohepatitis model rats were randomly assigned into 3 groups as follows: 1 sham group and 2 duodenal–jejunal bypass groups. The 2 duodenal–jejunal bypass groups were defined according to the bilio-pancreatic limb length: 30 cm (30-DJB group) and 0 cm (0-DJB group). Pathology findings and blood biochemistry, inflammatory cytokine and lipopolysaccharides receptor mRNA in the liver and common channel, and lipopolysaccharide-binding protein level in the portal vein were assessed. Results The reduction in plasma alanine aminotransferase and nonalcoholic fatty liver disease activity score in the 30-DJB group was not observed in the 0-DJB group, similar to the sham group. In the liver tissue, mRNA of inflammatory cytokines and lipopolysaccharide receptors, the area occupied by CD68-positive macrophages, and the number of CD3-positive T-lymphocytes on immunostaining were lower in the 30-DJB group; however, these findings were not observed in the 0-DJB group, and lipopolysaccharide-binding protein levels in the portal vein and mRNA expressions of inflammation-related genes in the common channel showed similar tendencies. Conclusion The bilio-pancreatic limb plays an important role in the beneficial effect of duodenal–jejunal bypass for nonalcoholic steatohepatitis. The bilio-pancreatic limb may suppress lipopolysaccharides-related cascades in the liver by reducing intestinal inflammation.

We report a case of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) after total proctocolectomy followed with ileal pouch-anal anastomosis (TPC-IPAA) for ulcerative colitis (UC). The patient was a 46-year-old woman. She was diagnosed with UC of pancolitis in 2000. High grade dysplasia was detected in the transverse colon after a surveillance colonoscopy in 2021. She underwent laparoscopy-assisted TPC-IPAA. On the sixth postoperative day, she had a decreased level of consciousness that worsened on the following day. Her laboratory data showed a serum sodium level of 108 mEq/L and the plasma osmolality was 234 mOsm/kg. We did not find any other abnormalities in the laboratory examination that could cause hyponatremia. Computed tomography scan showed no central nervous system disturbances such as a pituitary tumor, antidiuretic hormone-producing tumors, or pulmonary diseases. The patient was diagnosed with Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) caused by surgical invasion. We started to administer 3% sodium chloride slowly to improve the hyponatremia. Her serum sodium level became normal and stable. Although it is rare for SIADH to be caused by abdominal surgery, if hyponatremia is observed after surgery, the possibility of postoperative SIADH should be considered.

Background: Oral antibiotics, such as ciprofloxacin (CFX), are widely used for the treatment of acute and chronic pouchitis. Most bacterial mutations that confer quinolone resistance are at Ser-83 and Asp-87 in the gyrA gene and Ser-80 and Glu-84 in the parC gene. Methods: We obtained 51 stool samples from 43 patients who were diagnosed with ulcerative colitis and underwent ileal pouch-anal anastomosis. Patients were divided into 2 groups: 13 patients with CFX treatment of pouchitis and 30 patients without pouchitis. After extraction of fecal DNA, the amount of Escherichia coli 16S rRNA, gyrA, and parC gene DNA were measured using real-time polymerase chain reaction (PCR). Possible mutations at gyrA 83 and 87 and at parC 80 and 84 were investigated by PCR cloning and sequencing, and mutation rates were quantified by rapid PCR-restriction fragment length polymorphism. Results: Samples from both CFX-treated and -untreated patients had comparable levels of gyrA and parC gene DNA. Nucleic acid and amino acid mutations were identified at gyrA 83 and 87, and at parC 80 and 84. We successfully quantified mutation rates at gyrA 83 and 87, and at parC 84, all of which were significantly higher in samples from CFX-treated patients (70, 84, and 38%) than from CFX-untreated patients (13, 11, and 5%). Conclusion: E. coli in patient pouches may have mutations in their gyrA and parC genes that produce CFX resistance. Mutation rates of these genes were significantly higher in samples from CFX-treated patients. This study contributes to understanding the decrease and loss of CFX effectiveness against pouchitis.

Background Antimesenteric cutback end‐to‐end isoperistaltic anastomosis (Sasaki‐Watanabe anastomosis; Sasaki‐W anastomosis), which was developed in our department, is a novel hand‐sewn anastomotic technique for Crohn's disease intended to prevent anastomotic stenosis and preserve the peripheral circulation. Aim The aim of the present study is to present the surgical technique of Sasaki‐W anastomosis and to assess the safety and the early results of the surgical anastomotic recurrence of Sasaki‐W anastomosis. Patients and Methods The present study was a single‐center retrospective cohort study. As an early‐period group, 13 patients with Crohn's disease, who were mainly selected from cases considered to be at high risk of recurrence, underwent 15 Sasaki‐W anastomoses from August 2009 to January 2012. As a late‐period group, 36 patients with Crohn's disease, who were selected regardless of risk factors, underwent 37 Sasaki‐W anastomoses from September 2016 to March 2020. The medical data including patient characteristics, surgical records, postoperative details, and surgical recurrences were assessed. Results There were no intraoperative complications. With a median follow‐up of 107 mo, surgical recurrence occurred in one patient at 106 mo after surgery in the early‐period group. The cumulative surgical recurrence‐free rate in the early‐period group was 100% at 5 y and 86% at 10 y after surgery. No patients required reoperation in the late‐period group. Conclusion Sasaki‐W anastomosis is safe and feasible. Although long‐term study is needed, this anastomotic technique can be a reasonable operative option for Crohn's disease., Antimesenteric cutback end‐to‐end isoperistaltic anastomosis (Sasaki‐Watanabe anastomosis; Sasaki‐W anastomosis) is a novel hand‐sewn anastomotic technique for Crohn’s disease intended to prevent anastomotic stenosis and preserve the peripheral circulation. Here we show the surgical technique and early results of surgical anastomotic recurrence.

After colectomy for ulcerative colitis (UC), very severe and sometimes lethal enteritis can develop. However, the clinical features remain uncertain because of the low incidence, diversity of symptoms, and undefined diagnostic criteria. The aim of this study was to define postoperative ulcerative colitis-related severe enteritis (UCRSE) and to investigate its clinical features. A retrospective multicenter study was performed as a survey of major medical facilities utilizing surgical supplies for inflammatory bowel disease in Japan from 2001 to 2014. UCRSE was defined as a case with massive intestinal bleeding, intestinal perforation, high-output stoma, and/or a requirement for medications, such as steroids and biologics. Patients with gastroduodenal lesions or pouchitis alone were excluded. The incidence, symptoms, involvement of bacteria, cytomegalovirus reactivation, treatment, and prognosis were examined for patients with UCRSE after colectomy. Forty-two (0.8%) out of 5284 cases met the criteria for UCRSE. Major symptoms were massive intestinal bleeding (76.2%), which required a median of 3850 (560–18900) mL blood transfusion; high-output stoma (38.1%) with excretion of fluid of 5000 (2000–7800) mL/day; and intestinal perforation (7.1%). Hypovolemic shock (35.7%) and/or disseminated intravascular coagulation (31.0%) developed as serious complications. Tests for cytomegalovirus reactivation were positive in 26.2% of cases. The presence of pathogenic bacteria was confirmed in only 5 cases. Corticosteroids or infliximabs were effective in half of the patients. Thirteen cases (31.0%) were treated surgically and 22 cases (56.4%) required maintenance therapy. The mortality rate was 11.9%. UCRSE is a rare but serious complication after colectomy and is sometimes life-threatening.

Duodenal–jejunal bypass (DJB) shows great effects on weight loss and diabetes improvement. Previously, we reported that the bilio-pancreatic (BP) limb plays an important role in glycemic improvement and in serum bile acid (BA) level increase as reported by Miyachi et al. (Surgery 159(5):1360–71, 2016). This study aimed to investigate the mechanism of BA elevation after DJB and the relationship between these effects and BP-limb length. Otsuka Long-Evans Tokushima Fatty rats with diabetes were randomly assigned into four groups: one sham group and three DJB groups. Three DJB groups were defined according to the BP-limb length: 0 cm, 15 cm, and 30 cm. The lengths of the alimentary limb and common channel were set equally in each DJB groups. Body weight, glucose tolerance, and BA levels in the liver, bile juice, portal vein, and intestinal contents were assessed postoperatively. Changes in enterohepatic circulation of BAs were assessed using labeled BA. BA elevation after DJB was higher with longer BP-limb. In the 30-cm group, the serum total BA level and BA levels in the portal vein, liver, and bile juice were greater than those in other groups. The enterohepatic circulation was shortened in the 15-cm and 30-cm groups. Shortening of the “enterohepatic circulation” by early reabsorption of BAs in the BP-limb, not by the early influx of bile juice into the ileum, was the main cause of BA elevation after DJB. Thus, glycemic improvement and elevation of BA concentration after DJB depend on the BP-limb length.

The Inflammatory Bowel Disease Questionnaire (IBDQ) is the most widely used disease-specific health-related quality of life questionnaire for patients with inflammatory bowel disease. However, little has been reported about the validation of IBDQ for patients with ulcerative colitis after surgery. The aim of this study was to assess the validity and reliability of the Japanese version of IBDQ in patients with ulcerative colitis after total proctocolectomy and ileal pouch anal anastomosis (IPAA). The validity and reliability of the Japanese IBDQ were assessed in patients with ulcerative colitis who had received IPAA in our hospital. We mailed them the Japanese IBDQ and a supplemental questionnaire on bowel function, which was developed at our institution. Internal consistency, discriminative validity, and factor validity were assessed. Of the 121 patients to whom we sent the questionnaires, 64 patients (53%) participated in this study. The Japanese IBDQ scores correlated well with Cronbach’s alpha value (0.800 to 0.923) and daily life satisfaction score (Pearson’s r, 0.492 to 0.700). The total IBDQ score and two subscale scores of the IBDQ, “bowel symptoms” and “systemic symptoms,” correlated well with daily bowel-movement frequency (Pearson’s r, −0.256 to −0.329). Factor analysis revealed a four-factor structure, and all correlations among factors were moderately positive (0.337 to 0.465). Although the factor distribution was not clearly divided into the four IBDQ subscales, these four factors showed a marked tendency to represent the IBDQ subscales independently. The Japanese IBDQ is a valid and reliable instrument for the assessment of Japanese patients with ulcerative colitis after IPAA.

We previously investigated fecal flora of the pouch after total proctocolectomy using terminal restriction fragment polymorphism analysis. Although the results of the cluster analysis demonstrated clearly that bacterial populations, including an unidentified bacteria generating a 213-bp PCR fragment, moved toward a colon-like community in the pouch, it did not track changes in the individual species of fecal bacteria.The aim of the present study was to estimate genome copy number of ten bacterial species, clusters, groups, or subgroups (including the bacteria generating 213-bp fragment in the previous study) in feces samples from pouches at various times following ileostomy closure.A total of 117 stool samples were collected from patients with ulcerative colitis after surgery as well as healthy volunteers. We used real-time polymerase chain reaction of the 16S rRNA gene to estimate genome copy numbers for the nine bacterial populations and the bacteria generating 213-bp fragment after identification by DNA sequencing.We demonstrated a time-dependent increase in the number of anaerobic and colon-predominant bacteria (such as Clostridium coccoides, C. leptum, Bacteroides fragilis and Atopobium) present in proctocolectomy patients after stoma closure. In contrast, numbers of ileum-predominant bacterial species (such as Lactobacillus and Enterococcus faecalis) declined.Our data confirm previous findings that fecal flora in the pouch after total proctocolectomy changes significantly, and further demonstrate that the number and diversity of ileal bacteria decreases while a more colon-like community develops. The present data are essential for the future analysis of pathological conditions in the ileal pouch.

Background Colonic transformation is defined by phenotypic alterations in the ileum after total proctocolectomy. Changes in microbiota of the ileal pouch and the roles of these microbes in colonic transformation, however, have not been addressed. Methods A total of 151 stool samples were collected from patients with ulcerative colitis patients and an ileostomy, those with an ileal pouch, and healthy control volunteers. Bacterial DNA was extracted from stool, and the diversity of complex bacteria was assessed by terminal restriction fragment length polymorphism (T-RFLP) analysis, a novel DNA-based approach that enables us to investigate the presence of nonculturable bacteria. To determine whether ileal pouch bacterial communities shift to a more colon-like distribution, the relative abundance of terminal restriction fragments that could be classified as “colonic,” “ileal,” or “common” was investigated. Results Cluster analysis demonstrated that most of the ileostomy samples were categorized into Cluster I or II and that less than 10% of ileostomy samples were classified into Cluster IV. In contrast, more than 90% of control samples were grouped in Cluster IV. In further analyses, the median lifetimes of pouches in Clusters I, II, III, and IV were significantly different at 11, 56, 265, and 310 days, respectively. T-RFLP patterns of the ileal pouch were characterized by a time-dependent decrease in “ileal” and increase in a part of “colonic” fragments, which represented mainly nonculturable bacteria such as the Clostridium coccoides group. Conclusion T-RFLP analysis demonstrated that a time-dependent shift to a “colon-like” bacterial community, including nonculturable bacteria, in the ileal pouch after total proctocolectomy.

Our aim was to determine whether the glucagon provocative test could be used in place of secretin test in patients with gastrinoma. Three patients with gastrinoma underwent the following examinations: (1) preoperative intravenous glucagon test to enable a definitive diagnosis, (2) intra-arterial glucagon injection test to localize the tumor, and (3) intraoperative and postoperative intravenous glucagon test to confirm the completeness of the resection. Serum gastrin levels increased in response to intravenous glucagon in all three patients preoperatively. Computed tomography scans revealed a tumor in the lesser omentum, pancreatic head, and the pancreatic uncinate in cases 1, 2, and 3, respectively. Intra-arterial glucagon test revealed that the feeding artery for the tumor was the left gastric artery in case 1 and the superior mesenteric artery in case 3. Resection of the remnant stomach with tumor, pancreaticoduodenectomy with portal vein resection, and enucleation of the tumor were performed in cases 1, 2, and 3, respectively. Serum gastrin levels did not increase in response to intravenous glucagon intraoperatively and postoperatively in cases 1 and 3. Although intravenous glucagon caused a slight increase in serum gastrin in case 2, no recurrent tumors were evident. These results indicate that the glucagon provocative test is a suitable alternative to testing with secretin, which is not commercially available in Japan.

The aim of the present study was to determine if calcium polycarbophil ameliorates diarrhea after ileal J-pouch anal anastomosis for ulcerative colitis. Twenty-one randomized patients were given either bifidobacterium (3 g/day) plus calcium polycarbophil (3 g/day), in the polycarbophil group (11 patients), or bifidobacterium (3 g/day), in the control group (10 patients), p.o. for 6 months. Anal manometry was performed and bowel function (stool frequency, stool consistency, and nighttime soiling) was assessed via a questionnaire before and 1, 3, and 6 months after drug administration. Eight patients were deemed eligible in each group; five patients were excluded from the study, including two patients whose stool consistency was too firm and who experienced difficulty in defecating attributed to polycarbophil. Anal manometry and stool consistency did not change with time and did not differ between the polycarbophil and the control groups. Stool frequency decreased with time in both groups and did not differ between the groups. Nighttime soiling improved with time in the polycarbophil group but did not change in the control subjects. These results suggest that polycarbophil might be able to improve nighttime soiling without obviously affecting stool frequency and consistency after ileal J-pouch anal anastomosis for ulcerative colitis.

The aim was to study determinants of postoperative bowel function after restorative proctocolectomy for ulcerative colitis. Medical records of patients who underwent proctocolectomy with ileal J pouch-anal anastomosis (IPAA) in two- or three-stage operations and whose status of defecation was known via a questionnaire were retrospectively reviewed. Bowel function, including stool frequency, stool consistency, and degree of nighttime soiling, was correlated with age at the time of surgery, time after ileostomy closure, mean resting anal pressure, longitudinal length of ileal J pouch, and duration of fecal diversion by using univariate and multivariate analyses. Stool frequency decreased significantly with time after ileostomy closure in both univariate and multivariate analyses. Stool frequency tended to be less in patients having a long J pouch, but the correlation was not significant (P = 0.071) in univariate analysis. Nighttime soiling ameliorated with time after ileostomy closure in multivariate, but not univariate, analysis. Deterioration of nighttime soiling was seen in patients whose duration for fecal diversion was long, both in univariate (P = 0.068) and multivariate (P = 0.052) analyses. Stool consistency was related to none of the five factors investigated. These results indicate that as the time after surgery increases, stool frequency decreases and nighttime soiling ameliorates. Delaying ileostomy closure because of anticipated postoperative incontinence does not significantly alter postoperative continence.

Purpose The aim of this study was to investigate the association between 5-fluorouracil (5-FU)-related adverse events (AEs) in Japanese patients with gastrointestinal cancer treated with 5-FU and the patient genotypes DPYD, MTHFR, OPRT, and TYMS. Methods Sequence analyses of 33 gene polymorphisms in four genes were performed using genomic DNA extracted from peripheral blood mononuclear cells of 103 patients with gastric (n = 34) or colorectal (n = 69) cancer. The 5-FU-related AEs of 157 regimens in these 103 patients were evaluated based on the medical records of patients in each of three groups: the intravenous administration group (i.v. group, n = 51), oral administration group (p.o. group, n = 106), and all-regimens group (both i.v. and p.o. group, n = 157). The associations between the incidence of AEs and each genotype were statistically analyzed. Results Six single-nucleotide polymorphisms (SNPs) were identified (three SNPs in DPYD: c.496A>G, c.1905+1G>A, and c.2303C>A; two SNPs in MTHFR: c.677C>T and c.1298A>C; and one SNP in OPRT: c.638G>C). Among them, the patients in the all-regimens group carrying any one of three DPYD SNPs showed statistically significant associations with the incidence of AEs of any type and fatigue. Furthermore, the MTHFR SNP c.1298A>C was significantly associated with the incidence of neutropenia. A similar trend was observed in the p.o. group, but not in the i.v. group. Conclusion These findings suggest that the DPYD SNPs c.496A>G, c.1905+1G>A, and c.2303C>A and the MTHFR SNP c.1298A>C may be predictive factors for the occurrence of severe 5-FU-related AEs. Citation Format: Masahide Toshima, Shinobu Ohnuma, Michiiro Tanaka, Koh Miura, Wataru Fujibuchi, Taiki Kajiwara, Toshihiro Komura, Hiroaki Musha, Sho Haneda, Katsuyoshi Kudoh, Atsushi Kohyama, Takeshi Naitoh, Michiaki Unno. Single nucleotide polymorphisms of DPYD and MTHFR predict adverse events associated with 5-fluorouracil in patients with gastrointestinal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2832. doi:10.1158/1538-7445.AM2014-2832