Search

Background and Aim: Colitis-associated intestinal cancer (CAC) can develop in patients with inflammatory bowel disease; however, the malignant grade of CAC may differ from that of sporadic colorectal cancer (CRC). Therefore, we compared histological findings distinct from cancer stage between CAC and sporadic CRC to evaluate the features of CAC., Methods: We reviewed the clinical and histological data collected from a nationwide database in Japan between 1983 and 2020. Patient characteristics were compared to distinguish ulcerative colitis (UC), Crohn's disease (CD), and sporadic CRC. Comparisons were performed by using all collected data and propensity score-matched data., Results: A total of 1077 patients with UC-CAC, 297 with CD-CAC, and 136 927 with sporadic CRC were included. Although the prevalence of well or moderately differentiated adenocarcinoma (Tub1 and Tub2) decreased according to tumor progression for all diseases (P < 0.01), the prevalence of other histological findings, including signet ring cell carcinoma, mucinous carcinoma, poorly differentiated adenocarcinoma, or squamous cell carcinoma, was significantly higher in CAC than in sporadic CRC. Based on propensity score-matched data for 982 patients with UC and 268 with CD, the prevalence of histological findings other than Tub1 and Tub2 was also significantly higher in those with CAC. At pT4, mucinous carcinoma occurred at a significantly higher rate in patients with CD (45/86 [52.3%]) than in those with sporadic CRC (13/88 [14.8%]) (P < 0.01)., Conclusion: CAC, including early-stage CAC, has a higher malignant grade than sporadic CRC, and this difference increases in significance with tumor progression., (© 2024 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Purpose: To determine the methylation level of the miR-124 promoter in non-neoplastic rectal mucosa of patients with pediatric-onset ulcerative colitis (UC) to predict UC-associated colorectal cancer (UC-CRC)., Methods: Between 2005 and 2017, non-neoplastic rectal tissue specimens were collected from 86 patients with UC, including 13 patients with UC-CRC; cancer tissues were obtained from the latter group. The methylation status of the miR-124 promoter was quantified using bisulfite pyrosequencing and compared between pediatric- and adult-onset UC patients., Results: Patients with pediatric-onset UC experienced a significantly shorter disease duration than those with adult-onset UC. The levels of miR-124 promoter methylation in non-neoplastic rectal mucosa were positively correlated with the age at the diagnosis and duration of UC. The rate of increase in miR-124 methylation was accelerated in patients with pediatric-onset UC compared to those with adult-onset UC. Furthermore, the miR-124 methylation levels in non-neoplastic rectal mucosa were significantly higher in patients with UC-CRC than in those with UC alone (P = 0.02). A receiver operating characteristic analysis revealed that miR-124 methylation in non-neoplastic tissue discriminated between patients with pediatric-onset UC with or without CRC., Conclusion: miR-124 methylation in non-neoplastic rectal mucosa may be a useful biomarker for identifying patients with pediatric-onset UC who face the highest risk of developing UC-CRC., (© 2023. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Purpose: To assess the severity of preoperative myopenia and myosteatosis in pediatric patients with inflammatory bowel disease (IBD) and examine their impact on postoperative complications., Methods: The subjects of this retrospective study were 30 pediatric patients with IBD (22 with ulcerative colitis (UC) and 8 with Crohn's disease (CD)) and 67 age-matched controls. Preoperative body mass index (BMI), psoas muscle index (PMI), and intramuscular adipose tissue content were compared between the patient groups, to investigate their association with postoperative complications., Results: BMI and PMI were significantly lower in the IBD patients than in the controls (p < 0.0001, p < 0.0001, respectively). CD was associated with significantly lower BMI and PMI (p = 0.01, p = 0.01, respectively) than UC. Intramuscular adipose tissue content was comparable between the IBD patients and the controls and between the UC and CD patients. There were no significant differences among the three indices in relation to the presence or absence of postoperative complications in patients with IBD. When limited to surgical site infection (SSI), only PMI was significantly lower in the patients with SSI than in those without SSI (p = 0.04)., Conclusions: Although BMI and PMI were lower preoperatively in pediatric IBD patients than in controls, only myopenia seemed to affect the development of SSI., (© 2022. The Author(s) under exclusive licence to Springer Nature Singapore Pte Ltd.)

Background: Patients with longstanding inflammatory bowel disease are at high risk of developing intestinal cancers. In this study, we aimed to elucidate the differences between intestinal cancers associated with ulcerative colitis and Crohn's disease., Methods: Intestinal cancers in ulcerative colitis and Crohn's disease patients treated between 1983 and 2020 at 43 Japanese institutions were retrospectively analyzed.., Results: A total of 1505 intestinal cancers in 1189 ulcerative colitis and 316 Crohn's disease patients were studied. Almost all of ulcerative colitis-associated cancers (99%) were in the colon and rectum, whereas half of Crohn's disease-associated cancers (44%) were in the anus, with 11% in the small intestine. Ulcerative colitis-associated cancers were diagnosed more frequently by surveillance (67% vs. 25%, P < 0.0001) and at earlier stages (stages 0-1, 71% vs. 27%, P < 0.0001) compared with Crohn's disease-associated cancers. Colorectal cancers associated with Crohn's disease showed a significantly worse 5-year overall survival rate than those associated with ulcerative colitis (stage 2, 76% vs. 89%, P = 0.01, stage 3, 18% vs. 68%, P = 0.0009, and stage 4, 0% vs. 13%, P = 0.04). Surveillance correlated with earlier diagnoses for ulcerative colitis- and Crohn's disease-associated intestinal cancers, whereas shorter intervals between endoscopic examinations correlated with an earlier cancer diagnosis in ulcerative colitis patients but not in Crohn's disease patients., Conclusions: The clinical and oncological features of ulcerative colitis- and Crohn's disease-associated cancers were very different. Crohn's disease-associated cancers were diagnosed at more advanced stages and were detected less frequently by surveillance. Additionally, they showed a significantly poorer prognosis., (© 2022. Japanese Society of Gastroenterology.)

Purpose: We aimed to identify predictive factors for the development of chronic pouchitis after ileal pouch-anal anastomosis in patients with ulcerative colitis., Methods: Three hundred eighty-seven patients who underwent ileal pouch-anal anastomosis for diagnosis of ulcerative colitis from January 2002 to March 2019 were included in this retrospective analysis., Results: Of 115 patients with pouchitis, 40 patients exhibited acute pouchitis, and 75 patients exhibited chronic pouchitis. Of 75 patients with chronic pouchitis, 11 patients were diagnosed with chronic antibiotic-refractory pouchitis. Multivariate analysis revealed that early pouchitis onset and modified Pouchitis Disease Activity Index score ≥ 7 were independent predictive factors for chronic pouchitis (p = 0.0004 and p = 0.029, respectively). Mean onset of pouchitis after intestinal continuity was significantly earlier in patients with chronic pouchitis than in patients with acute pouchitis (acute pouchitis vs. chronic pouchitis: 3.72 ± 2.98 years vs. 1.85 ± 2.40 years, p < 0.0001). Total modified Pouchitis Disease Activity Index score was significantly higher in patients with chronic pouchitis than in patients with acute pouchitis (acute pouchitis vs. chronic pouchitis: 5.9 ± 1.2 vs. 6.9 ± 1.6, p = 0.0020)., Conclusion: Patients with ulcerative colitis were more likely to develop chronic pouchitis if they exhibited early onset or severe disease activity at onset. Evaluation of both factors can aid in early treatment decisions to alleviate chronic pouchitis., (© 2020. The Society for Surgery of the Alimentary Tract.)

Objective: Patients with ulcerative colitis (UC) often develop arthropathy. The purpose of this study was to determine the frequency of and risk factors for arthropathy in patients with UC who underwent total colectomy which is the final radical treatment lead to remission., Methods: Patients who underwent total colectomy from January 2007 to April 2016 were analyzed for the development of arthropathy. The type of arthropathy and risk factors for developing arthropathy were analyzed by clinical and endoscopic severity classification, extraintestinal manifestations (EIMs) and medical treatment., Results: Total of 219 patients who underwent total colectomy with sufficient medical records were analyzed. Forty-eight cases (21.9%) had EIMs, and 40 cases (18.2%) developed arthropathy (57.0% polyarthropathy; 42.5% peripheral arthropathy). Multivariate analysis showed that severity of Matts classification grade 3 or 4 versus grade 1 or 2 (hazard ratio [HR] 2.31, 95% confidence interval [CI] 1.22-4.36, p  < .05) and EIMs other than arthropathy (HR 3.29, 95% CI 1.43-7.58, p  < .05) were risk factors for the development of arthropathy., Conclusion: This study showed that approximately one fifth of patients with UC who underwent total colectomy developed arthropathy. The risk factors for the development of arthropathy were preoperative endoscopic disease activity and EIMs.

Background: Although the etiology of pouchitis remains unknown, inflammatory cytokines are significantly associated with the pathogenesis of pouchitis. The cytokine responses that characterize inflammatory bowel diseases (IBD) are key pathogenic components of the disease. Although cytokine profiles in the colonic mucosa have been investigated in experimental colitis models or IBD patients, cytokine profiles in the ileal mucosa at colectomy have been rarely assessed., Aim: To assess the relationship between pouchitis and T helper (Th) cytokines in the ileal mucosa collected at the time of colectomy and pouch construction., Methods: This retrospective study involved 68 consecutive patients from January 2004 to May 2011 who underwent ileal pouch-anal anastomosis for ulcerative colitis. Samples were obtained from the terminal ileum of resected specimens at time of total colectomy or subtotal colectomy. mRNA expression levels of Th cytokines (IFN-γ, IL-23A, IL-5, IL-13 and IL-17A) were determined., Results: Forty of 68 patients (58.8%) developed pouchitis. There was no association between IL-23A expression levels and incidence of pouchitis (p = 0.301). Patients with elevated IFN-γ had a significantly higher incidence of pouchitis compared with low IFN-γ patients (p = 0.043). Univariate analysis demonstrated a total dose of prednisolone > 7000 mg administered before colectomy (p = 0.04) and high IFN-γ expression (p = 0.02) were significant risk factors for pouchitis onset. In multivariate analysis, elevated IFN-γ messenger(m)RNA levels were significantly associated with pouchitis onset (p = 0.03)., Conclusion: IFN-γ expression in the normal ileal mucosa at the time of colectomy may be an important factor in the pathophysiology of pouchitis.

Background: The predictive factors for chronic pouchitis after ileal pouch-anal anastomosis (IPAA) in pediatric-onset ulcerative colitis (UC) remain unclear. This study evaluated the predictive factors for chronic pouchitis after IPAA in patients with pediatric UC., Methods: The data from 52 patients with pediatric-onset UC who underwent IPAA in Mie University Hospital were retrospectively reviewed. The endoscopy surveillance was performed yearly or at the timing of the symptom. Chronic pouchitis was defined as antibiotic-dependent/-refractory and relapsing cases. Potential predictors of chronic pouchitis were analyzed., Results: During the first 5 years after IPAA, pouchitis was identified in 32.7%. Of these patients, 12 (70.6%) developed chronic pouchitis. The predictor of chronic pouchitis was a preoperative history of immunomodulator use before IPAA (p = 0.04). Life table analysis revealed that patients with chronic pouchitis tended to develop pouchitis earlier after IPAA than did patients without chronic pouchitis (p = 0.012). Receiver operating characteristic curve analysis showed that the occurrence of pouchitis within 15 months after IPAA surgery predicted the development of chronic pouchitis (sensitivity, 92%; specificity, 80%)., Conclusion: In pediatric patients with UC, the predictive factors for chronic pouchitis are immunomodulator use and early occurrence of the first episode of pouchitis within 15 months after IPAA., Level of Evidence: III., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The predictive factors for the development of pouchitis after ileal pouch-anal anastomosis (IPAA) in pediatric-onset ulcerative colitis (UC) have not been well investigated. The present study aimed to determine the predictive factors for the development of pouchitis after IPAA in the pediatric UC population., Methods: The data from 54 patients with pediatric-onset UC who underwent IPAA in Mie University Hospital between 2000 and 2017 were retrospectively reviewed. A modified pouchitis disease activity index of ≥5 was defined as pouchitis. Potential preoperative, intraoperative, and postoperative predictors for pouchitis including various demographic and clinical variables were analyzed using Cox regression analysis, Students' t-tests, Mann-Whitney U tests, and Kaplan-Meier curves. The optimal cutoff value for continuous variables was determined using the receiver operating characteristic curve analysis., Results: Pouchitis was identified in 17 (31.5%) patients within 5 y of follow-up. In multivariable analysis, the independent predictors for pouchitis were preoperative cumulative steroid dose of >10,000 mg (P = 0.0056) and >65% neutrophils just before IPAA (P = 0.032). Multivariate analysis revealed that the independent predictors of pouchitis were a total steroid dose of >10,000 mg (P = 0.0002) and a neutrophil percentage of >65% (P = 0.0078). No patient for whom both of these independent predictors were negative developed pouchitis, whereas >40% of patients who had one or both predictors developed pouchitis., Conclusions: In pediatric patients with UC, the predictive factors for pouchitis development are a greater cumulative total dose of steroids and a greater percentage of neutrophils before IPAA., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Orally administered Qing-dai, called indigo naturalis in Latin, is reportedly useful for the treatment of ulcerative colitis. We herein describe two patients with ulcerative colitis who developed colitis with wall thickening and edematous changes during oral administration of the powdered form of Qing-dai. In Case 1, a 35-year-old man developed colitis similar to ischemic colitis with bloody stool that recurred each time he ingested Qing-dai. He had no signs of recurrence upon withdrawal of Qing-dai. In Case 2, a 43-year-old woman underwent ileocecal resection for treatment of an intussusception 2 months after beginning oral administration of Qing-dai. Edema and congestion but no ulceration were present in the mucosa of the resected specimen. Both patients exhibited abdominal pain with bloody diarrhea, and abdominal computed tomography showed marked wall edema affecting an extensive portion of the large bowel.

Background/aims: Pouchitis is one of the main complications after ileal pouch-anal anastomosis in patients with ulcerative colitis. The aim of this study was to determine whether the use of colonic histological criteria can predict the development of pouchitis., Methodology: We retrospectively reviewed 147 patients' clinical data and performed a histological evaluation of the resected total colon using Tanaka's criteria, which comprise the following 6 factors: ulceration (H1), crypt abscesses (H2), degree of mononuclear cell infiltration (MNCI) (H3), segmental distribution of MNCI (H4), eosinophil infiltration (H5), and extent of disease of resected colon (H6)., Results: The development of pouchitis and chronic pouchitis within 3 years after restoration of gastrointestinal continuity was recognized in 52 (35.4%) and 26 (17.7%) of the 147 patients, respectively. Using various combinations of each score, the H3 + H4 - H5 scores of patients with pouchitis or chronic pouchitis were significantly higher than those of patients without. A H3 + H4 - H5 score of >0.4 was a statistically significant risk factor for the development of both pouchitis and chronic pouchitis., Conclusions: The combination of the degree of MNCI, segmental distribution of MNCI, and eosinophil infiltration from histological criteria has utility in predicting the future development of pouchitis, especially chronic pouchitis., (© 2017 S. Karger AG, Basel.)

Afferent limb syndrome (ALS) is caused by an obstruction of the afferent intestinal limb after ileal pouch-anal anastomosis. Here, we describe the first case of ALS to be successfully treated by a laparoscopic approach. A 27-year-old man underwent ileal pouch-anal anastomosis for ulcerative colitis. He was subsequently diagnosed with ALS and underwent ileopexy with laparotomy at 33 years old. Then, 21 months after the first ileopexy, he underwent laparoscopic ileopexy for ALS recurrence. The operative findings revealed a shortened fixed portion of the afferent limb adhering to the right pelvic retroperitoneum, which was regarded as the cause of the acute angulation. The portion of the afferent limb fixed to the abdominal wall was extended under laparoscopic visualization by suturing above the level of the iliac crest. At the 12-month follow-up, the patient remained free of symptoms of obstruction. Laparoscopic ileopexy should be the procedure of choice for patients with ALS., (© 2017 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.)

Aims: We defined small bowel obstruction occurring around the limbs of the ileostomy as stoma-related obstruction (SRO) and investigated the clinical characteristics and predictive factors of SRO., Methods: From January 2002 to March 2016, 309 consecutive patients who underwent ileal pouch-anal anastomosis (IPAA) for ulcerative colitis were enrolled. Two-stage IPAA with diverting ileostomy was analyzed. We assessed the possible associations between SRO and clinical factors., Results: A total of 205 patients met the inclusion criteria. Fifty-three (25.8%) patients with SRO before ileostomy closure were identified for review. All patients with SRO were at least transiently resolved by intubation though orifice of ileostomy (98.1%) or nasally (3.7%). In 18 (33.9%) patients, the ileostomy was taken down ahead of schedule and the small bowel obstruction improved in all cases. Multivariate analysis revealed that age at surgery <16 years old and body mass index <21 were significant predictive factors for SRO (P = 0.013 and 0.0012, respectively)., Conclusion: Younger age at surgery and low body mass index may be significant predictive factors for SRO after IPAA with diverting ileostomy in patients with ulcerative colitis.

Purpose: Restorative proctocolectomy with ileal pouch-anal anastomosis is a surgical procedure for ulcerative colitis, but pouch failure or pelvic sepsis still occurs in some patients. We conducted this study to investigate the cause of pouch failure and evaluate defecatory function after pelvic sepsis., Methods: A total of 234 patients who underwent restorative proctocolectomy were enrolled. We analyzed the cause of pouch failure, as well as defecatory function and manometric outcomes, with and without the complication of pelvic sepsis., Results: Pelvic sepsis developed in 29 (12.3%) of the 234 patients who underwent restorative proctocolectomy (pelvic sepsis group). The pelvic sepsis led to pouch failure in two of these patients (as a vaginal fistula in one and ileo-anal anastomotic leakage in one). Of the remaining majority of patients who did not suffer pelvic sepsis (control group), nine suffered pouch failure (as vaginal fistula in four, perianal abscess in two, pouch-spinal marrow fistula in one, and chronic pouchitis in two). There were no significant differences in defecatory function or manometric outcomes between the two groups. In the pelvic sepsis group, stool frequency was significantly correlated with white blood cell count (P = 0.01) and the duration until onset of pelvic sepsis (P < 0.01)., Conclusions: Pelvic sepsis after restorative proctocolectomy for ulcerative colitis does not affect defecatory and manometric function, but control of the inflammation caused by pelvic sepsis is integral for defecatory function.

Purpose: The coexistence of sarcopenia is associated with postoperative complications, including infection after abdominal surgery. We evaluated the association between sarcopenia and surgical site infection (SSI) after surgery for ulcerative colitis., Methods: The subjects of this retrospective study were 69 patients who underwent restorative proctocolectomy with perioperative abdominal computed tomography (CT). Sarcopenia was diagnosed by measuring the cross-sectional area of the right and left psoas muscles as the total psoas muscle area on CT images. We assessed whether sarcopenia was associated with SSI and clinical factors, including nutritional and inflammatory markers., Results: The lowest quartiles defined as sarcopenia in men and women were 567.4 and 355.8 mm 2 /m 2 , respectively. According to this classification, 12 men and 6 women had sarcopenia. Patients with sarcopenia had a lower body mass index (p = 0.0004) and a higher C-reactive protein concentration (p = 0.05) than those without sarcopenia. SSIs were identified in 12 patients (17.3 %) and included six pelvic abscesses and seven wound infections. According to multivariate analysis, sarcopenia was an independent risk factor for SSI (odds ratio = 4.91, 95 % confidence interval 1.09-23.5, p = 0.03)., Conclusion: Sarcopenia is predictive of SSI after pouch surgery for ulcerative colitis.

Purpose: Afferent limb syndrome (ALS) is a type of small bowel obstruction (SBO) caused by obstruction of the afferent intestinal limb after ileal pouch-anal anastomosis (IPAA). The aim of this study was to reveal the clinical features and management of ALS., Methods: Of 320 patients undergoing IPAA for ulcerative colitis, we analyzed data from patients presenting with SBO., Results: Six of 19 patients with SBO were diagnosed with ALS. All patients with ALS presented with recurrent intermittent obstructive symptoms before admission, whereas 15 % of patients without ALS presented with these symptoms (P < 0.0005). Among the six patients with ALS, four patients required surgery, although they underwent transanal decompression for each episode of obstruction. The proportion of surgery was higher in the ALS group (P < 0.01). Acute angulation of the afferent limb was recognized in four cases and followed by fixation of the afferent limb. No further surgery was required in any patient following the last fixation., Conclusions: SBO after IPAA may be caused by acute angulation of the afferent limb of the ileal J-pouch. Most patients with ALS may eventually require fixation of the afferent limb due to acute angulation of the afferent limb.

Afferent limb obstruction can be a persistent complication after restorative proctocolectomy with ileal pouch-anal anastomosis. We present a case of afferent limb obstruction complicated by a long efferent limb of the ileal pouch that we successfully treated with side-to-side anastomosis of the afferent and efferent limbs. The procedure involved using a transanal endoscopic stapling device assisted by transanal endoscopy with a thin intestinal video endoscope. This allowed reliable, safe visualization of the lesion from the tight pouch-anal anastomosis and facilitated repair with an endoscopic stapling device. Because the technique was performed without enterotomy, it reduced the risks of contamination and leakage from transabdominal small bowel anastomosis. Laparotomy view also prevented of injury to the pouch itself and entrapment of the mesentery of the afferent and efferent limbs of the pouch between the stapler anvils., (© 2016 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.)

Aim: The current trial was designed to study and compare the postoperative outcomes and systemic acute responses between patients undergoing laparoscopic-ileal pouch anal anastomosis (LAP-IPAA) and open IPAA for ulcerative colitis., Methods: The clinical records of patients who underwent 89 restorative proctocolectomy procedures with IPAA were reviewed. After determining which patients underwent LAP-IPAA versus open IPAA, an equivalent number of controls matched for age and ulcerative colitis severity were selected., Results: Twenty of 22 patients who underwent laparoscopic surgery met the inclusion criteria. Patients who underwent LAP-IPAA had significantly shorter times to first walking (P=0.021) and food intake (P=0.0003). The LAP-IPAA group had significantly lower interleukin-6 and interleukin-1ra levels soon after surgery (P=0.011 and P=0.0076). The LAP-IPAA group had significantly lower C-reactive protein levels on postoperative day 1 (P=0.0027)., Conclusions: LAP-IPAA is a less-invasive operative procedure than open IPAA with respect to the postoperative systemic inflammatory response and postoperative recovery.

Background: Although the pathogenesis of pouchitis is incompletely understood, steroid and FK506 therapy are significantly associated with pouchitis. These medical treatments are regulated by the FK506-binding protein (FKBP) 4 and FKBP5 genes., Aim: This study aimed to evaluate the relationship between pouchitis and FKBP4 and FKBP5 mRNA expression in ileal mucosa at the time of colectomy., Methods: Ileal mucosa specimens were collected from 71 patients who underwent ileal pouch-anal anastomosis for ulcerative colitis. FKBP4 and FKBP5 mRNA expression was evaluated. The relationship between mRNA expression and clinicopathological factors, including developed pouchitis, was investigated., Results: Of these 71 patients, 25 (35.2 %) patients developed pouchitis in a mean duration of 20.2 months (range 0-68 months). FKBP4 mRNA levels in patients who received an immunomodulator were significantly higher than those in untreated patients (0.167 ± 0.060 vs 0.131 ± 0.065, p = 0.009). However, FKBP5 mRNA levels in patients who received a three-stage operation were significantly lower than those in the other patients (1.97 ± 1.15 vs 2.70 ± 1.12, p = 0.02). A total dose of prednisolone >9.4 g (HR 2.84, p = 0.02) before colectomy and FKBP5 mRNA level higher than the median (HR 4.49, p = 0.01) were identified as factors related to pouchitis., Conclusions: FKBP5 mRNA levels in ileal mucosa at the time of colectomy are significantly associated with pouchitis and may be a predictive factor for developing pouchitis.

Background: Histological segmental distribution of ulcerative colitis (UC) may represent an early finding of newly diagnosed UC, especially in pediatric patients; a sign of Crohn's disease; or a predictor of refractory UC. However, its significance remains unknown. This study was performed to compare the final pathologic findings in resected total colon and rectum specimens between pediatric and adult patients with refractory UC who underwent proctocolectomy and clarify the significance of segmental distribution in pediatric patients with UC., Methods: Ninety patients with medically refractory UC (14 with childhood-onset UC and 76 with adult-onset UC) who underwent a two-staged operation comprising total proctocolectomy and ileal J-pouch anal anastomosis in the first stage were included in this study. We retrospectively reviewed all patients' medical records and performed a histological evaluation of the resected total colon using Geboes' grading system for histological inflammation activity of UC and factors of Tanaka's criteria for refractory UC., Results: Histological segmental distribution was more frequently observed in the resected colon at surgery in pediatric (64%) than in adult patients (21%) with refractory UC. The administration of immunomodulators or anti-TNF-α antibody within 30 days before surgery was more frequently performed in adults than in children. Patients with refractory UC with a segmental distribution had a statistically significant relationship with shorter duration before surgery (P = 0.0009), male gender (P = 0.0342), and higher activity of disease inflammation in rectum (P = 0.0399). Multivariate analysis revealed the statistically significant relationship between segmental distribution and disease duration before surgery ≤ 6 years (P = 0.0031)., Conclusions: Endoscopists should perform biopsies of both normal and abnormal mucosa throughout the total colon and follow changes in the pathological pattern because segmental distribution is an important predictor of prognosis.

Purpose: A prospective, multicenter, observational study was performed to investigate the risk factors of surgical site infection (SSI) in patients with ulcerative colitis (UC)., Methods: From 2009 to 2010, perioperative clinicopathological data were collected from patients who had undergone surgery for UC within the research period, for up to 6 consecutive months in 13 hospitals in Japan. The primary outcome was the development of SSI., Results: A total of 195 patients with UC who underwent colorectal surgery were enrolled. SSI was diagnosed in 38 (19.5 %) patients, in the form of incisional infection in 23 (11.8 %), organ/space infection in 16 (8.2 %), and both in 1 (0.5 %). There were no significant risk factors associated with an increased risk of development of incisional SSI. An American Society of Anesthesiologists physical status of ≥ 3 was indicated as the only significant risk factor for organ/space SSI (P = 0.02) compared with other factors, such as a neutrophil count of >100 × 10(2)/mm(3), albumin level of <3.5 g/dl, perioperative packed red blood cell transfusion, fair or poor colonic cleanliness, and therapeutic use of antibiotics., Conclusion: Poor general physical status was the significant independent risk factor for organ/space SSI in patients with UC in Japan.

Pyoderma gangrenosum (PG) is an idiopathic, inflammatory, ulcerative skin disorder; the etiology and pathogenesis of which are still poorly understood. It is one of the most important extraintestinal manifestations that can appear in the course of ulcerative colitis (UC). Although skin ulcers with destructive and necrotizing components are more commonly observed on the lower extremities and trunk, PG at stomal sites (peri-stomal PG) has been increasingly reported in patients with inflammatory bowel diseases (IBDs), including UC. Although PG at various surgical sites has been reported as an unusual presentation of PG, postoperative PG developing at the ileal pouch-anal anastomosis (IPAA) has not been reported previously. We herein report the first published case of a patient with UC who developed peri-anastomotic PG after IPAA during the postoperative tapering of systemic corticosteroids.

Purpose: The aim of this study was to evaluate the sexual activity after restorative proctocolectomy with ileal J-pouch-anal anastomosis (ileoanal anastomosis) in Japanese patients with ulcerative colitis., Methods: Sixty-one patients who had undergone ileoanal anastomosis and were followed for at least 6 months after surgery were randomly selected. Their quality of life was assessed using the Japanese version of the Inflammatory Bowel Disease Questionnaire. Scores of three or less for the item "Sex life" were predetermined to represent poor sexual activity. The medical staff then asked them the reasons for this using a non-structured interview and open-ended questions., Results: Overall, 19 patients reported poor sexual activity. There was a significant difference in the scores for "Social functions" other than Sex life between individuals with poor and good sexual activities (21.6 ± 4.6 vs. 24.1 ± 4.2, P = 0.016). Ileoanal anastomosis after the age of 40 (OR 22, P = 0.02) and a total preoperative corticosteroid dose ≥15 g (OR 7.4, P = 0.04) were significant risk factors for poor sexual activity after ileoanal anastomosis., Conclusion: Our results suggest that ileoanal anastomosis results in relatively poor sexual activity, which was associated with other social functions, older age and a higher dose of corticosteroids administered to Japanese patients with ulcerative colitis.

Aim: To retrospectively analyze manometric findings in patients with ulcerative colitis who underwent redo-ileo anal anastomosis for pouch-related complications., Methods: Functional and anal manometric parameters were analyzed before, immediately after, and 6 months after the procedure in 17 patients who underwent redo-ileo anal anastomosis between 2001 and 2012., Results: Of the 17 patients, 13 showed stoma closure and 9 have maintained gastrointestinal continuity with functional pouches. Manometric findings were similar before and immediately after redo-ileo anal anastomosis, including length of high-pressure zone (p = 0.11) and maximum resting and (p = 0.060) squeezing (p = 0.69) pressures, but maximum resting pressure improved significantly 6 months later (p = 0.021). Univariate analysis showed that ulcerative colitis duration <3 years before ileo anal anastomosis (p = 0.0073), interval between pouch-related complications and ileo anal anastomosis <2 years (p = 0.040), and persistent abscess before diversion ileostomy (p = 0.0024) were significant risk factors for pouch failure after redo-ileo anal anastomosis., Conclusions: Although maximum resting pressure was significantly reduced 3 months after redo-ileo anal anastomosis, it returned to preoperative levels after 6 months. The length of the high-pressure zone and the maximum squeezing pressure were not affected by this procedure.

Goal: To clarify whether the expression of nitrative and oxidative DNA damage markers in the rectal mucosa of patients with ulcerative colitis (UC) could be used to predict UC-associated neoplasia., Background: A longer duration of UC can increase the risk of developing UC-associated cancer (UCAC). Effective diagnostic markers are being sought to provide more selective screening and treatment strategies for patients with long-standing UC., Study: A total of 141 patients with UC who underwent a proctocolectomy were enrolled in this study. The expression of 8-nitroguanine (8-NG), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), and inducible nitric oxide synthase (iNOS) in the rectal mucosa were evaluated using immunohistochemistry (IHC) and assessed relative to the pathogenesis of UC-associated neoplasia., Results: Eighteen patients (12.8%) had UC-associated neoplasia including low-grade or high-grade dysplasia and UCAC. IHC scores of 8-NG in UC-associated neoplasia group was significantly higher than in non-neoplasia group (P<0.0001). In contrast, IHC score of 8-oxodG in non-neoplasia group was significantly decreased compared with UC-associated neoplasia group (P=0.0028). In logistic regression analysis, duration of disease >8 years, high IHC scores of 8-NG, and low 8-oxodG in the rectal mucosa were significantly associated with the development of UC-associated neoplasia (P<0.01). The expression of 8-NG was more frequently observed in patients with UCAC than in patients with sporadic colorectal cancer (P<0.01)., Conclusion: These results suggest that evaluating the expression levels of 8-NG in the rectal mucosa may be a useful biomarker for detecting patients with UC-associated neoplasia.

Objective: This study aims to evaluate the clinical characteristics of patients with postoperative ulcerative colitis developing extremely early-onset pouchitis within 4 weeks of restoration of gastrointestinal continuity., Material and Methods: This retrospective study involved 225 consecutive patients from January 2000 to May 2011 who underwent ileal pouch-anal anastomosis for ulcerative colitis with a minimum follow-up of 12 months. Extremely early-onset pouchitis was defined as pouchitis developing within 4 weeks of restoration of gastrointestinal continuity. Patients with pouchitis were divided into extremely early-onset pouchitis and non-extremely early-onset pouchitis groups for comparison., Results: Of 212 patients who met the inclusion criteria, 62 had pouchitis (29.2 %). Eight (3.8 %) patients developed extremely early-onset pouchitis. There was a significant difference in the dosage of steroid per month just before colectomy between the two groups (P = 0.039). The modified Pouchitis Disease Activity Index score for patients with extremely early-onset pouchitis was higher than in patients with non-extremely early-onset pouchitis (P = 0.0009). The occurrence of extremely early-onset pouchitis was associated with the development of chronic pouchitis (P = 0.0056)., Conclusion: Extremely early-onset pouchitis may be related to high steroid dosages before colectomy and may be more severe than pouchitis that occurs >4 weeks after restoration of gastrointestinal continuity.

Purpose: To clarify health-related quality of life (HRQOL) by self-evaluation after restorative proctocolectomy with ileal J-pouch anal anastomosis (IPAA) in children with ulcerative colitis, a questionnaire using the Pediatric Quality of Life Inventory™ 4.0 (PedsQL) was administered., Methods: The PedsQL was administered to 13 consecutive children (mean age 14.5 years) who underwent IPAA between 2005 and 2010 in our hospital and age-matched healthy controls. The mean duration after IPAA was 2.5 years (range 0.08-6 years) at the time of this study. Healthy children completed the same questionnaire by retrospective imaging during the past 1 month by the PedsQL evaluation policy., Results: Patients' total score and each functioning score after IPAA reached the same levels as those in healthy controls. Soiling, pouchitis occurrence, and bowel movements had no significant relationship to the PedsQL total score and each functioning score., Conclusions: Interference of physical activity, emotional status, and social life caused by refractory ulcerative colitis (UC) worsens patients' HRQOL. IPAA could resolve these problems in children with UC and result in an HRQOL comparable with that in healthy children.

Background: Long-term functional results of ileal pouch-anal anastomosis (IPAA) with mucosal proctectomy (MP) for ulcerative colitis (UC) are satisfactory but may be compromised by perianal fistulae., Methods: We analyzed the effect of the level of MP (above or below the dentate line) on the risk of perianal fistulae in 151 patients undergoing IPAA for UC., Results: A postoperative perianal fistula occurred in 12 patients (10 with MP from the level above the dentate line and 2 below). Patients developing perianal fistulae after IPAA were significantly younger at IPAA (23 vs. 32 years, p = 0.015). Age <25 years at UC onset (hazard ratio, HR, 3.5, p = 0.041), age <30 years at IPAA (HR 4.3, p = 0.015) and MP above the dentate line (HR 4.7, p = 0.010) were significant risk factors for perianal fistulae after IPAA. Multivariate analysis showed that age <30 years at IPAA (HR 4.4, p = 0.018) and MP above the dentate line (HR 6.0, p = 0.012) were significant risk factors., Conclusion: IPAA with MP below the dentate line for UC might reduce the risk of postoperative perianal fistulae., (Copyright © 2013 S. Karger AG, Basel.)

Background: No previous studies have examined predictive factors for chronic pouchitis after ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) with consideration of changes in pouchitis subtypes during follow-up. This study evaluated the independent predictive factors for chronic pouchitis., Methods: A total of 244 consecutive patients who underwent IPAA were enrolled. We assessed the possible associations between pouchitis and clinical factors using Cox proportional hazard regression., Results: 231 patients met the inclusion criteria. 66 (28.5%) patients developed pouchitis. In 9 of 44 (20.4%) patients, antibiotic-responsive pouchitis at the first episode changed into chronic pouchitis after the occurrence of a subsequent episode. The median duration from occurrence of antibiotic-responsive pouchitis to alteration into chronic pouchitis was 502 (range 147-1,697) days. Overall pouchitis was finally classified into 35 acute pouchitis and 31 chronic pouchitis cases. Multivariate analysis revealed that a ≥ 7.5-g cumulative steroid dose before colectomy and a ≥ 500-mg monthly steroid dose just before colectomy were significant predictive factors for chronic pouchitis (p = 0.0001 and 0.0095, respectively)., Conclusion: Patients with UC and a higher cumulative steroid dose before colectomy or higher monthly steroid dose just before colectomy may have a predictive factor for developing chronic pouchitis., (Copyright © 2013 S. Karger AG, Basel.)

Purpose: We studied macrophage migration inhibitory factor (MIF)-related neutrophil dysfunction in patients with ulcerative colitis (UC), under conditions of surgical stress, focusing in particular on total preoperative steroid dosages., Methods: Neutrophils were isolated from peripheral blood samples obtained from 21 UC patients soon after radical surgery for UC. The patients were divided into two subgroups according to their total preoperative prednisolone dosages. The neutrophil phagocytosis, viable cell, and cell necrosis rates after exposure to Escherichia coli were evaluated by flow cytometry. The supernatant concentrations of mediators after exposure to E. coli were evaluated by enzyme-linked immunosorbent assay., Results: There was a significant positive correlation between the levels of MIF and the total preoperative dosage of prednisolone. More viable neutrophils from the high-dosage steroid group patients than from the low-dosage steroid group patients tended to undergo necrosis, followed by the release of neutrophil elastase after exposure to E. coli. The levels of anti-inflammatory cytokines were not enhanced after E. coli stimulation, but the levels of proinflammatory cytokines in the supernatants of neutrophils from the high-dosage steroid group patients were increased significantly., Conclusion: Steroid-overdosed UC patients with MIF-related neutrophil dysfunction may be at increased risk of destructive local inflammation following surgery.

Purpose: The aim of the present study was to review the complications and growth after proctocolectomy and ileal J-pouch anal anastomosis (IPAA) in pediatric ulcerative colitis (UC) patients receiving prolonged steroid therapy., Patients and Methods: We experienced 209 patients with UC who received IPAA between September 2000 and June 2009, and reviewed the medical records of 16 pediatric (<15 years of age at operation and >1 year follow-up) patients., Results: The total dose of preoperative prednisolone (PSL) was 9,829 +/- 9,283 mg (mean +/- 1SD 880-30,000 mg). The dose of preoperative PSL was significantly related to the occurrence of preoperative major steroid-related complications (SRC). Older patients (>11 years at operation) grew more slowly compared with younger patients (< or =11 years at operation) for 5 years. There was a significant difference in height between PSL high-dose (>10,000 mg) and PSL low-dose (< or =10,000) patients for 5 years after colectomy. The mean height of PSL high-dose patients did not reach the standard level during the 5-year follow-up., Conclusion: Preoperative prolonged high steroid therapy may disturb growth recovery of pediatric patients with UC, while early induction of colectomy allowed pediatric patients with PSL dependency to become free of steroids and get normal growth.

Extension of the inflammatory process to the terminal portion of the ileum in patients with ulcerative colitis is commonly known as backwash ileitis (BWI). To the best of our knowledge, few studies of severe BWI have been reported in the English literature, and surgical strategies for this disease have not been discussed. We report 2 patients with ulcerative colitis and severe BWI, with concomitant ileal bleeding and perforation. In both cases, staged operation without sacrificing the involved area of the terminal ileum led to ileal pouch-anal anastomosis, with a favorable postoperative outcome. Our cases suggest that the underlying pathophysiologic conditions in BWI may be reversible, and the involved lesion can be salvaged in some cases.

Background: There is some evidence that large preoperative doses of steroids are a causative factor for postoperative higher morbidity in ulcerative colitis (UC) patients. This study aimed to assess steroid-related changes in functional profiles of neutrophils in UC patients to estimate the immunological changes under surgical stress., Methods: Neutrophils were extracted from peripheral blood of 30 UC patients and 30 healthy controls. UC patients whose neutrophils were isolated were divided into two subgroups according to their total preoperative dosage of prednisolone: group H, > or =10,000 mg; group L, <10,000 mg. Expression of neutrophil surface antigens was analyzed and neutrophil phagocytosis was evaluated. Patterns of cell death of neutrophils were evaluated by co-culturing with Escherichia coli. Production of inflammatory mediators in cultured neutrophils was assessed., Results: There were no significant differences in the expression rates of TLR4, CD11b, and CD16b on neutrophils (CD15(+) cells) between the two patient groups and controls. There was also no significant difference in neutrophil phagocytosis between the two patient groups and controls. The neutrophil necrosis rate in group H was higher than that in group L and the controls 3 h after exposure to E. coli. Neutrophils from group H released the highest levels of proinflammatory cytokines following interleukin-1beta or lipopolysaccharide stimulation. Neutrophils from group H also released the highest levels of proteolytic enzymes., Conclusions: Steroid-overdosed UC patients may have a functional deficit in neutrophils, which may cause a postsurgical systemic "storm" of inflammatory mediators.

Aims: The present study was designed to assess whether preoperative neutrophil priming under surgical stress has causal effects on the postoperative clinical outcomes of ulcerative colitis (UC) patients., Patients and Methods: In 63 consecutive UC patients, perioperative changes in cytokines and neutrophil elastase (NE) were quantified and their relationships to postoperative infectious complications (PICs) were evaluated., Results: A preoperative increase in NE (high group: Group H) was associated with longer disease duration and greater preoperative total amount of steroids administered. Patients in Group H developed more PICs than those in the low NE group when they underwent surgery >240 min. In Group H, the NE level remained high after longer duration surgery, but decreased rapidly after shorter duration surgery. Multivariate analyses revealed that the total amount of steroids used and preoperative NE level were independent risk factors for predicting PICs in the longer operation group., Conclusion: Preoperative neutrophil activation may become a risk factor for postoperative morbidity when the patients undergo intense surgical stress. The most important procedures for preventing postoperative morbidity in high-risk UC patients may be reducing surgical stress and/or controlling neutrophil activation perioperatively.