Changes in the rate of and trends in colectomy for ulcerative colitis during the era of biologics and calcineurin inhibitors based on a Japanese nationwide cohort study.

PURPOSE: We evaluated the recent incidence of surgery and the changing surgery trends for ulcerative colitis (UC) in Japan due to the increasing use of anti-tumor necrosis factor (TNF) agents. METHODS: A questionnaire survey was performed to assess the number of surgeries, surgical indications, surgical timing, and immunosuppressive treatments before surgery between 2007 and 2017. RESULTS: A total of 3801 surgical cases were reported over 11 years. The prevalence of UC surgery decreased over the period studied. The rate of prednisolone (PSL) use did not change. The prevalence of both calcineurin inhibitors (CNIs) and anti-TNF agents increased during the period studied (p < 0.01). The prevalence of urgent/emergent surgery did not change. The most distinctive change in surgical indications was the increase in cancer/dysplasia (CAC), the prevalence of which increased from 20.2% in 2007 to 34.8%. CONCLUSION: The prevalence of UC surgery seems to be decreasing according to the increasing rate of anti-TNF agent and CNI administration. However, the indication of CAC significantly increased. Further research should evaluate whether or not long-term remission maintained with several agents can lead to increasing CAC.

Predictive value of myenteric and submucosal plexitis for postoperative Crohn's disease recurrence.

OBJECTIVES: To assess the predictive values of myenteric and submucosal plexitis for postoperative endoscopic recurrence of Crohn's disease (CD). METHODS: A retrospective study of CD patients who underwent intestinal resection between 1995 and 2013 in the Department of Surgery 2, Tokyo Women's Medical University was performed. Proximal resection margins were analyzed and plexitis was evaluated by counting the number of inflammatory cells in myenteric and submucosal plexuses. The sizes of the most severely inflamed ganglion (MIG) were measured. Multiple regression analysis was used to identify independent risk factors for postoperative endoscopic recurrence. RESULTS: Of the 51 included patients, 40 patients underwent colonoscopy after surgery. Endoscopic recurrence was observed in 21 patients (52.5%). Mean duration (±standard deviation) from surgery to recurrence was 49.7±34.7 months. Endoscopic recurrence rates at 1, 3, and 5 years were 5.0%, 24.1%, and 45.1%, respectively. Submucosal plexitis and myenteric plexitis were observed in 36 (90.0%) and 37 patients (92.5%), respectively. On multivariate analysis, initial intestinal resection, rate of plexitis <50%, size of the MIG in the myenteric plexus ≥867 µm2, and total number of inflammatory cells in the submucosal plexus ≥8 were independent risk factors for postoperative endoscopic recurrence. CONCLUSIONS: Pathological findings of proximal resection margins, especially submucosal plexitis and large sizes of myenteric plexus, are predictive of postoperative endoscopic recurrence in CD.

Factors affecting the quality of life of patients after gastrectomy as assessed using the newly developed PGSAS-45 scale: A nationwide multi-institutional study.

AIM: To identify certain clinical factors other than the type of gastrectomy which affect the postoperative quality of life (QOL) of patients after gastrectomy. METHODS: The postgastrectomy syndrome assessment scale (PGSAS)-45 was designed to assess the severity of symptoms, the living status and the QOL of gastrectomized patients. It consists of 45 items, of which 22 are original items while 23 were retrieved from the SF-8 and Gastrointestinal Symptoms Rating Scale questionnaires with permission. A nationwide surveillance study to validate PGSAS was conducted and 2368 gastric cancer patients who underwent various types of gastrectomy at 52 medical institutions were enrolled. Of these, 1777 patients who underwent total gastrectomy (TG) reconstructed with Roux-Y (n = 393), distal gastrectomy (DG) reconstructed with Billroth-I (n = 909), or DG reconstructed with Roux-Y (n = 475) were evaluated in the current study. The influence of the type of gastrectomy and other clinical factors such as age, sex, duration after surgery, the symptom severity, the degree of weight loss, dietary intake, and the ability for working on the postoperative QOL (i.e., dissatisfaction for daily life subscale, physical component summary and mental component summary of the SF-8) were examined by multiple regression analysis (MRA). In addition, importance of various symptoms such as esophageal reflux, abdominal pain, meal-related distress, indigestion, diarrhea, constipation and dumping on the postoperative living status and QOL were also appraised by MRA. RESULTS: The postoperative QOL were significantly deteriorated in patients who underwent TG compared to those after DG. However, the extent of gastrectomy was not an influential factor on patients' QOL when adjusted by the MRA. Among various clinical factors, the symptom severity, ability for working, and necessity for additional meals were the most influential factors to the postoperative QOL. As for the individual symptoms, meal-related distress, dumping, abdominal pain, and esophageal reflux significantly affected the postoperative QOL in that order, while the influence of indigestion, diarrhea and constipation was insignificant. CONCLUSION: Several clinical factors such as the symptom severity (especially in meal-related distress and dumping), ability for working and necessity for additional meals were the main factors which affected the patients' well-being after gastrectomy.

Current State of and Problems Related to Cancer of the Intestinal Tract Associated with Crohn's Disease in Japan.

BACKGROUND/AIM: Cancer of the intestinal tract (small and large intestine) associated with Crohn's disease has a low incidence but can be fatal if it develops. Thus, the key question is how to deal with this type of cancer. The current study surveyed major medical facilities that treat inflammatory bowel disease (IBD) surgically in Japan in order to examine the clinical features of cancer of the intestinal tract associated with Crohn's disease and explore ways to deal with this cancer in the future. PATIENTS AND METHODS: Sixteen major medical facilities that treat IBD surgically were surveyed regarding cancer of the intestinal tract associated with Crohn's disease. The medical facilities had treated 3,454 patients with Crohn's disease, 122 of whom had developed intestinal cancer. The medical facilities were surveyed regarding those 122 patients. RESULTS: The incidence of intestinal cancer associated with Crohn's disease has increased yearly. Cancer most often developed in the left side of the colon and, particularly, in the rectum and anal canal. Seventy-six percent of cases were diagnosed preoperatively, 4% were diagnosed intraoperatively, while the remaining 20% were diagnosed pathologically after surgery. The most prevalent histological type of cancer was mucinous carcinoma (50%). Forty-two percent of cancers were differentiated, with 4% being poorly differentiated. The surgical procedure performed most often (67%) was abdominoperineal resection. The 5-year survival rate by stage was 88% for Stage I, 68% for Stage II, 71% for Stage IIIa, 25% for Stage IIIb and 0% for Stage IV. Overall, the 5-year survival rate was 52%. CONCLUSION: Gastrointestinal (GI) cancer associated with Crohn's disease had an incidence of 3.5%, but also involved a poor prognosis with a 5-year survival rate of 52%. Early detection through surveillance is crucial to improving the prognosis for patients. However, surveillance of the intestinal tract with endoscopy or contrast studies is technically and diagnostically hampered by Crohn's disease and intestinal strictures. A biopsy of the anal canal, a common site of cancer, can readily be performed and constitutes the first step in surveillance.

Has widespread use of biologic and immunosuppressant therapy for ulcerative colitis affected surgical trends? Results of a questionnaire survey of surgical institutions in Japan.

PURPOSE: The aim of the study is to assess the relationship between the introduction of biologic and immunosuppressant therapy and the number of patients undergoing surgery for ulcerative colitis (UC). METHODS: A questionnaire survey about patients undergoing surgery for UC was sent to 26 teaching hospitals throughout Japan. The questionnaire period spanned from 2008 to 2013, to account for the introduction of tacrolimus (2009) and infliximab (2010). RESULTS: The total number of patients who underwent surgery was 297, 291, 273, 255, 300, and 305 in 2008, 2009, 2010, 2011 2012, and 2013, respectively. The emergency surgery rate remained stable at 32-34 % each year. The proportion of patients who underwent surgery for cancer increased from 13.8 % in 2008 to 20 % in 2013. In 2013, 41, 38, and 6 % of patients who underwent surgery had received treatment with a biologic, tacrolimus, and cyclosporine, respectively. No institution reported an increase in postoperative complications among patients treated with immunosuppressive drugs. CONCLUSIONS: The number of patients undergoing surgery decreased temporarily soon after infliximab and tacrolimus first became widely available, but subsequently increased again. The emergency surgery rate remained unchanged throughout the study period. These data show that immunosuppressive drugs have had little effect on the risk of postoperative complications.

Treatment strategy for preventing pouchitis as a postoperative complication of ulcerative colitis: the significance of the management of cuffitis.

PURPOSE: The aim of this study was to examine the risk factors for and to evaluate strategies for preventing pouchitis as a postoperative complication of ulcerative colitis (UC). METHODS: A total of 119 cases of UC in which restorative proctocolectomy with an ileal pouch-anal anastomosis (IPAA) was performed at our institution between 2000 and 2012 was investigated; nine patients in whom it was impossible to close the ileostomy due to an intractable anal fistula or pelvic abscess were excluded. RESULTS: The cumulative risk of developing pouchitis 5 years after IPAA with stoma closure was 31.0%. Significant relationships with pouchitis were found for the surgical indication (p = 0.0126) and surgical method (p = 0.0214). A significant correlation was found between pouchitis and cuffitis. Pouchitis was significantly more common in the cases with cuffitis than in those without (p = 0.0002). There was also a significantly different cumulative incidence observed between the cases with and without cuffitis (p < 0.0001). In addition, pouchitis had a greater tendency to recur in the cases with cuffitis than in those without (p = 0.2730). CONCLUSION: The cumulative incidence rate of pouchitis was 10.6% at 1 year, 15.1% at 2 years and 31.0% at 5 years. Controlling cuffitis is important to prevent pouchitis.

[Long-term outcomes of ileal pouch-anal canal anastomosis in children with ulcerative colitis].

The present study investigated the long-term outcomes of restorative proctocolectomy in pediatric patients with ulcerative colitis (UC). We report a series of 25 patients who underwent total proctocolectomy with ileal pouch-anal canal anastomosis (IACA). Surgery was performed for medically intractable colitis and severe colitis in 14 and 11 patients, respectively. Early and late complications were observed in 6 (24%) and 14 (56%) patients, respectively. The long-term quality of life outcomes were satisfactory, including both bowel function and social function. Growth retardation was observed in 6 patients. Five patients exhibited catch-up growth and 3 patients overcame growth retardation. Patients with growth retardation tended to have a younger onset and longer duration of UC, as well as a longer duration and higher total dose of steroid use. In conclusion, the long-term outcomes of pediatric patients with UC undergoing IACA are satisfactory. Furthermore, to minimize the risk of growth retardation, surgery should be performed without delay.

Colorectal small cell carcinoma in ulcerative colitis with identical rare p53 gene mutation to associated adenocarcinoma and dysplasia.

Colorectal small cell carcinomas (SCCs) are rare tumors and are infrequently associated with ulcerative colitis (UC). We report a case of primary rectal SCC combined with adenocarcinoma arising in left-sided UC. Immunohistochemically, tumor cells were positive for chromogranin A, synaptophysin, and CD56 in the SCC but not in the adenocarcinoma. The patient simultaneously developed multiple lesions of adenocarcinoma and high-grade dysplasia in the sigmoid colon and rectum. To elucidate whether SCC might evolve from multipotential cells in dysplasia and/or adenocarcinoma, we examined the mutational status of TP53 and KRAS. The same clonality of these lesions including SCC was confirmed by the presence of an identical single nucleotide point mutation in TP53. KRAS mutation was not observed in these lesions. Thus, these lesions seem to have developed from the same origin. Long-standing inflammation leading to dysplasia might be responsible for the development of some SCCs in UC particularly when they are combined with dysplasia and/or adenocarcinoma.