Subcutaneous incision of the fistula tract and internal sphincterotomy (SIFT-IS): a novel surgical procedure for transsphincteric anal fistula.

AIM: The aetiology of anal fistula has not been fully clarified. One of the causes of anal fistulas may be the markedly deep crypts that characterize the primary openings. We developed subcutaneous incision of the fistula tract and internal sphincterotomy (SIFT-IS) to eradicate these deep crypts. The aim of this study was to evaluate outcomes in patients with anal fistula treated with SIFT-IS. METHOD: A retrospective study was performed over a 2-year period. Patients with transsphincteric anal fistula who underwent SIFT-IS were enrolled. The primary endpoint was the anal fistula healing rate at 16 weeks postoperatively. The secondary endpoints were healing time, postoperative complications and clinical continence status. RESULTS: One hundred and fifty one patients were enrolled. Primary healing was accomplished in 129 patients (85%). There were 17 patients (11%) with a remnant fistula and five (3%) with a recurrence. The remnant fistulas healed spontaneously at more than 16 weeks postoperatively in seven patients. The median healing time was 6 (3-96) weeks. Surgical intervention was required in seven patients with a remnant fistula and four with recurrence. At the final follow-up, the wounds had healed in 148 patients (98%). No significant postoperative complications or incontinence were observed. CONCLUSION: Subcutaneous incision of the fistula tract and internal sphincterotomy is a promising surgical option for transsphincteric anal fistulas, with a satisfactory healing rate.

Adenocarcinoma within anorectal fistulae: different clinicopathological characteristics between Crohn's disease-associated type and the usual type.

Adenocarcinoma within anorectal fistulae is rare and is sometimes associated with Crohn's disease. Crohn's disease-associated adenocarcinoma within anorectal fistulae has a poor prognosis; however, little is known about the clinicopathological differences between Crohn's disease-associated adenocarcinoma within anorectal fistulae and usual adenocarcinoma within anorectal fistulae. We retrospectively searched patients' charts and pathology archives at Tokyo Yamate Medical Center and Tokyo Medical and Dental University Hospital for adenocarcinoma within anorectal fistulae. Clinical and pathological data were collected and immunohistochemical examinations were conducted. Overall survival rate was estimated using the Kaplan-Meier method. Prognostic factors of overall survival were assessed using univariate and multivariate Cox regression analyses. We examined 82 cases of adenocarcinoma within anorectal fistulae. Fifty-nine of 82 cases (72%) had usual adenocarcinoma within anorectal fistulae, while the remaining 23 cases (28%) had Crohn's disease-associated adenocarcinoma within anorectal fistulae. Patients with Crohn's disease-associated adenocarcinoma within anorectal fistulae were diagnosed at a younger age and at a more advanced stage than those with usual adenocarcinoma within anorectal fistulae. Macroscopic and histological types were also different between usual adenocarcinoma within anorectal fistulae and Crohn's disease-associated adenocarcinoma within anorectal fistulae. Crohn's disease-associated adenocarcinoma within anorectal fistulae included more ulcerative types and high-grade adenocarcinomas. The rate of lymphovascular invasion was higher in Crohn's disease-associated adenocarcinoma within anorectal fistulae. Immunohistochemically, the expression of E-cadherin, p53, and MUC5AC differed between usual adenocarcinoma within anorectal fistulae and Crohn's disease-associated adenocarcinoma within anorectal fistulae. Patients with Crohn's disease-associated adenocarcinoma within anorectal fistulae exhibited worse overall survival than those with usual adenocarcinoma within anorectal fistulae, and vascular invasion was the strongest significant independent predictor of overall survival in patients with adenocarcinoma within anorectal fistulae. In conclusion, usual adenocarcinoma within anorectal fistulae and Crohn's disease-associated adenocarcinoma within anorectal fistulae have different clinicopathological characteristics and should be considered separate clinical entities.

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.

Daikenchuto, a traditional Japanese herbal medicine, for the maintenance of surgically induced remission in patients with Crohn's disease: a retrospective analysis of 258 patients.

PURPOSE: Despite numerous studies, the best postoperative therapy for Crohn's disease is still undefined. We retrospectively evaluated the effects of postoperative maintenance therapy with daikenchuto, a traditional Japanese Kampo medicine, on the reoperation rate at 3 years in patients with Crohn's disease. METHODS: A total of 258 patients who underwent surgery for Crohn's disease were identified for the study. For the prevention of postoperative recurrence, patients were stratified to receive 5-aminosalicylic acid, azathioprine or daikenchuto, and their effects on preventing reoperation at 3 years were evaluated. RESULTS: Of the 258 patients, 44 required reoperation with intestinal resection within 3 years due to disease recurrence. The 3-year reoperation rate was significantly lower in the postoperative daikenchuto group than in the non-daikenchuto group (11.3 vs. 24.5 %, P = 0.01), and was similarly significantly lower in the postoperative 5-aminosalicylic acid group than in the non-5-aminosalicylic acid group (14.8 vs. 29.6 %, P = 0.0049). A multivariate Cox analysis showed that postoperative daikenchuto (P = 0.035) and postoperative 5-aminosalicylic acid (P = 0.022) were significantly and independently associated with the rate of reoperation at 3 years in patients with Crohn's disease. CONCLUSION: We propose that continuous daikenchuto therapy is a clinically useful and feasible maintenance therapy for the prevention of postoperative reoperation in patients with Crohn's disease.

Risk factors for postoperative intra-abdominal septic complications after bowel resection in patients with Crohn's disease.

BACKGROUND: Postoperative intra-abdominal septic complications are a serious concern with regard to postoperative morbidity and mortality in Crohn's disease. OBJECTIVE: The aim of this study was to identify the clinical variables that potentially impact the risk of intra-abdominal septic complications in patients with Crohn's disease, as well al analyze the short-term prognosis in patients with postoperative intra-abdominal septic complications. DESIGN: This study is a retrospective review with the use of hospital medical records. SETTINGS: This investigation was conducted at a single-institution, tertiary referral center in Tokyo, Japan. PATIENTS: We reviewed 550 patients that had undergone 728 intestinal anastomoses during 633 operations for primary or recurrent Crohn's disease between January 2005 and December 2010. Postoperative intra-abdominal septic complications were defined as anastomotic leakage or intra-abdominal abscesses occurring within 1 month after surgery. MAIN OUTCOME MEASURE: Twenty-four clinical variables were evaluated as potential risk factors for postoperative intra-abdominal septic complications. These factors were analyzed by use of univariate and multivariate methods. RESULTS: Postoperative intra-abdominal septic complications occurred in 17 cases (2.7%), with no fatalities. Of the 17 patients, 13 had anastomotic leakage and 4 had intra-abdominal abscesses. In the univariate and multivariate analyses, penetrating type (p = 0.014), operation time >180 minutes (p = 0.004), and handsewn anastomoses (p = 0.005) were significantly independent risk factors for postoperative intra-abdominal septic complications. Patients experiencing intra-abdominal septic complications had significantly higher 1-year reoperation rates (41.2%) than patients without intra-abdominal septic complications (2.3%, p < 0.0001). LIMITATIONS: This study was limited by being a retrospective review, and the details regarding postoperative complications other than intra-abdominal septic complications were not completely available. CONCLUSIONS: Penetrating type, operation time >180 minutes, and handsewn anastomoses significantly increased the risk of postoperative intra-abdominal septic complications in Crohn's disease. Postoperative intra-abdominal septic complications had a negative influence on the short-term outcome in Crohn's disease.

Asymptomatic colonic intussusception in ulcerative colitis: a case report.

Intussusception in adults is, especially with ulcerative colitis (UC), rare and only described in a few cases. Most adult patients with intussusception develop abdominal pain or other symptoms of bowel obstruction. This case describes an 18-year-old male with UC who treated with 5-aminosalycilicacid and underwent annual screening colonoscopies. Two attempts revealed that it was impossible to achieve total surveillance through the colonoscopy because multiple polyps were preventing the colonoscope from traversing the entire colon. Therefore, CT scan was performed and colonic intussusception was discovered incidentally, and the patient underwent elective laparoscopic total colectomy. To the best of our knowledge, this is the first reported case of asymptomatic intussusception in the adult patient with UC. When total surveillance colonoscopy fails to yield results, a CT may be advisable to pick up such an asymptomatic intussusception.

Epithelioid Cell Granulomas in Crohn's Disease Are Differentially Associated With Blood Vessels and Lymphatic Vessels: A Sequential Double Immunostaining Study.

Crohn's disease (CD) is a gastrointestinal disorder of unknown etiology. CD-specific longitudinal ulcers show an association between disease pathogenesis and vasculature dysfunction. Granulomatous lymphangitis may also contribute to CD pathogenesis; meanwhile, vasculitis is the primary CD lesion. We investigated the association between granulomas and lymphatic and blood vessels to assess the role of vasculature in CD pathogenesis. Two small and large intestine specimens were obtained from four CD patients. From each specimen, 160 sequential sections were obtained and double immunohistochemical stained to label lymphatic and blood vessels in association with granulomas. We found that 289 of 342 granulomas (85%) were associated with a lymphatic vessel and 313 of 364 granulomas (86%) were associated with a blood vessel. Although intrablood vessel granulomas were not detected, intralymphatic vessel granulomas were. In the internal region of the granuloma, we found more blood vessels than lymphatic vessels. Hence, these results cumulatively demonstrate that CD epithelioid cell granulomas are differentially associated with lymphatic and blood vessels, suggesting both as essential for the formation and maintenance of these granulomas. Moreover, both lymphatic and blood vessels may participate in granulomatous inflammation in the primary CD lesions; however, additional studies with larger numbers of participants are required to validate our findings.

Distribution of Human Papillomavirus Genotype in Anal Condyloma Acuminatum Among Japanese Men: The Higher Prevalence of High Risk Human Papillomavirus in Men Who Have Sex with Men with HIV Infection.

Human papillomavirus (HPV) infection is known to cause anal condyloma acuminatum (CA) and squamous cell carcinoma. Men who have sex with men (MSM) with HIV infection are frequently co-infected with HPV, especially high risk HPV (HR-HPV) that causes anal squamous cell carcinoma. However, there are few reports of HPV genotype studies in anal lesion of Japanese men. We tried to estimate the distribution of HPV genotypes in anal CA tissue specimens from the Japanese men to elucidate the risk of anal cancer. A total of 62 patients who had anal CA surgically excised were enrolled. They included 27 HIV-positive MSM, 18 HIV-negative MSM, 1 HIV-positive man who have sex with women (MSW), and 16 HIV-negative MSW. HPV genotypes in anal CA tissue were determined by the polymerase chain reaction technique with reverse line blot hybridization. HR-HPV was detected in 45.2% of the CA tissue specimens and high grade squamous intraepithelial lesion (HSIL) was observed in 15.3%. Moreover, the prevalence of HR-HPV in the HIV-positive MSM (70.4%) was higher than the HIV-negative MSM (33.3%, p = .0311) or the HIV-negative MSW (18.8%, p = .0016). The conditional logistic regression analysis suggested HIV positivity as the primary risk factor for the HR-HPV infection in CA. In addition, HSIL was detected in higher frequency in CA tissues from HIV-positive MSM (25.9%) than HIV-negative MSW (0.0%, p = .0346). HR-HPV and HSIL were frequently detected in anal CA tissues from Japanese MSM patients with HIV infection, suggesting the necessity of surveillance for this population.

Cross-talk between RORγt+ innate lymphoid cells and intestinal macrophages induces mucosal IL-22 production in Crohn's disease.

BACKGROUND: Interleukin (IL)-22-producing RORγt innate lymphoid cells (ILCs) play a pivotal role in intestinal immunity. Recent reports demonstrated that ILCs contribute to mucosal protection and intestinal inflammation in mice. In humans, numbers of RORγt ILCs are significantly increased in the intestine of patients with Crohn's disease (CD), suggesting that ILCs may be associated with intestinal inflammation in CD. However, the mechanism by which ILCs are regulated in the intestine of patients with CD is poorly understood. This study aimed to determine the activation mechanism of intestinal ILCs in patients with CD. METHODS: CD45 lineage marker ILCs were isolated from intestinal lamina propria of patients with CD. ILCs were then subdivided into 4 distinct populations based on the expression of CD56 and CD127. Purified ILC subsets were cocultured with intestinal CD14 macrophages, and IL-22 production was evaluated. RESULTS: CD127CD56 and CD127CD56 ILC, but not CD127CD56 or CD127CD56 ILC, subsets expressed RORγt and produced IL-22. IL-22 production by these ILC subsets was enhanced when ILCs were cocultured with intestinal macrophages. IL-23 or cell-to-cell contact was required for macrophage-mediated activation of ILCs. IL-22 production by ILCs was perturbed in inflamed mucosa compared with noninflamed mucosa. IL-22 induced the expression of Reg1α and Claudin-1 in human intestinal epithelial organoids. CONCLUSIONS: RORγt ILCs might enhance mucosal barrier function through the upregulation of Reg1α through production of IL-22. Although CD14 macrophages augment intestinal inflammation in patients with CD, macrophages also promote a negative feedback pathway through the activation of IL-22 production by RORγt ILCs.

Immunohistochemical analysis of chromogranin A and p53 expressions in ulcerative colitis-associated neoplasia: neuroendocrine differentiation as an early event in the colitis-neoplasia sequence.

Pancellular dysplasia involving neuroendocrine cells has been shown to be comparatively rare but crucially implicated in the development of neuroendocrine tumors in ulcerative colitis (UC). We attempted to clarify the prevalence of chromogranin A expression as a marker of neuroendocrine differentiation in UC-associated neoplasia by immunohistochemical analyses of 26 lesions of low-grade dysplasia (LGD), 32 high-grade dysplasias (HGDs) and 27 invasive cancers (INVs), along with p53 expression. We additionally assessed the utility of these proteins for differential diagnosis between LGD and HGD. Chromogranin A was considered positive when immunoreactive cells were more than 5% of neoplastic lesions, and the positivity tended to be higher in HGDs (57.7%) or INVs (46.7%) than LGDs (32.0%). Focal or diffuse nuclear staining for p53 was defined as positive. The positive rate for p53 was also higher in HGDs (59.4%; P = 0.037) or INVs (59.3%) than LGDs (30.8%). A similar trend was found in co-positivity for both proteins (HGDs, 30.7%/INVs, 26.7% versus LGDs, 12.0%). No positivity for both proteins was identified in the non-neoplastic mucosa. The combination of the two proteins improved the sensitivity (66.7%), specificity (80.0%), positive predictive value (72.7%) and negative predictive value (75.0%) for HGD as compared to p53 alone (sensitivity, 57.7%; specificity 68.0%; positive predictive value, 65.2%; negative predictive value, 60.7%). In conclusion, we show here that neuroendocrine differentiation is relatively common and represents an early event in the UC-neoplasia pathway in which p53 and chromogranin A are coordinately up-regulated. Immunohistochemical assessment of their expression might provide a useful adjunct tool for grading dysplasia in UC.

Free-breathing diffusion-weighted imaging for the assessment of inflammatory activity in Crohn's disease.

PURPOSE: To investigate the application of free-breathing diffusion-weighted MR imaging (DWI) to the assessment of disease activity in Crohn's disease. MATERIALS AND METHODS: Thirty-one patients with Crohn's disease were investigated using free-breathing DWI without special patient preparation or IV or intraluminal contrast agent. The bowel was divided into seven segments, and disease activity was assessed visually on DWI. For quantitative analysis, the apparent diffusion coefficient (ADC) was measured in each segment. The findings of a conventional barium study or surgery were regarded as the gold standard for evaluating the diagnostic ability of DWI to assess disease activity. RESULTS: Upon visual assessment, the sensitivity, specificity, and accuracy for the detection of disease-active segments were 86.0, 81.4, and 82.4%, respectively. In the quantitative assessment, the ADC value in the disease-active area was lower than that in disease-inactive area in small and large bowels (1.61 +/- 0.44 x 10(-3) mm(2)/s versus 2.56 +/- 0.51 x 10(-3) mm(2)/s in small bowel and 1.52 +/- 0.43 x 10(-3) mm(2)/s versus 2.31 +/- 0.59 x 10(-3) mm(2)/s in large bowel, respectively, P<0.001). CONCLUSION: Free-breathing DWI is useful in the assessment of Crohn's disease. The accuracy of DWI is high in evaluating disease activity, especially in the small bowel, and the ADC may facilitate quantitative analysis of disease activity.

Enterocele: what is the clinical implication?

PURPOSE: Because of the rarity of diagnosis, the clinical implication of enterocele remains unclear. This study was designed to clarify the characteristic symptoms and the role of surgical treatment for enterocele. METHODS: We reviewed a defecography database prospectively maintained from 1998 to 2004. Defecography was performed with oral barium to opacify the small bowel in all patients. Enterocele was defined as the small bowel falling down beyond the level of the vaginal vault practically, it was <3 cm from the anorectal angle in the lateral view. Patients' clinical information was collected using a questionnaire. Patients with intractable symptoms underwent surgical repair. RESULTS: Among 912 patients on defecography, 104 patients (11 percent) revealed an enterocele (18 males mean age, 63 (range, 21-86) years). Concomitant abnormal findings, such as perineal descent, rectocele, and rectal intussusception, were encountered in 79 patients (76 percent). Only 25 patients (24 percent) had isolated enteroceles. Characteristic symptoms were difficulty emptying (61 patients), postevacuation discomfort (54 patients), and pelvic pain (28 patients). Eleven patients (10 females) underwent Douglas' pouch repair. Three of the 11 patients reported complete resolution of pelvic pain. The remaining eight patients experienced reduced symptoms, mainly resolution of pelvic heaviness, but still had difficulty emptying or postevacuation discomfort. CONCLUSIONS: This study suggests that the characteristic symptoms of enterocele are: difficulty emptying, postevacuation discomfort, and pelvic pain or heaviness. Selected patients with pelvic pain rather than obstructed defecatory symptoms might benefit from surgical repair.