Predictive Factors of Surgical Recurrence in Patients with Crohn's Disease on Long-Term Follow-Up: A Focus on Histology.

In patients with Crohn's disease (CD) that underwent surgery, predictive factors of surgical recurrence have been only partially identified. The aim of our study was to identify potential factors associated with an increased risk of surgical recurrence. A monocentric retrospective observational study was conducted including patients diagnosed with CD, according to ECCO criteria who received their first ileocolic resection. Overall, 162 patients were enrolled in our study; 54 of them were excluded due to a lack of sufficient data. The median follow-up was 136.5 months, IQR 91.5−176.5, and the surgical recurrence rate after the median follow-up was 21.3%. In the multivariate analysis, an age ≤ 28 years at the first surgical resection (aHR = 16.44, p < 0.001), current smoking (aHR = 15.84, p < 0.001), female sex (aHR = 7.58, p < 0.001), presence of granulomas at local lymph nodes (aHR = 12.19, p < 0.001), and treatment with systemic corticosteroids after the first surgical resection (aHR = 7.52, p = 0.002) were factors significantly associated with a risk of surgical recurrence, while cryptitis resulted in a protective factor (aHR = 0.02, p < 0.001). In conclusion, the heterogeneous spectrum of factors associated to the risk of surgical recurrence in patients with CD that underwent ileocolic resection supports the need of a personalized follow-up taking into account different clinical, surgical, and histologic features.

The role of topical therapy for perianal fistulizing Crohn's disease: are we forgetting something?

INTRODUCTION: Rectal inflammation is the principal risk factor for the development of perianal fistulizing Crohn's disease. However, no topical therapy direct to rectal healing is discussed in European' guidelines. The aim of this systematic review was to evaluate the role of topical therapy in healing the rectal inflammation in Crohn's disease. EVIDENCE ACQUISITION: A MEDLINE search of all studies published in English until December 2018 was conducted. Articles were identified using the strings "Crohn's disease and topical therapy" or "perianal Crohn's disease and topical therapy." EVIDENCE SYNTHESIS: Contradictory results about the efficacy of topical metronidazole were present. No benefit from topical tacrolimus use was demonstrated. Mesalazine suppositories induced and maintained remission of rectal inflammation in 50% of patients with rectal Crohn's disease. Few data were available about the role of local therapy for the fistulous tract in Crohn's disease. Local mesenchymal stem cells therapy could be a promising new approach. CONCLUSIONS: Due to the disappoint success rate of current strategy in perianal fistulizing Crohn's disease, the role of rectal inflammation as a causative factor and the fair success rate of topical therapy with mesalazine suppositories in the healing of rectal inflammation without relevant side effects, more studies are advisable in this field.

Adnexal localization of Crohn’s disease and recurrent massive ovary cysts

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"Small is beautiful" A series of ileo-anal anastomoses performed with the 25 - mm circular stapler.

AIM: With the idea that a small diameter stapler should cause less sphincter trauma, we began to use the 25mm circular stapler to perform ileo-pouch-anal anastomosis (IPAA) and we report our experience. MATERIAL OF STUDY: A retrospective study using a bowel function questionnaire and a quality of life questionnaire has been conducted on a group of patients who underwent IPAA using a 25mm stapler RESULTS: We performed IPAA using a 25mm circular stapler in 37 patients. Postoperative mortality was nil and morbidity was 27%. One anastomotic stenosis occurred. Long term follow-up information was available on 28 patients. Mean follow-up was 70 months (range 8-177). Mean number of bowel movements was 4.5 (range 2-10, median 4.5) during the day and 0.9 (range 0-10, median 0) at night. Out of 28 patients, 19 (68%) were fully continent and 32% had occasional soiling, no one reported incontinence. All patients except one were able to withold their stool for more than 15 minutes. Daytime pad use was: never 86%, occasionally 3%, frequently 11%; nightime pas use was never 86%, occasionally 7% and frequently 7%. Bowel regulating drugs use was never 82%, occasionally 14%, regularly 4%. Evacuation difficulties were: never 75%, occasionally 21%, frequently 4%. DISCUSSION: Our results compare favourably with the literature, which reports median bowel frequency 6-7.6/24h, 9.4- 33% urgency, 17-44% daytime soiling and 32-61% nighttime soiling. CONCLUSIONS: Our results must be considered preliminary but we found the 25-mm stapler safe and adequate to perform IPAA. KEY WORDS: IPAA, Ulcerative Colitis, Stapler, Function.

Adnexal localization of Crohn's disease and recurrent massive ovary cysts.

In a recent interesting case report, Saborit et al. reported three cases of ovarian involvement in Crohn's disease (CD). In the first two cases, there were pelvic abscesses due to fistulae of ileal loops affected by CD, with involvement of the right ovary, which also showed abscesses and typical granulomas. In the third case there was an ovarian abscess, extension of the process by contiguity. Granulomatous affectation of the ovaries is rare, with only 18 cases reported in the literature to date. Of this, in 17 cases the proposed mechanism of disease manifestation is direct fistulization between the small intestine and the ovary, which allows passage of vegetable material and results in the formation of reactive granulomas. In only one case a patient that did not demonstrate the histological features of either fistula-related disease (an intact ovarian capsule was found) or idiopathic granulomatous disease caused by the multiplicity of the granulomas and the presence of central necrosis has been reported. The authors therefore suggested that their findings were consistent with a diagnosis of metastatic CD of the ovary.

Prevalence and prognostic value of hepatic histological alterations in patients with Crohn's disease.

UNLABELLED: Variable degrees of liver histological changes in patients with Crohn's disease (CD) have been reported. OBJECTIVE: To evaluate the liver histological alterations and their prognostic significance in patients affected by CD without abnormalities of liver biochemical parameters and ultrasound features. MATERIAL AND METHODS: A prospective, single-blind study, including 35 consecutive patients with CD that underwent bowel resection with a contemporary performance of liver biopsy from 1992 to 2003. EXCLUSION CRITERIA: the presence of standard causes of liver disease, such as alcohol consumption exceeding 20 g/day, primary sclerosing cholangitis, viral infections, celiac disease, metabolic syndrome and alterations of the metabolism. Patients were followed up with regular evaluation of hepatic cytolysis, cholestasis, synthesis and ultrasound performance. After a mean interval of 14 years (from May to December 2013), liver fibrosis was assessed by Fibroscan®. RESULTS: Histological alterations were shown in 60% of patients, without serious liver injuries (no case of inflammation or significant fibrosis). Fibroscan® was performed in 33 subjects and no significant changes were observed (mean value of liver stiffness: 5.2 ± 1.2 kPa). The minimal microscopic damage did not evolve either in patients with a normal histology or in those with an altered histology at baseline (p = 0.9). Only patients who took azathioprine had a statistically significant increase of liver stiffness values (5.7 ± 1.5 kPa vs 4.7 ± 1.3 kPa, p = 0.017). CONCLUSIONS: Patients with CD do not need additional examinations compared to the general population, unless clinical or biochemical abnormalities are found.

Glucose breath test and Crohn's disease: Diagnosis of small intestinal bacterial overgrowth and evaluation of therapeutic response.

OBJECTIVE: Small intestinal bacterial overgrowth (SIBO) is characterized by an abnormal proliferation of bacterial species in the small bowel. It has been shown that patients with Crohn's disease (CD) have a higher risk of SIBO development. The aim of the present study was to investigate SIBO prevalence in CD patients, possible clinical predictors of SIBO development and response to antibiotic therapy. MATERIAL AND METHODS: Sixty-eight patients (42 male, 26 female; mean age 49.3 ± 12.8 years) with CD reporting abdominal complaints were prospectively evaluated for SIBO with H2/CH4 glucose breath test (GBT). RESULTS: Of the 68 patients enrolled, 18 (26.5%) tested positive for SIBO. Patients with SIBO exhibited increased stool frequency and significant reduction of stool solidity (p = 0.014), were older than patients tested negative to GBT (54.3 ± 13.0 years vs. 47.5 ± 12.3 years, p = 0.049), reported a longer history of CD (21.2 ± 10.3 years vs. 15.7 ± 10.2 years, p = 0.031) and showed a significant higher frequency of prior surgery (p = 0.001), revealing an association of number of surgical procedures (OR = 2.8315, 95% CI = 1.1525-6.9569, p = 0.023) with SIBO. Breath test normalization occurred in 13/15 patients evaluated after antibiotic and probiotic therapy. Although vitamin B12 levels were lower in patients with SIBO (p = 0.045) and a significant improvement was found after treatment (p = 0.011), this could be due to the heterogeneity, regarding vitamin B12 treatment, in our cohort. CONCLUSION: SIBO is a frequent but underestimated condition in CD, which often mimics acute flare, effectively identified with GBT and could be treated with a combined antibiotic and probiotic therapy.

Power Doppler sonography to predict the risk of surgical recurrence of Crohn's disease.

PURPOSE: The aim of this work is to investigate the role of power Doppler sonography as an additional predictor of surgical recurrence in Crohn's disease. METHODS: A sample of 33 patients, with ileal or ileocolonic Crohn's disease, that had underwent intestinal resection, were retrospectively enrolled. All patients had bowel ultrasonography 7-16 months after resection. Power Doppler sonography of the preanastomotic ileum was evaluated as a possible prognostication tool to assess the risk of long-term need for reoperation. RESULTS: The absolute incidence of surgical recurrence in those who had a positive power Doppler was 42 %, while that of those who had a negative power Doppler was 28.6 %. Combining the power Doppler with bowel wall thickness, the surgical recurrence risk grew from 41.2 % of those with a positive power Doppler and thickness >3 mm to 55.6 % of those with a positive power Doppler and thickness >6 mm. CONCLUSIONS: Power Doppler look to be another useful prediction tool for the personalization of patient's care. It could be useful to perform power Doppler in all patients with a wall thickness >5 mm: for those who have a positive power Doppler it may be indicated as a more aggressive prophylactic therapy.

Unusual Presentation of Recurrent Early Stage Endometrial Carcinoma 28 Years after Primary Surgery.

Endometrial carcinoma is the most common neoplasia of female genital tract. The prognosis of early stage disease (FIGO I and FIGO II) is excellent: recurrence after surgery is less than 15%, most of which are reported within 3 years after primary treatment. Herein we report a case of late rectal recurrence from FIGO Ib endometrial adenocarcinoma. Patient had also familiar and personal history of colonic adenocarcinoma and previous findings of microsatellite instability (MSI); molecular analysis evidenced heterozygotic somatic mutation in MLH1 gene. Twenty-eight years after hysterectomy and bilateral salpingoovariectomy, a rectal wall mass was detected during routine colonoscopy. Patients underwent CT scan, pelvic MRI, and rectal EUS with FNA: histopathological and immunohistochemical analysis revealed differentiated carcinoma cells of endometrial origin. No neoadjuvant treatment was planned and low rectal anterior resection with protective colostomy was performed; histology confirmed rectal lesion as metastasis from endometrial carcinoma. Recurrence of early stage endometrial carcinoma after a long period from primary surgery is possible. It is important to keep in mind this possibility in order to set a correct diagnostic and therapeutic algorithm, including preoperative immunohistochemical staining, and to plan a prolonged follow-up program.

Role of bowel ultrasound as a predictor of surgical recurrence of Crohn's disease.

BACKGROUND: In Crohn's disease natural history, about 80% of the patients require surgery, which is not curative: unfortunately, the disease recurs in many patients. OBJECTIVE: To investigate the role of intestinal ultrasound to predict the risk of post-operative surgical recurrence in Crohn's disease. MATERIAL AND METHODS: A total of 196 patients, with ileal or ileocolonic Crohn's disease, undergoing intestinal resection, were retrospectively enrolled. All patients underwent bowel ultrasonography 6-15 months after resection. Wall thickness at the anastomosis level was measured, and thickening >3 mm was evaluated as risk factor of long-term need for reoperation. RESULTS: Patients who have a bowel wall thickness >3 mm have an risk ratio (RR) of surgical recurrence = 2.1 [95% confidence interval (CI) = 1.12-3.74] higher than those with a thickness of ≤3 mm. The absolute incidence of new surgical intervention is 13% in patients with thickness of 3 mm, 28% in patients with thickness >3 mm, 29,1% with thickness >4 mm, 34% with thickness >5 mm, and 40% with thickness >6 mm. CONCLUSIONS: Bowel wall thickness >3 mm at ultrasound may be a non-invasive predictor of early surgical recurrence after ileo-colonic resection.

Side-to-side stapled anastomosis strongly reduces anastomotic leak rates in Crohn's disease surgery.

PURPOSE: Anastomotic configuration may influence anastomotic leak rates. The aim of this study was to determine whether a side-to-side stapled ileocolonic anastomosis produces lower anastomotic leak rates than those with a handsewn end-to-end ileocolonic anastomosis after ileocecal or ileocolonic resection for Crohn's disease. METHODS: A series of 122 consecutive patients underwent elective ileocecal or ileocolonic resection with ileocolonic anastomosis for Crohn's disease from January 1998 to June 2003: 71 had handsewn end-to-end anastomosis and 51 had side-to-side stapled anastomosis. The choice between the two anastomoses was left to the surgeon's preference. A retrospective analysis was performed to assess if there was any difference in anastomotic leak rates. RESULTS: The two groups were comparable in terms of age, gender, preoperative presence of abscess or fistula, history of smoking, and albumin levels. More patients were taking steroids in the handsewn group than in the stapled group. In the handsewn group there were 10 anastomotic leaks (14.1 percent) and in the stapled group there was 1 anastomotic leak (2.0 percent) (risk difference, +12.1 percent; 95 percent confidence interval, 1.7-22.2; P = 0.02). Anastomotic configuration was the sole variable that influenced anastomotic leak rates at univariate analysis. Mortality was 1.4 percent in the handsewn group and 0 percent in the stapled group. Complications other than anastomotic leak developed in 11 patients in the hand-sewn group and in 6 patients in the stapled group. Mean postoperative hospital stay was 12.3 days in the handsewn group and 9.7 days in the stapled group (P = 0.03). Excluding those patients who had an anastomotic leak, the difference was still present (handsewn group, 10.1 days; stapled group, 9.1 days; P = 0.04). CONCLUSION: Although confirmation from randomized, controlled trials is required, side-to-side stapled anastomosis seems to substantially decrease anastomotic leak rates in surgical patients with Crohn's disease, compared with handsewn end-to-end anastomosis. Postoperative hospital stay decreased in the stapled anastomosis group, and this was not entirely a result of decreased anastomotic leak rates.