Management and outcomes of surgical patients with intestinal Behçet's disease and Crohn's disease in southwest China.

BACKGROUND: Gastrointestinal involvement in Behçet's disease (GIBD) and Crohn's disease (CD) are inflammatory diseases sharing a considerable number of similarities. However, different from CD, the operative and postoperative management of GIBD remains largely empirical because of the lack of comprehensive treatment guidelines. AIM: To compare surgical patients with GIBD and those with CD in a medical center and identify notable clinical features and effective postoperative treatment for surgical patients with GIBD. METHODS: We searched patients diagnosed with CD and GIBD who underwent operations for gastrointestinal complications from 2009 to 2015 at West China Hospital of Sichuan University. A total of 10 surgical patients with GIBD and 106 surgical patients with CD were recruited. Information including demographic data, medication, and operative and postoperative parameters were collected and analyzed. As the incidence of surgical GIBD is low, their detailed medical records were reviewed and compared to previous studies. Moreover, the prognoses of CD and GIBD were evaluated respectively between groups treated with biological and non-biological agents. RESULTS: Indication for first surgery was often acute intestinal perforation for GIBD patients (7/10 vs 0/106, P < 0.001), whereas intestinal fistulae (0/10 vs 44/106, P = 0.013) and ileus (0/10 vs 40/106, P = 0.015) were the indications for surgical CD patients. Approximately 40% of patients with GIBD and 23.6% of patients with CD developed postoperative complications, 50% of patients with GIBD and 38.7% of patients with CD had recurrence postoperatively, and 40% (4/10) of patients with GIBD and 26.4% (28/106) of patients with CD underwent reoperations. The average period of postoperative recurrence was 7.87 mo in patients with Behçet's disease (BD) and 10.43 mo in patients with CD, whereas the mean duration from first surgery to reoperation was 5.75 mo in BD patients and 18.04 mo in CD patients. Surgical patients with GIBD more often used corticosteroids (6/10 vs 7/106, P < 0.001) and thalidomide (7/10 vs 9/106, P < 0.001) postoperatively, whereas surgical patients with CD often used infliximab (27/106), azathioprine, or 6-mercaptopurine (74/106) for maintenance therapy. CONCLUSION: Patients suffering GIBD require surgery mostly under emergency situations, which may be more susceptible to recurrence and reoperation and need more aggressive postoperative treatment than patients with CD.

Clinicopathologic features of Good's syndrome: Two cases and literature review.

BACKGROUND: Good's syndrome (GS) is an immunodeficiency disease, causing thymoma, low or absent B-cells, hypogammaglobulinemia, and defects in cell-mediated immunity. The most common clinical presentation is recurrent infection, followed by refractory diarrhea, due to the immunodeficiency. However, there are only few reports on intestinal endoscopy and pathology. CASE SUMMARY: We report here two typical GS cases with diarrhea as the prominent manifestation. Both cases presented with thymoma combined with immunodeficiency, characterized by hypogammaglobulinemia, low or absent B lymphocytes, and decreased T-cells with inverted CD4+/CD8+ T-cell ratio, while two GS patients were evaluated by endoscopy revealed mucosal edema and fine-granular or nodular appearance changes in the small intestine. Histological examination showed chronic inflammation and villous atrophy. A very interesting finding is that the inflammatory cell infiltration in the two GS cases was different. In one case, predominantly CD138+ plasma cells with only scattered CD3+ T-cells infiltration were revealed, while in another, it showed predominantly T-cells infiltration without plasma cells in the lamina propria. Although GS cases shared various clinical characteristics with common variable immunodeficiency (CVID) cases, they still differed from CVID cases in terms of its late onset, lack of familial clusters, low or absent peripheral blood B lymphocytes, absence of lymphoid hyperplasia, and plasma cells infiltration in the lamina propria in some patients. Although both patients had been diagnosed previously with recurrent diarrhea, respiratory infection, and thymoma, the association between these conditions and the possibility of GS was not recognized. The patients had remained misdiagnosed for 2 and 4 years, respectively, even after receiving the diagnosis of thymoma. The rarity of GS was likely the primary cause for the lack of disease recognition. Reporting of these cases will help to alert clinicians and raise awareness of this disease. CONCLUSION: GS should be considered among the differential diagnoses for patients with unexplained recurrent diarrhea and opportunistic infection. Although it was regarded as a subset of CVID with thymoma, GS had a different clinical-pathological feature from CVID.

Chromoendoscopy with targeted biopsies is superior to white-light endoscopy for the long-term follow-up detection of dysplasia in ulcerative colitis patients: a multicenter randomized-controlled trial.

BACKGROUND: Data from single-center experience or small sample-sized studies have shown that chromoendoscopy (CE) might be superior to white-light endoscopy (WLE) for dysplasia surveillance in ulcerative colitis (UC) patients. We performed a prospective randomized trial with a long-term follow-up to compare the detection rate of dysplasia among WLE with targeted biopsies (WLT), WLE with random biopsies (WLR), and dye-based CE with targeted biopsies (CET) in UC patients. METHODS: Patients with long-standing UC were enrolled from 11 medical centers from March 2012 to December 2013 and randomized into three arms (WLT, WLR, and CET). Only high-definition endoscopy was used in all three groups. The patients were followed up by annual endoscopy with biopsies through December 2017. RESULTS: With a median follow-up time of 55 months, a total of 122 patients with 447 colonoscopies were finally analysed in the per-protocol set: WLT (n = 43), WLR (n = 40), and CET (n = 39). A total of 34 dysplastic lesions were found in 29 colonoscopies of 21 patients. WLR and CET could identify more colonoscopies that diagnosed dysplasia than WLT (8.1% and 9.7% vs 1.9%; P = 0.014 and 0.004, respectively). WLR obtained more biopsied samples than WLT and CET (16.4 ± 5.1 vs 4.3 ± 1.4 and 4.3 ± 1.4; both P < 0.001). During the second half of the follow-up (37 - 69 months), CET could identify more colonoscopies that diagnosed dysplasia than WLT (13.3% vs 1.6%, P = 0.015) and showed a trend for increasing the detection rate compared with WLR (13.3% vs 4.9%, P = 0.107). CONCLUSIONS: For a better outcome of cancer/dysplasia surveillance in patients with long-standing UC, CET appeared to be more effective than WLT and less tedious than WLR. CET was found to be particularly useful when a long-term (>3 years) follow-up was conducted for dysplasia surveillance. The trial was registered on www.chictr.org.cn (ChiCTR1900023689).

Chinese research into severe ulcerative colitis has increased in quantity and complexity.

AIM: To investigate the current state of research output from Chinese studies into severe ulcerative colitis (SUC) using a bibliometric analysis of publications. METHODS: The contents of the Chinese periodical databases WANFANG, VIP, and China National Knowledge Infrastructure were searched for all papers regarding UC or SUC published in last the 15 years (from 2001 to 2015). The number of publications in each year was recorded to assess the temporal trends of research output. All SUC related publications were downloaded and the complexity of this research was evaluated with methods described previously. The number of patients with SUC reported each year was recorded and their clinical characteristics were analyzed using information available in the relevant papers. RESULTS: There were 13499 publications regarding UC published in Chinese medical journals between 2001 and 2015, of which 201 focused on SUC. The number of publications increased rapidly with more than half of all papers being published in the most recent 5-year period. There was a significant increase in analytical studies and clinical trials over the study period (P < 0.01), with research into the management of SUC, included pharmacotherapy, nutrition support as well as surgery, predominating. Almost half (46.2%) of the observational analytical studies and clinical trials focused on Traditional Chinese Medicine, with little research on the efficacy of cyclosporin and infliximab in disease management. About 6222 patients with SUC were reported in the 201 SUC relevant papers, with a ratio of male/female of 1.38. The number of patients reported in each 5-year period significantly increased. The colectomy rate and short-term mortality rate were 7.7% and 0.8% respectively. The most commonly employed operation was total proctocolectomy with ileal pouch-anal anastomosis. CONCLUSION: The output and complexity of research related to SUC in China increased significantly over the previous 15 years, however few of these studies focused on salvage therapy.

Hereditary angioedema: A rare cause of recurrent abdominal pain.

Hereditary angioedema is a rare autosomal dominant inherited disease which is characterized by an episodic, self-limiting increase in vascular permeability. Symptoms commonly involve in nonpitting, nonpruritic skin swellings. We present a case of hereditary angioedema. The patinets complained of a recurrent abdominal pain without accompanying skin swelling whose diagnosis was delayed nearly 20 years and accepted an unnecessary surgery. According to the decreased serum C1-inhibitor and C4 concentration, the patient was finally diagnosed with hereditary angioedema type I. After treatment with danazole, the patient reported a significant decrease in the frequency of attacks and the severity of pain. HAE is a rare cause of abdominal pain, however it needs to be taken as one of the differential diagnosis of various acute abdomens in order to avoid unnecessary surgeries.

Role of selective cyclooxygenase-2 inhibitors in exacerbation of inflammatory bowel disease: A systematic review and meta-analysis.

BACKGROUND: In the general population, selective cyclooxygenase (COX)-2 inhibitors have been associated with fewer gastrointestinal adverse effects (AEs) than NSAIDs, but whether they are associated with exacerbations in patients with inflammatory bowel disease (IBD) remains controversial. OBJECTIVE: The aim of this study was to review published and unpublished findings to determine whether the use of COX-2 inhibitors increased the risk for IBD exacerbations relative to placebo in the treatment of IBD. METHODS: A systematic search of MEDLINE (1966-July 2007), EMBASE (1980-July 2007), the Cochrane Library (2007 Issue 4), US Food and Drug Administration records, and data on file at Novartis Pharmaceuticals Corporation, Pfizer US Pharmaceutical Group, and Merck & Co., Inc., using the search terms celecoxib, rofecoxib, valdecoxib, etoricoxib, lumiracoxib, cyclooxygenase 2 inhibitor, Crohn's disease, ulcerative colitis, and inflammatory bowel disease, was performed to identify randomized, placebo-controlled clinical trials of 5 COX-2 inhibitors in patients with IBD. The publications were fully reviewed for quality. Data on trial design, patient characteristics, intervention drugs, dosages, and outcomes were collected using a predetermined data-extraction form. A meta-analysis was performed based on the publications that met the inclusion/exclusion criteria. RESULTS: Of 588 studies identified in the electronic search, 574 were excluded after screening the titles and abstracts. Fourteen related to the use of COX-2 inhibitors in patients with IBD were reviewed. Two randomized, controlled trials comparing COX-2 inhibitors with placebo were identified. In the first trial, 82 patients were randomized to receive etoricoxib (60-120 mg/d) and 77 to receive placebo. The exacerbation rates were 10.5% (8/76) in the active-treatment group and 11.4% (8/70) in the placebo group (relative risk [RR], 0.92; 95% CI, 0.37-2.32). In the second trial, 112 patients were treated with celecoxib (200 mg BID) and 110 received placebo. The exacerbation rates were 3.7% (4/107) in the celecoxib group and 2.7% (3/110) in the placebo group (RR, 0.73; 95% CI, 0.17-3.18). Of these patients, 5 were lost to follow-up because of AEs. In the meta-analysis comparing COX-2 inhibitors and placebo, the RR was 0.86 (95% CI, 0.39-1.88). No statistically significant differences in IBD relapse rates were found between COX-2 inhibitors and placebo. CONCLUSIONS: The results from this meta-analysis suggest that insufficient data were available to determine the impact of COX-2 inhibitors on IBD exacerbations. The relatively smaller risk for AEs makes the short-term use of COX-2 inhibitors potentially attractive, but the long-term benefits remain unclear. Further studies with sound methodology and large sample sizes are needed to evaluate the tolerability of COX-2 inhibitors in the treatment of IBD.

[Expression and function of interleukin-18 in mouse dextran sulfate sodium colitis].

OBJECTIVE: Interleukin-18 (IL-18) is a proinflammatory cytokine that induces Th1 cytokines production and may play a role in the pathogenesis of inflammatory bowel diseases. This study was aimed at detecting the expression and role of IL-18 in colonic mucosa of dextran sulfate sodium (DSS) colitic mice. METHODS: Expression of IL-18 in colon of DSS colitis was determined by immunohistochemistry. Extract and supernatant of intestinal epithelial cells (IEC) from colon of DSS colitis mice were used to stimulate splenic mononuclear cells (SMC); IFN-gamma and IL-2 concentrations in supernatant of SMC were measured by ELISA. The levels of expression of IL-18 in extract or supernatant of IEC were examined by Western blot. RESULTS: Colon epithelial cells and part of lamina propria mononuclear cells were stained positive for IL-18 antibody. Stimulation assay and Western blot indicated that IL-18 positive proteins were present in both IEC extract and supernatant. CONCLUSION: Colon epithelial cells in mice with DSS colitis express and secret pro IL-18 and active IL-18.

Significance of glucocorticoid receptor expression in colonic mucosal cells of patients with ulcerative colitis.

AIM: Glucocorticoid (GC) resistant ulcerative colitis (UC) remains a serious disease and is difficult to manage. Although the molecular basis of GC insensitivity is still unknown, GC receptors (GRalpha and GRbeta) may play an important role in it. This study was aimed to investigate the relationship between the expression of GRalpha and GRbeta in colonic mucosal cells of patients with UC, the efficacy of GC therapy and the intensity of inflammation. METHODS: Twenty-five cases of UC were classified into: GC sensitive (n = 16) and GC resistant (n = 9) cases. Patients consisted of mild (n = 6), moderate (n = 8) and severe (n = 11) cases. GRalpha and GRbeta expression in colonic mucosal specimens were investigated by immunohistochemistry, and compared between GC resistant and sensitive groups, and also among various degrees of inflammation. RESULTS: All cases were positive for GRalpha and GRbeta expression. Both positive association between GRalpha expression and the response of UC to GC and strong negative association between GRbeta expression and the response of UC to GC were identified. There was no significant association between GRalpha/GRbeta expression and the degree of inflammation of UC. CONCLUSION: These findings suggest that both GRalpha and GRbeta may play an important role in the action of GC, and that GRbeta functions as a dominant negative inhibitor of GRalpha. Expression of GRalpha and GRbeta in colonic mucosal cells of patients with UC may serve as predictors of glucocorticoid response, but can not function as markers of inflammatory intensity.

[Study on glucocorticoid receptor alpha and beta in colonic mucosal cell of patients with ulcerative colitis].

OBJECTIVE: To investigate the relationship of the expression of GRalpha and GRbeta in the colonic mucosal cell of patients with ulcerative colitis to the efficacy of glucocorticoid (GC) therapy and the intensity of inflammation. METHODS: GRalpha expression and GRbeta expression in the colonic mucosal specimens were assessed by means of immunohistochemistry. Then comparative analyses were made on the GRalpha and GRbeta expression between the GC resistant group and GC sensitive group at various levels of inflammation. A normal response group was observed for comparison. RESULTS: The staining intensities of both GRalpha and GRbeta in colonic mucosal specimens showed significant differences between the GC resistant group, GC sensitive group and normal response group. No association between the expression of GRalpha and GRbeta and the degree of inflammation was found. CONCLUSION: These findings suggest that both GRalpha and GRbeta play an important role in the mechanism of the action of GC, and GRbeta functions as a dominant negative inhibitor of GRalpha in there. The expression of GRalpha and GRbeta in the colonic mucosal cell of patients with ulcerative colitis may serve as predictors of glucocorticoid response, but cannot be used as the markers of the severity of inflammation.