Evolving endoscopic technologies for the detection of dysplasia in inflammatory bowel diseases

Patients with long-standing and extensive ulcerative colitis (UC) and colonic Chron's disease (CD) have an increased risk of CRC compared with the general population. Although no large controlled trials have proven that surveillance reduces mortality, cancer prevention in inflammatory bowel disease depends on the detection of dysplasia during scheduled surveillance colonoscopy and is widely recommended by gastroenterological associations. Dysplasia in IBD may occur in flat mucosa or in raised lesions (DALM) which have sometimes endoscopic features similar to adenoma (adenoma-like DALM). Recently, new endoscopic techniques to facilitate the distinction between dysplastic and actively inflamed or normal mucosa have been proposed. Chromoendoscopy significantly increases the sensitivity of detecting subtle dysplastic lesions and has emerged as the new standard of cancer surveillance in patients with IBD. Confocal laser endomicroscopy (CLE) is a novel technique that enables the endoscopist to obtain real time in vivo microscopic images of the gastrointestinal mucosa and can be used for targeting biopsies to relevant areas. CLE in conjunction with chromoendoscopy proved able to increase the diagnostic yield of dysplasia in ulcerative colitis and reduce the number of biopsies needed. The role of digital filtering technologies (virtual chromoendoscopy) and autofluorescence in IBD surveillance will be also discussed.     

The Differential Diagnosis of Acute Colitis: Clues to a Specific Diagnosis

This review describes a systematic approach to the interpretation of colonic biopsy specimens of patients with acute colitis. Five main histologic patterns are discussed: acute colitis, focal active colitis, pseudomembranous colitis, hemorrhagic colitis, and ischemic colitis. For each pattern, the most common etiologic associations and their differential diagnoses are presented. Strategies based on histologic analysis and clinical considerations to differentiate acute from chronic colitides are discussed.     

Increased expression of minichromosome maintenance protein 2 in active inflammatory bowel disease

OBJECTIVE: Minichromosome maintenance protein 2 (Mcm2) is an accurate indicator of cell cycle entry in tissue samples, but its expression in inflammatory bowel disease (IBD) has not previously been investigated. We have used immunohistochemistry to assess the expression of Mcm2, in comparison to the existing proliferation marker Ki-67, in active IBD and IBD without inflammatory activity. MATERIALS AND METHODS: For this experimental study, sections from colonic biopsy and resection specimens of 48 patients with IBD (5 inactive/quiescent Crohn's disease (CD), 13 active CD, 19 inactive/quiescent ulcerative colitis (UC) and 11 active UC) and 15 normal controls were immunostained with antibodies to Mcm2 and Ki-67. The percentage of immunopositive epithelial nuclei was determined by calculating a labelling index (LI) for entire glands and for gland thirds (superficial, middle and basal). RESULTS: The Mcm2 LI was significantly increased in the superficial third of glands in active vs. inactive/quiescent UC (P < 0.0001) and active vs. inactive/quiescent CD (P = 0.001). The Mcm2 LI was significantly greater than the Ki-67 LI in active IBD, both in entire glands (P < 0.0001) and in the superficial third of glands (UC, P = 0.001; CD, P = 0.0002). Mcm2 LIs for entire glands were significantly higher in UC (all cases) compared to CD (all cases) (P = 0.032). CONCLUSIONS: There is increased cell cycle entry, as indicated by expression of Mcm2 and to a lesser extent Ki-67, in the superficial third of colonic glands in active IBD compared to inactive/quiescent IBD. Detection of Mcm2 may contribute to improved histological assessment of small tissue biopsies and may enable the development of a direct stool-based test for detection of active IBD and potentially for assessment of disease activity.     

Current medical therapy for chronic inflammatory bowel diseases

Chronic idiopathic inflammatory bowel diseases (IBD) include Crohn's disease (CD), ulcerative colitis (UC), and colonic IBD type unclassified (IBDU). This article focuses upon current medical therapies for adult CD and UC, and is organized according to therapy for the corresponding disease type, stage, and severity.     

Clinicopathologic features and outcome of mycophenolate‐induced colitis in renal transplant recipients

Reports on the clinical course of mycophenolic acid (MPA)‐related colitis in kidney transplant recipients are scarce. This study aimed at assessing MPA‐related colitis incidence, risk factors, and progression after kidney transplantation. All kidney transplant patients taking MPA who had colonic biopsies for persistent chronic diarrhea, between 2000 and 2012, at the Kidney Transplantation Unit of Botucatu Medical School Hospital, Brazil, were included. Cytomegalovirus (CMV) immunohistochemistry was performed in all biopsy specimens. Data on presenting symptoms, medications, immunosuppressive drugs, colonoscopic findings, and follow‐up were obtained. Of 580 kidney transplant patients on MPA, 34 underwent colonoscopy. Colonoscopic findings were associated with MPA usage in 16 patients. The most frequent histologic patterns were non‐specific colitis (31.3%), inflammatory bowel disease (IBD)‐like colitis (25%), normal/near normal (18.8%), graft‐versus‐host disease‐like (18.8%), and ischemia‐like colitis (12.5%). All patients had persistent acute diarrhea and weight loss. Six of the 16 MPA‐related diarrhea patients (37.5%) showed acute dehydration requiring hospitalization. Diarrhea resolved when MPA was switched to sirolimus (50%), discontinued (18.75%), switched to azathioprine (12.5%), or reduced by 50% (18.75%). No graft loss occurred. Four patients died during the study period. Late‐onset MPA was more frequent, and no correlation with MPA dose or formulation was found.     

Colorectal cancer in patients with inflammatory bowel disease after liver transplantation for primary sclerosing cholangitis

BACKGROUND: Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) may have an increased risk of developing colorectal cancer (CRC) after liver transplantation (LT). We evaluated our patients with PSC after LT to identify risk factors for CRC and its impact on survival. PATIENTS AND METHODS: A total of 152 patients (108 men, 100 with IBD) with PSC who underwent 173 LTs between 1986 and May 2000 were analyzed in three groups: (1) PSC without IBD (n=52); (2) PSC with colectomy (pre-LT and at LT) (n=17, colectomy pre-LT in 13 and simultaneous colectomy at LT in four); and (3) PSC with IBD and an intact colon (n=83). The following factors were studied: age, gender, liver, and renal biochemistry, international normalized ratio, Child-Pugh stage, operative time, blood use, hospital stay, immunosuppression, risk of CRC, retransplantation rate, and mortality. RESULTS: The incidence of CRC after LT was 5.3% (8/152) compared with 0.6% (7/1,184) in non-PSC cases (P<0.001). All CRCs in the PSC group were in patients with IBD and an intact colon. The cumulative risk of developing CRC in the 83 patients with an intact colon and IBD was 14% and 17% after 5 and 10 years, respectively (PSC non-IBD group 0% risk after 10 years, P<0.06). The multivariate analysis showed three significant variables related to the risk of developing CRC: colonic dysplasia after LT (P<0.0003), duration of colitis more than 10 years (P<0.002), and pancolitis (P<0.004). The cause of death in patients with CRC was cancer related in 75% of cases with a reduced 5-year survival of 55% versus 75% without CRC (not significant). CONCLUSION: Patients with PSC undergoing LT with a long history of ulcerative colitis and pancolitis have an increased risk of developing CRC with reduced survival. We advocate long-term aggressive colonic surveillance and colectomy in selected high-risk patients with longstanding severe colitis.     

Indeterminate colitis (nonspecific inflammatory bowel disease)

Distinguishing of indeterminate colitis from ulcerative colitis or Crohn's disease in more than 10% of IBD cases as separate diagnostic category (IIBD) is defined by: first, overlapping or paucity of features of two major IBD forms in acute fulminant colitides and few chronic slowly progressive cases without differentiating markers of chronicity, and second, inability to reach specific diagnosis during or after completed clinical, radiological, endoscopical and histopathological examination of chronic colitis with inconclusive presentation of IBD-compatible cases. It implicates the contemporary category of IIBD, until some new relevant data of further clinical (preferably natural history and course of the disease) and histopathological examination of prior biopsies will possibly reclassify 20-75% of these cases into ulcerative colitis category (up to 40%) or Crohn's disease (up to 25%) at a median of 10 years' follow-up. The presence of ileal and/or perianal disease as well as later evident granulomatous and/or fissuring disease, including cases with pouchitis and diversion colitis in addition, could be helpful in favouring of Crohn's disease. Lacking specific signs of disease, IIBD is not a distinct entity. Still, many patients remain in this category. The most far is acute fulminant disease in adolescents and young adults with unusual distribution of transmural inflammation with deep fissuring ulcerations, sometimes of "collar-stud" type and normal mucosa between them, often with relative rectal sparing. There is significant risk of relapse and complications, but mild clinical course and even spontaneous regression are also reported. Failure of ileal pouch-anal anastomosis surgery is about 20% more frequent then in ulcerative colitis with overall worse prognosis in life expectations. Diagnostic problems and the main presentations are discussed in detail, as well as genetic and etiopathogenetic basis for heterogeneity of IBD.     

Ras oncogene p21 levels parallel malignant potential of different human colonic benign conditions

Ras oncogenes are a specific family of genes believed to play a role in malignant transformation and tumor growth in humans. To gain a better understanding of the role these oncogenes may play in malignant transformation, we evaluated the levels of a ras gene protein product (p21) in formaldehyde-fixed, paraffin-embedded specimens of normal human colonic mucosa, hyperplastic polyps, tubular adenomas, villous adenomas, and epithelium from a patient with ulcerative colitis. The p21 protein content was measured using the RAP-5 monoclonal antibody in a semiquantitative immunohistochemical assay. The titer value was expressed as the highest dilution of antibody giving definite staining using the avidin-biotin peroxidase method. Differences in p21 titer values among all classes of polyps were significant (hyperplastic polyps values were less than tubular adenomas values, which were less than villous adenoma values). The p21 titers obtained from ulcerative colitis specimens were similar to those obtained from villous adenomas. We conclude that the levels of ras oncogene protein product increase with the malignant potential of benign human colonic conditions. These findings suggest that the ras oncogene protein product may play an important role in the malignant transformation of benign lesions of the human colon. If these findings are confirmed, as technology progresses to allow molecular probes to measure gene products in biopsy specimens, high-risk patients could be monitored and treated before actual malignant transformation occurs.     

Prevalence and significance of inflammatory bowel disease-like morphologic features in collagenous and lymphocytic colitis

Collagenous colitis (CC) and lymphocytic colitis (LC) are clinical syndromes characterized by the presence of chronic watery diarrhea, few or no endoscopic abnormalities and biopsies that typically show normal crypt architecture, increased mononuclear inflammation in the lamina propria, absence of neutrophils, and increased intraepithelial lymphocytes. Patients with CC also have a thickened subepithelial collagen layer. We have noted, anecdotally, that biopsy specimens from some patients with CC or LC contain certain histologic features, such as Paneth cell metaplasia (PM), that are normally seen in inflammatory bowel disease (IBD), or other types of healed colitis, and thus may cause diagnostic difficulty. Therefore, the purpose of this study was to evaluate the prevalence and significance of IBD-like morphologic features in colonic mucosal biopsies from patients with CC or LC. Five hundred thirty-one routinely processed hematoxylin and eosin-stained colonic mucosal biopsies from 150 patients with clinically, endoscopically, and histologically confirmed CC (79 patients, male/female ratio: 14/65, mean age: 60 yr) or LC (71 patients, male/female ratio: 13/58, mean age: 55 yr) were evaluated in a blinded fashion for a variety of histologic features, including active crypt inflammation (cryptitis +/- crypt abscess), surface ulceration, Paneth cell metaplasia, crypt architectural irregularity, number of intraepithelial lymphocytes, and thickness of the subepithelial collagen layer (CC only). The results were compared between CC and LC and correlated with the clinical and endoscopic data. None of the patients had or developed IBD during the study period. Active crypt inflammation was a common finding in both groups, seen in 24 of 79 CC patients (30%) and 27 of 71 LC patients (38%). Surface ulceration was not seen in any of the LC biopsies but was present in 2 of 79 (2.5%) CC patients. Paneth cell metaplasia was frequent in both groups and significantly more common in CC compared with LC patients. Forty-four percent of CC patients, but only 9 of 63 (14%) of LC patients had Paneth cell metaplasia (p <0.001). Crypt architectural irregularity, although rare, was present in 6 of 79 patients with CC (7.6%) and 3 of 71 (4.2%) patients with LC. In patients with CC, the presence of Paneth cell metaplasia was associated with more severe disease characterized by the presence of abdominal pain (p <0.001) and a higher frequency of bowel movements (>3 bowel movements/day) (p = 0.06). Also, active crypt inflammation correlated with antibiotic use at the time of clinical presentation (p = 0.04) and was present in the only two patients who had positive stool cultures (one each for and ). However, none of the other histologic findings correlated with any of the other clinical or endoscopic features, such as type of symptoms, stool consistency, type of medical treatment, associated autoimmune diseases or outcome (complete, partial, or no resolution) in either group of patients. Pathologists should be aware that some histologic features normally associated with IBD such as crypt irregularity and neutrophilic cryptitis and crypt abscesses are not uncommon in patients with CC or LC and that the presence of one or more of these features should not necessarily be interpreted as evidence against either of these diagnoses.     

Biopsy diagnosis of colitis: possibilities and pitfalls

The histopathologic diagnosis of inflammation is common in colorectal biopsies but is of limited value, if not further specified. We reviewed 280 endoscopic colorectal biopsy specimens for nonneoplastic disease from 100 consecutive patients in order to assess (a) the frequency of inflammation in excess of the physiologic infiltrate, (b) the frequency with which the cause of the inflammation could be specified, and (c) the interobserver variability in diagnosing inflammation. Based on the reviewers' impression, each case was classified into one of three categories: (I) normal or nonspecific change, (II) nonspecific inflammation, and (III) inflammation suggestive or diagnostic of specific cause. Inflammation was diagnosed in 68% of cases. The majority of these cases (75%) showed features typically associated with specific types of colitis, including Crohn's disease (n = 16), ulcerative colitis (n = 13), inflammatory bowel disease not otherwise specified (n = 5), infectious colitis (n = 6), ischemic colitis (n = 4), solitary rectal ulcer syndrome (n = 3), radiation colitis (n = 2), and lymphocytic colitis (n = 2). Interobserver variability was greatest in biopsy specimens interpreted by the reviewers as normal or showing nonspecific changes, most of which had been diagnosed as mild inflammation by the original pathologists. Etiologic classification of colitis was lacking in 59% of the cases interpreted by the reviewers as suggestive or diagnostic of a specific cause. We conclude that (a) the majority of colorectal biopsy specimens from patients with nonneoplastic disease in this series show inflammation, (b) the majority of such cases allow a specific cause of colitis to be suggested or firmly diagnosed, and (c) pathologists tend to overdiagnose the physiologic inflammatory infiltrate as evidence of colitis and underdiagnose specific etiologic types of colitis.     

Oral Administration of Taurolidine Ameliorates Chronic DSS Colitis in Mice

Taurolidine (TRD) has antimicrobial and anti-inflammatory properties. However, the anti-inflammatory effects of TRD in inflammatory bowel diseases (IBD) have not been investigated. Here, we have analyzed the toxicity of TRD after oral long-term application in mice and examined the impact of oral TRD in a dextran sulfate sodium (DSS) model of experimental colitis. Female C57/BL6 mice received TRD in various concentrations (0.1% to 0.4%) for 60 days. Toxicity was evaluated by use of a disease activity index (DAI) and histological examination of major metabolic organs. Furthermore, the impact of 0.2% TRD on a chronic DSS colitis was examined by daily DAI, histological crypt damage score (CDS), bacterial translocation into mesenteric lymph nodes (MLN), and colonic expression of tumor necrosis factor (TNF) α, transforming growth factor (TGF) β, interleukin (IL)-1β, IL-6, cytochrome oxidase (COX)-2, and monocyte chemotactic protein (MCP)-1 by real-time polymerase chain reaction (PCR). Oral TRD administration for 60 days was well tolerated by the animals and did not show any toxic effects in terms of DAI and histological changes. TRD treatment of DSS colitis led to increased survival of 100%, compared to 33% in the untreated colitis group (p ≤. 005). Clinical amelioration was mirrored by significantly reduced DAI and CDS in the TRD treated colitis. Colonic cytokine expression and bacterial translocation into MLN showed no differences between both groups.

We thus report for the first time that oral application of TRD results in amelioration of an experimental IBD model. We hypothesize direct intraluminal antimicrobial effects of TRD as well as anti-inflammatory effects during the acute phase of DSS colitis.     

Oral administration of taurolidine ameliorates chronic DSS colitis in mice.

Taurolidine (TRD) has antimicrobial and anti-inflammatory properties. However, the anti-inflammatory effects of TRD in inflammatory bowel diseases (IBD) have not been investigated. Here, we have analyzed the toxicity of TRD after oral long-term application in mice and examined the impact of oral TRD in a dextran sulfate sodium (DSS) model of experimental colitis. Female C57/BL6 mice received TRD in various concentrations (0.1% to 0.4%) for 60 days. Toxicity was evaluated by use of a disease activity index (DAI) and histological examination of major metabolic organs. Furthermore, the impact of 0.2% TRD on a chronic DSS colitis was examined by daily DAI, histological crypt damage score (CDS), bacterial translocation into mesenteric lymph nodes (MLN), and colonic expression of tumor necrosis factor (TNF) alpha, transforming growth factor (TGF) beta, interleukin (IL)-1beta, IL-6, cytochrome oxidase (COX)-2, and monocyte chemotactic protein (MCP)-1 by real-time polymerase chain reaction (PCR). Oral TRD administration for 60 days was well tolerated by the animals and did not show any toxic effects in terms of DAI and histological changes. TRD treatment of DSS colitis led to increased survival of 100%, compared to 33% in the untreated colitis group (p < or = .005). Clinical amelioration was mirrored by significantly reduced DAI and CDS in the TRD treated colitis. Colonic cytokine expression and bacterial translocation into MLN showed no differences between both groups. We thus report for the first time that oral application of TRD results in amelioration of an experimental IBD model. We hypothesize direct intraluminal antimicrobial effects of TRD as well as anti-inflammatory effects during the acute phase of DSS colitis.     

AMACR immunostaining is useful in detecting dysplastic epithelium in Barrett's esophagus, ulcerative colitis, and Crohn's disease

Alpha-methylacyl-CoA racemase (AMACR) catalyzes the racemization of alpha-methyl, branched carboxylic coenzyme A thioesters, and is overexpressed in a variety of neoplasms, such as prostate and colon cancer. The aim of this study was to evaluate AMACR expression in the metaplasia-dysplasia-carcinoma sequence in Barrett's esophagus (BE), ulcerative colitis (UC), and Crohn's disease (CD) and to determine whether its expression can be used to detect dysplastic epithelium in these conditions. One hundred thirty-four routinely processed biopsy and/or resection specimens from 134 patients with BE [M/F ratio: 5.7, mean age: 67 y (36 negative (intestinal metaplasia only), 14 indefinite for dysplasia (IND), 16 low-grade dysplasia (LGD), 32 high-grade dysplasia (HGD), and 36 invasive adenocarcinoma (ACA)] and 74 specimens from 74 patients with inflammatory bowel disease (IBD) [56 with ulcerative colitis, 18 with Crohn's disease, M/F ratio: 1.8, mean age: 55 y (17 negative, 7 IND, 26 LGD, 10 HGD, and 14 ACA)] were immunostained with a monoclonal AMACR antibody (p504S). The degree of cytoplasmic staining in all cases was evaluated in a blinded fashion according to the following grading system: 0, negative (0% cells positive); 1+, 1% to 10% cells positive; 2+, 10% to 50% cells positive; or 3+, >50% cells positive. In patients with BE, AMACR was not expressed in any negative foci (0%) but was significantly increased (P<0.0001) in foci of LGD (38%), HGD (81%), and ACA (72%). Three of 14 (21%) IND foci from 3 BE patients were only focally positive (grade 1: 7%, 2: 14%). However, 1 of these 3 patients had follow-up information available and had developed ACA subsequently. Similarly, in patients with IBD, AMACR was not expressed in any foci considered negative for dysplasia, but was significantly increased (P<0.0001) in foci of LGD (96%), HGD (80%), and ACA (71%). Only 1/7 (14%) IND focus from 1 patient was focally positive (grade 1). The sensitivity for the detection of LGD and HGD in BE and IBD was 38% and 81%, and 96% and 80%, respectively, for the 2 types of disorders. The specificity was 100% for both BE and IBD. AMACR is involved in the neoplastic progression in BE and IBD. The high degree of specificity of AMACR for dysplasia/carcinoma in BE and IBD suggests that it may be useful to detect neoplastic epithelium in these conditions.     

Inflammatory bowel disease in the pediatric patient

Inflammatory bowel disease (IBD) is a general term used to describe two chronic bowel disorders, Crohn's disease (CD) and ulcerative colitis (UC), both of which are characterized by autoimmune-related inflammation of the intestines. UC is limited to the colonic mucosa, whereas CD can involve any part of the intestinal tract from the mouth to the anus. The true etiology of UC and CD is still unknown, although extensive research has identified some genetic and environmental factors. This article discusses current clinical concepts of both diseases in the pediatric population.     

Significance of CEA in gastric and colorectal cancer

The determination of serum CEA (Sandwich method) and CEA staining (PAP method) of excised specimens were performed in patients with gastric or colorectal cancer, and the biological characteristics of each cancer and the factors to increase serum CEA were studied with the following results: As colonic cancer has strong CEA productivity, serum CEA can be useful for the detection of cancer, and especially effective for the postoperative observation. Gastric cancer has weak CEA productivity, and serum CEA is not so useful in the detection of cancer and the judgement of resectability. The CEA positive rate of tissue with CEA staining was 80% in gastric cancer, 100% in colonic cancer, and were nearly equal to the CEA positive rate of serum in the group of terminal stage. In the mode of CEA staining of cancerous cells, IV type was observed most frequently in gastric cancer, and I type in colonic cancer. Among the resected cases showing more than 7ng/ml serum CEA, differentiated type, lymph node metastasis (+), the degree of tissue staining with CEA staining, the mode of cell staining O or I type in gastric cancer and I type in colonic cancer were observed in common.     

Premalignant and malignant changes in idiopathic inflammatory bowel disease

It is well known that patients with long-standing inflammatory bowel disease (IBD), ulcerative colitis (UC) or Crohn's disease(CD) are at increased risk for developing colorectal cancer (CC). Before adenocarcinoma develops, the intestinal epithelium progress through a premalignant phase of dysplasia, which can be identified via mucosal biopsy and routine tissue histology. Surveillance colonoscopy and prophylactic colectomy for dysplasia or asymptomatic cancer is advised as a method of reducing cancer-related mortality. Many physicians suggests that surveillance for extensive colitis should begin after 8 to 10 years of disease, and surveillance for left-sided colitis should begin after 15-20 years. Colonoscopy is recommended with frequent biopsies, at least every 10 cm in all four quadrants, and with biopsy of any suspicious lesion. The emerging field of colon cancer genetics has identified several important tumor markers that have potential to improve sensitivity for detection of early neoplasia.     

Spontaneous and shock-associated ischemic colitis

Ischemic changes in the colon that progress to gangrene present diagnostic and therapeutic difficulties associated with poor survival. During the past 10 years, 36 patients with colonic ischemia were treated. Two clinical groups were evident. The spontaneous ischemic colitis group (type I) included 17 patients who were well before the onset of gastrointestinal symptoms. The cause of type I ischemic colitis is not apparent; it is attributed to occlusive or nonocclusive ischemia. The other group (type II) included 19 patients who developed ischemia of the colon associated with shock secondary to various disease processes. Radiographic evidence of distended bowel correlated well with full-thickness necrosis as determined clinically or pathologically. Twenty-one patients died, for a mortality rate of 58 percent. While full-thickness gangrene was fatal in 71 percent of the patients, mucosal necrosis only was associated with an 88 percent survival rate. The results of treatment should improve with an increased awareness of ischemic colitis, earlier appropriate operative intervention, and more appropriate use of ileostomy and colostomy.     

Laparoscopic subtotal colectomy for acute or severe colitis complicating inflammatory bowel disease: a case-matched study in 88 patients

BACKGROUND: The aim of this study was to assess the morbidity of laparoscopic subtotal colectomy (STC) with or without anastomosis in patients with acute or severe colitis (SAC) complicating inflammatory bowel disease (IBD) who failed medical treatment. METHODS: Forty patients undergoing laparoscopic STC for SAC complicating IBD were identified and well-matched for age, gender, ASA score, and IBD severity at the time of colectomy (acute colitis vs steroid dependence only) with 48 patients undergoing open STC. RESULTS: There was no operative mortality. Mean (+/-SD) operative time was similar after laparoscopic and open STC (253 +/- 56 vs 231 +/- 75 min; NS). Two patients (5%) required conversion into laparotomy due to intensive adhesions (n = 1) and colonic fistula (n = 1). Overall morbidity and hospital stay was similar after laparoscopic STC and open STC (35% vs 56%) (9 +/- 3 vs 12 +/- 7 days) (P > .1) respectfully. After laparoscopic STC, 84% of the patients underwent restorative intestinal continuity (with either ileorectal or ileoanal anastomosis) through reoperative laparoscopy (n = 15) or elective incision at the site of previous stoma (n = 16). CONCLUSIONS: This case-matched study suggests that laparoscopic STC was as safe and effective as open STC for IBD patients with SAC. A laparoscopic STC allows restoration of intestinal continuity restoration (ie, ileal pouch anal or ileorectal anastomosis) through a laparoscopic approach or elective incision for the majority of the patients. For these reasons, laparoscopic approach represents the best approach for colitis-complicating IBD.     

Pathology of inflammatory bowel diseases (IBD): variability with time and treatment

The diagnosis of chronic idiopathic IBD and the differential diagnosis between Crohn's disease and ulcerative colitis can be made in most cases on cumulative clinical, radiological, endoscopical, biochemical and pathological evidence. Diagnostic difficulties can however, occur in fulminant colitis, in early onset disease and in long-standing disease. The microscopic evaluation of disease activity is based on the presence of active inflammation. Effective medical treatment has however, an influence upon the morphology and the evolution of the lesions and hence can affect the diagnostic features and the microscopic features used for the assessment of disease activity. A literature review was performed on clinical drug trials in IBD and the effect of the drugs upon the microscopic features. Several studies have shown that the diagnostic microscopic features and the features characteristic for disease activity vary with time and treatment. For an adequate analysis of biopsy samples of patients with IBD the pathologist should be aware of the duration of the symptoms and the type of treatment given to the patient.     

溃疡性结肠炎患者结肠黏膜中TIPE2表达的研究

目的：探讨肿瘤坏死因子α诱导蛋白8样因子2（TIPE2）在溃疡性结肠炎中的表达及意义。方法：1）采用免疫组织化学SP法检测TIPE2在溃疡性结肠炎中的表达,并分析TIPE2的表达与溃疡性结肠炎发生、发展的关系;2）采用RT-PCR检测TIPE2 mRNA在溃疡性结肠炎中的表达。结果：1）TIPE2蛋白在溃疡性结肠炎（42.5%）中较正常结肠组织（17.1%）表达增强,差异有统计学意义（χ2=5.645,P〈0.05）。TIPE2在溃疡性结肠炎中的表达与患者的年龄、性别、病变分布范围无关,与病变分期有关,活动期较缓解期患者阳性率高（P〈0.05）。2）RT-PCR结果显示TIPE2 mRNA在溃疡性结肠炎的含量较正常结肠组织高（P〈0.05）。结论：TIPE2参与了溃疡性结肠炎的发生、发展。