[Show abstract][Hide abstract] ABSTRACT: Aim
Ileal pouch-anal anastomosis (IPAA) is a surgical option for patients with intractable ulcerative colitis (UC) and familial adenomatous polyposis (FAP). Evacuation difficulty is a functional problem that can occur after IPAA and its mechanism is not well understood. We investigated whether defecating pouchogram is useful to assess patients with evacuation difficulty.
Defecating pouchograms between 2006 and 2014 were reviewed. Features of defecating pouchograms were correlated with symptoms. Demographic, clinical and radiological variables were analysed.
87 patients had defecating pouchgram for evacuation difficulty of whom 35 had mechanical causes (long-cuff n = 11, stenosis n = 22). Fifty-two patients (mean age 48.2 years, 33 female) had functional pouch evacuation difficulty. In this group more patients complained of high frequency (P = 0.005) and initiation problems (P = 0.049) than mechanically obstructed patients. Common findings on defecating pouchogram were residual barium (n = 24), slow evacuation (n = 18) and mucosal irregularity (n = 17). Anismus (n = 15) and pelvic floor disorders (n = 10) showed statistically significant correlation with symptoms of straining, anal pain, incontinence and urgency.
Defecating pouchogram may be useful to identify functional disorders in patients complaining of straining, anal pain, incontinence or urgency who may benefit from behavioural therapy.
European Society of Coloproctology, Dublin, Ireland; 09/2015
[Show abstract][Hide abstract] ABSTRACT: Background:
Tight junction proteins (TJPs) and dendritic cells (DC) are critical in the pathogenesis of inflammatory bowel diseases. The ileal pouch formed by restorative proctocolectomy provides a unique human model for studying the pathogenesis of inflammatory bowel diseases. Data implicate the microbiota in the pathogenesis of pouchitis, while the role of innate immune factors remains unclear. We performed longitudinal and cross-sectional studies of patients after restorative proctocolectomy and assessed TJP and DC characteristics in the ileal pouch.
Mucosal biopsies were taken from the ileal pouch of patients with ulcerative colitis (UC) and familial adenomatous polyposis (n = 8). Of patients with UC, one group (n = 5) was followed longitudinally over the first year after ileostomy closure, another group had pouchitis (n = 15), and another group no inflammation (n = 18). Dendritic cell phenotype and epithelial cell TJP expression were assessed using flow cytometric analysis.
Increased epithelial expression of the "pore-forming" TJP claudin 2, and DC expression of gut-homing markers CCR 9 and integrin β7, occurred early after ileostomy closure. In patients with UC with pouchitis, epithelial expression of ZO-1 and claudin 1 were reduced, DC were activated with increased CD40, and Toll-like receptor 4 expression increased. In pouchitis, DC expressing CCR 9 were decreased, whereas DC expressing β7 increased.
Abnormalities were found in TJP expression in the pouch of patients with UC, in particular, increased expression of the pore-forming claudin 2 as an early event in the development of pouch inflammation and an aberrant DC phenotype was characterized in the ileal pouch of patients with UC.
[Show abstract][Hide abstract] ABSTRACT: CD40 is a co-stimulatory molecule belonging to the tumor necrosis factor superfamily and is essential in activation of dendritic cells. Dendritic cells (DCs) are antigen-presenting cells capable of initiating cytotoxic T-lymphocyte immune response against cancer cells. However, there are few studies on the characterization of DCs in cancer, specifically their expression of CD40, despite its implication in cancer immunotherapy. We reviewed available data on the expression of CD40 on DCs in various cancers, and its implications for cancer immunotherapy.
Current Cancer Drug Targets 08/2014; 14(7). DOI:10.2174/1568009614666140828103253 · 3.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The number of patients diagnosed with advanced colonic polyps has increased due to screening. The outcome of hemicolectomy for benign lesions is poorly documented. We present a case-matched study comparing the results of hemicolectomy for benign and malignant polyps performed in two institutions.
Data for consecutive patients undergoing surgery for benign colonic polyps (BCP) were prospectively collected in two hospitals. Each patient was matched for age, sex, ASA grade, site and type of resection (laparoscopic, open, and converted) with two controls who underwent surgery for colon cancer (CC). The length of stay (LOS) and 30-day outcome were analysed adjusting for potential confounders. Multilevel linear and logistic regression analyses were performed.
46 patients having hemicolectomy for BCP were matched with 81 patients with CC. The median size of BCP was 4 (IQR 2.5,5.4) cm. Patients with BCP had a marginally longer LOS [median 5.5 (IQR 4,8) days and 5 (IQR 3,7) days (p=0.04)]. Twenty one (46%) of 46 patients with BCP had a postoperative complication compared with 25(31%) of 81 CC (p=0.12,OR=2.11;CI 0.82-5.41). Four (9%) of 46 patients with BCP underwent reoperation and further 3 (7%) were readmitted compared with one (1%) and 2 (2%) of 81 patients with CC (p=0.07 and 0.28). There was no mortality in either group.
Complications following hemicolectomy for BCP or CC are not significantly different. The results of the study provide further impetus to develop local full thickness colonic excision for benign colonic lesions as an alternative to major surgery. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
This review summarizes the published methods of colonic EFTR, examining data on feasibility and safety. Due to the introduction of bowel cancer screening programs, there is an increasing incidence of complex colonic polyps and early colonic cancer that requires segmental colectomy. Traditional radical surgery is associated with significant morbidity, and there is a need for alternative treatments.
Systematic literature search identified articles describing EFTR techniques of colon, published between 1990 and 2012. Complication rates, anastomotic bursting pressures, procedure duration, specimen size and quality, and postmortem findings were analyzed.
Five research groups reported four EFTR techniques using endoscopic stapling devices, T-tags, compression closure, or laparoscopic assistance for defect closure before or after specimen resection. A total of 113 procedures were performed in 99 porcine models, with an overall success rate of 89 and 4 % mortality. The intraoperative complication rate was 22 % (0-67 %). Post-resection closure methods more commonly resulted in failure to close the defect (5-55 %) and a high incidence of abnormal findings at postmortem examination (84 %). Significant heterogeneity was observed in procedure duration (median or mean 3-233 min) and size of the excised specimen (median or mean 1.7-3.6 cm). Anastomotic bursting pressures and specimen quality were poorly documented.
The technique of EFTR is developing, but the inability to close the resection defect reliably is a major obstacle. The review highlights the challenges that need to be addressed in future preclinical studies.
[Show abstract][Hide abstract] ABSTRACT: : Juvenile polyposis syndrome is phentoypically and genotypically heterogeneous. It is associated with an increased risk of GI cancers, and surveillance is recommended. Few data exist that detail the outcomes of surveillance in juvenile polyposis syndrome.
: The aim of this study was to review clinical features, genetic mutations, and long-term outcome data in patients with juvenile polyposis syndrome.
: This study is a retrospective review.
: The Polyposis Registry, St Mark's Hospital, was used in the performance of this study.
: Patients with juvenile polyposis syndrome who were followed up at our institution were included.
: Forty-four patients (27 male) from 30 kindreds were included. Fifteen were diagnosed by screening, and 29 presented symptomatically. Nineteen patients had SMAD4 mutation and 9 had BMPR1A mutation. Five patients (11%) had valvular heart disease. Telangiectasia/vascular abnormalities were observed in 4 (9%) patients, and macrocephaly was observed in 5 (11%). Six patients (14%) developed cancer; 4 had cancer at the time of diagnosis of juvenile polyposis syndrome, 3 developed cancer while on surveillance (1 patient had a second primary). All patients with advanced upper GI disease had SMAD4 mutations. Where germline mutation was known, all patients with telangiectasia had SMAD4 mutation. Seven patients required GI surgery at our institution: colectomy and ileorectal anastomosis (1), restorative proctocolecotomy (1), anteroposterior excision for rectal cancer (1), gastrectomy (2), and laparotomy and intraoperative enteroscopy (1). There were no complications of endoscopic surveillance. Colonic polyps predominated; 535 of 767 (69.8%) of colonic polyps were right sided. One patient had a solitary significant small-bowel polyp. Sixty-five juvenile polyps contained dysplasia (mild to moderate). Two patients had severe dysplasia or cancer found in carpeting polyps.
: This is a retrospective review. The cohort size, although modest, is good for such a rare condition.
: Extraintestinal features are common. Gastrointestinal surveillance is safe. Most colonic polyps are right sided, and detecting dysplasia is uncommon. Carpeting polyps are of particular concern.
Diseases of the Colon & Rectum 10/2012; 55(10):1038-43. DOI:10.1097/DCR.0b013e31826278b3 · 3.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Duodenal polyposis is found in the majority of patients with familial adenomatous polyposis. Endoscopic surveillance programmes grade the severity of duodenal disease according to the Spigelman classification (stages 0-IV) to identify patients at risk of developing adenocarcinoma. To evaluate the progression of duodenal polyposis in patients with a previous diagnosis of Spigelman stage IV disease who have been downstaged by endoscopic or pharmacological means. A database search of a large polyposis registry identified patients who had been downstaged from stage IV disease and had further opportunity for disease progression. These patients were divided into three groups according to their new Spigelman stage. A measure of a patient's disease progression was obtained by the increase in stage over the recommended follow up time period for their new, reduced, Spigelman stage. Group 1 (n = 16) were downstaged to stage III disease, with 50 % progressing back to stage IV over the recommended 1-year follow up period. Group 2 (n = 19) were downstaged to stage II disease, with 84 % progressing over the recommended 3-year follow up period. Group 3 (n = 6) were downstaged to stage I disease, with 100 % progressing over the recommended 5-year follow up period. Patients downstaged from Spigelman stage IV demonstrate an increased rate of disease progression in comparison to reported rates of primary disease progression. An amendment to the current endoscopic surveillance protocol is recommended to ensure that once a patient has been diagnosed with stage IV disease they are treated as a high-risk patient in perpetuity.
Familial Cancer 07/2012; 11(4). DOI:10.1007/s10689-012-9546-2 · 1.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Familial adenomatous polyposis-related desmoid tumors can present with a liquefied center containing gas, accompanied by abdominal pain and sepsis. To date the optimal management of such patients has not been documented.
The aim of this study was to review our experience of managing these desmoids grouped together as "intra-abdominal desmoids with air-fluid level" and present a management algorithm.
This is a retrospective study of prospectively maintained polyposis registry database.
This study was conducted at a tertiary referral center specializing in familial adenomatous polyposis and desmoid disease.
Nine patients with intra-abdominal desmoid and air-fluid level were analyzed for the purpose of this study.
Two hundred and forty-six patients were identified with desmoid tumor. Of these, a total of 9 patients had an intra-abdominal desmoid with air-fluid level; 7 were women. Age range at diagnosis was 20 to 41 years. The median time from primary surgery to desmoid tumor development was 24 months (range, 0-48 months), and the median time for further progression to air-fluid level was 24 months (range, 0-226 months). Desmoid tumor size ranged from 10 cm to greater than 20 cm in diameter. Two patients were successfully managed with antibiotics alone, and 2 patients were managed with percutaneous drainage and antibiotics. The other 5 patients required surgical intervention involving either excision or drainage with or without proximal defunctioning/exclusion. There was a single 30-day mortality.
This study was limited by the small number of patients.
The majority of intra-abdominal desmoids with an air-fluid level require surgical intervention. Antibiotics and percutaneous drainage are only successful in a limited number of patients. We present our current treatment algorithm based on this experience.
Diseases of the Colon & Rectum 07/2012; 55(7):810-4. DOI:10.1097/DCR.0b013e318257fa93 · 3.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Dendritic cells (DC) dictate not only the type of T-cell immunity, but also homing patterns of T cells in mice. In humans, we characterized normal human gut DC and tested whether gut-specific homeostatic DC could be generated from blood precursors by factors in the gut microenvironment.
We characterized the phenotype and function of healthy human gut DC compared with blood and skin DC, and studied whether conditioning of blood DC in the presence of colonic biopsy supernatants (Bx-SN) induced gut-like phenotype and functions.
Blood DC mostly expressed both gut and skin homing markers, indicating potential to migrate to both major immune surface organs, and induced multi-homing T cells. However, DC within gut or skin did not demonstrate this multi-homing phenotype, were tissue-specific, and induced tissue-specific T cells. Human gut DC were less stimulatory for allogeneic T cells than their dermal and blood counterparts. Human blood DC cultured in vitro lost homing marker expression. Conditioning of human enriched blood DC with colonic Bx-SN from healthy controls induced a gut-homing phenotype and a homeostatic profile. Moreover, Bx-SN-conditioned DC demonstrated a restricted T-cell stimulatory capacity and preferentially induced gut-specific T cells. Retinoic acid and transforming growth factor beta (TGF-β) mediated the acquisition of the gut-homing and homeostatic properties, respectively, induced by colonic Bx-SN on blood enriched DC.
Tissue-specific factors manipulate immunity via modulating characteristics of DC and may provide tools to generate tissue-specific immunotherapy.
[Show abstract][Hide abstract] ABSTRACT: Although Non-steroidal anti-inflammatory drugs reduce colorectal adenoma burden in familial adenomatous polyposis (FAP), the utility of combining chemopreventive agents in FAP is not known. We conducted a randomised trial of celecoxib (CXB) versus CXB+diflouromethylornithine (DFMO) to determine the synergistic effect, if any.
The primary endpoint was % change in adenoma count in a defined field. Secondary endpoints were adenoma burden (weighted by adenoma diameter) and video review of entire colon/rectal segments. Adverse event (AEs) were monitored by National Cancer Institution toxicity criteria.
112 subjects were randomised: 60 men and 52 women at a mean age of 38 years. For the 89 patients who had landmark-matched polyp counts available at baseline and 6 months, the mean % change in adenoma count over the 6 months of trial was -13.0% for CXB+DFMO and -1.0% for CXB (p=0.69). Mean % change in adenoma burden was -40% (CXB+DFMO) vs -27% (CXB) (p=0.13). Video-based global polyp change was -0.80 for CXB+DFMO vs -0.33 for CXB (p=0.03). Fatigue was the only significant AE, worse on the CXB arm (p=0.02).
CXB combined with DFMO yielded moderate synergy according to a video-based global assessment. No significant difference in adenoma count, the primary endpoint, was seen between the two study arms. No evidence of DFMO-related ototoxicity was seen. There were no adverse cardiovascular outcomes in either trial arm and no significant increase in AEs in the CXB+DFMO arm of the trial. Differences in outcomes between primary and secondary endpoints may relate to sensitivity of the endpoint measures themselves.
ClinicalTrials.gov number N01-CN95040.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
[Show abstract][Hide abstract] ABSTRACT: Familial adenomatous polyposis (FAP) is a dominantly inherited condition caused by germline mutation of the APC gene resulting in formation of numerous large bowel adenomas in late childhood or adolescence. Unless these are removed, colorectal cancer inevitably develops. Prophylactic surgical treatment is required to prevent this. In surgical decision making, considerations should include genotype-phenotype correlation, perioperative morbidity and risk of impaired sexual and reproductive function in young patients after major pelvic surgery. Colectomy with ileorectal anastomosis remains an appropriate prophylactic procedure in many patients. However, in those with high-density polyposis or a genotype predictive of aggressive disease, restorative proctocolectomy is preferable. There is a range of other features, as FAP is essentially a systemic disease. These include duodenal and peri-ampullary adenomas and carcinoma, desmoid tumors, papillary-type thyroid carcinoma and pancreatic carcinoma among others. With improved management that reduces the risk of colorectal cancer, these extracolonic manifestations have become of increasing clinical significance. For all FAP patients, including those undergoing proctocolectomy, thorough surveillance is of vital importance as there remains a risk of developing neoplasia. Despite advances in surgical techniques, screening and surveillance, life expectancy in patients with FAP is still less than that of the general population.
Annals of Gastroenterology 03/2012; 25(3):201-206.
[Show abstract][Hide abstract] ABSTRACT: Aim: Present quality of life (QoL) instruments for inflammatory bowel disease (IBD) do not evaluate many social aspects of patients' lives that are potentially important in clinical decision making. We have developed a new Social Impact of Chronic Conditions - IBD questionnaire (SICC-IBD) to assess these areas. Method: A 34-item questionnaire was piloted to determine quality of life relating to education, personal relationships, employment, independence and finance. It was compared with the SF-36v2 and Inflammatory Bowel Disease (IBDQ) questionnaires in 150 patients with chronic ulcerative colitis on an endoscopic surveillance register who had never had surgery. Results: Reliability and validity testing enabled the questionnaire to be shortened to only 8 items. There was a high level of reliability (Cronbach's alpha = 0.72). The questionnaire correlated well with the social functioning domain of the SF-36 (r(s) =0.56) and was able to distinguish clinical severity of disease. Conclusion: The SICC-IBD is a new tool for assessment of patients with ulcerative colitis, which has identified new aspects of social disability for further study and for potential use as an additional tool in therapy decisions.