Susan K Clark

St. Mark's Hospital, Harrow, England, United Kingdom

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Publications (47)279.69 Total impact

  • Journal of Pediatric Surgery 03/2015; DOI:10.1016/j.jpedsurg.2015.03.049 · 1.31 Impact Factor
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    ABSTRACT: 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.
    Inflammatory Bowel Diseases 09/2014; 20(11). DOI:10.1097/MIB.0000000000000182 · 5.48 Impact Factor
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    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; · 3.58 Impact Factor
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    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.
    Colorectal Disease 10/2013; 16(3). DOI:10.1111/codi.12468 · 2.02 Impact Factor
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    European Cancer Congress 2013, Amsterdam; 09/2013
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    European Cancer Congress 2013, Amsterdam; 09/2013
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    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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
    Surgical Endoscopy 04/2013; 27(10). DOI:10.1007/s00464-013-2946-z · 3.31 Impact Factor
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    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 · 3.20 Impact Factor
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    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 · 1.62 Impact Factor
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    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 · 3.20 Impact Factor
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    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.
    Gastrointestinal Endoscopy 04/2012; 75(4):AB285. DOI:10.1016/j.gie.2012.03.725 · 4.90 Impact Factor
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    Vera N Tudyka, Susan K Clark
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    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.
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    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.
    Inflammatory Bowel Diseases 01/2012; 18(7):1275-86. DOI:10.1002/ibd.21893 · 5.48 Impact Factor
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    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.
    Colorectal Disease 11/2011; DOI:10.1111/j.1463-1318.2011.02880.x · 2.02 Impact Factor
  • Annals of Surgery 01/2011; 254(4):669-670. DOI:10.1097/SLA.0b013e318230669c · 7.19 Impact Factor
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    ABSTRACT: The study compared the risk of adenoma or carcinoma formation in the anorectal segment after either mucosectomy with manual anastomosis or stapled ileoanal anastomosis (IAA) following restorative proctocolectomy (RPC) for familial adenomatous polyposis (FAP). Few data exist on the risk of adenoma formation after either technique in FAP. All endoscopy and histology reports for patients having RPC for FAP attending for annual pouchoscopy from 1978 to 2007 were reviewed. The incidence, timing, and histological characteristics of adenoma or carcinoma formation were recorded. Of the 206 patients, 140 attended for endoscopic follow-up for a median of 10.3 years after RPC. Fifty-two patients developed neoplastic transformation in the anorectal segment, with a cumulative risk at 10 years of 22.6% after mucosectomy with manual anastomosis and 51.1% after stapled IAA (P < 0.001). The median time to first adenoma was longer after mucosectomy with handsewn anastomosis than after stapled IAA (10.1 vs 6.5 years, P < 0.001). On multivariate analysis, stapled IAA (hazard ratio= 3.45, 95% confidence interval = 1.01–4.98) and age at RPC older than 40 years (hazard ratio = 2.20, 95% confidence interval = 1.01–4.89) were significantly associated with increased risk of adenoma formation. Nine patients developed a large (>10 mm) adenoma. One patient (handsewn ileoanal anastomosis) developed adenocarcinoma in the anorectal mucosa at 13 years and required pouch excision. Adenoma formation in the anorectal mucosa after RPC for FAP is common but carcinoma is rare. The risk is lower after mucosectomy with handsewn anastomosis than after stapled IAA. Regular endoscopic surveillance after either technique is mandatory.
    Annals of surgery 12/2010; 253(2):314-7. DOI:10.1097/SLA.0b013e318f3f498 · 7.19 Impact Factor
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    ABSTRACT: Familial adenomatous polyposis (FAP) is a dominantly inherited colorectal cancer (CRC) syndrome with an untreated lifetime prevalence of CRC close to 100% and extracolonic manifestations (ECM) of increasing clinical significance. This study examined the effect of systematic callup and prophylactic colectomy on FAP survival. Patients diagnosed, treated and followed-up at our institution were analysed. 'Callups' were those identified via the callup system; 'probands' were those identified by other means. Proportions were analysed by Chi-squared or Fischer's exact test. Mortality rates were indirectly standardised to the UK population. Survival curves from birth were estimated by Kaplan-Meier. A total of 439 patients (293 callups, 146 probands) were analysed. Crude mortality rates (CMRs) of callups and probands were 4.85 per 1,000 person years (PY) and 9.71 per 1,000 PY, respectively-a rate ratio of 0.50 (95% CI 0.34-0.72, P = 0.0001). The standardised mortality ratio (SMR) of callups was non-significantly lower than probands (4.12 vs. 4.70). Callups experienced non-significantly lower age-band specific SMR up to 45 years. More probands died of CRC (42.4 vs. 22.5%, P = 0.025), whereas more callups died of ECM (30.6 vs. 13.4%, P = 0.027). Median survival was 64 years for callups and 60 years for probands; survival curves did not differ significantly (P = 0.253). The crude mortality rate of callups is approximately half that of probands. As fewer callups die of CRC, a greater proportion die of ECMs. Callups experienced non-significantly reduced mortality up to 45 years. Whilst the FAP callup system reduces CRC risk, mortality attributable to ECMs needs to be addressed.
    Familial Cancer 11/2010; 10(1):11-20. DOI:10.1007/s10689-010-9394-x · 1.62 Impact Factor
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    ABSTRACT: Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome with a penetrance close to 100% at the age of 40 years. The incidence is thought to be equal among both sexes, but we noticed an excess of males undergoing primary surgery for FAP at our institution. The aim of the study is to investigate the hypothesis that FAP patients produce an excess of affected male offspring. We identified all families with known APC mutation in the polyposis registry at St Mark's from its foundation until October 2009. We analysed their pedigrees with respect to gender of the affected individuals with progeny and to the gender and mutation status of their offspring. Only individuals with complete data regarding their offspring (gender and mutation status) were included. We identified 666 (324 males and 342 females) affected individuals with progeny. We analysed the progeny of 368 (182 males, 186 females) affected individuals with complete data on all offspring: 235 (27.5%) affected males, 212 (24.8%) affected females, 207 (24.3%) unaffected males and 200 (23.4%) unaffected females. The overall ratio of affected/unaffected and male/female offspring did not differ from the expected 50%. Further sub-analysis by gender of parents did not show any statistically significant difference in gender and mutation status of offspring. In addition the mean number of children per affected parent did not depend on gender (males 2.34; females 2.30). This study shows that gender does not influence the genetic transmission of FAP. The excess of males undergoing primary surgery at our institution is probably a result of referral bias.
    Familial Cancer 09/2010; 9(3):405-6. DOI:10.1007/s10689-010-9341-x · 1.62 Impact Factor
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    ABSTRACT: The objective of our study was to assess the utility of MR enterography compared with capsule endoscopy for the detection of small-bowel polyps in patients with Peutz-Jeghers syndrome (PJS). Adult patients with PJS scheduled for surveillance capsule endoscopy were prospectively recruited and underwent MR enterography and capsule endoscopy. Polyps > 10 mm were regarded as clinically relevant. When appropriate, large polyps (> 15 mm) were removed at enteroscopy, enabling correlation with MR enterography and capsule endoscopy findings. Interobserver agreement for MR enterography and capsule endoscopy was calculated. Patient comfort, convenience, and test preference were assessed. Nineteen patients (median age, 39.6 years) underwent both procedures. There was no significant difference between techniques for the detection of polyps > 10 mm (18 vs 23 polyps at capsule endoscopy and MR enterography, respectively; p = 0.35) or in the number of patients in whom > 10 mm polyps were detected (eight vs 11 patients at capsule endoscopy and MR enterography, respectively; p = 0.38). However, in three patients, large polyps (> 15 mm) detected on MR enterography were not detected on capsule endoscopy; large polyps were seen in six patients at capsule endoscopy and in nine patients at MR enterography (p = 0.25). Interobserver agreement was high for MR enterography but was only fair for capsule endoscopy (kappa = 0.81 and 0.27, respectively). Size assessments of large polyps (> 15 mm) appeared more reproducible with MR enterography than with capsule endoscopy. Patients rated capsule endoscopy as more comfortable than MR enterography. There was no significant difference between the techniques with regard to patient convenience or preference. MR enterography is a promising alternative to capsule endoscopy for small-bowel surveillance in adults with PJS. Although our results suggest that capsule endoscopy is more comfortable for the patient, MR enterography may be less prone to missing large polyps and may be more reliable in their size assessment.
    American Journal of Roentgenology 07/2010; 195(1):108-16. DOI:10.2214/AJR.09.3174 · 2.74 Impact Factor
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    ABSTRACT: To identify, compare, and contrast the microbiota in patients with and without pouchitis after restorative proctocolectomy (RPC) for ulcerative colitis (UC) and familial adenomatous polyposis (FAP). Pouchitis is the most common complication following RPC. An abnormal host-microbial interaction has been implicated. We investigated the pouch microbiota in patients with and without pouchitis undergoing restorative proctocolectomy for UC and FAP. Mucosal pouch biopsies, taken from 16 UC (pouchitis 8) and 8 FAP (pouchitis 3) patients were analyzed to the species (or phylotype) level by cloning and sequencing of 3184 full-length bacterial 16S rRNA genes. There was a significant increase in Proteobacteria (P = 0.019) and a significant decrease in Bacteroidetes (P = 0.001) and Faecalibacterium prausnitzii (P = 0.029) in the total UC compared with the total FAP cohort, but only limited differences were found between the UC nonpouchitis and pouchitis groups and the FAP pouchitis and nonpouchitis groups. Bacterial diversity in the FAP nonpouchitis group was significantly greater than in UC nonpouchitis (P = 0.019) and significantly greater in UC nonpouchitis compared with UC pouchitis (P = 0.009). No individual species or phylotype specifically associated with either UC or FAP pouchitis was found. UC pouch patients have a different, less diverse, gut microbiota than FAP patients. A further reduction in bacterial diversity but no significant dysbiosis occurs in those with pouchitis. The study suggests that a dysbiosis occurs in the ileal pouch of UC RPC patients which predisposes to, but may not directly cause, pouchitis.
    Annals of surgery 07/2010; 252(1):90-8. DOI:10.1097/SLA.0b013e3181e3dc8b · 7.19 Impact Factor

Publication Stats

624 Citations
279.69 Total Impact Points

Institutions

  • 2001–2015
    • St. Mark's Hospital
      Harrow, England, United Kingdom
  • 2010–2013
    • Imperial College London
      • Division of Surgery
      Londinium, England, United Kingdom
  • 2012
    • North West London Hospitals NHS Trust
      Harrow, England, United Kingdom