Short-term efficacy and safety of three novel sphincter-sparing techniques for anal fistulae: a systematic review.

BACKGROUND: The surgical treatment of complex anal fistulae, particularly those involving a significant portion of the anal sphincter in which fistulotomy would compromise continence, is challenging. Video-assisted anal fistula treatment (VAAFT), fistula tract laser closure (FiLaC™) and over-the-scope clip (OTSC®) proctology system are all novel sphincter-sparing techniques targeted at healing anal fistulae. In this study, all published articles on these techniques were reviewed to determine efficacy, feasibility and safety. METHODS: A systematic search of major databases was performed using defined terms. All studies reporting on experience of these techniques were included and outcomes (fistula healing and safety) evaluated. RESULTS: Eighteen studies (VAAFT-12, FiLaC™-3, OTSC®-3) including 1245 patients were analysed. All were case series, and outcomes were heterogeneous with follow-up ranging from 6 to 69 months and short-term (< 1 year) healing rates of 64-100%. Morbidity was low with only minor complications reported. There was one report of minor incontinence following the first reported study of FiLaC™, and this was treated successfully at 6 months with rubber band ligation of hypertrophied prolapsed mucosa. There are inconsistencies in the technique in studies of VAAFT and FiLaC™. CONCLUSIONS: All three techniques appear to be safe and feasible options in the management of anal fistulae, and short-term healing rates are acceptable with no sustained effect on continence. There is, however, a paucity of robust data with long-term outcomes. These techniques are thus welcome additions; however, their long-term place in the colorectal surgeon's armamentarium, whether diagnostic or therapeutic, remains uncertain.

Natural history of anorectal sepsis.

BACKGROUND: Progression from anorectal abscess to fistula is poorly described and it remains unclear which patients develop a fistula following an abscess. The aim was to assess the burden of anorectal abscess and to identify risk factors for subsequent fistula formation. METHODS: The Hospital Episode Statistics database was used to identify all patients presenting with new anorectal abscesses. Cox regression analysis was undertaken to identify factors predictive of fistula formation. RESULTS: A total of 165 536 patients were identified in the database as having attended a hospital in England with an abscess for the first time between 1997 and 2012. Of these, 158 713 (95·9 per cent) had complete data for all variables and were included in this study, the remaining 6823 (4·1 per cent) with incomplete data were excluded from the study. The overall incidence rate of abscess was 20·2 per 100 000. The rate of subsequent fistula formation following an abscess was 15·5 per cent (23 012 of 148 286) in idiopathic cases and 41·6 per cent (4337 of 10 427 in patients with inflammatory bowel disease (IBD) (26·7 per cent coded concurrently as ulcerative colitis; 47·2 per cent coded as Crohn's disease). Of all patients who developed a fistula, 67·5 per cent did so within the first year. Independent predictors of fistula formation were: IBD, in particular Crohn's disease (hazard ratio (HR) 3·51; P < 0·001), ulcerative colitis (HR 1·82; P < 0·001), female sex (HR 1·18; P < 0·001), age at time of first abscess 41-60 years (HR 1·85 versus less than 20 years; P < 0·001), and intersphincteric (HR 1·53; P < 0·001) or ischiorectal (HR 1·48; P < 0·001) abscess location compared with perianal. Some 2·9 per cent of all patients presenting with a new abscess were subsequently diagnosed with Crohn's disease; the median time to diagnosis was 14 months. CONCLUSION: The burden of anorectal sepsis is high, with subsequent fistula formation nearly three times more common in Crohn's disease than idiopathic disease, and female sex is an independent predictor of fistula formation following abscess drainage. Most fistulas form within the first year of presentation with an abscess.

Haemorrhoids: modern diagnosis and treatment.

Haemorrhoids present often to primary and secondary care, and haemorrhoidal procedures are among the most common carried out. They may co-exist with more serious pathology, and correct evaluation is important. In most cases a one-off colonoscopy in patients aged 50 or above with flexible sigmoidoscopy in younger patients is reasonable. Many people with haemorrhoids do not require treatment. Topical remedies provide no more than symptomatic relief-and even evidence for this is poor. Bulk laxatives alone may improve symptoms of both bleeding and prolapse and seem as effective as injection sclerotherapy. Rubber band ligation is effective in 75% of patients in the short term, but does not treat prolapsed haemorrhoids or those with a significant external component. Conventional haemorrhoidectomy remains the most effective treatment in the long term, the main limitation being post-operative pain. Metronidazole, topical sphincter relaxants and operative technique have all been shown to reduce pain. Stapled haemorrhoidectomy and haemorrhoidal artery ligation techniques are probably less effective but less painful. Long-term data are poor for all procedures, with many studies reporting only 1-3 years of follow-up data. Haemorrhoids are common in pregnancy, occurring in 40% of women. They can usually be treated conservatively during pregnancy, with any treatment delayed until after delivery. Acutely strangulated haemorrhoids may be treated either conservatively or operatively. There is an increased risk of anal stenosis after acute surgery, but the risks of sepsis and sphincter damage are less significant than previously thought. The majority of patients who are treated conservatively will still require definitive treatment at a later date.

Management of tailgut cysts in a tertiary referral centre: a 10-year experience.

AIM: Tailgut cysts are rare congenital lesions typically presenting as presacral masses. A variable clinical presentation often leads to misdiagnosis and unsuccessful operations. METHOD: A retrospective analysis was performed of tailgut cysts presenting to one surgeon at St Mark's hospital between 2003 and 2013. The patient demographic data and clinicopathological and radiological features, together with perioperative details and recurrence, were reviewed. RESULTS: A total of 17 patients (15 women) with a median age of 35 (21-64) years were included in the study. The mean duration of symptoms before referral was 40 months, with sepsis predominating in 12 cases. Fifteen of the patients had previously undergone surgery (mean 2.9 procedures). A posterior surgical approach was adopted in all patients with a coccygectomy performed in 13. A loop colostomy was formed in three patients. Two of them went on to have a secondary pull-through operation after an initial failed local repair of rectal injury. One case was reported to show malignant degeneration on histological examination. There was one recurrence during a median follow-up period of 13 (3-36) months. CONCLUSION: Tailgut cysts are an uncommon yet important cause of chronic perianal sepsis. Suspicion should be raised in a patient, usually female, presenting with a history of unsuccessful procedures. Diagnosis can be made by clinical assessment and MRI. Complete excision usually resolves the problem.

What role do bacteria play in persisting fistula formation in idiopathic and Crohn's anal fistula?

AIM: The aetiology of Crohn's disease-related anal fistula remains obscure. Microbiological, genetic and immunological factors are thought to play a role but are not well understood. The microbiota within anal fistula tracts has never been examined using molecular techniques. The present study aimed to characterize the microbiota in the tracts of patients with Crohn's and idiopathic anal fistula. METHOD: Samples from the fistula tract and rectum of patients with Crohn's and idiopathic anal fistula were analysed using fluorescent in situ hybridization, Gram staining and scanning electron microscopy were performed to identify and quantify the bacteria present. RESULTS: Fifty-one patients, including 20 with Crohn's anal fistula, 18 with idiopathic anal fistula and 13 with luminal Crohn's disease and no anal fistula, were recruited. Bacteria were not found in close association with the luminal surface of any of the anal fistula tracts. CONCLUSION: Anal fistula tracts generally do not harbour high levels of mucosa-associated microbiota. Crohn's anal fistulas do not seem to harbour specific bacteria. Alternative explanations for the persistence of anal fistula are needed.

Systematic review: the combined surgical and medical treatment of fistulising perianal Crohn's disease.

BACKGROUND: The management of perianal Crohn's fistulas represents a significant challenge. A combination of medical and surgical therapy, guided by radiology, is often required. AIM: To review systematically the literature to assess fistula healing rates with medical treatment (anti-TNF-α therapies ± immunomodulators) or surgical treatment alone, compared with combined medical and surgical treatment in fistulising perianal Crohn's disease (CD). METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. Two independent reviewers searched the literature. RESULTS: Twenty-four articles were included. The total population was 1139 patients; 460 (40%) received single treatment with either medical or surgical therapy, and 679 (60%) received combined medical and surgical therapy. Eight studies compared single and combination therapy, with a total population of 797 patients (single therapy: n = 448, combination therapy: n = 349). In the single therapy group, 191/448 were in complete remission (43%). This was lower than the healing rate of the combination therapy group 180/349 (52%). No response to therapy was noted in 34% (153/448) of the single therapy group compared with 23% (80/349) of the combination group. CONCLUSIONS: Combined surgical and medical (anti-TNF-α ± immunomodulators) therapy may have additional beneficial effects on perianal fistula healing in patients with Crohn's disease, compared with surgery or medical therapy alone. A well-designed Crohn's perianal fistula clinical trial is required in a multidisciplinary medical and surgical setting, with clearly defined end points of clinical (and likely patient reported outcomes) and radiological healing.

Outcomes of laparoscopic and open restorative proctocolectomy.

BACKGROUND: The literature on laparoscopic restorative proctectomy (RP) and proctocolectomy (RPC) is limited. This study compared clinical outcomes of laparoscopic RP and RPC with those of conventional open surgery at one centre. METHODS: Data were analysed from consecutive patients undergoing RPC and RP between November 2006 and November 2011. A standard laparoscopic technique was developed during the first 2 years, performed by two laparoscopic surgeons, with selection of patients who had not previously undergone open colectomy. Study endpoints included postoperative length of stay, 30-day morbidity, readmission, reoperation, pouch function and failure. RESULTS: A total of 207 patients were included; open surgery was performed in 131 (63·3 per cent) and a laparoscopic procedure in 76 (36·7 per cent). There were no significant differences in patient demographics. The conversion rate was 9 per cent (7 of 76). The median (i.q.r.) duration of operation was shorter for open than for laparoscopic procedures: 208 (178-255) versus 285 (255-325) min respectively (P < 0·001). Laparoscopic RPC had a shorter length of stay: median (i.q.r.) 6 (4-8) versus 8 (7-12) days (P < 0·001). The rate of minor complications was lower in the laparoscopic group (33 versus 50·4 per cent; odds ratio (OR) 0·48, 95 per cent confidence interval 0·27 to 0·87).There were no significant differences in total complications (51 per cent after laparoscopy versus 61·5 per cent after open surgery; OR 0·66, 0·37 to 1·17), anastomotic leakage, major morbidity, 30-day readmission, reoperation and stoma closure rates. Pouch failure (including permanent stoma) occurred in 14 (7·7 per cent) of 181 patients. Three patients died, all in the open surgery group. CONCLUSION: Laparoscopic RPC is feasible with some short-term advantages.

Clinical outcomes of colo-anal pull-through procedure for complex rectal conditions.

AIM: Pull-through with colo-anal sleeve anastomosis may be used as a last resort to avoid permanent diversion in patients with complex rectal conditions. This procedure allows the preservation of intestinal continuity by minimizing the hazards of deep dissection in an inflamed and fibrosed pelvis. METHOD: A retrospective study was performed of colo-anal pull-through procedures carried out between January 1998 and December 2012 at St Mark's Hospital by one surgeon. Patients were identified from operative logbooks and their case notes were reviewed. Thirty-four patients (21 women) with a median age of 54 (21-75) years underwent the pull-through operation for complex rectal conditions involving fistulae and/or a hostile pelvis as a final attempt to restore intestinal continuity. RESULTS: The median length of hospital stay was 7.5 (5-45) days. Median follow-up was 23 (3-71) months. There was no peri-operative mortality. There were two (6%) outright failures. Early complications occurred in 14 (41%) patients and late complications in 10 (29%). Fistulae recurred in seven (25%) of 28 patients but with further treatment four healed, giving an overall healing rate of 89%. Normal continence was achieved in 19 (79%) of 24 patients who were evaluated. CONCLUSION: In clinically difficult rectal situations the colo-anal pull-through procedure is a suitable salvage procedure to restore intestinal continuity before considering a permanent stoma.

Fistulotomy in the tertiary setting can achieve high rates of fistula cure with an acceptable risk of deterioration in continence.

INTRODUCTION: Surgery is the mainstay of treatment of anal fistulas. Low fistulas are often laid open, but higher fistulas present a more difficult problem. Patient choice centres on a compromise between risk of recurrence and risk of impairment of continence. We aimed to determine the efficacy and safety of fistulotomy at a tertiary referral centre, in particular the additional risk of impairment of continence following fistulotomy of the often recurrent, multiply-operated patients seen. METHODS: Patients undergoing surgery under the senior author (RKSP) for an anal fistula during the study period (2005-2006) were identified, and a thorough review of the patients' clinical records was undertaken. Demographic, fistula anatomy, treatment and follow-up data were obtained. RESULTS: Eighty-four patients underwent either fistulotomy (50), insertion of permanent loose (drainage) seton (28) or EUA with or without drainage of abscess. Mean length of follow up was 11 months (SD 14.22). In the fistulotomy group, we found an overall success rate of 93 %. Secondary extensions were associated with failure to achieve cure (P = 0.008). Nine patients (20 %) suffered deterioration in continence after surgery. A longer time to referral was associated with impaired final continence. In the group referred from a surgeon in secondary care, 91 % of patients were cured, and continence impairment (mostly minor) rose from 32 % at referral to 40 % after surgery. CONCLUSIONS: We have shown that it is safe and reasonable to offer fistulotomy to appropriate patients despite previous surgery and within the tertiary setting. By so doing, a very high rate of healing can be achieved in patients who have previously failed. The additional risk of impairment of continence is around one in five, and in the majority will represent only minor incontinence.

Ligation of the intersphincteric fistula tract in the management of anal fistula. A systematic review.

AIM: Over the last 5 years, the ligation of the intersphincteric fistula tract (LIFT) procedure has become increasingly popular as a sphincter-preserving technique for the treatment of anal fistula. The aim of this article was to review the published literature on the LIFT procedure. METHOD: The Cochrane database and EMBASE were searched from January 1980 to November 2012, and PubMed from January 1966 to November 2012. All peer-reviewed studies that investigated the LIFT procedure for the treatment of anal fistula were eligible for inclusion. Technical notes, commentaries, letters and meeting abstracts were excluded. The primary outcome measured was the overall fistula closure rate in relation to the length of follow-up. RESULTS: Twenty-nine articles were originally identified using the search criteria. Thirteen were finally included for analysis. Sample sizes ranged from 18 to 93 patients, with a pooled total of 498. Most fistulae, 494 (99%), were of cryptoglandular aetiology, of which 470 (94%) were transsphincteric. Overall success rates ranged from 40 to 95%, with a pooled success of 71% (352 of 495 patients; 3 of 498 were lost to follow-up). Follow-up ranged from 1 to 55 months, with a reported mean or median of 4 to 19.5 months. One hundred and eighty-three patients were formally assessed for continence, out of whom 11 (6%) had a minor disturbance. CONCLUSION: Overall the systematic review shows that the LIFT procedure appears to be an effective sphincter-conserving approach for the treatment of transsphincteric anal fistula with a pooled healing rate of 71% over a mean or median follow-up period ranging from 4 to 19.5 months.

Surgical management of rectovaginal fistula in a tertiary referral centre: many techniques are needed.

AIM: Surgery is the mainstay of treatment for rectovaginal fistula (RVF). Published success rates vary with initial success being around 50% rising to 80% with repeated surgery. Fistulae in Crohn's disease are more likely to recur. METHOD: A retrospective study was performed of RVF repair carried out between 2003 and 2008 in a tertiary referral centre. Patients undergoing surgery for an RVF under the senior author during the study period were identified and their clinical notes were reviewed. RESULTS: Thirty-five patients underwent 50 operations. The median age was 42 years and 83% were tertiary referrals. Two patients were lost to follow-up. Healing occurred in 19 (58%) of 33 patients after a mean of 1.4 operations. The median time to success was 11 (2.5-48) months. The 'curative' group had an overall success of 73% (19 of 26). Seventy-five per cent of non-inflammatory bowel disease patients and 67% of those with Crohn's disease had successful treatment of the RVF. Twenty-four of 35 patients (67%) underwent creation of a stoma. Sixteen of 24 (67%) were deemed fit for restoration of continuity. No demographic or disease related factors were found to influence healing. CONCLUSION: Cure of RVF can be achieved by a range of surgical approaches including abdominal and anal. A variety of different anal techniques are necessary, depending on the integrity of the anal sphincter and the presence or absence of perineal descent/internal intussusception.

Imaging assessment of desmoid tumours in familial adenomatous polyposis: is state-of-the-art 1.5 T MRI better than 64-MDCT?

OBJECTIVE: Desmoid tumour is a common extraintestinal manifestation of patients with familial adenomatous polyposis (FAP) who have undergone prophylactic colectomy. We aimed to determine whether MRI provides equivalent or better assessment of desmoid tumours than CT, the current first-line investigation. METHODS: Following ethics approval and informed consent, FAP patients with known desmoid tumour underwent contrast-enhanced 64-slice multidetector CT (MDCT) and 1.5 T MRI (incorporating T(1) weighted, T(2) weighted, short tau inversion-recovery and T(1) weighted with contrast, axial, sagittal and coronal sequences). The number, site, size, local extent, tumour signal intensity and desmoid-to-aorta enhancement ratio were analysed. RESULTS: MRI identified 23 desmoid tumours in 9 patients: 9 intra-abdominal desmoid (IAD) tumours, 10 abdominal wall desmoid (AWD) tumours and 4 extra-abdominal desmoid (EAD) tumours. CT identified only 21 desmoids; 1 EAD and 1 AWD were not identified. The two modalities were equivalent in terms of defining local extent of desmoid. Five IAD tumours involved the bowel, six caused ureteric compression and none compromised the proximal superior mesenteric artery. There was no difference in median desmoid size: 56.7 cm(2) (range 2-215 cm(2)) on MDCT and 56.3 cm(2) (3-215 cm(2)) on MRI (p=0.985). The mean MRI enhancement ratio, at 1.12 (standard deviation 0.43), was greater than the CT enhancement ratio, which was 0.48 (0.16) (p<0.0001). High signal intensity on T(2) MRI was associated with increased MRI enhancement ratio (p=0.006). CONCLUSIONS: MRI is at least equivalent (and may be superior) to MDCT for the detection of desmoid tumours in FAP. Coupled with the advantage of avoiding radiation, it should be considered as the primary imaging modality for young FAP patients.

Laparoscopic total colectomy and ileorectal anastomosis (IRA), supported by an enhanced recovery programme in cases of familial adenomatous polyposis.

AIM: Familial adenomatous polyposis (FAP) is associated with an almost 100% chance of colorectal cancer by the age of 50 years. Surgery is the only prophylaxis. The study compared the outcome of prophylactic laparoscopic colectomy and ileorectal anastomosis (IRA) with conventional open surgery. METHOD: A case-control study was carried out including all cases of proven FAP undergoing prophylactic laparoscopic colectomy with IRA between 1 April 2006 and 31 March 2008 using a standardized technique within an enhanced recovery programme (ERAS). All data were collected prospectively. Controls were identified retrospectively from patients who underwent open prophylactic IRA before 31 March 2008 and were matched for age, gender, BMI and ASA. Outcomes included duration of surgery, complications, length of stay, readmission and mortality. RESULTS: During the study period 25 patients underwent laparoscopic IRA. The median operating time was longer in the laparoscopic group (235 vs 180 mins, P < 0.0001) but the median hospital stay was shorter (6 vs 9 days, P = 0.002). Overall there were fewer complications in the laparoscopic group (20%vs 40%, P = 0.3). CONCLUSION: Laparoscopic prophylactic colectomy with IRA in FAP is safe and feasible, and combined with ERAS leads to accelerated recovery and possibly fewer complications than open surgery. FAP patients undergoing prophylactic IRA should be offered laparoscopic surgery.

Peutz-Jeghers syndrome: intriguing suggestion of gastrointestinal cancer prevention from surveillance.

BACKGROUND: Peutz-Jeghers syndrome is characterized by GI polyps and mucocutaneous pigmentation and carries an increased risk of GI cancer. GI polyps may bleed or cause intussusception. Luminal GI surveillance is recommended, but there are few data detailing outcomes from GI surveillance in Peutz-Jeghers syndrome. OBJECTIVE: This study aimed to assess outcomes from GI surveillance in patients with Peutz-Jeghers syndrome. DESIGN: This study is a retrospective review, using hospital and registry notes and endoscopy and histology reports. SETTING: The investigation was conducted at a tertiary referral center. PATIENTS: All patients with Peutz-Jeghers syndrome who were followed up at St Mark's hospital were included. MAIN OUTCOME MEASURES: The primary outcomes measured were surveillance procedures performed, complications, and long-term outcomes. RESULTS: Sixty-three patients from 48 pedigrees were included; the median age when patients were first seen was 20 years (range, 3-59). Only baseline investigations were performed in 12 patients. The remaining patients were followed up for 683 patient years, a median of 10 years (range, 2-41). Seven hundred seventy-six procedures were performed to assess the GI tract. These led to 5 double-balloon enteroscopies, 1 push enteroscopy, and 71 surgical procedures. Of the surgical procedures, 20 were performed as a result of baseline investigations, 12 arose from investigations of symptoms, and 39 were due to surveillance of asymptomatic patients. No emergency surgical interventions were performed. No luminal GI cancers were diagnosed. Of the 2461 polypectomies performed, 6 polyps contained atypia or dysplasia. Six complications arose from endoscopy or surgical intervention, requiring 5 laparotomies to manage these complications. CONCLUSION: GI surveillance in Peutz-Jeghers syndrome is relatively safe and avoids the need for emergency surgery for small-bowel polyps. The lack of GI cancers may reflect that surveillance and polypectomy have prevented cancer from developing, although the detection of neoplasia or dysplasia is uncommon.

Gastrointestinal polyps and cancer in Peutz-Jeghers syndrome: clinical aspects.

The two main problems in the management of the gastrointestinal tract in patients with Peutz-Jeghers syndrome (PJS) are the long term cancer risk and managing polyp related complications, such as intussusception and bleeding. In this article we will focus mainly on the clinical management of these problems. We will highlight some of the controversies regarding gastrointestinal PJS polyps, cancer development and cancer risk. We will review the available literature, particularly focusing on clinical data, to provide insights into these controversies. We describe guidelines for the surveillance and management of gastrointestinal polyps in PJS and review the data behind current recommendations.

For many high anal fistulas, lay open is still a good option.

BACKGROUND: Optimal treatment for high/complex anal fistulas is uncertain. We have studied one surgeon's results over a ten-year period, concentrating on high fistulas. METHODS: Demographic, fistula anatomy and treatment data were recorded for all patients undergoing surgery for anal fistula. Outcome data were recorded for patients who had been followed up for a minimum of 4 weeks. RESULTS: One hundred and eighty patients were studied. Outcome data were available for 52 low and 84 high fistulas. Fistulotomy was performed for 50 low and 48 high fistulas, with closure rates of 98 and 96%, respectively. There was fistula recurrence in two patients with high fistulas. Symptoms of sphincter disturbance were similar after lay open of low and high fistulas. Treatment of a high fistula by drainage seton had a lower rate of inadvertent passage of flatus but a similar rate of minor soiling compared with fistulotomy. CONCLUSIONS: Lay open of low and high anal fistulas is effective and associated with a similar, predictable rate of minor sphincter disturbance, amounting to a third to one quarter of patients with mild leakage of flatus and mucus. Patients with high fistulas can be cured, but when a surgeon is in doubt, a second opinion at an expert centre should be sought before definitive intervention.

Review article: medical, surgical and radiological management of perianal Crohn's fistulas.

BACKGROUND: Crohn's anal fistulas are common and cause considerable morbidity. Their management is often difficult; medical and surgical treatments rarely lead to true healing with frequent recurrence and complications. AIM: To examine medical treatments previously and currently used, surgical techniques and the important role of optimal imaging. METHODS: We conducted a literature search in the Pub Med database using Crohn's, Anal Fistula, Surgery, Imaging and Medical Treatment as search terms. RESULTS: Antibiotics and immunosuppressants have a role, but slow initial response, side effects and relatively low remission rates of up to around a third with frequent recurrence limit their value. Long-term infliximab produces clinical remission in 36-58% of patients with combined medical and surgical management achieving optimal outcomes. Traditional and newer surgical procedures often have a high rate of recurrence with a significant risk of temporary or, in up to 10% of cases, permanent stomas, incontinence and unhealed or slowly healing wounds in 30%. CONCLUSIONS: Management of Crohn's anal fistulas remains challenging. Established principles are to drain infection, use setons as required, aggressively manage active proctitis, give antibiotics, immunosuppressants and employ anti-TNFα therapy, and they demand significant co-operation between gastroenterologists and surgeons.

The role of cell proliferation and crypt fission in adenoma aggressiveness: a comparison of ileoanal pouch and rectal adenomas in familial adenomatous polyposis.

AIM: In patients with familial adenomatous polyposis (FAP), ileoanal pouch cancer is rare whereas rectal cancer is common, despite polyp initiation at the two sites being similar at the molecular level. This study investigated whether the disparity in adenoma aggressiveness reflects underlying differences in histogenesis. METHOD: Normal mucosal biopsies and 2-3 mm adenomas from patients with FAP were dissected into individual crypts. Crypt area, morphology, fission and mitoses were analysed for crypts from pouch, rectum and supra-anastomotic ileum. Immunohistochemistry of similar archival samples was performed for lysozyme, ß-catenin and TP53 expression. RESULTS: The morphology of normal crypts was similar at each site, although crypt area differed. The area of normal pouch crypts was intermediate between rectum and ileum. The area of adenomatous crypts of rectum and pouch was similar, but the latter had increased asymmetrical fission. Crypt mitoses were proportional to area in all tissues, but crypt fission was reduced in adenomatous crypts from the rectum compared with the pouch. Pouch adenomas retained lysozyme expression as seen in normal ileum. Nuclear ß-catenin accumulation was similar, but TP53 expression was increased in rectal adenomas. CONCLUSION: Diminutive polyps from rectum and pouch differ in morphology and proliferation. Aggressiveness in rectal polyps is not conferred by increased crypt proliferation, fission, or activation of the Wnt signalling pathway. Increased TP53 expression suggests other molecular mechanisms may be responsible. While crypt mitoses are proportional to crypt area, the threshold for fission may be site specific, indicating that tissue origin may influence histogenesis and thus malignant potential.

Risk factors predicting desmoid occurrence in patients with familial adenomatous polyposis: a meta-analysis.

AIM: Desmoid tumours (DT) are myofibroblastic proliferations occurring in 15% of patients with familial adenomatous polyposis (FAP). Several small series have analysed the incidence of DT and predisposing risk factors. Using meta-analytical techniques, this study aimed to identify risk factors for DT development in patients with FAP. METHOD: Studies of sporadic DT were excluded. The study end-points were the incidence of DT in FAP and DT development by gender, adenomatous polyposis coli (APC) mutation, family history of DT and previous abdominal surgery. A random effect Mantel-Haenszel model was used to calculate odds ratios for each risk factor and age group. RESULTS: Ten studies of 4625 patients with FAP fulfilled our inclusion criteria. A total of 559 (12%) patients developed DT. Cumulative analysis demonstrated that 80% of DT developed by age 40, the peak incidence rate being in the second and third decades. A positive family history of DT was the most significant risk factor (OR 7.02, 95% CI 4.15-11.9, P < 0.001). An APC mutation 3' to codon 1399 (OR 4.37, 95% CI 2.14-8.91, P < 0.001) and previous abdominal surgery (OR 3.35, 95% CI 1.33-8.41, P = 0.01) were also implicated. Women were more likely to develop DT (OR 1.57, 95% CI 1.13-2.18, P = 0.007). CONCLUSION: There is consistency amongst polyposis registries in documenting the incidence and risk factors for DT development. Having a positive family history for DT is of greater significance than a 3' mutation, suggesting the existence of modifier genes, independent of the APC genotype-phenotype correlation. Few of these risk factors are modifiable. Delaying prophylactic surgery could be appropriate in female patients with a 3' APC mutation and attenuated polyposis.

Risk factors for secondary proctectomy in patients with familial adenomatous polyposis.

BACKGROUND: Colectomy and ileorectal anastomosis (IRA) or restorative proctocolectomy are performed for prophylaxis in familial adenomatous polyposis (FAP). After IRA patients may require secondary proctectomy for worsening polyposis or rectal cancer. Outcomes after IRA were evaluated and risk factors predictive of progressive rectal disease identified. METHODS: Parametric survival analysis was used to identify predictors of progressive rectal disease in all patients undergoing an IRA for FAP at a single centre. Hazard ratios (HRs) were calculated for phenotype, genotype, sex, age at surgery and presence of colonic cancer. RESULTS: Of 427 patients who underwent IRA, 48 (11.2 per cent) developed rectal cancer and 77 (18.0 per cent) required proctectomy for worsening polyposis over a median follow-up of 15 (range 7-25) years. By the age of 60 years half of the patients retained their rectum. Rectal polyp count exceeding 20 (HR 30.99, 95 per cent confidence interval 9.57 to 100.32; P < 0.001), APC mutation codon 1250-1450 (HR 3.91, 1.45 to 10.51; P = 0.007), colonic polyp count 500 or more (HR 2.18, 1.24 to 3.82; P = 0.006) and age less than 25 years at the time of surgery (HR 1.99, 1.17 to 3.37; P = 0.011) were independent predictors of progressive rectal disease. CONCLUSION: The risk of proctectomy after IRA for FAP is based on patient genotype, phenotype and age at surgery.