Allogenic Stem Cells in Anal Fistulas of Crohn's Disease: From Promising Premises to Real Life Experience.

BACKGROUND: Allogenic adipocyte stem cells represent an unprecedented opportunity for regenerative therapy to treat Crohn anal fistulas. Apart from the results of one 8-year-old trial, scientific evidence remains scarce. METHODS: Data from consecutive patients treated with darvadstrocel for Crohn anal fistulas were reviewed at 6 first tertiary reference centers. The judgment criteria combined asymptomatic status plus clinical occlusion of the fistula tract and MRI-confirmed healing of the tract (no inflammation and/or disappearance of the tract). Both clinical and MRI-confirmed healing of the tract defined a deep remission. Clinical remission was defined by an absence of complaint, occlusion of all external openings, and no fistula discharge. RESULTS: A total of 116 patients were extracted (median follow-up after cell stem injection: 11 [6-14] months). No severe adverse events were reported after surgery except for subsequent anal surgery in 29 (25%) patients. Fifty-one (44%) patients had clinical remission defined by the absence of complaints, the occlusion of all external openings, and the presence of no fistula discharge. Deep remission was observed in 23 (29%) patients. Patients with clinical remission more often received combined therapy (immunosuppressant antitumor necrosis factors) than those with no improvement (31 of 51 [61%] vs 23 of 65 [35%]; P = .007). Regression analysis showed that high fistulas (odds ratio, 3.8 [1.1-12.5]; P = .03) and younger age (<38 years, odds ratio, 2.3 [1.0-58;4]; P = .02) were associated with a better outcome. CONCLUSIONS: Allogeneic stem cell treatment of Crohn's anal fistulas results in complete remission in less than half of patients, with a significant reintervention rate.

In a multicenter experience in real life, allogeneic stem cell treatment of Crohn's anal fistulas results in complete remission in less than half of patients, with a significant reintervention rate.

Prospective and multicentre study of radiofrequency treatment in anal fistula.

BACKGROUND: The most effective treatment for anal fistula is fistulotomy, but it involves a risk of anal incontinence. To reduce this morbidity, sphincter-sparing treatments have been developed, but their success in real life is often less than 50%. The aim is to determine the clinical healing rate 6 months after radiofrequency treatment. METHODS: We planned to evaluate 50 patients from three French proctology centres. Treatment efficacy was evaluated at 6 and 12 months by means of clinical and magnetic resonance imaging examination. We evaluated morbidity and healing prognostic factors. RESULTS: Fifty patients with a mean age of 51 years (22-82) were included. Eleven patients had a low trans-sphincteric fistula (LTS), 21 patients had a high trans-sphincteric fistula (HTS), eight had a complex fistula and nine had Crohn's disease fistula. After 6 months, 17 patients (34.7%) had a clinically healed fistula, including five (45.5%) with LTS fistula, seven (33.3%) with HTS fistula, one (12.5%) with complex fistula, four (44.4%) with Crohn's disease, with no significant difference between these fistula types (p: 0.142). At 12 months, the healing rate was identical. MRI in 15 out of 17 clinically healed patients showed a deep remission of 73.3% at 12 months. Energy power was associated with the success of the treatment. There was an 8.2% incidence of post-surgical complications with 4.1% being abscesses (one required surgical management). Postoperative pain was minor. No new cases or deterioration of continence have been shown. CONCLUSION: Radiofrequency is effective in 34.7% of the cases as an anal fistula treatment in this first prospective study, with low morbidity and no effect on continence. Clinical healing was deep (MRI) in three-quarters at 1 year. The increase in energy power during the procedure seems to be a key point to be analysed to optimise results.

Relationship between clinical remission of perianal fistulas in Crohn's disease and serum adalimumab concentrations: A multi-center cross-sectional study.

BACKGROUND: Crohn's disease (CD) is complicated by perianal fistulas in approximately 20% of patients. Achieving permanent fistula closure remains a challenge for physicians. An association between serum anti-tumor necrosis factor-α concentrations and clinical outcomes in patients with CD has been demonstrated; however, little information is available on serum adalimumab (ADA) concentrations and remission of perianal fistulas in such patients. AIM: To study the relationship between serum ADA concentrations and clinical remission of CD-associated perianal fistulas. METHODS: This cross-sectional study of patients with CD-associated perianal fistulas treated with ADA was performed at four French hospitals between December 2013 and March 2018. At the time of each serum ADA concentration measurement, we collected information about the patients and their fistulas. The primary study endpoint was clinical remission of fistulas defined as the absence of drainage (in accordance with Present's criteria), with a PDAI ≤ 4, absence of a seton and assessment of the overall evaluation as favorable by the proctologist at the relevant center. We also assessed fistula healing [defined as being in clinical and radiological (magnetic resonance imaging, MRI) remission] and adverse events. RESULTS: The study cohort comprised 34 patients who underwent 56 evaluations (patients had between one and four evaluations). Fifteen patients had clinical remissions (44%), four of whom had healed fistulas on MRI. Serum ADA concentrations were significantly higher at evaluations in which clinical remission was identified than at evaluations in which it was not [14 (10-16) vs 10 (2-15) µg/mL, P = 0.01]. Serum ADA concentrations were comparable at the times of evaluation of patients with and without healed fistulas [11 (7-14) vs 10 (4-16) µg/mL, P = 0.69]. The adverse event rate did not differ between different serum ADA concentrations. CONCLUSION: We found a significant association between high serum ADA concentrations and clinical remission of CD-associated perianal fistulas.

Treatment of anal fissures: Results from a national survey on French practice.

BACKGROUND: Treatment of an anal fissure (AF) is based on medical treatment (nonoperative therapies) and surgical procedures. However, the choice of treatment and its role in therapeutic strategy vary from one country to another, and to date, no standard French recommendation is currently available. Our aim was to assess French practices in the treatment of AFs. METHODS: A national survey of members of the French National Society of Colo-Proctology (SNFCP) was carried out using an online questionnaire (1) to evaluate French practice and (2) to compare them with guidelines of other societies. RESULTS: Two hundred responses were obtained among the 300 registered members, representing a participation rate of 67%. Members of the SNFCP agree with all scientific societies on the importance of first-line medical treatment, with surgery proposed as a second-line treatment in the case of the failure of well-conducted medical treatment. However, calcium channel blockers and topical nitrates as first-line treatment are rarely prescribed in France. Priority is therefore given to "simple" topical healing products and oral analgesics on demand. Similarly, surgical management differs since LIS is the "gold standard" in most guidelines, whereas in France, despite the data in the literature, fissurectomy is the first-line treatment. CONCLUSIONS: Our study indicated the fissure treatment discrepancies of France with other countries concerning the usage of topical treatments and the choice of first-line surgical treatments that is currently considered a "French exception".

Surgical closure, mainly with glue injection and anti-tumour necrosis factor α, in fistulizing perianal Crohn's disease: A multicentre randomized controlled trial.

AIM: In patients with fistulizing perianal Crohn's disease (CD), the need for a secondary surgical step is not defined. The aim was to assess the efficacy of surgical closure compared to a single seton removal in patients with drained fistulizing perianal CD treated with adalimumab. METHODS: This was a multicentre, randomized controlled trial, comparing seton removal + surgical closure (closure group) to seton removal alone (control group) with a stratification according to the American Gastroenterological Association classification. The primary end-point was fistula closure at month 12 defined by the association of the following criteria: no seton, absence of a visible external opening, absence of discharge from the tract after finger compression, absence of an internal opening, absence of perianal pain/abscess and absence of fistula-related abnormalities. RESULTS: Among the 64 included patients (262 expected) (48 complex fistula, 75%), 33 were randomized to the closure group and 31 to the control group. In the closure group, 26 patients (78.8%) had glue. At month 12, overall fistula closure was achieved in 35 of the evaluable 58 patients (60%): 18/32 (56%) in the surgery group and 17/26 (65%) in the control group (P = 0.479). In the closure group, fistula closure was observed in 13/25 (52%) and 5/7 (71%) patients with complex and simple fistula respectively (P = 0.426), compared with 12/18 (67%) and 5/8 (63%), respectively in the control group (P = 1.000). CONCLUSIONS: Seton removal alone seems to be no more effective than a secondary surgical step (in particular glue injection) in patients having fistulizing perianal CD controlled by an initial drainage combined with adalimumab. The results should be interpreted with caution.

Pedictors of Perianal Fistula Relapse in Crohn's Disease.

BACKGROUND: Despite an optimal medico-surgical management of perineal Crohn's disease (PCD), fistula relapse still occurs in 30% of patients. Our aim was to determine predictors of fistula relapse in patients in remission after treatment of a PCD lesion. METHODS: Consecutive patients treated for fistulizing PCD have been included in a retrospective study when they achieved fistula remission within 3 months after the surgery. Remission was defined as the absence of any draining fistula at clinical examination. Primary outcome was the occurrence of a fistula relapse, defined as a subsequent perianal draining fistula or an abscess confirmed clinically and/or by pelvic MRI. RESULTS: One hundred and thirty-seven patients (57% female, median age: 35 years) corresponding to 157 abscess events, including 120 (76.4%) treated by anti-TNF after drainage, achieved fistula remission after surgery. During the follow-up period (median duration: 43 months [interquartile range 26 to 64]), 34 (22%) patients experienced a fistula relapse within a median time of 1.8 years. Survival without fistula was 96.7% at 1 year, 78.4% at 3 years, and 74.4% at 5 years. Fistula relapse rates were not different in patients receiving infliximab or adalimumab (P = 0.66). In patients treated by anti-TNF at inclusion, discontinuation of anti-TNF therapy (odds ratio 3.49, P = 0.04), colonic location (OR 6.25, P = 0.01), and stricturing phenotype (odds ratio 4.39, P = 0.01) were independently associated with fistula relapse in multivariate analysis. CONCLUSION: In patients achieving fistula remission of PCD, relapse rates are low and are not different between infliximab and adalimumab. Discontinuation of anti-TNF therapy is associated with increased relapse rate.

Correction to: Prevalence of anal symptoms in general practice: a prospective study.

Following publication of the original article [1], the authors reported an error to one of the 'study groups' in the authorship section.

Clinical practice guidelines from the French National Society of Coloproctology in treating chronic constipation.

Chronic constipation is a common symptom that regularly affects the quality of life of adult patients. Its treatment is mainly based on dietary rules, laxative drugs, perineal rehabilitation and surgical treatment. The French National Society of Coloproctology offers clinical practice recommendations on the basis of the data in the current literature, including those on recently developed treatments. Most are noninvasive, and the main concepts include the following: stimulant laxatives are now considered safe drugs and can be more easily prescribed as a second-line treatment; biofeedback therapy remains the gold standard for the treatment of anorectal dyssynergia that is resistant to medical treatment; transanal irrigation is the second-line treatment of choice in patients with neurological diseases, but it may also be proposed for patients without neurological diseases; and although interferential therapy may be a new promising treatment, it needs further evaluation.

Elaboration and validation of Crohn's disease anoperineal lesions consensual definitions.

AIM: To establish consensual definitions of anoperineal lesions of Crohn's (APLOC) disease and assess interobserver agreement on their diagnosis between experts. METHODS: A database of digitally recorded pictures of APLOC was examined by a coordinating group who selected two series of 20 pictures illustrating the various aspects of APLOC. A reading group comprised: eight experts from the Société Nationale Française de Colo Proctologie group of study and research in proctology and one academic dermatologist. All members of the coordinating and reading groups participated in dedicated meetings. The coordinating group initially conducted a literature review to analyse verbatim descriptions used to evaluate APLOC. The study included two phases: establishment of consensual definitions using a formal consensus method and later assessment of interobserver agreement on the diagnosis of APLOC using photos of APLOC, a standardised questionnaire and Fleiss's kappa test or descriptive statistics. RESULTS: Terms used in literature to evaluate visible APLOC did not include precise definitions or reference to definitions. Most of the expert reports on the first set of photos agreed with the main diagnosis but their verbatim reporting contained substantial variation. The definitions of ulceration (entity, depth, extension), anal skin tags (entity, inflammatory activity, ulcerated aspect), fistula (complexity, quality of drainage, inflammatory activity of external openings), perianal skin lesions (abscess, papules, edema, erythema) and anoperineal scars were validated. For fistulae, they decided to follow the American Gastroenterology Association's guidelines definitions. The diagnosis of ulceration (κ = 0.70), fistulae (κ = 0.75), inflammatory activity of external fistula openings (86.6% agreement), abscesses (84.6% agreement) and erythema (100% agreement) achieved a substantial degree of interobserver reproducibility. CONCLUSION: This study constructed consensual definitions of APLOC and their characteristics and showed that experts have a fair level of interobserver agreement when using most of the definitions.

Prevalence of anal symptoms in general practice: a prospective study.

BACKGROUND: Anal disorders are largely underestimated in general practice. Studies have shown patients conceal anal symptoms leading to late diagnosis and treatment. Management by general practitioners is poorly described. The aim of this study is to assess the prevalence of anal symptoms and their management in general practice. METHODS: In this prospective, observational, national study set in France, all adult patients consulting their general practitioner during 2 days of consultation were included. Anal symptoms, whether spontaneously revealed or not, were systematically collected and assessed. For symptomatic patients, the obstacles to anal examination were evaluated. The general practitioner's diagnosis was collected and a proctologist visit was systematically proposed in case of anal symptoms. If the proctologist was consulted, his or her diagnosis was collected. RESULTS: From October 2014 to April 2015, 1061 patients were included by 57 general practitioners. The prevalence of anal symptoms was 15.6% (95% CI: 14-18). However, 85% of these patients did not spontaneously share their symptoms with their doctors, despite a discomfort rating of 3 out of 10 (range 1-5). Although 65% of patients agreed to an anal examination, it was not proposed in 45% of cases with anal symptoms. Performing the examination was associated with a significantly higher diagnosis rate of 76% versus 20% (p < 0.001). Proctologist and general practitioner diagnoses were consistent in 14 out of 17 cases. CONCLUSIONS: Patients' concealed anal symptoms are significant in general practice despite the impact on quality of life. Anal examination is seldom done. Improved training of general practitioners is required to break the taboo.

[Diet and lifestyle rules in chronic constipation in adults: From fantasy to reality ]. / Les règles hygiéno-diététiques dans la constipation chronique de l'adulte : du fantasme à la réalité .

Chronic constipation is one of the most common chronic gastrointestinal complaints and a frequent reason for consultation. Lifestyle modification and dietary advice attract a lot of patients, often dissatisfied with a long-term drug intake. These behavioral modifications are recommended as a first-line approach in the treatment of chronic mild constipation in the majority of current guidelines despite a low level of evidence. Fiber supplementation is probably the most relevant measure because of a satisfactory level of proof. It improves stool frequency and consistency. It has a positive effect on excessive straining and colonic transit time. The recommended daily fiber intake is at least 20 to 25g. To avoid side effects like bloating and abdominal pain, it must be gradually adjusted after a several days period. The benefice of increasing water intake or daily physical exercise in the treatment of chronic constipation have a lack of evidence, except specific situations such as elderly, hospitalized, institutionalized, dehydrated people or people consuming fluids less than 500mL/day. Change in environmental defecation conditions or bowel habits are probably anecdotal recommendations.

[Anal acute pain]. / Douleurs proctologiques aiguës

Anal acute pain. Anal pain is a symptom commonly reported during consultation for ano-rectal disease. It is a nonspecific symptom, associated with both emergency and chronic pathologies, and with both benign and serious conditions. Aetiological diagnosis is not always easily established during initial visit. In a patient without significant past medical history, when no sign of severe problem is present, and when clinical examination is normal, a second visit can help establishing diagnosis. When an abscess is suspected, antibiotherapy will not cure the patient, and may expose to occurrence of septic complications. When immediate intervention for an abscess is not possible, incision will control pain and infection for a few days. Haemorrhoidal thrombosis is another frequent aetiology of acute pain. Diagnosis is not difficult, and when appropriate medical treatment does not alleviate pain, incision under local anaesthesia is indicated. Pain associated with anal fissure is typicaly ryhthmed by stool passage. For non healing fissures, surgery may be proposed. Fecaloma, trauma, herpes virus infection and foreign body are less frequent, and clinical context is often suggestive.

Douleurs proctologiques aiguës. La douleur est un symptôme fréquent en consultation proctologique. Non spécifique, elle peut révéler aussi bien une urgence qu'une pathologie chronique, une pathologie grave qu'une affection bénigne. Le diagnostic causal n'est pas toujours facile dès la première consultation. En l'absence de diagnostic précis, après un examen clinique de bonne qualité et en l'absence d'antécédent notable, il peut être judicieux de prévoir une nouvelle consultation après quelques jours de traitement symptomatique. En cas de suspicion de suppuration, prescrire un traitement antibiotique ne guérit pas le patient et peut l'exposer à des complications septiques graves. En présence d'un abcès, si l'intervention n'est pas possible rapidement, l'incision permet de contrôler provisoirement l'infection et de soulager le malade. La thrombose hémorroïdaire est une autre cause fréquente de douleurs aiguës. Son diagnostic est simple et, en cas de thrombose externe isolée avec un caillot et en échec du traitement médical, une évacuation du caillot sous anesthésie locale est rapidement salvatrice. La fissure anale est de symptomatologie assez typique, avec son rythme défécatoire en trois temps. En cas de non-cicatrisation ou de récidives fréquentes, une résection chirurgicale doit être envisagée. Fécalome, traumatismes, primo-infection herpétique et corps étranger sont beaucoup plus rares et surviennent dans un contexte clinique souvent évocateur.

Combined approach with infliximab, surgery, and methotrexate in severe fistulizing anoperineal Crohn's disease: results from a prospective study.

BACKGROUND: Infliximab is the only medical therapy that has been proven to be effective in fistulizing Crohn's disease (CD), but the recurrence rate of fistulas is high despite maintenance therapy. The aim of this prospective study was to evaluate the short- and long-term efficacy of a combined schedule with infliximab, methotrexate, and sphincter-sparing surgery in patients with severe fistulizing anoperineal CD. METHODS: From January 2006 to November 2007, all consecutive patients in three referral centers with severe fistulizing anoperineal CD were prospectively included after primary drainage. At inclusion, patients received three infliximab infusions at weeks 0, 2, and 6, and maintenance therapy with methotrexate. A second optimized surgical step consisting of at least removal of setons was performed between the second and the third infliximab infusions. RESULTS: Thirty-four CD patients (26 women; median age 38.5 years) with complex anoperineal fistula were enrolled (including 9 with recto-vaginal fistulas, and 10 with anorectal stenosis). At week 14 the response rate was 85% with 74% complete responders. At 1 year, 50% were still responders; luminal CD worsening was the major cause of relapse. Median Perineal Disease Activity Index (PDAI) and magnetic resonance imaging (MRI) scores significantly decreased from baseline to week 50. CONCLUSIONS: A combined approach with infliximab induction, two surgical sphincter-sparing steps and methotrexate is effective in achieving short-term response in severe fistulizing anoperineal CD. The best maintenance regimen remains to be determined.

Characterization of human pre-elafin mutants: full antipeptidase activity is essential to preserve lung tissue integrity in experimental emphysema.

Pre-elafin is a tight-binding inhibitor of neutrophil elastase and myeloblastin; two enzymes thought to contribute to tissue damage in lung emphysema. Previous studies have established that pre-elafin is also an effective anti-inflammatory molecule. However, it is not clear whether both functions are linked to the antipeptidase activity of pre-elafin. As a first step toward elucidating the structure/function relationship of this protein, we describe here the construction and characterization of pre-elafin variants with attenuated antipeptidase potential. In these mutants, the P1' methionine residue of the inhibitory loop is replaced by either a lysine (pre-elafinM25K) or a glycine (pre-elafinM25G) residue. Both mutated variants are stable and display biochemical properties undistinguishable from WT (wild-type) pre-elafin. However, compared with WT pre-elafin, their inhibitory constants are increased by one to four orders of magnitude toward neutrophil elastase, myeloblastin and pancreatic elastase, depending on the variants and enzymes tested. As suggested by molecular modelling, this attenuated inhibitory potential correlates with decreased van der Waals interactions between the variants and the enzymes S1' subsite. In elastase-induced experimental emphysema in mice, only WT pre-elafin protected against tissue destruction, as assessed by the relative airspace enlargement measured using lung histopathological sections. Pre-elafin and both mutants prevented transient neutrophil alveolitis. However, even the modestly affected pre-elafinM25K mutant, as assayed in vitro with small synthetic substrates, was a poor inhibitor of the neutrophil elastase and myeloblastin elastolytic activity measured with insoluble elastin. We therefore conclude that full antipeptidase activity of pre-elafin is essential to protect against lung tissue lesions in this experimental model.

Increased local levels of granulocyte colony-stimulating factor are associated with the beneficial effect of pre-elafin (SKALP/trappin-2/WAP3) in experimental emphysema.

Few therapeutic options are offered to treat inflammation and alveolar wall destruction in emphysema. The effect of recombinant human pre-elafin, an elastase inhibitor, was evaluated in porcine pancreatic elastase (PPE)-induced emphysema in C57BL/6 mice. In a first protocol, mice received a single instillation of pre-elafin (17.5 pmol/mouse) at 1 h post-PPE and were sacrificed up to 72 h post-PPE. A single instillation of pre-elafin significantly reduced PPE-induced neutrophil accumulation in lungs, as assessed by bronchoalveolar lavage (BAL), by 51%, 71% and 67% at 24, 48 and 72 h, respectively. In a second protocol, mice also received a single dose of PPE, but pre-elafin three times a week for 2 weeks. After 2 weeks, pre-elafin significantly reduced the PPE-induced increase in BAL macrophage numbers, airspace dimensions and lung hysteresivity by 74%, 62% and 52%, respectively. Since G-CSF was previously shown to reduce emphysematous changes in mice, the BAL levels of this mediator were measured 6 h post-PPE in animals treated as described in the first protocol. Pre-elafin significantly increased G-CSF levels in PPE-exposed mice compared to sham- and PPE only-exposed animals. This suggests that the beneficial effects of pre-elafin could be mediated, at least in part, by its ability to increase G-CSF levels in the lung.

Proteins with whey-acidic-protein motifs and cancer.

The importance of early diagnosis to reduce the morbidity and mortality from cancer has led to a search for new sensitive and specific tumour markers. Molecular techniques developed over the past few years allow simultaneous screening of thousands of genes, and have been applied to different cancers to identify many genes that are modulated in various cancers. Of these, attention has focused on genes coding for a family of proteins with whey-acidic-protein (WAP) motifs. Most notably, the genes coding for elafin, antileukoproteinase 1 (previously called secretory leucocyte proteinase inhibitor, SLPI), WAP four disulphide core domain protein 1 (previously called prostate stromal protein 20 kDa, PS20), and WAP four disulphide core domain protein 2 (previously called major human epididymis-specific protein E4, HE4), have been identified as candidate molecular markers for several cancers. In this review, we assess data for an association between cancer and human WAP proteins, and discuss their potential role in tumour progression. We also propose a new mechanism by which WAP proteins might have a role in carcinogenesis.

Local excision of large rectal villous adenomas: long-term results.

PURPOSE: Transanal excision of rectal villous adenomas is a widely used surgical technique, because it is a one-step procedure, requiring no sophisticated instrumentation, and allowing complete histologic analysis of the excised tumor. Therefore, it ranks alongside radical surgery and palliative destructive procedures, but its results are highly variable in the published series. This discrepancy may be explained by the variable completeness of tumor excision because of potential dissection difficulties. Because intraoperative exposure may be a major limiting factor, one of us (JF) has developed a tractable cutaneomucous flap procedure to lower the rectal tumor to the anal verge, where control of the dissection line is easier. This retrospective review of consecutive patients operated on during ten-year period reports long-term results after transanal excision for large rectal villous adenomas with the tractable flap technique. PATIENTS: From 1978 to 1988, 207 consecutive patients (100 males), mean age 68 (range, 24-90) years, were operated on for an apparently benign villous rectal adenoma. Twenty-one patients (10 percent) were referred after failure of previous treatments: 11 endoscopic, 8 surgical, 1 laser, 1 radiotherapy. Mean distance of lower tumor edge from anal margin was 5.6 (range, 0-13) cm and was <10 cm in 82 percent. RESULTS: Three patients (1.5 percent), including one with a Tis carcinoma, underwent a secondary treatment for immediate gross failure of resection: one further local excision and two palliative laser destructions. Immediate postoperative course was uneventful for 96 percent; there was one death from perineal gangrenous infection, four cases of hemorrhage, and three urinary retentions. Subsequently one case of transient fecal incontinence and 11 medically managed stenoses were noted. Mean size of resected tumor was 5.4 (range, 1-17) cm. Deep excision margins concerned the rectal muscular layers in 199 patients (96 percent) and perirectal fat in 8 (4 percent). Specimen margins were negative for cancer in 175 (85 percent) and positive or unknown in 32 cases. Histologic evaluation demonstrated in situ cancer in 28 (14 percent) and invasive carcinoma in 9 (4 percent). In three patients (1 percent), two abdominoperineal resections were immediately performed (one T2 with a mucinous contingent, one T3) and one adjuvant radiotherapy (one undifferentiated T2). Four patients (2 percent) did not return for postoperative evaluation. For the remaining 198 patients, mean follow-up was 74 +/- 34 (median, 75; range, 1-168) months. Forty-four died from unrelated causes. Recurrence occurred in seven (3.6 percent) and was malignant in two, who subsequently died. Specific recurrence-free probability was 99.5 percent at one year, 96 percent at five years, and 95 percent at ten years. A lesion size >6 cm (10 vs. 1 percent for smaller tumors) and the presence of an invasive carcinoma (20 vs. 3 percent without invasive carcinoma) were significantly associated with an increased probability of recurrence at five years. CONCLUSION: Providing that adequate intraoperative exposure is obtained and advanced malignant tumors receive immediate secondary treatment, transanal resection of clinically benign, large rectal villous adenomas is safe and effective. It is an alternative to rectal resection, which exposes the patient to potentially adverse effects, and also to destructive procedures, which preclude any histologic evaluation of the tumor.