Autologous Myoblasts for the Treatment of Fecal Incontinence: Results of a Phase 2 Randomized Placebo-controlled Study (MIAS).

OBJECTIVE: The aim of this study was to evaluate the efficacy of intrasphincteric injections of autologous myoblasts (AMs) in fecal incontinence (FI) in a controlled study. SUMMARY OF BACKGROUND DATA: Adult stem cell therapy is expected to definitively cure FI by regenerating damaged sphincter. Preclinical data and results of open-label trials suggest that myoblast therapy may represent a noninvasive treatment option. METHODS: We conducted a phase 2 randomized, double-blind, placebo-controlled study of intrasphincteric injections of AM in 24 patients. The study compared outcome after AM (n = 12) or placebo (n = 12) injection using Cleveland Clinic Incontinence (CCI), score at 6 and 12 months. Patients in the placebo group were eligible to receive frozen AM after 1 year. RESULTS: At 6 months, the median CCI score significantly decreased from baseline in both the AM (9 vs 15, P = 0.02) and placebo (10 vs 15, P = 0.01) groups. Hence, no significant difference was found between the 2 groups (primary endpoint) at 6 months. At 12 months, the median CCI score continued to ameliorate in the AM group (6.5 vs 15, P = 0.006), while effect was lost in the placebo group (14 vs 15, P = 0.35). Consequently, there was a higher response rate at 12 months in the treated than the placebo arm (58% vs 8%, P = 0.03). After delayed frozen AM injection in the placebo group, the response rate was 60% (6/10) at 12 months. CONCLUSIONS: Intrasphincteric AM injections in FI patients have shown tolerance, safety, and clinical benefit at 12 months despite a transient placebo effect at 6 months.

[Ischemic cholangiopathy induced by extended burns]. / Cholangiopathie ischémique secondaire à des brûlures étendues.

Ischemic cholangiopathy is a recently described entity occurring mainly after hepatic grafts. Very few cases after intensive care unit (ICU) for extended burn injury were reported. We report the case of a 73-year-old woman consulting in an hepatology unit, for a jaundice appearing during a hospitalisation in an intensive care unit and increasing from her leaving from ICU, where she was treated for an extended burn injury. She had no pre-existing biological features of biliary disease. Biological tests were normal. Magnetic resonance imaging acquisitions of biliary tracts pointed out severe stenosing lesions of diffuse cholangiopathy concerning intrahepatic biliary tract, mainly peri-hilar. Biopsie from the liver confirmed the diagnosis, showing a biliary cirrhosis with bile infarcts. This case is the fourth case of ischemic cholangiopathy after extended burn injury, concerning a patient without a prior history of hepatic or biliary illness and appearing after hospitalisation in intensive care unit.

Predicting factors of fistula healing and clinical remission after infliximab-based combined therapy for perianal fistulizing Crohn's disease.

UNLABELLED: Perianal fistulizing Crohn's disease (PFCD) treatment is based on fistula drainage, antibiotics, immunosuppressant (IS) drugs, and infliximab. Our aim was to study the effectiveness of combination therapy on PFCD and to search for clinical or imaging features associated with the initial complete clinical response and its stability overtime. PATIENTS AND METHODS: All patients with PFCD treated in our tertiary center between 2000 and 2005 by infliximab in combination with seton placement and/or IS and evaluated by MRI before treatment were included in the study. Basal clinical and MRI characteristics were recorded. Response to treatment was evaluated after the infliximab induction regiment and at the end of the follow-up. RESULTS: Twenty-six patients were included and followed-up for an average 4.9 years. A complex fistula was present in 69% (18/26 patients) of cases and eight (8/26 patients) had an ano-vaginal fistula. After infliximab induction therapy, 13 patients (50%) achieved a complete clinical response. The initial clinical response was significantly associated with the absence of both, active intestinal disease (54% vs. 8%, P = 0.03) and active proctitis (77% vs. 23%, P = 0.01). No initial MRI characteristics were linked to the initial response. In multivariate analysis, only the presence of active proctitis was associated with the lack of response (P = 0.047). At the end of the follow-up, 42% of the patients remained in clinical remission. No clinical characteristics were associated to sustained response when among long-standing responders two exhibited a normal post-treatment MRI. CONCLUSION: An initial complete response of PFCD was observed in half of the patients after combined therapy including infliximab that decreased to 42% later on. Complete healing of fistulas on MRI was possible but unusual. The initial response seemed related to the absence of active intestinal disease, especially in the rectum, when the long-term response could not be predicted by the basal characteristics of patients.

Magnetic resonance imaging may predict deep remission in patients with perianal fistulizing Crohn's disease.

AIM: To evaluate the imaging course of Crohn's disease (CD) patients with perianal fistulas on long-term maintenance anti-tumor necrosis factor (TNF)-α therapy and identify predictors of deep remission. METHODS: All patients with perianal CD treated with anti-TNF-α therapy at our tertiary care center were evaluated by magnetic resonance imaging (MRI) and clinical assessment. Two MR examinations were performed: at initiation of anti-TNF-α treatment and then at least 2 years after. Clinical assessment (remission, response and non-response) was based on Present's criteria. Rectoscopic patterns, MRI Van Assche score, and MRI fistula activity signs (T2 signal and contrast enhancement) were collected for the two MR examinations. Fistula healing was defined as the absence of T2 hyperintensity and contrast enhancement on MRI. Deep remission was defined as the association of both clinical remission, absence of anal canal ulcers and healing on MRI. Characteristics and imaging patterns of patients with and without deep remission were compared by univariate and multivariate analyses. RESULTS: Forty-nine consecutive patients (31 females and 18 males) were included. They ranged in age from 14-70 years (mean, 33 years). MRI and clinical assessment were performed after a mean period of exposure to anti-TNF-α therapy of 40 ± 3.7 mo. Clinical remission, response and non-response were observed in 53.1%, 20.4%, and 26.5% of patients, respectively. Deep remission was observed in 32.7% of patients. Among the 26 patients in clinical remission, 10 had persisting inflammation of fistulas on MRI (T2 hyperintensity, n = 7; contrast enhancement, n = 10). Univariate analysis showed that deep remission was associated with the absence of rectal involvement and the absence of switch of anti-TNF-α treatment or surgery requirement. Multivariate analysis demonstrated that only the absence of rectal involvement (OR = 4.6; 95%CI: 1.03-20.5) was associated with deep remission. CONCLUSION: Deep remission is achieved in approximately one third of patients on maintenance anti-TNF-α therapy. Absence of rectal involvement is predictive of deep remission.

Focal nodular hyperplasia occurring after blunt abdominal trauma.

Focal nodular hyperplasia of the liver is a benign neoplasm. The pathogenesis is unknown, but it was hypothesized that focal nodular hyperplasia may be a response to a vascular abnormality. We report on a case of focal nodular hyperplasia that developed in a young patient 1 year after a blunt hepatic injury.

[Lower gastrointestinal bleeding due to ileal lipoma. Diagnosis contribution of contrast enhanced helical CT]. / Hémorragie digestive due à un lipome iléal invaginé. Apport de la scanographie hélicoïdale avec injection.

Jejunoileal gastrointestinal hemorrhage is uncommon and difficult to diagnose. Ileal lipoma is an unusual cause of jejunoileal bleeding. We report the case of a 45-Year-old patient admitted for acute gastrointestinal bleeding. The patient was taking aspirin at admission. A bleeding intussuscepted ileal lipoma was localized with a contrast enhanced helical computed tomography. This diagnosis was confirmed by laparotomy.

[Retrorectal cystic hamartomas. Report of one case]. / Hamartome kystique rétrorectal. A propos d'une observation.

Retrorectal cystic hamartomas (RCH) are rare congenital lesions of the presacral space, of which 68 cases are reported under different terms. Clinicopathologic features are usually constant and similar to the present case. A 23-year-old woman complained of abdominal and perineal pains for several months. Physical examination revealed a nodular mass in the posterior part of the rectum. A pelvic MRI showed a 5.5 cm cystic retrorectal mass compressing the rectum. The patient underwent surgical resection. Pathologic examination found an ill-defined nodular mass, composed by numerous cysts surrounded by fibroadipose tissue. Cysts were lined by different epithelia: keratinized and non keratinized squamous, transitional, ciliated and mucus-producing columnar epithelia. Few mucinous glands were noted, connected to some cysts. These epithelial structures were surrounded by connective tissue in which well-differentiated bundles of smooth muscle fibers were present without well-formed muscularis. The RCH differential diagnosis includes principally congenital cysts: epidermal cysts, cystic teratomas, dermoid cysts, anal gland cysts and rectal duplications. An embryologic origin of RCH from remnants of the postanal gut is currently accepted. Loco-regional inflammatory process frequently complicates this lesion and can cause perirectal fistulae. RCH also possesses a malignancy potential, with development of adenocarcinomas. To avoid these complications, complete excision is recommended.

Gender influence on defecographic abnormalities in patients with posterior pelvic floor disorders.

AIM: To compare defecographic abnormalities in symptomatic men and women and to analyze differences between men and age- and symptom-matched women. METHODS: Sixty-six men (mean age: 55.4 years, range: 20-81 years) who complained of constipation and/or fecal incontinence and/or pelvic pain underwent defecography after intake of a barium meal. Radiographs were analyzed for the diagnosis of rectocele, enterocele, intussusception and perineal descent. They were compared with age- and symptom-matched women (n = 198) who underwent defecography during the same period. RESULTS: Normal defecography was observed in 22.7% of men vs 5.5% of women (P < 0.001). Defecography in men compared with women showed 4.5% vs 44.4% (P < 0.001) rectocele, and 10.6% vs 29.8% (P < 0.001) enterocele, respectively. No difference was observed for the diagnosis of intussusception (57.6% vs 44.9%). Perineal descent at rest was more frequent in women (P < 0.005). CONCLUSION: For the same complaint, diagnosis of defecographic abnormalities was different in men than in women: rectocele, enterocele and perineal descent at rest were observed less frequently in men than in women.

Radiologic evaluation of pelvic floor disorders.

Several imaging modalities are available ranging from fluoroscopic techniques to ultrasonography and MRI for the evaluation of patients with pelvic floors disorders. High-resolution ultrasonography and MRI not only provide superior delineation of the pelvic floor anatomy but also reveal pathology and functional changes. This article focuses on standard imaging procedures including defecography, ultrasonography, and MRI and discusses its use in clinical practice by illustrating both normal and abnormal patterns.

Defecographic disorders in anal incontinent women: relation to symptoms and anal endosonographic patterns.

OBJECTIVE: The need for a defecography in incontinent women is still debatable. We prospectively evaluated the prevalence of defecographic abnormalities in incontinent women in order to determine whether any symptom or endosonographic findings could be associated with a particular defecographic pattern. MATERIAL AND METHODS: Fifty incontinent women (aged 30-87 years) underwent defecography and anal endosonography to look for pelvic floor descent, rectocele, intussusception, enterocele and the presence of anal sphincter defects. Other symptoms, i.e. straining at stools and pelvic pressure, were recorded. RESULTS: Twenty-five cases of external sphincter defect (12 associated with an internal defect) and 4 cases of isolated internal defect were identified. Defecography identified 25 patients with perineal descent at rest, 28 with perineal descent at straining, 30 with rectocele, 30 with intussusception and 14 with enterocele. Three defecographies were normal. In the 29 women with sphincter defects, the prevalence of defecographic abnormalities did not differ from that observed in the 21 women without sphincter defects. In women complaining of straining at stools (n=26) or idiopathic pelvic pressure (n=32), the prevalence of defecographic abnormalities did not differ from that observed in women who did not have these symptoms. CONCLUSIONS: The prevalence of pelvic floor disorders in incontinent women was similar whether associated symptoms or anal sphincter defects were present or not. When defecography has to be performed to investigate female anal incontinence, neither clinical nor endosonographic features can predict a higher diagnostic efficiency.

Defecography in symptomatic older women living at home.

BACKGROUND: complaints of defecation disorders in older patients living at home is an emerging problem. Little is known about radiological examination of this population. OBJECTIVE: this study aimed to analyse the yield of defecography in women older than 75 years, living at home and complaining of defecation disorders. DESIGN AND SETTINGS: prospective study of patients referred to a radiology department in a tertiary-care medical centre in Rouen, France. SUBJECTS AND METHODS: 52 women (mean age: 78, range: 75-93) complaining of constipation, faecal incontinence or pelvic pain underwent defecography. Defecography was performed after intake of a barium meal and vaginal opacification. Radiographs were analysed accordingly with the established criteria. RESULTS: defecography showed perineal descent in 27 patients, rectocele in 29, intussusception in 33 and enterocele in 14. A combination of abnormalities was found in 40 women. Only 3 studies were normal. There was no significant association between symptoms and pelvic disorders revealed by defecography. CONCLUSIONS: defecography in symptomatic women aged 75 years and over did not raise any technical difficulty. It revealed a 77% rate of abnormalities, but there was no relationship between the symptoms and the detected abnormalities.