Fibrin glue is effective healing perianal fistulas in patients with Crohn's disease.

BACKGROUND & AIMS: Fibrin glue is a therapeutic for fistulas that activates thrombin to form a fibrin clot, which mechanically seals the fistula tract. We assessed the efficacy and safety of a heterologous fibrin glue that was injected into the fistula tracts of patients with Crohn's disease (ClinicalTrials.gov No. NCT00723047). METHODS: This multicenter, open-label, randomized controlled trial included patients with a Crohn's disease activity index < or =250 and fistulas between the anus (or low rectum) and perineum, vulva, or vagina, that drained for more than 2 months. Magnetic resonance imaging or endosonography was performed to assess fistula tracts and the absence of abscesses. Patients were stratified into groups with simple or complex fistulas and randomly assigned to receive fibrin glue injections (n = 36) or only observation (n = 41) after removal of setons. The primary end point was clinical remission at week 8, defined as the absence of draining, perianal pain, or abscesses. At week 8, a fibrin glue injection was offered to patients who were not in remission. RESULTS: Clinical remission was observed in 13 of the 34 patients (38%) of the fibrin glue group compared with 6 of the 37 (16%) in the observation group; these findings demonstrate the benefit of fibrin glue (odds ratio, 3.2; 95% confidence interval: 1.1-9.8; P = .04). The benefit seemed to be greater in patients with simple fistulas. Four patients in the fibrin glue group and 6 in the observation group had adverse events. CONCLUSIONS: Fibrin glue injection is a simple, effective, and well-tolerated therapeutic option for patients with Crohn's disease and perianal fistula tracts.

Remnant liver volume to body weight ratio > or =0.5%: A new cut-off to estimate postoperative risks after extended resection in noncirrhotic liver.

BACKGROUND: Before extended hepatectomy of five or more segments, the remnant liver volume (RLV) is usually calculated as a ratio of RLV to total liver volume (RLV-TLV) and must be >20% to 25%. This method can lead to compare parts of normal liver parenchyma to others compromised by biliary or vascular obstruction or by portal vein embolization. Extrapolating from living-donor liver transplantation, we hypothesized that RLV to body weight ratio (RLV-BWR) could accurately assess the functional limit of hepatectomy. STUDY DESIGN: From September 2000 to December 2004, volumetric measurements of RLV using computed tomography were obtained before right-extended hepatectomy in 31 patients. RLV-BWR of 0.5% as a critical point for patient course was compared with stratification by RLV-TLV (< or =25% or >25% and < or =20% or >20%). RESULTS: Three-month morbidity and mortality were not significantly different between groups RLV-TLV < or = and >25% and between groups RLV-TLV < or = and >20%, but increased significantly in group RLV-BWR < or = 0.5% compared with group RLV-BWR > 0.5% (p = 0.038 and p = 0.019, respectively) with an non-significant increase in death from liver failure (p = 0.077). CONCLUSIONS: RLV-BWR was more specific than RLV-TLV in predicting postoperative course after extended hepatectomy. Patients with an anticipated RLV < or = 0.5% of body weight are at considerable risk for hepatic dysfunction and postoperative mortality.

Colectomy with ileorectal anastomosis preserves female fertility in ulcerative colitis.

OBJECTIVES: Restorative proctocolectomy with ileoanal anastomosis (IPAA) is the surgical standard for patients with ulcerative colitis (UC). Significant reduction in female fertility and fecundity after IPAA has been shown in recent studies. In selected cases, colectomy with ileorectal anastomosis (IRA) is another surgical option. The aim of this study was to evaluate fertility in women with UC who underwent IRA. PATIENTS AND METHODS: This study included all women with UC who underwent IRA between 1962 and 1999 and who were 40 years old or younger at the time of surgery, and older than 18 years of age at the time of the interview. Data were collected using a structured telephone interview concerning reproductive behavior and waiting times to pregnancy. RESULTS: Among 40 eligible patients, 37 whose mean age at IRA was 28 years (range 11-39) answered the questionnaire. Twenty-two were unmarried, not wishful of pregnancy and/or already had children. Among 15 females wishing children after IRA, 10 (66%) became pregnant: one had therapeutic abortion, two had a miscarriage, four had 1 child, two had 2 children and one had 4 children. Five patients were sterile after IRA. CONCLUSION: These preliminary results suggest that IRA for UC preserves female fertility. If confirmed in other series this information should be provided to young women with UC before deciding surgical option.

Small bowel adenocarcinoma in patients with Crohn's disease compared with small bowel adenocarcinoma de novo.

BACKGROUND: Data concerning small bowel adenocarcinoma (SBA) in Crohn's disease (CD) come from case reports and small retrospective series. The aim of this study was to further describe SBA in patients with CD and compare it with SBA de novo. METHODS: Twenty patients with CD with SBA recruited in French university hospitals were studied and compared with 40 patients with SBA de novo recruited from a population-based registry. SBA occurred after a median time of 15 years of CD and was located within the inflamed areas of the ileum (n=19) or jejunum (n=1), whereas in patients with SBA de novo, it was distributed all along the small intestine. Median age at diagnosis of SBA was 47 years (range, 33-72 yr) in patients with CD and 68 years (range, 41-95 yr) in those with SBA de novo. RESULTS: The cumulative risk of SBA, assessed in a subgroup of patients, was 0.2% and 2.2% after 10 and 25 years of ileal CD, respectively. SBA accounted for 25% and 45% of the risk of gastrointestinal carcinoma after 10 and 25 years of CD, respectively. Diagnosis was made preoperatively in 1/20 patients with CD and 22/40 patients with SBA de novo. Signet ring cells were found in 35% of patients with CD but not in patients with SBA de novo. Relative survival was not significantly different in these 2 categories of patients (54 versus 37% and 35 versus 30% in patients with and without CD at 2 and 5 yr, respectively). CONCLUSIONS: SBA in CD is different from SBA de novo. It arises from longstanding ileal inflammation and is difficult to diagnose. SBA cumulative risk increases after 10 years of CD and is likely to cause premature mortality in patients with early-onset CD.

Impaired expression of the peroxisome proliferator-activated receptor alpha during hepatitis C virus infection.

BACKGROUND AND AIMS: Liver inflammation, fibrosis, and dyslipidemia are common features in patients with chronic hepatitis C virus (HCV) infection. Because peroxisome proliferator-activated receptor alpha (PPARalpha) is highly expressed in the liver and is involved in the regulation of lipid metabolism and inflammation, we sought to determine whether HCV infection may locally impair PPARalpha expression and activity. METHODS: PPARalpha expression was investigated in liver biopsy specimens of 86 untreated patients with HCV infection and controls, by using real-time polymerase chain reaction (PCR), Western blot analysis, and immunohistochemistry. PPARalpha activity was assessed by quantification of the key gene target carnitine palmitoyl acyl-CoA transferase 1 (CPT1A) messenger RNA (mRNA). The influence of HCV core protein on PPARalpha mRNA expression was analyzed in vitro by real-time PCR in HCV core-expressing HepG2 cells activated with the PPARalpha ligand fenofibric acid. RESULTS: Hepatic concentrations of PPARalpha and CPT1A expressed by hepatocytes were impaired profoundly in the livers of untreated patients with HCV infection compared with controls. A mean decrease of 85% in PPARalpha mRNA expression paralleled with a lack of CPT1A mRNA induction also were observed in HCV core-expressing HepG2 cells compared with controls. CONCLUSIONS: HCV infection is related to altered expression and function of the anti-inflammatory nuclear receptor PPARalpha. These results identify hepatic PPARalpha as one mechanism underlying the pathogenesis of HCV infection, and as a new therapeutic target in traditional treatment of HCV-induced liver injury.

Long-term results of percutaneous management for anastomotic biliary stricture after orthotopic liver transplantation.

The purpose of this study was to evaluate the results of percutaneous transhepatic management (PTM) of anastomotic biliary strictures (BS). Among 168 liver transplant adult recipients, BS was identified in 30 patients. In 6 patients, narrowing of the anastomosis was found early, and in all cases disappeared spontaneously with prolonged draining of the bile tube. Within a mean time of 14 months after transplantation, 24 patients had symptomatic BSs, revealed by cholestasis (n = 17) or cholangitis (n = 7). Twenty-two patients underwent PTM as first treatment of BS (balloon dilatation or stent placement). We evaluated the primary and secondary patency rate of PTM. In 1 patient, PTM failed because the stricture could not be passed with the guide wire, necessitating conversion to a Roux-en-Y choledochojejunostomy (CDJ). Fourteen patients were treated by percutaneous balloon dilatation from which 8 patients (57.2%) were recurrence-free with a mean follow-up of 61 months. One patient with a patent biliary anastomosis underwent retransplantation for acute rejection. Twelve patients received metallic expandable stent placement as their primary treatment (n = 7) or after failure of balloon dilatation (n = 5). Recurrent stricture was found in 7 cases (58%) and was treated by PTM (n = 6) or surgery (n = 1). The primary patency rate for PTM was 58.8% at 12 months and the secondary patency rate 88.4%, with a mean follow-up of 47 months (median: 44 months). The mortality rate was 3.5% (one death). PTM with balloon dilatation, stent placement, or both, represent a safe method to treat anastomotic BSs after orthotopic liver transplantation (OLT) resulting in a secondary patency rate of 88% at 5 years.

Changes in the bacterial flora of the neoterminal ileum after ileocolonic resection for Crohn's disease.

OBJECTIVE: Bacterial agents have been implicated in the early recurrence of Crohn's disease after ileocolectomy. The aim of our study was to identify and quantify bacteria associated with the ileal mucosa in patients and controls and to correlate specific bacteria with recurrence. METHODS: The predominant bacterial microflora of the ileum were enumerated and identified, aerobically and anaerobically, in biopsies obtained at the time of surgery or by endoscopy from 61 patients with Crohn's disease and 10 ileocolectomy controls. The 61 specimens were comprised of 13 ileal biopsies taken from resection specimens, seven taken after ileostomy, and 41 taken after ileocolectomy. RESULTS: Ileocolectomy induced a significant increase in bacterial counts and variety in the neoterminal ileum in both patients and controls that was not observed in ileostomy biopsies. Comparison between patients and controls revealed greater numbers of Escherichia coli and enterococci in Crohn's disease and of bifidobacteria and ruminococci in controls. Early recurrence was associated with high counts of E. coli and bacteroides and the frequent isolation of fusobacteria. CONCLUSION: After ileocolectomy, colonization of the neoterminal ileum is increased. Our data suggest that increases in the populations of specific bacteria such as E. coli, enterococci, bacteroides, and fusobacteria may be important in postoperative recurrence of Crohn's disease.