A prospective national study on colonoscopy and sigmoidoscopy in 2000 in France

AIM: The aim of this study was to evaluate the practice of colonoscopy and sigmoidoscopy in France in 2000. METHODS: A prospective study was conducted in November 2000 using questionnaires sent to all gastroenterologists practicing in France (N=2858) who were asked to reply to items concerning colonoscopies and sigmoidoscopies performed on two workdays chosen in advance. The response rate was 32.8%. Data were extrapolated to establish estimates for the entire year. RESULTS: An estimated 894000 colonoscopies and 115320 sigmoidoscopies were performed in 2000. Single-use material was used in 22.1% of the procedures. Indications for endoscopy were mainly hematochezia (21.6%), gastrointestinal symptoms (35%) and surveillance of patients with a history of previous polypectomy (15%). Colorectal cancer screening was the indication for 20% of colonoscopies. Abnormal findings were reported for 54.8% of the endoscopies (polyps for 287218 procedures and cancer for 32799). Failure was noted in 4.9% of colonoscopies. The complication rate was 0.48%. Most polyps were adenomas (64.4%) or hyperplasic polyps (28.1%). The overall estimated number of colonoscopies with polypectomy was 224133. CONCLUSION: In 2000 there was an increased rate of colonoscopy for colorectal cancer screening (20%) but an overall decrease (2.5%) in the total number of colonoscopies compared to 1999. Abnormal findings were disclosed by 54.8% of the procedures. Extrapolation from these data indicates that colonoscopic screening enabled the diagnosis of 32799 colorectal cancers.     

Azathioprine induced liver disease: nodular regenerative hyperplasia of the liver and perivenous fibrosis in a patient treated for multiple sclerosis.

Azathioprine hepatotoxicity has been described mainly in renal transplant recipients. Most reported cases are related to lesions of the venous system of the liver: peliosis hepatis, veno-occlusive disease of the liver, perisinusoidal fibrosis, and nodular regenerative hyperplasia of the liver. The most common clinical manifestation of these hepatic vascular lesions is portal hypertension. We present a case of nodular regenerative hyperplasia and perivenous fibrosis in a patient receiving azathioprine for multiple sclerosis. Histological abnormalities were similar to those described in renal transplant patients, and azathioprine was the only potential hepatotoxic agent present.     

Perforation of the esophagus with the gastrocamera fiberscope

Five patients with perforation of the esophagus due to gastroscopy are reported. Possible causes of this injury are discussed. It is maintained that adequate deflection of the instrument tip is important for prevention of perforations.     

Serum/plasma homocysteine levels in patients with systemic lupus erythematosus: a systematic review and meta-analysis

Clinical Rheumatology - Published studies have shown contradictory results in the association of serum/plasma levels of homocysteine (HCY) with systemic lupus erythematosus (SLE). This study is to...     

Tryptophan metabolites suppress the Wnt pathway and promote adverse limb events in chronic kidney disease

Chronic kidney disease (CKD) imposes a strong and independent risk for peripheral artery disease (PAD). While solutes retained in CKD patients (uremic solutes) inflict vascular damage, their role in PAD remains elusive. Here, we show that the dietary tryptophan-derived uremic solutes including indoxyl sulfate (IS) and kynurenine (Kyn) at concentrations corresponding to those in CKD patients suppress β-catenin in several cell types, including microvascular endothelial cells (ECs), inhibiting Wnt activity and proangiogenic Wnt targets in ECs. Mechanistic probing revealed that these uremic solutes downregulated β-catenin in a manner dependent on serine 33 in its degron motif and through the aryl hydrocarbon receptor (AHR). Hindlimb ischemia in adenine-induced CKD and IS solute–specific mouse models showed diminished β-catenin and VEGF-A in the capillaries and reduced capillary density, which correlated inversely with blood levels of IS and Kyn and AHR activity in ECs. An AHR inhibitor treatment normalized postischemic angiogenic response in CKD mice to a non-CKD level. In a prospective cohort of PAD patients, plasma levels of tryptophan metabolites and plasma’s AHR-inducing activity in ECs significantly increased the risk of future adverse limb events. This work uncovers the tryptophan metabolite/AHR/β-catenin axis as a mediator of microvascular rarefaction in CKD patients and demonstrates its targetability for PAD in CKD models.     

Tankyrase represses autoinflammation through the attenuation of TLR2 signaling

Dysregulation of Toll-like receptor (TLR) signaling contributes to the pathogenesis of autoimmune diseases. Here, we provide genetic evidence that tankyrase, a member of the poly(ADP-ribose) polymerase (PARP) family, negatively regulates TLR2 signaling. We show that mice lacking tankyrase in myeloid cells developed severe systemic inflammation with high serum inflammatory cytokine levels. We provide mechanistic evidence that tankyrase deficiency resulted in tyrosine phosphorylation and activation of TLR2 and show that phosphorylation of tyrosine 647 within the TIR domain by SRC and SYK kinases was critical for TLR2 stabilization and signaling. Last, we show that the elevated cytokine production and inflammation observed in mice lacking tankyrase in myeloid cells were dependent on the adaptor protein 3BP2, which is required for SRC and SYK activation. These data demonstrate that tankyrase provides a checkpoint on the TLR-mediated innate immune response.