Biliary transporter gene mutations in severe intrahepatic cholestasis of pregnancy: Diagnostic and management implications.

BACKGROUND AND AIMS: Clinical syndromes associated with biallelic mutations of bile acid (BA) transporters usually present in childhood. Subtle mutations may underlie intrahepatic cholestasis of pregnancy (ICP) and oral contraceptive steroid (OCS) induced cholestasis. In five women with identified genetic mutations of such transporters, with eight observed pregnancies complicated by ICP, we examined relationships between transporter mutations, clinical phenotypes, and treatment outcomes. METHODS: Gene mutation analysis for BA transporter deficiencies was performed using Next Generation/Sanger sequencing, with analysis for gene deletions/duplications. RESULTS: Intrahepatic cholestasis of pregnancy was early-onset (9-32 weeks gestation) and severe (peak BA 74-370 µmol/L), with premature delivery (28+1 -370 weeks gestation) in 7/8 pregnancies, in utero passage of meconium in 4/8, but overall good perinatal outcomes, with no stillbirths. There was generally no response to ursodeoxycholic acid and variable responses to rifampicin and chelation therapies; naso-biliary drainage appeared effective in 2/2 episodes persisting post-partum in each of the two sisters. Episodic jaundice occurring spontaneously or provoked by non-specific infections, and OCS-induced cholestasis, had previously occurred in 3/5 women. Two cases showed biallelic heterozygosity for several ABCB11 mutations, one was homozygous for an ABCB4 mutation and a fourth case was heterozygous for another ABCB4 mutation. CONCLUSIONS: Early-onset or recurrent ICP, especially with previous spontaneous or OCS-induced episodes of cholestasis and/or familial cholestasis, may be attributable to transporter mutations, including biallelic mutations of one or more transporters. Response to standard therapies for ICP is often incomplete; BA sequestering therapy or naso-biliary drainage may be effective. Optimized management can produce good outcomes despite premature birth and evidence of fetal compromise.

Randomised controlled trial comparing modified Sano's and narrow band imaging international colorectal endoscopic classifications for colorectal lesions.

AIM: To assess the utility of modified Sano's (MS) vs the narrow band imaging international colorectal endoscopic (NICE) classification in differentiating colorectal polyps. METHODS: Patients undergoing colonoscopy between 2013 and 2015 were enrolled in this trial. Based on the MS or the NICE classifications, patients were randomised for real-time endoscopic diagnosis. This was followed by biopsies, endoscopic or surgical resection. The endoscopic diagnosis was then compared to the final (blinded) histopathology. The primary endpoint was the sensitivity (Sn), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of differentiating neoplastic and non-neoplastic polyps (MS II/IIo / IIIa / IIIb vs I or NICE 1 vs 2/3). The secondary endpoints were "endoscopic resectability" (MS II/IIo/IIIa vs I/IIIb or NICE 2 vs 1/3), NPV for diminutive distal adenomas and prediction of post-polypectomy surveillance intervals. RESULTS: A total of 348 patients were evaluated. The Sn, Sp, PPV and NPV in differentiating neoplastic polyps from non-neoplastic polyps were, 98.9%, 85.7%, 98.2% and 90.9% for MS; and 99.1%, 57.7%, 95.4% and 88.2% for NICE, respectively. The area under the receiver operating characteristic curve (AUC) for MS was 0.92 (95%CI: 0.86-0.98); and AUC for NICE was 0.78 (95%CI: 0.69, 0.88). The Sn, Sp, PPV and NPV in predicting "endoscopic resectability" were 98.9%, 86.1%, 97.8% and 92.5% for MS; and 98.6%, 66.7%, 94.7% and 88.9% for NICE, respectively. The AUC for MS was 0.92 (95%CI: 0.87-0.98); and the AUC for NICE was 0.83 (95%CI: 0.75-0.90). The AUC values were statistically different for both comparisons (P = 0.0165 and P = 0.0420, respectively). The accuracy for diagnosis of sessile serrated adenoma/polyp (SSA/P) with high confidence utilizing MS classification was 93.2%. The differentiation of SSA/P from other lesions achieved Sp, Sn, PPV and NPV of 87.2%, 91.5%, 89.6% and 98.6%, respectively. The NPV for predicting adenomas in diminutive rectosigmoid polyps (n = 150) was 96.6% and 95% with MS and NICE respectively. The calculated accuracy of post-polypectomy surveillance for MS group was 98.2% (167 out of 170) and for NICE group was 92.1% (139 out of 151). CONCLUSION: The MS classification outperformed the NICE classification in differentiating neoplastic polyps and predicting endoscopic resectability. Both classifications met ASGE PIVI thresholds.

Detection and characterization of early malignancy in the esophagus: what is the best management algorithm?

Barrett's esophagus is a known precursor for esophageal adenocarcinoma. Early detection of dysplasia provides a window of opportunity for curative intervention. Several image-enhanced technologies have been developed to improve visualization of neoplasia. These however have not been found to be superior to the standard four quadrant random biopsy protocol. Patients are risk-stratified based on the degree of dysplasia found on biopsies and undergo either surveillance or treatment. Endoscopic therapy has become the mainstay of treatment for early neoplasia.

Endoscopic imaging in Barrett's esophagus.

Barrett's esophagus is the only known precursor that predisposes patients to the development of esophageal adenocarcinoma. The current recommended surveillance method is targeted biopsies of any abnormalities followed by random four-quadrant biopsies every 2 cm using standard white light endoscopy. Compliance with this and sampling error are two of the biggest problems. Several novel imaging technologies have been developed to aid the diagnosis of early neoplasia in Barrett's esophagus. There are emerging data that some of these new modalities can increase the yield of detecting dysplasia. This review will discuss some of the present available techniques and technologies including chromoendoscopy, narrow-band imaging, autofluorescence imaging, optical coherence tomography, confocal endomicroscopy and endocytoscopy. Based on the current evidence, these imaging modalities appear to be promising as adjunctive tools to white light endoscopy. A few of them, nevertheless, remain experimental due to expense, lack of expertise, generalizability as well as reproducibility of results.