Christian Gerges

Standardized Long-Term Follow-Up After Endoscopic Resection of Large, Nonpedunculated Colorectal Lesions: A Prospective Two-Center Study

OBJECTIVES:Endoscopic removal of large, nonpedunculated colorectal lesions is challenging. Long-term outcome data based on standardized protocols, including detailed inspection of the resection site, are scarce. The aims of the present study were to evaluate the safety and efficacy of endoscopic resection (ER) of large, nonpedunculated lesions (LNLs; >20 mm) and to assess the long-term recurrence rate afterward.METHODS:A total of 243 consecutive patients (141 men, 102 women) with 252 adenomas (>20 mm) was followed up using a standardized protocol after complete ER. After endoscopic treatment, the patients received standardized follow-up examinations after 3–6 months and 12 months. The postpolypectomy scar was re-examined, assessed for residual neoplasia, and biopsied at each follow-up colonoscopy.RESULTS:Evident residual neoplasia was noted after 3–6 months in 58 of 183 lesions (31.69%). After 12 months, 126 LNLs were examined, with 19 late recurrences (16.37%). Twenty-one (6.5%) postpolypectomy scars were not detected during 321 surveillance examinations. Biopsy evidence of residual/recurrent lesions was found in 16 of 228 macroscopically inconspicuous polypectomy scars (7%). All residual adenomas were treated using ER and/or argon plasma coagulation. There were 43 complications with the 252 lesions (17%), including 20 major complications (7.9%), all managed conservatively.CONCLUSIONS:A detailed study design with systematic biopsies of inconspicuous scars reveals a significant number of residual adenomas after completed resection. However, these residual neoplasias can be effectively treated at follow-up colonoscopies.

Genome-wide association studies in oesophageal adenocarcinoma and Barrett's oesophagus: a large-scale meta-analysis

Summary Background Oesophageal adenocarcinoma represents one of the fastest rising cancers in high-income countries. Barretts oesophagus is the premalignant precursor of oesophageal adenocarcinoma. However, only a few patients with Barretts oesophagus develop adenocarcinoma, which complicates clinical management in the absence of valid predictors. Within an international consortium investigating the genetics of Barretts oesophagus and oesophageal adenocarcinoma, we aimed to identify novel genetic risk variants for the development of Barretts oesophagus and oesophageal adenocarcinoma. Methods We did a meta-analysis of all genome-wide association studies of Barretts oesophagus and oesophageal adenocarcinoma available in PubMed up to Feb 29, 2016; all patients were of European ancestry and disease was confirmed histopathologically. All participants were from four separate studies within Europe, North America, and Australia and were genotyped on high-density single nucleotide polymorphism (SNP) arrays. Meta-analysis was done with a fixed-effects inverse variance-weighting approach and with a standard genome-wide significance threshold (p<5 × 10−8). We also did an association analysis after reweighting of loci with an approach that investigates annotation enrichment among genome-wide significant loci. Furthermore, the entire dataset was analysed with bioinformatics approaches—including functional annotation databases and gene-based and pathway-based methods—to identify pathophysiologically relevant cellular mechanisms. Findings Our sample comprised 6167 patients with Barretts oesophagus and 4112 individuals with oesophageal adenocarcinoma, in addition to 17 159 representative controls from four genome-wide association studies in Europe, North America, and Australia. We identified eight new risk loci associated with either Barretts oesophagus or oesophageal adenocarcinoma, within or near the genes CFTR (rs17451754; p=4·8 × 10−10), MSRA (rs17749155; p=5·2 × 10−10), LINC00208 and BLK (rs10108511; p=2·1 × 10−9), KHDRBS2 (rs62423175; p=3·0 × 10−9), TPPP and CEP72 (rs9918259; p=3·2 × 10−9), TMOD1 (rs7852462; p=1·5 × 10−8), SATB2 (rs139606545; p=2·0 × 10−8), and HTR3C and ABCC5 (rs9823696; p=1·6 × 10−8). The locus identified near HTR3C and ABCC5 (rs9823696) was associated specifically with oesophageal adenocarcinoma (p=1·6 × 10−8) and was independent of Barretts oesophagus development (p=0·45). A ninth novel risk locus was identified within the gene LPA (rs12207195; posterior probability 0·925) after reweighting with significantly enriched annotations. The strongest disease pathways identified (p<10−6) belonged to muscle cell differentiation and to mesenchyme development and differentiation. Interpretation Our meta-analysis of genome-wide association studies doubled the number of known risk loci for Barretts oesophagus and oesophageal adenocarcinoma and revealed new insights into causes of these diseases. Furthermore, the specific association between oesophageal adenocarcinoma and the locus near HTR3C and ABCC5 might constitute a novel genetic marker for prediction of the transition from Barretts oesophagus to oesophageal adenocarcinoma. Fine-mapping and functional studies of new risk loci could lead to identification of key molecules in the development of Barretts oesophagus and oesophageal adenocarcinoma, which might encourage development of advanced prevention and intervention strategies. Funding US National Cancer Institute, US National Institutes of Health, National Health and Medical Research Council of Australia, Swedish Cancer Society, Medical Research Council UK, Cambridge NIHR Biomedical Research Centre, Cambridge Experimental Cancer Medicine Centre, Else Kröner Fresenius Stiftung, Wellcome Trust, Cancer Research UK, AstraZeneca UK, University Hospitals of Leicester, University of Oxford, Australian Research Council.

Expandable metal stents for malignant hilar biliary obstruction.

Most patients with malignant hilar stenoses are candidates for palliation. For this purpose, biliary drainage plays a major role in improving liver function and managing or avoiding cholangitis. Endoscopic interventions are less invasive than the percutaneous approach and should be considered as the first-line drainage procedures in most cases. Transhepatic interventions should be reserved for endoscopic failures or performed as a complementary approach in a combined procedure. After successful endoscopic access to biliary obstruction, implantation of self-expandable metal stents offers advantages over plastic endoprostheses in terms of stent patency and number of reinterventions.

Supportive evidence for FOXP1, BARX1, and FOXF1 as genetic risk loci for the development of esophageal adenocarcinoma.

The Barretts and Esophageal Adenocarcinoma Consortium (BEACON) recently performed a genome‐wide association study (GWAS) on esophageal adenocarcinoma (EAC) and Barretts esophagus. They identified genome‐wide significant association for variants at three genes, namely CRTC1, FOXP1, and BARX1. Furthermore, they replicated an association at the FOXF1 gene that has been previously found in a GWAS on Barretts esophagus. We aimed at further replicating the association at these and other loci that showed suggestive association with P < 10−4 in the BEACON sample. In total, we tested 88 SNPs in an independent sample consisting of 1065 EAC cases and 1019 controls of German descent. We could replicate the association at FOXP1, BARX1, and FOXF1 with nominal significance and thereby confirm that genetic variants at these genes confer EAC risk. In addition, we found association of variants near the genes XRCC2 and GATA6 that were strongly (P < 10−5) although not genome‐wide significantly associated with the BEACON GWAS. Therefore, both variants and corresponding genes represent promising candidates for future EAC association studies on independent samples.

Direct retrograde cholangioscopy with a new prototype double-bending cholangioscope

BACKGROUND AND STUDY AIMS Direct retrograde cholangioscopy (DRC) enables high quality video imaging of the bile ducts and allows intraductal treatment with optical control. We evaluated the feasibility, success, and complications of a new third-generation prototype cholangioscope. PATIENTS AND METHODS All consecutive patients from two tertiary endoscopy centers who had undergone DRC with the prototype were included. Indications for DRC were: evaluation of indeterminate strictures, filling defects, and complex bile duct stones. Technical success was investigated in terms of indication and treatment performed. All adverse events were recorded. RESULTS DRC with the prototype was performed in 74 patients. Therapeutic interventions included laser or electrohydraulic lithotripsy and stone removal, among others. The papilla was entered in 72/74 patients (97 %). The targeted bile duct segment was reached in 62 /74 patients (84 %), with an anchoring balloon catheter needed in 21/74 (28 %). Mean investigation time was 21 minutes (15 - 27 minutes) CONCLUSIONS DRC using the prototype is feasible, safe, and attains access to the bile ducts in almost all patients, with less need of an anchoring balloon catheter compared with the standard technique and short investigation and fluoroscopy times.

The Barrett‐associated variants at GDF7 and TBX5 also increase esophageal adenocarcinoma risk

Barretts esophagus (BE) and esophageal adenocarcinoma (EAC) represent two stages within the esophagitis‐metaplasia‐dysplasia‐adenocarcinoma sequence. Previously genetic risk factors have been identified that confer risk to BE and EAC development. However, to which extent the genetic variants confer risk to different stages of the BE/EAC sequence remains mainly unknown. In this study we analyzed three most recently identified BE variants at the genes GDF7 (rs3072), TBX5 (rs2701108), and ALDH1A2 (rs3784262) separately in BE and EAC samples in order to determine their risk effects during BE/EAC sequence. Our data show that rs3072 at GDF7 and rs2701108 at TBX5 are also associated with EAC and conclude that both loci confer disease risk also at later stages of the BE/EAC sequence. In contrast, rs3784262 at ALDH1A2 was highly significantly associated with BE, but showed no association with EAC. Our data do not provide evidence that the ALDH1A2 locus confers equal risk in early and late stages of BE/EAC sequence.

Motorized spiral colonoscopy: a first single-center feasibility trial

BACKGROUND Cecal intubation rate represents a key procedural quality parameter in diagnostic colonoscopy. However, even experienced investigators report 10 % of all colonoscopies to be difficult and intubation of the cecum is sometimes impossible. A recently developed novel motorized spiral endoscope might potentially overcome some limitations of standard colonoscopy by actively pleating the bowel onto the endoscope. The study aim was to evaluate the feasibility and safety of motorized spiral colonoscopy (MSC) for diagnostic colonoscopy. METHODS 30 consecutive patients with an indication for diagnostic colonoscopy were enrolled in a proof-of-concept single-center trial. RESULTS 13 men and 17 women (mean age 68.9 years, range 30 - 90) were enrolled; 43.3 % had diverticula. Mean procedure time was 20.8 min (range 11.4 - 55.3). Cecal intubation rate was 96.7 %. One incomplete colonoscopy occurred because of an unexpected postinflammatory stricture. Adenoma detection rate was 46.6 %. No severe adverse events occurred. CONCLUSIONS Results indicate that MSC is safe and effective for diagnostic colonoscopy. It potentially offers advantages in terms of ease and it may facilitate therapeutic interventions.

Endoscopic treatment of pancreatic duct stones under direct vision: Revolution or resignation? Systematic review

The main treatment aim in chronic pancreatitis (CP) is symptom control and especially pain relief. Management of stone‐predominant CP is challenging and requires a multidisciplinary approach. Extracorporeal shock wave lithotripsy (ESWL) has emerged as the cornerstone of non‐surgical treatment as a result of disappointing results of available endoscopic treatment options during the last decades. With new developments in the field of direct peroral pancreatoscopy (POP) and intracorporeal lithotripsy, direct intraluminal treatment of main pancreatic duct (MPD) stones returns to the spotlight.

Endobiliary polypectomy of biliary tumor using a prototype dedicated cholangioscope with double-bending technology

A67-year-oldwomanwas admittedwith recurrent episodes of upper-abdominal pain, obstructive jaundice, and cholangitis. One year earlier, a complicated open cholecystectomy had been performed because of symptomatic gallbladder stones. Several previous conventional ERCPs showed recurrent obstructing bile duct stones and filling defects of the proximal common bile duct (CBD), necessitating a continuous indwell of biliary plastic stents. EUS and magnetic resonance imaging again confirmed a filling defect of the proximal CBD, suggesting a bile duct stone. During ERCP with single-operator cholangioscopy (Fig. 1), a large stone in the proximal CBD could be visualized. After electrohydraulic lithotripsy under direct vision, cholangioscopy revealed a lumen-obstructing large pedunculated polypoid mass of the CBD that was hidden under the stone surface as the underlying cause of obstruction and recurrent stone formation. Repeated cholangioscopically guided microforceps biopsy was performed, but the results of examination were negative for the histologic diagnosis of the lesion, suggesting a subepithelial localization. EUS andmagnetic resonance imaging showedno evidence of deep infiltration. Direct per-oral cholangioscopywith a prototype dedicated cholangioscope with double-bending tech-