GWAS meta-analysis of 16 790 patients with Barrett's oesophagus and oesophageal adenocarcinoma identifies 16 novel genetic risk loci and provides insights into disease aetiology beyond the single marker level.

OBJECTIVE: Oesophageal cancer (EC) is the sixth leading cause of cancer-related deaths. Oesophageal adenocarcinoma (EA), with Barrett's oesophagus (BE) as a precursor lesion, is the most prevalent EC subtype in the Western world. This study aims to contribute to better understand the genetic causes of BE/EA by leveraging genome wide association studies (GWAS), genetic correlation analyses and polygenic risk modelling. DESIGN: We combined data from previous GWAS with new cohorts, increasing the sample size to 16 790 BE/EA cases and 32 476 controls. We also carried out a transcriptome wide association study (TWAS) using expression data from disease-relevant tissues to identify BE/EA candidate genes. To investigate the relationship with reported BE/EA risk factors, a linkage disequilibrium score regression (LDSR) analysis was performed. BE/EA risk models were developed combining clinical/lifestyle risk factors with polygenic risk scores (PRS) derived from the GWAS meta-analysis. RESULTS: The GWAS meta-analysis identified 27 BE and/or EA risk loci, 11 of which were novel. The TWAS identified promising BE/EA candidate genes at seven GWAS loci and at five additional risk loci. The LDSR analysis led to the identification of novel genetic correlations and pointed to differences in BE and EA aetiology. Gastro-oesophageal reflux disease appeared to contribute stronger to the metaplastic BE transformation than to EA development. Finally, combining PRS with BE/EA risk factors improved the performance of the risk models. CONCLUSION: Our findings provide further insights into BE/EA aetiology and its relationship to risk factors. The results lay the foundation for future follow-up studies to identify underlying disease mechanisms and improving risk prediction.

Motorized spiral enteroscopy-assisted ERCP in surgically altered anatomy: early experience from a retrospective cohort study.

BACKGROUND : Motorized spiral enteroscopy (MSE) was recently introduced into clinical practice. The aim of the current study was to evaluate the feasibility and safety of MSE for biliopancreatic interventions in patients with surgically altered anatomy. METHODS : Patients with surgically altered anatomy receiving MSE-assisted ERCP at a single, endoscopy referral center were retrospectively enrolled between January 2016 and June 2021. RESULTS : 36 patients (14 female, 22 male), median age 67 years (range 43-88), with biliary (n = 35) and pancreatic (n = 1) indications for MSE-ERCP, were enrolled. The majority (75.0 %) had relevant comorbidities (American Society of Anesthesiologists class III). Surgical reconstruction included Roux-en-Y (n = 30) and Billroth II (n = 6). Technical success rates for enteroscopy, cannulation, and interventions were 86.1 %, 83.9 %, and 100 %, respectively. The overall MSE-ERCP success rate was 72.2 %. One major complication occurred (2.8 %; delayed post-sphincterotomy bleeding). CONCLUSIONS : This is the first study to demonstrate the feasibility and safety of MSE-assisted ERCP in postsurgical patients with altered anatomy at an expert center. These data justify further evaluation of this new technique, preferably in a prospective multicenter trial.

Digital single-operator pancreatoscopy for the treatment of symptomatic pancreatic duct stones: a prospective multicenter cohort trial.

BACKGROUND: Digital single-operator pancreatoscopy (DSOP)-guided lithotripsy is a novel treatment modality for pancreatic endotherapy, with demonstrated technical success in retrospective series of between 88 % and 100 %. The aim of this prospective multicenter trial was to systematically evaluate DSOP in patients with chronic pancreatitis and symptomatic pancreatic duct stones. METHODS: Patients with symptomatic chronic pancreatitis and three or fewer stones ≥ 5mm in the main pancreatic duct (MPD) of the pancreatic head or body were included. The primary end point was complete stone clearance (CSC) in three or fewer treatment sessions with DSOP. Current guidelines recommend extracorporeal shock wave lithotripsy (ESWL) for MPD stones > 5 mm. A performance goal was developed to show that the CSC rate of MPD stones using DSOP was above what has been previously reported for ESWL. Secondary end points were pain relief measured with the Izbicki pain score (IPS), number of interventions, and serious adverse events (SAEs). RESULTS: 40 chronic pancreatitis patients were included. CSC was achieved in 90 % of patients (36/40) on intention-to-treat analysis, after a mean (SD) of 1.36 (0.64) interventions (53 procedures in total). The mean (SD) baseline IPS decreased from 55.3 (46.2) to 10.9 (18.3). Overall pain relief was achieved in 82.4 % (28/34) after 6 months of follow-up, with complete pain relief in 61.8 % (21/34) and partial pain relief in 20.6 % (7/34). SAEs occurred in 12.5 % of patients (5/40), with all treated conservatively. CONCLUSION: DSOP-guided endotherapy is effective and safe for the treatment of symptomatic MPD stones in highly selected patients with chronic pancreatitis. It significantly reduces pain and could be considered as an alternative to standard ERCP techniques for MPD stone treatment in these patients.

Motorised spiral enteroscopy: first prospective clinical feasibility study.

OBJECTIVE: Currently available methods for small bowel endoscopy are often time consuming; motorised PowerSpiral Enteroscopy (PSE) is a further development of spiral enteroscopy to facilitate the approach to the small bowel. The aim of this bicentric prospective trial was to study feasibility and yield of peroral PSE. DESIGN: Consecutive patients with suspected small bowel disease and indication for antegrade enteroscopy were included in two tertiary referral centres. Primary objective was diagnostic yield of antegrade PSE. Secondary objectives included technical success (defined as successful endoscope insertion at least to ligament of Treitz), depth of maximum insertion (DMI), median insertion time to DMI, rate of therapeutic procedures and adverse events. RESULTS: During a 30-month period, 140 procedures were performed on 132 patients (58 female, 74 male; median age: 68 (20-100) years) under general anaesthesia. Overall diagnostic yield of PSE was 74.2%; with 68.2% of procedures including some form of endotherapy. Technical success rate of PSE was 97%; median DMI was 450 cm (0-600) with a median insertion time to DMI of 25 min (3-122). Antegrade panenteroscopy to the cecum was achieved in 14 cases (10.6%). Overall adverse event (AE) rate was 14.4%; two major serious AEs occurred (1.5%), one delayed perforation, one bleeding from Mallory-Weiss lesion. CONCLUSION: This pilot clinical trial demonstrates that PSE is effective for diagnostic and therapeutic antegrade enteroscopy and may compare favourably with traditional methods of deep enteroscopy in ease of use and procedural duration. More comparative data are required to assess clinical application and safety of PSE. TRIAL REGISTRATION NUMBER: NCT02965209.

Germline variation in the insulin-like growth factor pathway and risk of Barrett's esophagus and esophageal adenocarcinoma.

Genome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal component analysis was employed to evaluate pathway-level and gene-level associations with BE/EAC, using genotypes for 270 single-nucleotide polymorphisms (SNPs) in or near 12 IGF-related genes, ascertained from 3295 BE cases, 2515 EAC cases and 3207 controls in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) GWAS. Gene-level signals were assessed using Multi-marker Analysis of GenoMic Annotation (MAGMA) and SNP summary statistics from BEACON and an expanded GWAS meta-analysis (6167 BE cases, 4112 EAC cases, 17 159 controls). Global variation in the IGF pathway was associated with risk of BE (P = 0.0015). Gene-level associations with BE were observed for GHR (growth hormone receptor; P = 0.00046, false discovery rate q = 0.0056) and IGF1R (IGF1 receptor; P = 0.0090, q = 0.0542). These gene-level signals remained significant at q < 0.1 when assessed using data from the largest available BE/EAC GWAS meta-analysis. No significant associations were observed for EAC. This study represents the most comprehensive evaluation to date of inherited genetic variation in the IGF pathway and BE/EAC risk, providing novel evidence that variation in two genes encoding cell-surface receptors, GHR and IGF1R, may influence risk of BE.

Microvascular Disease in Chronic Thromboembolic Pulmonary Hypertension: Hemodynamic Phenotyping and Histomorphometric Assessment.

BACKGROUND: Pulmonary endarterectomy (PEA) is the gold standard treatment for patients with operable chronic thromboembolic pulmonary hypertension. However, persistent pulmonary hypertension (PH) after PEA remains a major determinant of poor prognosis. A concomitant small-vessel arteriopathy in addition to major pulmonary artery obstruction has been suggested to play an important role in the development of persistent PH and survival after PEA. One of the greatest unmet needs in the current preoperative evaluation is to assess the presence and severity of small-vessel arteriopathy. Using the pulmonary artery occlusion technique, we sought to assess the presence and degree of small-vessel disease in patients with chronic thromboembolic pulmonary hypertension undergoing PEA to predict postoperative outcome before surgery. METHODS: Based on pulmonary artery occlusion waveforms yielding an estimate of the effective capillary pressure, we partitioned pulmonary vascular resistance in larger arterial (upstream resistance [Rup]) and small arterial plus venous components (downstream resistance) in 90 patients before PEA. For validation, lung wedge biopsies were taken from nonobstructed and obstructed lung territories during PEA in 49 cases. Biopsy sites were chosen according to the pulmonary angiogram still frames that were mounted in the operating room. All vessels per specimen were measured in each patient. Percent media (%MT; arteries) and intima thickness (%IT; arteries, veins, and indeterminate vessels) were calculated relative to external vessel diameter. RESULTS: Decreased Rup was an independent predictor of persistent PH (odds ratio per 10%, 0.40 [95% CI, 0.23-0.69]; P=0.001) and survival (hazard ratio per 10%, 0.03 [95% CI, 0.00-0.33]; p=0.004). Arterial %MT and %IT of nonobstructed lung territories and venous %IT of obstructed lung territories were significantly increased in patients with persistent PH and nonsurvivors. Rup correlated inversely with %MT (r=-0.72, P<0.001) and %IT (r=-0.62, P<0.001) of arteries from nonobstructed lung territories and with %IT (r=-0.44, P=0.024) of veins from obstructed lung territories. Receiver operating characteristic analysis disclosed that Rup <66% predicted persistent PH after PEA, whereas Rup <60% identified patients with poor prognosis after PEA. CONCLUSIONS: Pulmonary artery occlusion waveform analysis with estimation of Rup seems to be a valuable technique for assessing the degree of small-vessel disease and postoperative outcome after PEA in chronic thromboembolic pulmonary hypertension.

Sex-Specific Genetic Associations for Barrett's Esophagus and Esophageal Adenocarcinoma.

BACKGROUND & AIMS: Esophageal adenocarcinoma (EA) and its premalignant lesion, Barrett's esophagus (BE), are characterized by a strong and yet unexplained male predominance (with a male-to-female ratio in EA incidence of up to 6:1). Genome-wide association studies (GWAS) have identified more than 20 susceptibility loci for these conditions. However, potential sex differences in genetic associations with BE/EA remain largely unexplored. METHODS: Given strong genetic overlap, BE and EA cases were combined into a single case group for analysis. These were compared with population-based controls. We performed sex-specific GWAS of BE/EA in 3 separate studies and then used fixed-effects meta-analysis to provide summary estimates for >9 million variants for male and female individuals. A series of downstream analyses were conducted separately in male and female individuals to identify genes associated with BE/EA and the genetic correlations between BE/EA and other traits. RESULTS: We included 6758 male BE/EA cases, 7489 male controls, 1670 female BE/EA cases, and 6174 female controls. After Bonferroni correction, our meta-analysis of sex-specific GWAS identified 1 variant at chromosome 6q11.1 (rs112894788, KHDRBS2-MTRNR2L9, PBONF = .039) that was statistically significantly associated with BE/EA risk in male individuals only, and 1 variant at chromosome 8p23.1 (rs13259457, PRSS55-RP1L1, PBONF = 0.057) associated, at borderline significance, with BE/EA risk in female individuals only. We also observed strong genetic correlations of BE/EA with gastroesophageal reflux disease in male individuals and obesity in female individuals. CONCLUSIONS: The identified novel sex-specific variants associated with BE/EA could improve the understanding of the genetic architecture of the disease and the reasons for the male predominance.

Total motorized spiral enteroscopy: first prospective clinical feasibility trial.

BACKGROUND AND AIMS: Motorized spiral enteroscopy (MSE) was recently introduced into clinical practice and shown to be safe and effective for antegrade enteroscopy. The aim of the current trial was to prospectively study the efficacy and safety of MSE for visualization of the entire small bowel. METHODS: All consecutive patients with indications for complete enteroscopy meeting the inclusion criteria were enrolled in a prospective observational bicentric trial, starting with antegrade MSE; a retrograde approach was performed if MSE remained incomplete from antegrade. The primary objective was to ascertain the total enteroscopy rate (TER); secondary objectives were diagnostic yield, procedural success, time, depth of maximum insertion (DMI), therapeutic yield, and adverse events (AEs). RESULTS: Thirty patients (16 women, 14 men; median age 64 years [range, 37-100]) were enrolled. Technical success rate of antegrade MSE (advancement beyond the ligament of Treitz) and retrograde MSE (advancement beyond the ileocecal valve [ICV]) were 100% and 100%, respectively. Overall TER was 70%: 16.6% antegrade approach alone and 53.4% bidirectional approach. Median antegrade DMI distal from the ligament of Treitz was 490 cm (range, 160-600); median insertion time 26 minutes (range, 15-110). The median retrograde DMI beyond the ICV was 120 cm (range, 40-600), and median insertion time was 17 minutes (range, 1-68). Overall diagnostic and therapeutic yields were 80% and 86.7%, respectively. Overall AE rate was 16.7%. No serious AEs occurred. CONCLUSIONS: This prospective study showed that complete enteroscopy is feasible with MSE, either from antegrade alone or bidirectionally, with high success rates and short procedural duration. These results justify further evaluation of MSE in a large prospective multicenter study, preferably with inclusion of a control group. (Clinical trial registration number: NCT03438695.).

Endoscopic retrograde pancreatography-guided versus endoscopic ultrasound-guided technique for pancreatic duct cannulation in patients with pancreaticojejunostomy stenosis: a systematic literature review.

BACKGROUND: Stenosis of the pancreaticojejunostomy is a well-known long-term complication of pancreaticoduodenectomy. Traditionally, the endoscopic approach consisted of endoscopic retrograde pancreatography (ERP). Endoscopic ultrasound (EUS)-guided intervention has emerged as an alternative, but the success rate and adverse event rate of both treatment modalities are poorly known. We aimed to compare the outcome data of both interventions. METHODS: We performed a systematic literature search using the Pubmed/Medline and Embase databases in order to summarize the available data regarding efficacy and complications of ERP- and EUS-guided pancreatic duct (PD) drainage and compare these outcome data using uniform outcome measures in a multilevel logistic model. RESULTS : 13 studies were included, involving 77 patients who underwent ERP-guided drainage, 145 who underwent EUS-guided drainage, and 12 patients who underwent both modalities. An EUS-guided approach was significantly superior to an ERP-guided approach with regard to pancreatic duct opacification (87 % vs. 30 %; P < 0.001), cannulation success (79 % vs. 26 %; P < 0.001), and stent placement (72 % vs. 20 %; P < 0.001). An EUS-guided approach also appeared superior with regard to clinical outcomes such a pain resolution. The adverse event rate between the two treatment modalities could not be compared due to insufficient data. All included studies were found to be of low quality. CONCLUSION: Based on limited available data, EUS-guided PD intervention appears superior to ERP-guided PD intervention.

Endoscopic techniques to reduce recurrence rates after colorectal EMR: systematic review and meta-analysis.

BACKGROUND: Colorectal endoscopic mucosal resection (EMR) is an effective, safe, and minimally invasive treatment for large lateral spreading and sessile polyps. The reported high recurrence rate of approximately 20% is however one of the major drawbacks. Several endoscopic interventions have been suggested to reduce recurrence rates. We conducted a systematic review and meta-analysis to assess the efficacy of endoscopic interventions targeting the EMR margin to reduce recurrence rates. METHODS: We searched in PubMed and Ovid for studies comparing recurrence rates after interventions targeting the EMR margin with standard EMR. The primary outcome was the recurrence rate at the first surveillance colonoscopy (SC1) assessed histologically or macroscopically. For the meta-analysis, risk ratios (RRs) were calculated and pooled using a random effects model. The secondary outcome was post-procedural complication rates. RESULTS: Six studies with a total of 1335 lesions were included in the meta-analysis. The techniques performed in the intervention group targeting the resection margin were argon plasma coagulation, snare tip soft coagulation, extended EMR, and precutting EMR. The interventions reduced the adenoma recurrence rate with more than 50%, resulting in a pooled RR of 0.37 (95% CI 0.18, 0.76) comparing the intervention group with the control groups. Overall post-procedural complication rates did not increase significantly in the intervention arm (RR 1.30; 95% CI 0.65, 2.58). CONCLUSION: Interventions targeting the EMR margin decrease recurrence rates and may not result in more complications.

Percutaneous transhepatic cholangioscopy using a single-operator cholangioscope (pSOC), a retrospective, observational, multicenter study.

BACKGROUND AND AIMS: Percutaneous cholangioscopy (PC) is more complex and invasive than a transpapillary approach, with the need for a large percutaneous tract of 16 French (Fr) on average in order to advance standard percutaneous cholangioscopes. The aim of this study was to investigate whether percutaneous single-operator cholangioscopy (pSOC) using the SpyGlass™ DS system is feasible, safe, and effective in PC for diagnostic and therapeutic indications. MATERIALS AND METHODS: The data of 28 patients who underwent pSOC in 4 tertiary referral centers were retrospectively analyzed. Technical and clinical success for therapeutic procedures was assessed as well as diagnostic accuracy of pSOC-guided biopsies and visualization. Adverse events and the required number and size of dilatations were reviewed. RESULTS: 25/28 (89%) patients had a post-surgical altered anatomy. The average number of percutaneous dilatations prior to pSOC was 1.25 with a mean dilatation size of 11 French. Histopathology showed a 100% accuracy. Visual impression showed an overall accuracy of 96.4%. Technical and clinical success was achieved in 27/28 (96%) of cases. Adverse events occurred in 3/28 (10.7%) cases. CONCLUSION: pSOC is a feasible, safe, and effective technique for diagnostic and therapeutic indications. It may be considered an alternative approach in clinical cases where gastrointestinal anatomy is altered. It has the potential to reduce peri-procedural adverse events and costs. Prospective randomized-controlled trials are necessary to confirm the previously collected data.

Digital single-operator peroral cholangioscopy-guided biopsy sampling versus ERCP-guided brushing for indeterminate biliary strictures: a prospective, randomized, multicenter trial (with video).

BACKGROUND AND AIMS: Accurately diagnosing indeterminate biliary strictures is challenging but important for patient prognostication and further management. Biopsy sampling under direct cholangioscopic vision might be superior to standard ERCP techniques such as brushing or biopsy sampling. Our aim was to investigate whether digital single-operator cholangioscopy (DSOC) compared with standard ERCP workup improves the diagnostic yield in patients with indeterminate biliary strictures. METHODS: Patients with an indeterminate biliary stricture on the basis of MRCP were randomized to standard ERCP visualization with tissue brushing (control arm [CA]) or DSOC visualization and DSOC-guided biopsy sampling (study arm [SA]). This was a prospective, international, multicenter trial with a procedure-blinded pathologist. RESULTS: The first sample sensitivity of DSOC-guided biopsy samples was significantly higher than ERCP-guided brushing (SA 68.2% vs CA 21.4%, P < .01). The sensitivity of visualization (SA 95.5% vs CA 66.7%, P = .02) and overall accuracy (SA 87.1% vs CA 65.5%, P = .05) were significantly higher in the SA compared with the CA, whereas specificity, positive predictive value, and negative predictive value showed no significant difference. Adverse events were equally low in both arms. CONCLUSIONS: DSOC-guided biopsy sampling was shown to be safe and effective with a higher sensitivity compared with standard ERCP techniques in the visual and histopathologic diagnosis of indeterminate biliary strictures. (Clinical trial registration number: NCT03140007.).

Digital single-operator video cholangioscopy in treating refractory biliary stones: a multicenter observational study.

BACKGROUND: Standard endoscopic treatment might fail to treat biliary stone disease. Here, we investigated the efficacy and safety of recently introduced digital single-operator video cholangioscopy (SOVC) for the treatment of difficult biliary stones. METHODS: Digital SOVC procedures, performed in two tertiary referral centers between 2015 and 2018, were retrospectively analyzed. Only patients with a previous failure of endoscopic standard treatment and a SOVC-based biliary stone treatment using electrohydraulic lithotripsy (EHL) or laser lithotripsy (LL) were included. The primary endpoint was to evaluate the stone removal rate per procedure and per patient. RESULTS: In total, 75 examinations with a digital SOVC-assisted biliary stone treatment, performed in 60 patients, were identified. Biliary stones were mainly located extrahepatic (64%) and less frequently intrahepatic (36%). The median stone size was 20 mm (interquartile range [IQR]: 10-25 mm) and the median stone number was 1 (IQR: 1-2). Digital SOVC-based treatment of biliary stone disease was successful in 95% of patients and 15% needed at least two treatment sessions. Evaluated per procedure, a complete stone removal was accomplished in 67% of all examinations (including initial and repeated procedures), while an incomplete stone removal was observed in 33% of cases. The per procedure analyzes revealed that the success rates for a complete stone removal were similar between LL and EHL (66% vs. 68%; p = 0.87). Complications, such as postinterventional cholangitis and pancreatitis occurred in 16% of examinations; however, except from one case, all were mild or moderate and no procedure-associated mortality occurred. CONCLUSIONS: Digital SOVC-assisted biliary stone treatment is highly effective even in cases with difficult biliary stones and might be considered the new standard of care for these patients. Furthermore, mild up to moderate complications were intermittently observed which might document the complexity of our included cases.

No Association Between Vitamin D Status and Risk of Barrett's Esophagus or Esophageal Adenocarcinoma: A Mendelian Randomization Study.

BACKGROUND & AIMS: Epidemiology studies of circulating concentrations of 25 hydroxy vitamin D (25(OH)D) and risk of esophageal adenocarcinoma (EAC) have produced conflicting results. We conducted a Mendelian randomization study to determine the associations between circulating concentrations of 25(OH)D and risks of EAC and its precursor, Barrett's esophagus (BE). METHODS: We conducted a Mendelian randomization study using a 2-sample (summary data) approach. Six single-nucleotide polymorphisms (SNPs; rs3755967, rs10741657, rs12785878, rs10745742, rs8018720, and rs17216707) associated with circulating concentrations of 25(OH)D were used as instrumental variables. We collected data from 6167 patients with BE, 4112 patients with EAC, and 17,159 individuals without BE or EAC (controls) participating in the Barrett's and Esophageal Adenocarcinoma Consortium, as well as studies from Bonn, Germany, and Cambridge and Oxford, United Kingdom. Analyses were performed separately for BE and EAC. RESULTS: Overall, we found no evidence for an association between genetically estimated 25(OH)D concentration and risk of BE or EAC. The odds ratio per 20 nmol/L increase in genetically estimated 25(OH)D concentration for BE risk estimated by combining the individual SNP association using inverse variance weighting was 1.21 (95% CI, 0.77-1.92; P = .41). The odds ratio for EAC risk, estimated by combining the individual SNP association using inverse variance weighting, was 0.68 (95% CI, 0.39-1.19; P = .18). CONCLUSIONS: In a Mendelian randomization study, we found that low genetically estimated 25(OH)D concentrations were not associated with risk of BE or EAC.

In-depth haemodynamic phenotyping of pulmonary hypertension due to left heart disease.

The commonest cause of pulmonary hypertension (PH) is left heart disease (LHD). The current classification system for definitions of PH-LHD is under review. We therefore performed prospective in-depth invasive haemodynamic phenotyping in order to assess the site of increased pulmonary vascular resistance (PVR) in PH-LHD subsets.Based on pulmonary artery occlusion waveforms yielding an estimate of the effective capillary pressure, we partitioned PVR in larger arterial (Rup, upstream resistance) and small arterial plus venous components (Rds, downstream resistance). In the case of small vessel disease, Rup decreases and Rds increases. Inhaled nitric oxide (NO) testing was used to assess acute vasoreactivity.Right ventricular afterload (PVR, pulmonary arterial compliance and effective arterial elastance) was significantly higher in combined post- and pre-capillary PH (Cpc-PH, n=35) than in isolated post-capillary PH (Ipc-PH, n=20). Right ventricular afterload decreased during inhalation of NO in Cpc-PH and idiopathic pulmonary arterial hypertension (n=31), but remained unchanged in Ipc-PH. Rup was similar in Cpc-PH (66.8±10.8%) and idiopathic pulmonary arterial hypertension (65.0±12.2%; p=0.530) suggesting small vessel disease, but significantly higher in Ipc-PH (96.5±4.5%; p<0.001) suggesting upstream transmission of elevated left atrial pressure.Right ventricular afterload is driven by elevated left atrial pressure in Ipc-PH and is further increased by elevated small vessel resistance in Cpc-PH. Cpc-PH is responsive to inhaled NO. Our data support current definitions of PH-LHD subsets.

Impact of 2 generational improvements in colonoscopes on adenoma miss rates: results of a prospective randomized multicenter tandem study.

BACKGROUND AND AIMS: Numerous randomized studies have shown that changing certain features of colonoscopes, usually incorporated when switching from one endoscope generation to the next, mostly do not increase adenoma yield. There is, however, indirect evidence that it may be necessary to skip one instrument generation (ie, changing from one generation to the next but one) to achieve this effect. METHODS: We compared the latest-generation colonoscopes from one company (Olympus Exera III, 190-C) with the next to last one (Olympus 160/5-C) in a prospective multicenter study randomized for the order of colonoscopes in a tandem fashion, involving 2 different examiners. Patients with increased risk for colorectal neoplasia undergoing colonoscopy (positive fecal occult blood test, personal/familial history of colorectal cancer/adenoma, rectal bleeding, recent change in bowel movements) were included. The primary outcome was the adenoma miss rate with the 190 (190-C) colonoscope in comparison with the 160/5 colonoscope (160/5-C). RESULTS: A total of 856 patients (48.8% male; mean age, 58.3 years) with a personal (41%) or family (38%) history of colorectal neoplasia, rectal bleeding (19%), and other indications were included. Of the 429 patients in the 190-C first group, 16.6% (95% confidence interval [CI], 13.0%-20.1%) had at least one adenoma missed during the first procedure, compared with 30.2% (95% CI, 25.9%-34.6%) in the group with 160/5-C first (P < .001). Similarly, the adenoma detection rate during the first colonoscopy was 43.8% versus 36.5% (P = .030) for 190-C versus 160/5-C, respectively. CONCLUSIONS: This randomized tandem trial showed lower adenoma miss rates and higher adenoma detection rates for the newer 190 colonoscopes compared with the 160/5 series. These results suggest that it takes multiple improvements, such as those implemented over 2 instrument generations, before an effect on adenoma (miss) rate can be observed. (Study registration number: ISRCTN 2010-A01256-33.).

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.