Identification of visible lesions during surveillance endoscopy for Barrett's esophagus: a video-based survey study.

BACKGROUND AND AIMS: Visible lesion (VL) detection is essential in patients with Barrett's esophagus (BE). We sought to assess the rate of VL detection by academic and community endoscopists using high-definition white-light endoscopy (HD-WLE) and narrow-band imaging (NBI) during surveillance endoscopy. METHODS: Fifty endoscopists were invited to participate in a prospective video survey study. Participants viewed 25 standardized clips of patients referred for endoscopic therapy. Participants noted identification of anatomic landmarks and VLs using HD-WLE and NBI and reported practice-level data. The criterion standard of VL identification was established by consensus of 5 BE experts. Our primary outcome was the rate of VL identification using HD-WLE and NBI. RESULTS: Forty-four of 50 participants completed the study (22 academic and 22 community). Compared with the criterion standard, participants did not identify 28% (HD-WLE) and 31% (NBI) of VLs. Community endoscopists had more experience (>5 years in practice: community 85% vs academic 54.5%, P = .041; >5 surveillance endoscopies a month: community 85% vs academic 31.8%, P = .046). Across all participants, VL detection using NBI improved significantly with a minimum of 5 surveillance endoscopies per month (area under the curve = .72; 95% confidence interval, .56-.85; P = .006). CONCLUSIONS: Despite improved endoscope resolution and availability of virtual chromoendoscopy, the overall rate of VL detection remains low. Identification of VLs using NBI may be volume dependent. Further education and training efforts focused on VL detection during BE surveillance endoscopy are needed.

Threshold evaluation for optimal number of endoscopic treatment sessions to achieve complete eradication of Barrett's metaplasia.

BACKGROUND: Endoscopic eradication therapy (EET) is the standard of care for Barrett's esophagus (BE)-associated neoplasia. Previous data suggest the mean number of EET sessions required to achieve complete eradication of intestinal metaplasia (CE-IM) is 3. This study aimed to define the threshold of EET sessions required to achieve CE-IM. METHODS: The TREAT-BE Consortium is a multicenter outcomes cohort including prospectively enrolled patients with BE undergoing EET. All patients achieving CE-IM were included. Demographic, endoscopic, and histologic data were recorded at treatment onset along with treatment details and surveillance data. Kaplan-Meier analysis was performed to define a threshold of EET sessions, with 95 %CI, required to achieve CE-IM. A secondary analysis examined predictors of incomplete response to EET using multiple logistic regression and recurrence rates. RESULTS: 623 patients (mean age 65.2 [SD 11.6], 79.6 % male, 86.5 % Caucasian) achieved CE-IM in a mean of 2.9 (SD 1.7) EET sessions (median 2) and a median total observation period of 2.7 years (interquartile range 1.4-5.0). After three sessions, 73 % of patients achieved CE-IM (95 %CI 70 %-77 %). Age (odds ratio [OR] 1.25, 95 %CI 1.05-1.50) and length of BE (OR 1.24, 95 %CI 1.17-1.31) were significant predictors of incomplete response. CONCLUSION: The current study found that a threshold of three EET sessions would achieve CE-IM in the majority of patients. Alternative therapies and further diagnostic testing should be considered for patients who do not have significant response to EET after three sessions.

Practice patterns, techniques, and outcomes of flexible endoscopic myotomy for Zenker's diverticulum: a retrospective multicenter study.

BACKGROUND: Flexible endoscopic myotomy has been increasingly performed for Zenker's diverticulum using various endoscopic techniques and devices. The main aims of this study were to assess practice patterns and compare outcomes of endoscopic myotomy for Zenker's diverticulum. METHODS: Procedures performed at 12 tertiary endoscopy centers from 1/2012 to 12/2018 were reviewed. Patients (≥ 18 years) with Zenker's diverticulum who had dysphagia and/or regurgitation and underwent endoscopic myotomy were included. Outcomes assessed included technical success, clinical success, and adverse events. RESULTS: 161 patients were included. Traditional endoscopic septotomy was performed most frequently (137/161, 85.1 %) followed by submucosal dissection of the septum and myotomy (24/161, 14.9 %). The hook knife (43/161, 26.7 %) and needle-knife (33/161, 20.5 %) were used most frequently. Overall, technical and clinical success rates were 98.1 % (158/161) and 78.1 % (96/123), respectively. Adverse events were noted in 13 patients (8.1 %). There was no significant difference in technical and clinical success between traditional septotomy and submucosal dissection groups (97.1 % vs. 95.8 %, P = 0.56 and 75.2 % vs. 90.9 %, P  = 0.16, respectively). Clinical success was higher with the hook knife (96.7 %) compared with the needle-knife (76.6 %) and insulated tip knife (47.1 %). Outcomes were similar between centers performing > 20, 11 - 20, and ≤ 10 procedures. CONCLUSIONS: Flexible endoscopic myotomy is an effective therapy for Zenker's diverticulum, with a low rate of adverse events. There was no significant difference in outcomes between traditional septotomy and a submucosal dissection approach, or with centers with higher volume, though clinical success was higher with the hook knife.

Underutilization of Lynch Syndrome Screening at Two Large Veterans Affairs Medical Centers.

BACKGROUND: Lynch syndrome (LS) is the most common hereditary colorectal cancer (CRC) syndrome, yet is grossly under-recognized. Multiple professional societies recommend screening all CRCs for LS by performing tumor testing. The veterans affairs system has not adopted universal tumor testing as a national performance metric and leaves screening for LS to clinical care at individual sites. AIMS: Describe adherence to LS screening in the VA system. METHODS: Dual-center, retrospective review of all CRCs diagnosed between 2010 and 2016. Rates of tumor testing, personal and family history of cancer were extracted from the medical record. Univariate and multivariate regression analysis was performed to determine predictors of tumor-based screening for LS. RESULTS: A total of 421 cancers were reviewed. 15.1% of all cancers underwent either MSI and/or IHC for LS screening over the study period. There was improvement in LS screening from 3% of all CRCs in 2010 to 45% of all CRCs in 2016. 34% and 70% of patients did not have documentation of CRC in first- and second-degree relatives, respectively. Of the 73 patients who met one of the Revised Bethesda Criteria or had a PREMM1,2,6 score of ≥ 5, 34% and 56% underwent tumor testing, respectively. Younger age, non-Caucasian race, meeting Bethesda or PREMM1,2,6 criteria and right-sided tumor location were predictors of undergoing tumor testing. CONCLUSIONS: CRC tumor screening for LS is grossly inadequate when left to routine clinical care. Our results lend support to implementation of reflexive universal tumor testing within the VA system.

Pancreatoscopy-guided laser dissection and ablation for treatment of benign and neoplastic pancreatic disorders: an initial report (with videos).

BACKGROUND AND AIMS: Per-oral pancreatoscopy (POP) permits direct evaluation of the pancreatic duct for the visualization and sampling of neoplastic lesions and treatment of pancreatic duct stones by using intraductal lithotripsy techniques. Pancreatic laser endotherapy of mucosa has been described in animal models for tumor ablation, but human experience is lacking. We describe 3 unique and challenging clinical situations that benefited from pancreatic laser dissection and ablation. CASE DESCRIPTION: Case 1 was a 75-year-old woman with presumed divisum-associated chronic pancreatitis who had recurrent acute pancreatitis despite minor papilla sphincterotomy and therapeutic stent placement. POP showed a side-branch intraductal papillary mucinous neoplasm within the neck of the pancreas. POP-guided holmium laser ablation of neoplastic tissue was performed, followed by pancreatic stent placement every 6 months, with no further hospitalizations at 20 months of follow-up. Case 2 was a 69-year-old woman with divisum-associated chronic calcific pancreatitis and recalcitrant mid-body stenosis. Previous attempts at balloon dilation and stent placement failed to resolve the stenosis. POP-guided holmium laser dissection of the stenosis was pursued, with immediate radiographic resolution. Case 3 was a 65-year-old woman with chronic calcific pancreatitis and a large stone burden who underwent POP-guided electrohydraulic lithotripsy and partial stone extraction followed by stent placement. Unfortunately, the stent fractured during the subsequent removal attempt because the fragment was impacted in the pancreatic body. POP-guided laser dissection and lithotripsy were used to debulk dense fibrous tissue and stones surrounding the stent fragment, respectively, followed by removal. CONCLUSIONS: Pancreatoscopy-guided laser endotherapy is a novel and potentially useful technique to manage difficult benign and neoplastic pancreatic disorders.

Technical feasibility, diagnostic yield, and safety of microforceps biopsies during EUS evaluation of pancreatic cystic lesions (with video).

BACKGROUND AND AIMS: Through-the-needle microforceps are a recent addition to the EUS armamentarium for evaluation of pancreatic cystic lesions (PCLs). The main aim of this study was to assess the technical feasibility, diagnostic yield, and safety of EUS-guided microforceps biopsy for PCLs. METHODS: Our electronic endoscopy database was queried to identify patients who underwent EUS-guided FNA (EUS-FNA) of PCLs and microforceps biopsies during the same procedure. A biopsy was done on the wall of the cyst with the microforceps through the 19-gauge needle, and cyst fluid was collected for cytology and carcinoembryonic antigen (CEA) levels. Adverse events were recorded per published American Society for Gastrointestinal Endoscopy criteria. RESULTS: Twenty-seven patients underwent EUS-FNA and microforceps biopsy of PCLs from February 2016 to July 2017. Fourteen cysts were located in the pancreatic head and/or uncinate, and 13 were located in the body and/or tail region. Microforceps biopsies were technically successful in all cases and provided a pathology diagnosis in 24 of 27 cases (yield 88.9%). Microforceps biopsies diagnosed mucinous cyst in 9 patients (33.3%), serous cystadenoma in 4 (14.8%), neuroendocrine tumor in 1 (3.7%), and benign and/or inflammatory cyst in 10 (37.1%). In 7 patients (26%), microforceps biopsy results drastically changed the diagnosis, providing diagnoses otherwise not suggested by cytology or cyst fluid CEA levels. However, cytology provided a diagnosis of mucinous cyst in 4 cases (14.8%) not detected by microforceps biopsies. No adverse events were noted. CONCLUSION: Microforceps biopsies were associated with high technical success, and an excellent safety profile and may be a useful adjunctive tool, complementing existing EUS-FNA sampling protocols for PCLs.

Orexin-neuromodulated cerebellar circuit controls redistribution of arterial blood flows for defense behavior in rabbits.

We investigated a unique microzone of the cerebellum located in folium-p (fp) of rabbit flocculus. In fp, Purkinje cells were potently excited by stimulation of the hypothalamus or mesencephalic periaqueductal gray, which induced defense reactions. Using multiple neuroscience techniques, we determined that this excitation was mediated via beaded axons of orexinergic hypothalamic neurons passing collaterals through the mesencephalic periaqueductal gray. Axonal tracing studies using DiI and biotinylated dextran amine evidenced the projection of fp Purkinje cells to the ventrolateral corner of the ipsilateral parabrachial nucleus (PBN). Because, in defense reactions, arterial blood flow has been known to redistribute from visceral organs to active muscles, we hypothesized that, via PBN, fp adaptively controls arterial blood flow redistribution under orexin-mediated neuromodulation that could occur in defense behavior. This hypothesis was supported by our finding that climbing fiber signals to fp Purkinje cells were elicited by stimulation of the aortic nerve, a high arterial blood pressure, or a high potassium concentration in muscles, all implying errors in the control of arterial blood flow. We further examined the arterial blood flow redistribution elicited by electric foot shock stimuli in awake, behaving rabbits. We found that systemic administration of an orexin antagonist attenuated the redistribution and that lesioning of fp caused an imbalance in the redistribution between active muscles and visceral organs. Lesioning of fp also diminished foot shock-induced increases in the mean arterial blood pressure. These results collectively support the hypothesis that the fp microcomplex adaptively controls defense reactions under orexin-mediated neuromodulation.

Pre-transplant left ventricular diastolic dysfunction is associated with post transplant acute graft rejection and graft failure.

INTRODUCTION: Acute cellular rejection (ACR) is a significant cause of morbidity and graft failure in liver transplant recipients (LTR). Diastolic dysfunction (DD) is frequently present in patients with cirrhosis undergoing liver transplantation. However, it is unclear if DD leads to ACR. METHODS: Data was collected retrospectively for consecutive LTR between January 2000 and December 2010. Demographic data and mortality related data was obtained from social security index. Primary outcome was biopsy proven ACR. Graft failure and all-cause mortality were also evaluated. DD was evaluated as a predictor of these outcomes. Other echocardiographic indices were also assessed as predictors of ACR by using Cox proportional hazard modeling adjusted for covariates. RESULTS: A total of 970 LTR (mean age 53.2 ± 10 years, women 34.6 % and white 64.5 %) were followed for 5.3 ± 3.4 years. Patients with DD (n = 145, 14.9 %) were significantly more likely to develop ACRs (HR 10.56; 95 % CI 6.78-16.45, p value = 0.0001) as well as graft failure (HR 2.09; 95 % CI 1.22-3.59, p value = 0.007) and all-cause mortality (HR 1.52; 95 % CI 1.08-2.13, p = 0.01). There was an increase in the risk of these outcomes with worsening of DD, when adjusted for various risk factors such as donor and recipient age, gender, race, Framingham risk score, pre-transplant MELD, transplant etiology and cold ischemia time. CONCLUSION: Pre-transplant DD is significantly associated with increased risk of allograft rejection, graft failure and mortality. This signifies the importance of cardiac evaluation during the pre-transplant period.

Adherence to quality indicators and best practices in surveillance endoscopy of Barrett's esophagus: A video-based assessment.

Background and study aims Adherence to quality indicators (QIs) and best practices (BPs) for endoscopic surveillance of Barrett's esophagus (BE) is low based on clinical documentation which is an inaccurate representation of events occurring during procedures. This study aimed to assess adherence to measurable QI and BP using video evaluation. Methods We performed a single center video-based retrospective review of surveillance endoscopies performed for BE ≥1 cm between March 1, 2018 and October 1, 2020. Adherence to QIs and BPs was assessed through video review and documentation. Videos were evaluated by five gastroenterologists. Interrater variability was determined using 10 videos before reviewing the remaining 128 videos. A generalized linear regression model was used to determine predictors of adherence to QIs and BPs. Results There were 138 endoscopies reviewed. Inspection with virtual chromoendoscopy (VC) occurred in 75 cases (54%) on video review with documentation in 50 of these cases (67%). Adherence to the Seattle protocol (SP) occurred in 74 cases (54%) on video review with documentation in 28 of these cases (38%). Use of VC or the SP was documented but not observed on video review in 16 (12%) and 30 (22%) cases, respectively. Length of BE was associated with increased use of the Prague classification (odds ratio [OR] 1.21, 95% confidence interval [CI] 1.07-1.37) while years in practice was associated with a decreased likelihood of VC use (OR 0.93, 95% CI 0.88-0.99). Conclusions This study validates prior data demonstrating poor adherence to QIs and BPs and highlights discrepancies between clinical documentation and events occurring during procedures.

Clinical predictors of post-liver transplant new-onset heart failure.

Objectives of this study were (1) to evaluate preoperative predictors of systolic and diastolic heart failure in patients undergoing liver transplantation (LT) and (2) to describe the prognostic implications of systolic and diastolic heart failure in these patients. The onset of heart failure after orthotopic LT remains poorly understood. Data were obtained for all LT recipients between January 2000 and December 2010. The primary outcome was post-LT heart failure: systolic (ejection fraction ≤ 50%), diastolic, or mixed heart failure. Patients underwent echocardiographic evaluation before and after LT. Pretransplant variables were evaluated as predictors of heart failure with Cox proportional hazards model. 970 LT recipients were followed for 5.3 ± 3.4 years. Ninety-eight patients (10.1%) developed heart failure in the posttransplant period. There were 67 systolic (6.9%), 24 diastolic (2.5%), and 7 mixed systolic/diastolic (0.7%) heart failures. Etiology was ischemic in 18 (18.4%), tachycardia-induced in 8 (8.2%), valvular in 7 (7.1%), alcohol-related in 4 (4.1%), hypertensive heart disease in 3 (3.1%), and nonischemic in majority of patients (59.2%). Pretransplant grade 3 diastolic dysfunction, diabetes, hypertension, mean arterial pressure ≤ 65 mm Hg, mean pulmonary artery pressure ≥ 30 mm Hg, mean pulmonary capillary wedge pressure ≥ 15 mm Hg, hemodialysis, brain natriuretic peptide level and QT interval > 450 ms were found to be predictive for the development of new-onset systolic heart failure. However beta-blocker use before LT and tacrolimus after LT were associated with reduced development of new-onset systolic heart failure. In conclusion, pretransplant risk factors, hemodynamic variables, and echocardiographic variables are important predictors of post-LT heart failure. In patients undergoing LT, postoperative onset of systolic or diastolic heart failure was found to be an independent predictor of mortality.

Heparin-induced thrombocytopenia: is it a graft-threatening complication?

Heparin-induced thrombocytopenia (HIT), a prothrombotic complication of heparin therapy, can lead to serious thromboembolic events and cause significant morbidity and mortality. We aim to study the prevalence of HIT in the transplant population at our institute. This is a retrospective, single-center study which looked into the transplant database over a 25-year period. In patients with clinical suspicion of HIT, the 4T score was used, and laboratory tests such as ELISA HIT antibody and functional serotonin release assay, along with clinical manifestation of thromboembolic events were reviewed. Medical records of 2800 patients who underwent transplantation from January 1985 to December 2010 were reviewed. HIT antibody assay was performed in 262 patients from this group in which HIT was suspected. Of these, only 48 patients were HIT antibody positive along with moderate to high 4T score. The mean 4T score was 6.75 ± 1.4. Thrombotic complications were seen in 11 patients, with the highest in cardiac transplant recipients. Direct thrombin inhibitor (DTI) therapy was used in only eight patients who had thrombotic event. No other complications or mortality was reported in any of the HIT antibody-positive transplant patients. To our knowledge, this is the first study of its kind that has shown very low incidence of HIT in the transplant population except for in cardiac transplant recipients.

Isolated diastolic hypertension and its risk factors in semi-rural population of South India.

BACKGROUND: Isolated diastolic hypertension (IDH) has been actively discussed for the last two decades because of its prevalence in a younger population and its association with cardiovascular disease. Furthermore, the association of IDH is significant in South Asian Countries such as India because relatively younger populations are known to have a higher risk of cardiovascular events. OBJECTIVE: The objective of this study is to find prevalence of IDH and its risk correlates in a semiurban population of South Indian state of Andhra Pradesh. METHODS: Data were collected using the modified World Health Organization - STEPwise approach to Surveillance (WHO STEPS) questionnaire for 16,636 individuals from a group of villages under Thavanampalle Mandal. Collated data were analyzed for prevalence and risk factors of IDH. RESULTS: Prevalence of IDH was found to be 4.0% with mean age of 46.0 (±SD 13.6) years and a relatively higher prevalence in men (5.3%) as compared with women (3.2%). The prevalence of IDH peaked in the fifth decade of life (40-49 years of age) and declined thereafter. Among various risk factors that were analyzed for their association with IDH, only age, body weight, and body mass index retained their significance in multivariate binary logistic regression analysis. CONCLUSION: There is a significant prevalence of IDH below 50 years of age in the semiurban population of South India. As IDH in young and middle age is known to be associated with increased risk of cardiovascular events and end organ involvement, it highlights need for study and development of effective IDH management strategies to reduce associated morbidity and mortality.

Prevalence and correlates of hypertension in a semi-rural population of Southern India.

While elevated blood pressure is a recognized risk factor for cardiovascular disease, the prevalence of hypertension still remains unclear for most populations. A door-to-door survey was conducted using modified WHO STEPS questionnaire in a group of villages under the Thavanampalle Mandal of Chittoor District in the state of Andhra Pradesh of South India. Data were collated and analyzed for 16,636 individuals (62.3% females and 37.7% males) above 15 years of age. Overall, prevalence of hypertension (as per JNC-7 classification) was found to be 27.0% (95% CI, 26.3, 27.7) in the surveyed community with 56.7% of the total hypertensives being diagnosed for the first time during the survey. An additional 39.1% had their blood pressure readings in the prehypertensive range. Among the known Hypertensives on treatment only 46.2% had a blood pressure recording within acceptable limits, with 31.2% in the prehypertensive range and only 15.0% in the normal range. Systolic blood pressure (SBP) of the surveyed population showed a continuous linear increase with age, but diastolic blood pressure (DBP) peaked and started reducing in early fifth decade in males. Male gender, increasing age, higher body mass index (BMI), increased waist-hip ratio, increased body weight, family history of hypertension, death of spouse, and diabetes were found to be positively correlated with hypertension. Risk factors of alcohol intake, use of ground nut/palm oil, and family history of diabetes lost their independent predictive ability for hypertension on multivariate logistic regression analysis. The level of physical activity was also not found to be a significant predictor of hypertension in the study population.

Socioeconomic and Racial Disparities: a Case-Control Study of Patients Receiving Transcatheter Aortic Valve Replacement for Severe Aortic Stenosis.

BACKGROUND: We sought to quantify socioeconomic disparities in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) at an urban, tertiary referral center. METHODS: This retrospective case-control study identified 67 patients with severe AS (aortic valve [AV] area ≤1 cm2 or AV area index ≤0.60 cm2/m2 or AV velocity ≥40 mmHg) who underwent TAVR from November 5, 2013 to June 10, 2014. Study subjects were matched to controls with severe AS without TAVR in a 4:1 age-frequency match. Demographic data were collected using electronic medical records. Area-based median household income was obtained by geocoding patients' addresses and linking with census data. Charlson comorbidity index for all subjects was calculated. RESULTS: Income disparity was significant in that with every $10,000 increase in income, the odds of receiving TAVR increased by 10% (p = 0.05). Non-blacks were significantly more likely to receive TAVR than blacks (odds ratio [OR] 2.812, confidence interval [CI] 1.007-7.853; p = 0.048). No differences in comorbidities were found between the two groups. Post hoc analysis to identify etiologies of the found disparities examined differences of AV area and AV area index, indication for two-dimensional echocardiography (echo), symptoms prior to echo, and action after echo within the control group. Black race significantly impacted the TAVR status despite the same AV area (OR 0.33, CI 0.09-0.97, p = 0.043). After echo, blacks were more likely to decline AVR, be lost to follow-up, and not be referred to cardiology (OR 4.41, CI 1.43-13.64; p = 0.010). CONCLUSION: Socioeconomic and racial disparities were associated with patients with severe AS receiving TAVR at a major referral center. This study emphasizes the importance of improving access to standard of care for these subgroups of cardiac patients.

Predictors of fecal transplant failure.

BACKGROUND: Clostridium difficile infection (CDI) is a significant healthcare burden, with increased morbidity and mortality. Traditional treatment regimens using antibiotics for recurrent CDI are significantly less successful compared with 80-90% with fecal microbiota transplantation (FMT). There is a paucity of data on failure rates and mortality after FMT in CDI. This study aims to identify the rates of failure, relapse, and mortality associated with FMT as well as the risk factors for FMT failure. METHODS: A large retrospective cohort study was carried out including all patients who underwent FMT from December 2012 through May 2014. Patient factors (demographics, comorbidities, immune-suppression, transplant history, antibiotics used, hospitalization, and surgeries), disease factors (number of episodes of CDI, treatments, and severity), and transplant factors (route and number of FMT) were examined. Failure of treatment was defined as no resolution of diarrhea in patients who had been treated with one or more fecal microbiota transplantation within 90 days of FMT. RESULTS: A total of 201 patients (age 66.6±18.3 years, 62.2% women) were included. The overall failure rate was 12.4%. Patients with failed fecal transplant had increased number of FMTs compared with those who responded (mean 1.92±0.997 vs. 1.29±0.615; P=0.004). No colectomies or death related to CDI were found in our patient population. Significant predictors of failure were female sex (P=0.016), previous hospitalization (P=0.006), and surgery before FMT (P=0.005). The overall mortality rate was 9.0% and failure of FMT was associated with an increased risk of death (odds ratio=5.833, confidence interval 2.01-16.925; P<0.05). CONCLUSION: FMT is a suitable alterative to antibiotic use for recurrent CDIs, with a high success rate. The results indicate that hospital-acquired CDI may be a predictor of failure of FMT.