Recent Progress and Perspective of an Evolving Carbon Family From 0D to 3D: Synthesis, Biomedical Applications, and Potential Challenges.

A variety of imaging techniques are available for detecting biological processes with sufficient penetration depth and temporal resolution. However, inflammation, cardiovascular, and cancer-related disorders might be difficult to diagnose with typical bioimaging methods because of the lack of resolution in the imaging of deep tissues. Therefore, nanomaterials are the most promising candidate to overcome this hurdle. This review is on the utilization of carbon-based nanomaterials (CNMs), ranging from zero-dimension (0D) to three-dimension (3D), in the development of fluorescence (FL) imaging, photoacoustic imaging (PAI), and biosensing for the early detection of cancer. Nanoengineered CNMs, such as graphene, carbon nanotubes (CNTs), and functional carbon quantum dots (QDs), are being further studied for multimodal biometrics and targeted therapy. CNMs have many advantages over conventional dyes in FL sensing and imaging, including clear emission spectra, long photostability, low cost, and high FL intensity. Nanoprobe production, mechanical illustrations, and diagnostic therapeutic applications are the key areas of focus. The bioimaging technique has facilitated a greater understanding of the biochemical events underlying multiple disease etiologies, consequently facilitating disease diagnosis, evaluation of therapeutic efficacy, and drug development. This review may lead to the development of interdisciplinary research in bioimaging and sensing as well as possible future concerns for researchers and medical physicians.

A Combined DNA/RNA-based Next-Generation Sequencing Platform to Improve the Classification of Pancreatic Cysts and Early Detection of Pancreatic Cancer Arising From Pancreatic Cysts.

OBJECTIVE: We report the development and validation of a combined DNA/RNA next-generation sequencing (NGS) platform to improve the evaluation of pancreatic cysts. BACKGROUND AND AIMS: Despite a multidisciplinary approach, pancreatic cyst classification, such as a cystic precursor neoplasm, and the detection of high-grade dysplasia and early adenocarcinoma (advanced neoplasia) can be challenging. NGS of preoperative pancreatic cyst fluid improves the clinical evaluation of pancreatic cysts, but the recent identification of novel genomic alterations necessitates the creation of a comprehensive panel and the development of a genomic classifier to integrate the complex molecular results. METHODS: An updated and unique 74-gene DNA/RNA-targeted NGS panel (PancreaSeq Genomic Classifier) was created to evaluate 5 classes of genomic alterations to include gene mutations (e.g., KRAS, GNAS, etc.), gene fusions and gene expression. Further, CEA mRNA ( CEACAM5 ) was integrated into the assay using RT-qPCR. Separate multi-institutional cohorts for training (n=108) and validation (n=77) were tested, and diagnostic performance was compared to clinical, imaging, cytopathologic, and guideline data. RESULTS: Upon creation of a genomic classifier system, PancreaSeq GC yielded a 95% sensitivity and 100% specificity for a cystic precursor neoplasm, and the sensitivity and specificity for advanced neoplasia were 82% and 100%, respectively. Associated symptoms, cyst size, duct dilatation, a mural nodule, increasing cyst size, and malignant cytopathology had lower sensitivities (41-59%) and lower specificities (56-96%) for advanced neoplasia. This test also increased the sensitivity of current pancreatic cyst guidelines (IAP/Fukuoka and AGA) by >10% and maintained their inherent specificity. CONCLUSIONS: PancreaSeq GC was not only accurate in predicting pancreatic cyst type and advanced neoplasia but also improved the sensitivity of current pancreatic cyst guidelines.

Prospective, Multi-Institutional, Real-Time Next-Generation Sequencing of Pancreatic Cyst Fluid Reveals Diverse Genomic Alterations That Improve the Clinical Management of Pancreatic Cysts.

BACKGROUND & AIMS: Next-generation sequencing (NGS) of pancreatic cyst fluid is a useful adjunct in the assessment of patients with pancreatic cyst. However, previous studies have been retrospective or single institutional experiences. The aim of this study was to prospectively evaluate NGS on a multi-institutional cohort of patients with pancreatic cyst in real time. METHODS: The performance of a 22-gene NGS panel (PancreaSeq) was first retrospectively confirmed and then within a 2-year timeframe, PancreaSeq testing was prospectively used to evaluate endoscopic ultrasound-guided fine-needle aspiration pancreatic cyst fluid from 31 institutions. PancreaSeq results were correlated with endoscopic ultrasound findings, ancillary studies, current pancreatic cyst guidelines, follow-up, and expanded testing (Oncomine) of postoperative specimens. RESULTS: Among 1933 PCs prospectively tested, 1887 (98%) specimens from 1832 patients were satisfactory for PancreaSeq testing. Follow-up was available for 1216 (66%) patients (median, 23 months). Based on 251 (21%) patients with surgical pathology, mitogen-activated protein kinase/GNAS mutations had 90% sensitivity and 100% specificity for a mucinous cyst (positive predictive value [PPV], 100%; negative predictive value [NPV], 77%). On exclusion of low-level variants, the combination of mitogen-activated protein kinase/GNAS and TP53/SMAD4/CTNNB1/mammalian target of rapamycin alterations had 88% sensitivity and 98% specificity for advanced neoplasia (PPV, 97%; NPV, 93%). Inclusion of cytopathologic evaluation to PancreaSeq testing improved the sensitivity to 93% and maintained a high specificity of 95% (PPV, 92%; NPV, 95%). In comparison, other modalities and current pancreatic cyst guidelines, such as the American Gastroenterology Association and International Association of Pancreatology/Fukuoka guidelines, show inferior diagnostic performance. The sensitivities and specificities of VHL and MEN1/loss of heterozygosity alterations were 71% and 100% for serous cystadenomas (PPV, 100%; NPV, 98%), and 68% and 98% for pancreatic neuroendocrine tumors (PPV, 85%; NPV, 95%), respectively. On follow-up, serous cystadenomas with TP53/TERT mutations exhibited interval growth, whereas pancreatic neuroendocrine tumors with loss of heterozygosity of ≥3 genes tended to have distant metastasis. None of the 965 patients who did not undergo surgery developed malignancy. Postoperative Oncomine testing identified mucinous cysts with BRAF fusions and ERBB2 amplification, and advanced neoplasia with CDKN2A alterations. CONCLUSIONS: PancreaSeq was not only sensitive and specific for various pancreatic cyst types and advanced neoplasia arising from mucinous cysts, but also reveals the diversity of genomic alterations seen in pancreatic cysts and their clinical significance.

External nasal dilator decreases N95 respirator-related respiratory effort and symptoms in gastrointestinal endoscopy unit staff.

Background and study aims N95-filtering facepiece respirators (FFR) use is associated with physiological changes and symptoms due to impaired nasal airflow and increased breathing resistance. We prospectively studied the effect of using an external nasal dilator (END) in gastroenterology laboratory (gastrointestinal lab) staff using N95FFR. Patients and methods N95FFR qualitative saccharine fit testing was performed on study participants with and without an END. Prospective data collection and comparisons included: 1) survey of perceived symptoms and difficulty of performing one day of gastrointestinal procedures with N95FFR and 1 day of gastrointestinal procedures with END plus N95FFR in random sequence; and 2) vitals and respiratory belt plethysmography in ten gastroenterologists performing simulated colonoscopy while wearing a surgical mask (SM), N95FFR plus SM, END plus N95FFR plus SM for 20 minutes each in random sequence and rapid succession. Results Twenty-nine of 31 participants passed the N95FFR and the END plus N95FFR fit test. Twenty-two participants (12 physicians; 11 males; mean age 44.1 years, range 31-61) performed 1 day of gastrointestinal procedures with an N95FFR and 1 day of gastrointestinal procedures with an END plus N95FFR. Significantly less difficulty with nasal breathing and severity of symptoms including breathing difficulty, headache, fatigue and frustration, occurred while using an END plus N95FFR. Respiratory plethysmography peak-to-trough measurement showed an increase during the N95FFR stage compared to the END plus N95FFR stage and the SM stage. Conclusions N95FFR related respiratory changes and symptom development may be mitigated by END use.

Non-functional pancreatic neuroendocrine tumours: ATRX/DAXX and alternative lengthening of telomeres (ALT) are prognostically independent from ARX/PDX1 expression and tumour size.

OBJECTIVE: Recent studies have found aristaless-related homeobox gene (ARX)/pancreatic and duodenal homeobox 1 (PDX1), alpha-thalassemia/mental retardation X-linked (ATRX)/death domain-associated protein (DAXX) and alternative lengthening of telomeres (ALT) to be promising prognostic biomarkers for non-functional pancreatic neuroendocrine tumours (NF-PanNETs). However, they have not been comprehensively evaluated, especially among small NF-PanNETs (≤2.0 cm). Moreover, their status in neuroendocrine tumours (NETs) from other sites remains unknown. DESIGN: An international cohort of 1322 NETs was evaluated by immunolabelling for ARX/PDX1 and ATRX/DAXX, and telomere-specific fluorescence in situ hybridisation for ALT. This cohort included 561 primary NF-PanNETs, 107 NF-PanNET metastases and 654 primary, non-pancreatic non-functional NETs and NET metastases. The results were correlated with numerous clinicopathological features including relapse-free survival (RFS). RESULTS: ATRX/DAXX loss and ALT were associated with several adverse prognostic findings and distant metastasis/recurrence (p<0.001). The 5-year RFS rates for patients with ATRX/DAXX-negative and ALT-positive NF-PanNETs were 40% and 42% as compared with 85% and 86% for wild-type NF-PanNETs (p<0.001 and p<0.001). Shorter 5-year RFS rates for ≤2.0 cm NF-PanNETs patients were also seen with ATRX/DAXX loss (65% vs 92%, p=0.003) and ALT (60% vs 93%, p<0.001). By multivariate analysis, ATRX/DAXX and ALT status were independent prognostic factors for RFS. Conversely, classifying NF-PanNETs by ARX/PDX1 expression did not independently correlate with RFS. Except for 4% of pulmonary carcinoids, ATRX/DAXX loss and ALT were only identified in primary (25% and 29%) and NF-PanNET metastases (62% and 71%). CONCLUSIONS: ATRX/DAXX and ALT should be considered in the prognostic evaluation of NF-PanNETs including ≤2.0 cm tumours, and are highly specific for pancreatic origin among NET metastases of unknown primary.

Significance of Uncinate Duct Dilatation in IPMNs: A New High-risk Criterion?

OBJECTIVE: To evaluate the significance of UDD in IPMNs. BACKGROUND: The uncinate process of the pancreas has an independent ductal drainage system. International consensus guidelines of IPMNs still consider it as a branch-duct, even though it is the main drainage system for the uncinate process. METHODS: A retrospective review of all surgically treated IPMNs at our institution after 2008 was performed. Preoperative radiological studies were reviewed by an abdominal radiologist who was blinded to the pathological results. In addition to the Fukuoka criteria, presence of UDD was recorded. Using multivariate analysis, the pathological significance of UDD in predicting advanced neoplasia [high grade dysplasia or invasive carcinoma (HGD/ IC)] was determined. RESULTS: Two hundred sixty patients were identified (mean age at diagnosis was 68 years and 49% were females): 122 (47%) had HGD/IC. UDD was noted in 59 (23%), of which 36 (61%) had HGD/IC (P < 0.003). On multivariate analysis, UDD was an independent predictor of HGD/IC (odds ratio = 2.99, P < 0.04). Subgroup analysis on patients with IPMNs confined to the dorsal portion of the gland (n = 161), also demonstrated UDD to be a significant predictor of HGD/IC in those remote lesions (odds ratio: 4.41, P = 0.039). CONCLUSIONS: This is the largest study to evaluate the significance of UDD in IPMNs and shows it to be a high-risk feature. This association persisted for remote IPMNs limited to the dorsal pancreas, suggesting UDD may be associated with an aggressive phenotype even in remote IPMN lesions.

Laparoscopic-assisted ERCP following RYGB: a 12-year assessment of outcomes and learning curve at a high-volume pancreatobiliary center.

INTRODUCTION: Treatment of pancreaticobiliary pathology following Roux-en-Y gastric bypass (RYGB) poses significant technical challenges. Laparoscopic-assisted endoscopic retrograde cholangiopancreatography (LA-ERCP) can overcome those anatomical hurdles, allowing access to the papilla. Our aims were to analyze our 12-year institutional outcomes and determine the learning curve for LA-ERCP. METHODS: A retrospective review of cases between 2007 and 2019 at a high-volume pancreatobiliary unit was performed. Logistic regression was used to identify predictors of specific outcomes. To identify the learning curve, CUSUM analyses and innovative methods for standardizing the surgeon's timelines were performed. RESULTS: 131 patients underwent LA-ERCP (median age 60, 81% females) by 17 surgeons and 10 gastroenterologists. Cannulation of the papilla was achieved in all cases. Indications were choledocholithiasis (78%), Sphincter of Oddi dysfunction/Papillary stenosis (18%), management of bile leak (2%) and stenting/biopsy of malignant strictures (2%). Median total, surgical and ERCP times were 180, 128 and 48 min, respectively, and 47% underwent concomitant cholecystectomy. Surgical site infection developed in 9.2% and post-ERCP pancreatitis in 3.8%. Logistic regression revealed multiple abdominal operations and magnitude of BMI decrease (between RYGB and LA-ERCP) to be predictive of conversion to open approach. CUSUM analysis of operative time demonstrated a learning curve at case 27 for the surgical team and case 9 for the gastroenterology team. On binary cut analysis, 3-5 cases per surgeon were needed to optimize operative metrics. CONCLUSION: LA-ERCP is associated with high success rates and low adverse events. We identify outcome benchmarks and a learning curve for new adopters of this increasingly performed procedure.

Tumor Size Differences Between Preoperative Endoscopic Ultrasound and Postoperative Pathology for Neoadjuvant-Treated Pancreatic Ductal Adenocarcinoma Predict Patient Outcome.

BACKGROUND & AIMS: The assessment of therapeutic response after neoadjuvant treatment and pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) has been an ongoing challenge. Several limitations have been encountered when employing current grading systems for residual tumor. Considering endoscopic ultrasound (EUS) represents a sensitive imaging technique for PDAC, differences in tumor size between preoperative EUS and postoperative pathology after neoadjuvant therapy were hypothesized to represent an improved marker of treatment response. METHODS: For 340 treatment-naïve and 365 neoadjuvant-treated PDACs, EUS and pathologic findings were analyzed and correlated with patient overall survival (OS). A separate group of 200 neoadjuvant-treated PDACs served as a validation cohort for further analysis. RESULTS: Among treatment-naïve PDACs, there was a moderate concordance between EUS imaging and postoperative pathology for tumor size (r = 0.726, P < .001) and AJCC 8th edition T-stage (r = 0.586, P < .001). In the setting of neoadjuvant therapy, a decrease in T-stage correlated with improved 3-year OS rates (50% vs 31%, P < .001). Through recursive partitioning, a cutoff of ≥47% tumor size reduction was also found to be associated with improved OS (67% vs 32%, P < .001). Improved OS using a ≥47% threshold was validated using a separate cohort of neoadjuvant-treated PDACs (72% vs 36%, P < .001). By multivariate analysis, a reduction in tumor size by ≥47% was an independent prognostic factor for improved OS (P = .007). CONCLUSIONS: The difference in tumor size between preoperative EUS imaging and postoperative pathology among neoadjuvant-treated PDAC patients is an important prognostic indicator and may guide subsequent chemotherapeutic management.

High Rate of Inappropriate Fecal Immunochemical Testing at a Large Veterans Affairs Health Care System.

INTRODUCTION: Colonoscopies and fecal immunochemical tests (FITs) are the preferred modalities for colorectal cancer (CRC) screening. In addition to proper patient selection, appropriate fecal immunochemical testing requires that negative tests be repeated annually, positive tests lead to a diagnostic colonoscopy, and FIT not be performed within 5 years of a colonoscopy with adequate bowel preparation. We sought to study the frequency of inappropriate FITs at the Veterans Affairs Pittsburgh Health Care System in Pennsylvania. METHODS: A retrospective quality assurance study was undertaken of veterans undergoing FIT in a 3-year period (2015-2017). We calculated the rate of a negative initial FIT in 2015/2016 followed by a second FIT in 2016/2017 in a random selection of veterans (3% SE, 95% CI). Demographics were compared in an equal random number of veterans that did and did not have a follow-up FIT (5% SE, 95% CI of all negative FIT). We also calculated the rate of completing colonoscopy following a positive FIT in a random selection of veterans (3% SE, 95% CI). Finally, we investigated use of FIT following a colonoscopy for all veterans in the study period. RESULTS: A total of 6,766 FITs were performed; 4,391 unique veterans had at least 1 negative FIT, and 709 unique veterans had a positive FIT. Of 1,742 veterans with at least 1 negative FIT, 870 were eligible for repeat testing during the study period, and only 543 (62.4%) underwent at least 2 FITs. There was no significant demographic difference in veterans that had only 1 or at least 2 FITs. Of 410 veterans with a positive FIT, 113 (27.5%) did not undergo a subsequent colonoscopy within 1 year due to patient refusal, or failure to schedule or keep a colonoscopy appointment. Of 832 veterans who had both a FIT and colonoscopy in the interval, 108 veterans underwent colonoscopy with a subsequent FIT (1.6% of total FITs performed). Of these, 95 (88%) were judged to be inappropriate. Thirteen instances of FIT following colonoscopy were appropriate based on patient preference to undergo fecal immunochemical testing for CRC screening modality after undergoing colonoscopy with an inadequate bowel preparation. CONCLUSIONS: Veterans underwent inappropriate testing due to failure to undergo serial FIT after a negative result (37.6%), failure to complete colonoscopy following a positive FIT (27.5%), and undergoing inappropriate FIT following a recent colonoscopy (88%). Efforts are still required to improve both patient and provider education and adherence to appropriate fecal immunochemical testing and CRC screening guidelines.

Safety and efficacy of band ligation and auto-amputation as adjunct to EMR of colonic large laterally spreading tumors, and polyps not amenable to routine polypectomy.

INTRODUCTION: The safety and efficacy of colonic band ligation and auto-amputation (1) as adjunct to endoscopic mucosal resection of large laterally spreading tumors and (2) for polyps not amenable to routine polypectomy due to polyp burden or difficult location remain unknown. METHODS: An institutional review board-approved retrospective single-institution study was undertaken of patients undergoing colonic band ligation and auto-amputation from 2014 to date. Patients with indications of 'endoscopic mucosal resection for laterally spreading tumors' and 'polyp not amenable to snare polypectomy' were included in the study. Data were collected on patient demographics, colonoscopy details (laterally spreading tumors/polyp characteristics, therapies applied, complications), pathology results, and follow-up (polyp eradication based on endoscopic appearance and biopsy results). RESULTS: Patients undergoing endoscopic mucosal resection for laterally spreading tumors: Thirty-two patients (31 males, aged 68 ±â€„9.17 years) underwent endoscopic mucosal resection-band ligation and auto-amputation of 34 laterally spreading tumors (40 ±â€„10.9 mm). A median of 2 ±â€„1.09 bands were placed. Follow-up colonoscopy and biopsy results confirmed complete eradication in 21 laterally spreading tumors (70%). Nine (30%) laterally spreading tumors required additional endoscopic therapy to achieve complete eradication. Four (13%) patients underwent surgery for cancer, and two of them had resection specimens negative for cancer or residual adenoma. One patient suffered post-polypectomy syndrome. Patients undergoing band ligation and auto-amputation for polyps not amenable to snare polypectomy: Seven patients underwent band ligation and auto-amputation due to serrated polyposis syndrome (one patient) and innumerable polyps, or polyps in difficult locations (extension into diverticula: two patients; terminal ileum: two patients; appendiceal orifice: one patient; anal canal: one patient). The patient with serrated polyposis syndrome achieved dramatic decrease in polyp burden, but not eradication. Follow-up in five of the six remaining patients documented polyp eradication. The patient with serrated polyposis syndrome suffered from rectal pain and tenesmus following placement of 18 bands. CONCLUSIONS: Band ligation and auto-amputation in the colon may be a safe and effective adjunct to current endoscopic mucosal resection and polypectomy methods and warrants further study. PLAIN LANGUAGE SUMMARY: Colonoscopy with rubber band placement to aid in complete removal of large polyps and polyps in technically challenging locationsColonoscopy is a commonly performed procedure for the early detection of colon and rectal cancer, and prevention through polyp removal.During colonoscopy, sometimes situations are encountered making polyp removal difficult. These can include the presence of larger polyps or the location of a polyp in an area that makes removal technically challenging or high risk.A particularly challenging situation arises when after extensive effort there is still polyp tissue remaining that cannot be removed using routine techniques. We are interested in exploring a technique which involves the placement of a rubber band after sucking a small area of the colon lining into a cap loaded onto the tip of the colonoscope. With time the rubber band strangulates the tissue and falls off along with captured tissue and passes out of the colon naturally.To assess the effectives of this technique we studied patients that have undergone this procedure at our GI unit. We identified 32 patients with 34 large polyps between 4cm to 6cm that we placed rubber bands on polyp tissue after we were unable to completely remove the polyp. On their follow up colonoscopy, complete polyp removal was successful in 21 polyps. We were also able to achieve complete polyp removal in 9 of the remaining large polyps after additional treatment. Four patients underwent surgery because cancer was found in analysis of polyp tissue.In 5 of 6 patients with polyps in difficult locations (e.g. partly within the lumen of the appendix), placement of a rubber band led to complete removal of polyp tissue.Two patients in our study population had mild adverse events that were managed with simple measures.We believe our results show promise for our described technique and this technique should be tested in larger studies.

A Pancreatic Cancer Multidisciplinary Clinic Eliminates Socioeconomic Disparities in Treatment and Improves Survival.

AIMS: National studies have demonstrated disparities in the treatment and survival of pancreatic cancer patients based on socioeconomic status (SES). This study aimed to identify specific differences in perioperative management and outcomes based on patient SES and to study the role of a multidisciplinary clinic (MDC) in mitigating any variations. METHODS: The study analyzed patients undergoing pancreaticoduodenectomy for pancreatic ductal adenocarcinoma in a large hospital system. The patients were categorized into groups of high and low SES and whether they were managed by the authors' pancreatic cancer MDC or not. The study compared differences in disease characteristics, receipt of multimodality therapy, perioperative outcomes, and recurrence-free and overall survival. RESULTS: Of the 162 low-SES patients and 119 high-SES patients, 54% were managed in the MDC. Outside the MDC, low-SES patients were less likely to receive neoadjuvant chemotherapy and had less minimally invasive surgery, a longer OR time, less enhanced recovery participation, and more major complications (p < 0.05). No SES disparities were observed among the MDC patients. Despite similar tumor characteristics, the low-SES patients had inferior median overall survival (21 vs 32 months; p = 0.005), but the MDC appeared to eliminate this disparity. Low SES correlated with inferior survival for the non-MDC patients (17 vs 32 months; p < 0.001), but not for the MDC patients (24 vs 25 months; p = 0.33). These findings persisted in the multivariable analysis. CONCLUSION: A pancreatic cancer MDC standardizes treatment decisions, eliminates disparities in surgical outcomes, and improves survival for low-SES patients.

Acute physiologic effects of N95 respirator use on gastroenterologists performing simulated colonoscopy.

BACKGROUND AND AIMS: During the severe acute respiratory syndrome coronavirus 2 pandemic, N95 filtering facepiece respirator (FFR) use was required while performing aerosol-generating procedures. We studied the physiologic effects of N95 FFR use in a cohort of gastroenterologists performing simulated colonoscopies. METHODS: Data collection and comparisons included (1) symptoms and change in vital signs in 12 gastroenterologists performing simulated colonoscopy for 60 minutes while wearing a surgical mask (SM) and faceshield (FS); N95 FFR, SM, and FS; and powered air-purifying respirator (PAPR) and (2) respiratory belt plethysmography and continuous electrocardiographic frequency-based heart rate (HR) variability indices including very low frequency power (measures intracardiac sympathetic tone) and low frequency to high frequency ratios (intracardiac sympathetic to vagal ratio) in 11 gastroenterologists performing simulated colonoscopy while wearing an SM (15 minutes), N95 FFR and SM (60 minutes), and SM (15 minutes) in rapid sequence. RESULTS: Ten of 12 gastroenterologists (83%) reported symptoms with N95 FFR use, most commonly breathing difficulty, frustration, fatigue, and headache. Nine of these gastroenterologists (75%) had associated significant HR elevation. Respiratory peak to trough measurement showed a significant increase (F(2) = 7.543, P = .004) during the N95 FFR stage, which resolved after removal of the N95 FFR. Although not statistically different, all gastroenterologists showed a decrease in sympathetic to vagal ratios and an increase in intracardiac sympathetic effects in the N95 FFR stage. PAPR use was better tolerated but was associated with headache and elevated HR in 4 gastroenterologists (33%). CONCLUSIONS: N95 FFR use by gastroenterologists is associated with development of acute physiologic changes and symptoms.

Performance of the Veterans Choice Program for Improving Access to Colonoscopy at a Tertiary VA Facility.

INTRODUCTION: The Veterans Choice Program (VCP) was designed to provide a pathway for veterans to access health care in the community if wait times at the US Department of Veterans Affairs (VA) were > 30 days. However, the performance of this program, in terms of timeliness, quality assurance, and overall utilization by veterans for colonoscopy is not well studied. METHODS: We reviewed records of veterans at VA Pittsburgh Healthcare System (VAPHS) who underwent VCP colonoscopy from June 2015 through March 2017. We compared the number of days from the scheduling encounter to the first available colonoscopy at VAPHS to the actual colonoscopy through the VCP. Additionally, we examined the availability of procedure and pathology results, documentation of quality metrics, and if clear follow-up recommendations were present in community care records. We then separately examined VCP utilization in a representative sample (5% margin of error, 95% CI) of all colonoscopy referrals through the VCP. RESULTS: During the study period 3,855 veterans were eligible for colonoscopy via the VCP, and 190 colonoscopies were performed through VCP. Records were absent for 29 exams (15.3%). There was no statistically significant difference for the number of days from a veteran's initially scheduled first-available colonoscopy at VAPHS when compared with the actual VCP colonoscopy (median 2 days earlier, P = .62). Pathology results were absent in 14 of 118 (11.9%) patient records, and follow-up recommendations were absent in 29 of 161 (18%) cases. Documentation of colonoscopy quality metrics were deficient in 27% to 70% of procedure reports. In a utilization sample of 350 veterans, only 26 (7.4%) veterans referred for colonoscopy had documented VCP colonoscopies, and 231 (66%) had a VAPHS colonoscopy. The median actual wait time for colonoscopy was 61 days for VAPHS and 66 days through VCP (P = .15). CONCLUSIONS: Colonoscopies referred through the VCP were not performed sooner in aggregate compared with the first available colonoscopy at VAPHS, although there was wide variability in wait times. We recommend additional mechanisms be put into place when outsourcing to community care: Ensure seamless and require prompt transfer of records back to the VA, require reporting of quality metrics standard at the VA for community care colonoscopies, and establish clinically meaningful wait-time thresholds for referral into the community, rather than static ones.

Integrating next-generation sequencing to endoscopic retrograde cholangiopancreatography (ERCP)-obtained biliary specimens improves the detection and management of patients with malignant bile duct strictures.

OBJECTIVE: Despite improvements in imaging, serum CA19-9 and pathological evaluation, differentiating between benign and malignant bile duct strictures remains a diagnostic conundrum. Recent developments in next-generation sequencing (NGS) have opened new opportunities for early detection and management of cancers but, to date, have not been rigorously applied to biliary specimens. DESIGN: We prospectively evaluated a 28-gene NGS panel (BiliSeq) using endoscopic retrograde cholangiopancreatography-obtained biliary specimens from patients with bile duct strictures. The diagnostic performance of serum CA19-9, pathological evaluation and BiliSeq was assessed on 252 patients (57 trainings and 195 validations) with 346 biliary specimens. RESULTS: The sensitivity and specificity of BiliSeq for malignant strictures was 73% and 100%, respectively. In comparison, an elevated serum CA19-9 and pathological evaluation had sensitivities of 76% and 48%, and specificities of 69% and 99%, respectively. The combination of BiliSeq and pathological evaluation increased the sensitivity to 83% and maintained a specificity of 99%. BiliSeq improved the sensitivity of pathological evaluation for malignancy from 35% to 77% for biliary brushings and from 52% to 83% for biliary biopsies. Among patients with primary sclerosing cholangitis (PSC), BiliSeq had an 83% sensitivity as compared with pathological evaluation with an 8% sensitivity. Therapeutically relevant genomic alterations were identified in 20 (8%) patients. Two patients with ERBB2-amplified cholangiocarcinoma received a trastuzumab-based regimen and had measurable clinicoradiographic response. CONCLUSIONS: The combination of BiliSeq and pathological evaluation of biliary specimens increased the detection of malignant strictures, particularly in patients with PSC. Additionally, BiliSeq identified alterations that may stratify patients for specific anticancer therapies.

Risk of bacterial exposure to the endoscopist's face during endoscopy.

BACKGROUND AND AIMS: Nonuniversal use of facial protection during endoscopy may place endoscopists at risk of exposure to blood and body fluids; however, the frequency of exposure is unknown. METHODS: A prospective 6-month study of 4 gastroenterologists using a face shield during endoscopy was undertaken. The face shield was swabbed in a standardized fashion before and at the end of the session. Controls included pre- and post-swabs of face shields placed on the (1) endoscopy suite wall, (2) remote patient intake bay wall, and (3) after deliberate contamination with a colonoscope immediately after colonoscopy. The swabs were cultured for 48 hours, and growth was reported as no growth or by number of colony-forming units (CFUs). The groups were compared for +CFU rate and CFU number. RESULTS: A total of 1100 procedures were performed in 239 endoscopy sessions. The +CFU rate in the pre-endoscopy groups (2%-4.8%, not significant) was significantly lower than the postendoscopist face shield (45.8%, P < .001) and endoscopy suite wall groups (21.4%, P < .001), respectively. Using a cut-off of >15 CFUs as an indicator of definite exposure, the occurrence rate was 5.6 per 100 half days of endoscopy to the endoscopist's face and 3.4 per 100 half days of endoscopy 6 feet away. CONCLUSIONS: This is the first study to quantify the rate of unrecognized exposure to the endoscopist's face to potentially infectious biologic samples during endoscopy (5.6/100 days of endoscopy). This exposure may result in transmission of infectious diseases. As such, we recommend the use of universal facial protection during GI endoscopy.

Enhanced response of tamoxifen toward the cancer cells using a combination of chemotherapy and photothermal ablation induced by lentinan-functionalized multi-walled carbon nanotubes.

A lentinan (LEN) functionalized multi-walled carbon nanotubes (MWCNTs) drug delivery system, using tamoxifen (TAM) as a model anticancer agent, was developed by a simple non-covalent approach. This developed system (MWCNTs-TAM-LEN) possessed good stability, water dispersibility and extraordinary photothermal properties. It was demonstrated by the in vitro experiments that MWCNTs-TAM-LEN had enhanced cellular uptake, antitumor activity and cell apoptosis on Mcf-7 cells in comparison with TAM and MWCNTs-TAM. The cell inhibition rate and apoptosis rate of Mcf-7 cells treated by MWCNTs-TAM-LEN with near-infrared (NIR) were 67.1% and 66.5% higher than that of equivalent concentration of TAM with NIR irradiation treatment, respectively. The enhanced antitumor efficacy of MWCNTs-TAM-LEN was realized via the synergistic function of chemotherapy and photothermal ablation under NIR laser irradiation.

One step endoscopic ultrasound guided management of pelvic abscesses: a case series.

BACKGROUND: Endoscopic management of pelvic abscesses not amenable to percutaneous drainage has been described. The technique employs endoscopic ultrasound (EUS)-guided placement of stents or drains, which may require multiple procedures, is cumbersome and uncomfortable for the patient. We describe the successful management of these abscesses in a single step involving EUS-guided lavage and instillation of antibiotics. METHODS: Six consecutive patients with seven symptomatic pelvic abscesses not amenable to percutaneous drainage were referred for EUS-guided drainage. The abscesses were aspirated with a 19-gauge needle under EUS guidance and serially lavaged with an equal aspirate to instillation volume of sterile saline until cleared of pus. The residual cavity was then instilled with gentamicin 40 mg/ml. Patients were followed clinically and radiographically with repeat computed tomography or magnetic resonance imaging. RESULTS: All patients had rapid resolution of symptoms. The abscesses disappeared completely in four patients. One patient with recurrent diverticulitis and abscess had marked decrease in abscess size and inflammation to permit planned sigmoid resection. One patient with Crohn's disease had clinical improvement and marked decrease in abscess size, permitting outpatient management of Crohn's disease. CONCLUSIONS: EUS-guided lavage and instillation of antibiotics is a simple, one-step approach in the management of pelvic abscesses and may obviate the need for prolonged drain management and repeat procedures in select cases.