Histological assessment of new cholangioscopy-guided forceps in ERCP biliary stricture sampling: a blinded comparative study.

Background and study aims Obtaining quality tissue during ERCP biliary stricture sampling is of paramount importance for a timely diagnosis. While single-operator cholangioscopy (SOC)-guided biopsies have been suggested to be the superior biliary tissue acquisition modality given direct tissue visualization, less is known about the specimen histological quality. We aimed to analyze the specimen quality of SOC biopsies and compare the new generation forceps with prior "legacy" forceps. Patients and methods Patients who underwent SOC from January 2017-August 2021 for biliary sampling were reviewed. In February 2020, the SOC-guided biopsy forceps were changed from legacy SpyBite to the SpyBite Max forceps (max). Specimens were assessed by blinded pathologists for crush artifact (none, mild, or severe) and gross size (greatest dimension in mm). Crush artifact and gross size were compared between the two groups. The diagnostic performance characteristics for cholangiocarcinoma (CCA), were assessed in an exploratory fashion. Results Eighty-one patients (max = 27, legacy = 54) with similar baseline characteristics were included in this study. On blinded pathological assessment, 58 % had crush artifact, without significant differences between the two groups (Max 63 % vs. Legacy 56 %; P  = 0.64). A similar mean specimen size was found (max 3 mm vs. legacy 3.2 mm; P  = 0.24). The overall prevalence of CCA was 40 %. The sensitivity, specificity, positive predictive value, and negative predictive value of the entire cohort using a combination of cytology, fluorescence in situ hybridization, and SOC-guided biopsies were 78.1 %, 91.8 %, 86.2 %, and 86.5 %, respectively. No difference between legacy or max groups was found. Conclusions A high rate of crush artifact was found in SOC-guided biopsy specimens. Further investigation regarding proper biopsy technique and handling is necessary to increase the diagnostic yield with SOC-guided biopsies.

End-stage renal disease is associated with increased post endoscopic retrograde cholangiopancreatography adverse events in hospitalized patients.

AIM: To determine if end-stage renal disease (ESRD) is a risk factor for post endoscopic retrograde cholangiopancreatography (ERCP) adverse events (AEs). METHODS: We performed a retrospective cohort study using the Nationwide Inpatient Sample (NIS) 2011-2013. We identified adult patients who underwent ERCP using the International Classification of Diseases 9th Revision (ICD-9-CM). Included patients were divided into three groups: ESRD, chronic kidney disease (CKD), and control. The primary outcome was post-ERCP AEs including pancreatitis, bleeding, and perforation determined based on specific ICD-9-CM codes. Secondary outcomes were length of hospital stay, in-hospital mortality, and admission cost. AEs and mortality were compared using multivariate logistic regression analysis. RESULTS: There were 492175 discharges that underwent ERCP during the 3 years. The ESRD and CKD groups contained 7347 and 39403 hospitalizations respectively, whereas the control group had 445424 hospitalizations. Post-ERCP pancreatitis (PEP) was significantly higher in the ESRD group (8.3%) compared to the control group (4.6%) with adjusted odd ratio (aOR) = 1.7 (95%CI: 1.4-2.1, a P < 0.001). ESRD was associated with significantly higher ERCP-related bleeding (5.1%) compared to the control group 1.5% (aOR = 1.86, 95%CI: 1.4-2.4, a P < 0.001). ESRD had increased hospital mortality 7.1% vs 1.15% in the control OR = 6.6 (95%CI: 5.3-8.2, a P < 0.001), longer hospital stay with adjusted mean difference (aMD) = 5.9 d (95%CI: 5.0-6.7 d, a P < 0.001) and higher hospitalization charges aMD = $+82064 (95%CI: $68221-$95906, a P < 0.001). CONCLUSION: ESRD is a risk factor for post-ERCP AEs and is associated with higher hospital mortality. Careful selection and close monitoring is warranted to improve outcomes.

Assessment of pancreatic neuroendocrine tumor cytologic genotype diversity to guide personalized medicine using a custom gastroenteropancreatic next-generation sequencing panel.

BACKGROUND: Recent genetic studies have highlighted that alterations in MEN1, chromatin remodeling genes, and mammalian target of rapamycin (mTOR) pathway genes are the most frequent molecular events identified in pancreas neuroendocrine tumors (pNETs). The prognostic or predictive impact of these biomarkers and other less frequently observed aberrations, i.e. PTEN, TSC2 and PIK3CA are relatively unknown. The aims of this targeted next generation sequencing (NGS) study were to assess tumor cytology genotype diversity, to survey for potential adverse prognostic biomarkers and the prevalence of mTOR pathway variants. METHODS: Using a custom 15 gene gastroenteropancreatic neuroendocrine tumor panel, targeted NGS of archived (2002-2013) primary pNETs (n=90) and pNET liver metastasis (n=32) cytology smears was performed. RESULTS: The genetic variant landscape revealed that 21% and 28% of primary and metastatic liver pNETs harbored ≥ 2 variants per tumor, respectively. The most prevalent primary tumor variants were in the MEN1 (42%), DAXX (11%), ATRX (10%), and TSC2 (8%) genes. Patients harboring aberrations in TSC2, KRAS or TP53 were more likely to experience disease progression and reduced overall survival, when compared to individuals who were wild-type. The prevalence of these potential prognostic biomarkers in early disease was observed in 3.3% of the primary tumor cohort. mTOR pathway variants including alterations in PTEN, TSC2 and PIK3CA were identified in 10% and 12.5% of primary tumors and pNET liver metastasis, respectively. CONCLUSION: Cytology based tumor genotyping revealed a broad spectrum of genetic variants including possible adverse prognostic biomarkers, reflective of an aggressive phenotype. It also demonstrated the prevalence of potential predictive biomarkers for mTOR pathway inhibitor sensitivity.

Money-back guarantees.

As fertility rates among women of advanced reproductive age have steadily increased, so has the utilization of fertility services. National health policies provide infertility treatment coverage in several developed countries; however, in the United States infertility treatment is largely privately funded, resulting in limited access to care. In response to the lack of insurance coverage, many practices offer fertility treatment on a risk-sharing or contingency fee basis. The ethical delivery of care under the auspices of these programs requires adherence to core principles including transparency, patient autonomy, and the delivery of appropriate medical care. Moreover, concerns regarding patient understanding and decision making have also been of foremost concern. Patients must be able to fully appreciate the financial and clinical implications of contingency fee programs. To further explore patient comprehension and satisfaction, we surveyed participants in our shared risk assisted reproductive technology program. The overwhelming majority of respondents felt adequately informed of and fairly charged for their treatment. Our results demonstrate that shared risk programs can receive strong endorsement from participants, which may lead to improved utilization of and perseverance with fertility treatment.

EUS-FNA assessment of extramesenteric lymph node status in primary rectal cancer.

BACKGROUND: Preoperative staging is an essential factor in the multidisciplinary management of rectal cancer. The accuracy of imaging alone with CT, magnetic resonance imaging, or rigid endorectal US is poor. The addition of EUS-FNA may enhance extramesenteric lymph node metastases detection (M1 disease) and overall staging accuracy. OBJECTIVE: To evaluate the frequency of extramesenteric lymph node visualization by EUS and the rate of extramesenteric lymph node metastases by FNA. Secondary goals were to evaluate the clinical, endoscopic, and sonographic features associated with extramesenteric lymph node metastases, disease progression, and overall mortality. DESIGN: Retrospective cohort study. SETTINGS: Tertiary referral center. RESULTS: Forty-one of 316 patients (13%) with primary rectal cancer over a 6-year period had M1 disease by EUS-FNA. Significant clinical, endoscopic, and sonographic features associated with extramesenteric lymph node metastases included the serum carcinoembryonic antigen level, tumor length 4 cm and longer, annularity 50% or more, sessile morphology, and lymph node size. The sensitivity and specificity of CT for extramesenteric lymph node metastases were 44% and 89%, respectively. Twenty-three of 316 rectal cancer endosonographic procedures (7.3%) were up-staged by FNA, which established extramesenteric lymph node metastases. Over a 4-year follow-up, disease progression and overall mortality of patients with extramesenteric lymph node metastases was observed in 6 patients (14.6%) and 14 patients (34%), respectively. CONCLUSIONS: Preoperative EUS-FNA identification of extramesenteric lymph node metastases outside of standard radiation fields or total mesorectal excision resection margins could affect medical and surgical planning.

Ethical application of Shared Risk programs in assisted reproductive technology.

Shared Risk programs require adherence to core principles: transparency, patient autonomy, and appropriate medical care. These programs improve utilization of and perseverance with fertility treatment, receiving strong patient endorsements.

Prospective cytological assessment of gastrointestinal luminal fluid acquired during EUS: a potential source of false-positive FNA and needle tract seeding.

OBJECTIVES: Endoscopic ultrasound (EUS) fine needle aspiration (FNA) can result in false-positive cytology and can also cause needle tract seeding. Our goal was to evaluate a potential cause, namely, the presence of malignant cells within gastrointestinal (GI) luminal fluid, either as a result of tumor sloughing from luminal cancers or secondary to FNA of extraluminal sites. METHODS: During EUS, luminal fluid that is usually aspirated through the echoendoscope suction channel and discarded was instead submitted for cytological analysis among patients with cancer and benign disease. Pre- and post-FNA luminal fluid samples were collected to discern the role of FNA in inducing a positive cytology. When not performing FNA, one sample was collected for the entire examination. The final diagnosis was based on strict clinicopathological criteria and >or=2-year follow-up. This study was conducted in a tertiary referral center. RESULTS: We assessed the prevalence of luminal fluid-positive cytology among patients with luminal (e.g., esophageal), extraluminal (e.g., pancreatic), and benign disease. Among the 140 patients prospectively enrolled with sufficient sampling and follow-up, an examination of luminal fluid cytology showed positive results for malignancy in luminal and extraluminal cancer patients, 48 and 10%, respectively. This included 8 out of 23 esophageal, 4 of 5 gastric, and 9 of 15 rectal cancers. The positive luminal fluid cytology rate with luminal cancers was not affected by performing FNA. Post-FNA luminal fluid cytology was positive in 3 out of 26 with pancreatic cancers. Cytological examination of luminal fluid aspirates did not demonstrate malignant cells in any patient with nonmalignant disease. CONCLUSIONS: Malignant cells are commonly present in the GI luminal fluid of patients with luminal cancers and can also be found in patients with pancreatic cancer after EUS FNA. Further study is needed to determine the impact of these findings on cytological interpretation, staging, risk of needle tract seeding, and patient care and outcomes.

Prospective assessment of EUS criteria for lymphadenopathy associated with rectal cancer.

BACKGROUND: There are few data that assess the accuracy of echo characteristics for predicting lymph-node (LN) metastases in patients with rectal cancer. OBJECTIVE: To identify nodal echo characteristics and size predictive of malignant infiltration and to determine if any combination of standard nodal criteria has sufficient predictive value to preclude FNA. DESIGN: Prospective uncontrolled study. SETTING: Tertiary-referral hospital. PATIENTS: Seventy-six patients (68% men) with untreated rectal cancer; 52 had visualized LNs. INTERVENTION: EUS-guided FNA. MAIN OUTCOME MEASUREMENTS: Evaluation of perirectal nodal morphology accuracy that corresponds to malignant cytology and identification of echo criteria, including LN size, to have sufficient predictive value to predict malignancy. RESULTS: Forty-three of 52 patients (83%) underwent FNA of a visualized LN. Nodal hypoechogenicity and short-axis length >or=5 mm were factors independently predictive of malignancy. The number of malignant nodal echo features per node did not distinguish benign from malignant pathology, except when all 4 features were present. Only 68% of malignant LN had >or=3 echo characteristics. An optimum LN short-axis or long-axis length cutoff value of 6 mm or 9 mm were 90% and 95% specific, respectively, for the presence of malignancy by receiver operating characteristic analysis. LIMITATIONS: FNA was performed in a subset of identified LNs. CONCLUSIONS: Nodal echo features alone are often inadequate to establish the presence of locoregional metastatic disease by EUS. These data support the value of FNA to confirm the presence of malignancy in place of relying on imaging criteria.

Establishing a true assessment of endoscopic competence in ERCP during training and beyond: a single-operator learning curve for deep biliary cannulation in patients with native papillary anatomy.

BACKGROUND: Deep cannulation of the common bile duct (CBD) in patients with native papillary anatomy can be used as a marker of competence at ERCP. OBJECTIVE: The primary aim of this study was to analyze a single-operator learning curve for supervised ERCPs in patients with native papillary anatomy and to assess the development of endoscopic competence, defined as the ability to deeply cannulate the CBD in the setting > or =80% of the time. Posttraining outcomes were evaluated as proof of training. DESIGN: A retrospective review: 1097 ERCP procedures were analyzed, 697 were performed during ERCP training (July 2002-July 2003), 400 were performed after training as an independent operator, 499 and 303 procedures for training and posttraining periods, respectively, were performed with the intent of deep cannulation of CBD in patients with native papillary anatomy. Procedures were chronologically grouped into subsets. Success rates were plotted against time. SETTING: Single center. MAIN OUTCOME MEASUREMENTS: Rate of successful deep biliary cannulation. RESULTS: The successful cannulation rate increased from 43% at the beginning of training to > or =80% after 350 to 400 supervised procedures. The success rate continued to improve posttraining with an aggregated success rate of >96% for the next 300 procedures performed as an independent operator. LIMITATIONS: Single operator. CONCLUSIONS: Achievement of a satisfactory success rate for deep biliary cannulation in patients with native papillary anatomy should be tracked by ERCP trainers and trainees. The consistent achievement of > or =80% success at deep biliary cannulation in such patients should become a standard for ERCP training programs to produce skilled and competent therapeutic biliary endoscopists.

Assessment of the impact of an educational course on knowledge of appropriate EUS indications.

BACKGROUND: The knowledge level of EUS among gastroenterologists likely influences the appropriateness of requested indications for EUS. It remains unknown what the impact is of a short EUS course, involving didactic teaching, on knowledge levels of EUS indications for EUS. The aim of this study was to assess the impact of a 3-day educational course on knowledge levels of attending gastroenterologists regarding the appropriateness of indications for EUS. METHODS: A questionnaire was designed that tested knowledge of indications for EUS in 4 anatomic sites: esophagus, gastroduodenum, hepatopancreatobiliary system, and colorectum. This questionnaire was distributed to all attendees of a 3-day EUS educational course. All attendees completed the survey before and immediately after the course. RESULTS: A total of 24 gastroenterologists completed the pre- and post-course survey. Before the course, respondents scored highest in questions on EUS applications in the gastroduodenum (94%) and the hepatopancreatobiliary system (88%) compared with the esophagus (72%) and the colorectum (74%). Statistically significant improvements in knowledge were recorded in all organ categories: gastroduodenum (100%, p = 0.002 vs. pretest score), hepatopancreatobiliary system (99%, p < 0.0001), esophagus (92%, p < 0.0001), and colorectum (93%, p = 0.0004). The biggest improvement was observed in knowledge levels for the esophagus (20%) and the colorectum (18%). CONCLUSIONS: There was a consistent improvement in the gastroenterologists' knowledge levels of EUS indications among all organ categories after an educational course. Our findings suggest that education enhances gastroenterologists' understanding of EUS. Future studies should seek to assess the impact of these improved knowledge levels on the appropriateness of EUS referral patterns.

Prospective risk assessment of bacteremia and other infectious complications in patients undergoing EUS-guided FNA.

BACKGROUND: There are few data regarding the risk of bacteremia with EUS-guided FNA. This study prospectively evaluated the frequency of bacteremia and other infectious complications after EUS-guided FNA. METHODS: Patients referred for EUS-guided FNA of the upper GI tract lesions were considered for enrollment. Patients were excluded if there was an indication for preprocedure administration of antibiotics based on ASGE guidelines, had taken antibiotics within the prior 7 days, or if they had a pancreatic cystic lesion. Blood cultures were obtained immediately before the procedure, after routine endoscopy/radial EUS, and 15 minutes after EUS-guided FNA. RESULTS: Fifty-two patients underwent EUS-guided FNA at 74 sites (mean 1.4 sites/patient) totaling 266 passes of the fine needle (mean 5.1 FNA/patient). Coagulase negative Staphylococcus was grown in cultures from 3 patients (5.8%; 95% CI [1%, 15%]) and was considered a contaminant. Three patients (5.8%; 95% CI [1%, 15%]) developed bacteremia: Streptococcus viridans (n = 2), unidentified gram-negative bacillus (n = 1). No signs or symptoms of infection developed in any patient. CONCLUSION: EUS-guided FNA of solid lesions in the upper GI tract should be considered a low-risk procedure for infectious complications that does not warrant prophylactic administration of antibiotics for prevention of bacterial endocarditis.