EUS-guided hydrogel injection to separate pancreatic head carcinoma from duodenum for enhanced radiotherapy: Multi-site feasibility study.

Background and study aims The proximity of a pancreas head tumor to the duodenum often limits delivery of an ablative dose of radiation therapy. This study evaluated the feasibility and safety of using an injectable polyethylene glycol (PEG) hydrogel between the head of the pancreas and duodenum. Patients and methods In a multi-site feasibility cohort study of patients with localized pancreatic cancer, PEG hydrogel was injected under endoscopic ultrasound guidance to temporarily position the duodenum away from the pancreas. Procedure characteristics were recorded, including hydrogel volume and space created. Patients were monitored for adverse events (AEs) and radiotherapy toxicity. Results In all six intent-to-treat patients (four with borderline resectable, two with locally advanced disease), the ability to place and visualize PEG hydrogel and create space between the duodenum and the head of the pancreas was successful. There were no procedure-related AEs resulting in radiotherapy delay. There were no device-related AEs and no reports of pancreatitis. Conclusions PEG hydrogel was successfully placed, created space between the duodenum and the head of the pancreas, and was not associated with major toxicity. Enhancing radiotherapy for pancreatic cancer by using PEG hydrogel to create peri-duodenal space could have beneficial implications for treatment and warrants more exploration.

The multidisciplinary pancreatic cyst clinic: A collaborative approach to streamlined management.

BACKGROUND: Pancreatic cysts are often incidentally detected on routine imaging studies. Of these, mucinous cysts have a malignant potential. Several guidelines propose different management strategies, and implementation in patient care is inconsistent in the absence of dedicated infrastructure. METHODS: To address the challenges of pancreatic cyst diagnosis and management, we established a multidisciplinary pancreas cyst clinic (PCC) within our health system. This clinic encompasses both tertiary care academic centers and community hospitals, with leadership from surgical oncology, gastroenterology, and radiology. Our PCC's primary goal is to provide accurate diagnosis and tailored management recommendations for all patients with pancreatic cysts. Additionally, we maintain a prospective database to study the disease's natural history and the outcomes of various treatment strategies. CLINIC INFRASTRUCTURE: The clinic meets once per week for 45 min virtually via Zoom in the mornings. Patients are referred via electronic medical record (EMR) order, telephone call, or email from patient or referring provider. A dedicated advanced practice provider reviews referrals several times per day, calls patients to gather clinical data, ensures imaging is uploaded, and coordinates logistical aspects of the meeting during the dedicated time. Conferences are attended by representatives from surgery, radiology, medical pancreatology, and interventional gastroenterology. Each patient case is reviewed in detail and recommendations are submitted to referring providers and patients via an EMR message and letter. For patients requiring imaging surveillance, patients are followed longitudinally by the referring provider, gastroenterology team, or surgical team. For patients requiring endoscopic ultrasound (EUS) or surgical consultation, expedited referral to these services is made with prompt subsequent evaluation. RESULTS: A total of 1052 patients from our health system were evaluated between 2020 and 2021. Of these, 196 (18.6 %) underwent EUS, 41 (3.9 %) underwent upfront surgical resection, and the remainder were referred to gastroenterology (141-13.4 %), surgery (314-29.8 %), or back to their referring provider (597-56.7 %) for ongoing surveillance in collaboration with their primary care provider (PCP). Of cysts under surveillance, 61.3 % remained stable, 13.2 % increased in size, and 2 % decreased in size. A total of 2.3 % of patients were recommended to discontinue surveillance. CONCLUSIONS: The PCC provides infrastructure that has served to provide multidisciplinary review and consensus recommendations to patients with pancreatic cysts. This has served to improve the application of guidelines while providing individualized recommendations to each patient, while aiding non-expert referring providers throughout the region.

Impact of preoperative endoscopic procedures on adverse event rates after surgical resection for main-duct and mixed-type intraductal papillary mucinous neoplasms (IPMNs).

BACKGROUND: Main-duct (MD-) and mixed-type (MT-) IPMNs harbor an increased risk of pancreatic cancer and warrant surgical resection. Preoperative endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) are important in the diagnosis of IPMNs. The aim of this study was to investigate whether endoscopic procedures manipulating the MD impact postoperative adverse events in patients with MD- and MT-IPMNs. METHODS: We performed a retrospective study of 369 patients who underwent resections for MD- or MT-IPMN at two tertiary centers (2000-2019). Multivariable logistic regression analyses were performed for postoperative adverse events to compare the risks between intervention (ERCP, EUS-FNA with branch duct (BD) aspirated, EUS-FNA with MD aspirated from the duct directly or cyst/mass arising from MD) versus no-intervention group. RESULTS: 33.1 % of patients had a preoperative ERCP and 69.4 % had EUS-FNA. Postoperative adverse events included: 30-day readmission (12.7 %), delayed gastric emptying (13.8 %), pancreatic fistula (10.3 %), abdominal abscess (5.7 %), cardiopulmonary adverse events (11.4 %), and mortality (1.4 %). The model was adjusted for potential confounders. There were no significant differences between the ERCP and no-ERCP groups for specific adverse events. Compared to no-EUS-FNA groups, groups of EUS-FNA with BD aspiration and EUS-FNA with MD aspiration from the main pancreatic duct directly or cyst/mass arising from MD did not show a significant increase in specific adverse events. CONCLUSIONS: Postoperative adverse events were not significantly increased among patients who had ERCP or EUS-FNA before surgical resection for MD- or MT-IPMNs. Endoscopic procedures directly sampling the MD can be safely pursued for diagnostic purposes in selected cases.

A Multi-Institutional Safety and Feasibility Study Exploring the Use of Hydrogel to Create Spatial Separation between the Pancreas and Duodenum in Patients with Pancreatic Cancer.

PURPOSE: The administration of dose-escalated radiation for pancreatic adenocarcinoma remains challenging because of the proximity of dose-limiting stomach and bowel, particularly the duodenum for pancreatic head tumors. We explore whether endoscopic injection of a temporary, absorbable hydrogel into the pancreatico-duodenal (PD) groove is safe and feasible for the purpose of increasing spatial separation between pancreatic head tumors and the duodenum. METHODS AND MATERIALS: Six patients with localized pancreatic adenocarcinoma underwent endoscopic injection of hydrogel into the PD groove. Safety was assessed based on the incidence of procedure-related adverse events resulting in a delay of radiation therapy initiation. Feasibility was defined as the ability to create spatial separation between the pancreas and duodenum, as assessed on simulation CT. RESULTS: All 6 patients were able to undergo endoscopic injection of hydrogel into the PD groove. No device-related events were experienced at any point in follow-up. Presence of hydrogel in the PD groove was apparent on simulation CT in all 6 patients. Mean space created by the hydrogel was 7.7 mm +/- 2.4 mm. In 3 patients who underwent Whipple resection, presence of hydrogel in the PD groove was pathologically confirmed with no evidence of damage to the duodenum. CONCLUSIONS: Endoscopic injection of hydrogel into the PD groove is safe and feasible. Characterization of the dosimetric benefit that this technique may offer in the setting of dose-escalated radiation should also be pursued, as should the ability of such dosimetric benefit to translate into clinically improved tumor control.

IPMN-LEARN: A linear support vector machine learning model for predicting low-grade intraductal papillary mucinous neoplasms.

Backgrounds/Aims: We aimed to build a machine learning tool to help predict low-grade intraductal papillary mucinous neoplasms (IPMNs) in order to avoid unnecessary surgical resection. IPMNs are precursors to pancreatic cancer. Surgical resection remains the only recognized treatment for IPMNs yet carries some risks of morbidity and potential mortality. Existing clinical guidelines are imperfect in distinguishing low-risk cysts from high-risk cysts that warrant resection. Methods: We built a linear support vector machine (SVM) learning model using a prospectively maintained surgical database of patients with resected IPMNs. Input variables included 18 demographic, clinical, and imaging characteristics. The outcome variable was the presence of low-grade or high-grade IPMN based on post-operative pathology results. Data were divided into a training/validation set and a testing set at a ratio of 4:1. Receiver operating characteristics analysis was used to assess classification performance. Results: A total of 575 patients with resected IPMNs were identified. Of them, 53.4% had low-grade disease on final pathology. After classifier training and testing, a linear SVM-based model (IPMN-LEARN) was applied on the validation set. It achieved an accuracy of 77.4%, with a positive predictive value of 83%, a specificity of 72%, and a sensitivity of 83% in predicting low-grade disease in patients with IPMN. The model predicted low-grade lesions with an area under the curve of 0.82. Conclusions: A linear SVM learning model can identify low-grade IPMNs with good sensitivity and specificity. It may be used as a complement to existing guidelines to identify patients who could avoid unnecessary surgical resection.

"Evolving Trends in Pancreatic Cystic Tumors: A 3-Decade Single-Center Experience With 1290 Resections".

OBJECTIVE: The aim of this study was to describe our institutional experience with resected cystic tumors of the pancreas with emphasis on changes in clinical presentation and accuracy of preoperative diagnosis. SUMMARY BACKGROUND DATA: Incidental discovery of pancreatic cystic lesions has increased and has led to a rise in pancreatic resections. It is important to analyze surgical outcomes from these procedures, and the prevalence of malignancy, pre-malignancy and resections for purely benign lesions, some of which may be unintended. METHODS: Retrospective review of a prospective database spanning 3 decades. Presence of symptoms, incidental discovery, diagnostic studies, type of surgery, postoperative outcomes, and concordance between presumptive diagnosis and final histopathology were recorded. RESULTS: A total of 1290 patients were identified, 62% female with mean age of 60 years. Fifty-seven percent of tumors were incidentally discovered. Ninety-day operative mortality was 0.9% and major morbidity 14.4%. There were 23 different diagnosis, but IPMN, MCN, and serous cystadenoma comprised 80% of cases. Concordance between preoperative and final histopathological diagnosis increased by decade from 45%, to 68%, and is presently 80%, rising in parallel with the use of endoscopic ultrasound, cytology, and molecular analysis. The addition of molecular analysis improved accuracy to 91%. Of misdiagnosed cases, half were purely benign and taken to surgery with the presumption of malignancy or premalignancy. The majority of these were serous cystadenomas. CONCLUSIONS: Indications and diagnostic work-up of cystic tumors of the pancreas have changed over time. Surgical resection can be performed with very low mortality and acceptable morbidity and diagnostic accuracy is presently 80%. About 10% of patients are still undergoing surgery for purely benign lesions that were presumed to be malignant or premalignant. Further refinements in diagnostic tests are required to improve accuracy.

Concordance of EUS and MRI/MRCP findings among high-risk individuals undergoing pancreatic cancer screening.

BACKGROUND/OBJECTIVES: Surveillance with endoscopic ultrasonography (EUS) and MRI/magnetic retrograde cholangiopancreatography (MRCP) is recommended for individuals at high risk for pancreatic cancer. We sought to characterize the findings of these surveillance exams and define the level of concordance between these two modalities. METHODS: 173 asymptomatic high-risk individuals (HRIs) meeting criteria for pancreatic cancer surveillance underwent EUS, MRI/MRCP, or both between 2008 and 2021. Clinical records were reviewed in all cases. RESULTS: HRIs underwent an average of 3.6 ± 3.2 surveillance exams over a period of 3.3 ± 3.5 years. Abnormalities including intraductal papillary mucinous neoplasms (IPMNs), solid lesions, and parenchymal irregularities were identified in 50.9% (n = 88). Four of these abnormalities (2.3%) had worrisome features, defined by cyst size, thickened/enhancing cyst walls, rapid growth rate, or change in main pancreatic duct diameter. All four worrisome lesions were seen on both MRI/MRCP and EUS. No pancreatic cancers were detected. Baseline EUS and MRI/MRCP exams were compared in 106 patients for concordance, and most (n = 66, 62.3%) were concordant. High levels of concordance were specifically observed for a dilated main pancreatic duct (p < 0.01) and cystic lesions >5 mm (p = 0.01). Among discordant cases, most (30/40; 75%) involved abnormal tissue heterogeneity seen primarily on EUS. None of these discordant lesions ultimately developed worrisome features. CONCLUSIONS: Worrisome pancreatic lesions were uncommon in our high-risk pancreatic cancer population and were detected by both EUS and MRI/MRCP. There was mild discordance with respect to less worrisome findings, but these discrepancies were not associated with any adverse clinical outcomes.

Multiinstitutional Validation Study of Cyst Fluid Protein Biomarkers in Patients With Cystic Lesions of the Pancreas.

OBJECTIVE: Prospective evaluation of 2 clinical-molecular models in patients with unknown pathology who underwent endoscopic ultrasound with fine-needle aspiration (EUS-FNA) for a cystic lesion of the pancreas. SUMMARY OF BACKGROUND DATA: Preoperative prediction of histologic subtype (mucinous vs nonmucinous) and grade of dysplasia in patients with pancreatic cystic neoplasms is challenging. Our group has previously published 2 clinical-molecular nomograms for intraductal papillary mucinous neoplasms (IPMN) that incorporated both clinical/radiographic features and cyst fluid protein markers (sFASL, CA72-4, MMP9, IL-4). METHODS: This multiinstitutional study enrolled patients who underwent EUS-FNA for a cystic lesion of the pancreas. Treatment recommendations regarding resection were based on standard clinical, radiographic, and endoscopic features. Predicted probabilities of high-risk IPMN (high-grade dysplasia/invasive cancer) were calculated using the previously developed clinical-molecular nomograms. RESULTS: Cyst fluid was obtained from 100 patients who underwent diagnostic EUS-FNA. Within this group there were 35 patients who underwent resection, and 65 were monitored radiographically. Within the group that underwent resection, 26 had low-risk IPMN or benign non-IPMN lesions, and 9 had high-risk IPMN. Within the surveillance group, no patient progressed to resection or developed cancer after a median follow-up of 12months (range: 0.5-38). Using the clinical/radiographic nomogram alone, 2 out of 9 patients with high-risk IPMN had a predicted probability >0.5. In the clinical-molecular models, 6 of 9 patients in model 1, and 6 of 9 in model 2, had scores >0.5. CONCLUSIONS: This prospective study of patients with unknown cyst pathology further demonstrates the importance of cyst fluid protein analysis in the preoperative identification of patients with high-risk IPMN. Longer follow-up is necessary to determine if this model will be useful in clinical practice.

Outcomes of EUS-guided transluminal gallbladder drainage in patients without cholecystitis.

BACKGROUND AND OBJECTIVES: Cholecystectomy is the gold standard for most gallbladder-related disease. However, many patients with gallbladder disease are poor surgical candidates. Current nonsurgical gallbladder drainage (GBD) methods include percutaneous cholecystostomy and endoscopic ultrasound-guided transluminal GBD (EUS-GBD). Outcomes for EUS-GBD for the treatment of noncholecystitis (NC) gallbladder disease have not been defined. MATERIALS AND METHODS: Cases were identified using procedural data from a quaternary academic hospital for endoscopic procedures from 2015 to 2020. Patients who underwent EUS-GBD for acute cholecystitis, biliary colic, gallstone pancreatitis, and secondary prevention of gallstone disease were included. RESULTS: Fifty-five cases of EUS-GBD were identified over the 5-year study period. Forty-one cases were performed for acute cholecystitis, and 15 were performed for other NC indications. Indications for NC drainage included primary treatment of symptomatic biliary colic and secondary prevention of gallstone pancreatitis and choledocholithiasis. There was no statistically significant difference in complications, mortality, or reintervention requirements. There was a 13.3% rate of immediate complications in the NC group, which were all medically managed. CONCLUSIONS: EUS-GBD appears to be a safe and effective way to manage gallstone disease in nonsurgical candidates with NC gallbladder-related disease. Overall complications and readmissions were infrequent. Complication rates were similar to those published in patients who underwent EUS-GBD for acute cholecystitis.

Pancreatic acinar cell carcinoma: A multi-center series on clinical characteristics and treatment outcomes.

BACKGROUND: Acinar cell carcinoma (ACC) is a very rare tumor of the exocrine pancreas, representing less than 1% of all pancreatic malignancies. The majority of data regarding ACC are limited to small case series. METHODS: This is a retrospective study conducted at a large healthcare system from 1996 to 2019. Patients with pathologically confirmed ACC were included, and demographic data, tumor characteristics, and treatment outcomes were abstracted by chart review. Survival curves were obtained by using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Sixty-six patients with ACC were identified. The median patient age at diagnosis was 64, and 42% presented with metastatic disease. The majority presented with abdominal pain or pancreatitis (69%), and laboratory parameters did not correlate with tumor size, metastatic disease, or survival. Several somatic abnormalities were noted in tumors (BRCA2, TP53, and mismatch-repair genes). In patients with localized disease that underwent resection, the median time to develop metastatic lesions was 13 months. The median overall survival (OS) was 24.7 months from diagnosis, with a survival difference based on metastatic disease at diagnosis (median 15 vs 38 mos). Surgery was associated with improved survival in non-metastatic cases (p = 0.006) but not metastatic cases (p = 0.22), and chemotherapy showed OS benefit in metastatic disease (p < 0.01). Patients with metastatic ACC treated after 2010 utilized more platinum-based agents, and there was a OS benefit to FOLFOX or FOLFIRINOX chemotherapy compared to gemcitabine or capecitabine-based regimens (p = 0.006). CONCLUSION: Pancreatic ACC patients often present with advanced disease. Surgery was associated with survival benefit among patients presenting with localized disease. The use of FOLFOX or FOLFIRINOX chemotherapy regimens was associated with improved OS in metastatic patients. These data add to our knowledge in this rare malignancy, and improves understanding about the genomic underpinnings, prognosis and treatment for acinar cancers.

Preoperative cholangitis is an independent risk factor for mortality in patients after pancreatoduodenectomy for pancreatic cancer.

OBJECTIVES: Preoperative biliary stenting is required for patients with obstructive jaundice from pancreatic adenocarcinoma who are receiving neoadjuvant chemotherapy. While in most patients this approach results in durable biliary drainage, some patients develop cholangitis during neoadjuvant treatment. Further, several studies have shown that preoperative cholangitis in patients with hepatobiliary malignancies can result in substantially unfavorable outcomes. The aim of this study was to evaluate the impact of preoperative cholangitis in patients who underwent pancreaticoduodenectomy after completing neoadjuvant chemotherapy. METHODS: Participants: all adult patients (n = 449) diagnosed with pancreatic adenocarcinoma from January 1st, 2013 to March 31st, 2018 who pursued treatment at the Massachusetts General Hospital were screened. Of these 449 patients, 97 met final inclusion criteria of receiving neoadjuvant chemotherapy with intent to pursue curative surgery. Data were collected via retrospective chart review including baseline characteristics, survival, episodes of preoperative cholangitis, and surgical complications. RESULTS: In patients completing successful pancreaticoduodenectomy surgery, preoperative cholangitis is associated with increased mortality (HR 2.67, 95% CI:1.16-6.13). This finding is independent of postoperative outcomes or tumor recurrence rate. The presence of cholangitis did not impact completion of neoadjuvant chemotherapy (92% vs 85%, p = 0.5) or ability to proceed to surgery (76% vs 75%, p = 1.0). Preoperative cholangitis was not associated with postoperative morbidity (42.1% vs 45.1%, p = 1.0). CONCLUSIONS: One episode of cholangitis during neoadjuvant chemotherapy is associated with increased mortality following successful pancreaticoduodenectomy, independent of immediate postoperative outcomes or tumor recurrence. Preoperative cholangitis does not affect ability to pursue neoadjuvant chemotherapy or complete successful surgery. Patients who develop cholangitis during the neoadjuvant chemotherapy treatment phase may reflect a distinct phenotype of patients with PDAC with a complex and more challenging clinical course.

Cytomorphologic characteristics of next-generation sequencing-positive bile duct brushing specimens.

INTRODUCTION: Cytology of bile duct brushings (BDBs) is a specific, but insensitive, test for malignancy. Next-generation sequencing (NGS) of BDBs has recently been shown to improve sensitivity. We analyzed the cytologic features of NGS-positive (NGS+) and NGS-negative (NGS-) BDBs and correlated the morphology with the presence of mutations. MATERIALS AND METHODS: A total of 96 BDBs were analyzed for 29 cytologic features by 2 pathologists who were unaware of the original diagnosis and NGS results. Clinicopathologic follow-up was used to determine the patient outcomes (ie, benign, low-grade neoplasm, malignant [carcinoma/high-grade dysplasia]). RESULTS: We analyzed 74 NGS+ BDBs from 66 patients and 22 NGS- BDBs from 22 patients. During follow-up, 58 of 66 NGS+ patients (88%) had malignancy compared with 0% of NGS- patients (P < 0.001). Fewer than 50% of the malignant cases had been interpreted as malignant on cytology; however, 100% had demonstrated mutations using NGS. Within the NGS+ cases, 53% showed late mutations (TP53, SMAD4, and CDKN2A) supportive of a high-risk stricture. Significant morphologic differences were seen in the background appearance, presence of single cells, architectural disarray, nucleomegaly, anisonucleosis, irregular nuclear borders, increased nuclear/cytoplasmic ratio, nuclear hyperchromasia, nucleoli, abnormal groups, clusters, and/or single cells, and overall impression. Naked nuclei, nucleomegaly, anisonucleosis, and coarse chromatin were more common in BDBs with late mutations than in those with KRAS/GNAS (Kirsten rat sarcoma viral oncogene homolog/guanine nucleotide binding protein, α-stimulating complex locus) mutations only. Cytology had a sensitivity of 16% and a specificity of 100% for malignancy. In contrast, NGS had a sensitivity of 100% and a specificity of 73%. Late mutations were 100% specific for malignancy compared with mutations in KRAS/GNAS only, of which 69% were malignant. CONCLUSIONS: We found significant overlap in the cytomorphologic features between neoplastic and non-neoplastic BDBs, and more than one half of cancer cases had been interpreted as "nonmalignant" on cytology. NGS showing late mutations was 100% specific for malignancy. Adding genetic testing to BDB cytology would be a valuable ancillary test for the detection of malignancy, and reflex testing should be considered.

Evaluating triage protocols for endoscopic ultrasound-guided fine needle biopsies of the pancreas.

INTRODUCTION: Pancreatic endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) acquires both direct smear and small core biopsy specimens. The triage protocols for pancreatic FNBs to cytopathology (CP) or gastrointestinal surgical pathology (GIP) are controversial and vary by institution. MATERIAL AND METHODS: Pancreatic EUS-FNBs obtained with the SharkCore FNB were reviewed from January 2014 to June 2019. The specimen characteristics and pathology data, including tissue triage, were obtained from the electronic medical records. We assessed the diagnostic yield, defined as malignant, specific neoplastic, or benign, and the operating characteristics at the time of rapid on-site evaluation (ROSE) and final diagnosis. RESULTS: We reviewed 324 pancreatic FNBs from 313 patients. Of the 324 FNBs, 260 (80%) obtained concurrent direct smear and core biopsy specimens, 30 (12%) of which were divided between CP and GIP. Of the 51 core-only specimens, 47 (92%) were reviewed by CP and 4 (8%) by GIP. ROSE improved the overall diagnostic yield by 10% and accuracy by 9%. When core specimens were reviewed independently, the diagnostic accuracy was 93% for CP (n = 248) and 100% for GIP (n = 33). All false-negative results of the CP-reviewed cores were due to sampling error. Concurrent smear review improved EUS-FNB performance, increasing the negative predictive value by 10% and accuracy by 3% compared with core review alone. CONCLUSIONS: CP and GIP can accurately interpret pancreatic EUS-FNB specimens. However, triage of concurrent EUS-FNB-acquired smear and core specimens to CP may be most efficient as CPs are trained to assess adequacy at the time of ROSE, as well as interpret all parts of the biopsy, minimizing the risk of discordant pathology reports.

Rising Prevalence of Opioid Use Disorder and Predictors for Opioid Use Disorder Among Hospitalized Patients With Chronic Pancreatitis.

OBJECTIVES: We aimed to evaluate the prevalence, impact, and predictors of opioid use disorder (OUD) in hospitalized chronic pancreatitis (CP) patients. METHODS: A retrospective cohort study was performed using the National Inpatient Sample database from 2005 to 2014. Patients with a primary diagnosis of CP and OUD were included. The primary outcome was evaluating the prevalence and trend of OUD in patients hospitalized with CP. Secondary outcomes were to (1) assess the impact of OUD on health care resource utilization and (2) identify predictors of OUD in hospitalized CP patients. RESULTS: A total of 176,857 CP patients were included, and OUD was present in 3.8% of patients. The prevalence of OUD in CP doubled between 2005 and 2014. Patients with CP who had OUD were found to have higher mean length of stay (adjusted mean difference, 1.2 days; P < 0.001) and hospitalization costs (adjusted mean difference, US $1936; P < 0.001). Independent predictors of OUD in CP patients were obesity, presence of depression, and increased severity of illness. CONCLUSIONS: Opioid use disorder-related diagnoses are increasing among CP patients and are associated with increased health care resource utilization. Our study identifies patients at high-risk for OUD whose pain should be carefully managed.

Diagnostic yield of the SharkCore EUS-guided fine-needle biopsy.

INTRODUCTION: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the standard diagnostic procedure for many intrathoracic and intra-abdominal lesions. Next-generation fine-needle biopsies (FNBs) can increase diagnostic yield by procuring tissue suitable for histological processing. We evaluate the diagnostic yield and operating characteristics of the SharkCore (SC; Medtronic Corp., Minneapolis, MN) FNB in a tertiary referral facility. MATERIALS AND METHODS: We performed a single-center retrospective review of SC-FNB-acquired tissue between January 2014 and March 2018. Patient demographic data, endoscopic features, and pathology data were obtained from the electronic medical record. Diagnostic yield was assessed by the ability to obtain a definitive diagnosis, defined as malignant or benign interpretations. Operating characteristics were also calculated. RESULTS: A total of 179 lesions were sampled with the SC-FNB in 157 patients (mean age: 63 years, 57% male). Of these, 31 lesions were concomitantly sampled with a conventional FNA needle. Most lesions were pancreatic (49%). Diagnostic yield was 86%, which was independent of lesion location, lesion size and needle gauge. Diagnostic accuracy was highest when both histology and cytology specimens were analyzed concurrently (96.5%). In patients with a history of chronic pancreatitis, accuracy, sensitivity, and negative predictive value were reduced (71.4%, 20.0%, and 69.2%, respectively). Rapid onsite evaluation (ROSE) occurred in 64.8% of cases and was more likely to be diagnostic at the time of rapid evaluation if SC-acquired tissue was utilized versus FNA-acquired tissue (P = 0.03); however, final diagnostic yield did not differ between needles (P = 0.13). CONCLUSIONS: SC-FNB shows high diagnostic yield and accuracy and provides diagnostic tissue for ROSE. SC-FNB is an effective alternative to conventional FNA.

Feasibility and safety of microforceps biopsy in the diagnosis of pancreatic cysts.

BACKGROUND AND AIMS: The tissue acquisition and diagnostic yield of cyst fluid cytology is low-to-moderate and rarely provides a specific diagnosis. The aim of this study was to compare the tissue acquisition and diagnostic tissue yield of microforceps biopsy (MFB) with cyst fluid cytology. METHODS: In this multicenter study, data of 42 patients who had cysts both aspirated by EUS-guided FNA (EUS-FNA) and biopsy specimens were then obtained with an MFB device, were collected. Cytology analysis of cyst fluid and histologic analysis of biopsy specimens were done. Acquisition yield was defined as percentage of patients with tissue present in the aspirate or biopsy. Diagnostic tissue yield was evaluated at 3 levels: the ability of differentiation between mucinous and/or nonmucinous cysts, detection of high risk for malignancy, and specific cyst type diagnosis. RESULTS: The mean patient age was 69 years. Sixteen pancreatic cysts (38.1%) were located in the head, 17 (40.5%) in the body, and 9 (21.4%) in the tail. The mean cyst size was 28.2 mm (12-60 mm); 25 of 42 (60%) were septated. The EUS-FNA tissue (fluid) acquisition yield was 88.1% (37/42). The MFB tissue acquisition yield was 90.4% (38/42). The diagnostic cytology yield to differentiate between mucinous and/or nonmucinous cysts was 47.6% (20/42), and the MFB histologic yield to differentiate between mucinous and/or nonmucinous cysts was 61.9% (26/42) (P = .188). The percentage of cysts at high risk for malignancy by cytology was 54.7% (23/42), and MFB was 71.5% (30/42) (P = .113). However, the ability of MFB to provide a specific cyst type diagnosis was 35.7% (15/42), and that for cytology was 4.8% (2/42) (P = .001). Surgical histology was concordant with that of MFB in 6 of 7 patients (85%), and with that of cytology in 1 of 7 patients (15%). CONCLUSION: The cyst tissue acquisition yield for MFBs was 90%. Although cytology of cyst fluid and MFB were comparable in distinguishing mucinous and nonmucinous cysts and detecting cysts at high risk for malignancy, MFB was far superior to cytology for providing a specific cyst diagnosis.

A proficiency-based virtual reality endoscopy curriculum improves performance on the fundamentals of endoscopic surgery examination.

INTRODUCTION: The fundamentals of endoscopic surgery (FES) examination is a national test of knowledge and skill in flexible gastrointestinal endoscopy. The skill portion of the examination involves five tasks that assesses the following skills: scope navigation, loop reduction, mucosal inspection, retroflexion, and targeting. This project aimed to assess the efficacy of a proficiency-based virtual reality (VR) curriculum in preparing residents for the FES skills exam. METHODS: Experienced (>100 career colonoscopies) and inexperienced endoscopists (<50 career colonoscopies) were recruited to participate. Six VR modules were identified as reflecting the skills tested in the exam. All participants were asked to perform each of the selected modules twice, and median performance was compared between the two groups. Inexperienced endoscopists were subsequently randomized in matched pairs into a repetition (10 repetitions of each task) or proficiency curriculum. After completion of the respective curriculum, FES scores and pass rates were compared to national data and historical institutional control data (endoscopy-rotation training alone). RESULTS: Five experienced endoscopists and twenty-three inexperienced endoscopists participated. Construct valid metrics were identified for six modules and proficiency benchmarks were set at the median performance of experienced endoscopists. FES scores of inexperienced endoscopists in the proficiency group had significantly higher FES scores (530 ± 86) versus historical control (386.7 ± 92.2, p = 0.0003) and higher pass rate (proficiency: 100%, historical control 61.5%, p = 0.01). CONCLUSION: Trainee engagement in a VR curriculum yields superior FES performance compared to an endoscopy rotation alone. Compared to the 2012-2016 national resident pass rate of 80, 100% of trainees in a proficiency-based curriculum passed the FES manual skills examination.

Value of adding GNAS testing to pancreatic cyst fluid KRAS and carcinoembryonic antigen analysis for the diagnosis of intraductal papillary mucinous neoplasms.

BACKGROUND AND AIM: Molecular analysis of pancreatic cyst fluid (PCF) has been proposed as a novel method for differentiating pancreatic cystic lesions (PCL). The present study aimed to investigate the value of GNAS testing when added to KRAS and carcinoembryonic antigen (CEA) testing of PCF for the diagnosis of intraductal papillary mucinous neoplasms (IPMN). METHODS: Prospectively collected endoscopic ultrasonography fine-needle aspiration (EUS-FNA) data were analyzed retrospectively for GNAS and KRAS mutations and CEA results. IPMN were histologically confirmed or supported by imaging and EUS-FNA findings (KRAS, CEA, cytology). Performance characteristics of GNAS added to KRAS and CEA for the diagnosis of IPMN were calculated. RESULTS: The study population consisted of 197 patients with cyst fluid test results. Cysts were histologically classified in 33 patients and by clinical criteria in 164 patients. The IPMN group included 108 patients and the non-IPMN group included 89 patients. GNAS was positive in 51 patients (47.2%) with IPMN. Forty-two of these patients (82.3%) also had a KRAS mutation. Adding GNAS to KRAS increased the diagnostic accuracy from 76.6% to 79.1% (P > 0.05). Adding GNAS to CEA increased the diagnostic accuracy from 66.4% to 80.7 % (P < 0.05), but did not achieve a diagnostic superiority to KRAS testing alone (80.7% vs 76.6%, P > 0.05). The diagnostic accuracy of the triple combination was significantly better than all single tests (P < 0.05). CONCLUSION: GNAS mutation is a highly specific test for IPMN. When GNAS testing is added to CEA and KRAS, a significantly greater overall accuracy (86.2%) is achieved.