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Impact of comprehensive family history and genetic analysis in the multidisciplinary pancreatic tumor clinic setting

Everett, Jessica N; Dettwyler, Shenin A; Jing, Xiaohong; Stender, Cody; Schmitter, Madeleine; Baptiste, Ariele; Chun, Jennifer; Kawaler, Emily A; Khanna, Lauren G; Gross, Seth A; Gonda, Tamas A; Beri, Nina; Oberstein, Paul E; Simeone, Diane M
BACKGROUND:Genetic testing is recommended for all pancreatic ductal adenocarcinoma (PDAC) patients. Prior research demonstrates that multidisciplinary pancreatic cancer clinics (MDPCs) improve treatment- and survival-related outcomes for PDAC patients. However, limited information exists regarding the utility of integrated genetics in the MDPC setting. We hypothesized that incorporating genetics in an MDPC serving both PDAC patients and high-risk individuals (HRI) could: (1) improve compliance with guideline-based genetic testing for PDAC patients, and (2) optimize HRI identification and PDAC surveillance participation to improve early detection and survival. METHODS:Demographics, genetic testing results, and pedigrees were reviewed for PDAC patients and HRI at one institution over 45 months. Genetic testing analyzed 16 PDAC-associated genes at minimum. RESULTS:Overall, 969 MDPC subjects were evaluated during the study period; another 56 PDAC patients were seen outside the MDPC. Among 425 MDPC PDAC patients, 333 (78.4%) completed genetic testing; 29 (8.7%) carried a PDAC-related pathogenic germline variant (PGV). Additionally, 32 (9.6%) met familial pancreatic cancer (FPC) criteria. These PDAC patients had 191 relatives eligible for surveillance or genetic testing. Only 2/56 (3.6%) non-MDPC PDAC patients completed genetic testing (p < 0.01). Among 544 HRI, 253 (46.5%) had a known PGV or a designation of FPC, and were eligible for surveillance at baseline; of the remainder, 15/291 (5.2%) were eligible following genetic testing and PGV identification. CONCLUSION/CONCLUSIONS:Integrating genetics into the multidisciplinary setting significantly improved genetic testing compliance by reducing logistical barriers for PDAC patients, and clarified cancer risks for their relatives while conserving clinical resources. Overall, we identified 206 individuals newly eligible for surveillance or genetic testing (191 relatives of MDPC PDAC patients, and 15 HRI from this cohort), enabling continuity of care for PDAC patients and at-risk relatives in one clinic.
PMID: 35906821
ISSN: 2045-7634
CID: 5277102

Post-transplant biliary complications: advances in pathophysiology, diagnosis, and treatment

Fasullo, Matthew; Patel, Milan; Khanna, Lauren; Shah, Tilak
Liver transplantation (LT) is the only curative therapy in patients with end-stage liver disease. Long-term survival is excellent, yet LT recipients are at risk of significant complications. Biliary complications are an important source of morbidity after LT, with an estimated incidence of 5%-32%. Post-LT biliary complications include strictures (anastomotic and non-anastomotic), bile leaks, stones, and sphincter of Oddi dysfunction. Prompt recognition and management is critical as these complications are associated with mortality rates up to 20% and retransplantation rates up to 13%. This review aims to summarise our current understanding of risk factors, natural history, diagnostic testing, and treatment options for post-transplant biliary complications.
PMID: 35552193
ISSN: 2054-4774
CID: 5214812

Standardization of EUS imaging and reporting in high-risk individuals of pancreatic adenocarcinoma: consensus statement of the Pancreatic Cancer Early Detection Consortium (PRECEDE)

Gonda, Tamas A; Farrell, James; Wallace, Michael; Khanna, Lauren; Janec, Eileen; Kwon, Richard; Saunders, Michael; Siddiqui, Uzma; Brand, Randall; Simeone, Diane
BACKGROUND AND AIMS/OBJECTIVE:Pancreatic ductal adenocarcinoma is an aggressive disease most often diagnosed after local progression or metastatic dissemination, precluding resection and resulting in a high mortality rate. For individuals with elevated personal risk of the development of pancreatic cancer, EUS is a frequently used advanced imaging and diagnostic modality. However, there is variability in the expertise and definition of EUS findings among gastroenterologists, as well as lack of standardized reporting of relevant findings at the time of examination. Adoption of standardized EUS reporting, using a universally accepted and agreed upon terminology, is needed. METHODS:A consensus statement designed to create a standardized reporting template was authored by a multidisciplinary group of experts in pancreatic diseases that includes gastroenterologists, radiologists, surgeons, oncologists, and geneticists. This statement was developed using a modified Delphi process as part of the Pancreatic Cancer Early Detection Consortium (PRECEDE) and >75% agreement was required to reach consensus. RESULTS:We identified reporting elements and present standardized reporting templates for EUS indications, procedural data, EUS image capture, and descriptors of findings, tissue sampling, and for postprocedural assessment of adequacy. CONCLUSIONS:Adoption of this standardized EUS reporting template should improve consistency in clinical decision making for individuals with elevated risk of pancreatic cancer by providing complete and accurate reporting of pancreatic abnormalities. Standardization will also help to facilitate research and clinical trial design by using clearly defined and consistent imaging descriptions, thus allowing for comparison of results across different centers.
PMID: 34736932
ISSN: 1097-6779
CID: 5038412

Management of pancreatic fluid collections

Bhakta, Dimpal; de Latour, Rabia; Khanna, Lauren
Pancreatic fluid collections often develop as a complication of acute pancreatitis but can be seen in a variety of conditions including chronic pancreatitis, trauma, malignancy or post-operatively. It is important to classify a pancreatic fluid collection in order to optimize treatment strategies and management. Most interventions are targeted towards the management of delayed complications of pancreatitis, including pancreatic pseudocysts and walled-off necrosis (WON), which often develop days to weeks after the initial episode of pancreatitis. Surgical, percutaneous, and endoscopic interventions are all possible methods for treatment of pancreatic fluid collections, however endoscopic drainage with endoscopic ultrasound has become first-line. Advances within endoscopic drainage strategies have also led to innovative changes in the specific stents used for treatment, with possible options including double pigtail plastic stents, fully covered self-expanding metal stents and lumen-apposing metal stents (LAMS).
PMID: 35548474
ISSN: 2415-1289
CID: 5214572

Social determinants of weight loss following transoral outlet reduction (TORE) at a safety-net hospital [Meeting Abstract]

Dornblaser, D W; Laljee, S; Khanna, L; Goodman, A; Tzimas, D; De, Latour R
Introduction: Roux-En-Y gastric bypass (RYGB) is a bariatric surgery for weight loss (WL) among obese patients. Weight regain (WR) is a common complication of RYGB. One anatomic etiology of WR after RYGB is dilation of the gastrojejunal (GJ) anastomosis outlet. Transoral Outlet Reduction (TORe) is an endoscopic therapy using a full thickness endoscopic suturing device to narrow the GJ outlet. Given the novelty of bariatric endoscopy, most insurance does not cover the cost. There is little data on outcomes of bariatric endoscopy in underserved populations. Our study aimed to assess the impact of socioeconomic and demographic factors on WL after TORe at our safety net hospital.
Method(s): We performed a retrospective chart review of patients who underwent TORe for post- RYGB WR from November 2016 to September 2020. Data collected included age, gender, ethnicity, highest education level, income, marital status, insurance status, number of children and procedural outcomes (weight, metabolic parameters). We performed a multivariable linear regression analysis using R
ISSN: 1572-0241
CID: 5084232

Cancer surveillance awareness and practice among families at increased risk for pancreatic adenocarcinoma

Everett, Jessica N; Burgos, Gabriela; Chun, Jennifer; Baptiste, Ariele; Khanna, Lauren G; Oberstein, Paul E; Simeone, Diane M
BACKGROUND:Early detection of pancreatic ductal adenocarcinoma (PDAC) is an important goal for improving survival. Individuals who meet published guidelines for surveillance may be underidentified, and family communication about risk represents a pathway to increasing participation in surveillance. We investigated the uptake of and barriers to surveillance in at-risk relatives of clinic patients. METHODS:We conducted a retrospective record review of patients with personal or family history of PDAC evaluated over 12 months. The first relative presenting to clinic (proband) reported surveillance status and reasons for nonparticipation for at-risk relatives. Descriptive analyses and Fisher's exact tests were conducted to evaluate differences in surveillance participation. RESULTS:Among 193 at-risk relatives, 21% were in surveillance. The primary reasons for nonparticipation were lack of awareness (36%) and lack of interest (24%). Neither the sex nor the cancer status of probands impacted surveillance. At-risk relatives with familial pancreatic cancer (FPC) who also carried relevant pathogenic germline variants (PGVs) were more likely to undergo surveillance than those with FPC or PGVs alone (P = .003). Among families with PGVs, 59% of relatives potentially eligible for surveillance had not completed genetic testing. CONCLUSION/CONCLUSIONS:PDAC surveillance is underutilized in high-risk families. Communication interventions to address informational needs and decisional support could improve outcomes.
PMID: 33721345
ISSN: 1097-0142
CID: 4823462

Donning a new approach to the practice of gastroenterology: perspectives from the COVID-19 pandemic epicenter

Sethi, Amrita; Swaminath, Arun; Latorre, Melissa; Behin, Daniel S; Jodorkovsky, Daniela; Calo, Delia; Aroniadis, Olga; Mone, Anjali; Mendelsohn, Robin B; Sharaiha, Reem Z; Gonda, Tamas A; Khanna, Lauren G; Bucobo, Juan Carlos; Nagula, Satish; Ho, Sammy; Carr-Locke, David L; Robbins, David H
The COVID-19 pandemic is seemingly peaking now in New York City and has triggered significant changes to the standard management of gastrointestinal diseases. Priorities such as minimizing viral transmission, preserving (personal protective equipment) PPE, and freeing hospital beds have driven unconventional approaches to managing GI patients. Conversion of endoscopy units to COVID units and redeployment of gastroenterology (GI) fellows and faculty has profoundly changed the profile of most GI services. Meanwhile, consult and procedural volumes have been drastically reduced. In this review we share our collective experiences, how we have changed our practice of medicine, in response to the COVID surge. While we will review our management of specific consults and conditions, the overarching theme focuses primarily on non-invasive measures and maximizing medical therapies. Endoscopic procedures have been reserved for those timely interventions that are most likely to be therapeutic. The role of multidisciplinary discussion, while always important, has now become critical. And the support of our faculty and trainees remains essential. Local leadership can encourage well-being by frequent team check-ins and foster trainee development through remote learning. Advancing a clear vision and a transparent process for how to organize and triage care in the recovery phase will allow for a smooth transition to our "new normal."
PMID: 32330565
ISSN: 1542-7714
CID: 4397502


Bhakta, D; De, Latour R; Haber, G B; Gross, S A; Janec, E; Saraceni, M; Khanna, L
Introduction: Pancreatic cystic lesions (PCL) are increasingly identified on cross-sectional imaging. Types include intraductal papillary mucinous neoplasms (IPMN), mucinous cystic neoplasms (MCN), serous cystadenoma (SCA), solid pseudopapillary tumors (SPT) and pseudocysts. Given the risk of malignancy associated with MCN and IPMN with high risk features, accurate PCL diagnosis is essential. Endoscopic ultrasound (EUS) with fine needle aspiration (FNA) of cyst fluid for cytology remains important for the classification of PCL, but is limited by the ability to obtain a sufficient sample and cellularity of fluid. The specificity for malignant cytology is 94%, but sensitivity remains low at 51%. Recently, introduction of a novel microforceps biopsy (MFB) device (Moray Micro Forceps, US Endoscopy, Mentor, OH) has enabled EUS-guided through-the-needle biopsies of PCL through a 19-gauge needle. The aim of this study is to compare the technical success and diagnostic yield for PCL using MFB versus cyst fluid studies alone, along with identifying adverse events associated with MFB.
Method(s): We conducted a retrospective chart review of adult patients with PCL diagnosed by cross sectional imaging undergoing EUS-guided FNA with MFB at 2 tertiary academic centers from November 2016 to November 2019. FNA of PCL was performed and cyst fluid was sent for cytology, carcinoembryonic antigen (CEA) levels, and mutational analysis. Cyst biopsy was performed using MFB.
Result(s): 14 patients were included. 71% were female. Median age was 60 years. Location of cysts in pancreas were head (4), body (6), and tail (4). MFB was technically successful in 12 of 14 cases (yield 86%) including 1 case where no cyst fluid was able to be obtained. There were no reported adverse outcomes (bleeding, pancreatitis, perforation, infection, abdominal pain). MFB diagnosed IPMN in 2 patients, neither of which were identified by cytology but were identified by fluid mutational analysis; MCN in 2 patients, 1 of which was identified by cytology; and SCA in 1 patient where cytology was concerning for a mucinous lesion. Both MFB and cytology were concerning for pseudocyst in 1 patient who ultimately was found to have MCN.
Discussion(s): The technical success of MFB is high and is associated with increased overall diagnostic yield without significant adverse events. For distinguishing PCL types, MFB provided additive diagnostic information to fluid cytology in 4 of 14 patients in our study. Including mutational analysis which identified IPMN in 2 patients where cytology was negative, MFB still provided further diagnostic information in 2 additional patients. This study suggests that the addition of MFB to EUS-guided sampling for cytology, CEA and mutational analysis further augments PCL diagnosis. Future studies should elucidate the role of MFB in combination with mutational analysis. [Formula presented]
ISSN: 0016-5107
CID: 4469932


David, Y N; Kakked, G; Dixon, R E; Nieto, J; Deshmukh, A A; Krafft, M R; Shah-Khan, S M; Nasr, J Y; Trindade, A J; Hoerter, N A; Khanna, L; Tzimas, D; Kedia, P; Kumbhari, V; Itani, M I; Farha, J; Chapman, C G; Kasmin, F; Gress, F G; Nagula, S; Greenwald, D A; DiMaio, C J; Waye, J D; Kumta, N A
Background: Endoscopic Ultrasound guided biliary drainage (EUS-BD) has been demonstrated as a safe and effective alternative to Endoscopic Retrograde Cholangiopancreatography (ERCP) in malignant biliary obstruction. Various plastic and metal stents have previously been used for drainage, with recently increasing use of lumen apposing metal stents (LAMS). However there is limited data to guide patient selection, choice of stent, or method of placement. This study examines the rates of technical success, clinical success, and adverse events associated with the use of LAMS for EUS-BD.
Method(s): A retrospective study was conducted at 10 institutions. It included all cases of biliary obstruction that EUS-BD was performed using a LAMS. Collected data points were clinical and technical factors, adverse events and mortality. Main outcomes were technical success (defined as successful LAMS placement), clinical success (50% decline in bilirubin at 2 weeks), recurrence of biliary obstruction, and adverse events.
Result(s): 72 patients were included with median follow up of 56 days. Descriptive data is in Table 1 and Table 2. Most obstructions (89%) were at the distal common bile duct and the main etiology was pancreatic cancer (82%). Mean pre-procedure bilirubin was 19.2 mg/dl and common bile duct size was 22.7 mm. ERCP was attempted initially in 47% of patients. In patients where technical success (97%) was achieved, 100% clinical resolution was noted. Median time to clinical success was 1 day. Biliary obstruction recurred in 6% of cases, though no predicting factors were identified. A total of 9 (12.5%) (6 mild, 1 moderate, 2 severe) non-LAMS related adverse events were reported. There were 11 (15%) LAMS associated adverse events (6 food impaction, 4 bleeding, 1 migration). Elective LAMS removal without fistula closure was performed in 3 cases and was not associated with recurrent biliary obstruction or adverse events. 17% of patients died during follow up but no deaths were attributed to the procedure.
Conclusion(s): EUS-BD with LAMS is effective in relieving malignant biliary obstruction with low rates of recurrence. There was high technical success with this procedure and this resulted in clinical resolution in all successful cases. No other clinical or technical factors were associated with initial technical or clinical success, recurrent biliary obstruction or adverse events. Further prospective studies are needed to validate these findings and generate longer term data. [Formula presented] [Formula presented]
ISSN: 1097-6779
CID: 4472122


Beauvais, J C; O'Donnell, M; Matta, B; Saraceni, M; Bedi, G; Skinner, M J; Tzimas, D; Shah, P C; Serouya, S; Goodman, A J; Janec, E; De, Latour R; Vareedayah, A A; Yuen, W; Sofia, Yuen P Y; Khanna, L; Haber, G B
Background: Lumen-apposing self-expandable metal stents (LAMS) have transformed the management of pancreatic fluid collections over the last two decades. There has since been significant interest in expanding the utility of LAMS for additional therapies such as the management of benign luminal strictures. However, there remains little data on their efficacy and safety when used for this indication. The goal of this study was to define the technical success, clinical success, and complication rates of LAMS when used in the management of benign strictures Methods: This was a retrospective multicenter evaluation of the safety, efficacy, and long-term clinical durability of LAMS in the treatment of benign strictures. The study took place between June 2018 and November 2019. Data collection included demographic information, indication, stent size, use of concurrent balloon dilation including dilation diameter, stent stabilization technique, intra-procedure and post-procedure complications, clinical improvement, and post-procedure follow up outcomes.
Result(s): 30 patients underwent placement of LAMS for a benign luminal stricture, with one having two stents placed during the index procedure at separate areas of stenoses resulting in a total of 31 stents placed. In total, 19 stents were 15 x 10 mm and 12 stents were 20 x 10 mm. No intra-procedural complications were noted. The technical success of deployment was 100%. Clinical resolution of symptoms was present in 25 (83%) patients. Of the patients who experienced clinical improvement, 17 underwent stent removal after an average of 6.4 weeks, and clinical recurrence occurred in 7 (41%) patients. The mean time to recurrence of symptoms after stent removal was 7 weeks. Univariate subgroup analysis revealed 15 x 10 mm stents were associated with clinical improvement (OR 12.86, 95% CI: 1.27-130.57, p 0.031). Each patient who did not clinically improve developed pain (3) or stent migration (2). In total 11 (37%) patients developed minor post-procedure adverse event. Stent migration was seen in 5 (17%) cases. Bleeding and pain were noted in 1 (3%) and 7 (23%) patients, respectively. Ulceration was found in 4 patients.
Conclusion(s): LAMS is a durable, safe option for patients with benign luminal strictures. Overall technical success was 100% and clinical success was 83%. The data also suggests better clinical outcomes with 15 x 10 mm stents, when compared to 20 x 10 mm stents. Pain is the most common adverse event but easily managed. [Formula presented]
ISSN: 1097-6779
CID: 4472152