Minor Papilla Research Articles

Dorsal pancreatic agenesis: a case report.

Herein, we present a case of a 50-year-old woman who presented to general outpatient department with a complaint of abdominal pain. The patient was diagnosed with cholelithiasis with a contrast-enhanced computed tomography finding of dorsal pancreatic agenesis on a detailed workup. However, the patient did not have any other associated anomalies or symptoms associated with dorsal pancreatic agenesis. The patient was managed for cholelithiasis with laparoscopic cholecystectomy. Failure in development due to aberrant embryogenesis may cause partial or complete agenesis of the dorsal pancreas. The minor papilla, the accessory pancreatic duct, the body, and the tail of the pancreas are not present in the case of complete dorsal agenesis. Most cases of dorsal pancreatic agenesis are asymptomatic and diagnosed incidentally, whereas some of the cases may present with other associated abnormalities. It is almost always diagnosed via imaging modalities. Dorsal pancreatic agenesis is a very rare congenital anomaly of the pancreas. It can be diagnosed via various imaging modalities and almost always remains a radiological diagnosis with incidental findings.

Precut papillotomy on a minor papilla followed by balloon papilloplasty to provide a complete pancreatic-duct drainage in tropical pancreatitis with reverse pancreas divisum.

Video 1Demonstration of the precut on minor papilla and papilloplasty with pancreatoscopy.

Neuroendocrine carcinoma of the minor papilla with pancreas divisum: a case report and review of the literature

BackgroundNeuroendocrine tumors of the minor papilla are very rare, and only 20 cases have been reported in the literature. Neuroendocrine carcinoma of the minor papilla with pancreas divisum has not been reported previously, making this the first reported case. Neuroendocrine tumors of the minor papilla have been reported in association with pancreas divisum in about 50% of cases reported in the literature. We herein present our case of neuroendocrine carcinoma of the minor papilla with pancreas divisum in a 75-year-old male with a systematic literature review of the previous 20 reports of neuroendocrine tumors of the minor papilla.Case presentationA 75-year-old Asian man was referred to our hospital for evaluation of dilation of the main pancreatic duct noted on abdominal ultrasonography. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography showed a dilated dorsal pancreatic duct, which was not connected to the ventral pancreatic duct; however, it opened to the minor papilla, indicating pancreas divisum. The common bile duct had no communication with the pancreatic main duct and opened to the ampulla of Vater. A contrast-enhanced computed tomography scan showed a 12-mm hypervascular mass near the ampulla of Vater. Endoscopic ultrasonography showed a defined hypoechoic mass in the minor papilla with no invasion. The biopsies performed at the previous hospital found adenocarcinoma. The patient underwent a subtotal stomach-preserving pancreaticoduodenectomy. The pathological diagnosis was neuroendocrine carcinoma. At the 15-year follow-up visit, the patient was doing well with no evidence of tumor recurrence.ConclusionIn our case, because the tumor was discovered during a medical check-up relatively early in the course of disease, the patient was doing well at the 15-year follow-up visit, with no evidence of tumor recurrence. Diagnosing a tumor of the minor papilla is very difficult because of the relatively small size and submucosal location. Carcinoids and endocrine cell micronests in the minor papilla occur more frequently than generally thought. It is very important to include neuroendocrine tumors of the minor papilla in the differential diagnosis of patients with recurrent pancreatitis or pancreatitis of unknown cause, especially for patients with pancreas divisum.

Rendezvous-assisted endoscopic retrograde pancreatography in a patient with annular pancreas and coexisting pancreas divisum.

An 18-year-old female was hospitalized for chronic pancreatitis of unknown origin. No history of alcohol abuse and hereditary diseases were found. Enhanced computed tomography (CT) and magnetic resonance cholangiography revealed dilated pancreatic duct system and abnormal pancreatic tissue incompletely wrapping around the second portion of the duodenum ([Fig. 1], [Fig. 2]). Endoscopic retrograde pancreatography (ERP) with intended minor papilla cannulation was attempted and yet failed due to the polypoid nodular papilla ([Fig. 3]).

A rare case of pancreatic acinar cell carcinoma presenting a submucosal tumor.

A 66-year-old man, who underwent distal gastrectomy with Billroth I reconstruction for gastric cancer, regularly underwent upper endoscopy as a routine examination. Unlike 1 year earlier [Figure 1a], a submucosal tumor-like lesion was identified near the minor papilla [Figure 1b], but the opening of the minor papilla could not be confirmed. Computed tomography revealed a mass (26 mm × 10 mm) protruding from the duodenal wall into the duodenal lumen [Figure 2] without pancreatic duct dilation. EUS using a linear array echoendoscope showed that the hypoechoic and smooth-marginal mass adjacent to the pancreatic head [Figure 3a] and the accessory pancreatic duct could not be recognized. EUS using a miniature probe showed that the mass was mainly located in the muscularis propria of the duodenal wall [Figure 3b]. The initial diagnosis was a duodenal gastrointestinal stromal tumor; however, EUS-guided fine-needle biopsy of the mass revealed suspicious pancreatic acinar cell carcinoma (PACC). A pancreaticoduodenectomy was performed. Macroscopically, a gray-white mass with a 25-mm maximum diameter was found in the duodenal submucosa on the cut surface [Figure 4a]. The boundary between the mass and the pancreatic parenchyma was unclear. Predominant growth of the tumor was observed within the accessory pancreatic duct by loupe image [Figure 4b]. No invasive growth or cystic formation was found. The tumor cells having irregular, hyperchromatic nuclei and eosinophilic cytoplasm proliferated mainly in an acinar or tubular pattern [Figure 4c]. The neoplastic cells were diffusely positive for anti-trypsin [Figure 4d] and bcl-10, whereas they were negative for a neuroendocrine marker, chromogranin or synaptophysin. Finally, the pathological diagnosis was a PACC at stage TisN0M0.Figure 1: (a) Endoscopic image showing no abnormality of the duodenal wall and minor papilla 1 year ago. (b) Endoscopic image showing a submucosal tumor-like lesion near the original minor papillaFigure 2: Contrast-enhanced computed tomography showing a mass (arrow) protruding from the duodenal wall into the duodenal lumen located in contact with the pancreatic headFigure 3: (a) EUS using a linear array echoendoscope showing a hypoechoic and smooth-marginated mass outside the pancreatic head. (b) EUS using a miniature probe showing the mass mainly located in the muscularis propria of the duodenal wallFigure 4: (a) Gross examination of resected specimen revealed a gray-white, solid lesion mainly occupying the duodenal submucosa on the cut surface. (b) A tumor with intraductal growth was observed by loupe image of histologic specimen (H and E). Normal pancreatic parenchyma (arrow). (c) Tumor cells having irregular, hyperchromatic nuclei and eosinophilic cytoplasm proliferated resembling acini of the pancreas (H and E, × 200). (d) Immunohistochemically, the neoplastic cells were positive for anti-trypsin (×40)PACC is a rare pancreatic tumor,[1] which is typically a solid tumor with expansive growth.[2] A PACC that predominantly grows within the main pancreatic ducts is extremely rare.[3] There has not been any reported case of PACC growing in the accessory pancreatic duct and presenting a submucosal tumor. In this case, there are some hypotheses regarding the specific tumor appearance: PACC originating from (1) pancreatic parenchyma near the accessory pancreatic duct and (2) ectopic pancreas[4] or submucosal pancreatic parenchyma.[5] However, it is a limitation that it was difficult to prove the hypotheses. Authors’ contributions R.S. treated the patient and wrote the manuscript; H.K., H.N., S.H., T.M., K.S., T.Y., H.A., M.K., M.F., T.M., M.F., K.O., E.T., T.U., A.T., and A.I. treated the patient and contributed writing the manuscript; T.T. performed pathological diagnosis and contributed writing the manuscript; all authors approved the final manuscript. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest Masaki Kuwatani is an Editorial Board Member of the journal. This article was subject to the journal’s standard procedures, with peer review handled independently of the editor and his research group.

Endoscopic ultrasound-guided rendezvous in pancreas divisum with a nondilated pancreatic duct.

Pancreas divisum is the most common congenital malformation of the pancreas, in which a single pancreatic duct does not form in the 7th week of gestation. It usually causes no symptoms or complications, but a small percentage of persons with this malformation develop recurrent acute pancreatitis. Patients with recurrent acute pancreatitis may benefit from endoscopic sphincterotomy of the minor papilla to open up the outflow of the dorsal pancreatic duct [1] [2].

A shot in the light: rendezvous endoscopic ultrasonography-guided pancreatic duct drainage in treatment of recurrent pancreatitis with pancreas divisum.

A 34-year-old man with recurrent pancreatitis was referred for endoscopic retrograde cholangiopancreatography (ERCP) [1], but cannulation of the main pancreatic duct (MPD) repeatedly failed at several teaching hospitals owing to pancreas divisum and invisible minor papilla orifice ([Fig. 1]) [2]. Thus, we decided to perform rendezvous endoscopic ultrasonography (EUS)-guided pancreatic duct drainage (EUS-PD-RV) ([Video 1]).

Severe acute necrotizing pancreatitis after endoscopic biopsy of the minor duodenal papilla

Severe acute necrotizing pancreatitis after endoscopic biopsy of the minor duodenal papilla

A Case of Primary Adenocarcinoma of the Minor Duodenal Papilla

A Case of Primary Adenocarcinoma of the Minor Duodenal Papilla

Endoscopic interventions for pancreas malformations and diseases in children

Introduction. Malformations and diseases of the pancreas are associated with the risk of complications. Interventional endoscopy is one of the ways to solve this problem.Material and methods. 24 patients (3–17 y.o.) were included in the study. 36 interventional endoscopic interventions were performed. Results. Transpapillary interventions were performed in 10 patients, all of them had anomalies of the ductal system. Stenosis of the distal pancreatic ducts was detected in 3 cases, in which stenting of the Wirsung duct was performed. Virsungolithiasis was confirmed in 3 cases, in which an anomaly of the ducts in the form of an incomplete split gland was detected in 2 patients. Pancreas divisum was detected in 1 patient, which required sphincterotomy of the minor duodenal papilla. Transmural interventions were performed in 13 cases: puncture – in 7 patients with intra- or parapancreatic cystic formations; drainage – in 6 patients with pancreatic pseudocysts. One child with traumatic rupture of the pancreas had a combined intervention (transpapillary and transmural). Discussion. The etiology of pancreatitis in children is associated with developmental anomalies and genetic factors. The leading pathogenetic factor in the development of complications is hypertension in the ducts of the gland. Traditional surgical interventions for pancreatitis are often traumatic and are accompanied by a high risk of complications. The introduction of minimally invasive techniques, such as interventional endoscopy, can solve the problem in some diseases of the pancreas.Conclusion. Transpapillary interventions can effectively eliminate hypertension in the pancreatic ducts in case of their dilatation and virsungolithiasis. Transmural interventions can be used to clarify the etiology of pancreatic cysts, as well as to drain pancreatic pseudocysts.

Safety and efficacy of minor papillotomy in children and adolescents with pancreas divisum

IntroductionPancreas Divisum (PD) is a common pancreatic ductal variant which is twice as common in pediatric patients with acute recurrent pancreatitis (ARP) relative to the general population (14% vs. 7%). Endoscopic retrograde cholangiopancreatography (ERCP) with minor papillotomy has been performed to facilitate drainage of pancreatic juice from the diminutive minor papilla to prevent pancreatitis and pancreatic damage. MethodsWe searched our prospectively-maintained endoscopy databases for patients 18 and younger who underwent ERCP with minor papillotomy between 2009 and 2019. Demographic data, indications, procedural interventions and findings, as well as available clinical outcomes data were analyzed. Results54 ARP/PD patients underwent ERCP with minor papillotomy. Median age was 14 (range 7–18) years, and 26 (48.1%) patients were female. Post-ERCP pancreatitis developed in 10/54 patients (18.5%). 12-month post-ERCP clinical trajectory was available in 47/54 (87%) patients and most patients (38/47, 80.8%) improved clinically after minor papillotomy, with 9/47 (19.1%) experiencing resolution of pancreatitis episodes and none indicated worsening severity or frequency of pancreatitis episodes following ERCP. ConclusionThe majority of children and adolescents with PD and ARP who underwent ERCP with minor papillotomy experienced subjective improvement in their symptoms following the intervention. These data suggest that ERCP with minor papillotomy for pediatric patients with PD and ARP is beneficial and may be curative in a subset of patients—higher rates of improvement than have been previously reported in adults.

S2814 Diverting Disaster: EUS-Guided Trans-Gastric Biliary Drainage

Introduction: Lumen-apposing metal stents (LAMS) are a relatively new intervention that can be used for high risk surgical cases, such as malignant obstructions not amenable to ERCP. There are few case reports using LAMS with Endoscopic Ultrasound (EUS) to achieve drainage and palliative therapy in these situations, especially using a gastric over duodenal approach. In this case, we add to the growing body of literature supporting a transgastric approach for biliary drainage using LAMS. Case Description/Methods: A 73 year-old male was admitted due to concerns for obstructive jaundice. He presented with pruritis, nausea, vomiting, copious nasogastric tube bilious output and a total bilirubin of 19.8mg/dL. MRCP revealed a distal CBD stricture measuring 12 mm in length, marked intrahepatic and extrahepatic biliary dilatation and an 8mm dilated pancreatic duct. EGD revealed a submucosal mass within the duodenal bulb causing gallbladder impingement (a). EUS was then completed and revealed similar findings to MRCP including an atrophic pancreas and severely dilated gallbladder (b). The ampullary mass, noted on CT, was also identified under EUS and fine needle biopsy was performed. A 10mm x 10mm LAMS was placed under endoscopic and fluoroscopic visualization within the flanges in the gallbladder and the antrum of the stomach (c) and resolved the patient’s symptoms the next day. Surgical pathology demonstrated pancreatic ductal carcinoma of the major and minor papillae, pancreatic head and uncinate process. Discussion: Interventions for obstructive jaundice include ERCP with biliary stenting, percutaneous transhepatic biliary drainage, EUS with LAMS placement, as well as surgery. While ERCP is the first line option, the patient’s distorted ampullary anatomy would have made cannulation and stenting challenging and high risk. Percutaneous drainage would expose the patient to risk of dislodging, obstructing, leaking, and infection. Seen below, LAMS has a relatively large diameter which allows for immediate biliary drainage, proven by the patient’s rapid relief of symptoms. Since a duodenal approach is more commonly used, current literature displays only a small number of cases showcasing the technical success of gastric approach for CBD access via LAMS, for instance, in the setting of duodenal stenosis. Our case demonstrates the versatility of the Axios stent with another successful alternative approach and proves a transgastric approach with LAMS is a viable alternative to surgery for malignant obstructive jaundice.Figure 1.: Image a: Dilated minor and major papillae with evidence of duodenal obstruction. b: EUS view of the dilated gallbladder. c: Biliary drainage from gallbladder after LAMS placement.

S1675 Blame It on the Bamboo Stump: A Pancreatic Ductal Disruption Successfully Managed With Two-Step Endoscopic Therapy

Introduction: Non-penetrating, isolated pancreatic injuries are rare, and the management is not well-established and challenging. Most injuries are managed by surgery, but recently several case reports discuss endoscopic therapy for treatment of main pancreatic duct disruption. We report a case of pancreatic injury from falling on a bamboo stump with complete pancreatic ductal disruption and complete pancreas divisum with a dominant dorsal duct that was successfully nonoperatively managed through endoscopic therapy. Case Description/Methods: An 18-year-old male transferred for worsening abdominal pain from a grade IV pancreatic injury complicated by pancreatic ascites and massive pancreatic fluid collections (PFCs) sustained a month prior after a non-penetrating fall onto a bamboo rod in the Caribbean. He had failed conservative therapy and 2 attempts with ERCP for pancreatic duct (PD) stent placement. CT A/P and MRCP showed a 13cm cyst consistent with hemorrhagic pancreatic pseudocyst (Figure A-B). Labs showed leukocytosis, elevated lipase and LFTs, but he was hemodynamically stable. US-guided paracentesis drained 250mL of fluid consistent with pancreatic ascites. To allow for pancreatic edema reduction, we elected for a 2-step procedure with separate EUS and ERCP. EUS showed multiple PFCs s/P endoscopic cyst-gastrostomy with Axios stent (Figure C-D). Repeat CT A/P showed decrease in size of the PFCs (Figure E). He was discharged and returned in one week for ERCP that revealed a surprising complete pancreas divisum and total disrupted main dorsal PD, which was endoscopically treated with sphincterotomy of the minor papilla and a long PD stent across the disruption (Figure F-H). The Axios stent was removed a week later, and 4 weeks later we successfully removed the PD stents from both the major and minor papillae. He made an uneventful recovery and remains well. Discussion: Pancreatic disruption syndrome or Disconnected Pancreatic Duct Syndrome (DPDS) is an interruption of pancreatic duct continuity, usually from necrotizing pancreatitis, but can occur with blunt or penetrating abdominal injury, as in our patient. Endoscopic management is a minimally invasive option for DPDS and pancreatic ascites. Our patient had severe pancreatic injury managed using 2-stage endoscopic therapy, demonstrating a successful treatment strategy for pancreatic injury with total main DPDS. Further studies are required regarding the selection of patients, safety, and long-term outcomes.Figure 1.: Image A: CT A/P (coronal) demonstrating edematous pancreas with significant peripancreatic fat stranding, with a peripherally enhancing hypodense fluid collection near the body and tail of the pancreas measuring approximately 4.0 x 4.8 x 13 cm in the maximum AP, RL and SI dimensions (red arrow). Image B: MRCP (coronal) Abutting the pancreatic body is a multilobulated rim-enhancing complex fluid collection that extends from the level of the diaphragmatic hiatus to just above the level of the aortoiliac bifurcation and measures 6.8 x 9.7 x 19.1 cm (AP by TR by SI, red arrow). Image C-D: EUS demonstrating large pancreatic fluid collection (PFC, left) and s/P Axios cyst-gastrostomy (right). Image E: CT A/P (coronal) demonstrating cyst-gastrostomy placement with interval decrease in PFC. Image F-H: Pancreatogram showed extravastion of contrast material at the junction of proximal 2/3 and distal1/3 of the dorsal PD c/w disrupted dorsal PD (Complete Pancreas divisum, left). Placement of a 5 Fr 9 cm Zimmon PD stent with pigtail crossing the disruption at the minor papilla (center). Pancreatogram showing no extravasation of contrast material s/P PD stent placement.

S1888 A Curious Case of Recurrent Pancreatitis: A Case Report

Introduction: Annular pancreas, a congenital anomaly characterized by incomplete rotation of the ventral pancreatic bud, causes a ring of pancreatic tissue to encircle the duodenum. It is commonly accompanied by pancreatic divisum, which occurs when the main pancreatic duct and accessory duct fail to fuse. Patients often present with recurrent pancreatitis due to partial obstruction of the pancreatic duct caused by fibrosis. Case Description/Methods: A 72-year-old Caucasian male presented with recurrent episodes of acute pancreatitis. A CT abdomen (Figure A) revealed pancreatic tissue surrounding the second portion of the duodenum consistent with an annular pancreas. A pancreatic duct stone was also noted. An MRCP (Magnetic resonance cholangiopancreatography) was consistent with annular pancreas with persistent dilation of the main and accessory pancreatic ducts and a 6mm stone noted in the pancreatic duct (Figure B). On an initial ERCP (Endoscopic retrograde cholangiopancreatography), the pancreatic duct could not be cannulated through the major papilla and minor papilla could not be identified due to inflammation. An EUS (Endoscopic ultrasound) was performed, which was suggestive of pancreas divisum. The minor papilla was cannulated, and a stent was placed in the pancreatic duct. In a subsequent ERCP (Figure C), the patient had the pancreatic stone removed, with complete resolution of his symptoms. Discussion: Typically, patients with annular pancreas present with symptoms during childhood. While infrequent, some patients remain asymptomatic until 20-50 years of age. This case demonstrates the potential to remain asymptomatic until even 72 years of age. Thus, it is important for physicians to be aware of the clinical manifestations of annular pancreas, as they could arise at any stage in life. By increasing awareness surrounding annular pancreas and management of its complications, we hope to increase the rate of early intervention.Figure 1.: Image 1A. Contrast-enhanced axial CT of the abdomen at the level of the pancreatic head. The pancreas (white bracket) is seen surrounding the 2nd part of the duodenum (white asterisk), compatible with annular pancreas. A 6 mm calcification (circled) is present in the region of the minor papilla (arrows indicating pancreatic ducts). Image 1B. Coronal MRCP images. Annular pancreas, with only a thin rim of pancreatic tissue surrounding the duodenum. The dorsal duct is best shown to wrap completely around the duodenum on MRCP images (arrow). Image 1C. ERCP fluoro image showing the previously placed pancreatic duct stent (which does appear to have a loop-like configuration) and the pancreatic stone.

S1922 A Twisted Plot: Pancreas Divisum With Right-Sided Pancreaticopleural Fistula

Introduction: We report on a 53-year-old male with a past medical history significant for chronic pancreatitis who presented with a right-sided pleural effusion secondary to pancreaticopleural fistula with pancreatic divisum. Pleural effusion secondary to pancreaticopleural fistula (PPF) is a rare complication of acute or chronic pancreatitis and usually presents with a left-sided pleural effusion. This case also highlights the difficulty and significant delay in diagnosing pancreas divisum on cross-sectional imaging. Case Description/Methods: A 53-year-old male with a medical history significant for chronic pancreatitis complicated by pancreatic ascites, walled-off necrosis, splenic and portal vein thrombosis, alcoholic gastritis, and polysubstance use presented with five days of dyspnea with new and worsening oxygen requirements. Chest x-ray showed a new moderate right-sided pleural effusion. Pleural fluid analysis revealed elevated lipase of >3,000 U/L and amylase of 21,008 U/L concerning for a pancreaticopleural fistula. MRI of pancreas showed a disconnected duct at the tail of the pancreas with a fistula extending into the mediastinum and peritoneum. During ERCP a bulging minor papilla was noted. After failed initial attempts at cannulating ventral duct, minor papilla was approached and dorsal duct was cannulated. Pancreatogram revealed a complete pancreatic divisum with a leak in the tail of the pancreas. A temporary plastic stent was placed in the dorsal duct after minor papilla sphincterotomy. The patient's symptoms resolved and he was discharged home with outpatient follow-up (Figure). Discussion: PPF is a rare complication of pancreatitis that typically presents as large, recurrent, left-sided pleural effusion often refractory to thoracentesis management. Transpapillary stent placement in the pancreatic duct is widely used in the management of PPF. Our case shows a rare right-sided presentation of PPF in the setting of a newly diagnosed pancreas divisum missed on numerous previous cross-sectional imaging. High clinical suspicion of underlying divisum raised by endoscopic and imaging findings led to successful endoscopic management of this complex case.Figure 1.: MRCP Pancreas showing pancreas divisum and disconnected duct.

Editorial introductions.

Editorial introductions.

A case series of choledochal cyst with pancreatic divisum: A rare association.

Choledochal cysts (CC) are congenital cystic dilations of the biliary tree usually associated with abnormal pancreaticobiliary ductal junction (APBDJ), but its association with pancreatic divisum has been rarely described. We encountered four cases of CC associated with pancreatic divisum (PD). Three had Type 3 PD and one had Type 1 PD. Two cases presented with pancreatic complications, with one case requiring preoperative minor papilla sphincterotomy for recurrent pancreatitis. The association of CC with PD is infrequent, and the variable presentation alters management strategy. PD may be one of the factors responsible for complications associated with CC.

Antegrade balloon dilation of the minor duodenal papilla to facilitate serial pancreatic juice aspiration cytology.

Antegrade balloon dilation of the minor duodenal papilla to facilitate serial pancreatic juice aspiration cytology.

Endoscopic management of tumors of minor ampulla: a multicenter study.

Background and study aims Papillary and duodenal carcinoma are aggressive cancers with poor 5-year survival rates. Papillectomy is a well-established treatment for early-stage carcinoma of the major papilla. Tumors arising in the minor papilla are relatively rare and there is little research available on the endoscopic management of these tumors. Patients and methods The purpose of this study was to establish the safety and efficacy of endoscopic papillectomy in the management of minor papillary tumors. A total of six patients undergoing ERCP for papillectomy for minor papillary tumor at four hospitals were included in this study over a period of 5 years. Results Papillectomy was technically successful in all six patients. Pathology revealed adenoma in three patients, adenoma with high-grade dysplasia in one patient, carcinoma in one patient, and carcinoid tumor in one patient. For follow-up, one patient had an additional tumor identified at 2 years which was found to be a recurrence of the original adenoma. This patient was treated with repeat papillectomy with no further evidence of recurrence. Conclusions In our pilot study, we demonstrate that endoscopic papillectomy appears safe and effective in the management of minor papillary tumors.

Abstract 1876: ROCKETS Science: A novel processing toolbox for light sheet microscopy reveals unknown binding sites for EpCAM-targeted antibodies

Abstract Summary: We present a novel light sheet fluorescence microscopy (LSFM)-based imaging platform and corresponding set of procedures for greatly improved preclinical investigation of the biodistribution of novel drug candidates by the example of an EpCAM-targeting antibody. Methods: An anti-EpCAM antibody (G.8.8R) was applied intravenously to mice. Whole mice or individual organs were optically cleared following novel protocols, which we termed Rapid Optical Clearing Kit for Enhanced Tissue Scanning (ROCKETS). The procedures enabled processing of mouse organs and entire bodies for LSFM. For the GI tract, we developed 3D-Swiss rolls, a method that enables fixation, clearing and imaging of intestines in a compact form as a whole. The new procedures allowed us to investigate the biodistribution of G.8.8R in the entire mouse body and highly detailed in individual organs. Results: The ROCKETS concept achieved full transparency of any mouse organ, the entire GI tract and whole mouse bodies. All positive organs were easily identified in scans of whole mice, thereby providing excellent guidance for scanning of positive individual organs at higher magnifications. We detected G8.8R bound to all normal cuboidal and columnar epithelia, as well as in lymphoid organs and were able to reproducibly score binding levels. All reported EpCAM+ tissues in mice were accessed by G8.8R after intravenous application and binding was restricted to basolateral membranes of epithelia, as expected from published expression analyses. Moreover, we detected G8.8R in tissues that were reported EpCAM- or were not investigated, e.g. gustatory papillae of the tongue, choroid plexi in the brain or lingual mucous salivary glands. 3D-Swiss rolls of the GI tract revealed a highly heterogeneous binding pattern in the stomach, while the pattern along the small intestine was overall homogeneous. All binding was restricted to basolateral membranes of epithelial cells. We detected a general gradient of signals, decreasing from the bottom of the crypts to differentiated cells in all tissues, corresponding to described EpCAM downregulation with progressing differentiation. Furthermore, we first describe significantly increased signals at the common bile duct, major and minor duodenal papillae, as well as the mucosa in proximity of Peyer's patches (PP). Conclusions: The developed ROCKETS toolbox allowed for simple preparation of mouse organs and bodies for high-quality LSFM imaging. Our investigations of the highly heterogeneous biodistribution of G8.8R revealed previously unknown EpCAM binding locations, which may have far-reaching implications for EpCAM-targeting therapeutics in general, many of which failed in clinical studies due to dose limiting toxicities. In the future, the developed LSFM-imaging platform may contribute valuable data to preclinical drug development studies of any targeted therapeutic. Citation Format: Joerg P. Mueller, Nils O'Brien, Franz Osl, Frank Herting, Christian Klein, Pablo Umana, Sara Colombetti, Thomas Poeschinger, Andreas Beilhack. ROCKETS Science: A novel processing toolbox for light sheet microscopy reveals unknown binding sites for EpCAM-targeted antibodies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1876.