Large Duct Research Articles

Cholangioscopic inspection immediately after endoscopic retrograde cholangiopancreatography for large common bile duct stone may be beneficial to discover potential cholangiocarcinoma resulting from choledocholithiasis.

Cholangioscopic inspection immediately after endoscopic retrograde cholangiopancreatography for large common bile duct stone may be beneficial to discover potential cholangiocarcinoma resulting from choledocholithiasis.

Interdisciplinary Management of Large Nasopalatine Duct Cyst in a Pediatric Patient: A Rare Diagnosis

Interdisciplinary Management of Large Nasopalatine Duct Cyst in a Pediatric Patient: A Rare Diagnosis

SINONASAL ADAMANTINOMA-LIKE EWING SARCOMA: A CASE EXPANDING THE MORPHOLOGIC SPECTRUM

Adamantinoma-like Ewing sarcoma (ALES) is an exceedingly rare sinonasal malignancy defined by complex epithelial differentiation and EWSR1-FLI1 gene fusion. A 43-year-old female presented with painful facial swelling and proptosis. Computed tomography showed an exuberant heterogeneous tumor in the right sphenoid sinus that extended into the maxillary sinus, parapharyngeal space, orbit, and anterior cranial fossa. Microscopic analysis revealed sheets of monotonous basaloid cells with regular nuclear membranes and discernible nucleoli. Additionally, large foamy cells, ducts, whorls, and foci of abrupt keratinization were identified. Tumor cells were diffusely positive for AE1/3, p40, and CD99, and negative for NUT. The Ki-67 proliferation index was 40%. EWSR1 rearrangement was detected by FISH, confirming the final diagnosis of sinonasal ALES. Pathologists should consider ALES when evaluating aggressive sinonasal tumors composed of basaloid cells with focal keratinization. Immunopositivity for AE1/3, p40, and CD99, and molecular confirmation of EWSR1 rearrangement are essential for diagnosis. Adamantinoma-like Ewing sarcoma (ALES) is an exceedingly rare sinonasal malignancy defined by complex epithelial differentiation and EWSR1-FLI1 gene fusion. A 43-year-old female presented with painful facial swelling and proptosis. Computed tomography showed an exuberant heterogeneous tumor in the right sphenoid sinus that extended into the maxillary sinus, parapharyngeal space, orbit, and anterior cranial fossa. Microscopic analysis revealed sheets of monotonous basaloid cells with regular nuclear membranes and discernible nucleoli. Additionally, large foamy cells, ducts, whorls, and foci of abrupt keratinization were identified. Tumor cells were diffusely positive for AE1/3, p40, and CD99, and negative for NUT. The Ki-67 proliferation index was 40%. EWSR1 rearrangement was detected by FISH, confirming the final diagnosis of sinonasal ALES. Pathologists should consider ALES when evaluating aggressive sinonasal tumors composed of basaloid cells with focal keratinization. Immunopositivity for AE1/3, p40, and CD99, and molecular confirmation of EWSR1 rearrangement are essential for diagnosis.

Nipple Adenoma: Clinicopathologic Characterization of 50 Cases.

Nipple adenoma (NA) is a rare, benign proliferation of the nipple ducts. It may be clinically mistaken for Paget disease or squamous cell carcinoma; thus, microscopic evaluation is paramount. A large case series of NA has not been undertaken since the 1980s. Therefore, we undertook this study to evaluate the clinicopathologic characteristics of NA, emphasizing differential diagnoses and follow-up data. We retrieved 50 cases from our in-house archives or consultation files between 2003 and 2022. Available slides were reviewed, and clinical data and follow-up information were obtained. Cases must have exhibited a dense ductal proliferation in the breast tissue with proximity to the nipple epidermis. All patients were women; median age was 56 years. In all, 68% of patients were symptomatic; 53% demonstrated a skin growth. Overall, 67% were excised completely, either primarily (33%) or via re-excision after biopsy (33%). Four histologic patterns were noted: adenosis (dense proliferation of small-to-medium ducts); large duct (medium-to-large caliber ducts); papillary-like (frond-like architecture with branching, slit-like lumens); and pseudoinfiltrative (ducts squished and distorted by dense stromal fibrosis). Follow-up in 44 patients (88%) with a median time of 66 months showed no evidence of recurrence. NA demonstrates a wide spectrum of histopathologic variation. Subtyping of this entity is unlikely to be clinically relevant. Differentiation from invasive carcinoma or other histologic mimics (syringocystadenoma papilliferum, syringomatous adenoma) may be difficult. Simple excision is curative, and recurrence is rare. A definitive link to invasive carcinoma has not been established.

GABA treatment does not induce neogenesis of new endocrine cells from pancreatic ductal cells

ABSTRACT Previous studies indicated that ductal cells can contribute to endocrine neogenesis in adult rodents after alpha cells convert into beta cells. This can occur through Pax4 mis-expression in alpha cells or through long-term administration of gamma-aminobutyric acid (GABA) to healthy mice. GABA has also been reported to increase the number of beta cells through direct effects on their proliferation, but only in specific genetic mouse backgrounds. To test whether GABA induces neogenesis of beta cells from ductal cells or affects pancreatic cell proliferation, we administered GABA or saline over 2 or 6 months to Sox9CreER;R26RYFP mice in which 60–80% of large or small ducts were efficiently lineage labeled. We did not observe any increases in islet neogenesis from ductal cells between 1 and 2 months of age in saline treated mice, nor between 2 and 6 months of saline treatment, supporting previous studies indicating that adult ductal cells do not give rise to new endocrine cells during homeostasis. Unlike previous reports, we did not observe an increase in beta cell neogenesis after 2 or 6 months of GABA administration. Nor did we observe a significant increase in the pancreatic islet area, the number of insulin and glucagon double positive cells, or cell proliferation in the pancreas. This indicates that the effect of long term GABA administration on the pancreas is minimal or highly context dependent.

Modified endoscopic submucosal tunnel dissection for large esophageal submucosal gland duct adenoma: A case report

With the recent improvement of endoscopic techniques, endoscopic ultrasound-guided fine needle aspiration and endoscopic submucosal tunnel dissection (ESTD) have been widely used for accurate diagnosis and dissection acceleration of esophageal tumors.We used a modified submucosal tunnel technique during endoscopic en bloc resection in a 58-year-old man with large esophageal submucosal gland duct adenoma (ESGDA). During modified ESTD, the oral end of the involved mucosa was cut transversely, followed by a submucosal tunnel created from the proximal to the distal end, and the anal end of the involved mucosa blocked by the tumor was incised. As a result of retaining submucosal injection solutions using the submucosal tunnel technique, it was possible to reduce the amount of injection required and increase the efficiency and safety of dissection.Modified ESTD is an effective treatment strategy for large ESGDAs. Single-tunnel ESTD appears to be a time-saving procedure compared with conventional endoscopic submucosal dissection.

Extra-hepatic portal vein obstruction leading to portal cavernoma cholangiopathy without liver dysfunction

In adults, EHPVO mainly occurs following thrombosis, while in children it may be related to congenital malformations and/or neonatal umbilical venous catheterization. EHPVO leads to the cavernous transformation of the portal vein in the absence of recanalization. Portal cholangiopathy (also referred to as portal biliopathy) is common in patients with long-standing chronic PVT. It is due to compression of the large bile ducts by the venous collaterals (portal cavernoma) that form in patients with chronic PVT. Typically, symptoms of portal cholangiopathy include jaundice, biliary colic and pruritus.

Caroli syndrome associated with atrial septal defect and polydactyly: a case report

IntroductionCaroli disease is multifocal segmental dilatation of the large intrahepatic bile ducts that connect to the main duct. It is considered a rare disease with an incidence rate of 1 in 1,000,000 births. There are two types of Caroli: the first type is the simple type, Caroli disease, which includes only cystic dilatation of the intrahepatic bile ducts. The second is called Caroli syndrome, which consists of Caroli disease and congenital hepatic fibrosis and might lead to portal hypertension leading to esophageal varices and splenomegaly. Atrial septal defect is one of the most common congenital heart diseases, occurring when the connection between the left and the right atriums fails to close. Polydactyly is one of the most common congenital malformations of the hands and feet. It manifests in excess fingers on the hands or toes.Case presentationA 6-year-old Arab girl presented to the hospital with abdominal pain for the last month with abdominal enlargement. The patient was already diagnosed with Caroli disease and polydactyly (six fingers on each limb) when she was born. Investigations including complete blood count, blood smear, bone marrow biopsy, esophagoscopy, abdominal ultrasound, and computed tomography scan showed splenomegaly associated with hypersplenism, fourth-grade non-bleeding varices, intrahepatic cystic formations in the left and right lobes, and an atrial septal defect with a left-to-right shunt. The patient was scheduled for a splenectomy after she was vaccinated with the appropriate vaccines. After follow-up for a week in the hospital, complete blood count showed an improvement. A month after that, the patient had liver abscesses and biliary fistula that were treated appropriately and her symptoms resolved.ConclusionThe association of liver diseases, polydactyly, and congenital heart diseases is extremely rare and was only documented few times in the literature. However, to our knowledge, atrial septal defect has never been part of this combination before. The family history also makes this case unique and strongly suggests genetic etiology.

Large duct intrahepatic cholangiocarcinoma arising from intraductal papillary neoplasm of bile duct: A rare case report

Large duct intrahepatic cholangiocarcinoma arising from intraductal papillary neoplasm of bile duct: A rare case report

Clinicopathological, etiological and molecular characteristics of intrahepatic cholangiocarcinoma subtypes classified by mucin production and immunohistochemical features

ABSTRACTBackgroundIntrahepatic cholangiocarcinoma (ICC) can be divided into two morphological subtypes: large duct type and small duct type ICC. This study aims to verify the feasibility of the classification criteria and clinicopathological characteristics of ICC.Research design and methodsICC patients were divided into the large and small type ICC by morphological and immunohistochemical patterns. Subsequently, clinicopathological data of the two groups was compared and the multivariate COX regression was used to verify the clinical significance of ICC subtypes. In addition, IDH1/2 mutation, KRAS mutation and FGFR2 translocation was also evaluated.ResultsTotally, 32, 61 and 13 tumors were defined as large, small and the indeterminate-duct type ICC respectively. Clinicopathologically, the large and small duct type ICC showed distinct morphological features. Compared with the small duct type ICC, the large duct type ICC had higher levels of serum tumor markers, vascular invasion, lymph node metastasis, and postoperative recurrence. Furthermore, positive FGFR2 rearrangement occurred only in small duct type ICC and IDH1/2 was mutated mainly in small duct type ICC.ConclusionsThe subclassification system was applicable and the ICC subtypes had distinct clinicopathological characteristics, prognostic outcome, and IDH1/2 mutation pattern.

Gallbladder perforation following peroral cholangioscopy‐guided lithotripsy: A case report

Peroral cholangioscopy-guided lithotripsy is highly effective in clearing difficult bile duct stones. It can cause adverse events, such as cholangitis and pancreatitis; however, gallbladder perforation is extremely rare. Herein, we describe the case of a 77-year-old woman who developed gallbladder perforation following peroral cholangioscopy -guided lithotripsy. She was referred to our hospital to treat multiple large bile duct stones. She underwent peroral cholangioscopy-guided lithotripsy because of conventional lithotripsy failure. After a cholangioscope was advanced into the bile duct, saline irrigation was used for visualization. Electronic hydraulic lithotripsy was performed, but it took time for fragmentation because the calculus was hard. The 2-h endoscopic procedure did not completely remove the stone, and treatment was discontinued after placing a biliary plastic stent and nasobiliary tube. After the endoscopic procedure, she started experiencing right hypochondrial pain, which worsened the next day. Computed tomography showed a gallbladder wall defect in the gallbladder fundus with pericholecystic fluid. She was diagnosed with gallbladder perforation and underwent emergency surgery. A perforation site was found at the gallbladder fundus. Open cholecystectomy, choledochotomy, and extraction of residual bile duct stones were performed. The patient was discharged 9 days post-surgery without any complications. The saline irrigation used for visualization may have caused a surge in intra-gallbladder pressure, resulting in gallbladder perforation. Therefore, endoscopists may need to conserve irrigation water during peroral cholangioscopy-guided lithotripsy.

AN 84-YEAR-OLD PATIENT WITH CAROLI SYNDROME: WHAT IS THE PROGNOSIS OF THIS CONDITION?

We describe a case of advanced and rare Caroli syndrome with an atypical clinical presentation of a space-occupying lesion with slow progression.The atypical presentation could be misdiagnosed as metastatic neoplasm.

Early spontaneous closure of large arterial ducts in two term neonates with Ebstein anomaly after failed attempts of transcatheter closure.

In neonatal Ebstein's anomaly of the tricuspid valve, prolonged ductal patency in patients without anatomic pulmonary valve atresia can be deleterious. Circular shunts may develop in patients with different degrees of pulmonary and tricuspid insufficiency. Closure of the arterial duct may result in haemodynamic improvement in particular scenarios. The transcatheter approach is a valuable closure alternative despite some technical difficulties in large-sized arterial ducts and low birth weight neonates. Herein, we report on two consecutive term newborns with Ebstein's anomaly and large arterial ducts in whom mechanical stimulus of the arterial duct during failed attempts of transcatheter closure led after two days to definitive closure followed by good clinical outcomes.

A104 INVISIBLE COLONIC MALIGNANCY AND POSSIBLE IDIOSYNCRATIC DRUG-INDUCED LIVER INJURY FROM VEDOLIZUMAB IN A PATIENT WITH ULCERATIVE COLITIS, PRIMARY SCLEROSING CHOLANGITIS AND AUTOIMMUNE HEPATITIS OVERLAP SYNDROME

Abstract Background Inflammatory bowel disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract. Due to an increased risk of developing colorectal cancer, regular surveillance for dysplastic lesions via colonoscopy is recommended. Invisible dysplasia is the abnormal development of cells noted on pathology with no visible lesion seen during colonoscopy. Primary sclerosing cholangitis (PSC) is an immune-mediated liver disease leading to progressive stricturing and fibrosis of the bile ducts. There is significant association between PSC and IBD, as up to 80% of patients with PSC having underlying IBD. Drug induced liver injury (DILI) is a common cause of acute liver failure in most Western countries. Most cases of DILI are self-limited, with resolution of laboratory and clinical findings after cessation of the offending agent. Purpose To describe a case of invisible colonic malignancy and possible idiosyncratic drug-induced liver injury from vedolizumab (VDZ) in a patient with ulcerative colitis (UC), PSC and autoimmune hepatitis (AIH) overlap syndrome. Method Patient consent was obtained. Information from electronic records was extracted, including admission notes and procedural reports. A literature review was performed using Pubmed. Result(s) A 32-year-old Caucasian female with UC on VDZ with PSC and AIH had multiple colonoscopies performed demonstrating multifocal low-grade dysplasia. However, she remained resistant to surgery. She presented to clinic with tea-coloured urine, fatigue, and scleral icterus. Investigations revealed conjugated hyperbilirubinemia with elevation in hepatocellular liver enzymes. Imaging was consistent with large duct PSC, and liver biopsy showed grade 2 chronic hepatitis raising the possibility of large bile duct obstruction. She underwent liver transplant assessment and VDZ was held. Her bilirubin and liver enzymes recovered. Given multiple colonoscopies showing multifocal dysplastic changes and the patient declining other biologics, she would ultimately undergo total proctocolectomy with end ileostomy. Pathology demonstrated mucinous adenocarcinoma with a signet ring component. Conclusion(s) Both mucinous adenocarcinoma and signet ring carcinoma are more aggressive malignancies associated with poor prognosis. Found more often in younger patients, they are often diagnosed in later stages with lymphovascular invasion. Here, there was no evidence of metastases in any of the 40 lymph nodes examined, which indicated more favourable prognosis. The mechanism by which VDZ potentially causes liver injury is unknown. Multiple therapies for PSC-AIH overlap and IBD were entertained as causative agents. However, significant improvement in clinical symptoms and serologic parameters following cessation of VDZ was temporally suggestive. This case simultaneously highlights the importance of both timely colectomy in IBD patients with high-risk features during surveillance and early recognition and cessation of potential causative medications which induce liver injury. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

A252 LONG-TERM OUTCOMES IN INFLAMMATORY BOWEL DISEASE PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS: KINGSTON HEALTH SCIENCES CENTER LOCAL EXPERIENCE

Abstract Background IBD-PSC remains a poorly understood entity due to it’s low incidence and the heterogeneity found within this patient population. Patients with IBD-PSC have 0.3-2.8% lifetime risk of developing hepatocellular carcinoma, up to a 20% lifetime risk of developing Cholangiocarcinoma and a 20-30% lifetime risk of developing Colorectal Cancer (Fung et al. World J Gastroenterol 2019). To better understand long-term outcomes in this population, the use of large population level data can be useful but requires case validation. Purpose A large multicenter Canadian retrospective cohort study is ongoing with the goals of identifying an algorithm to identify IBD-PSC patients and compare long-term outcomes of IBD-PSC patients with a matched IBD cohort (Ricciuto et al, ongoing). This abstract describes the local data within Kingston Health Sciences Centre (KHSC) from this Canadian multi-center study and evaluates the use of ICD codes for the identification of IBD-PSC. Method This is a single centre retrospective cohort study of patients with IBD-PSC within KHSC from January 1993 - December 2021. Patients with potential IBD-PSC were initially identified locally using ICD codes for IBD and cholangitis. Charts were reviewed and IBD-PSC diagnosis was confirmed using pathology from liver biopsies and imaging. Those confirmed to have IBD-PSC then had data manually extracted from the local health administrative system. Outcomes of interest were divided into patient demographics, disease phenotype at diagnosis of IBD-PSC and therapies. Patients were followed until death, leaving the KHSC network or the end of the follow-up period. Result(s) Of the 862 patients identified using ICD codes, 16 (2%) were confirmed to have IBD-PSC after chart review. 50% of included patients had other autoimmune diseases. The median age of diagnosis of PSC was 34 years (IQR=22-43) while the median age of diagnosis of IBD was 22 (IQR=15-38). Large duct PSC was found in 88% of patients. Six patients had disease that was exclusively intra-hepatic. Two patients were found to have PSC with auto-immune hepatitis overlap. Mean ALP at diagnosis was 402 (IQR=208-506). Four patients developed cirrhosis, two of which experienced hepatic decompensation. Three patients underwent liver transplant. 81% of patients had ulcerative colitis. At the index lower endoscopy, 33% of patients had Mayo 3 colitis and 75% had involvement of the right colon. During follow up in our study, 81% of patients required systemic steroids and 33% required biologic therapy. Conclusion(s) ICD codes alone cannot reliably identify patients with IBD-PSC. The characteristics of the patients in our local experience are in keeping with existing literature. Completion of this multi-center study will allow for a greater sample size, a matched control group and a better understanding of the long-term impacts of this disease. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Circular RNA in liquid biopsy as biomarkers toward precision medicine

Circular RNA in liquid biopsy as biomarkers toward precision medicine

Pathological survey of precursor lesions in cholangiocarcinoma.

To clarify the pathological significance of two precursors (high-grade biliary intraepithelial neoplasm [BilIN] and intraductal papillary neoplasm of bile duct [IPNB]) in cholangiocarcinomas (CCAs). Ninety-one cases of CCA (47 distal CCAs [dCCAs], 31 perihilar CCAs [pCCAs] and 13 intrahepatic CCAs of large duct type [LD-iCCAs]) were examined for their association with precursors. Neoplastic intraepithelial lesions without underlying infiltrating carcinoma in the surrounding mucosa of CCAs were considered to reflect high-grade BilIN. High-grade BilIN and IPNB were subdivided into gastric, biliary, intestinal and oncocytic subtypes, while CCAs were subdivided into gastrobiliary, intestinal and oncocytic subtypes. The postoperative overall survival (OS) was examined. Fifty-four and 8 of 91 CCAs were associated with high-grade BilIN and IPNB, respectively, while these precursors were unidentifiable in the remaining CCAs. A majority of CCAs were of the gastrobiliary subtype, while the intestinal subtype was occasionally detected, and the oncocytic subtype was rare. CCAs with high-grade BilIN showed a similar postoperative OS to CCAs without precursors, while CCAs with IPNB showed a favorable postoperative OS compared to CCAs without precursors. CCAs were frequently associated with precursors; high-grade BilIN may be a major precursor and IPNB a minor one. CCAs with IPNB showed a favorable postoperative OS compared to CCAs with high-grade BilIN.

Asbestos exposure as an additional risk factor for small duct intrahepatic cholangiocarcinoma: a pilot study

Intrahepatic cholangiocarcinoma (iCCA) is a rare malignancy, recently classified in small duct and large duct morphological subtypes. Growing evidence suggests asbestos as a putative risk factor for iCCA, albeit no correlation between asbestos and iCCA morphology has been investigated so far. The aim of the present study was to assess the relationship between asbestos exposure and iCCA morphological subtype. Forty patients with surgically removed iCCA were prospectively enrolled: asbestos exposure was assessed according to the Italian National Mesothelioma Register questionnaire. From the surgical iCCA specimens the main histopathological variables were collected, including the small duct (sd-iCCA, 32 patients) and large duct subtypes (ld-iCCA, 8 patients). Five sd-iCCA cases had a definite/probable occupational exposure to asbestos, while no cases of ld-iCCA were classified as being occupationally exposed (definite/probable). Other kind of asbestos exposure (i.e. possible occupational, familial, environmental) were recorded in 16 sd-iCCA and 3 ld-iCCA. Cases with unlikely exposure to asbestos were 11 sd-iCCA (35.5%) and 5 ld-iCCA (62.5%). In conclusion, these findings seem to indicate that sd-iCCA might be more frequently associated to asbestos exposure rather than ld-iCCA, suggesting that asbestos fibres might represent a parenchymal, rather than a ductal risk factor for iCCA. This pilot study must be confirmed by further case–control studies or large independent cohorts.

Preoperative subcategorization based on magnetic resonance imaging in intrahepatic cholangiocarcinoma

BackgroundAppropriate preoperative identification of iCCA subtype is essential for personalized management, so the aim of this study is to investigate the role of MR imaging features in preoperatively differentiating the iCCA subtype.MethodsNinety-three patients with mass-forming intrahepatic cholangiocarcinoma (iCCA, 63 small duct type and 30 large duct type) were retrospectively enrolled according to the latest 5th WHO classification (mean age, males vs. females: 60.66 ± 10.53 vs. 61.88 ± 12.82, 50 men). Significant imaging features for differentiating large duct iCCA and small duct iCCA were identified using univariate and multivariate logistic regression analyses, and a regression-based predictive model was then generated. Furthermore, diagnostic performance parameters of single significant imaging features and the predictive model were obtained, and corresponding receiver operating characteristic (ROC) curves were subsequently presented.ResultsThe univariate analysis showed that tumor in vein, arterial phase hypoenhancement, intrahepatic duct dilatation, lack of targetoid restriction and lack of targetoid appearance in T2 were predictors of large duct type iCCA. Arterial phase hypoenhancement, intrahepatic duct dilatation and lack of targetoid restriction were independent predictors for large duct type iCCA in multivariate analysis. The regression-based predictive model has achieved the best preoperative prediction performance in iCCA subcategorization so far. The area under the ROC curve of the regression-based predictive model was up to 0.91 (95% CI: 0.85, 0.98), and it was significantly higher than every single significant imaging feature.ConclusionsArterial phase hypoenhancement, intrahepatic duct dilatation and lack of targetoid restriction could be considered reliable MR imaging indicators of large duct type iCCA. MR imaging features can facilitate noninvasive prediction of iCCA subtype with satisfactory predictive performance.

Radiation-free digital cholangioscopy-guided removal of bile duct foreign body and holmium laser lithotripsy for large common bile duct stones.

Digital cholangioscopy (SpyGlass; Boston Scientific, Marlborough, Massachusetts, USA) allows direct visualization of the biliary system for therapeutic interventions [1]. This is a report of cholangioscopy-guided removal of a biliary plastic stent and holmium laser lithotripsy for large common bile duct (CBD) stones.