Variant anatomy of the biliary system as a cause of pancreatic and peri-ampullary cancers

Muraki, Takamura; Reid, Michelle D.; Pehlivanoğlu, Burçin; González, Raúl; Sekhar, Aarti; Memiş, Bahar; Xue, Yue; Cheng, Jiqi; Jang, Kee Taek; Mittal, Pardeep; Cardona, Kenneth; Kooby, David A.; Maithel, Shishir K.; Sarmiento, Juan M.; El‐Rayes, Bassel F.; Lomberk, Gwen; Urrutia, Raúl; Christians, Kathleen K.; Tsai, Susan; Evans, Douglas B.; Adsay, Volkan

doi:10.1016/j.hpb.2020.03.014

Cited by 12 publications

(6 citation statements)

References 42 publications

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“…A minor ductal cell population (defined as MUC5B-positive ductal cells), characterised by higher expression levels of genes related to mucin secretion, such as TFF3, has been described, which, according to our gene and protein expression data (figure 5A–B, online supplemental figure 5), could be related to intestinal IPMN. It is tempting to speculate that exposure of the ductal cell compartment to environmental carcinogens, for example, due to bile reflux as a consequence of an anatomic variation at the pancreato-biliary junction46 47 or to an altered oral, gastric and intestinal microbiome,48 could induce an intestinal phenotype switch as first adaptive response of a ‘susceptible’ cell type, followed by dysplasia and cancer. Since the ductal cell compartment is the only one that can achieve long-term expansion in organoids obtained from adult healthy mice,49 such a ‘susceptible’ cell type might represent an adult progenitor-like cell residing in the pancreatic ducts.…”

Section: Discussionmentioning

confidence: 99%

Molecular heterogeneity and commonalities in pancreatic cancer precursors with gastric and intestinal phenotype

Liffers

Godfrey

Frohn

et al. 2022

Gut

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ObjectiveDue to the limited number of modifiable risk factors, secondary prevention strategies based on early diagnosis represent the preferred route to improve the prognosis of pancreatic ductal adenocarcinoma (PDAC). Here, we provide a comparative morphogenetic analysis of PDAC precursors aiming at dissecting the process of carcinogenesis and tackling the heterogeneity of preinvasive lesions.DesignTargeted and whole-genome low-coverage sequencing, genome-wide methylation and transcriptome analyses were applied on a final collective of 122 morphologically well-characterised low-grade and high-grade PDAC precursors, including intestinal and gastric intraductal papillary mucinous neoplasms (IPMN) and pancreatic intraepithelial neoplasias (PanIN).ResultsEpigenetic regulation of mucin genes determines the phenotype of PDAC precursors. PanIN and gastric IPMN display a ductal molecular profile and numerous similarly regulated pathways, including the Notch pathway, but can be distinguished by recurrent deletions and differential methylation and, in part, by the expression of mucin-like 3. Intestinal IPMN are clearly distinct lesions at the molecular level with a more instable genotype and are possibly related to a different ductal cell compartment.ConclusionsPDAC precursors with gastric and intestinal phenotype are heterogeneous in terms of morphology, genetic and epigenetic profile. This heterogeneity is related to a different cell identity and, possibly, to a different aetiology.

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Section: Discussionmentioning

confidence: 99%

Molecular heterogeneity and commonalities in pancreatic cancer precursors with gastric and intestinal phenotype

Liffers

Godfrey

Frohn

et al. 2022

Gut

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“…Humans and non-human primates are predisposed to a variety of mechanical, inflammatory, and neoplastic conditions at the MDP that further predispose the development of biliary and pancreatic inflammation and neoplasia. 18,25,31,33 Given their similar anatomy, we suspect that cats may also suffer from similar conditions with related sequelae, but reports in the literature are few and limited to antemortem observations. 13 In this study, over a quarter of necropsied cats had histologic evidence of MDPitis, and cats with MDPitis were 6.64 times more likely to have concurrent triaditis.…”

Section: Discussionmentioning

confidence: 99%

Histologic characterization of the major duodenal papilla and association with concurrent biliary, pancreatic, and intestinal pathology in cats

et al. 2023

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Conjoining of the major pancreatic duct and common bile duct at the major duodenal papilla (MDP) is suspected to predispose cats to the clinical syndrome of “triaditis.” However, microanatomy of the MDP or presence of lesions at the MDP has not been assessed in cats with or without triaditis. The aims of this study were to characterize feline MDP histomorphology and to identify associations between MDP anatomy/disease and the presence of biliary, pancreatic, or intestinal inflammation or neoplasia. Histologic assessment was prospectively performed on the MDP, duodenum, jejunum, ileum, liver, and pancreas from 124 client-owned cats undergoing postmortem examination. The majority of cats (104/124, 84%) had a complex ductular network at the MDP, with no distinction between pancreatic and common bile ducts. Lymphoid aggregates at the MDP were common (63/124, 51%). Inflammation of the MDP (MDPitis) was present in 35 of 124 cats (28%) and was often concurrent with cholangitis, pancreatitis, or enteritis (32/35, 91%), but was only associated with enteritis (19/35, 54%, P < .05). Triaditis was less common (19/124, 15%), but was associated with both conjoined MDP anatomy (19/19, 100%, P < .05) and MDPitis (12/19, 63%, P < .05). Neoplasia was present in 37 of 124 cats (29%), with lymphoma (28/37, 78%) predominating. Enteropathy-associated T-cell lymphoma type 2 (EATL2) was most common ( n = 16/37, 43%) and was associated with triaditis and MDPitis ( P < .05). These findings suggest that anatomy, immune activation, and/or inflammation of the MDP may play a role in the pathogenesis of triaditis. Further studies are needed to elucidate the relationships between triaditis, MDPitis, and EATL2.

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“…The signi cance of a low CD union was rst described by Eisendrath in 1918 who noted that such anatomy might predispose to inadvertent bile duct injury during cholecystectomy [1]. Reports concerning the further clinical signi cance of this anatomic anomaly are relatively rare, but they observed an association with gallstone pancreatitis, Mirrizi syndrome, gallbladder cancer, and cystic dilatation of the biliary duct [2].…”

Section: Main Textmentioning

confidence: 99%

“…Despite the potential surgical complications associated with these rare congenital malformations, CD aberrations have been demonstrated to predispose to several pathologic pancreaticobiliary conditions. For example, a low union of the CD has previously been associated with a higher risk of pancreatitis and even periampullary cancer and this association was ascribed to an anatomy-induced pressure process leading to chemical/bilious irritation [2]; this association is probably supported also by the shorter and lesser exposure of the biliary epithelium to the protective or dilutional effect of peri-biliary mucus glands in the upper biliary tree which happens in the presence of a low union [1]. In addition, previous studies have found an association between low insertion of the CD and choledocholithiasis [10] which can be due to increased retrograde pressure in the CD leading to both bile stagnation and impaired gallbladder emptying.…”

Section: Main Textmentioning

confidence: 99%

An exceedingly rare case of separated drainage of the cystic duct, the common bile duct and the main pancreatic duct documented on magnetic resonance cholangiopancreatography

Brandi

Fiscaletti²,

Renzulli

2023

Preprint

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Anatomical variations of the intra- and extra-hepatic biliary system are common, including those affecting the course and insertion point of the cystic duct. Adequate knowledge of such variations and an appropriate roadmap before any surgical, endoscopic or percutaneous procedure help in preventing associated iatrogenic complications. Magnetic resonance cholangiopancreatography (MRCP) can precisely delineate the anatomy of the biliary system preoperatively. We report the case of a 72-year-old female patient who presented with chronic right upper quadrant abdominal pain of 6 months duration, which had acutely worsened over the previous 2 weeks, and no other comorbidities. Blood tests were normal. Abdominal ultrasound revealed a slight dilatation of the common hepatic duct (10 mm) but no gallstones or sludge were demonstrated. MRCP excluded choledocholithiasis but revealed a cystic duct coursing medial to the common bile duct before anastomosing at the level of the ampulla of Vater. Trifurcation (Type 2 variant) of the intra-hepatic bile system was also observed. To the best of the Authors’ knowledge, this is the very first report of this exceptionally rare anatomic cystic duct anomaly on MRCP.

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Variant anatomy of the biliary system as a cause of pancreatic and peri-ampullary cancers

Cited by 12 publications

References 42 publications

Molecular heterogeneity and commonalities in pancreatic cancer precursors with gastric and intestinal phenotype

Molecular heterogeneity and commonalities in pancreatic cancer precursors with gastric and intestinal phenotype

Histologic characterization of the major duodenal papilla and association with concurrent biliary, pancreatic, and intestinal pathology in cats

An exceedingly rare case of separated drainage of the cystic duct, the common bile duct and the main pancreatic duct documented on magnetic resonance cholangiopancreatography

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