Intrahepatic Ducts Research Articles

Hepatolithiasis: Epidemiology, presentation, classification and management of a complex disease.

The term hepatolithiasis describes the presence of biliary stones within the intrahepatic bile ducts, above the hilar confluence of the hepatic ducts. The disease is more prevalent in Asia, mainly owing to socioeconomic and dietary factors, as well as the prevalence of biliary parasites. In the last century, owing to migration, its global incidence has increased. The main pathophysiological mechanisms involve cholangitis, bile infection and biliary strictures, creating a self-sustaining cycle that perpetuates the disease, frequently characterised by recurrent episodes of bacterial infection referred to as syndrome of "recurrent pyogenic cholangitis". Furthermore, long-standing hepatolithiasis is a known risk factor for development of intrahepatic cholangiocarcinoma. Various classifications have aimed at providing useful insight of clinically relevant aspects and guidance for treatment. The management of symptomatic patients and those with complications can be complex, and relies upon a multidisciplinary team of hepatologists, endoscopists, interventional radiologists and hepatobiliary surgeons, with the main goal being to offer relief from the clinical presentations and prevent the development of more serious complications. This comprehensive review provides insight on various aspects of hepatolithiasis, with a focus on epidemiology, new evidence on pathophysiology, most important clinical aspects, different classification systems and contemporary management.

Targeting pathogenic CD8+ tissue-resident T cells with chimeric antigen receptor therapy in murine autoimmune cholangitis

Primary biliary cholangitis (PBC) is a cholestatic autoimmune liver disease characterized by autoreactive T cell response against intrahepatic small bile ducts. Here, we use Il12b-/-Il2ra-/- mice (DKO mice) as a model of autoimmune cholangitis and demonstrate that Cd8a knockout or treatment with an anti-CD8α antibody prevents/reduces biliary immunopathology. Using single-cell RNA sequencing analysis, we identified CD8+ tissue-resident memory T (Trm) cells in the livers of DKO mice, which highly express activation- and cytotoxicity-associated markers and induce apoptosis of bile duct epithelial cells. Liver CD8+ Trm cells also upregulate the expression of several immune checkpoint molecules, including PD-1. We describe the development of a chimeric antigen receptor to target PD-1-expressing CD8+ Trm cells. Treatment of DKO mice with PD-1-targeting CAR-T cells selectively depleted liver CD8+ Trm cells and alleviated autoimmune cholangitis. Our work highlights the pathogenic role of CD8+ Trm cells and the potential therapeutic usage of PD-1-targeting CAR-T cells.

Enfermedades inflamatorias de páncreas y vía biliar

Inflammatory involvement of the bile duct and pancreas can present in different ways depending on the etiology and place of involvement. These are rare diseases; the most common is autoimmune pancreatitis, which has two subtypes: type 1, which is considered the pancreatic manifestation of systemic IgG4-related disease (IgG4-RD) and type 2, which is considered a primarily pancreatic disease. The most common clinical presentation is in the form of jaundice and pancreatic masses with or without abdominal pain, which necessitates a differential diagnosis with pancreatic adenocarcinoma. Treatment is based on corticosteroids, with good response rates, but there is a non-negligible risk of recurrence which sometimes requires treatment with anti-CD20 (rituximab) or immunosuppressants. IgG4-RD can also affect the bile duct, in which case it is called IgG4-related sclerosing cholangitis, and treatment is similarly based on corticosteroids. Lastly, recurrent pyogenic cholangitis is a rare type of inflammatory disease of the bile duct characterized by the formation of recurrent intrahepatic and extrahepatic bile duct stones and recurrent episodes of cholangitis that often require endoscopic, radiological, or surgical treatment in addition to medical treatment.

Anatomical, Radiological, and Corrosion Casting of the Liver, Gallbladder, and Biliary Duct System of Local Breed Cattle (Bos ttaurus)

Local breed cattle's liver, reddish-brown, occupies the right hypochondriac region with 35.2 ± 3.24 cm long and 5.5 ± 0.5 kg weight. Connected by left and right triangular ligaments; and falciform ligaments with the diaphragm, and hepatorenal ligament with the right kidney. While the coronary ligament encompassing the caudal vena cava divides into dorsal and ventral branches, enclosing the nuda region. The round ligament connects the umbilical fissure to the umbilicus. The lesser omentum on the liver's visceral surface connects the stomach and duodenum through hepatogastric and hepatoduodenal ligaments, respectively. The liver has, parietal and visceral surfaces; right, left, ventral, and dorsal borders; and left, right, caudate, and quadrate liver lobes that are not clearly separated, except for the caudate. The gallbladder has a dark green color and pear-shaped morphology, measures 16 ± 1.5 cm, and is located in a shallow cystic fossa. Consisting of the neck, forms an inverted funnel shape, body, and fundus. The diameters were 2 ± 0.3, 6 ± 1.2, and 4 ± 1.3 cm, respectively. The biliary tract consists of extrahepatic and intrahepatic ducts. The extrahepatic ducts have a left duct of 3 ± 0.5 cm and a right duct of 2 ± 0.25 cm. Converging to form a common hepatic duct 8 ± 0.5 cm. The cystic duct is 3± 0. cm, joins with the common hepatic duct ventrally. The intrahepatic ducts consisted of primary, secondary, tertiary, interlobular, intralobular, and intercalated ducts. The left hepatic duct received 9 ± 1 of dorsal primary ducts and 8 ± 2 ventral primary ducts. The right hepatic duct receives 4 ± 1 dorsal ducts and 2 ± 1 ventral ducts.

Application of Laennec extrathecal blockade combined with indocyanine green fluorescence imaging in laparoscopic anatomic hepatectomy.

To investigate the safety and application value of combining Laennec extracapsular occlusion with ICG fluorescence imaging in laparoscopic anatomic hepatectomy. Complete laparoscopic dissection was performed outside the Laennec sheath, blocking Glisson's pedicle of the corresponding liver segment or lobe. An appropriate amount of indocyanine green (ICG) dye was intravenously injected, and the boundary line between the pre-cut liver segment and liver lobe was identified using fluorescence laparoscopy. Complete resection of the liver segment or lobe was performed based on anatomical markers. Clinical data, including operation time, intraoperative blood loss, postoperative hospital stay, and postoperative complications, were collected. A total of 14 cases were included in the study, including seven cases of primary liver cancer, three cases of metastatic liver cancer, three cases of intrahepatic bile duct calculi, and one case of hepatic hemangioma. All 14 patients underwent anatomic hepatectomy under fluorescent laparoscopy, with four cases involving the right liver, seven cases involving the left liver, two cases involving the right anterior lobe, and one case involving the right posterior lobe. Combining laparoscopic follow-up of the Laennec membrane with Glisson outer sheath block and intraoperative ICG fluorescence imaging provides real-time guidance for locating the resection boundaries during anatomic hepatectomy. This approach helps in controlling intraoperative bleeding, reducing operation time, and ensuring high safety. It holds significant value in clinical application.

Safety and efficacy of novel oblique-viewing scope for B2-endoscopic ultrasound-guided hepaticogastrostomy.

Endoscopic ultrasound (EUS)-guided hepaticogastrostomy (EUS-HGS) performed at the intrahepatic bile duct segment 3 (B3) is widely used for biliary drainage. Although performing post-puncture procedures is easier in the intrahepatic bile duct segment 2 (B2) when using a conventional oblique-viewing (OV) EUS scope, this method may cause transesophageal puncture and severe adverse events. We evaluated the safety and efficacy of B2 puncture using a novel OV-EUS scope. In this single-center retrospective study, we prospectively enrolled and collected data from 45 patients who consecutively underwent EUS-HGS procedures with a novel OV-EUS scope between September 2021 and December 2022 at our cancer center. The technical success rates of B2-EUS-HGS and EUS-HGS were 93.3% (42/45) and 97.8% (44/45), respectively. The early adverse event rate was 8.9% (4/45) with no cases of scope changes or transesophageal punctures. The median procedure time was 13 minutes (range, 5-30). B2-EUS-HGS can be performed safely with the novel EG-740UT (Fujifilm) OV-scope without transesophageal puncture and with a high success rate. B2-EUS-HGS using this novel OV scope may be the preferred strategy for EUS-HGS.

CHARACTERISTICS OF INTRAHEPATIC BILE DUCT IN HUMANS AND MAMMALS WITH DIFFERENT TYPES OF NUTRITION

Bile acids are the main component of the content of the bile ducts and ensure the rate of water entry into the bile ducts, and therefore the rate of primary bile formation. Regulation of the fl ow of bile acids into the ducts through the appropriate transport systems is responsible for the intensity of bile secretion. These regulators are mainly bile acids themselves, which can modulate the function of bile acid transporters by two main mechanisms. Acute changes in the functional activity of membrane bile acid transporters occur mainly through post-transcriptional mechanisms, while chronic adaptive responses are realized by regulating their transcription.The aim of the study was to investigate the structural organization of intrahepatic bile ducts in humans and mammals in relation to the type of diet.Material and methods. The studies were conducted on the livers of a pig, a fox, a sheep, which were selected from the same breed, aged 1 year, and humans aged 50-60 years. The walls of intrahepatic bile ducts were studied. Paraffi n blocks were made according to the generally accepted method. Hematoxylin- eosin staining was used. Microphotography was performed with a Micromed XS-5510 microscope using a DCM 900 microphotomount. Processing of the obtained photos was performed using the TSView program. Processing of the obtained morphometric parameters was carried out according to the generally accepted rules of variation statistics. Using Microsoft Excel 2019 software based on the Windows 10 cooperative system. The results are presented as the mean value of the trait (M) and standard deviation (SD) for each sample or as a percentage increase compared to the control. The nonparametric Mann- Whitney test was used to determine the statistical signifi cance of intergroup diff erences, which was considered statistically signifi cant at P<0.05.Results. In the study of histological specimens, we found that the mucous membrane of the intrahepatic bile ducts diff ers depending on the type of meal. The results showed that mammals with a carnivorous and herbivorous meal had a more complex structure of the inner lining of the bile ducts compared to omnivorous mammals and humans. Thus, the revealed structural diff erences in the bile ducts of humans and mammals, in our opinion, indicate an adaptive restructuring and functioning of epithelial cells, which were caused by species- specifi c features of the diet.

Association of Cystic Dilatation of the Common Bile Duct and Intestinal Volvulus in Children

Cystic dilation of the common bile duct is a congenital condition defined by a communicative dilation of the extrahepatic bile duct, whether associated with or without dilation of the intrahepatic bile duct. Intestinal malrotation, on the other hand, refers to a failure of rotation and fixation of the primitive intestinal loop during embryonic life. The association of cystic dilation of the common bile duct with intestinal volvulus is a very rare occurrence, posing a significant diagnostic and therapeutic challenge. Here, we present a case of an 8-year-old girl admitted for the management of cystic dilation of the common bile duct associated with intestinal volvulus, which was surgically treated with a favorable outcome.

Abstract 1626: Clonal expansion in bile duct associated with chronic inflammation

Abstract Introduction: Chronic inflammation has been implicated in cancer development in many tissues and has recently been associated with promoted clonal expansion in non-cancer tissues. Primary sclerosing cholangitis (PSC) is a chronic progressive disease of unknown etiology affecting the bile ducts and has been associated with a substantially increased risk of cholangiocarcinoma. Clonal dynamics in the normal bile duct and PSC epithelium remains poorly understood because of the limited accessibility to normal/inflamed bile ducts. In this study, we established a method to detect somatic mutations accumulated in the bile duct epithelium and investigated a mutation rate in normal bile duct cells and clonal expansion in PSC epithelium. Methods: We established single cell-derived organoids from bile, which were subjected to whole genome sequencing to measure the age-related mutation rate in normal epithelial cell in the bile ducts. We next established organoids from multiple sites in perihilar bile ducts and collected epithelial samples from intrahepatic bile ducts obtained by laser-capture microdissection (LCM) from patients with PSC who underwent total hepatectomy for liver transplantation, for which we performed whole exome sequencing to investigate clonal expansion in PSC-involved bile ducts. Results: In total, 14 single cell-derived organoid lines were established from 2 patients with PSC and 3 control individuals. Based on the whole genome sequencing of those organoids, the number of mutations found in non-PSC bile duct epithelium increases with age at an annual mutation rate of 34.3 mutations per genome per year, which did not substantially differ from the rate in the PSC epithelium, suggesting that the inflammatory process in PSC hardly affected the mutations in PSC epithelium. To further investigate clonal expansion in the PSC epithelium, a total of 120 bulk organoid samples from perihilar bile ducts in 3 PSC patients and 111 LCM samples from intrahepatic bile ducts in 4 PSC patients were analyzed. In perihilar bile duct-derived organoids, we detected a median of 13 [1-30] somatic mutations per exome in samples derived from perihilar bile ducts and 20 [5-41] mutations per exome in those from intrahepatic LCM samples. Most mutations were detected in a single sample but some mutation clusters were shared by adjacent samples, which expanded in an area as large as 13 mm in length. Expanded clones harbored mutations in known cancer-driver genes, such as ARID1A and KRAS, which were enriched in segmental bile ducts, suggesting their role in the clonal expansion. Conclusions: Here, we established the method to detect somatic mutations accumulated in the normal/inflamed bile duct epithelium using an organoid-based analysis of clonal somatic mutations. Our results revealed clonal expansion existing in PSC epithelium and open up a way to the better understanding of carcinogenesis in the bile duct. Citation Format: Hirona Maeda, Nobuyuki Kakiuchi, Takashi Ito, Eri Ogawa, Masahiro Shiokawa, Norimitsu Uza, Hiroko Tanaka, Yasuhito Nannya, Hideki Makishima, Yuzo Kodama, Etsuro Hatano, Satoru Miyano, Seishi Ogawa. Clonal expansion in bile duct associated with chronic inflammation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1626.

Abstract 6884: Evaluating tumor-infiltrating immune cells helps predicting prognosis in biliary tract cancer

Abstract Background: The tumor microenvironment (TME) is composed of not only cancer cells but also an extracellular matrix and many types of non-cancerous cells, including fibroblasts and immune cells. In recent years, infiltrating immune cells in TME are known as a predictor of chemotherapy and immunotherapy effectiveness. The purpose of this study is to evaluate infiltrations of lymphocytes and macrophages in biliary tract cancers (BTCs). Methods: Clinical data and tissues were obtained from 130 patients who underwent surgical treatment for BTCs (intrahepatic, perihilar, and distal bile duct cancer, gallbladder cancer, and ampullary cancer) at our institution between 2001 and 2017.The immunohistochemical evaluation was performed to evaluate the number of CD8+ T cells, CD4+ T cells and FOXP3+ T cells and CD68+ Macrophages around the tumor cells. We defined Immunoscore based on the status of infiltrating immune cells. With CD8-high, CD4-high, and FOXP3-high TILs and CD68-low TAMs as one factor, the number of factors was counted in each case, and Immunoscore was assigned a score of 5 stages, from 0 to 4. It was high for the score of 3-4 and low for the score of 0-2. Also, to evaluate the correlation with TME and systemic inflammatory reaction, we examined blood inflammatory biomarker from peripheral blood samples. Results: A total of 59 cases had high Immunoscore and 71 cases had low Immunoscore. Patients with high Immunoscore showed significantly superior overall survival (OS) and recurrence free survival (RFS) than those with low Immunoscore (median OS 60.8 vs. 26.4 months, p = 0.001; median RFS not reached vs. 17.2 months, p < 0.001). For OS, low Immunoscore, positive lymph node metastasis, presence of distant metastasis, and high serum CA19-9 level were independent poor prognostic factors (hazards ratio 2.05, 3.48, 1.7, and 2.05; p = 0.01, p = 0.005, p = 0.05, and p = 0.01, respectively). For RFS, low Immunoscore, T classification of pT3-4, and presence of distant metastasis were independent poor prognostic factors with hazards ratio of 2.41 (p = 0.001), 2.16 (p = 0.005), and 3.58 (p = 0.005), respectively. Patients with high preoperative Neutrophil-to-lymphocyte ratio (NLR) had a significantly lower average number of CD8+ T cells as compared to patients with low NLR (p = 0.02). Preoperative NLR was associated with infiltrating CD8+ T cells in TME. Conclusions: High Immunoscore group had significantly longer OS and RFS and was an independent good prognostic factor. Also, infiltrating CD8+ T cells in TME correlated preoperative NLR. Our findings indicated that in biliary tract cancer, the evaluation of infiltrating immune cells in TME was useful to predict patient prognosis, and preoperative NLR may predict the tumor infiltrating CD8+ T cells. Citation Format: Kousuke Hatta, Ryota Tanaka, Kenjiro Kimura, Shinpei Eguchi, Go Ohira, Hiroji Shinkawa, Kohei Nishio, Masahiko Kinoshita, Shigeaki Kurihara, Shuhei Kushiyama, Takahito Kawaguchi, Naoki Tani, Koichi Nakanishi, Mizuki Yoshida, Takeaki Ishizawa. Evaluating tumor-infiltrating immune cells helps predicting prognosis in biliary tract cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6884.

An operative case of gastric cancer with ectopic bile duct drainage in the lesser curvature of the stomach

BackgroundAmong the various anomalies of the biliary system, a double common bile duct with ectopic drainage in the stomach is rare. Furthermore, ectopic bile ducts are extremely rare in gastric cancers.Case presentationA 67-year-old man was admitted to our hospital with gastric cancer and ectopic left extrahepatic bile duct drainage in the stomach. Pre-operative testing revealed no communication between the intrahepatic bile ducts. Distal gastrectomy and bile duct jejunostomy were performed. The post-operative course was uneventful, and the patient did not exhibit recurrence for 39 mo.ConclusionsAlthough it is uncertain whether sustained bile exposure from an ectopic bile duct is related to gastric cancer, short-term follow-up might be necessary because of the possibility of gastric cancer.

Clinical observation of the patient with monolobar form Caroli disease

Objective. To demonstrate a case of a rare congenital liver disease, Caroli disease, characterized by segmental non-obstructive fibrocystic dilatation of the intrahepatic bile ducts. Main points. Caroli disease was first described by the French doctor Jacques Caroli in 1958. There are 2 types of Caroli disease: True type with dilation of the intrahepatic bile ducts, usually affecting one segment and with a tendency to form stones and develop cholangitis. The second type, which is combined with congenital hepatic fibrosis, polycystic kidney disease and is more common than the true type. When the disease is accompanied by CHF, it is called Caroli syndrome or Grumbach disease. It is important to remember about Crowley’s disease and include it in the differential range of diseases of the biliary tract and liver, such as cholangitis, secondary biliary cirrhosis, portal hypertension of unknown etiology, cholangiocarcinoma. Conclusion.The diagnosis of Caroli disease and Caroli syndrome is made using imaging studies. Treatment is largely supportive and should be individualized, with prognosis depending on the severity of the disease and the presence of concomitant renal dysfunction.

Transjugular Liver Biopsy: The Key to a Rare Etiology of Cholestatic Hepatitis after Bone Marrow Transplantation

Introduction: Hematopoietic stem cell transplantation (HSCT) is associated with multiple complications, such as sinusoidal obstruction syndrome (SOS) (hepatomegaly, ascites, jaundice, and thrombocytopenia) and graft-versus-host disease (GVHD) (with the skin, gastrointestinal tract, and liver being the main targets). These entities may present overlapping clinical findings, being considered differential diagnoses, but their coexistence is rare. Case Presentation: A 29-year-old male with acute myeloid leukemia underwent HSCT. On day (D)+20, he developed hyperbilirubinemia, pleural effusion, ascites, and painful hepatomegaly. Abdominal ultrasound was suggestive of SOS, and defibrotide was initiated. On D+44, acute cutaneous, intestinal, and hepatic GVHD developed which improved after treatment with methylprednisolone. On D+132, there was worsening cholestasis and abdominal pain. MRCP revealed strictures in several segments of the intrahepatic bile ducts and irregularity of the main bile duct. Due to aggravation of liver enzyme changes and clinical worsening, he was admitted to the Intensive Care Unit. Due to persistence of severe hyperbilirubinemia (30 mg/dL) and thrombocytopenia (30,000 cell/uL), he underwent a hepatic hemodynamic study which revealed a hepatic venous pressure gradient of 10 mm Hg. The transjugular liver biopsy revealed canalicular hepatic cholestasis, bile duct injury, and focal hepatocellular necrosis suggestive of GVHD as well as injury to centrilobular veins and centrilobular necrosis compatible with possible SOS. Mycophenolate mofetil was started, but on D+195, the patient died of septic shock. Discussion/Conclusion: This case is notable for its complexity and for demonstrating the rare coexistence of histological features of SOS and GVHD. Although the clinical and laboratory findings may be sufficient for the diagnosis, it is important to highlight the importance of liver hemodynamic study and transjugular liver biopsy in these patients who often have severe thrombocytopenia, for the characterization and histological confirmation of cholestatic hepatitis, especially when the etiology may be multifactorial.

The Trend of Years of Life Lost due to Gastrointestinal Cancers in Fars (Iran) 2004-2019.

Gastrointestinal cancers can cause major health problems globally since their burden is increasing in many countries. We aimed to investigate the trend of years of life lost due to gastrointestinal cancers in Fars Province, southern Iran during the 2004-2019. In this cross-sectional survey study, we obtained the information regarding all deaths due to gastrointestinal cancers in Fars Province from the electronic population-based death registration system (EDRS). Years of Life Lost (YLL) was calculated using the YLL template of 2015 by the WHO. To examine the trend for different years, join point regression based on the log-linear model was used. Joinpoint regression analysis describes changing trends over successive periods of time and the increasing or decreasing rate within each period. During the years of 2004-2019, 9742 deaths due to gastrointestinal cancers occurred in Fars Province. 6013 (61.72%) cases were male and 3729 (38.28%) cases were female (Male / Female Sex Ratio: 1.61). Overall, 4152 cases (42.63%) were due to gastric cancer and 2112 cases (21.68%) were due to liver cancer. Total years of life lost due to premature death from gastrointestinal cancers during the 16-year study period was 73565 yr (2.33 per 1000 persons) in men, 52766 yr (1.71 per 1000 persons) in women, and 126331 yr (2.02 per 1000 persons) in both sexes. Among all cancers, the highest mortality rates in both sexes belong to gastric cancer. This study showed the trend of YLL rate of malignant neoplasms of liver and intrahepatic bile ducts, esophagus, oral cavity, and colon cancer were increasing in both sexes, however, the trend of YLL rate for malignant neoplasms of the small intestine was decreasing in both sexes. Variation of GI cancers patterns and trends around the Fars Province indicated that a more comprehensive control plan is needed to control these variations.

Mimicking Motor Proteins: Wall-Guided Self-Navigation of Microwheels.

Untethered micro/nanorobots (MNRs) show great promise in biomedicine. However, high-precision targeted in vivo navigation of MNRs into both deep and tiny microtube networks comes with big challenges because the present medical imaging cannot simultaneously meet the requirements of high resolution, high penetration depth, and high real-time performance. Inspired by intracellular motor proteins that transport cargo along cytoskeletal tracks, this study proposed a microtube inwall-guided targeted self-navigation strategy of magnetic microwheels (μ-wheels) that relies only on interactions with a microtube inwall, compared to conventional techniques that rely on real-time imaging and tracking of MNRs. By presetting the direction of the rotating magnetic field, the μ-wheel realized targeted navigation along the inwall. The propulsion principles behind it are elaborated. The targeted self-navigation of the μ-wheels in three-dimensional microtube networks, a spiral microtube, and an intrahepatic bile duct of a pig was conducted. Lastly, based on the strategy, a practical tumor early detection method was proposed and verified by means of magnetic resonance imaging. The microtube inwall-guided targeted self-navigation strategy reduces the dependence of in vivo targeted navigation of MNRs on the real-time performance of medical imaging technology and greatly contributes to the development of MNRs in biomedical applications.

Van Gogh-like 2 is essential for the architectural patterning of the mammalian biliary tree

In the developing liver, bipotent epithelial progenitor cells undergo lineage segregation to form hepatocytes, which constitute the bulk of the liver parenchyma, and biliary epithelial cells (cholangiocytes), which comprise the bile duct (a complex tubular network that is critical for normal liver function). Notch and TGFβ signalling promote the formation of a sheet of biliary epithelial cells, the ductal plate, that organises into discontinuous tubular structures. How these structures elongate and connect to form a continuous duct remains undefined. We aimed to define the mechanisms by which the ductal plate transitions from a simple sheet of epithelial cells into a complex and connected bile duct. By combining single-cell RNA sequencing of embryonic mouse livers with genetic tools and organoid models we functionally dissected the role of planar cell polarity in duct patterning. We show that the planar cell polarity protein VANGL2 is expressed late in intrahepatic bile duct development and patterns the formation of cell-cell contacts between biliary cells. The patterning of these cell contacts regulates the normal polarisation of the actin cytoskeleton within biliary cells and loss of Vangl2 function results in the abnormal distribution of cortical actin remodelling, leading to the failure of bile duct formation. Planar cell polarity is a critical step in the post-specification sculpture of the bile duct and is essential for establishing normal tissue architecture. Like other branched tissues, such as the lung and kidney, the bile ducts use planar cell polarity signalling to coordinate cell movements; however, how these biochemical signals are linked to ductular patterning remains unclear. Here we show that the core planar cell polarity protein VANGL2 patterns how cell-cell contacts form in the mammalian bile duct and how ductular cells transmit confluent mechanical changes along the length of a duct. This work sheds light on how biological tubes are patterned across mammalian tissues (including within the liver) and will be important in how we promote ductular growth in patients where the duct is mis-patterned or poorly formed.

Aggressive Pediatric Adrenal Cortical Carcinoma With a Novel Translocation t(20;22) and intergenic fusion of MN1 and ZNF341: A Case Report and Literature Review

Caroli disease involves several different entities in contrast to Caroli syndrome. We herein report two cases of congenital localized dilatation of the intrahepatic bile ducts exhibiting a unique morphology distinct from other types of Caroli disease. Specifically, the dilatation was limited to the second- and third-order intrahepatic bile ducts, and the dilated bile ducts abruptly connected to normal-sized ducts on both the upstream and downstream sides. Both cases are prenatally diagnosed and have been asymptomatic for nearly a decade. Nine other cases were identified in the English and Japanese literature, suggesting that this is a specific subtype of Caroli disease.

Hereditary hemorrhagic telangiectasia with hepatic arteriovenous shunt diagnosed due to liver damage

A 53-year-old woman was diagnosed with liver dysfunction in August 20XX. Computed tomography (CT) revealed multiple hepatic AV shunts, and she was placed under observation. In March 20XX + 3, she developed back pain, and CT performed during an emergency hospital visit showed evidence of intrahepatic bile duct dilatation. She was referred to our gastroenterology department in May 20XX + 3. We conducted investigations on suspicion of hereditary hemorrhagic telangiectasia (HHT) with hepatic AV shunting based on contrast-enhanced CT performed at another hospital. HHT is generally discovered due to epistaxis, but there are also cases where it is diagnosed during examination of liver damage.

Intrahepatic cholangiocarcinoma: Evolving strategies in management and treatment.

Intrahepatic cholangiocarcinoma is the second most frequent primary liver cancer after hepatocellular carcinoma. According to International Classification of Diseases-11 (ICD-11), intrahepatic cholangiocarcinoma is identified by a specific diagnostic code, different with respect to perihilar-CCA or distal-CCA. Intrahepatic cholangiocarcinoma originates from intrahepatic small or large bile ducts including the second-order bile ducts and has a silent presentation that combined with the highly aggressive nature and refractoriness to chemotherapy contributes to the alarming increasing incidence and mortality. Indeed, at the moment of the diagnosis, less than 40% of intrahepatic cholangiocarcinoma are suitable of curative surgical therapy, that is so far the only effective treatment. The main goals of clinicians and researchers are to make an early diagnosis, and to carry out molecular characterization to provide the patient with personalized treatment. Unfortunately, these goals are not easily achievable because of the heterogeneity of this tumor from anatomical, molecular, biological, and clinical perspectives. However, recent progress has been made in molecular characterization, surgical treatment, and management of intrahepatic cholangiocarcinoma and, this article deals with these advances.

Design of an improved percutaneous transhepatic cholangio drainage tube based on MRCP imaging data

Objective: Quantified MRCP imaging data was used as a reference for design and preparation of a modified percutaneous transhepatic cholangio drainage (PTCD) tube. Methods: 3.0 T upper abdominal MR and MRCP imaging data of 2 300 patients treated from July 2015 to July 2020 at the Department of Radiology of the Affiliated Cancer Hospital of Zhengzhou University were screened and a total of 381 patients diagnosed with biliary duct structures were identified. Causative etiologies among these patients included pancreatic adenocarcinoma (pancreatic head), cholangiocarcinoma, ampullary carcinoma, as well as intrahepatic and/or extrahepatic bile duct dilation. An improved PTCD tube was designed based on MRCP quantification of left and right hepatic and common hepatic duct length. Results: In the setting of biliary obstruction caused by malignancy, the distance of the left hepatic duct from its origin to the point of left and right hepatic duct confluence was 15.9±3.8 mm, while the distance of the right hepatic duct from its origin to the point of left and right hepatic duct confluence was 12.4±3.2 mm; the length of the bile duct from its origin to the point of left and right hepatic duct confluence was 34.0±8.1 mm. The improved PTCD tube design incorporated an altered length of the drainage orifice. Conclusion: MRCP imaging of the biliary tract is effective for measuring biliary tract length in the setting of pathological dilation. Based on our biliary tract measurements, a modified PTCD tube was designed to more effectively meet drainage requirements and manage biliary obstruction caused by Bismuth-Corlette type Ⅱ and Ⅲ malignancies.