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14 pages, 522 KB  
Hypothesis
Lymphoplasmacytic Gastritis in Cheetahs Under Human Care: A Bile Acid-Driven Gastroenteropathy Arising from Disrupted Feeding Ecology
by Adrian S. W. Tordiffe
Animals 2026, 16(10), 1494; https://doi.org/10.3390/ani16101494 - 13 May 2026
Viewed by 904
Abstract
Lymphoplasmacytic gastritis (LPG) is one of the most prevalent chronic diseases affecting cheetahs (Acinonyx jubatus) under human care, yet its underlying cause remains unresolved. Gastric inflammation occurs in the majority of adult captive cheetahs but is uncommon in free-ranging populations, suggesting [...] Read more.
Lymphoplasmacytic gastritis (LPG) is one of the most prevalent chronic diseases affecting cheetahs (Acinonyx jubatus) under human care, yet its underlying cause remains unresolved. Gastric inflammation occurs in the majority of adult captive cheetahs but is uncommon in free-ranging populations, suggesting that management-related factors contribute to disease pathogenesis. This review proposes that LPG represents a bile acid-driven gastroenteropathy arising from disruption of the natural feeding ecology of the cheetah. In free-ranging systems, cheetahs consume large episodic meals separated by prolonged fasting intervals and ingest whole-prey containing substantial connective tissue and collagen. In captivity, feeding patterns are typically characterized by smaller, more frequent meals and diets dominated by lean skeletal muscle with reduced structural complexity. I hypothesize that this mismatch alters gastric emptying kinetics, disrupts coordinated pancreatic and biliary secretion, and destabilizes fat digestion. Inefficient lipolysis may impair micelle formation and promote bile acid mislocalization within the gastrointestinal tract, increasing mucosal exposure to hydrophobic bile acids capable of inducing chemical epithelial injury. Within this framework, lymphoplasmacytic gastritis is interpreted as a secondary inflammatory reaction to chronic bile acid-mediated mucosal stress rather than a primary immune-mediated disorder. The model also provides a mechanistic explanation for the frequent coexistence of gastritis with fat and protein maldigestion in captive cheetahs. Differential responses to antimicrobial therapy, glucocorticoids, sulfasalazine, pancreatic enzyme supplementation, and bile acid-modifying agents are broadly consistent with this proposed mechanism. Recognition of LPG as a physiologically driven gastroenteropathy has important implications for management, emphasizing restoration of feast–fast feeding patterns, inclusion of collagen-rich carcass components, and targeted modulation of bile acid composition and signaling. Full article
(This article belongs to the Section Zoo Animals)
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14 pages, 219 KB  
Article
The Role of Modern Radiological Procedures in Diagnosing Blunt Liver Injuries Manifested by Upper Gastrointestinal Bleeding
by Piotr Tomasz Arkuszewski, Maciej Adam Rybicki, Bartłomiej Białas and Konrad Szymczyk
J. Clin. Med. 2025, 14(1), 175; https://doi.org/10.3390/jcm14010175 - 31 Dec 2024
Cited by 1 | Viewed by 2206
Abstract
Objectives: Posttraumatic upper gastrointestinal bleeding (UGIB) is a very rare consequence of blunt liver trauma. It can be quite a diagnostic challenge for clinicians, as it can clinically manifest many weeks after the trauma or be scantily symptomatic. Methods: The following article would [...] Read more.
Objectives: Posttraumatic upper gastrointestinal bleeding (UGIB) is a very rare consequence of blunt liver trauma. It can be quite a diagnostic challenge for clinicians, as it can clinically manifest many weeks after the trauma or be scantily symptomatic. Methods: The following article would like to provide an analysis of clinical cases of 13 patients following blunt liver injuries, the main symptoms of which was bleeding into the gastrointestinal tract through the biliary tree. The article is research of the published literature concentrating on the influence of modern diagnostic methods (scintigraphy, USG and CT) on the diagnosis and long-term survival of patients with haemobilia caused by blunt liver trauma. In each patient, the condition was presented with UGIB symptoms following blunt trauma, before initiation of operative treatment or before death. The cases were divided into 2 groups: prior to and after introduction of modern diagnostic procedures, and then compared together. Results: The study indicates that liver damage can cause symptoms of UGIB, even after minor abdominal trauma and with delayed and uncharacteristic symptoms. Conclusions: Modern diagnostic methods, such as ultrasound, scintigraphy and CT, make it easier to identify these injuries and choose appropriate treatment, reducing the risk of death. Full article
(This article belongs to the Special Issue Advances in Trauma Treatment)
7 pages, 1098 KB  
Case Report
Biodegradable Stents: A Breakthrough in the Management of Complex Biliary Tract Injuries: A Case Report
by Ottavia Cicerone, Giulio Di Gioia, Maria Pajola, Anna Gallotti, Antonio Mauro D’Agostino, Nicola Cionfoli, Riccardo Corti, Pietro Quaretti and Marcello Maestri
Reports 2024, 7(4), 95; https://doi.org/10.3390/reports7040095 - 9 Nov 2024
Cited by 1 | Viewed by 2704
Abstract
Background and Clinical Significance: Biliary tract injuries are a recognized complication of laparoscopic cholecystectomy. Early diagnosis and prompt management are crucial to minimize complications such as bile leaks, strictures, and fistula formation. This case report highlights the use of a biodegradable biliary [...] Read more.
Background and Clinical Significance: Biliary tract injuries are a recognized complication of laparoscopic cholecystectomy. Early diagnosis and prompt management are crucial to minimize complications such as bile leaks, strictures, and fistula formation. This case report highlights the use of a biodegradable biliary stent in managing a complex biliary injury and discusses the impact of delayed diagnosis on treatment outcomes. Case Presentation: We present the case of a 30-year-old male who sustained a Strasberg E2 biliary tract injury during a laparoscopic cholecystectomy. Initially misdiagnosed, the injury was only recognized on the fourth postoperative day. The patient underwent a Roux-en-Y hepaticojejunostomy and subsequently developed a postoperative biliary fistula, which was managed with percutaneous drainage. A biodegradable biliary stent was later placed to address a stricture and minimize the need for future interventions. One year later, the patient presented with symptoms of cholangitis, and radiological findings revealed a narrowing of the biliary lumen. The stricture was resolved and an endoscopic gastrojejunal shunt was placed to prevent further complications. The patient is currently in good condition with no signs of further complications. Conclusions: This case emphasizes the importance of early diagnosis in managing biliary tract injuries and highlights the potential of biodegradable stents to reduce the need for repeat interventions. Despite a delayed diagnosis necessitating complex surgical procedures, the use of a biodegradable stent proved effective in managing postoperative complications. Further studies are needed to evaluate the long-term efficacy of biodegradable stents in similar clinical scenarios. Full article
(This article belongs to the Section Surgery)
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11 pages, 273 KB  
Study Protocol
Outcomes and Predictors of 30-Day Readmission in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization between 2016 and 2018
by Ifrah Fatima, Mohamed Ahmed, Wael T. Mohamed, Vinay Jahagirdar, Kevin F. Kennedy and Alisa Likhitsup
Gastroenterol. Insights 2024, 15(1), 87-97; https://doi.org/10.3390/gastroent15010006 - 22 Jan 2024
Viewed by 2448
Abstract
Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The 5-year survival rate for liver cancer in the US has improved from 3% four decades ago to 20% now. Transarterial chemoembolization (TACE) is the treatment of choice for stage [...] Read more.
Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The 5-year survival rate for liver cancer in the US has improved from 3% four decades ago to 20% now. Transarterial chemoembolization (TACE) is the treatment of choice for stage B/intermediate-stage HCC. Complications of TACE include hepatic encephalopathy, liver failure, post-embolization syndrome, duodenal ulcers, liver abscesses, acute cholecystitis, and injury to the biliary tract. This study evaluates the 30-day readmission rate and predictors of readmission among patients with HCC undergoing TACE. Methods: The 2016–2018 Healthcare Cost and Utilization Project (HCUP) database, which includes the National Readmission Database (NRD), was used. All adult patients with HCC who underwent TACE were identified using the International Classification of Diseases (ICD-10). The rate of 30-day readmissions after TACE and the associated diagnoses were identified. Logistic regression was used to obtain adjusted odds ratios for variables associated with 30-day readmission. Results: A total of 566 patients underwent TACE between 2016–2018. Sixty-five patients were excluded due to death and unavailability of 30-day readmission data. The procedure was performed in large (80.4%), metro-teaching hospitals (94.5%). Mean patient age was 65.1 ± 9.9 years, and 74% of patients were male. Among the 501 patients, 81 (16.2%) were readmitted within 30 days. The mean age for readmitted patients was 63.2 ± 11.0 and 69.1% were male. The mean length of stay at readmission was 5.5 ± 7.3 days. A total of 7.4% of patients had neurological disorders, 17.3% had weight loss, 30.9% had fluid and electrolyte imbalance, and 21.0% had hepatic encephalopathy. The most common primary diagnoses at 30-day readmission were liver cell carcinoma, sepsis, and liver failure. Univariate analysis for variables associated with 30-day readmission included hepatic encephalopathy (OR 3.45; 95% CI 1.8–6.62; p = 0.0002), underlying neurological disorders (OR 3.28; 95% CI 1.16–9.3; p = 0.03), weight loss (OR 2.82; 95% CI 1.42–5.61; p = 0.003), and Medicaid status (OR 1.74; 95% CI 1.05–2.88; p = 0.03). Multivariable analysis showed hepatic encephalopathy (OR 2.91; 95% CI 1.4, 6.04; p = 0.04) and weight loss (OR 2.37; 95% CI 1.13–4.96; p = 0.02) were associated with hospital readmission. Conclusions: Weight loss and hepatic encephalopathy were predictors for 30-day readmission after a TACE procedure for HCC. Full article
(This article belongs to the Section Liver)
12 pages, 2833 KB  
Case Report
Hepatico-Duodenal Fistula Following Iatrogenic Strasberg Type E4 Bile Duct Injury: A Case Report
by Bozhidar Hristov, Daniel Doykov, Desislav Stanchev, Krasimir Kraev, Petar Uchikov, Gancho Kostov, Siyana Valova, Eduard Tilkiyan, Katya Doykova and Mladen Doykov
Medicina 2023, 59(9), 1621; https://doi.org/10.3390/medicina59091621 - 7 Sep 2023
Cited by 4 | Viewed by 3232
Abstract
Introduction: Gallstone disease (GSD) is among the most common disorders worldwide. Gallstones are established in up to 15% of the general population. Laparoscopic cholecystectomy (LC) has become the “gold standard” for treatment of GSD but is associated with a higher rate of certain [...] Read more.
Introduction: Gallstone disease (GSD) is among the most common disorders worldwide. Gallstones are established in up to 15% of the general population. Laparoscopic cholecystectomy (LC) has become the “gold standard” for treatment of GSD but is associated with a higher rate of certain complications, namely, bile duct injury (BDI). Biliary fistulas (BF) are a common presentation of BDI (44.1% of all patients); however, they are mainly external. Post-cholecystectomy internal BF are exceedingly rare. Case report: a 33-year Caucasian female was admitted with suspected BDI after LC. Strasberg type E4 BDI was established on endoscopic retrograde cholangiopancreatography (ERCP). Urgent laparotomy established biliary peritonitis. Delayed surgical reconstruction was planned and temporary external biliary drains were positioned in the right and left hepatic ducts. During follow-up, displacement of the drains occurred with subsequent evacuation of bile through the external fistula, which resolved spontaneously, without clinical and biochemical evidence of biliary obstruction or cholangitis. ERCP established bilio-duodenal fistula between the left hepatic duct (LHD) and duodenum, with a stricture at the level of the LHD. Endoscopic management was chosen with staged dilation and stenting of the fistulous tract over 18 months until fistula maturation and stricture resolution. One year after stent extraction, the patient remains symptom free. Discussion: Management of post-cholecystectomy BDI is challenging. The optimal approach is determined by the level and extent of ductal lesion defined according to different classifications (Strasberg, Bismuth, Hannover). Type E BDI are managed mainly surgically with a delayed surgical approach generally deemed preferable. Only three cases of choledocho-duodenal fistulas following LC BDI currently exist in the literature. Management is controversial, with expectant approach, surgical treatment (biliary reconstruction), or liver transplantation being described. Endoscopic treatment has not been described; however, in the current paper, it proved to be successful. More reports or larger case series are needed to confirm its applicability and effectiveness, especially in the long term. Full article
(This article belongs to the Special Issue Advances in Cholecystitis and Cholecystectomy)
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22 pages, 1336 KB  
Review
The Role of the Gastrointestinal Microbiome in Liver Disease
by Nicholas Shalaby, Dorit Samocha-Bonet, Nadeem O. Kaakoush and Mark Danta
Pathogens 2023, 12(9), 1087; https://doi.org/10.3390/pathogens12091087 - 27 Aug 2023
Cited by 11 | Viewed by 3987
Abstract
Liver disease is a major global health problem leading to approximately two million deaths a year. This is the consequence of a number of aetiologies, including alcohol-related, metabolic-related, viral infection, cholestatic and immune disease, leading to fibrosis and, eventually, cirrhosis. No specific registered [...] Read more.
Liver disease is a major global health problem leading to approximately two million deaths a year. This is the consequence of a number of aetiologies, including alcohol-related, metabolic-related, viral infection, cholestatic and immune disease, leading to fibrosis and, eventually, cirrhosis. No specific registered antifibrotic therapies exist to reverse liver injury, so current treatment aims at managing the underlying factors to mitigate the development of liver disease. There are bidirectional feedback loops between the liver and the rest of the gastrointestinal tract via the portal venous and biliary systems, which are mediated by microbial metabolites, specifically short-chain fatty acids (SCFAs) and secondary bile acids. The interaction between the liver and the gastrointestinal microbiome has the potential to provide a novel therapeutic modality to mitigate the progression of liver disease and its complications. This review will outline our understanding of hepatic fibrosis, liver disease, and its connection to the microbiome, which may identify potential therapeutic targets or strategies to mitigate liver disease. Full article
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14 pages, 1239 KB  
Article
Usefulness of Endoscopic Retrograde Cholangiopancreatography in the Diagnosis and Treatment of Traumatic Pancreatic Injury in Children
by Seong Chan Gong, Sanghyun An, In Sik Shin and Pil Young Jung
Diagnostics 2023, 13(12), 2044; https://doi.org/10.3390/diagnostics13122044 - 13 Jun 2023
Cited by 10 | Viewed by 2701
Abstract
Pediatric trauma patients are increasing, and trauma is the leading cause of death in children. Pancreatic injury is known as the fourth most common solid organ injury, but the diagnosis of pancreatic injury is often delayed due to the retroperitoneal location of the [...] Read more.
Pediatric trauma patients are increasing, and trauma is the leading cause of death in children. Pancreatic injury is known as the fourth most common solid organ injury, but the diagnosis of pancreatic injury is often delayed due to the retroperitoneal location of the pancreas and the low sensitivity and specificity of diagnostic tests. Endoscopic retrograde cholangiopancreatography (ERCP) is an important test for the diagnosis and treatment of various biliary tract and pancreatic diseases. However, cases of performing ERCP in traumatic pancreatic injury in children have been rarely reported. Thus, we aimed to evaluate the usefulness of ERCP in traumatic pancreatic injury in children. Between January 1983 and December 2022, pediatric patients under the age of 18 who were treated for traumatic pancreatic injury at a single institution were recruited and retrospectively analyzed. Patient characteristics and clinical outcomes were assessed. Thirty-one patients were enrolled in this study. Among them, 15 (48.4%) patients underwent ERCP. The time to diet was significantly longer in the ERCP group. There were no statistically significant differences in other characteristics between the ERCP and the non-ERCP group. In nine (60%) patients of the ERCP group, ERCP was used for therapeutic intervention or as a decision-making tool for surgery, and was used to resolve pancreas-related complications. ERCP may be useful for the diagnosis and treatment of traumatic pancreatic injury in children. In addition, ERCP can be safely applied in children, and complications related to ERCP also may not increase. When obscure pancreatic injury is suspected, it is necessary to consider performing ERCP. Full article
(This article belongs to the Special Issue Diagnosis and Management of Traumatic Injury)
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12 pages, 599 KB  
Article
Educational Scoring System in Laparoscopic Cholecystectomy: Is It the Right Time to Standardize?
by Elisa Reitano, Simone Famularo, Bernard Dallemagne, Kohei Mishima, Silvana Perretta, Pietro Riva, Pietro Addeo, Horacio J. Asbun, Claudius Conrad, Nicolas Demartines, David Fuks, Mariano Gimenez, Melissa E. Hogg, Charles Chung-Wei Lin, Jacques Marescaux, John B. Martinie, Riccardo Memeo, Olivier Soubrane, Michel Vix, Xiaoying Wang and Didier Mutteradd Show full author list remove Hide full author list
Medicina 2023, 59(3), 446; https://doi.org/10.3390/medicina59030446 - 23 Feb 2023
Cited by 1 | Viewed by 4287
Abstract
Background and Objectives: Laparoscopic cholecystectomy (LC) is one of the most performed surgeries worldwide. Procedure difficulty and patient outcomes depend on several factors which are not considered in the current literature, including the learning curve, generating confusing and subjective results. This study [...] Read more.
Background and Objectives: Laparoscopic cholecystectomy (LC) is one of the most performed surgeries worldwide. Procedure difficulty and patient outcomes depend on several factors which are not considered in the current literature, including the learning curve, generating confusing and subjective results. This study aims to create a scoring system to calculate the learning curve of LC based on hepatobiliopancreatic (HPB) experts’ opinions during an educational course. Materials and Methods: A questionnaire was submitted to the panel of experts attending the HPB course at Research Institute against Digestive Cancer-IRCAD (Strasbourg, France) from 27–29 October 2022. Experts scored the proposed variables according to their degree of importance in the learning curve using a Likert scale from 1 (not useful) to 5 (very useful). Variables were included in the composite scoring system only if more than 75% of experts ranked its relevance in the learning curve assessment ≥4. A positive or negative value was assigned to each variable based on its effect on the learning curve. Results: Fifteen experts from six different countries attended the IRCAD HPB course and filled out the questionnaire. Ten variables were finally included in the learning curve scoring system (i.e., patient body weight/BMI, patient previous open surgery, emergency setting, increased inflammatory levels, presence of anatomical bile duct variation(s), and appropriate critical view of safety (CVS) identification), which were all assigned positive values. Minor or major intraoperative injuries to the biliary tract, development of postoperative complications related to biliary injuries, and mortality were assigned negative values. Conclusions: This is the first scoring system on the learning curve of LC based on variables selected through the experts’ opinions. Although the score needs to be validated through future studies, it could be a useful tool to assess its efficacy within educational programs and surgical courses. Full article
(This article belongs to the Section Surgery)
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24 pages, 1110 KB  
Review
Regulation of Carcinogenesis by Sensory Neurons and Neuromediators
by Nuray Erin, Galina V. Shurin, James H. Baraldi and Michael R. Shurin
Cancers 2022, 14(9), 2333; https://doi.org/10.3390/cancers14092333 - 9 May 2022
Cited by 37 | Viewed by 8157
Abstract
Interactions between the immune system and the nervous system are crucial in maintaining homeostasis, and disturbances of these neuro-immune interactions may participate in carcinogenesis and metastasis. Nerve endings have been identified within solid tumors in humans and experimental animals. Although the involvement of [...] Read more.
Interactions between the immune system and the nervous system are crucial in maintaining homeostasis, and disturbances of these neuro-immune interactions may participate in carcinogenesis and metastasis. Nerve endings have been identified within solid tumors in humans and experimental animals. Although the involvement of the efferent sympathetic and parasympathetic innervation in carcinogenesis has been extensively investigated, the role of the afferent sensory neurons and the neuropeptides in tumor development, growth, and progression is recently appreciated. Similarly, current findings point to the significant role of Schwann cells as part of neuro-immune interactions. Hence, in this review, we mainly focus on local and systemic effects of sensory nerve activity as well as Schwann cells in carcinogenesis and metastasis. Specific denervation of vagal sensory nerve fibers, or vagotomy, in animal models, has been reported to markedly increase lung metastases of breast carcinoma as well as pancreatic and gastric tumor growth, with the formation of liver metastases demonstrating the protective role of vagal sensory fibers against cancer. Clinical studies have revealed that patients with gastric ulcers who have undergone a vagotomy have a greater risk of stomach, colorectal, biliary tract, and lung cancers. Protective effects of vagal activity have also been documented by epidemiological studies demonstrating that high vagal activity predicts longer survival rates in patients with colon, non-small cell lung, prostate, and breast cancers. However, several studies have reported that inhibition of sensory neuronal activity reduces the development of solid tumors, including prostate, gastric, pancreatic, head and neck, cervical, ovarian, and skin cancers. These contradictory findings are likely to be due to the post-nerve injury-induced activation of systemic sensory fibers, the level of aggressiveness of the tumor model used, and the local heterogeneity of sensory fibers. As the aggressiveness of the tumor model and the level of the inflammatory response increase, the protective role of sensory nerve fibers is apparent and might be mostly due to systemic alterations in the neuro-immune response. Hence, more insights into inductive and permissive mechanisms, such as systemic, cellular neuro-immunological mechanisms of carcinogenesis and metastasis formation, are needed to understand the role of sensory neurons in tumor growth and spread. Full article
(This article belongs to the Special Issue The Tumor Neuroenvironment)
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11 pages, 631 KB  
Article
Liver Injury in Patients with COVID-19 without Underlying Liver Disease
by Monika Pazgan-Simon, Sylwia Serafińska, Michał Kukla, Marta Kucharska, Jolanta Zuwała-Jagiełło, Iwona Buczyńska, Kamila Zielińska and Krzysztof Simon
J. Clin. Med. 2022, 11(2), 308; https://doi.org/10.3390/jcm11020308 - 8 Jan 2022
Cited by 19 | Viewed by 3163
Abstract
SARS-CoV-2 shows a high affinity for the ACE-2 receptor, present on the epithelial cells of the upper and lower respiratory tract, within the intestine, kidneys, heart, testes, biliary epithelium, and—where it is particularly challenging—on vascular endothelial cells. Liver involvement is a rare manifestation [...] Read more.
SARS-CoV-2 shows a high affinity for the ACE-2 receptor, present on the epithelial cells of the upper and lower respiratory tract, within the intestine, kidneys, heart, testes, biliary epithelium, and—where it is particularly challenging—on vascular endothelial cells. Liver involvement is a rare manifestation of COVID-19. Material and Methods: We reviewed 450 patients admitted due to the fact of SARS-CoV-2 infection (COVID-19) including 88 with liver injury. Based on medical history and previous laboratory test results, we excluded cases of underlying liver disease. The analysis involved a clinical course of COVID-19 in patients without underlying liver disease as well as the type and course of liver injury. Results: Signs and symptoms of liver injury were present in 20% of patients, mostly presenting as a mixed-type pattern of injury with less common cases of standalone hepatocellular (parenchymal) or cholestatic injury. The liver injury symptoms resolved at the end of inpatient treatment in 20% of cases. Sixteen patients died with no cases where liver injury would be deemed a cause of death. Conclusions: (1) Liver injury secondary to COVID-19 was mild, and in in 20%, the signs and symptoms of liver injury resolved by the end of hospitalization. (2) It seems that liver injury in patients with COVID-19 was not associated with a higher risk of mortality. (3) The underlying mechanism of liver injury as well as its sequelae are not fully known. Therefore, caution and further monitoring are advised, especially in patients whose liver function tests have not returned to normal values. Full article
(This article belongs to the Section Gastroenterology & Hepatopancreatobiliary Medicine)
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18 pages, 1087 KB  
Review
Progress and Current Limitations of Materials for Artificial Bile Duct Engineering
by Qiqi Sun, Zefeng Shen, Xiao Liang, Yingxu He, Deling Kong, Adam C. Midgley and Kai Wang
Materials 2021, 14(23), 7468; https://doi.org/10.3390/ma14237468 - 6 Dec 2021
Cited by 23 | Viewed by 4971
Abstract
Bile duct injury (BDI) and bile tract diseases are regarded as prominent challenges in hepatobiliary surgery due to the risk of severe complications. Hepatobiliary, pancreatic, and gastrointestinal surgery can inadvertently cause iatrogenic BDI. The commonly utilized clinical treatment of BDI is biliary-enteric anastomosis. [...] Read more.
Bile duct injury (BDI) and bile tract diseases are regarded as prominent challenges in hepatobiliary surgery due to the risk of severe complications. Hepatobiliary, pancreatic, and gastrointestinal surgery can inadvertently cause iatrogenic BDI. The commonly utilized clinical treatment of BDI is biliary-enteric anastomosis. However, removal of the Oddi sphincter, which serves as a valve control over the unidirectional flow of bile to the intestine, can result in complications such as reflux cholangitis, restenosis of the bile duct, and cholangiocarcinoma. Tissue engineering and biomaterials offer alternative approaches for BDI treatment. Reconstruction of mechanically functional and biomimetic structures to replace bile ducts aims to promote the ingrowth of bile duct cells and realize tissue regeneration of bile ducts. Current research on artificial bile ducts has remained within preclinical animal model experiments. As more research shows artificial bile duct replacements achieving effective mechanical and functional prevention of biliary peritonitis caused by bile leakage or obstructive jaundice after bile duct reconstruction, clinical translation of tissue-engineered bile ducts has become a theoretical possibility. This literature review provides a comprehensive collection of published works in relation to three tissue engineering approaches for biomimetic bile duct construction: mechanical support from scaffold materials, cell seeding methods, and the incorporation of biologically active factors to identify the advancements and current limitations of materials and methods for the development of effective artificial bile ducts that promote tissue regeneration. Full article
(This article belongs to the Special Issue Biomimetic Composites and Design)
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30 pages, 3218 KB  
Review
Bile Acids and GPBAR-1: Dynamic Interaction Involving Genes, Environment and Gut Microbiome
by Piero Portincasa, Agostino Di Ciaula, Gabriella Garruti, Mirco Vacca, Maria De Angelis and David Q.-H. Wang
Nutrients 2020, 12(12), 3709; https://doi.org/10.3390/nu12123709 - 30 Nov 2020
Cited by 49 | Viewed by 8109
Abstract
Bile acids (BA) are amphiphilic molecules synthesized in the liver from cholesterol. BA undergo continuous enterohepatic recycling through intestinal biotransformation by gut microbiome and reabsorption into the portal tract for uptake by hepatocytes. BA are detergent molecules aiding the digestion and absorption of [...] Read more.
Bile acids (BA) are amphiphilic molecules synthesized in the liver from cholesterol. BA undergo continuous enterohepatic recycling through intestinal biotransformation by gut microbiome and reabsorption into the portal tract for uptake by hepatocytes. BA are detergent molecules aiding the digestion and absorption of dietary fat and fat-soluble vitamins, but also act as important signaling molecules via the nuclear receptor, farnesoid X receptor (FXR), and the membrane-associated G protein-coupled bile acid receptor 1 (GPBAR-1) in the distal intestine, liver and extra hepatic tissues. The hydrophilic-hydrophobic balance of the BA pool is finely regulated to prevent BA overload and liver injury. By contrast, hydrophilic BA can be hepatoprotective. The ultimate effects of BA-mediated activation of GPBAR-1 is poorly understood, but this receptor may play a role in protecting the remnant liver and in maintaining biliary homeostasis. In addition, GPBAR-1 acts on pathways involved in inflammation, biliary epithelial barrier permeability, BA pool hydrophobicity, and sinusoidal blood flow. Recent evidence suggests that environmental factors influence GPBAR-1 gene expression. Thus, targeting GPBAR-1 might improve liver protection, facilitating beneficial metabolic effects through primary prevention measures. Here, we discuss the complex pathways linked to BA effects, signaling properties of the GPBAR-1, mechanisms of liver damage, gene-environment interactions, and therapeutic aspects. Full article
(This article belongs to the Special Issue Nutrition and Dietary Intake for Liver-Related Diseases)
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26 pages, 1348 KB  
Review
Role of Chemokines in the Biology of Cholangiocarcinoma
by Alessandra Caligiuri, Mirella Pastore, Giulia Lori, Chiara Raggi, Giovanni Di Maira, Fabio Marra and Alessandra Gentilini
Cancers 2020, 12(8), 2215; https://doi.org/10.3390/cancers12082215 - 7 Aug 2020
Cited by 18 | Viewed by 4759
Abstract
Cholangiocarcinoma (CCA), a heterogeneous tumor with poor prognosis, can arise at any level in the biliary tree. It may derive from epithelial cells in the biliary tracts and peribiliary glands and possibly from progenitor cells or even hepatocytes. Several risk factors are responsible [...] Read more.
Cholangiocarcinoma (CCA), a heterogeneous tumor with poor prognosis, can arise at any level in the biliary tree. It may derive from epithelial cells in the biliary tracts and peribiliary glands and possibly from progenitor cells or even hepatocytes. Several risk factors are responsible for CCA onset, however an inflammatory milieu nearby the biliary tree represents the most common condition favoring CCA development. Chemokines play a key role in driving the immunological response upon liver injury and may sustain tumor initiation and development. Chemokine receptor-dependent pathways influence the interplay among various cellular components, resulting in remodeling of the hepatic microenvironment towards a pro-inflammatory, pro-fibrogenic, pro-angiogenic and pre-neoplastic setting. Moreover, once tumor develops, chemokine signaling may influence its progression. Here we review the role of chemokines in the regulation of CCA development and progression, and the modulation of angiogenesis, metastasis and immune control. The potential role of chemokines and their receptors as possible biomarkers and/or therapeutic targets for hepatobiliary cancer is also discussed. Full article
(This article belongs to the Special Issue Research Progress of Biliary Tract Cancers)
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15 pages, 1011 KB  
Review
A State-of-the-Art Review on the Evolving Utility of Endoscopic Ultrasound in Liver Diseases Diagnosis
by Wisam Sbeit, Anas Kadah, Mahmud Mahamid, Rinaldo Pellicano, Amir Mari and Tawfik Khoury
Diagnostics 2020, 10(8), 512; https://doi.org/10.3390/diagnostics10080512 - 23 Jul 2020
Cited by 14 | Viewed by 4295
Abstract
Liver diseases are amongst the most common diseases worldwide and manifest as a parenchymatic and/or biliary injury due to several causes as well as focal liver lesions, ranging from benign to malignant ones. The diagnosis of liver diseases is based mainly on biochemical [...] Read more.
Liver diseases are amongst the most common diseases worldwide and manifest as a parenchymatic and/or biliary injury due to several causes as well as focal liver lesions, ranging from benign to malignant ones. The diagnosis of liver diseases is based mainly on biochemical and advanced imaging studies and, when required, on liver biopsy. Endoscopic ultrasound (EUS), which combines endoscopy and ultrasonography, is one of the main examination techniques used in gastroenterology as it is applied to evaluate abnormalities in the lumen of the upper and lower gastrointestinal tract and to define pancreatic and hepato-biliary features, often in chronic patients. Given its high spatial resolution and its proximity to the liver, EUS is gaining popularity in the diagnostic work up of liver diseases. This is a comprehensive overview of the current literature on the diagnostic indications for EUS use in patients with liver diseases. We performed a MEDLINE\PubMed and Embase search, and all articles that were relevant, after reviewing abstracts, were assessed and the full text was analyzed to extract data regarding technical success, diagnostic yield, bioptic characteristics, and complications rate. EUS-guided imaging and biopsy techniques in liver diseases have shown consistent favorable promising results among the reports through the literature, with an excellent diagnostic yield and safety profile, especially in the context of focal lesions and portal hypertension. The application of EUS in the diagnosis of liver diseases is a promising technique and should be considered as a first-line therapeutic option in selected cases. Full article
(This article belongs to the Special Issue The Advanced Role of Diagnostic Endoscopic Ultrasonography)
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16 pages, 1361 KB  
Review
Peribiliary Glands as the Cellular Origin of Biliary Tract Cancer
by Hayato Nakagawa, Yuki Hayata, Tomoharu Yamada, Satoshi Kawamura, Nobumi Suzuki and Kazuhiko Koike
Int. J. Mol. Sci. 2018, 19(6), 1745; https://doi.org/10.3390/ijms19061745 - 12 Jun 2018
Cited by 23 | Viewed by 7377
Abstract
The identification of the cellular origin of cancer is important for our understanding of the mechanisms regulating carcinogenesis, thus the cellular origin of cholangiocarcinoma (CCA) is a current topic of interest. Although CCA has been considered to originate from biliary epithelial cells, recent [...] Read more.
The identification of the cellular origin of cancer is important for our understanding of the mechanisms regulating carcinogenesis, thus the cellular origin of cholangiocarcinoma (CCA) is a current topic of interest. Although CCA has been considered to originate from biliary epithelial cells, recent studies have suggested that multiple cell types can develop into CCA. With regard to the hilar and extrahepatic bile ducts, peribiliary glands (PBGs), a potential stem cell niche of biliary epithelial cells, have attracted attention as the cellular origin of biliary tract cancer. Recent histopathological and experimental studies have suggested that some kinds of inflammation-induced CCA and intraductal papillary neoplasms of the bile duct are more likely to originate from PBGs. During inflammation-mediated cholangiocarcinogenesis, the biliary epithelial injury-induced regenerative response by PBGs is considered a key process. Thus, in this review, we discuss recent advances in our understanding of cholangiocarcinogenesis from the viewpoint of inflammation and the cellular origin of CCA, especially focusing on PBGs. Full article
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