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Inflammatory myofibroblastic tumors are rare tumors that have been described in virtually all organs. Even though they are extremely rare in the esophagus, several cases have been described in the literature. Surgical resection has been the therapeutic modality used in most of those cases. In this report, we describe a case of inflammatory myofibroblastic tumor that was successfully managed endoscopically for the first time with the endoscopic submucosal dissection technique., (© 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Cholangiocarcinoma (CCA) is a highly lethal cancer arising from the biliary tract epithelium. The cancer biology of this neoplasm is not well understood. To date, only a few CCA cell lines have been reported, which were mostly developed from Asian patients. In this study, we report and characterize a new intrahepatic CCA cell line, LIV27, derived from a surgically resected tumor in a 67-year-old Caucasian woman with primary sclerosing cholangitis (PSC). LIV27 cells grow well in collagen-coated flasks or plates with a doubling time of 57.8 h at passage 14. LIV27 cells have high tumorigenicity in nude mice and stain positive for CK7 and CK19, markers that differentiate CCA from hepatocellular carcinoma. Karyotype analysis showed that LIV27 is aneuploid. We established a single-locus short tandem repeat profile for the LIV27 cell line. This newly established cell line will be a useful model for studying the molecular pathogenesis of, and developing novel therapies for, cholangiocarcinoma.

An 80-year-old man was admitted due to biliary stricture with autoimmune pancreatitis. Although radiographical examinations suggested Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC), punched biopsies from the bile duct revealed adenocarcinoma. In the resected specimen, abundant N-terminus of Forkhead box P3 (Foxp3)-positive cells were localized in cholangiocarcinoma (CCA) tissue, while IgG4-positive cells were spread around the entire bile duct. Therefore, the case was diagnosed with IgG4-SC accompanied by CCA, not sporadic CCA. We herein report an informative case wherein IgG4-positive cells were abundant in CCA tissue and Foxp3 immunohistochemical staining allowed us to determine that this case had two entities.

Primary dural diffuse large B-cell lymphoma (PD-DLBCL) is a rare and aggressive B-cell non-Hodgkin lymphoma that can present in intracranial or intraspinal locations. Although the optimal management is unknown, PD-DLBCL therapy is often mirrored after primary central nervous system lymphoma therapy and aggressive treatment with a high dose methotrexate-based regimen is frequently used. Our comprehensive, retrospective study of 24 reported cases of PD-DLBCL provide the most complete analysis of this rare disease including data on biology, treatment outcomes, and survival. Our findings demonstrate good outcomes following induction treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), suggesting that these cases can be treated as DLBCL rather than primary central nervous system lymphoma, obviating the need for more aggressive and toxic approaches. The durable responses following R-CHOP also confirm that PD-DLBCL is not protected by the blood brain barrier., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Cholestatic liver diseases (CLDs) encompass a variety of disorders of abnormal bile formation and/or flow. CLDs often lead to progressive hepatic insult and injury and following the development of cirrhosis and associated complications. Many such complications are clinically silent until they manifest with severe sequelae, including but not limited to life-altering symptoms, metabolic disturbances, cirrhosis, and hepatobiliary diseases as well as other malignancies. Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are the most common CLDs, and both relate to mutual as well as unique complications. This review provides an overview of PSC and PBC, with a focus on preventive measures aimed to reduce the incidence and severity of disease-related complications., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest.

Purpose: We investigated the antitumor effect of the casein kinase II (CK2) inhibitor CX-4945 on cholangiocarcinoma (CCA)., Methods: We assessed the effect of CX-4945 alone and/or in combination with gemcitabine and cisplatin on cell viability, colony formation, and apoptosis of CCA cell lines and on in vivo growth of HuCCT1 xenografts., Results: CX-4945 dose-dependently decreased viability of HuCCT1, EGI-1, and Liv27 and decreased phospho-AKT/total AKT and phospho-PTEN/total PTEN ratios. CX-4945 significantly increased caspase 3/7 activity in a dose- and time-dependent manner. CX-4945 significantly enhanced the effect of gemcitabine or cisplatin on HuCCT1, EGI-1, and Liv27 cells and inhibited the phosphorylation of DNA repairing enzymes XRCC1 and MDC1. Further, CX-4945 alone significantly inhibited growth of HuCCT1 mouse xenograft tumors. Combining CX-4945 with gemcitabine and cisplatin was more potent than CX-4945 alone or gemcitabine/cisplatin. The effect of CX-4945 on cell proliferation, apoptosis, the PI3K/AKT pathway, and DNA repair was confirmed in the mouse xenografts., Conclusion: CX-4945 has an antiproliferative effect on CCA and enhances the effect of gemcitabine and cisplatin through its inhibitory effect on the PI3K/AKT pathway and DNA repair., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Hedgehog (HH) signaling participates in hepatobiliary repair after injury and is activated in patients with cholangiopathies. Cholangiopathies are associated with bile duct (BD) hyperplasia, including expansion of peribiliary glands, the niche for biliary progenitor cells. The inflammation-associated cytokine interleukin (IL)-33 is also up-regulated in cholangiopathies, including cholangiocarcinoma. We hypothesized that HH signaling synergizes with IL-33 in acute inflammation-induced BD hyperplasia. We measured extrahepatic BD (EHBD) thickness and cell proliferation with and without an IL-33 challenge in wild-type mice, mice overexpressing Sonic HH ( pCMV-Shh ), and mice with loss of the HH pathway effector glioma-associated oncogene 1 ( Gli1 lacZ/lacZ ). LacZ reporter mice were used to map the expression of HH effector genes in mouse EHBDs. An EHBD organoid (BDO) system was developed to study biliary progenitor cells in vitro . EHBDs from the HH overexpressing pCMV-Shh mice showed increased epithelial cell proliferation and hyperplasia when challenged with IL-33. In Gli1 lacZ/lacZ mice, we observed a decreased proliferative response to IL-33 and decreased expression of Il6 . The HH ligands Shh and Indian HH ( Ihh ) were expressed in epithelial cells, whereas the transcriptional effectors Gli1 , Gli2 , and Gli3 and the HH receptor Patched1 ( Ptch1 ) were expressed in stromal cells, as assessed by in situ hybridization and lacZ reporter mice. Although BDO cells lacked canonical HH signaling, they expressed the IL-33 receptor suppression of tumorigenicity 2. Accordingly, IL-33 treatment directly induced BDO cell proliferation in a nuclear factor κB-dependent manner. Conclusion: HH ligand overexpression enhances EHBD epithelial cell proliferation induced by IL-33. This proproliferative synergism of HH and IL-33 involves crosstalk between HH ligand-producing epithelial cells and HH-responding stromal cells.

Hepatocellular carcinoma (HCC) originates from hepatocytes usually secondary to chronic inflammation and cirrhosis. It is an important disease of global significance with a high incidence and mortality. It is the fifth and eighth most common cancer in males and females, respectively. HCC is also extremely lethal; in 2015 it was the second and sixth most common cause of death from cancer in males and females, respectively. Chronic viral hepatitis B and C are the most frequent risk factors for the development of HCC, and the global distribution of HCC largely mirrors that of chronic viral hepatitis. More recently, there has been a notable increase in the incidence of HCC as a result of obesity-related fatty liver disease. Here, we review the epidemiology of HCC, examine recent advances in our understanding of the pathogenesis of HCC, discuss the implications for identification of potential therapeutic targets, and provide the most updated recommendations on surveillance for HCC, with particular attention to the unique challenges and potential opportunities to reduce the burden of illness and death from HCC in sub-Saharan Africa.

Cholestatic liver diseases (CLDs) encompass a variety of disorders of bile formation and/or flow which generally result in progressive hepatobiliary injury and ultimately end-stage liver disease. Many patients with CLD are diagnosed between the ages of 20-50 years, a particularly productive period of life professionally, biologically and in other respects; it is not surprising, thus, that CLD is often associated with impaired health-related quality of life (HRQOL) and uncertainty regarding implications for and outcomes of pregnancy. Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are the most prominent CLDs, both having considerable morbidity and mortality and representing major indications for liver transplantation. These disorders, as a consequence of their complications (eg ascites, hepatic osteodystrophy), associated conditions (eg inflammatory bowel disease) and symptoms (eg pruritus and fatigue), can significantly impair an array of domains of HRQOL. Here we review these impactful clinical aspects of PSC and PBC as well as the topics of fertility and pregnancy., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Infection is the second most common cause of esophagitis, second only to gastroesophageal reflux, and represents a clinically important disorder. Immunosuppressed patients are at highest risk for infectious esophagitis, with CANDIDA, herpes simplex virus, and cytomegalovirus being the most common causative microorganisms. Here we provide a brief clinical review and present a case of concomitant oropharyngeal and presumed esophageal candidiasis in a patient with autoimmune hepatitis who was initiated on high-dose corticosteroid therapy and soon thereafter develop odynodysphagia and who was found to have herpes esophagitis diagnosed by endoscopy and histopathology.

Introduction: Based on extensive preclinical data and abundant evidence for clinical activity, vascular endothelial growth factor receptor (VEGFR) inhibitors are currently standard of care for metastatic renal cell carcinoma (mRCC). Axitinib is one of the most selective molecules in the class of anti-angiogenic agents, which confers an optimal profile between its safety and anti-cancer activity spectrum., Area Covered: In this review, the authors discuss the different stages that lead to the approval of axitinib in the clinic as well as the current perspectives for its clinical use with other promising therapies in mRCC such as immune checkpoint inhibitors and vaccines., Expert Opinion: In 2015, axitinib has emerged as one of the major agents used in mRCC. Based on robust preclinical data, this highly specific VEGFR inhibitor continues to be evaluated in different indications, including the adjuvant setting but also sequential administration with other molecularly targeted agents or combinations with immune therapies.

In the present case, a 49-year-old white female presented to the clinic with a 2-month history of nausea, vomiting, and right upper quadrant pain. On examination a 3-cm mass on the right anterior scalene muscle was noted. A computed tomography scan was performed revealing a 8.7 × 7.7 × 6.1 cm retroperitoneal mass with possible invasion of the inferior vena cava and right renal and left common iliac veins. An excisional biopsy was performed with pathology compatible with spindle cell sarcoma. The patient was then sent for follow-up at the sarcoma clinic as an outpatient. However, before chemotherapy was to be started the patient would be admitted to the hospital with progressively worse nausea and vomiting. At that time the patient's lab work showed lactic acidosis, acute renal failure, hyperuricemia, hyperphosphatemia, and hypocalcemia, which met the Cairo-Bishop criteria for tumor lysis syndrome (TLS). The patient was admitted to the intensive care unit and kidney dialysis initiated. The patient would become progressively obtunded at which time the family opted for hospice care. The patient eventually succumbed peacefully 3 days after her last admission. In this case report, we briefly review the literature on TLS in solid tumors, and we present a rare case of spontaneous TLS in a retroperitoneal sarcoma.

Background and Aims: Brivanib is a selective inhibitor of vascular endothelial growth factor receptor (VEGFR) and fibroblast growth factor receptor (FGFR) tyrosine kinases, which are both involved in mechanisms of liver fibrosis. We hypothesized that inhibition of VEGFR and FGFR by brivanib would inhibit liver fibrosis. We therefore examined the effect of brivanib on liver fibrosis in three mouse models of fibrosis., Methods: In vivo, we induced liver fibrosis by bile duct ligation (BDL), chronic carbon tetrachloride (CCl4), and chronic thioacetamide (TAA) administration. Liver fibrosis was examined by immunohistochemistry and Western immunoblotting. In vitro, we used LX-2 human hepatic stellate cells (HSCs) to assess the effect of brivanib on stellate cell proliferation and activation., Results: After in vivo induction with BDL, CCl4, and TAA, mice treated with brivanib showed reduced liver fibrosis and decreased expression of collagen Iα1 and α-smooth muscle actin in the liver. In vitro, brivanib decreased proliferation of HSCs induced by platelet-derived growth factor (PDGF), VEGF, and FGF. Brivanib also decreased stellate cell viability and inhibited PDGFBB-induced phosphorylation of its cognate receptor., Conclusion: Brivanib reduces liver fibrosis in three different animal models and decreases human hepatic stellate cell activation. Brivanib may represent a novel therapeutic approach to treatment of liver fibrosis and prevention of liver cancer.