High expression of cancer stem cell markers in cholangiolocellular carcinoma

Purpose Cholangiolocellular carcinoma (CLC) is an extremely rare malignant liver tumor. It is thought to originate from the ductules and/or canals of Hering, where hepatic stem cells (HpSC) are located, but there are few reports on cancer stem cell markers in CLC. Thus, we evaluated the significance of cancer stem cell markers, including CD133, CD44, and EpCAM, in CLC. Methods The subjects of this study were three patients with CLC and one patient with an intermediate type of combined hepatocellular cholangiocarcinoma (CHC). The cancer cell markers, CK7, CK19, and EMA, were evaluated immunohistochemically. Results Histological examination of the CLC revealed morphologically cholangiolar features and immunohistochemical examination revealed positivity for CD133, CD44, and EpCAM. On the other hand, in the intermediate type of CHC, only CD44 was positive, whereas CD133 and EpCAM were negative. Conclusion CLC may have stronger features derived from HpSCs than an intermediate type of CHC

Effect of histone deacetylase inhibitor in combination with 5-fluorouracil on pancreas cancer and cholangiocarcinoma cell lines

Background : Histone deacetylase (HDAC) is well known to be associated with tumorigenesis through epigenetic regulation, and its inhibitors (HDACIs) induce differentiation and apoptosis of tumor cells. We examined the therapeutic effects of valproic acid (VPA, a HDACI) with a combination of 5-fluorouracil (5-FU) in vitro. Methods : A human pancreas cancer cell line (SUIT-2) and a cholangiocarcinoma cell line (HuCCT1) were used. Cell viabilities were evaluated by a cell proliferation assay. We determined the anticancer effects of VPA combined with 5-FU in these cell lines. Results : Pancreas cancer (SUIT-2) : No effect of 5-FU (1.0 μM) was observed, but 17% and 30% of proliferationinhibitory effects were recognized in a dose of 2.5 or 5.0 μM, respectively. Cell viability was only weakly reduced by VPA (0.5 mM). However, in combination of 5-FU (1.0 μM) with VPA (0.5 mM), 19% of inhibitory effect was observed. Cholangiocarcinoma (HuCCT1) : 5-FU (1.0 μM) did not suppress the cell viability, but 5-FU (2.5 μM) suppressed by 23%. VPA (0.5 mM) did not suppress the cell viability, while VPA (1.0 mM) weakly decreased it by 11%. Combination of 5-FU (1.0 μM) and VPA (0.5 mM) markedly reduced the cell viability by 30%. Conclusion : VPA augmented the anti-tumor effects of 5-FU in cancer cell lines. Therefore, a combination therapy of 5-FU plus VPA may be a promising therapeutic option for patients with pancreas cancer and cholangiocarcinoma

Hilar cholangiocarcinoma accompanied by pancreaticobiliary maljunction without bile duct dilatation 20 years after cholecystectomy : report of a case

Pancreaticobiliary maljunction (PBM) is associated with the occurrence of biliary cancer due to pancreatobiliary reflux. From the perspective of carcinogenesis, the treatment for PBM is controversial. We herein report a case of hilar cholangiocarcinoma 20 years after the occurrence of gallbladder cancer. A 75-year-old man was referred to our hospital regarding an obstructive jaundice and bile duct tumor. A cholecystectomy was performed for cholelithiasis on this patient 20 years ago, and cancer in situ was detected. Computed tomography (CT) and endoscopic retrograde cholangiopancreatography (ERCP) revealed a tumor of the portal hepatic region and PBM without dilatation of the bile duct. Adenocarcinoma was detected from bile cytology, and we diagnosed hilar cholangiocarcinoma. Despite the biliary decompression, jaundice was prolonged and the patient passed away. Our case suggests that not only cholecystectomy but also biliary diversion is needed for PBM regardless of the existence of bile duct dilatation

Hepatic epithelioid angiomyolipoma with arterioportal venous shunting mimicking hepatocellular carcinoma : report of a case

A patient with hepatic epithelioid angiomyolipoma (Epi-AML) with arterioportal venous shunting, who was successfully treated by a laparoscopic left lateral sectionectomy, is presented herein. AML is an uncommon benign neoplasm of the liver. Tumors composed predominantly of epithelioid cells have been subcategorized into Epi-AML, and the treatment strategy for Epi-AML is currently undetermined. There are no reports describing Epi-AML with arterioportal venous shunting to date. An arterioportal venous shunting of the liver tumor was suggested to be one of the malignant signs of the liver tumor. It would be important to differentiate Epi-AML with arterioportal venous shunting from hepatocellular carcinoma and hypervascular metastatic tumors. Minimally invasive resection, such as laparoscopic hepatectomy, for patients having Epi-AML with arterioportal venous shunting may be recommended

Complication of portal vein thrombosis after right hemihepatectomy in a patient lacking the portal vein bifurcation

Absence of portal vein bifurcation is a rare anomaly. We report a patient with this anomaly who underwent right hemihepatectomy for treatment of hepatocellular carcinoma. Although the procedure was carefully performed with a preoperative three-dimensional simulation and intraoperative cholangiography, postoperative portal vein thrombosis occurred

脂肪由来幹細胞の栄養因子を介した肝傷害に対しての保護効果

Background In this study we investigated whether adipose-derived stem cells (ADSCs) had any beneficial protective effects on liver injury and regeneration in vivo. Moreover, we examined whether ADSCs protect hepatocytes by trophic molecules. Materials and Methods We transplanted ADSCs into mice after 70% hepatectomy (Hx) and ischemia-reperfusion (I/R), and observed liver injury and regeneration after reperfusion. We co-cultured hepatocytes with ADSCs using a Transwell System for seven days and evaluated the viabilities of hepatocytes and the cytokine levels in the culture medium. Bevacizumab was used in order to confirm the effect of VEGF on hepatocytes. Results ADSCs improved serum liver function at six hours after reperfusion in a non-lethal model and stimulated liver regeneration at 24 hours after reperfusion in a lethal model. VEGF levels in the culture medium increased by co-culture ADSCs with hepatocytes. ADSCs improved the viabilities of hepatocytes. The inhibited production of VEGF by bevacizumab did not affect the viability of hepatocytes. Conclusions ADSCs were able to ameliorate liver injury and stimulate liver regeneration in subsequent Hx and I/R injured model mice. Furthermore, hepatocytes were protected by the trophic molecules of the ADSCs. However, such protective effects might be provided by mechanisms other than VEGF signaling

Hepatic screlosed hemangioma which was misdiagnosed as metastasis of gastric cancer : report of a case

A screlosed hemangioma of the liver is rare among hepatic tumors. A 75 years old male was referred to our hospital for gastric cancer and a hepatic tumor. The histological finding of gastric cancer was revealed to be well differentiated adenocarcinoma. The liver tumor was 1.1×1.0 cm in size and located in segment 8 of the liver. Computed tomography (CT) showed it to be a tumor with ring enhancement. Magnetic resonance imaging (MRI) showed the tumor to have a low signal on T1-weighted and slightly high signal on T2-weighted images. Level of hemoglobin was 7.8 g/dl. It was thought to be persistent bleeding from gastric cancer. With diagnosis of liver metastasis from gastric cancer, chemotherapy is recommended. However, to control the bleeding from gastric cancer, we performed distal gastrectomy and wedge resection of liver (S8). The histological examination of the liver tumor revealed to be a hepatic sclerosed hemangioma with hyalinized tissue and collagen fibers. We report herein a case of the rare tumor which was misdiagnosed as a liver metastasis of gastric cancer

Steroids-producing nodules: a two-layered adrenocortical nodular structure as a precursor lesion of cortisol-producing adenoma

コルチゾール産生腫瘍の前駆病変を世界で初めて発見--副腎腫瘍の発生メカニズムの解明と副腎皮質疾患の治療への応用に期--京都大学プレスリリース. 2024-04-03.Background: The human adrenal cortex consists of three functionally and structurally distinct layers; zona glomerulosa, zona fasciculata (zF), and zona reticularis (zR), and produces adrenal steroid hormones in a layer-specific manner; aldosterone, cortisol, and adrenal androgens, respectively. Cortisol-producing adenomas (CPAs) occur mostly as a result of somatic mutations associated with the protein kinase A pathway. However, how CPAs develop after adrenocortical cells acquire genetic mutations, remains poorly understood. Methods: We conducted integrated approaches combining the detailed histopathologic studies with genetic, RNA-sequencing, and spatially resolved transcriptome (SRT) analyses for the adrenal cortices adjacent to human adrenocortical tumours. Findings: Histopathological analysis revealed an adrenocortical nodular structure that exhibits the two-layered zF- and zR-like structure. The nodular structures harbour GNAS somatic mutations, known as a driver mutation of CPAs, and confer cell proliferative and autonomous steroidogenic capacities, which we termed steroids-producing nodules (SPNs). RNA-sequencing coupled with SRT analysis suggests that the expansion of the zF-like structure contributes to the formation of CPAs, whereas the zR-like structure is characterised by a macrophage-mediated immune response. Interpretation: We postulate that CPAs arise from a precursor lesion, SPNs, where two distinct cell populations might contribute differently to adrenocortical tumorigenesis. Our data also provide clues to the molecular mechanisms underlying the layered structures of human adrenocortical tissues. Funding: KAKENHI, The Uehara Memorial Foundation, Daiwa Securities Health Foundation, Kaibara Morikazu Medical Science Promotion Foundation, Secom Science and Technology Foundation, ONO Medical Research Foundation, and Japan Foundation for Applied Enzymology