Search

The liver is the main organ responsible for drug metabolism; hepatocyte-based culture models play a fundamental role in understanding liver physiology. While different types of two-dimensional and three-dimensional liver models have been developed, the failure to accurately mimic native liver, including extracellular matrix (ECM) composition, complex structure, and rich vascular network as well as shortage of liver donors, impede their clinical translation. Herein, we have realized a “miniature human liver” based on the infusion of primary human hepatocytes into a decellularized liver template (DC-liver) made from the right liver lobe of mouse. We performed detergent-based decellularization of the mouse liver sections via portal vein (PV) perfusion and confirmed the successful removal of cell content, and the preservation of the vascular network. Subsequently, the DC-liver templates were recellularized at varying cell densities, including 3 × 106 and 1 × 107 cells/mL, and liver specific gene expression was assessed. Overall, hepatocytes in the recellularized liver constructs (RC-liver) expressed liver-specific mRNA expression markers (Hnf4α, Alb) at a level comparable to the unseeded, freshly isolated hepatocytes and to hepatocytes seeded inside collagen gels. However, the RC-liver with the highest cell density exhibited poor cell distribution and blockage of the PV, in general, hepatocytes showed elevated levels of Cyp1a1. Further analysis hinted at hypoxic conditions inside the constructs, showing higher mRNA expression levels of hypoxia-related genes (Hif-1α, Casp3, Zo-1). Fortunately, oxygen supplementation appeared to alleviate hypoxia, which markedly reduced expression levels of Hif-1α and Cyp1α1. As a proof-of-concept, primary human hepatocytes were also seeded into the DC-liver templates, and we could confirm liver specific mRNA expression (HNF4A, ALB, CYP3A4). Altogether, the above results indicate a profound potential in the use of DC-liver tissue for the fabrication of a miniature human liver, which may have potential application prospects for regenerative medicine, tissue engineering (TE) and other related disciplines.

Abstract Background Hepatic inflammatory pseudotumor (IPT) is a rare, benign, tumor-like lesion. Because there are no characteristic laboratory markers or radiological features, hepatic IPT is often misdiagnosed as a malignant neoplasm such as hepatocellular carcinoma (HCC). Case presentation A 68-year-old man with liver dysfunction due to chronic hepatitis C virus infection and alcoholic liver disease presented with hepatic tumors in segments III and VIII. The levels of serum alpha-fetoprotein (AFP) and its Lens culinaris agglutinin-reactive fraction, AFP lectin 3 (AFP-L3), were elevated to 822.8 ng/ml and 75.2%, respectively. The tumor showed contrast enhancement on contrast-enhanced computed tomography and various accumulation on positron emission tomography. Based on these biological and imaging features, HCC was suspected, and we performed laparoscopic partial hepatectomy for these two tumors. Pathological diagnosis revealed that both tumors were hepatic IPTs with no malignant characteristics. After hepatectomy, the serum AFP and AFP-L3 levels decreased to the normal range. Conclusion We report a very rare case of hepatic IPT with elevated serum AFP and AFP-L3, mimicking HCC. Clinicians should include this rare neoplasm in the differential diagnoses of hepatic tumors even when the serum markers for HCC are elevated.

Abstract Background An accurate diagnosis of the primary cancer or metastatic tumor is quite important because misdiagnosis may lead to the selection of incorrect adjuvant therapy and worse long-term outcomes after surgery. Here, we present a rare case with an unusual metastatic pattern mimicking a hilar cholangiocarcinoma originated from colon cancer Case presentation A 69-year-old man was referred to our hospital because of an upper bile duct stenosis. He had the past history of the sigmoidectomy for the primary colon cancer and the partial hepatectomy with radiofrequency ablation (RFA) for synchronous liver metastases 4 years ago. After 2 years from the initial operation, he had experienced the local recurrence of post-RFA lesion and had undergone a partial hepatectomy. According to the radiological findings of the bile duct stenosis, we diagnosed a hilar cholangiocarcinoma (Bismuth type II), and then he underwent the extended right hepatectomy with extrahepatic bile duct resection. Histological findings including the immune-histochemical examinations (CK7−, CK20+, CDX2+ and SATB2+) uncovered the metastatic tumor into extrahepatic bile duct originated from the primary colon cancer. Conclusion We experienced an extremely rare case with a colon cancer metastasis mimicking a hilar cholangiocarcinoma. In this case with a past history of colon cancer, an immunohistochemical staining led us to distinguish the primary hilar cholangiocarcinoma and the mimicking tumor.

Abstract Background Carcinosarcoma is a rare tumor that includes both carcinoma and sarcoma components. It develops commonly in the female reproductive tract, most often in the uterus. However, as there are a small number of similar cases in the English literature, we would like to present a rare case of a carcinosarcoma in Vater’s papilla. Case presentation A 76-year-old female patient was preoperatively diagnosed with a papillary adenocarcinoma in Vater’s papilla by endoscopic biopsy. The patient underwent subtotal stomach-preserving pancreaticoduodenectomy, and postoperative pathological examination diagnosed the carcinosarcoma. The patient received adjuvant chemotherapy with gemcitabine, but multiple liver metastases were found 3 months after the operation. Though chemotherapy with gemcitabine and cisplatin was introduced, she died owing to tumor progression 7 months after the operation. Conclusion Because carcinosarcoma of Vater’s papilla is a rare disease, a suitable treatment strategy has been unclear. We also present a review of the English literature regarding carcinosarcoma of Vater’s papilla.