Interaction between cadherins, vimentin, and V-set and immunoglobulin domain containing 1 in gastric-type hepatocellular carcinoma.

In hepatocellular carcinomas (HCCs), the role of the cell surface protein V-set and immunoglobulin domain containing 1 (VSIG1), which is known as a specific marker of the gastric mucosa and testis, has not yet been determined. We examined VSIG1 immunohistochemical (IHC) expression in 105 consecutive samples provided by HCC patients, along with the IHC expression of three of the biomarkers known to be involved in the epithelial-mesenchymal transition (EMT): vimentin (VIM), and E- and N-cadherin (encoded by CDH1 and CDH2 genes). IHC subcellular localization of thyroid transcription factor 1 (TTF1), in which nuclear-to-cytoplasmic translocation is known to cause a lineage shift from lung to gastric-type adenocarcinoma, was also checked. The obtained data were validated using the miRNET program. In the examined HCC samples, VSIG1 expression was observed in the cytoplasm of normal hepatocytes and downregulated in 47 of the 105 HCCs (44.76%). In 29 cases (27.62%), VSIG1 was co-expressed with cytoplasmic TTF1. VSIG1 expression was positively correlated with both E-cadherin and N-cadherin and negatively correlated with VIM (p < 0.0001). The VSIG1+/E-cadherin+/N-cadherin-/VIM phenotype was seen in 13 cases (12.4%) and was characteristic of well-differentiated (G1/2) carcinomas diagnosed in pT1/2 stages. Like pulmonary carcinomas, simultaneous cytoplasmic positivity of HCC cells for VSIG1 and TTF1 may be a potential indicator of a lineage shift from conventional to gastric-type HCC. The E-cadherin/VSIG1 complex can help suppress tumor growth by limiting HCC dedifferentiation. The miRNET-based interaction between VSIG1/VIM/CDH1/CDH2 genes might be interconnected by miR-200b-3p, a central regulator of EMT which also targets VIM and VSIG1.

Benefits of the 8th American Joint Committee on Cancer System for Hepatocellular Carcinoma Staging.

PURPOSE: We aimed to emphasize the prognostic impact of differences included in the 8th versus the previous 7th edition of AJCC (American Joint Committee on Cancer) Cancer Staging manual for hepatocellular carcinoma (HCC). METHODS: A number of 87 consecutive HCCs were retrospectively evaluated and staged, using the 7th and 8th edition of AJCC staging systems. The clinicopathological parameters were correlated with the overall survival rate. No preoperative chemotherapy was received by any of the patients. RESULTS: According to the 7th edition of AJCC manual, 52 of the 87 cases were staged as pT2 and 35 as pT1. After restaging, according to the 8th edition, 23 of the 52 pT2 cases were understaged as pT1b, and the rest of the 29 remained as pT2. Regarding the 35 HCCs classified as pT1, using 7th edition, all of them were restaged as pT1a. Compared to the 7th staging system, using the 8th edition of AJCC manual, the percentage of pT2 tumors significantly decreased, from 59.77 to 33.33%. The patient's gender, age, tumor focality, and grade of differentiation did not prove to have any prognostic value. Regarding pT stage, it does not influence the overall survival rate, independently from the used staging system. CONCLUSION: The staging criteria, in the most recent edition of AJCC, are simplified and allowed tumor understaging. These changes do not have independent prognostic value. The prognostic impact of pT understaging should be evaluated in larger cohorts.

Epithelial Mesenchymal and Endothelial Mesenchymal Transitions in Hepatocellular Carcinoma: A Review.

PURPOSE: To present a comprehensive review of the literature data, published between 2000 and 2019 on the PubMed and Web of Science databases, in the field of the tumor microenvironment in hepatocellular carcinoma (HCC). All the data were combined with the personal experiences of the authors. DESIGN: From 1002 representative papers, we selected 86 representative publications which included data on epithelial-to-mesenchymal transition (EMT), angiogenesis, cancer stem-like cells (CSCs), and molecular background of chemoresistance or resistance to radiotherapy. RESULTS: Although the central event concerns activation of the Wnt/ß-catenin pathway, other signal pathways, such as c-Met/HGF/Snail, Notch-1/NF-κB, TGF-ß/SMAD, and basic fibroblast growth factor-related signaling, play a role in the EMT of HCC cells. This pathway is targeted by specific miRNAs and long noncoding RNAs, as explored in this paper. A central player in the tumor microenvironment proved to be the CSCs which can be marked by CD133, CD44, CD90, EpCAM, and CD105. CSCs can induce resistance to cytotoxic therapy or, alternatively, can be synthesized, de novo, after chemo- or radiotherapy, especially after transarterial chemoembolization- or radiofrequency ablation-induced hypoxia. The circulating tumor cells proved to have epithelial, intermediate, or mesenchymal features; their properties have a critical prognostic role. CONCLUSION: The metastatic pathway of HCC seems to be related to the Wnt- or, rather, TGFß1-mediated inflammation-angiogenesis-EMT-CSCs crosstalk link. Molecular therapy should target this molecular axis controlling the HCC microenvironment.

Angiogenesis of hepatocellular carcinoma: An immunohistochemistry study.

BACKGROUND: Although hepatocellular carcinoma (HCC) is one of the most vascular solid tumors, antiangiogenic therapy has not induced the expected results. AIM: To uncover immunohistochemical (IHC) aspects of angiogenesis in HCC. METHODS: A retrospective cohort study was performed and 50 cases of HCC were randomly selected. The angiogenesis particularities were evaluated based on the IHC markers Cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF) A and the endothelial area (EA) was counted using the antibodies CD31 and CD105. RESULTS: The angiogenic phenotype evaluated with VEGF-A was more expressed in small tumors without vascular invasion (pT1), whereas COX-2 was rather expressed in dedifferentiated tumors developed in non-cirrhotic liver. The CD31-related EA value decreased in parallel with increasing COX-2 intensity but was higher in HCC cases developed in patients with cirrhosis. The CD105-related EA was higher in tumors developed in patients without associated hepatitis. CONCLUSION: In patients with HCC developed in cirrhosis, the newly formed vessels are rather immature and their genesis is mediated via VEGF. In patients with non-cirrhotic liver, COX-2 intensity and number of mature neoformed vessels increases in parallel with HCC dedifferentiation.

The use of heterologous bovine pericardium in the surgical treatment of large tracheo-oesophageal fistulas and dilaceration of the membranous wall of the trachea. Case report.

The tracheo-oesophageal fistula is a severe condition endangering the patients' live. The main cause of this condition is the prolonged ventilation. The purpose of this paper is to present an innovative technique in treating this affection. CASE REPORT: We present the case of a 32 years old female patient with multiple trauma due to traffic accident. The patient was hospitalized with the diagnosis of brain injury, subarachnoid hemorrhage, and fractured femur. After 11 days of mechanical ventilation and intubation via endotracheal route, the patient was diagnosed with a large (7x3 cm) tracheo-oesophageal fistula with dilaceration of the membranous wall of the trachea. A cervical and right thoracic approach was performed to repair the tracheo-oesophageal fistula. The reconstruction of the membranous wall of the trachea was performed by using heterologous bovine pericardium patch, and the of the esophageal defect using single-layer suture protected by a heterologous bovine pericardium patch. The postoperative evolution was favorable, the patient being discharged 22 days postoperatively and in good health after 6 months. To our knowledge this is the first reported case regarding the use of two heterologous bovine pericardium in the surgical treatment of large tracheo-oesophageal fistula with dilaceration of the membranous wall of the trachea to reconstruct the membranous wall of the trachea and to protect the esophageal suture. KEY WORDS: Heterologous bovine pericardium, Trachea-oesophageal fistula.

Giant hepatic metastasis in a patient with coin-like small cell lung carcinoma incidentally diagnosed at autopsy: A case report.

RATIONALE: Encephalopathy is a rare complication of hepatic metastases. In this paper we present a case of a patient with lung cancer and metastatic-related giant hepatomegaly. PATIENT CONCERNS: A 78-year-old previously healthy male was admitted in the Emergency room in hepatic coma. DIAGNOSES: The abdominal CT scan examination revealed a huge liver filled with solid nodules. INTERVENTIONS: No interventions were performed. OUTCOMES: The patient died at few hours after hospitalization. The autopsy showed a 6.5 kilograms liver with several whitish metastatic nodules and an occult prostate adenocarcinoma. The hilum of both lungs was free of tumor and a 10 mm white nodule was identified surrounding a small bronchus. No peripheral nodules were macroscopically identified. Under microscope, cluster of small cells were observed encasing a small bronchus with multiple minute coin-shaped subpleural foci. A massive intrapulmonary angiolymphatic invasion and metastases from small cell carcinoma in liver, lymph nodes and iliac crest bone marrow were also diagnosed. LESSONS: This case highlights the difficulty of diagnosis of aggressive lung carcinomas and the necessity of checking for metachronous tumors. The encephalopathy might be the result of metastatic damage of the liver parenchyma combined with the paraneoplastic effect of the tumor cells. Few than 25 cases of SCLCs with diffuse liver metastases and fulminant liver failure were reported to December 2016. This is the first reported case with a synchronous prostate cancer and a "coin-like" aspect of the SCLC.