Analysis of epithelial-mesenchymal transition markers in the histogenesis of hepatic progenitor cell in HBV-related liver diseases.

BACKGROUND: The origin and heterogeneity of hepatic progenitor cells (HPCs) remain unclear. This study aimed to investigate the involvement of epithelial-mesenchymal transition (EMT) in the histogenesis of HPCs. METHODS: Surgical liver specimens from patients with HBV-related hepatitis and cirrhosis were investigated with double immunofluorescence labeling to detect antigens associated with HPCs and EMT. Ductular reactions were subjected to quantitative reverse transcription PCR following isolation by laser capture microdissection. Electron microscopic examination was performed to find an ultrastructural evidence of EMT. RESULTS: The number of EpCAM-positive HPCs was proportional to the disease severity. The S100A4 expression of HPCs was firstly observed in mild hepatitis and increased significantly in moderate hepatitis, but decreased in severe hepatitis and cirrhosis. The levels of MMP-2, Twist, and Snail increased in direct proportion to the number of HPCs. Some hepatocytes adjacent to portal tracts in cirrhosis showed positivity for MMP-2. Although CK7 and E-cadherin levels decreased in mild and moderate hepatitis, HPCs re-expressed both of them in severe hepatitis and cirrhosis. However, HPCs expressed neither vimentin nor αSMA. The relative mRNA expression levels of EpCAM and EMT-associated markers supported immunohistochemical results. Electron microscopic examination demonstrated the existence of intercellular junctions among HPCs, cholangiocytes, and intermediate hepatocyte-like cells. CONCLUSION: We provided preliminary evidence for the involvement of EMT in the histogenesis of HPCs from cholangiocytes in HBV-related liver diseases. HPCs may re-transdifferentiate into hepatocytes, and the differentiation direction depends, at least in part, on interactions between HPCs and the surrounding microenvironment, especially the non-resolving inflammation caused by HBV infection.

Cutaneous clear cell/signet-ring cell squamous cell carcinoma arising in the right thigh of a patient with type 2 diabetes: combined morphologic, immunohistochemical, and etiologic analysis.

BACKGROUND: The clear cell/signet-ring cell variant of cutaneous squamous cell carcinoma (cSCC) is extremely rare. Its carcinogenesis has consistently been linked to ultraviolet radiation and HPV in the literature. However, there is little definite information about the contribution of diabetes mellitus (DM) to cSCC. CASE PRESENTATION: A 78-year-old Chinese woman with type 2 DM presented with a mushroom-like lump in her right thigh. Histological findings revealed that the lesion was mainly composed of clear cells and signet-ring cells. The septa of vacuoles in cytoplasm displayed positivity for periodic acid schiff (PAS) and cytokeratins such as AE1/AE3, CK5/6, CK14, and CK19. Malignant cells did not express CK7, CK8, CK18, CK20, p16, p53, or c-erbB-2, and the Ki-67 index was less than 5 %. We further explored the etiology of clear cell/signet-ring cell cSCC using human papillomavirus (HPV) type-specific PCR and genotyping and confirmed that the patient was not infected with HPV. Nucleus positivity for p63 indicated the involvement of the p53 family in the lesion. Meanwhile, the expression of fibroblast growth factor receptor-2 (FGFR2), a downstream effector of p63, was upregulated in tumor cells. CONCLUSIONS: This study provides the first report on the clear cell/signet-ring cell variant of cSCC found in the right thigh of a patient with type 2 DM. Metabolic imbalance in addition to conventional pathogens such as UV and HPV may contribute to the development of the lesion via p63/FGFR2 axis.

Furazolidone-based triple and quadruple eradication therapy for Helicobacter pylori infection.

AIM: To evaluate the efficacy of furazolidone-based triple and quadruple therapy in eradicating Helicobacter pylori (H. pylori) in a multi-center randomized controlled trial. METHODS: A total of 720 H. pylori positive patients with duodenal ulcer disease were enrolled at 10 different hospitals in Jiangxi province in China. The patients were randomly assigned to four treatment groups as follows: patients in Groups 1 and 3 received rabeprazole (10 mg), amoxicillin (1000 mg) and furazolidone (100 mg) twice daily for 7 and 10 d, respectively; patients in Groups 2 and 4 received rabeprazole (10 mg), bismuth (220 mg), amoxicillin (1000 mg) and furazolidone (100 mg) twice daily for 7 and 10 d, respectively. The primary outcome measure was H. pylori eradication rate 4 wk after treatment by intention-to-treat and per protocol analysis, while the secondary outcome measures were symptom and sign changes at the end of treatment and 4 wk after the end of treatment, as well as the proportion of patients who developed adverse events. RESULTS: The demographic data of the four groups were not significantly different. Overall, 666 patients completed the scheme and were re-assessed with the (13)C-urea breath test. The intention-to-treat analysis of the H. pylori eradication rates in Groups 1, 2, 3 and 4 were 74.44%, 82.78%, 78.89% and 86.11%, respectively. The H. pylori eradication rate in Group 4 was significantly higher than that in Group 1. According to the per protocol analysis, the H. pylori eradication rates in Groups 1, 2, 3 and 4 were 81.21%, 89.22%, 85.54% and 92.26%, respectively. The H. pylori eradication rate in Group 4 was significantly higher than that in Group 1. The number of adverse events was 15 (8.3%), 16 (8.9%), 15 (8.3%) and 17 (9.4%) in Groups 1, 2, 3 and 4, respectively, including dizziness, vomiting, diarrhea, nausea, skin rash, itchy skin, and malaise. The symptoms were relieved without special treatment in all of the patients. CONCLUSION: Both 7- and 10-d quadruple furazolidone-based therapies achieve satisfactory H. pylori eradication rates.

Clinicopathological characteristics and prognosis of gastric cancer with malignant ascites.

Management of gastric cancer with malignant ascites is a challenge, and limited data are available. We evaluated factors affecting survival for this condition to determine factors that predict survival outcome and to develop a rational treatment plan. We retrospectively studied 5,542 patients with gastric adenocarcinoma from January 2007 to December 2012. Among them, 347 patients (6.26%) were associated with malignant ascites. The patients' overall survival was compared among the different features. Three hundred forty-seven patients (153 females and 194 males; median age, 53 years) were enrolled, including 78 (22.5%) young patients and 63 (18.1%) elderly patients. One hundred forty-three (41.2%) patients presented with malignant ascites at the initial diagnosis of gastric cancer, and 211 (60.8%) received chemotherapy. After a median follow-up duration of 10.4 months, the median survival after the diagnosis of malignant ascites was 5.2 months (95% CI, 4.8-5.6 months), and the 1-year survival rate was 16.1 %. An ECOG score greater than 2 (P < 0.001), the presence of ascites with the diagnosis of gastric cancer (P < 0.001), no chemotherapy (P < 0.001), an albumin level less than 30 g/L (P = 0.013), an ascites volume greater than 2,000 mL (P = 0.019), Helicobacter pylori infection (P = 0.010), and metastases to other organs (P = 0.037) were associated with poor prognosis, and they were all independent prognostic factors. The survival of gastric cancer patients with malignant ascites is relatively short, and ECOG score and the presence of ascites with the diagnosis of gastric cancer are the most important prognostic factors. Additionally, chemotherapy could improve the overall survival.