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Background/Aims: This study was designed to assess the etiology and characteristics of chronic liver disease among the young male adults. It was also investigated whether grades of activity and status of fibrosis defined by the new histopathologic classification system of chronic hepatitis are related with alanine aminotransferase (ALT) level and HBeAg status in HBsAg-positive case. Methods: Peritoneoscopic findings, clinical features and histopathologic features of liver were investigated for 140 young men who received liver biopsy for military medical certificate from January 1994 to December 1997. These features were evaluated according to the grade and stage of chronic hepatitis. Results: In Korea, hepatitis B virus was the main cause of chronic hepatitis (87.7%) in young male adults and the infection of hepatitis C virus was rare (1.4%). Among HBsAg-positive cases with normal ALT level, 82.2% of them revealed chronic liver disease, and 48.3% of them showed chronic active hepatitis/cirrhosis in biopsy specimens. The grade of chronic hepatitis showed weak correlation with ALT level and the stage did not. There was no significant difference in the grade and stage of chronic hepatitis according to the serum HBeAg status. Conclusions: The most common cause of chronic liver disease in Korean young male adults was hepatitis B virus, and most (92.6%) of HBsAg-positive cases were proved to have chronic liver diseases histologically, regardless of the serum ALT level. According to new histopathologic classification system of chronic hepatitis, serum ALT level correlated with necroinflammatory activity of chronic hepatitis B, but not with fibrosis in HBsAg-positive cases.
Pathological features related to prognosis of hepatocellular carcinoma (HCC) include tumor differentiation grade, tumor size, vascular invasion and intrahepatic metastasis. HCCs are classified into early HCCs and progressed HCCs. Early HCCs are suggested to be the earliest lesion of HCC, corresponding to carcinoma in situ of the other organs. Early HCCs are well differentiated without vascular invasion and its prognosis is very good. In contrast, progressed HCCs are usually moderate to poor differentiated, even in the small sized (< 2cm) HCCs, and vascular invasion and intrahepatic metastasis are found in 27 % and 10%, respectively. The changes in transcriptomes of early HCCs are modest and homogenous, whereas extensive genetic alterations and subsequent activation of prognostic adverse signaling pathways occur only late during hepatocarcinogenesis, and are centered on TGF-ß, WNT, NOTCH, and epithelial-mesenchymal transition (EMT)-related genes highlighting the molecular diversity of progressed HCCs. Recently, new HCC subtypes have been reported based on pathological-molecular classification, and some of them have been reported to be related to poor prognosis. HCCs expressing stemness markers including K19 have been reported to have an aggressive behavior. HCCs with high expression of stemness markers (K19, EpCAM) show activation of YAP pathway, TP53 mutation, FGF19 amplification, and they correlate with aggressive gene expression signatures including S2 (Hoshida et al.) and G1 (Boyault et al.) subclasses. There are some characteristic clinicopathological features that have been more frequently seen in HCCs expressing stemness-related markers compared to those without these markers. HCCs with K19 expression, approximately 10-28% of HCCs show high serum alpha-fetoprotein (AFP) levels, chronic hepatitis B, and decreased overall and recurrence-free survival. HCCs with K19 expression are less frequently encapsulated compared to those without, imparting a more infiltrative growth pattern. Vascular invasion is more frequent in HCCs with K19 expression compared to those without. A fibrous stromal component is more frequently identified in HCCs with K19 expression compared to those without. There is a crosstalk between tumor epithelial cells and stromal cells, and K19 expression is regulated by fibroblast-derived HGF via a MET-ERK1/2-AP1 and SP1 Axis. HCCs with K19 expression are associated with increased expression of EMT-related genes and their proteins, and they are also associated with longer telomeres, increased hTERT expression and increased chromosomal instability, suggesting that HCCs with K19 expression have a survival advantage over those without by maintaining telomeres despite the increased chromosomal instability. Hypoxic microenvironment is known to be important in the generation and maintenance of stemness, and we found that HCCs with stemness (K19, EpCAM) and hypoxia (CAIX)-related markers showed more resistance to transarterial chemoembolization (TACE) and poorer outcome compared those without, and their tumor microenvironment was found to be altered under TACE-induced hypoxia, which might promote the aggressive biology of HCC. The expression of stemness and hypoxia-related markers were correlated each other, and evaluation for both markers of stemness and hypoxia may have an additional value in predicting HCC outcome, especially for TACE-treated HCCs. Scirrhous HCC subtype, which frequency is 4% of HCCs shows dense intratumoral fibrosis > 50% of tumor, and correlates with aggressive gene expression signature of G2 subclass (Boyault et al.). Its key molecular features are TSC1/2 mutations, and TGF-ß signaling activation. The fibrous stroma of scirrhous HCC contains abundant cancer-associated fibroblasts and tumor-infiltrating macrophages, suggesting a possible role for this complex tumor microenvironment in the aggressive behavior of scirrhous HCC. In fact, the majority of scirrhous HCCs have been demonstrated to express K19 or other “stemness”-related markers, and therefore, K19-positive HCCs and scirrhous HCCs may lie on the same spectrum of HCCs, with the latter being defined as containing more intratumoral fibrous stroma. Mactrotrabecular massive (MTM) HCC subtype is defined as trabecular pattern with more than 6-10 cells thickness in 50% of tumor. Its frequency is 5% of HCCs and reported to have a poor prognosis. It correlates with aggressive gene expression signature of G3 subclass (Boyault et al.). Its key molecular features are TP53 mutations and FGF19 amplication. Vessels that encapsulate tumor clusters (VETC), which is defined as ≥ 55% tumor area by CD34 immunostaining is a new HCC subtype related to poor prognosis. VETC was significantly associated to high serum AFP level, tumor size >5 cm, poor differentiation, macrotrabecular pattern, and frequent microvascular invasion. Therefore, the identification of pathologic biomarkers related to aggressiveness and poor prognosis on HCC tissues obtained by biopsy, resection or transplantation could provide useful information for treatment of HCC patient. Moreover, the recent accumulation of molecular-pathological data will hopefully lead to the development of targeted therapy for this aggressive subset of HCCs.
( Young Nyun Park ), ( Ruben Raphael Plentz ), ( Hae Ryoung Kim ), ( Friederike Nellessen ), ( Britta Heike Eva Langkopf ), ( Ludwig Wilkens ), ( Annarita Destro ), ( Barbara Fiamengo ), ( Michael Peter Manns) 대한간학회 2007 Clinical and Molecular Hepatology(대한간학회지) Vol.13 No.3(S)
Hepatocellular carcinomas (HCCs) are classified into early HCCs and progressed HCCs based on their gross features and histologic differentiation. Early HCCs are vaguely nodular and well-differentiated, and usually small. Progressed HCCs show distinct tumour margins grossly, and are usually moderately or poorly differentiated, and they may be small or large. Early HCCs correspond to “in situ carcinoma” of other organs, and have significantly higher 5-year survival rate and much less recurrence rate compared to progressed HCCs. There is a subtype of progressed HCC that is morphologically consistent with HCC, but characterized by expression of hepatic stem/progenitor cell markers, such as K19, epithelial cell adhesion molecule (EpCAM), and CD133. This subtype has been associated with earlier recurrence, reduced overall survival. Their characteristic histopathological features include more infiltrative growth pattern, vascular invasion, and fibrous stromal component compared to conventional HCCs. K19 expression was reported to be associated with increased expression of epithelial-mesenchymal transition-related genes and their proteins. It was also found to be associated with longer telomeres, increased hTERT expression and increased chromosomal instability, suggesting that these HCCs have a survival advantage over K19-negative HCCs by maintaining telomeres despite the increased chromosomal instability. Hypoxic microenvironment is important in the generation and maintenance of stemness, the expression of stemness (K19, EpCAM) and hypoxia (CAIX)-related markers were correlated each other, and HCC expressing these markers showed resistance to TACE and poorer outcome. Evaluation for both markers of stemness and hypoxia may have an additional value in predicting HCC outcome, especially for TACE-treated HCCs.
Purpose: To determine if it is feasible and safe for a surgeon to transition from using the posterolateral approach to direct anterior approach (DAA) by evaluating the first 53 cases of total hip arthroplasty using a DAA. Materials and Methods: A retrospective review of 52 patients who underwent THA using a DAA between July 2017 and December 2018. Reasons for THA were: femoral neck fracture (n=34), avascular necrosis (n=13), and arthritis (n=6). The mean age was 70 years old. An assessment of feasibility was made by analyzing mean operative time and blood loss. Cup inclination, anteversion, and leg length discrepancy (LLD) were measured using postoperative radiology. Safety of the DAA was judged using the incidence and nature of all complications. Results: The mean operative time was 112 minutes. 135 minutes for the 1st 10 cases, 100 minutes for 2nd 10 cases, 113 minutes for 3rd 10 cases, 119 minutes for 4th 10 cases, and 91 minutes for the final 13 cases. The mean blood loss was 724 mL. Average cup inclination was 40.27˚; 2 cases were out of safety angle. Mean anteversion was 16.18˚. No intraoperative fractures or infections were observed. LLD was detected in 3 cases, one of which underwent revision due to walking difficulty. Dislocation occurred in 3 cases, all within the first 20 cases, however, there was no recurrent dislocation. Conclusion: DAA for THA was deemed to be feasible and safe based on an assessment of operative time, blood loss and complications.
Recent findings indicate that Type 2 taste receptors (T2Rs) are expressed outside the gustatory system, including in the gastrointestinal tracts and the exocrine glands, such as the submandibular (SM), parotid (P), lacrimal (L) glands and pancreas (PC). Specifically, T2Rs are found in some of the gastrointestinal endocrine cells, and these cells secreted peptide hormones in response to stimulation by bitter-tasting compounds. The results show that T2Rs may have significant physiological roles besides bitter taste reception. The functions of the T2Rs in the exocrine glands remain poorly understood. An expression levels analysis of T2Rs will help to determine those functions in the exocrine glands. The expression levels of the T2Rs in the exocrine glands were discovered via the qPCR. C57BL/6J mice of 42~60-day-old were used. Messenger RNAs were extracted from S, P, L and PC. Cloned DNAs were synthesized by reverse transcription. Quantitative PCRs were performed using the SYBR Green method. The expression levels of the T2Rs were calculated as relative expression levels to that of the GAPDH. The statistical significance among the observed exocrine glands was tested using the variance analysis (ANOVA test). Tas2r108, out of murine 35 T2Rs, was the most highly expressed in every observed exocrine gland. This finding was similar to previous results from tongue papillae, but the expression levels were lower than those of the tongue papillae. Tas2r137 of SM, P, L and PC were expressed a little lower than that of tongue papillae. The T2Rs in the exocrine glands may play slightly different roles from those in the tongue. We suggest that physiological studies such as a patch clamp and functional Ca2+ imaging of acinar cells are necessary for understanding the Tas2r108 functions.