Time-degenerative Factors and the Risk of Hepatocellular Carcinoma after Antiviral Therapy among HCV Patients: A Model for Prioritization of Treatment

( Ming-lung Yu ),( Chung-feng Huang ),( Ming-lun Yeh ),( Jee-fu Huang ),( Chia-yen Dai ),( Wan-long Chuang ) 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

Aims: Age and hepatic fibrosis are the factors that increase the risk of hepatocellular carcinoma (HCC) over time. We aimed to explore their impac at the initiation of antiviral therapy on HCC among chronic hepatitis C (CHC) patients. Methods: A total of 1281 biopsy-proven CHC patients receiving interferon- based therapy were followed for a mean period of 5.5 years. Results: The 5-year cumulative incidence of HCC did not differ between non-SVR and SVR patients who were <40 years old (7.7 % vs. 0.5%, P=0.1), but was significantly higher in non-SVR patients between 40 and 55 years old (18.0% vs. 1.3%, P<0.001) and >55 years old (15.1% vs. 7.9%, P=0.03). Compared with SVR, non-SVR was independently predictive of HCC in patients 40-55 years old (hazard ratio [HR]/95% confidence intervals [CI]: 10.92/3.78-31.56, P<0.001) and >55 years old (HR/CI: 1.96/1.06-3.63, P=0.03) but not in patients <40 years old (HR/CI: 2.76/0.41-18.84, P=0.3). The 5-year cumulative incidence of HCC did not differ between non-SVR and SVR patients whose fibrosis stage was F0-1 (4.6% vs. 1.9%, P=0.25) but was higher in non-SVR patients with F2-3 (21.4% vs. 4.3%, P<0.001) or F4 (33.5% vs. 8.4%, P=0.002). Compared with SVR, non-SVR was independently predictive of HCC in patients with F2-3 (HR/CI: 4.36 /2.10-9.03, P<0.001) and F4 (HR/CI: 3.84/1.59-9.30, P=0.03) but not in those with F0-1 (HR/CI: 1.53/ 0.49-4.74, P=0.47). Conclusions: Delayed HCV clearance for patients with CHC > 40 years old or with a fibrosis stage > 2 increases the risk of HCC over time.

Comprehensive profiles and diagnostic value of menopausal-specific gut microbiota in premenopausal breast cancer

Hou Ming-Feng,Ou-Yang Fu,Li Chung-Liang,Chen Fang-Ming,Chuang Chieh-Han,Kan Jung-Yu,Wu Cheng-Che,Shih Shen-Liang,Shiau Jun-Ping,Kao Li-Chun,Kao Chieh-Ni,Lee Yi-Chen,Moi Sin-Hua,Yeh Yao-Tsung,Cheng Chi 생화학분자생물학회 2021 Experimental and molecular medicine Vol.53 No.-

In Western countries, breast cancer tends to occur in older postmenopausal women. However, in Asian countries, the proportion of younger premenopausal breast cancer patients is increasing. Increasing evidence suggests that the gut microbiota plays a critical role in breast cancer. However, studies on the gut microbiota in the context of breast cancer have mainly focused on postmenopausal breast cancer. Little is known about the gut microbiota in the context of premenopausal breast cancer. This study aimed to comprehensively explore the gut microbial profiles, diagnostic value, and functional pathways in premenopausal breast cancer patients. Here, we analyzed 267 breast cancer patients with different menopausal statuses and age-matched female controls. The α-diversity was significantly reduced in premenopausal breast cancer patients, and the β-diversity differed significantly between breast cancer patients and controls. By performing multiple analyses and classification, 14 microbial markers were identified in the different menopausal statuses of breast cancer. Bacteroides fragilis was specifically found in young women of premenopausal statuses and Klebsiella pneumoniae in older women of postmenopausal statuses. In addition, menopausal-specific microbial markers could exhibit excellent discriminatory ability in distinguishing breast cancer patients from controls. Finally, the functional pathways differed between breast cancer patients and controls. Our findings provide the first evidence that the gut microbiota in premenopausal breast cancer patients differs from that in postmenopausal breast cancer patients and shed light on menopausal-specific microbial markers for diagnosis and investigation, ultimately providing a noninvasive approach for breast cancer detection and a novel strategy for preventing premenopausal breast cancer.

Clinical Practice of Blood Transfusion in Orthotopic Organ Transplantation: A Single Institution Experience

Tsai, Huang-Wen,Hsieh, Fu-Chien,Chang, Chih-Chun,Su, Ming-Jang,Chu, Fang-Yeh,Chen, Kuo-Hsin,Jeng, Kuo-Shyang,Chen, Yun Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.17

Background: Orthotopic organ transplantation, a treatment option for irreversible organ dysfunction according to organ failure, severe damaged organ or malignancy in situ, was usually accompanied with massive blood loss thus transfusion was required. We aimed to evaluate the adverse impact of blood transfusion on solid organ transplantation. Materials and Methods: From January, 2009 to December, 2014, patients who received orthotopic organ transplantation at Far Eastern Memorial Hospital medical center were enrolled. Clinical data regarding anemia status and red blood cell (RBC) transfusion before, during and after operation, as well as patient outcomes were collected for further univariate analysis. Results: A total of 105 patients who underwent orthotopic transplantation, including liver, kidney and small intestine were registered. The mean hemoglobin (Hb) level upon admission and before operation were $11.6{\pm}1.8g/dL$ and $11.7{\pm}1.7g/dL$, respectively; and the nadir Hb level post operation and the final Hb level before discharge were $8.3{\pm}1.6g/dL$ and $10.2{\pm}1.6g/dL$, respectively. The median units (interquartile range) of RBC transfusion in pre-operative, peri-operative and post-operative periods were 0 (0-0), 2 (0-12), and 2 (0-6) units, respectively. Furthermore, the median (interquartile range) length of hospital stay (LHS) from admission to discharge and from operation to discharge were 28 (17-44) and 24 (16-37) days, respectively. Both peri-operative and post-operative RBC transfusion were associated with longer LHS from admission to discharge and from operation to discharge. Furthermore, it increased the risk of post-operative septicemia. While peri-operative RBC transfusion elevated the risk of acute graft rejection in patients who received orthotopic transplantation. Conclusions: Worse outcome could be anticipated in those who had received massive RBC transfusion in transplantation operation. Hence, peri-operative RBC transfusion should be avoided as much as possible.

Significant down-regulation of growth hormone receptor expression revealed as a new unfavorable prognostic factor in hepatitis C virus-related hepatocellular carcinoma

( Ching-chih Lin ),( Ta-wei Liu ),( Ming-lun Yeh ),( Yi-shan Tsai ),( Pei-chien Tsai ),( Chung-feng Huang ),( Jee-fu Huang ),( Wan-long Chuang ),( Chia-yen Dai ),( Ming-lung Yu ) 대한간학회 2021 Clinical and Molecular Hepatology(대한간학회지) Vol.27 No.2

Background/Aims: Growth hormone (GH) is the main regulator of somatic growth, metabolism, and gender dimorphism in the liver. GH receptor (GHR) signaling in cancer is derived from a large body of evidence, although the GHR signaling pathway involved in the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV)-related HCC, remains unclear. We aimed to explore the expression of GHR and analyze its association with clinicopathologic features and prognosis of patients with chronic hepatitis C and HCC. Methods: The expression of GHR mRNA was investigated by quantitative real-time polymerase chain reaction in paired tumors and adjacent non-tumorous (ANT) liver tissues of 200 patients with chronic hepatitis C and HCC. Western blotting and immunofluorescence assays using the HCV-infected Huh7.5.1 cell model was performed. Results: GHR mRNA was significantly lower in HCV-HCC tissues than in corresponding ANT liver tissues. GHR mRNA and protein levels also decreased in the HCV-infected Huh7.5.1 cell model. Notably, lower GHR expression was associated with age of >60 years (P=0.0111) and worse clinicopathologic characteristics, including alpha-fetoprotein >100 ng/mL (P=0.0403), cirrhosis (P=0.0075), vascular invasion (P=0.0052), pathological stage II-IV (P=0.0002), and albumin ≤4.0 g/dL (P=0.0055), which were linked with poor prognosis of HCC. Most importantly, the high incidence of recurrence and poor survival rates in patients with a low ratio of tumor/ANT GHR (≤0.1) were observed, indicating that low expression levels of GHR had great risk for development of HCC in patients with chronic hepatitis C. Conclusions: Our study demonstrates a significant down-regulation of GHR expression as a new unfavorable independent prognostic factor in patients with chronic hepatitis C and HCC. (Clin Mol Hepatol 2021;27:313-328)

Clinical Significance of Smudge Cells in Peripheral Blood Smears in Hematological Malignancies and Other Diseases

Chang, Chih-Chun,Sun, Jen-Tang,Liou, Tse-Hsuan,Kuo, Chin-Fu,Bei, Chia-Hao,Lin, Sheng-Jun,Tsai, Wei-Ting,Tan, N-Chi,Liou, Ching-Biau,Su, Ming-Jang,Yen, Tzung-Hai,Chu, Fang-Yeh Asian Pacific Journal of Cancer Prevention 2016 Asian Pacific journal of cancer prevention Vol.17 No.4

Background: It is reported that the percentage of smudge cells in the blood smear could be a prognostic indicator in chronic lymphocytic leukemia. However, the clinical significance of smudge cells in other hematological malignancies, solid tumors or non-malignant diseases is less clear. Hence, this study was conducted to survey the clinical significance of smudge cells in hematological cancers and other disorders. Materials and Methods: From January to November, 2015, the clinical data of patients who received blood examination with differential counts for clinical purpose and were found to have smudge cells in the peripheral blood film in Far Eastern Memorial Hospital were selected. The percentage of smudge cells and patient outcomes were evaluated for further univariate and survival analyses. Results: A total of 102 patients with smudge cells in their blood smears were included. Smudge cells were frequently presented in out-of-hospital cardiac arrest (OHCA; n=30), infections (n=23), hematological cancers (n=23) and solid cancers (n=10). There was no relationship between the percentage of smudge cells and the patient mortality in all diseases (OR: 1.08, 95% CI: 0.47-2.48, P=1.000) as well as the OHCA group (OR: 1.91, 95% CI: 0.38-9.60, P=0.694). It was observed that in patients with all cancers with the percentage of smudge cells less than 50% had a lower mortality rate in comparison with those who had the percentage of smudge cells of 50% or more (OR: 22.29, 95% CI: 2.38-208.80, P<0.001). Additionally, it was seemingly that patients with smudge cells of 50% or more had a lower survival rate than those with smudge cells less than 50% in all cancers with follow-up at 2-month intervals, but without statistical significance (P=0.064). Conclusions: Our survey indicated that in all cancers, those who had higher percentage of smudge cells were prone to have poor outcomes when compared with the subjects with lower percentage of smudge cells. This finding was quite different from the results of previous studies in which the race-ethnicity of most study populations was non-Asian; hence, further investigations are required. Besides, there was no apparent association of the percentage of smudge cells with patient outcomes in all diseases, including OHCA.

The Different Expression of Gene Profiles on Hepatocellular Carcinoma Cells with Different Intracellular Hepatitis C Viral Load

( Chia-yen Dai ),( Shu-chi Wang ),( Meng-hsuan Hsieh ),( Cheng-fu Yang ),( Ching-i Huang ),( Chung-feng Huang ),( Ming-lun Yeh ),( Jee-fu Huang ),( Wang-long Chung ),( Ming-lung Yu ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: The different hepatitis C virus (HCV) replication has been reported among individual hepatocytes in chronic HCV infection by identifying hepatocytes with different HCV RNA levels. We have previously established a fluorescence-activated cell sorting (FACS) protocol to study the effects of different intracellular viral loads in HCV-infected cells. The present study aimed to further study the gene expression on different hepatocellular carcinoma (HCC) cells with different HCV viral load. Methods: The JFH1-EYFP viral florescence intensity was used to sort the high and low viral load cells after 5 days infection in vitro which has been shown in our previous study that infected cells efficiently and accurately discriminated between high- and low-viral load cell populations. The next generation sequence-RNA sequence was used to clarify the mRNA and miRNA gene network between HCV-high and HCV-low infected cells of the HCC cell line. Venn diagram summarizing the probe sets that were differentially expressingbetween the Huh7.5.1 versus each differential viral load cell population and miRDB and miRTar databases were used to predict HVL and LVL/S2 unique miRNA target genes. Results: By analyzing the NGS dataset and miRNA microarray dataset, of the significant transcripts, three miRNA were unique for the LVL/S2 cells and nine miRNA unique for the HVL. Twenty-three miRNA were common for all 3 viral load groups. We verified them by q-PCR and data confirmed the array data expression level. We found that high viral loads were associated with cell inflammation- and cell death-associated pathway; and the low viral loads were associated many stress response- and cell adhesion molecular (CAMs)-related genes. Conclusions: With the established cell sorting protocol, we have demonstrated that different gene network between HCV-high and HCV-low infected cells in JFH1-EYFP infectious cells exists. Our results may provide a boarder gene regulation map between high and low viral load cell populations.

Percutaneous Endoscopic Interbody Debridement and Fusion for Pyogenic Lumbar Spondylodiskitis: Surgical Technique and the Comparison With Percutaneous Endoscopic Drainage and Debridement

Po-Ju Lai,Sheng-Fen Wang,Tsung-Ting Tsai,Yun-Da Li,Ping-Yeh Chiu,Ming-Kai Hsieh,Fu-Cheng Kao 대한척추신경외과학회 2021 Neurospine Vol.18 No.4

Objective: Surgical treatment of severe infectious spondylodiskitis remains challenging. Although minimally invasive percutaneous endoscopic drainage and debridement (PEDD) may yield good results in complicated cases, outcomes of patients with extensive structural damage and mechanical instability may be unsatisfactory. To address severe infectious spondylodiskitis, we have developed a surgical technique called percutaneous endoscopic interbody debridement and fusion (PEIDF), which comprises endoscopic debridement, bone-graft interbody fusion, and percutaneous posterior instrumentation. Methods: Outcomes of PEIDF in 12 patients and PEDD in 15 patients with infectious spondylodiskitis from April 2014 to July 2018 were reviewed retrospectively. Outcome were compared between 2 kinds of surgical procedures. Results: Patients in PEIDF group had significantly lower rate of revision surgery (8.3% vs. 58.3%), better kyphosis angle (-5.73°±8.74 vs. 1.07°±2.70 in postoperative; 7.09°±7.23 vs. 0.79°±4.08 in kyphosis correction at 1 year), and higher fusion rate (83.3% vs. 46.7%) than those who received PEDD. Conclusion: PEIDF is an effective approach for treating infectious spondylodiskitis, especially in patients with spinal instability and multiple medical comorbidities.

Max-throughput interference avoidance mechanism for indoor self-organizing small cell networks

Kuang-Hsun Lin,Cho-Hsin Tsai,Jen-Wei Chang,Yu-Chieh Chen,Hung-Yu Wei,Fu-Ming Yeh 한국통신학회 2017 ICT Express Vol.3 No.3

Since mobile traffic has been growing recently, the deployment of indoor small cells has become an attractive solution to enhance coverage. However, the increasing density of cells makes inter-cell interference more considerable. In this paper, we propose a max-throughput Interference Avoidance (MTIA) centralized algorithm to improve the system’s throughput. Based on signaling and reports, a central controller connected to each base station can properly turn off base stations that may induce a relatively strong interference, and thus increase SINR. We implemented the MTIA algorithm in an LTE TDD network simulation and showed that MTIA effectively reduces inter-cell interference and improves the system’s throughput.