Expanding Indications for Liver Transplant: Tumor and Patient Factors

( Kevin Ka-wan Chu ),( Kelly Hiu-ching Wong ),( Kenneth Siu-ho Chok ) 대한간학회 2021 Gut and Liver Vol.15 No.1

During the past few decades, liver transplant has developed from a high-mortality procedure to an almost routine procedure with good survival outcomes. The development of living donor liver transplant has increased the availability of liver grafts, and the scope of indications for liver transplant has been expanding ever since. The aim of this review is to provide an overview of such an expansion of scope. Various criteria have been proposed to expand the eligibility of patients with hepatocellular carcinoma exceeding the Milan criteria for liver transplant. Furthermore, liver transplant is increasingly performed as a treatment modality for cholangiocarcinoma, neuroendocrine liver metastasis and colorectal liver metastasis. The number of elderly patients receiving liver transplant is on the rise. Combined organ transplantation has also been adopted to treat patients with multiple organ failure. Going forward, further development of preoperative noninvasive predictors in tumor, patient and even donor factors is needed to identify patients at risk of poor outcomes and hence optimize patient management. (Gut Liver 2021;15:19-30)

Living Donor Liver Transplant Confers Better Survival for Elderly Recipients

( Chu Kevin Ka-wan ),( Chok Kenneth Siu-ho ),( Fung James Yan-yue ),( Chan Albert Chi-yan ),( Lo Chung Mau ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Increasing elderly patients are undergoing liver transplant as well as the relative percentage of elderly population. However, the perceived poor outcomes in the elderly prohibits the acceptance of living donor liver transplant in many centres. We reviewed current status of liver transplant in our centre and analyzed factors predicting survival outcome in elderly liver transplant recipients. Methods: Consecutive liver transplants for elderlies who reached age 65 performed between 2001 and 2016 were reviewed. The overall survival were compared between the deceased donor liver transplant (DDLT) and the living donor liver transplant (LDLT) groups. Results: DDLT and LDLT groups consisted of 24 and 17 recipients respectively. The overall 1-year and 3-year survival rates for the elderlies (n=41) were 87%, 78% respectively. LDLT recipients had better survival compared with DDLT, 94% vs 83% for 1-year and 94% vs 67% for 3-year, p=0.036. Univariate analysis was performed and identified predictive factors including pre-operative ICU stay (relative risk 3.74, 95% confidence interval 1.06-13.14, p=0.039), pre-operative hepatorenal syndrome (relative risk 6.01, 95% confidence interval 1.67-21.68, p=0.006) and mode of graft donation - LDLT (relative risk 0.09, 95% confidence interval 0.01-0.86, p=0.036). Long cold ischaemic time also had a negative correlation with survival (relative risk 4.30, 95% confidence interval 0.81-22.90, p=0.087). In multi multivariate analysis, LDLT (hazard ratio 0.11, 95% confidence interval 0.01-0.94, p=0.043) and pre-operative ICU stay (hazard ratio 5.60, 95% confidence interval 1.30-24.03, p=0.021) were independent predictive factors for survival. Conclusions: Good survival outcomes was achieved in selected elderly liver transplant recipients. Elderly recipients with living donors had better survival outcomes in contrast to those with deceased donors and LDLT was an independent protective factor for long term survival. Pre-operative ICU status was also an independent predictive of poorer long term survival.

Stand-Alone Cervical Cages in 2-Level Anterior Interbody Fusion in Cervical Spondylotic Myelopathy: Results from a Minimum 2-Year Follow-up

Eugene Pak-Lin Ng,Andrew Siu-Leung Yip,Keith Hay-Man Wan,Michael Siu Hei Tse,Kam Kwong Wong,Tik-Koon Kwok,Wing Cheung Wong 대한척추외과학회 2019 Asian Spine Journal Vol.13 No.2

Study Design: A retrospective review of patients who underwent 2-level anterior cervical discectomy and fusion (ACDF) with stand-alone polyetheretherketone (PEEK) cages for cervical spondylotic myelopathy (CSM). Purpose: To evaluate the efficacy of stand-alone PEEK cage in 2-level cervical interbody fusion for CSM. Overview of Literature: ACDF is a standard surgical procedure to treat degenerative disc disease. However, the use of additional anterior plating for 2-level ACDF remains controversial. Methods: We reviewed outcomes of patients who underwent 2-level ACDF with stand-alone PEEK cages for CSM over a 7-year period (2007–2015) in a regional hospital. Japanese Orthopaedic Association (JOA) score, fusion rate, subsidence rate, cage migration, and cervical alignment by the C2–7 angle as well as the local segmental angle (LSA) of the cervical spine were assessed. Results: In total, 31 patients (mean age, 59 years; range, 36–87 years) underwent 2-level ACDF with a cage-only construct procedure between 2007 and 2015. The minimum follow-up was 24 months; mean follow-up was 51 months. C3–5 fusion was performed in 45%, C4–6 fusion in 32%, and C5–7 fusion in 23%. Mean JOA score improved from 10.1±2.2 to 13.9±2.1 (p<0.01) at the 24-month follow-up. Fusion was achieved in all patients. Subsidence occurred in 22.5% of the cages but was not associated with differences in JOA scores, age, sex, or levels fused. Lordosis of the C2–7 angle and LSA increased after surgery, which were maintained for up to 1 year but subsequently disappeared after 2 years, yet the difference was not statistically significant. No cage migration was noted; two patients developed adjacent segment disease requiring posterior laminoplasty 3 years after ACDF. Conclusions: The use of a stand-alone PEEK cage in a 2-level cervical interbody fusion achieves satisfactory improvements in both clinical outcomes and fusion.

Quercetin-mediated Cell Cycle Arrest and Apoptosis Involving Activation of a Caspase Cascade through the Mitochondrial Pathway in Human Breast Cancer MCF-7 Cells

Chu-Chung Chou,Jai-Sing Yang,Hsu-Feng Lu,Siu-Wan Ip,Chyi Lo,Chih-Chung Wu,Jing-Pin Lin,Nou-Ying Tang,Jing-Gung Chung,Ming-Jen Chou,Ying-Hock Teng,Dar-Ren Chen 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.8

Dietary polyphenols have been correlated with a reduced risk of developing cancer. Quercetin (a natural polyphenolic compound) induced apoptosis in many human cancer cell lines, including breast cancer MCF-7 cells. However, the involvement of possible signaling pathways and the roles of quercetin in apoptosis are still undefined. The purpose of this study was to investigate the effects of quercetin on the induction of the apoptotic pathway in human breast cancer MCF-7 cells. When MCF-7 cells were treated with quercetin for 24 and 48 h and at various doses (10-175 μM), cell viability decreased significantly in time- and dose-dependent manners. Exposure of MCF-7 cells to 10-175 μM quercetin resulted in an approximate 90.25% decrease in viable cells. To explicate the mechanism underlying the antiproliferative effect of quercetin, cell cycle distribution and apoptosis in MCF-7 cells was investigated after exposure to 150 μM quercetin for 6-48 h. Quercetin caused a remarkable increase in the number of S phase (14.56%to 61.35%) and sub-G1 phase cells (0.1% to 8.32%) in a dose- and time-dependent manner. Quercetin caused S phase arrest by decreasing the protein expression of CDK2, cyclins A and B while increasing the p53 and p57 proteins. Following incubation with quercetin for 48 h, MCF-7 cells showed apoptotic cell death by the decreased levels of Bcl-2 protein and ΔΨ m and increased activations of caspase-6, -8 and -9. Moreover, quercetin increased the AIF protein released from mitochondria to nuclei and the GADD153 protein translocation from endoplasmic reticulum to the nuclei. These data suggested that quercetin may induce apoptosis by direct activation of the caspase cascade through the mitochondrial pathway in MCF-7 cells.

Chrysophanol-induced Necrotic-like Cell Death through an Impaired Mitochondrial ATP Synthesis in Hep3B Human Liver Cancer Cells

Chien-Hang Ni,Jing-Gung Chung,Po-Yuan Chen,Hsu-Feng Lu,Jai-Sing Yang,Hui-Ying Huang,Shin-Hwar Wu,Siu-Wan Ip,Chin-Tung Wu,Su-Yin Chiang,Jaung-Geng Lin,W. Gibson Wood 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.5

Liver cancer is the most common form of cancer in Taiwan and it usually responds to chemotherapy. However, patients often have side effects to the chemotherapeutic drugs. Thus new agents are urgently required to treat liver cancer. Chrysophanol, one of the anthraquinone derivatives, was reported to inhibit some human cancer cell growth which may be due to the induction of apoptosis similar to other anthraquinone derivatives though such actions have not been reported. In the present study, we reported that chrysophanol inhibits cell growth in Hep3B liver cancer cells based on the following observations: 1) induc cell morphological changes; 2) decreased percentage of viable cells; 3) induced S phase arrest of cell cycle progression; 4) induced DNA damage as measured by comet assay and DAPI staining. Chrysophanolinduced cell death however, seems to be related to necrotic processes rather than typical apoptosis. Chrysophanol induced reactive oxygen species and Ca2+ production and decreased mitochondrial membrane potential (ΔΨm) and ATP levels in Hep3B cells. No effects were observed on known protein regulators of apoptosis such as Bax and Bcl-2. Chrysophanolinduced cell death took place independently of caspase-8 and -9. Based on our findings, we propose that chrysophanol reduces cellular ATP levels causing a drop in energy resulting in necrotic-like cell death.