Publications by authors named "Yi-Hsin Liang"

11 Publications

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Chemotherapy agents stimulate dendritic cells against human colon cancer cells through upregulation of the transporter associated with antigen processing.

Sci Rep 2021 Apr 27;11(1):9080. Epub 2021 Apr 27.

Graduate Institute of Oncology, National Taiwan University, Taipei, Taiwan, R.O.C..

Single immunotherapy fails to demonstrate efficacy in patients with microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Research on immune reactions before and after systemic agents for mCRC is warranted. Our study examined cell line models to compare the expression of immune surface markers on colon cancer cells before and after chemotherapy agents. We also elucidated mechanisms underlying the effects of chemotherapy agents on immune surface markers. We used real-world clinical samples with NanoString analysis and the Perkin-Elmer Opal multiplex system. We established that chemotherapy agents, particularly 7-ethyl-10-hydroxycamptothecin (SN-38), the active metabolite of irinotecan, stimulated the expression of stimulatory MHC class I alleles through stimulation the pathway of transporters associated with antigen processing 1 and 2 (TAP1 and TAP2) in cell line models. Application of infected cell protein 47 (ICP-47), a specific inhibitor of the TAP1/TAP2, significantly inhibited expression of TAP1/TAP2 and also inhibited the expression of the downstream MHC class I. In the functional assay, SN-38 significantly promoted the phagocytosis of colon cancer cells by monocyte-derived dendritic cells (MoDCs). We confirmed that the expression of major histocompatibility complex (MHC) class I, significantly increased after first-line chemotherapy and targeted therapy in the samples of real-world patients with de novo mCRC. Our study provides new insights for novel immunotherapy combinations.
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http://dx.doi.org/10.1038/s41598-021-88648-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079421PMC
April 2021

Association between risk factors, molecular features and CpG island methylator phenotype colorectal cancer among different age groups in a Taiwanese cohort.

Br J Cancer 2021 Apr 12. Epub 2021 Apr 12.

Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan.

Background: CpG island methylator phenotype (CIMP) represents a carcinogenesis pathway of colorectal cancer (CRC) and the association between CIMP CRC, molecular features and risk factors in East Asian population is less studied.

Methods: We prospectively enrolled newly diagnosed CRC patients at the National Taiwan University Hospital. Clinicopathological data and risk factors for CRC were collected during interview. The tumour samples were subjected to CIMP, RAS/BRAF mutation and microsatellite instability tests. CIMP-high was determined when ≧3 methylated loci of p16, MINT1, MINT2, MINT31 and MLH1 were identified. Multivariate logistic regression was used to evaluate the association between risk factors and CIMP-high CRC.

Results: Compared with CIMP-low/negative CRC, CIMP-high CRC was associated with more stage IV disease, BRAF V600E mutation and high body mass index (BMI ≧ 27.5 kg/m) in younger patients (age < 50 y), and more right-sided tumour, BRAF V600E mutation, MSI-high and colorectal polyp in elder patients (age ≧ 50 y). Multivariate analyses showed that BMI ≧27.5 kg/m was significantly associated with CIMP-high CRC in younger patients.

Conclusions: We identified distinct clinicopathological features for CIMP-high CRC among different age groups in Taiwan. Our data suggest the association between BMI ≧27.5 kg/m and CIMP-high CRC in patients younger than 50 years.
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http://dx.doi.org/10.1038/s41416-021-01300-5DOI Listing
April 2021

Irinotecan and Oxaliplatin Might Provide Equal Benefit as Adjuvant Chemotherapy for Patients with Resectable Synchronous Colon Cancer and Liver-confined Metastases: A Nationwide Database Study.

Anticancer Res 2017 12;37(12):7095-7104

Graduate Institute of Oncology, College of Public Health, National Taiwan University, Taipei, Taiwan, R.O.C

Background: Although irinotecan and oxaliplatin are both standard treatments for advanced colon cancer, it remains unknown whether either is effective for patients with resectable synchronous colon cancer and liver-confined metastasis (SCCLM) after curative surgery.

Patients And Methods: A population-based cohort of patients diagnosed with de novo SCCLM between 2004 and 2009 was established by searching the database of the Taiwan Cancer Registry and the National Health Insurance Research Database of Taiwan. Patients who underwent curative surgery as their first therapy followed by chemotherapy doublets were classified into the irinotecan group or oxaliplatin group accordingly. Patients who received radiotherapy or did not receive chemotherapy doublets were excluded.

Results: We included 6,533 patients with de novo stage IV colon cancer. Three hundred and nine of them received chemotherapy doublets after surgery; 77 patients received irinotecan and 232 patients received oxaliplatin as adjuvant chemotherapy. The patients in both groups exhibited similar overall survival (median: not reached vs. 40.8 months, p=0.151) and time to the next line of treatment (median: 16.5 vs. 14.3 months, p=0.349) in both univariate and multivariate analyses. Additionally, patients with resectable SCCLM had significantly shorter median overall survival than patients with stage III colon cancer who underwent curative surgery and subsequent adjuvant chemotherapy, but longer median overall survival than patients with de novo stage IV colon cancer who underwent surgery only at the primary site followed by standard systemic chemotherapy (p<0.001).

Conclusion: Irinotecan and oxaliplatin exhibited similar efficacy in patients who underwent curative surgery for resectable SCCLM.
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http://dx.doi.org/10.21873/anticanres.12183DOI Listing
December 2017

Do-not-resuscitate consent signed by patients indicates a more favorable quality of end-of-life care for patients with advanced cancer.

Support Care Cancer 2017 02 4;25(2):533-539. Epub 2016 Oct 4.

Department of Oncology, National Taiwan University Hospital, No. 7, Chung-Shan South Rd, Taipei, 10002, Taiwan.

Purpose: Do-not-resuscitate (DNR) consent is crucial in end-of-life (EOL) care for patients with advanced cancer. However, DNR consents signed by patients (DNR-P) and surrogates (DNR-S) reflect differently on patient autonomy and awareness.

Methods: This retrospective study enrolled advanced cancer patients treated at National Taiwan University Hospital, Hsin-Chu Branch between 2012 and 2014. Patients who signed DNR consent at other hospitals were excluded; the remaining patients were subsequently classified into DNR-S and DNR-P groups.

Results: We enrolled 1495 patients. The most prevalent primary cancers were hepato-biliary-pancreatic (26.9 %), lung (16.3 %), and colorectal (14.0 %) cancers. We classified 965 (64.5 %) and 530 (35.5 %) patients into the DNR-S and DNR-P groups, respectively. Significant differences were observed between both groups regarding gender (p = 0.002), age (p < 0.001), and the Eastern Cooperative Oncology Group performance (p < 0.001) and educational (p < 0.001) status levels. The median survival times after DNR consent signature were 5.0 days (95 % confidence interval [CI] 4.4-5.6 days) and 14.0 days (95 % CI 12.1-15.9 days) in the DNR-S and DNR-P groups, respectively (p < 0.001). The median good death evaluation (GDE) scores were 5.4 (95 % CI 4.9-6.0) and 13.7 (95 % CI 12.7-14.6) in the DNR-S and DNR-P groups, respectively (p < 0.001). Univariate and multivariate analyses revealed that DNR-S was an independent factor for significantly low GDE scores (i.e., poor EOL care quality).

Conclusion: The DNR concept is emerging; however, the DNR-P percentage remains low (35.6 %) in patients with advanced cancer. DNR-P significantly improves the EOL care quality.
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http://dx.doi.org/10.1007/s00520-016-3434-5DOI Listing
February 2017

Cytotoxic Chemotherapy as First-Line Therapy for Advanced Non-Small-Cell Lung Cancer in Taiwan: Daily Practice.

J Cancer 2016 7;7(11):1515-23. Epub 2016 Jul 7.

7. Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; 8. Taiwan Cancer Registry, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan.

Aim: Cytotoxic chemotherapy is the standard first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) without specific gene alterations. This study examined the prescription pattern and the survival outcome of cytotoxic chemotherapy regimens in daily practice in Taiwan.

Methods: We established a population-based cohort of patients diagnosed with advanced NSCLC between 2005 and 2009 using the databases of Taiwan Cancer Registry and National Health Insurance in Taiwan. We then analyzed chemotherapy prescriptions and the survival outcomes of patients.

Results: A total of 25,008 patients with advanced NSCLC were identified, 17,443 (70.0%) of which received first-line chemotherapy and were therefore included in this study. Among them, 11,551 (66.2%) patients had adenocarcinoma and 3,292 (18.9%) patients had squamous cell carcinoma (SCC). Approximately 70% of the patients were diagnosed with NSCLC in medical centers. Platinum-based doublet chemotherapy was administered to 66.9% of the patients. Among all chemotherapy regimens, platinum with gemcitabine (33.8%) was the most common, irrespective of geographic region. The second and third most common regimens were vinorelbine alone (13.0%) and platinum with docetaxel (11.6%). The prevalence of platinum-based doublet chemotherapy regimens decreased from 71.4% in 2005 to 64.1% in 2009. Among patients with adenocarcinoma histology, those who received platinum with pemetrexed had longer OS than did patients who received other platinum-based regimens (p < 0.001).

Conclusion: Our findings reaffirm that in real-world practice, treatment plans of advanced NSCLC should be drawn up according to histology type.
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http://dx.doi.org/10.7150/jca.15180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964135PMC
July 2016

Young patients with colorectal cancer have increased risk of second primary cancers.

Jpn J Clin Oncol 2015 Nov 18;45(11):1029-35. Epub 2015 Sep 18.

Center for Comparative Effectiveness Research, National Center of Excellence for Clinical Trial and Research, National Taiwan University Hospital, Taipei City Taiwan Cancer Registry, Taipei City Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei City, Taiwan, ROC

Objective: Because the number of long-term survivors of colorectal cancer has increased, second primary cancer has become an important issue. However, previous studies were heterogeneous in design, and few data for Asia-Pacific area were available.

Methods: This was a retrospective population-based study conducted using the national database of the Taiwan Cancer Registry. Patients who have histology-proven primary colon cancer and rectal cancer from 1995 to 2005 were enrolled in this study. All second primary cancer events had to be histology proven. The standardized incidence ratio of second primary cancer was used as an indicator. Standardized incidence ratio was counted as the number of observed second primary cancer divided by the expected number of cancer cases in the general population.

Results: A total of 65 648 eligible index patients were enrolled, and 3810 second primary cancer events were identified. The standardized incidence ratio for all of the patients was 1.03 (95% confidence interval: 0.99-1.06), which implied that the risk of second primary cancer was not significantly elevated in the index patients compared with that of the general population. The standardized incidence ratio for the patients aged <50, 50-70 and >70 years was 2.52 (95% confidence interval: 2.28-2.78), 1.18 (95% confidence interval: 1.12-1.23) and 0.80 (95% confidence interval: 0.76-0.84), respectively. In young patients (aged <50 years), the standardized incidence ratio increase was statistically significant and persisted for over 10 years and this significantly increased across all subgroups. The small intestine, the large intestine, the female genital organs and the lungs were the most common sites of second primary cancer in young patients.

Conclusions: Young patients with colorectal cancer have an increased risk of developing second primary cancer.
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http://dx.doi.org/10.1093/jjco/hyv137DOI Listing
November 2015

Cetuximab Might Be Detrimental to Metastatic Colorectal Cancer Patients with KRAS Codon 12 Mutations.

Anticancer Res 2015 Jul;35(7):4207-14

Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan, R.O.C. Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan, R.O.C. Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, R.O.C.

Background: Anti-epidermal growth factor receptor (EGFR) monoclonal antibodies benefit patients with wild-type KRAS exon 2 metastatic colorectal cancer (mCRC). However, their effect in KRAS-mutant mCRC remains unclear.

Patients And Methods: This was a retrospective study enrolling 163 patients with unresectable KRAS-mutant mCRC diagnosed at the National Taiwan University Hospital between 2007 and 2011.

Results: The median overall survival (mOS) was 29.5 months in patients who had never used cetuximab and 19.0 months in those who had (p=0.040). The mOS was 32.0 months in patients with mutant KRAS codon 12 who had never used cetuximab and 17.5 months in those who had (p=0.017). In patients with mutant KRAS codon 13, the mOS was not significantly different. Univariate and multivariate Cox proportional hazards analysis revealed that absence of cetuximab treatment was an independent prognostic factor for longer mOS in patients with unresectable KRAS-mutant mCRC.

Conclusion: Cetuximab usage might be detrimental to patients with mCRC with mutant KRAS codon 12.
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July 2015

Oxaliplatin-based chemotherapy is more beneficial in KRAS mutant than in KRAS wild-type metastatic colorectal cancer patients.

PLoS One 2014 4;9(2):e86789. Epub 2014 Feb 4.

Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan ; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan ; Graduate Institute of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan.

To identify better regimens in currently available chemotherapy would be beneficial to KRAS mutant metastatic colorectal cancer (mCRC) patients because they have fewer treatment options than KRAS wild-type mCRC patients. Clinicopathologic features and overall survival (OS) of KRAS mutant and wild-type mCRC patients who had used oxaliplatin-based, irinotecan-based, bevacizumab-based, as well as cetuximab-based regimens were compared to those who had never-used oxaliplatin-based, irinotecan-based, bevacizumab-based, as well as cetuximab-based regimens respectively. Between 2007 and 2012, a total of 394 mCRC patients, in whom 169 KRAS mutant and 225 KRAS wild-type, were enrolled. In KRAS mutant patients who had used oxaliplatin-based regimens (N = 131), the OS was significantly longer than that in KRAS mutant patients who had never-used oxaliplatin-based regimens (N = 38). The OS was 28.8 months [95% confidence interval (CI): 23.2-34.4] in KRAS mutant patients who had used oxaliplatin-based regimens versus 17.8 months [95% CI: 6.5-29.1] in KRAS mutant patients who had never-used oxaliplatin-based regimens (P = 0.026). Notably, OS in KRAS wild-type mCRC patients who had used oxaliplatin-based regimens (N = 185) was not significantly longer than that in KRAS wild-type mCRC patients who had never-used oxaliplatin-based regimens (N = 40) (P = 0.25). Furthermore, the OS in KRAS mutant patients who had used either irinotecan-based, bevacizumab-based or cetuximab-based regimens was not significantly different than that in KRAS mutant patients who had never-used either irinotecan-based, bevacizumab-based or cetuximab-based regimens respectively. In multivariate analyses, patients who had used oxaliplatin-based regimens remains an independent prognostic factor for longer OS in KRAS mutant mCRC patients. In conclusion, oxaliplatin-based regimens are more beneficial in KRAS mutant than in KRAS wild-type mCRC patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0086789PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3913571PMC
December 2014

Modern prospection for hepatic arterial infusion chemotherapy in malignancies with liver metastases.

Int J Hepatol 2013 17;2013:141590. Epub 2013 Apr 17.

Department of Hemato-Oncology, E-Da Hospital, No. 1, Yi-da Road, Jiaosu Village, Yanchao, Kaohsiung 82445, Taiwan ; Department of Oncology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei City 10002, Taiwan.

Malignancy with liver metastasis plays an important role in daily oncology practice, especially for primary cancers of the gastrointestinal tract and hepatopancreatobiliary system. On account of the dual vascular supply system and the fact that most metastatic liver tumors are supplied by the hepatic artery, hepatic artery infusion chemotherapy (HAIC) is an appealing method for the treatment of liver metastases. Herein, we summarize recent study results reported in the literature regarding the use of HAIC for metastatic liver tumors, with special focus on colorectal cancer.
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http://dx.doi.org/10.1155/2013/141590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3652147PMC
May 2013

Hashimoto's encephalopathy as the cause of deteriorating consciousness during treatment of leptomeningeal carcinomatosis from breast cancer.

J Clin Oncol 2012 Nov 8;30(33):e358-9. Epub 2012 Oct 8.

National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.

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http://dx.doi.org/10.1200/JCO.2012.44.0826DOI Listing
November 2012

Disseminated microvascular pulmonary tumor embolism from non-small cell lung cancer leading to pulmonary hypertension followed by sudden cardiac arrest.

Lung Cancer 2011 Apr 17;72(1):132-5. Epub 2011 Feb 17.

Department of Oncology, National Taiwan University Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan.

Disseminated microvascular pulmonary tumor embolism (DMPTE) is extremely rare and invariably fatal. Typical symptoms and signs of DMPTE include shortness of breath and inadequate oxygenation. Here we demonstrate a patient with unexplained progressive pulmonary hypertension followed by sudden cardiac arrest, who finally diagnosed of DMPTE pathologically under veno-arterial extracorporeal membrane oxygenation (VA-ECMO) system support. A 59-year-old gentleman was diagnosed of advanced non-small cell lung cancer with clinical stage of T3N2M1 in February 2008. His disease had been controlled well for two years under first-line clinical trial and salvage pemetrexed treatment. In early January 2010, he suffered from dyspnea on exertion gradually, although cancer progression was not proven by computed tomography (CT) scan. Transthoracic echocardiography also revealed normal heart size and function. However, he was sent to emergency room (ER) one month later due to dyspnea where pulmonary hypertension was discovered by repeated echocardiography. Follow-up CT scan was shown neither evidences of tumor progression nor pulmonary thromboembolic event in all major pulmonary vessels. Unfortunately, he was found to be unconscious suddenly at ER during urination and diagnosed as pulse-less electrical activity. Cardiopulmonary resuscitation (CPR) was initiated immediately and he was sent to intensive care unit with VA-ECMO system under the impression of cardiovascular system dysfunction. He passed away 10 days after intensive treatment. A necropsy was performed after we received the inform consent from his family. DMPTE was confirmed by pathologists. Currently, diagnosis of DMPTE is challenging and treatment is limited although advances of modern medicine. DMPTE should be kept in mind if cancer patients have dyspnea, inadequate oxygen saturation and unexplained pulmonary hypertension during their disease courses that unexpected serious consequences, like sudden cardiac arrest, may happen.
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http://dx.doi.org/10.1016/j.lungcan.2010.12.022DOI Listing
April 2011