Yi‐Chen Yeh

Taipei Veterans General Hospital

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Hsiang‐Ling Ho

Taipei Veterans General Hospital

Teh‐Ying Chou

National Yang Ming Chiao Tung University

Teh‐Ying Chou

Taipei Veterans General Hospital

Po‐Kuei Hsu

Taipei Veterans General Hospital

Yu–Chung Wu

Taipei Medical University Hospital

Chao‐Hua Chiu

Taipei Veterans General Hospital

Chien‐Sheng Huang

Taipei Veterans General Hospital

Han‐Shui Hsu

Taipei Veterans General Hospital

Wen‐Hu Hsu

National Yang Ming Chiao Tung University

Chi‐Lu Chiang

National Yang Ming Chiao Tung University

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National Yang Ming Chiao Tung University

458

Taipei Veterans General Hospital

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National Taiwan University

173

National Yang Ming University Hospital

159

National Taipei University

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National Taiwan University Hospital

148

Taipei Medical University

Chang Gung University

National Cheng Kung University

China Medical University

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Recent Advances in the Diagnosis and Management of Multiple Primary Lung Cancer

Cancers (2022)

Chi‐Lu Chiang Ping‐Chung Tsai Yi‐Chen Yeh Yuan‐Hung Wu Han‐Shui Hsu

With the wide application of computed tomography in lung cancer screening, the incidence of multiple primary lung cancer (MPLC) has been increasingly reported. Despite the established criteria, the differentiation between MPLC and intrapulmonary metastasis remains challenging. Although histologic features are helpful in some circumstances, a molecular analysis is often needed. The application of next-generation sequencing could aid in distinguishing MPLCs from intrapulmonary metastasis, decreasing ambiguity. For MPLC management, surgery with lobectomy is the main operation method. Limited resection does not appear to negatively affect survival, and it is a reasonable alternative. Stereotactic ablative radiotherapy (SABR) has become a standard of care for patients refusing surgery or for those with medically inoperable early-stage lung cancer. However, the efficacy of SABR in MPLC management could only be found in retrospective series. Other local ablation techniques are an emerging alternative for the control of residual lesions. Furthermore, systemic therapies, such as targeted therapy for oncogene-addicted patients, and immunotherapy have shown promising results in MPLC management after resection. In this paper, the recent advances in the diagnosis and management of MPLC are reviewed.

10.3390/cancers14010242

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Citations (19)

Correction: A novel HIF1α-STIL-FOXM1 axis regulates tumor metastasis

Journal of Biomedical Science (2024)

Yiwei Wang Shu‐Chuan Chen De-Leung Gu Yi‐Chen Yeh Jhih-Jie Tsai

FOXM1

10.1186/s12929-024-01021-w

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Pulmonary neuroendocrine tumors: Study of 90 cases focusing on clinicopathological characteristics, immunophenotype, preoperative biopsy, and frozen section diagnoses

Journal of Surgical Oncology (2013)

Yi‐Chen Yeh Teh‐Ying Chou

Background and Objectives Pulmonary neuroendocrine tumors have a prognostic spectrum including typical carcinoid (TC), atypical carcinoid (AC), small cell carcinoma (SCLC), and large cell neuroendocrine carcinoma (LCNEC). We conducted a retrospective study to compare their clinicopathological characteristics, immunophenotype, preoperative biopsy and frozen section diagnoses, and prognosis. Methods Ninety cases of surgically treated pulmonary neuroendocrine tumors were studied. Immunohistochemical studies were performed using antibodies to chromogranin A, synaptophysin, and CD56. The preoperative biopsy and frozen section diagnoses were reviewed. Results The 5‐year survival rates for TC, AC, SCLC, and LCNEC were 96.6%, 66.7%, 42.4%, and 38.0%, respectively. T stage and pleural status correlated with outcome of SCLC and LCNEC, but N‐stage and overall TNM stage did not. In preoperative biopsy, accurate diagnosis was achieved in 5 of 11 TC, 2 of 4 AC, 6 of 15 SCLC, and 0 of 5 LCNEC cases. Using frozen sections, accurate diagnosis was achieved in 8 of 12 TC, 2 of 11 SCLC, and 0 of 11 LCNEC cases. Conclusions LCNEC was the most difficult to diagnose using either preoperative biopsy or frozen sections. T stage and pleural status can predict outcome of SCLC and LCNEC. J. Surg. Oncol. 2014 109:280–286 . © 2013 Wiley Periodicals, Inc.

Immunophenotyping

Synaptophysin

Chromogranin A

10.1002/jso.23497

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Citations (33)

Disseminated and massive tumor burden in a case of primary thymic mucinous adenocarcinoma

Journal of Cancer Research and Practice (2019)

Huiwen Liu Chih‐Yi Liu Yi‐Chen Yeh

Primary thymic mucinous adenocarcinoma is an extremely rare type of thymic carcinoma that is resistant to radiation and chemotherapy. We present a case of primary thymic mucinous adenocarcinoma with disseminated metastases and rapid progression, after concurrent chemoradiation and platinum-based doublet chemotherapy. Case and literature review also revealed poor outcomes for primary thymic mucinous adenocarcinoma patients receiving surgery and adjuvant therapy. We concluded the poor response of either resectable or unresectable primary thymic mucinous adenocarcinoma.

Mucinous carcinoma

Adjuvant Chemotherapy

Primary tumor

Thymic carcinoma

10.4103/jcrp.jcrp_13_19

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Abstract 3442: Genome-wide association study reveals potential biomarkers after pulmonary metastasectomy for head and neck cancer

Cancer Research (2018)

Hsueh‐Ju Lu Chih‐Cheng Hsieh Chi-Chun Yeh Yi‐Chen Yeh Muh‐Hwa Yang

Abstract Introduction: At least 10% of head neck cancer squamous cell carcinoma (HNSCC) progress to pulmonary metastases with overall survival (OS) around 12 months. Whether aggressively pulmonary metastasectomy (PM) improving survival or not is controversial. Method and materials: Different head neck cancer patients receiving PM from thoracic surgeon were enrolled from 2003 to 2012. Matched HNSCC and adenoid cystic carcinoma (ACC) samples as control were selected to perform whole-exon sequencing (WES) and identify potential biomarkers between short- and long- term surviving groups after metastasectomy. Identified mutant genes were mapped into possible signaling pathways by using DAVID ( https://david.ncifcrf.gov/). Result: A total of 31 head and neck cancer patients were enrolled and the survivals were different significantly among cancer types. Eight matched PM samples (3 short-term post-metastaectomy survival (PMS) HNSCC, 3 long-term HNSCC, and 2 ACC), with differently clinical outcomes (PMS, P = 0.016; OS, P = 0.015), were enrolled for WES. Eighteen percentages (18%, 306/1706) of identified genetic alternations were mapped into DAVID. Cancer-associated signal pathways were top-ranked related to short-term HNSCC; hematopoietic cell lineage associated pathways for long-term HNSCC; complement and coagulation cascades associated pathways for ACC. The overlapped genes between short-term HNSCC and ACC were relative to metabolic-associated pathway, such as branched-chain amino acid consumption (P < 0.001, fold enrichment (FE) = 7.97) and the metabolism of arginine and proline metabolism (P < 0.001, FE = 4.96). The overlapped genes between long-term HNSCC and ACC were relative to focal adhesion (P =0.008, FE = 2.84) and ECM-receptor interaction (P = 0.015, FE = 4.08). Conclusion: Genome-wide association study effectively separated clinical outcome of head neck cancer patients and successfully identified specific mutations for prognosis after PM. Basic characteristics of patients receiving whole-exon sequencing for pulmonary metastatic tumor.GroupAgeGenderPrimary tumor siteHistological typeInitial pathologic stagingBrief historyOverall survivalPost-metastasectomy survivalCase 1Short-term survival86.0MaleHypopharynxSquamous cell carcinomapT4aN2bSurgical resection followed by adjuvant radiotherapy; one metastatic nodule at right lower lung was resected.23.914.4Case 2Short-term survival60.9MaleOropharynxSquamous cell carcinomapT4aN1Surgical resection followed by adjuvant chemoradiotherapy; two metastatic nodules at right and left upper lung were resected.26.011.9Case 3Short-term survival47.1MaleOropharynxSquamous cell carcinomapT4aN2bInduction chemotherapy followed by definitive surgical resection and adjuvant chemoradiotherapy; one left upper lung metastasis was resected.22.87.1Case 4Long-term survival38.9MaleHypopharynxSquamous cell carcinomapT2N2bSurgical resection followed by adjuvant radiotherapy; multiple bilateral lung metastases with sequential wedge resection for left and right side lesions52.140.2Case 5Long-term survival51.3MaleHypopharynxSquamous cell carcinomapT3N2bSurgical resection followed by adjuvant chemoradiotherapy; 3 metastatic lesion at right upper, middle and left lower lung were resected.89.842.7Case 6Long-term survival54.4MaleHypopharynxSquamous cell carcinomapT4aN2bSurgical resection followed by adjuvant chemoradiotherapy; 2 metastatic lesions at bilateral lung apices with sequential wedge resection134.891.1Case 7Control39.6FemaleOral cavityAdenoid cystic carcinomapT4aNoSurgical resection followed by adjuvant chemoradiotherapy; 2 metastatic nodules at right upper and middle lung were resected130.187.0Case 8Control46.2FemaleRight maxillary sinus and nasal cavityAdenoid cystic carcinomaUnknownSurgical resection followed by adjuvant radiotherapy; 2 metastatic nodules at right upper and middle lung were resected195.079.9 Citation Format: Hsueh-Ju Lu, Chih-Cheng Hsieh, Chi-Chun Yeh, Yi-Chen Yeh, Muh-Hwa Yang, Chi-Ying F. Huang, Peter Mu-Hsin Chang. Genome-wide association study reveals potential biomarkers after pulmonary metastasectomy for head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3442.

Metastasectomy

10.1158/1538-7445.am2018-3442

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Ampicillin and Amoxicillin Use and the Risk of Klebsiella pneumoniae Liver Abscess in Taiwan

The Journal of Infectious Diseases (2013)

Yi-Tsung Lin Chia‐Jen Liu Yi‐Chen Yeh Tzeng‐Ji Chen Chang-Phone Fung

Background. Klebsiella pneumoniae liver abscess (KPLA) is prevalent in East Asia. Use of amoxicillin/ampicillin may lead to overgrowth of K. pneumoniae in the intestine and predispose to KPLA. We used an animal study and nationwide population-based database to investigate the association between ampicillin/amoxicillin use and KPLA in Taiwan.

10.1093/infdis/jit157

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Citations (49)

Associations Between Mutations and Histologic Patterns of Mucin in Lung Adenocarcinoma

The American Journal of Surgical Pathology (2014)

Kyuichi Kadota Yi‐Chen Yeh Sandra P. D’Angelo André L. Moreira Deborah Kuk

Multiple reports indicate that epidermal growth factor receptor (EGFR) mutations are associated with lepidic-pattern lung adenocarcinoma and that KRAS mutations are associated with invasive mucinous adenocarcinoma. We sought to investigate the association between EGFR and KRAS mutations and specific morphologic characteristics, such as predominant histologic subtype and mucinous features. Clinical data for 864 patients with resected lung adenocarcinoma that underwent molecular testing for EGFR and KRAS mutations were collected. Histologic subtyping was performed according to the IASLC/ATS/ERS lung adenocarcinoma classification, with attention given to signet-ring cell feature and extracellular mucin. EGFR mutations were detected using a polymerase chain reaction-based sizing assay, KRAS mutations were detected using Sanger sequencing, and ALK expression was detected using immunohistochemistry. Invasive mucinous adenocarcinoma was associated with KRAS mutation (P<0.001). Among invasive mucinous adenocarcinomas with KRAS mutation, a pure mucinous pattern was more common than a mixed mucinous/nonmucinous pattern (P=0.002). Invasive mucinous adenocarcinoma was associated with KRAS transition mutations (G→A) but not transversion mutations (G→T or G→C) compared with nonmucinous tumors (P=0.009). The lepidic-predominant group was associated with EGFR mutation compared with nonlepidic-predominant tumors (P=0.011). Extracellular mucin was associated with KRAS mutation (P<0.001), whereas signet-ring cell feature was not associated with EGFR or KRAS mutation (P=0.517). ALK expression was associated with signet-ring cell feature (P=0.001) but not with extracellular mucin (P=0.089). Our study shows that histologic patterns of mucin in lung adenocarcinoma-including invasive mucinous adenocarcinoma and extracellular mucin-are associated with KRAS mutation.

Signet ring cell

10.1097/pas.0000000000000246

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Citations (153)

Characteristics, treatment patterns, and prognostic factors in small cell lung cancer transformation of advanced non-small cell lung cancer with epidermal growth factor receptor mutation after tyrosine kinase inhibitor therapy.

Journal of Clinical Oncology (2024)

Ying-Ting Liao Chi‐Lu Chiang Ruei-Lin Sun Yi‐Chen Yeh Hsu-Ching Huang

e20569 Background: Small cell lung cancer transformation in advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation following tyrosine kinase inhibitor (TKI) therapy poses a challenging clinical scenario. This study aims to explore the characteristics, treatment patterns, and prognostic factors associated with this transformation. Methods: A total of 41 patients with transformed SCLC (tSCLC) were included. Patient characteristics, treatment details, and laboratory data were collected. Re-biopsy specimens and subsequent treatments were analyzed. Statistical analyses were conducted to identify factors associated with treatment response and survival outcomes. Results: The median age of the patients was 61.7 years old, with a median time from TKI treatment to small cell transformation of 22.2 months. The majority were female (58.5%), never smokers (80.5%), with 53.7% having stage IVB disease prior to EGFR-TKI treatment. The most prevalent initial EGFR mutation was exon 19 deletion (56.1%), and afatinib (46.3%) was the most commonly used EGFR-TKI. EGFR mutation analysis was performed in 68.3% of the tSCLC specimen, and acquired T790M was detected in 7.1% of the patients. Treatment patterns after transformation included various systemic therapies, with the most (63.4%) receiving etoposide plus platinum (EP) based chemotherapy in the first line setting. Among all the patients, 56.1% received EGFR-TKI and 22% received immune checkpoint inhibitors (ICI) throughout the post-transformation treatment course. Anemia (Hgb < 10g/dL) and ever use of EP were significant factors associated with post-transformation survival. The median progression-free survival (PFS) of the first line treatment was 3.27 months, and the overall survival (OS) was 10.43 months post transformation. Conclusions: Small cell lung cancer transformation in advanced NSCLC with EGFR mutation after TKI therapy is associated with diverse clinical characteristics and dismal outcomes. We presented the complexity of managing these cases in real-world practice. Anemia and ever use of EP affected post-transformation survival. Further research is warranted to optimize therapeutic strategies for this unique subset of patients.

10.1200/jco.2024.42.16_suppl.e20569

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De novo thymic carcinoma or malignant transformation: a myasthenic patient presented with multiple mediastinal tumours

Respirology Case Reports (2020)

Chu‐Pin Pai Chih‐Ming Lin Yi‐Chen Yeh Chien‐Sheng Huang Biing‐Shiun Huang

Abstract A 63‐year‐old man presented with bilateral ptosis, and detailed evaluation confirmed ocular myasthenia gravis with three anterior mediastinal masses on computed tomography (CT) of the chest. Extended thymectomy was performed, and pathology revealed two thymic carcinoma and one thymoma. After surgery, the patient is free from recurrence. Synchronous triple thymic carcinomas and thymoma have not been reported. The finding of this case report supports the hypothesis of malignant transformation of thymoma to thymic carcinoma. Thymic carcinoma should be considered in the differential diagnosis of multiple thymic tumours, and extended thymectomy should be the treatment of choice.

Thymic carcinoma

Thymectomy

Thymus Neoplasm

Mediastinal tumor

10.1002/rcr2.629

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Citations (2)

A novel HIF1α-STIL-FOXM1 axis regulates tumor metastasis

Journal of Biomedical Science (2022)

Yiwei Wang Shu‐Chuan Chen De-Leung Gu Yi‐Chen Yeh Jhih-Jie Tsai

Abstract Background Metastasis is the major cause of morbidity and mortality in cancer that involves in multiple steps including epithelial–mesenchymal transition (EMT) process. Centrosome is an organelle that functions as the major microtubule organizing center (MTOC), and centrosome abnormalities are commonly correlated with tumor aggressiveness. However, the conclusive mechanisms indicating specific centrosomal proteins participated in tumor progression and metastasis remain largely unknown. Methods The expression levels of centriolar/centrosomal genes in various types of cancers were first examined by in silico analysis of the data derived from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and European Bioinformatics Institute (EBI) datasets. The expression of STIL (SCL/TAL1-interrupting locus) protein in clinical specimens was further assessed by Immunohistochemistry (IHC) analysis and the oncogenic roles of STIL in tumorigenesis were analyzed using in vitro and in vivo assays, including cell migration, invasion, xenograft tumor formation, and metastasis assays. The transcriptome differences between low- and high-STIL expression cells were analyzed by RNA-seq to uncover candidate genes involved in oncogenic pathways. The quantitative polymerase chain reaction (qPCR) and reporter assays were performed to confirm the results. The chromatin immunoprecipitation (ChIP)-qPCR assay was applied to demonstrate the binding of transcriptional factors to the promoter. Results The expression of STIL shows the most significant increase in lung and various other types of cancers, and is highly associated with patients’ survival rate. Depletion of STIL inhibits tumor growth and metastasis. Interestingly, excess STIL activates the EMT pathway, and subsequently enhances cancer cell migration and invasion. Importantly, we reveal an unexpected role of STIL in tumor metastasis. A subset of STIL translocate into nucleus and associate with FOXM1 (Forkhead box protein M1) to promote tumor metastasis and stemness via FOXM1-mediated downstream target genes. Furthermore, we demonstrate that hypoxia-inducible factor 1α (HIF1α) directly binds to the STIL promoter and upregulates STIL expression under hypoxic condition. Conclusions Our findings indicate that STIL promotes tumor metastasis through the HIF1α-STIL-FOXM1 axis, and highlight the importance of STIL as a promising therapeutic target for lung cancer treatment.

Chromatin immunoprecipitation

Tumor progression

10.1186/s12929-022-00807-0

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Citations (13)