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"Chang, Chih-Ming"
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Utility of Sydney system for reporting the neck lymphadenopathy underwent real-time ultrasound guided fine-needle aspiration
2025
The Sydney lymphadenopathy cytology system was proposed in 2020, but its validation for neck ultrasound-guided fine-needle aspiration cytology remains to be explored. Patients with lymphadenopathy who underwent ultrasound and cytology were included. The final diagnosis relies on histology and consensus of the multidisciplinary team. Cytology results follow the Sydney system (L1-L5); L3-L5 categories indicate malignancy, and we further calculate sensitivity, specificity, and overall accuracy. From July 2020 to April 2023, a total of 208 patients were included, of which 68 had malignant tumors and 140 were benign cases. According to the Sydney system, the malignancy rates for L2 to L5 are 2%, 89%, 100%, and 98%, respectively. The Sydney system demonstrated 97% sensitivity, 99% specificity, and 99% accuracy in the diagnosis of neck lymphadenopathy. The study shows that the Sydney system is highly effective in reporting neck lymphadenopathy.
Journal Article
The implication of serum HLA-G in angiogenesis of multiple myeloma
2024
Background
Despite the advances of therapies, multiple myeloma (MM) remains an incurable hematological cancer that most patients experience relapse. Tumor angiogenesis is strongly correlated with cancer relapse. Human leukocyte antigen G (HLA-G) has been known as a molecule to suppress angiogenesis. We aimed to investigate whether soluble HLA-G (sHLA-G) was involved in the relapse of MM.
Methods
We first investigated the dynamics of serum sHLA-G, vascular endothelial growth factor (VEGF) and interleukin 6 (IL-6) in 57 successfully treated MM patients undergoing remission and relapse. The interactions among these angiogenesis-related targets (sHLA-G, VEGF and IL-6) were examined in vitro. Their expression at different oxygen concentrations was investigated using a xenograft animal model by intra-bone marrow and skin grafts with myeloma cells.
Results
We found that HLA-G protein degradation augmented angiogenesis. Soluble HLA-G directly inhibited vasculature formation in vitro. Mechanistically, HLA-G expression was regulated by hypoxia-inducible factor-1α (HIF-1α) in MM cells under hypoxia. We thus developed two mouse models of myeloma xenografts in intra-bone marrow (BM) and underneath the skin, and found a strong correlation between HLA-G and HIF-1α expressions in hypoxic BM, but not in oxygenated tissues. Yet when stimulated with IL-6, both HLA-G and HIF-1α could be targeted to ubiquitin-mediated degradation via PARKIN.
Conclusion
These results highlight the importance of sHLA-G in angiogenesis at different phases of multiple myeloma. The experimental evidence that sHLA-G as an angiogenesis suppressor in MM may be useful for future development of novel therapies to prevent relapse.
Journal Article
Functional and biochemical protection by combined N-acetylcysteine and D-methionine in guinea pig noise-induced hearing loss
by
Lo, Wu-Chia
,
Chang, Chih-Ming
,
Wu, Po-Hsuan
in
Acetylcysteine
,
Acoustics
,
Adenosine triphosphatase
2026
Purpose
This study examined whether combining antioxidants could enhance protection and permit lower dosing for treating noise-induced hearing loss (NIHL). The therapeutic effects of D-methionine (DMET) and N-acetylcysteine (NAC) were evaluated in a guinea pig model.
Methods
Ninety-six guinea pigs were randomly assigned to eight groups: control, saline, three NAC-only groups (100, 150, 200 mg/kg), and three NAC + DMET groups (100, 200, 400 mg/kg). One hour after six hours of broadband noise exposure, treatments were administered intraperitoneally every 12 h for seven days. Auditory brainstem responses (ABR) were measured before exposure and on day 14. Cochlear tissues were analyzed for Na⁺/K⁺-ATPase and Ca²⁺-ATPase activities and lipid peroxidation (LPO) levels.
Results
No significant body weight differences were observed between saline and treated groups. NAC alone and in combination with DMET improved ABR thresholds in a dose-dependent manner. The combined NAC (200 mg/kg) + DMET (400 mg/kg) group achieved complete ABR recovery. Noise-induced reductions in ATPase activities were dose-dependently reversed by both treatments. The highest-dose combination restored 87.3% of Na⁺/K⁺-ATPase and 94.7% of Ca²⁺-ATPase activity compared to controls. LPO levels declined with increasing NAC doses, with NAC 200 mg/kg alone showing the greatest reduction.
Conclusions
Combined NAC (200 mg/kg) and DMET (400 mg/kg) yielded the most substantial functional protection against NIHL. This combination was accompanied by lower LPO levels and higher Na⁺/K⁺-ATPase and Ca²⁺-ATPase activities in the cochlear lateral wall, indicating a potential role in maintaining cochlear homeostasis following acoustic injury.
Journal Article
A predictive model for advanced oropharyngeal cancer patients treated with chemoradiation
by
Lo, Wu-Chia
,
Chang, Chih-Ming
,
Hsieh, Chen-Hsi
in
Biomedical and Life Sciences
,
Biomedicine
,
Blood platelets
2022
Background
To analyze clinical characteristics in the prediction of death within 1 year in advanced oropharyngeal cancer patients treated with chemoradiation.
Methods
One hundred forty-seven advanced oropharyngeal cancer patients who underwent curative-intent chemoradiation treatment were retrospectively enrolled. The pre-treatment clinical parameters including inflammatory markers were reviewed.
Results
The 1-year death rate for all patients was 29% [95% confidence interval (CI): 23–37%]. In multivariate logistic regression analysis, hemoglobulin (Hb) < 13.5 g/dl was an independent indicator of death within 1-year [Odds ratio (OR) 5.85, 95% CI 2.17–15.75,
p
< 0.001]. Systemic immune inflammation (SII) ≥ 1820 was also a significant factor for prediction of death within 1 year (OR 4.78, 95% CI 1.44–15.85,
p
= 0.011). We further used gander, age, Hb and SII to develop a nomogram to predict death within 1 year. The c-index of the model was 0.75 (95%CI 0.66–0.83). For patients with low nomogram score (< 14) versus high nomogram score (≥ 14), the 1-year and 2-year OS rates were 91 and 71% versus 53 and 29%, respectively. (
p
< 0.001). A difference in the disease persistence or recurrence rate between patients with high and low nomogram score was significant (73 and 28%, respectively;
p
< 0.001).
Conclusions
The pre-treatment Hb < 13.5 g/dl and SII ≥ 1820 are associated with higher risks of death within 1-year in patients with advanced oropharyngeal cancers. Nomogram can aid in patient counseling and treatment modality adjustment. The development of a more effective treatment protocol for patients with high nomogram score will be essential.
Journal Article
Daratumumab‐Based Combinational Therapy as Second‐Line Treatment of Relapsed‐Refractory Multiple Myeloma: A Single‐Center Experience
2025
Background Daratumumab represents the first‐in‐class fully humanized monoclonal antibody that targets CD38 for the treatment of relapsed/refractory multiple myeloma (RRMM). Evidence from randomized controlled trials has shown daratumumab to be efficacious in the setting of second‐line combinational therapy for pretreated multiple myeloma. However, real‐world evidence that supports daratumumab use in daily clinical practice remains scarce. Aim The primary objective of this study was to describe the real‐world clinical and adverse effects observed in RRMM patients receiving daratumumab as second‐line therapy. Methods This was an observational case series with a retrospective chart review of pretreated multiple myeloma patients who received daratumumab‐based combinational therapy at an academic medical center. The primary end point was progression‐free survival. Additional end points included overall response rates, adverse effects of daratumumab therapy, and subsequent treatment options following daratumumab. Results Seventeen patients were included. The overall response rate of daratumumab in our patients with RRMM was 13/17 (76.5%), and the median progression‐free survival was 20 months when daratumumab was used in the second‐line setting. Common adverse effects included neutropenia (52.9%), thrombocytopenia (64.7%), anemia (35.7%), and pneumonia (35.3%). On follow‐up, 10 patients remained alive at the experimental cut‐off date, with 2 patients kept on daratumumab‐based combinational therapy; 5 patients were switched to carfilzomib‐based therapy; and 3 received best supportive care. Conclusion In our single‐center experience with Taiwanese RRMM patients, daratumumab in combinational therapy showed promising efficacy, and modest tolerance in the second‐line setting.
Journal Article
The outcomes and decision-making process for neck lymph nodes with indeterminate fine-needle aspiration cytology
by
Chang, Chih-Ming
,
Lo, Wu-Chia
,
Liao, Li-Jen
in
Biology and Life Sciences
,
Biomedical engineering
,
Biopsy
2021
This study aims to propose a cytological classification, to evaluate predictive factors of the final malignancy, and to suggest a proper management strategy for neck lymph nodes (LNs) with indeterminate cytology.
Patients who had neck lymphadenopathy with indeterminate cytology between 2007 and 2017 were analyzed retrospectively in a tertiary medical center. Cytological classification was conducted according to the cytological descriptions. We examined the clinical characteristics according to the final diagnosis of the neck lymphadenopathy.
According to the final diagnoses, there were 142 malignant and 95 benign neck LNs among 237 patients. Multivariate analyses using a stepwise logistic regression model showed that cytological classification [p < 0.001, OR = 5.67 (3.48-9.23)], prior history of malignancy [p = 0.01, OR = 2.97 (1.26-6.99)], long axis [p = 0.01, OR = 3.06 (1.33-7.06)], short-to-long axis (S/L) ratio [p = 0.047, OR = 2.15 (1.01-4.57)] and internal echogenicity [p = 0.01, OR = 2.72 (1.26-5.86)] were independent predictors of malignancy.
In patients who have neck LNs with indeterminate cytology, a cytological classification and four other predictors (prior history of malignancy, long axis ≥ 1.93 cm, S/L ratio ≥ 0.64 and heterogeneity of internal echogenicity) are statistically associated with the risk of malignancy and helpful in guiding further management.
Journal Article
Thyroid Nodule Detection and Classification on Small Datasets: An Ensemble Deep Learning Approach with Attention Mechanism and Focal Loss
2026
Background: Thyroid nodule classification on ultrasound remains challenging due to limited labeled data and marked class imbalance. This study proposes an integrated deep learning framework combining YOLO-based region-of-interest detection with an enhanced ResNet18 classifier. Methods: A total of 522 thyroid ultrasound images from 522 patients examined between July 2020 and June 2024 were included. The dataset comprised 467 images for training (399 benign, 68 malignant), 41 for independent testing (19 benign, 22 malignant), and 14 for internal validation (4 benign, 10 malignant). An external validation set of 36 images (22 benign, 14 malignant) was collected from online sources. ResNet18 with a convolutional block attention module was used to enhance feature extraction. To address small sample size and class imbalance, the training pipeline incorporated focal loss, weighted random sampling, mixup augmentation, cosine annealing learning rate scheduling, and a 5-fold cross-validation ensemble. Results: The ensemble model achieved 85.4% accuracy (95% CI: 74.5–96.2%), 86.4% sensitivity (95% CI: 72.0–100%), and 84.2% specificity (95% CI: 67.8–100%) on the independent test set. Internal validation yielded 85.7% accuracy, 90.0% sensitivity, and 75.0% specificity, while external validation demonstrated 77.8% accuracy, 78.6% sensitivity, and 77.3% specificity. These findings suggest that advanced regularization combined with ensemble learning improves generalizability despite limited data. Conclusions: This study demonstrates that a lightweight ResNet18 architecture with strategic optimization outperforms deeper networks on small medical datasets. The proposed framework demonstrated good diagnostic performance across multiple validation cohorts, offering a promising computer-aided diagnosis tool for thyroid nodule assessment.
Journal Article
The Applications and Potential Developments of Ultrasound in Oral Cancer Management
by
Lo, Wu-Chia
,
Chang, Chih-Ming
,
Liao, Li-Jen
in
Biopsy
,
Biopsy, Fine-Needle - methods
,
Biopsy, Large-Core Needle - methods
2022
Oral cancer is endemic and causes a great burden in Southern Asia. It is preferably treated by surgery with/without adjuvant radiotherapy (RT) or chemoradiation therapy, depending on the stage of the disease. Close or positive resection margin and cervical lymph node (LN) metastasis are important prognostic factors that have been presented to be related to undesirable locoregional recurrence and poor survival. Ultrasound (US) is a simple, noninvasive, time-saving, and inexpensive diagnostic modality. It can depict soft tissues very clearly without the risk of radiation exposure. Additionally, it is real-time and continuous image is demonstrated during the exam. Furthermore, the clinician can perform US-guided fine needle aspiration (FNA) or core needle biopsy (CNB) at the same time. US with/without US-guided FNA/CNB is reported to be of value in determining tumor thickness (TT), depth of invasion (DOI), and cervical LN metastasis, and in aiding the staging of oral cancer. DOI has a relevant prognostic value as reported in the eighth edition of the American Joint Committee on Cancer staging of oral cancer. In the present review, we describe the clinical applications of US in oral cancer management in different phases and potential applications in the future. In the pretreatment and surgical phase, US can be used to evaluate TT/DOI and surgical margins of oral cancer in vivo and ex vivo. The prediction of a malignant cervical LN (nodal metastasis) by the US-based prediction model can guide the necessity of FNA/CNB and elective neck dissection in clinical early-stage oral cancer. In the posttreatment surveillance phase, US with/without US-guided FNA or CNB is helpful in the detection of nodal persistence or LN recurrence, and can assess the possibility and extent of carotid artery stenosis after irradiation therapy. Both US elastography and US swallowing assessment are potentially helpful to the management of oral cancer.
Journal Article
Development of a Prognostic Model for Oral Cancer by Incorporating Novel Nodal Parameters Beyond Conventional TNM Staging
2025
Background: Oral cancer is a major global health burden with heterogeneous survival outcomes. This study aimed to identify clinicopathological factors, particularly lymph node-related parameters, associated with prognosis in patients with oral cancer and to construct a survival model for predicting overall survival (OS). Methods: A total of 174 patients with oral cancer who underwent surgery between January 2018 and November 2021 were retrospectively analyzed. Clinicopathological variables, including age, gender, body mass index (BMI), pathological T, N and overall stage, tumor subsite, perineural invasion (PNI), lymphovascular invasion (LVI), surgical margin status, lymph node yield (LNY), lymph node metastases (LNM), and lymph node ratio (LNR), were evaluated. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors for OS and disease-specific survival (DSS). Results: Univariate analysis showed that older age, lower BMI, advanced pathological stage, presence of PNI or LVI, positive/close margins, LNY < 15, LNM ≥ 3, and LNR ≥ 0.0454 were significantly associated with poorer OS. Multivariate analysis identified age ≥ 63 years, pathological stage 3–4, LNY < 15, LNM ≥ 3, and LNR ≥ 0.0454 as independent predictors of OS. LNR ≥ 0.0454 was the only independent predictor of DSS. A survival model incorporating age, pathological stage, LNY, LNM, and LNR demonstrated good discriminatory ability for OS. Conclusions: Multiple independent prognostic factors for oral cancer survival were identified. The proposed survival model provides a practical tool for risk stratification and may assist personalized treatment planning, with particular emphasis on lymph node-related parameters.
Journal Article
COVID-19: Taiwan’s epidemiological characteristics and public and hospital responses
by
Chang, Chih-Ming
,
Ho, Tai-Cheng
,
Su, Tsung-Hsien
in
Clinics
,
Comparative analysis
,
Coronaviruses
2020
Coronavirus disease 19 (COVID-19) is a global health threat with significant medical, economic, social and political implications. The optimal strategies for combating COVID-19 have not been fully determined and vary across countries.
By the end of February 2020 in Taiwan, 2,150 patients received diagnostic COVID-19 testing and 39 confirmed cases were detected. This is a relatively lower rate of infection compared to other Asian countries. In this article, we summarize the epidemiological characteristics of the 39 infected patients as well as public and hospital responses to COVID-19.
Thirty-nine COVID-19 cases and one death have been confirmed in Taiwan. Seventeen of these patients were infected by family members or in hospital wards, emphasizing how COVID-19 is mostly spread by close contact. We examined how hospital have responded to COVID-19, including their implementation of patient route control, outdoor clinics, hospital visit restrictions and ward and staff modifications. We also studied the public's use of face masks in response to COVID-19. These strategies may reduce the spread of COVID-19 in other countries.
The emergence and spread of COVID-19 is a threat to health worldwide. Taiwan has reported lower infected cases and its strategies may contribute to further disease prevention and control.
Journal Article