Chih-Hung Lin

Purpose: Existing T3 subclassifications for upper tract urothelial cancer (UTUC) are limited by heterogeneity and a primary focus on renal pelvis tumors. Our study aimed to propose a novel pT3 subclassification system specifically tailored to pT3 UTUC patients. Materials and Methods: This study analyzed 120 pT3 UTUC cases from a Taiwanese multicenter registry, using a standardized pathology report and a single pathologist for evaluation. Results: Univariate analysis revealed survival differences based on existing subclassifications. Multivariate analysis identified concurrent fat and parenchyma invasion as an independent predictor of worse overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Conclusions: This study proposes a novel pT3 subclassification incorporating fat and parenchyma invasion, applicable to all UTUC sites. This subclassification may improve risk stratification, guide treatment decisions, and ultimately enhance patient outcomes.

Background: Recent advances in immunosuppressive protocols have increasingly made hand allotransplantation a realistic reconstructive option with more than 100 cases performed worldwide. While attitudes toward allotransplantation have been assessed for North American surgeons and patients alike, similar assessments have previously remained unconducted in Asia in general and Taiwan in specific. This study examines the perceptions of both Taiwanese hand surgeons and hand reconstruction patients. Methods: An email-based survey was sent to all active members of the Taiwanese Society for Surgery of the Hand. Surgeon training backgrounds and practice profiles were gathered as well as current beliefs on indications, risks, ethicality, priority of psychosocial issues, and obstacles to implementation. Patients receiving rehabilitation at Chang Gung Memorial Hospital Linkou after severe upper extremity injuries were invited to complete a patient survey. Demographics, injury characteristics, understanding of allotransplantation and immunosuppression, willingness to donate, and willingness to receive transplantation were assessed. Results: Forty-four hand surgeons responded (24.3% response rate). The majority (61.4%) considered hand allotransplantation to be a high-risk operation, although 40% supported the development of hand allotransplantation under current techniques and immunosuppression. Bilateral hands loss was the most commonly accepted indication for transplant (90.9%), whereas dominant hand loss was less frequently accepted (43.2%). Treatment compliance and functional outcomes were the most frequent psychosocial issues of concern regarding patient counseling. Patient respondents were mostly in the fifth decade of life (29.5%) with at least a high school education (75.0%). Most were aware of the feasibility of hand transplantation (68.2%). Patients were more likely than surgeons to consider nondominant hand, multiple-digit, and thumb-only amputations as indications for transplantation. Functional outcomes and financial considerations were the most frequent patient concerns. Conclusions: This study indicates there is support for hand allotransplantation as a solution for limb loss in both hand surgeons and hand patients in Taiwan. This study adds to the lack of knowledge regarding surgeon and patient attitudes toward allotransplantation in Asia, although further work is required to assess the willingness of broader Taiwanese medical to refer candidates and for the general population to donate.

Context: Human epidermal growth factor receptor 2 (HER2) status of breast carcinomas is usually determined by immunohistochemical (IHC) staining and, if the IHC results are equivocal, in situ hybridization (ISH). Multiple ISH tests are sometimes required for multiple primary or metastatic tumors. A method for multiplex ISH test on tissues from multiple blocks is helpful in these situations. Object: To evaluate the clinical application of transferred-tissue microarray (TTM) followed by a dual-probe HER2 fluorescence in situ hybridization (FISH). Design: A 3×3 TTM technique was successfully established using 152 invasive mammary carcinoma tissue fragments. To evaluate detection of HER2 positive tumors, this cohort was enriched with tumors with IHC scores of 2 and 3. Results: The HER2 FISH analyses revealed that all transferred-tissue fragments were adequate for determining HER2 amplification. Tissue loss was minimal and had no major adverse effects on interpretation of the test results. Of the 81 tumors with IHC scores of 3, 72 (88.8%) were positive for HER2 FISH. The remaining tumors were negative for HER2 FISH in both TTM and reflex whole tissue section. Finally, FISH results for tumors with IHC scores of 2 were compared between TTM and whole tissue section. Concordance was high in overall positivity/negativity (100%), HER2 copy number (97.5%), and HER2/CEP17 ratio (100%). Conclusions: This novel technique is a reliable option for performing multiple HER2 FISH tests simultaneously in clinical and research-oriented settings with less tissue damage compared with conventional tissue microarray techniques.

Objective. Diagnosing melanocytic lesions is among the most challenging problems in the practice of pathology. The difficulty of physically masking melanin pigment and the similarity of its color to commonly used chromogens often complicate examination of the cytomorphology and immunohistochemical staining results for tumor cells. Melanin bleach can be very helpful for histopathological diagnosis of heavily pigmented melanocytic lesions. Although various depigmentation methods have been reported, no standardized methods have been developed. This study developed a fully automated platform that incorporates hydrogen peroxide–based melanin depigmentation in an automated immunohistochemical analysis. Methods and Materials. The utility of the method was tested in 1 cell block of malignant melanoma cells in pleural effusion, 10 ocular melanoma tissue samples, and 10 cutaneous melanoma tissue samples. Our results demonstrated that the proposed method, which can be performed in only 3 hours, effectively preserves cell cytomorphology and immunoreactivity. Results. The method is particularly effective for removing melanin pigment to facilitate histopathological examination of cytomorphology and for obtaining an unmasked tissue section for immunohistochemical analysis.

Atypical teratoid/rhabdoid tumor (AT/RT) is a rare pediatric central nervous system malignancy with poor outcome. AT/RT is infrequently located in the spinal cord. A 16-month-old boy presented with progressive urinary retention and weakness of the lower extremities. Magnetic resonance imaging of the spine revealed an intradural extramedullary mass occupying the spinal canal at the level of T10-L3. The tumor was successfully resected by using neuroendoscopy. Histopathology demonstrated rhabdoid cells with eccentric nuclei and eosinophilic cytoplasmic hyaline inclusions. Immunohistologically, the tumor cells showed positive for epithelial membrane antigen, vimentin and neuron-specific enolase, and negative for integrase interactor 1. After surgery, the patient showed significant improvement in sitting and other neurological signs but presenting with flaccid neurogenic bladder. Intrathecal chemotherapy under European Rhabdoid Registry (EU-RHAB) protocol with Doxorubicin, Carboplatin, Etoposide, Ifosfamide, Vincristine, Cyclophosphamide and Actinomycin-D was given. However, recurrent intradural extramedullary tumor at the level of T11-L2 developed in 3 months. We report a young Asian case of AT/RT in thoracolumbar spine with recurrent tumor shortly after complete surgical resection of the tumor.

Diagnosing melanocytic lesions is among the most challenging problems in the practice of pathology. The difficulty of physically masking melanin pigment and the similarity of its color to commonly used chromogens often complicate examination of the cytomorphology and immunohistochemical staining results for tumor cells. Melanin bleach can be very helpful for histopathological diagnosis of heavily pigmented melanocytic lesions. Although various depigmentation methods have been reported, no standardized methods have been developed. This study developed a fully automated platform that incorporates hydrogen peroxide-based melanin depigmentation in an automated immunohistochemical analysis. The utility of the method was tested in one cell block of malignant melanoma cells in pleural effusion, ten ocular melanoma tissue samples, and ten cutaneous melanoma tissue samples. Our results demonstrated that the proposed method, which can be performed in only 3 hours, effectively preserves cell cytomorphology and immunoreactivity. The method is particularly effective for removing melanin pigment to facilitate histopathological examination of cytomorphology and for obtaining an unmasked tissue section for immunohistochemical analysis.

Triple negative breast cancer (TNBC) displays higher risk of recurrence and distant metastasis. Due to absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), TNBC lacks clinically established targeted therapies. Therefore, understanding of the mechanism underlying the aggressive behaviors of TNBC is required for the design of individualized strategies and the elongation of overall survival duration. Here, we supported a positive correlation between β1 integrin and malignant behaviors such as cell migration, invasion, and drug resistance. We found that silencing of β1 integrin inhibited cell migration, invasion, and increased the sensitivity to anti-cancer drug. In contrast, activation of β1 integrin increased cell migration, invasion, and decreased the sensitivity to anti-cancer drug. Furthermore, we found that silencing of β1 integrin abolished Focal adhesion kinese (FAK) mediated cell survival. Overexpression of FAK could restore cisplatin-induced apoptosis in β1 integrin-depleted cells. Consistent to in vitro data, β1 integrin expression was also positively correlated with FAK (p = 0.031) in clinical tissue. More importantly, β1 integrin expression was significantly correlated with patient outcome. In summary, our study indicated that β1 integrin could regulate TNBC cells migration, invasion, drug sensitivity, and be a potential prognostic biomarker in TNBC patient survival.