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Biomedical subjects

Chuen Hsueh

Publications and source records attributed to Chuen Hsueh.

At least 19 recordsLinked to original sources

Polymorphism of C-terminal activation region 2 of Epstein-Barr virus latent membrane protein 1 in predicting distant failure and post-metastatic survival in patients with nasopharyngeal carcinoma.

BACKGROUND: The C-terminal activation region 2 (CTAR2) of Epstein-Barr virus latent membrane protein 1 is the major site that correlates with metastasis-related signaling pathway. The variation of CTAR2 sequence may affect the incidence of distant metastasis in patients with nasopharyngeal carcinoma (NPC). METHODS: Two hundred forty-nine specimens from consecutive patients with nonmetastatic NPC were collected. Amplification by polymerase chain reaction and sequence analysis of CTAR2 were performed. DNA sequence identical to the Cao strain was grouped as Cao CTAR2, whereas sequences differing from Cao made up non-Cao CTAR2. Clinical characteristics and CTAR2 status were subjected to statistical analysis for distant metastasis. RESULTS: Non-Cao CTAR2 was associated with a statistically significant lower distance metastasis and superior survival rate. A combination of clinical stage and CTAR2 expression provided an accurate method of identifying high risk of metastasis. CONCLUSION: NPC patients with non-Cao CTAR2 were less likely to have metastasis develop than those characterized by Cao CTAR2.

Adult↗

Renal cell carcinoma with t(X;17)(p11.2;q25) in a 6-year-old Taiwanese boy.

Pediatric renal cell carcinoma (RCC) associated with ASPL-TFE3 gene fusion resulting from balanced translocation, t(X;17)(p11.2;q25), is a distinctive tumor entity. It is uncommon, and most reported cases have exclusively come from Western societies. We report a case of t(X;17)(p11.2;q25) RCC in a 6-year-old Taiwanese boy. The patient presented with dysuria and intermittent hematuria for 1 year. Nonenhanced CT showed a well-defined homogeneous hyperdensity lesion in the upper pole of the left kidney. This patient refused to receive immediate surgical procedures but had routine follow-ups. After a 9-month follow-up, the patient underwent total nephrectomy with a favorable outcome. Final diagnosis is established based on the characteristic microscopic features, strong nuclear TFE-3 immunoreactivity, and the presence of type 1 TFE3-ASPL fusion gene detected by reverse transcriptasepolymerase chain reactions. No adjuvant therapy is given, and the patient is alive without evidence of disease for 1 year and 6 months.

Basic Helix-Loop-Helix Leucine Zipper Transcriptio↗

Clinical characteristics of poorly differentiated thyroid carcinomas compared with those of classical papillary thyroid carcinomas.

OBJECTIVE: The aim of this study was to compare the clinical presentation and prognosis of poorly differentiated thyroid carcinoma (PDTC) with those of classical papillary thyroid carcinoma (PTC) to identify the appropriate surgical modalities for use in conjunction with radioactive iodide ((131)I) therapy and external radiotherapy for treating PDTC. DESIGN: Sixty-seven PDTC patients (mean age 50.3 +/- 18.1 years, range 14-82 years) underwent surgery at the Chang Gung Medical Centre (CGMC), Linkou. To compare clinical presentations and treatment outcomes, 134 age- and gender-matched patients with classical PTC were selected randomly from the patient database at CGMC. RESULTS: Of the 67 PDTC patients, 53 underwent near-total thyroidectomy. Following surgery, 45 were administered (131)I for remnant ablation and treatment of distant metastatic disease. Forty-one of the 67 (61.2%) patients with PDTC and 26/134 (19.4%) with classical PTC failed to achieve disease-free status. Twenty-four of the 67 (34.3%) PDTC patients eventually died of thyroid cancer after a mean follow-up of 5.9 +/- 0.6 years. Age and TNM staging at surgery were significant indicators of PDTC patient survival and mortality. CONCLUSIONS: As the prognosis for PDTC patients is poorer than that for classical PTC patients, (131)I treatment following surgery is useful. To improve the survival rate, early diagnosis is crucial for PDTC.

Adolescent↗

Activation of DNA methyltransferase 1 by EBV LMP1 Involves c-Jun NH(2)-terminal kinase signaling.

EBV latent membrane protein 1 (LMP1) activates cellular DNA methyltransferases, resulting in hypermethylation and silencing of E-cadherin. However, the underlying mechanism remains to be elucidated. In this study, we show that LMP1 directly induces the dnmt1 promoter activity through its COOH-terminal activation region-2 YYD domain. Using (i) LMP1 mutants, (ii) dominant negative mutants c-jun NH(2)-terminal kinase (JNK)-DN, p38-DN, and constitutive active mutant IkappaB, as well as (iii) dsRNAs targeting c-Jun, JNK, and tumor necrosis factor receptor-associated death domain protein, and (iv) signal transduction inhibitors, we show that LMP1-mediated DNA methyltransferase-1 (DNMT1) activation involves JNK but not nuclear factor kappaB and p38/mitogen-activated protein kinase signaling. In addition, LMP1 is unable to activate dnmt1-P1 promoter with activator protein-1 (AP-1) site mutation. Chromatin immunoprecipitation assay results also confirm that LMP1 activates P1 promoter via the JNK-AP-1 pathway. Furthermore, chromatin immunoprecipitation assay data in LMP1-inducible cells disclose that LMP1 induces formation of a transcriptional repression complex, composed of DNMT1 and histone deacetylase, which locates on E-cadherin gene promoter. Treatment with JNK inhibitor, SP600125, prevents the formation of this repression complex. Statistical analyses of the immunohistochemical staining of 32 nasopharyngeal carcinoma (NPC) biopsies show LMP1 expression (18 of 32, 56.25%), DNMT1 expression (31 of 32, 97%), and phospho-c-Jun (27 of 32, 84.38%), suggesting that overexpression of these proteins is observed in NPC tumor. Overall, these results support a mechanistic link between JNK-AP-1 signaling and DNA methylation induced by the EBV oncogene product LMP1.

Cadherins↗

Survival of second and multiple primary tumors in patients with oral cavity squamous cell carcinoma in the betel quid chewing area.

We report the incidence, risk factor(s), and overall survival (OS) of second/multiple primary tumors (SPTs/MPTs) in oral cavity squamous cell carcinoma (OSCC) patients in betel quid chewing areas. Of 816 untreated OSCC patients who had radical surgery, 15.7% had either synchronous or metachronous SPTs. The SPTs (70.3%) were at the oral cavity. SPTs (18.8%) developed third primary tumors, with a significantly higher incidence in synchromous than metachronous SPTs (p=0.001). An optimal, but significantly lower, 5-year OS was observed in patients with SPTs/MPTs than without (54.0% vs. 67.2%, p=0.0195). By multivariate analyses, OSCC sub-sites (p=0.006) and lymphatic permeation (p=0.040) were independent risk factors for SPT rate. A significantly higher 5-year OS was observed in SPT patients receiving a second radical surgery at the oral cavity/soft palate than patients that did not (p=0.0001). A good survival rate can be obtained for OSCC patients with resectable SPTs/MPTs.

Adult↗

Surgical treatment of solitary thyroid nodules via fine-needle aspiration biopsy and frozen-section analysis.

BACKGROUND: Fine-needle aspiration biopsy (FNAB) and frozen-section analysis of managing solitary thyroid nodules continue to generate considerable controversy. METHODS: This study was a retrospective review of 619 patients with solitary thyroid nodules who underwent thyroidectomy. RESULTS: Of 540 FNABs, 35 (6.5%) were positive for malignancy, 276 (51.1%) were benign, and 229 (42.4%) were suspicious. Only 5.1% were false negative, and 11.4% were false positive. Diagnostic FNAB sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for malignancy were 86.1%, 59.7%, 33.0%, 94.9%, and 64.6%, respectively. Of 569 patients analyzed by frozen section, diagnosis was deferred in 86 (15.1%) patients, and results were positive for malignancy in 92 (16.2%) and benign in 391 (68.7%). No false-positive results were noted, but 2.3% (391) were false negative. Of 86 deferred frozen sections, 11 (12.8%) patients had malignant tumors confirmed by permanent section. Diagnostic frozen-section sensitivity, specificity, PPV, NPV, and accuracy for carcinoma were 82.1%, 100%, 100%, 95.8%, and 96.5%, respectively. Sensitivity, specificity, PPV, NPV, and accuracy for frozen-section analysis for diagnosis of carcinoma in patients with suspicious FNAB were 83.9%, 100%, 100%, 94.9%, and 96.0%, respectively. CONCLUSIONS: FNAB is a sensitive diagnostic modality in selecting patients who require surgery. Routine use of frozen-section analysis is unwarranted for benign FNAB results. Frozen section is specific and cost-effective in determining the extent of surgery in patients with suspicious or malignant FNABs.

Adolescent↗

Paraneoplastic syndrome and intrathoracic Castleman disease.

We report two cases of intrathoracic Castleman disease presenting with paraneoplastic syndrome. Patient 1 was a 10-year-old girl with short stature. She was found to have delayed bone age, slow growth velocity, and iron-deficiency anemia, which was refractory to treatment. Thrombocytosis and hypergammaglobulinemia were later detected. Chest X-ray revealed a hilar mass. Patient 2 was a 14-year-old boy who had severe cough, progressive mucocutaneous erosion, and dermatitis. Chest X-ray showed a mediastinal mass. Sections of skin biopsy showed findings consistent with pemphigus disease. In each case, the histological diagnosis of Castleman disease was made.

Adolescent↗

T4b oral cavity cancer below the mandibular notch is resectable with a favorable outcome.

According to the AJCC 2002 staging system, squamous cell carcinoma of the oral cavity (OSCC) with T4b is unresectable. Herein, we report on our surgical outcome for T4b OSCC. All patients were enrolled before 2002. From January 1996 to December 2000, 45 consecutive untreated T4b OSCC patients were included. According to the trans-axial plane of the mandibular notch on CT/MRI, seven were supra-notch T4b and 38 were infra-notch T4b tumors. Significantly higher 5-year loco-regional control and survivals were observed in patients with infra-notch T4b than with supra-notch T4b. In the infra-notch group, pN0-1 patients had a significantly higher 5-year loco-regional control and survivals than pN2 patients. Nerve invasion was the sole significant adverse factor for loco-regional control and survivals in the infra-notch T4b group with pN0-1. Our retrospective study demonstrated that OSCC patients of infra-notch T4b with pN0-1 and no nerve invasion might have a favorable surgical outcome.

Carcinoma, Squamous Cell↗

Clinical presentations and outcomes of surgical treatment of follicular variant of the papillary thyroid carcinomas.

BACKGROUND: The follicular variant of papillary thyroid carcinoma (FVPTC) presents with biological and morphological features similar to papillary thyroid carcinoma. Pre-operative diagnosis of FVPTC and its clinical course is important in identifying appropriate surgical procedures. METHODS: This study enrolled 85 patients, 68 females (mean age 41.4+/-13.7 years) and 17 males (mean age 50.1+/-12.3 years) with papillary thyroid carcinomas diagnosed as FVPTC. From the patient database at Chang Gung Medical Center (CGMC), 170 pure papillary thyroid carcinoma cases and 85 with minimally invasive follicular thyroid carcinomas of gender- and age-matched patients were randomly selected as control groups. All patients were categorized into high- and low-risk groups according to AMES criteria. RESULTS: Of the three groups, 7.1% (follicular), 11.8% (FVPTC) and 34.1% (pure papillary thyroid carcinoma) of patients presented with lymph node or soft tissue invasion (P=0.0001). Additionally, 29.4, 11.8 and 2.4% of patients with follicular carcinoma, FVPTC and pure papillary thyroid carcinoma, respectively, presented with distant metastases at the time of diagnosis. Of the 85 FVPTC cases, 75 underwent pre-operative fine needle aspiration cytology (FNAC) examination at CGMC. Only 11 cases were diagnosed pre-operatively with papillary thyroid carcinomas. Kaplan-Meier survival curves for these three groups demonstrated that follicular thyroid carcinoma had a prognosis worse than both papillary thyroid carcinomas. CONCLUSIONS: Most FVPTC cases were diagnosed as follicular neoplasm via pre-operative FNAC. In this study, FVPTC patients had a high ratio of distant metastases, few lymph node metastases and soft tissue invasion. Aggressive treatment was indicated for the high-risk FVPTC patients.

Adult↗

Surgical outcome of T4a and resected T4b oral cavity cancer.

BACKGROUND: The American Joint Committee on Cancer (AJCC) 2002 staging system (AJCC 2002) suggested that squamous cell carcinoma of the oral cavity (OSCC) with T4b is unresectable. The current retrospective results show that selected T4b patients were resectable with favorable outcomes. METHODS: From January 1996 to December 2000, 103 consecutive untreated T4 OSCC patients (reclassified by AJCC 2002) without carotid artery encasement and skull base extension were eligible for radical treatment. All received head-and-neck magnetic resonance imaging (MRI) and/or computed tomography (CT) scans before operation. The surgical principles were safety margins of > or =1 cm for primary tumors, modified/radical neck dissections for clinical lymph node-positive disease, and supraomohyoid neck dissection for lymph node-negative disease. In all, 95.1% of patients (98 of 103 patients) underwent free-flap reconstructions. Adjuvant radiotherapy or concomitant chemoradiotherapy was administered to those with pathological T4 (AJCC 1997), cervical lymph node metastasis, or close margins (< or =4 mm). Survivals were calculated according to the method of Kaplan and Meier. RESULTS: In all, 58 patients were classified as having T4a disease and 45 were classified as having T4b disease. No statistical difference was observed in the 5-year local control, neck control, disease-free survival, and overall survival rates between the T4a and T4b groups. In multivariate analyses, pathologic lymph node status (pN0-1 vs. pN2) was found to be the sole independent predictor for T4b for local control (P = .012), disease-free survival (P = .005), and overall survival (P = .008). CONCLUSIONS: Selected T4b OSCC patients were found to be resectable with outcomes that were comparable to those of T4a OSCC patients and may benefit from radical surgery, free-flap reconstruction, and adjuvant therapy. A pathologic lymph node status of > or =2 was found to be the sole independent predictor for T4b disease in local control and survival.

Adult↗

Extramedullary plasmacytoma of the thyroid.

Plasmacytomas of the thyroid are uncommon. A 19-year-old female presented with a palpable, 3.5-cm-diameter mass in the right thyroid lobe. Fine-needle aspiration cytology (FNAC) showed that lymphoma cells were likely. The patient underwent a right lobectomy. Final haematoxylin and eosin (HE) staining of the tumour confirmed a diagnosis of thyroid plasmacytoma. Immunohistochemical staining showed that plasma cells were stained strongly with IgA antibody. To date, this is the youngest patient with thyroid plasmacytoma in the literature. Diagnosis of thyroid plasmacytoma by fine-needle aspiration cytology is typically difficult, as it was for this patient. Currently, no treatment standard exists for thyroid plasmacytoma.

Adult↗

Higher distant failure in young age tongue cancer patients.

The objective of this study was to understand if the age of the patient at onset of tongue cancer was an adverse factor for patient survival and distant metastasis (DM). Data were collected from a retrospective database (January 1996-June 2003, n=296). Local control rates, neck control rates, DM rates, and survival curves were assessed by the Kaplan-Meier method. Prognostic variables were assessed by the log-rank test and Cox proportional hazards regression method. For the young group ( 40 years, n=220). No significant differences were seen in 5-year local and neck controls, disease-free, disease-specific and overall survivals between these two groups. We concluded that being <or=40 years of age at the onset of disease is a significant adverse factor for DM in tongue cancer.

Adult↗

Good tumor control and survivals of squamous cell carcinoma of buccal mucosa treated with radical surgery with or without neck dissection in Taiwan.

The aim was to analyze the survival and prognostic factors in 232 patients with squamous cell carcinoma of the buccal mucosa (BSCC) treated with radical surgery with or without neck dissection (ND). The 5-year survivals for local, locoregional control, overall, disease-free, and disease-specific were demonstrated. Pathologic nodal status was the independent risk factor for local and locoregional control. Both pathologic nodal status and cell differentiation were the significant prognostic factors of disease-free survival. For cT1N0, 11.1% had neck metastases. All were tumor depth of > or =6 mm. Our result showed a relatively better tumor control and survivals in BSCC with radical surgery with or without ND. The possible reason may be due to the benefit from widely surgical resection with ND and post-operative radiotherapy or concurrent chemoradiotherapy in those with risk factors. In treating early cT1N0, we suggest that elective ND is indicated only when tumor depth > or =6 mm.

Adult↗

The 30-bp deletion of Epstein-Barr virus latent membrane protein-1 gene has no effect in nasopharyngeal carcinoma.

OBJECTIVE: The specific 30-bp deletion of the Epstein-Barr virus (EBV)-derived latent membrane protein-1 gene has been suggested to be associated with the pathogenesis of nasopharyngeal carcinoma (NPC) and a more aggressive phenotype of some EBV-associated malignancies. METHODS: The authors conducted a retrospective cohort study. Between 1995 and 2001, 542 patients who had received complete courses of radiotherapy followed by at least 3 years of follow up were enrolled. Patients were divided into two groups according to the presence or absence of the 30-bp deletion in their tumor samples. RESULTS: A total of 446 (82.3%) patients were found to feature the 30-bp deletion, whereas 88 (16.2%) did not. Interestingly, dual infection was found in eight (1.5%) patients. No statistical significance was found in age, gender, NPC-presenting stage, radiosensitivity, and pathologic classification between the two groups. The actuarial 5-year overall survival rate and the distant metastasis-free rate for the 30-bp deletion and nondeletion group were not statistically different (61.3% vs. 65.4% and 68.1% vs. 73.1%; P = .132 and .135, respectively). In multivariate analysis, older age, nasopharyngeal recurrence, advanced tumor stage, and the development of distant metastasis were shown to be poorer prognosticators for overall survival, whereas the presence of 30-bp deletion was not. For distant metastasis, only advanced tumor stage was shown to be a poor prognosticator, whereas other variables, including the presence of 30-bp deletion, had no statistical significance. CONCLUSIONS: In this retrospective cohort, we have demonstrated that this specific 30-bp sequence deletion might be only the predominant variant rather than an NPC phenotype-associated polymorphism. Additionally, dual infection is a rare but possible phenomenon in the endemic NPC tumors.

Adolescent↗

Thymic lymphoepitheliomalike carcinoma in children: clinicopathologic features and molecular analysis.

Thymic lymphoepitheliomalike carcinoma (LELC) in children is extremely rare and we report 2 such cases with molecular analysis of Epstein-Barr virus (EBV) and its encoded latent membrane protein-1 as well as a literature review. Both of our patients were male, presented with a huge anterior mediastinal mass, expired within a year after diagnosis despite treatment. There were altogether 9 cases of thymic LELC in children. Their common clinical features include a male predominance, large tumor size, advanced clinical stage, and poor clinical outcome. All cases were associated with EBV and nearly half developed concurrent hypertrophic osteoarthropathy (HOA). Thymic LELC in children is an aggressive EBV-associated malignant tumor frequently accompanied by HOA. We proposed that EBV might play a role in the development of HOA through the interactions of latent membrane protein-1, vascular endothelial growth factor, and cyclooxygenases-2.

Adolescent↗

Lipoblastoma/lipoblastomatosis: a clinicopathologic study of 16 cases in Taiwan.

Lipoblastoma/lipoblastomatosis is an uncommon benign lipomatous tumor affecting mainly infants and children. It presents as a painless mass located frequently in upper and lower extremities. The present study was conducted to characterize the clinicopathologic features of lipoblastoma/lipoblastomatosis in a Chinese population. A retrospective survey of 16 cases of pathologically confirmed lipoblastoma/lipoblastomatosis from 1988 to 2002 was performed. The available clinical information and histological sections were reviewed. The study involved 10 males and 6 females ranging in age from 5 to 49 months (median, 11.5 months). The patients presented with mass involving neck (n = 5), inguina (n = 3), feet (n = 2), arm (n = 1), leg (n = 1), thorax (n = 1), mesentery (n = 1), buttock (n = 1), and presacral region (n = 1). The lesions were removed surgically. Histologically, the majority (11/16) of primary tumors were of diffuse type. Follow-up ranging from 5 to 125 months was available in 13 patients. Four patients experienced a recurrence of tumors in the neck (n = 2) and lower extremities (n = 2) 11-84 months after operation. The most common site of involvement of lipoblastoma/lipoblastomatosis in our series was the neck. A follow-up period of more than 3 years is recommended for patients with this condition.

Child, Preschool↗

Retroperitoneal teratomas in infancy and childhood.

Retroperitoneal teratoma poses a significant problem in the differential diagnosis of Wilms' tumor, neuroblastoma, and other intraabdominal tumors. In an attempt to establish the best diagnostic and treatment modality, we reviewed our experience with retroperitoneal teratomas at a single institution in a 5-year period. Between January 1998 and December 2002, retroperitoneal teratomas were identified in 10 patients, seven females and three males, ranging from age 4 days to 12 years, with seven patients under the age of 1 year. The presence of calcifications or bony structure within the tumor was revealed on abdominal ultrasound study or computed tomography in nine of the 10 lesions. Total excision was performed in nine patients; another patient with grade III immature teratoma received postoperative chemotherapy besides excision. One patient with grade III immature teratoma who did not receive postoperative chemotherapy had a local recurrence 6 months later and was treated by repeated surgical excision and postoperative chemotherapy. All of these patients were free of disease at 8 months to 5 years of follow-up. Retroperitoneal teratomas were usually noted in patients under the age of 1 year. Though large, they are mostly benign lesions with no apparent connection to the retroperitoneal organs and are amenable to curative excision, but histologic evidence of grade III immature teratoma or malignancy demands aggressive postoperative chemotherapy to prevent local recurrence.

Child↗