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Biomedical subjects

T S Sheen

Publications and source records attributed to T S Sheen.

At least 37 records · Page 2Linked to original sources

Circulating intercellular adhesion molecule 1 (ICAM-1), E-selectin and vascular cell adhesion molecule 1 (VCAM-1) in head and neck cancer.

The sera from patients with nasopharyngeal carcinoma (n = 30), oral carcinoma (n = 22) and laryngeal carcinoma (n = 22) was extracted before treatment. The concentration of circulating intercellular adhesion molecule 1 (ICAM-1), E-selectin and vascular cell adhesion molecule 1 (VCAM-1) was measured by enzyme-linked immunoassay and compared with those from normal subjects (n = 20). The concentration of circulating ICAM-1, E-selectin and VCAM-1 was significantly increased in nasopharyngeal carcinoma. Correspondingly, VCAM-1 and E-selectin were significantly increased in laryngeal carcinoma, whereas only E-selectin was elevated in oral carcinoma. The concentrations of these adhesion molecules did not significantly differ with respect to the early and late stages of these carcinomas. Elevated levels of soluble adhesion molecules in the sera of cancer patients at three different head and neck regions, although appearing to be implicated in these tumour formations, may be unrelated to tumour progression.

Adult↗

Induction with mitomycin C, doxorubicin, cisplatin and maintenance with weekly 5-fluorouracil, leucovorin for treatment of metastatic nasopharyngeal carcinoma: a phase II study.

The combination of cisplatin and 5-fluorouracil (5-FU) (PF) is the most popular regimen for treating metastatic nasopharyngeal carcinoma (NPC) but it is limited by severe stomatitis and chronic cisplatin-related toxicity. A novel approach including induction with mitomycin C, doxorubicin and cisplatin (MAP) and subsequent maintenance with weekly 5-FU and leucovorin (FL) were designed with an aim to reduce acute and chronic toxicity of PF. Thirty-two patients of NPC with measurable metastatic lesions in the liver or lung were entered into this phase II trial. Mitomycin C 8 mg m(-2), doxorubicin 40 mg m(-2) and cisplatin 60 mg m(-2) were given on day 1 every 3 weeks as initial induction. After either four courses or remission was achieved, patients received weekly dose of 5-FU 450 mg m(-2) and leucovorin 30 mg m(-2) for maintenance until disease progression. With 105 courses of MAP given, 5% were accompanied by grade 3 and 0% were accompanied by grade 4 stomatitis. The dose-limiting toxicity of MAP was myelosuppression. Forty per cent of courses had grade 3 and 13% of courses had grade 4 leukopenia. No grade 3 or 4 cisplatin-related toxicity was observed. The overall response rate was 94% (95% confidence interval (CI) 84.9-100%) with a complete response rate (CR) of 6% (95% CI: 0-15.2%) and a good partial response (PR) rate of 28% (95% CI 11.7-44.6%), which was optionally defined as observance of only equivocal lesion identifiable under imaging study. Twenty-seven cases entered weekly FL maintenance phase. The median duration of maintenance with weekly FL was 38 weeks (8-91 weeks). There was no grade 3 or 4 toxicity noted during weekly FL. The median progression-free survival and overall survival were 11.6+/-0.4 and 18.1+/-3.6 months respectively. Six patients with a median follow-up of 19.8 months (9.6-41.0 months) were still alive and five of them had disease under control with FL. Good responders (CR and good PR) had better survival than less satisfactory responders (PR and stable disease) (P = 0.05). From Cox's multivariate regression analysis, the only significant prognostic factor for survival was good response to MAP (P = 0.042). Liver metastasis was the only significant variable in the best subset regression model that predicted good response to MAP (CR and good PR) (P = 0.027). MAP was an effective combination for metastatic NPC with minimal stomatitis and cisplatin-related toxicity but had significant myelosuppression. Weekly FL was a maintenance therapy with minimal side-effects. The response rate and overall survival of MAP-FL were better than series previously reported even when a subset of patients with poor prognosis was selected. MAP-FL's role as neoadjuvant or adjuvant therapy is worthy of further study.

Adult↗

Epstein-Barr virus-encoded latent membrane protein 1 co-expresses with epidermal growth factor receptor in nasopharyngeal carcinoma.

Latent membrane protein 1 (LMP-1) is the only Epstein-Barr virus (EBV)-encoded oncogenic protein that has been detected in nasopharyngeal carcinoma (NPC), a cancer that is closely associated with EBV. Previous in-vitro studies have demonstrated that LMP-1 can upregulate epidermal growth factor receptor (EGFR) in epithelial cells. It was not established whether this cellular effect exists in NPC. To assess the association between LMP-1 and EGFR in NPC tissues, 60 NPC specimens were examined by immunohistochemistry using anti-LMP-1 antibody (CS 1-4) and anti-EGFR antibodies (EGFR 1, EGFR 1005). The results revealed that 41 (68.3%) specimens were immunopositive for LMP-1 and 44 (73.3%) specimens over-expressed EGFR. Morphologically, the expressions of LMP-1 and EGFR were homogeneously distributed in the tumor nests. In addition, the correlation between LMP-1 and EGFR was statistically significant (P<0.001, chi2 test, d.f. = 1). To elucidate further the correlation between LMP-1 and EGFR in vivo and in situ, an indirect dual immunofluorescence assay was conducted, using secondary antibodies conjugated with fluorescein isothiocyanate (FITC) or indocarbocyanine (Cy3). The results disclosed an intimate co-expression of LMP-1 and EGFR. In summary, the data indicate that over-expression of EGFR is a common phenomenon in NPC, and that EGFR is co-expressed with LMP-1 in NPC. Thus, EBV may play a role in the tumorigenesis of NPC through the effects of LMP-1 and EGFR.

ErbB Receptors↗

Treatment, outcomes, and prognostic factors of ear cancer.

Cancer of the ear is rare and a consensus has not been reached as to the most appropriate treatment. In this retrospective study, we examined the treatment modalities, prognostic factors, and outcomes of patients treated for ear cancer at the National Taiwan University Hospital during a 15-year period. The disease-free survival rates of patients with three different disease grades were compared using the log-rank test. The effects of prognostic factors on survival were examined with Cox's proportional hazard model. Of the 61 ear cancer patients treated from January 1982 through October 1996, 47 (36 men, 11 women; mean age, 54.6 yr) had complete records and were included in this study. The tumor originated from the middle ear in 29 (62%) patients and from the external ear canal in 18 (38%). A total of 37 patients underwent radical mastoidectomy to remove the gross tumor, while six underwent wide excision of the tumor. Concomitant parotidectomy or neck dissection was performed in seven patients. Thirty-eight patients received postoperative radiation therapy and five patients received chemotherapy for palliative treatment of recurrent or inoperable tumors. All but four (9%) of 43 patients developed facial nerve palsy postoperatively. There were no deaths directly related to surgery or other major complications, including cerebrospinal fluid leakage, meningitis, or hemiparesis. The 5-year disease-free survival rate was 53% overall (n = 47), but differed significantly among patients with different grades of disease (p = 0.038): 66% for grade I (n = 27), 44% for grade II (n = 17), and 0% for grade III (n = 3). Multivariate analysis revealed that cervical lymph node metastasis was a poor prognostic factor (relative hazard, 16.4; p < 0.001). These results suggest that mastoidectomy with postoperative radiation therapy can yield satisfactory outcomes, even in some cases of advanced (grade II) disease.

Adolescent↗

Increased mutagen sensitivity in patients with head and neck cancer is less pronounced in patients with nasopharyngeal carcinoma.

BACKGROUND: Mutagen sensitivity tested with bleomycin sulfate can determine a susceptible phenotype, which is relevant only in organs and tissues that have direct contact with the external environment. Patients with head and neck cancers have more mutagen sensitivity than control subjects without cancer, and the hypersensitive phenotype has a risk for the development of a second primary cancer. Head and neck cancers, however, represent a heterogeneous group of neoplasm. The biological behavior of nasopharyngeal carcinoma (NPC) and other head and neck cancers differs. OBJECTIVE: To evaluate the difference in mutagen sensitivity among patients without cancer, patients with NPC, patients with oral or oropharyngeal cancer (ORC), and patients with laryngeal or hypopharyngeal cancer (LHC). DESIGN: Peripheral blood was cultured at 37 degrees C, using 5% carbon dioxide, for 72 hours. After 67 hours of incubation, bleomycin in a concentration of 30 IU/L was added to induce chromatid breaks. The number of chromatid breaks per cell was scored in 50 metaphases of cultured lymphocytes and compared in the 4 groups. SUBJECTS: Patients with histologically proven squamous cell carcinoma of the mucosa of the upper digestive tract, which included 3 groups: patients with NPC, patients with ORC, and those with LHC. Control subjects were hospital inpatients with no tumor history. There were 35 patients in each group. RESULTS: The mean (+/-SD) number of breaks per cell in the control group and in the groups with NPC, ORC, and LHC were 0.80 (+/-0.32), 1.03 (+/-0.45), 1.30 (+/-0.44), and 1.35 (+/-0.46), respectively. All the cancer groups had significantly higher mean breaks per cell and a higher prevalence of hypersensitivity than the control group. Patients with NPC had a significantly lower mean number of breaks per cell than the group with ORC or that with LHC. CONCLUSIONS: Patients with NPC had less mutagen sensitivity than those with ORC or LHC. Our results support the clinical and epidemiological findings of a difference between NPC and other head and neck cancers. Environmental factors might play a less pronounced role in the carcinogenesis of NPC.

Adult↗

Antibody against the Epstein-Barr virus BHRF1 protein, a homologue of Bcl-2, in patients with nasopharyngeal carcinoma.

The Epstein-Barr virus (EBV) open reading frame BHRF1, a homologue of the oncogene bcl-2, was cloned from a patient with nasopharyngeal carcinoma (NPC) and overexpressed in Escherichia coli. The resulting recombinant BHRF1 fusion protein, with an apparent molecular weight of 35 KD, was used as antigen in an immunoblotting assay for IgG antibody in human sera. Anti-BHRF1 antibody was detected in 57 (61.3%) of 93 patients with NPC, 5 (5.7%) of 87 patients with nonmalignant diseases of the nasopharynx, and in 1 (1.3%) of 78 healthy blood donors. The positivity rate in these nonmalignant patients was 4.4 times that of the normal controls. Negative results were observed in four patients with infectious mononucleosis and patients with other cancers, including 4 with esophageal cancer, 11 with lung cancer, 10 with lymphoma, 13 with gastric carcinoma, 10 with cervical carcinoma, and 10 with other head and neck cancers. Antibody neutralizing EBV DNase and IgA antibody to viral capsid antigen (VCA) were assayed in parallel. The results showed that 7.5% of the NPC patients were negative for anti-DNase and anti-VCA antibodies and EBV infection could be detected by the anti-BHRF1 antibody alone. The demonstration of anti-BHRF1 antibody in most NPC sera strongly supports the hypothesis that the EBV BHRF1 protein is expressed in most NPC patients and its specific antibody can be a useful marker for the diagnosis of NPC.

Antibodies, Viral↗

Nasopharyngeal swab and PCR for the screening of nasopharyngeal carcinoma in the endemic area: a good supplement to the serologic screening.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common head and neck cancer in Taiwan. Early detection is the best way to improve survival for this disease. A prospective study was designed to assess the feasibility of a new screening method for NPC by use of polymerase chain reaction (PCR) based on the close association of NPC and Epstein-Barr virus (EBV). METHODS: One hundred thirty-three different tissues from nasopharynx, nose, and sinus were investigated by use of PCR to check for the presence of EBV genome. Subsequently, from April 1996 to March 1997, 55 patients were enrolled in a prospective screening study. All patients underwent nasopharyngeal swabs before biopsy. Polymerase chain reaction detection of EBV genome was conducted on swab samples. Anti-EBV viral capsid antigen (VCA) in IgA and IgG class were checked at the same visit. RESULTS: The EBV genome was present in 91.4% (85/93) of NPC tissues and in 25.0% (10/40) of non-NPC tissues (p < .001, chi2 test). Of the 55 swabs, 49 (89.1%) specimens obtained enough cells for PCR examination. Thirty of these 49 patients were pathologically proved NPC. The presence of EBV were 86.7% (26/30) in NPC group and 42.1% (8/19) in non-NPC group. The sensitivity and specificity were 86.7% and 57.9%, respectively, which were similar to those of serologic method (87.5% and 43.5%) when the cut-off point was set at anti-VCA IgG > or = 160 and IgA > or = 10. Combining both methods elevates the specificity to 84.2%. CONCLUSIONS: The sensitivity of this PCR screening method is similar to that of the serologic method. Combining both methods can greatly increase the specificity, indicating this new method is a good supplement to the serologic screening of this endemic disease.

Antibodies, Viral↗

Preservation of tubal function in patients with nasopharyngeal carcinoma, post-irradiation.

Nineteen nasopharyngeal carcinoma (NPC) patients were subjected to eustachian tube function testing before and 5 years after irradiation. Tubal patency and clearance function of the eustachian tube showed deterioration if maximum irradiation dosage was more than 70 Gy, whereas dynamic function of the eustachian tube was preserved. Development of middle ear complications in NPC patients post-irradiation was caused by both tubal and inflammatory factors. To preserve tubal function, maximum irradiation dosage to NPC should be limited to 70 Gy. To decrease the inflammatory reaction, firstly, middle ear effusion should be drained by repeated myringotomies instead of grommet insertion, and secondly, sinusitis should be evaluated and treated, because sinusitis can aggravate otitis media with effusion.

Adult↗

Partial vertical laryngectomy in the treatment of early glottic cancer.

Treatment of early glottic cancer is still controversial. A retrospective study was conducted to analyze the results of 49 partial vertical laryngectomies in our department. All patients except 1 were successfully decannulated. The quality of voice was suboptimal but serviceable in all patients. Overall, there were 9 recurrences: 7 in the larynx and 2 in the neck. In the laryngeal recurrence group, 5 of 6 patients were successfully salvaged with total laryngectomy. One patient died of acute renal failure 1 month after salvage operation. Another patient survived 4.5 years after cisplatin-based chemotherapy. In the neck recurrence group, 1 patient was successfully salvaged with neck dissection; the other was lost to follow-up after neck dissection. The actuarial 5-year survival rate was 97.4% and the larynx preservation rate was 88%. The recurrence rate was 14%, when 2 of the 7 laryngeal recurrences were excluded because they occurred beyond 5 years. The results of this series were encouraging. We suggest that partial vertical laryngectomy is a good treatment modality for selected early glottic cancers, especially those of the T1 group.

Adult↗

Usefulness of Doppler spectral analysis and power Doppler sonography in the differentiation of cervical lymphadenopathies.

OBJECTIVE: Our purpose was to depict the characteristics of the global vasculature of cervical lymphadenopathies and to clarify the efficiency of Doppler spectral analysis and power Doppler sonography in the differential diagnosis. SUBJECTS AND METHODS: Prospectively, 289 lymph node lesions underwent Doppler flow studies and were grouped as metastasis, lymphoma, tuberculosis, and benign lymphadenopathies. Sonographic assessments included vascular pattern and vascular density (presented as vascularity index) as revealed by power Doppler sonography. Vascular resistive index and pulsatility index were assessed by at least three flow samplings. Values of both the highest and the lowest resistance were analyzed. Vascularity index, resistive index, pulsatility index, nodal size, and age were correlated. RESULTS: Most benign lymphadenopathies (87%), tuberculous lymphadenopathies (72%), and lymphomas (71%) revealed an avascular or hilar vascular pattern. Vascular patterns of most metastatic lymphadenopathies (90%) were of spotted (26%), peripheral (11%), or mixed (53%) type. The vascularity indexes of metastatic lymphadenopathy (mean, 0.176) and lymphoma (mean, 0.122) were significantly higher than those of tuberculous and benign lymphadenopathy (mean, 0.054 and 0.042, respectively). In vascular resistance studies, the highest pulsatility index and resistive index in metastatic lymphadenopathy statistically exceeded those of benign lymphadenopathy, whereas no difference was found in the lowest values. Negative correlation was found between the vascularity index of metastatic lesions and their lowest vascular resistance, and positive correlation was found between vascularity index and nodal size in benign lymphadenopathies. CONCLUSION: In addition to vascular resistance assessed traditionally with Doppler spectral analysis, vascular pattern and vascular density assessed with power Doppler sonography can better differentiate the nature of lymphadenopathies.

Adolescent↗

Intraluminal involvement of thyroid cancer in the trachea.

Invasion of the air passage, especially with intraluminal involvement of well-differentiated thyroid carcinoma, is rare. Establishing a patent airway before surgery is necessary, but difficult and risky. We report a case of thyroid cancer with intraluminal invasion of the trachea. A 62-year-old schizophrenic woman presented with blood-tinged sputum and dyspnea. She had undergone a thyroid lobectomy 8 years previously. Computed tomography and bronchoscopy showed a protruding mass in the upper trachea and limited movement of the bilateral vocal folds. Emergency tracheostomy was performed to relieve impending apnea. Fine-needle aspiration of the left protruding thyroid gland showed papillary carcinoma. Because the tumor diffusely infiltrated the thyroid gland and intermingled with fibrosis due to the previous thyroid operation, and because there was limited movement of bilateral vocal folds, the patient underwent total laryngectomy, total thyroidectomy, total parathyroidectomy, and tracheal resection. Neither radioactive iodine nor external irradiation were given because of anticipated poor compliance due to schizophrenia. The postoperative course was smooth and thyroid hormone and calcium were supplemented regularly. The patient has lived well and without local recurrence for more than 3 years since the operation. She can speak with an artificial larynx.

Carcinoma, Papillary↗

Reconstruction of circumferential pharyngeal defect following cancer surgery with tubed pectoralis major myocutaneous flap and interdigitating anastomosis.

Hypopharyngeal cancer has a poor prognosis and the tumor may spread submucosally to involve all the pharyngeal mucosa. Reconstruction of circumferential defects after resection of hypopharyngeal cancer is a challenge. We describe our results using a tubed fan-shaped pectoralis major myocutaneous flap and distal interdigitating anastomosis to reconstruct a circumferential pharyngeal defect following surgical resection in six patients with advanced hypopharyngeal cancer. There was no perioperative mortality in this study. Fistula formation occurred in three patients and was corrected by secondary closure in two and spontaneous healing in one. Oral intake was started 2 weeks to 2 months after surgery. Four patients died of distant metastases within 24 months of follow-up and two survived without disease. Neither locoregional recurrence nor stenosis occurred. Our results show that the tubed fan-shaped pectoralis major myocutaneous flap with distal interdigitating anastomosis is a reliable way to reconstruct circumferential pharyngeal defects, and is relatively noninvasive.

Adult↗

Detection of transcripts initiated from two viral promoters (Cp and Wp) in Epstein-Barr virus-infected nasopharyngeal carcinoma cells and biopsies.

Different activation of Epstein-Barr virus (EBV) promoters results in distinct expression patterns of EBV nuclear antigens (EBNAs) and may further decide the role of EBV in the cellular pathogenesis. In EBV-associated nasopharyngeal carcinoma (NPC) biopsies, it has generally been believed that Q promoter (Qp)-initiated EBNA1 is the only EBNA gene to be expressed and that the other two viral promoters, Cp and Wp, which can lead to expression of EBNA1-6, are inactive. However, the failure to demonstrate the activities of Cp and Wp may have been due to the limited sensitivities of detection approaches used. In the present article, the EBV promoter usage and gene expression were re-examined in both EBV-infected NPC cells in vitro and NPC biopsies in vivo. An NPC cell line susceptible to EBV infection in vitro was established by transfection with a plasmid expressing a well-known EBV receptor, CR2. The presence of viral DNA and EBNA proteins was demonstrated in these EBV-infected cells using PCR and anticomplement immunofluorescence assay, respectively. As has been identified in NPC biopsies, viral transcripts of Qp-initiated EBNA1, latent membrane protein (LMP)1, LMP2A, LMP2B, and BamHI A genes, as well as the EBV-encoded small RNA (EBER)1 were detected in these in vitro-infected cells using reverse-transcription-PCR. Notably, viral transcripts initiated from Cp or Wp were also found in the infected cells. Furthermore, Cp- or Wp-initiated transcripts and EBNA2 mRNA were detected in some NPC biopsies. Taking advantage of this sensitive detection approach, our observation that Cp and Wp may be active in NPC cells raises the possibility that EBNA2 to 6, in addition to EBNA1, may play roles in the pathogenesis of NPC.

Adult↗

Nasopharyngeal angiofibroma: a reappraisal of clinical features and treatment at National Taiwan University Hospital.

Nasopharyngeal angiofibroma (NAF), occurring mostly in young men, is a histologically benign tumor with aggressive clinical behavior that includes repeated epistaxis and intractable nasal obstruction. This paper reviews our recent experience at National Taiwan University Hospital (NTUH), and compares the results with those of a previous study (1955-1980) at NTUH to highlight the developments in the treatment of NAF. Fifteen patients with a diagnosis of NAF from 1984 to 1997 were included, and their clinical presentations, radiographic studies, treatments, and outcomes were retrospectively analyzed. The results showed that the clinical and demographic features were similar in the two studies. The average number of patients decreased from 2.1 patients in the previous study to 1.1 patients in this study. The duration of symptoms in the current study (8 months) was shorter than that of the previous study (16 months). Previously, the treatment consisted of radiation followed by surgery if there was residual tumor. The current treatment modality is preoperative transarterial embolization followed by surgery. The estimated intraoperative blood loss was reduced from 750 mL in the first study to 400 mL in this study. The recurrence rate decreased from 11% to 7% and the absolute relapse-free rate rose from 56% to 73%. Owing to the development of modern imaging techniques, the advent of preoperative arterial embolization, and advances in surgical techniques, successful removal of highly vascular tumors has become more feasible. Preoperative selective embolization followed by excision is an effective treatment modality. This strategy, an alternative to radiotherapy, not only avoids the long-term complications induced by radiation, but also reduces the tumor recurrence rate.

Adolescent↗

Undifferentiated carcinoma of the major salivary glands.

BACKGROUND: Undifferentiated carcinoma of the salivary glands is a rare disease, the incidence of which is highest among the Inuit of Greenland and North America. It was demonstrated to be closely related to Epstein- Barr virus (EBV) infection. However, the relation of EBV to this tumor has not been studied to any great extent here in Taiwan because of the small number of cases. METHODS: Twelve cases of undifferentiated carcinoma of the salivary glands from the period 1977-1996 were retrieved from the cancer registry at National Taiwan University Hospital. The clinical data were analyzed retrospectively based on the medical records. Eleven formalin fixed, paraffin embedded tissue sections were used for in situ hybridization with an antisense probe complementary to EBV-encoded RNA 1 (EBER1). RESULTS: Ten of 12 tumors originated from the parotid gland and 2 from the submandibular gland. The patients' ages ranged from 22 to 63 years, with an average of 38.1 years. One patient was lost to follow-up, 2 patients died of metastatic disease, and the remaining 9 patients were all alive and disease free at last follow-up. The actuarial 5-year survival rate was 79.8%. In situ hybridization demonstrated EBER1 in 9 of the undifferentiated carcinomas with lymphoid stroma, but EBER1 was not demonstrated in the other 2 tumors without lymphoid stroma. CONCLUSIONS: Undifferentiated carcinoma with lymphoid stroma of the major salivary glands is closely associated with EBV. The mainstay of treatment is surgery and postoperative radiotherapy. The outcomes in this series were good except for two elderly patients who died of rapid and progressive distant metastases.

Adult↗

Salvage surgery for recurrent nasopharyngeal carcinoma.

OBJECTIVE: To assess the efficacy of salvage surgery for patients with recurrent nasopharyngeal carcinoma (NPC) at the primary site after radiotherapy. DESIGN: Retrospective analysis of 24 patients treated by transpalatal, transmaxillary, or transmandibular approach to resect the recurrent tumor, with maximum follow-up of 50 months. SETTING: Academic tertiary referral center. RESULTS: Radiotherapy before salvage surgery included 1 to 3 courses of radiation to the nasopharynx, with doses ranging from 60 to 190 Gy. Eighteen (75%) of the patients relapsed within 2 years, and 6 (25%) relapsed more than 6 years after the last irradiation. In 4 of 6 late-relapsing cases, the histopathological type changed to keratinizing squamous cell carcinoma, which is rare in cases of NPC in Taiwan. Fourteen patients (58%) survived for 8 to 50 months after surgery (median, 18 months). The surgical complications were tolerable. CONCLUSIONS: Salvage surgery is feasible in selected patients with recurrent disease at the primary site. Thus, we can offer alternative retreatment in addition to external irradiation for patients with recurrent NPC.

Carcinoma↗