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Biomedical subjects

P H Choi

Publications and source records attributed to P H Choi.

At least 19 recordsLinked to original sources

Loss of heterozygosity on the long arm of chromosome 11 in nasopharyngeal carcinoma.

Loss of heterozygosity (LOH) on the long arm of chromosome 11 had been reported in many types of solid tumors. In this study, we investigated the LOH patterns of chromosome 11 on 52 primary nasopharyngeal carcinomas using 10 microsatellite polymorphic markers. The results revealed that 28 of the 52 cases (53.8%) demonstrated LOH on at least one of the nine 11q microsatellite loci studied. The highest frequencies of LOH were found at the two loci D11S2000 (36.1%) and D11S934 (34.5 %), both located at 11q22-24. Two distinct regions of deletion were found at 11q, with the first one defined by INT-2 and D11S900 at 11q13.3-22, and the second region located between D11S2000 and D11S934 at 11q22-24. The two deletion regions overlap with the common areas of deletion reported in other tumor types. This suggests the presence of multiple putative tumor suppressor genes on chromosome 11q that may play a role in the development of nasopharyngeal carcinomas.

Aneuploidy

Nasopharyngeal carcinoma with metastatic disease to mediastinal and hilar lymph nodes: an indication for more aggressive treatment.

Nasopharyngeal carcinoma (NPC) is a highly chemo- and radiosensitive tumour, distinctive from other head and neck squamous cell carcinomas. Distant metastatic rates correlate directly with T and N stages. The prognosis of metastatic NPC is grave and long term survivors are anecdotal. We encountered an 18-year-old man with locoregionally advanced NPC, who was initially treated with neoadjuvant chemotherapy and radiotherapy, but subsequently relapsed 6 months later in the superior mediastinal and right hilar nodal regions. Further chemotherapy and consolidation radiotherapy resulted in complete remission. He is currently alive and free of disease 5 years and 6 months after the completion of salvage treatment. We recommend aggressive treatment of NPC with isolated intrathoracic nodal relapse and imaging of the mediastinum for non-metastatic Ho's Stage N3 NPC patients.

Adolescent

A prospective randomized study of chemotherapy adjunctive to definitive radiotherapy in advanced nasopharyngeal carcinoma.

PURPOSE: A prospective randomized trial was conducted to compare chemoradiotherapy against radiotherapy alone in the treatment of locoregionally advanced nasopharyngeal carcinoma. METHODS AND MATERIALS: Eighty-two patients with histologically proven nasopharyngeal carcinoma who had either Ho's N3 staging or any N stage with a nodal diameter of > or = 4 cm were entered. Seventy-seven patients were evaluated for tumor response and survival. The patients were randomized to receive two cycles of cisplatin 100 mg/m2 Day 1,5-fluorouracil 1000 mg/m2 24-h infusion Days 2, 3, and 4 before radical radiotherapy, and four cycles of postradiotherapy chemotherapy (37 patients) or radiotherapy alone (40 patients). All patients received radical radiotherapy to the nasopharynx and neck. The nasopharynx and upper neck were treated to 66 Gy by conventional fractionation and the lower neck to 58 Gy. Booster radiotherapy (7.5 Gy/two fractions/week) was given to any residual nodes after standard radiotherapy. RESULTS: The patient characteristics, including staging, were similar in both arms. The overall response rate to neoadjuvant chemotherapy was 81% (19% complete response, 62% partial response). The rates of radiotherapy for boosting parapharyngeal disease or residual lymph nodes were not significantly different in the two arms. The overall complete response rate to chemoradiotherapy was 100%, and to radiotherapy alone, 95%. Toxicities in the chemoradiotherapy arm were mainly myelosuppression, nephrotoxicity, and nausea and vomiting. The degree of mucositis was not significantly different in the two arms. There was no treatment-related death. The median follow up was 28.5 months. The 2-year overall survival was 80% in the chemoradiotherapy arm and 80.5% in the radiotherapy arm. The 2-year disease-free survival was 68% in the chemoradiotherapy arm and 72% in the radiotherapy arm, without significant difference between the two arms. The locoregional relapse rate, distant metastatic rate, and median time to relapse were also not significantly different between the two arms. CONCLUSION: Despite promising tumor response rates from Phase II trials, this prospective randomized trial has demonstrated no benefit from adjunctive chemotherapy to radiotherapy in the treatment of locoregionally advanced nasopharyngeal carcinoma.

Adult

A region of homozygous deletion on chromosome 9p21-22 in primary nasopharyngeal carcinoma.

Using 21 microsatellite polymorphic markers spanning both p and q arms, we have performed detailed deletion mapping on chromosome 9 in 18 primary nasopharyngeal carcinomas. All 18 tumors were informative at multiple loci. Eleven of the 18 cases (61%) demonstrated allelic deletion of chromosome 9. Among these 11, 6 cases are likely to be tumors with monosomy of chromosome 9. The other 5 cases demonstrated partial deletion by showing multiple areas of allelic loss. In one of the 5 cases, a homozygous deletion region was identified which includes D9S126, D9S171, and IFNA loci at 9p21-22, situated between loci D9S161 (9p21) and D9S162 (9p21-22). The presence of a homozygous deletion strongly suggests the presence of tumor suppressor gene(s) involved in the tumorigenesis of nasopharyngeal carcinoma. The same region has been reported to include some potential tumor suppressor gene loci in other cancers. This is the first reported finding of frequent genetic loss observed on chromosome 9 in nasopharyngeal carcinomas in addition to allelic loss on chromosome 3p at specific regions. Our results suggest that tumorigenesis and progression of nasopharyngeal carcinomas, like other solid tumors, involves multiple genetic changes associated with the inactivation of tumor suppressor genes.

Alleles

Patterns of early treatment failure in non-metastatic nasopharyngeal carcinoma: a study based on CT scanning.

Six hundred and twenty-eight patients with non-metastatic nasopharyngeal carcinoma were staged by CT scanning and treated with radical locoregional radiotherapy. Parapharyngeal boost radiation for bulky parapharyngeal involvement, neoadjuvant chemotherapy for bulky nodal metastases, and intracavitary 192Ir treatment for local persistence of tumour after external radiotherapy were also used as appropriate. Forty-eight patients had Ho's (1978) Stage I disease (7.6%), 167 Stage II (26.6%), 312 Stage III (49.7%) and 101 Stage IV (16.1%). At 2 years after treatment, 185 patients (29.5%) had developed recurrence; 112 had distant metastases (60.5%), and 75 had local failure (40.5%). Eighty-three patients had developed distant metastases alone, 73 patients locoregional failure alone and 29 patients had both locoregional and metastatic failure. The overall 2-year actuarial distant and local failure rates were 18.4% and 12.7% respectively. Distant metastasis is the major form of treatment failure which limits early survival. Seventy-four per cent of distant metastases were not associated with locoregional recurrence and had probably arisen from pre-existing occult foci. Our data also suggest that the advent of CT scanning has improved local tumour delineation and radiotherapy planning, and hence local control.

Adolescent

Nasopharyngeal carcinoma: genetic changes, Epstein-Barr virus infection, or both. A clinical and molecular study of 36 patients.

BACKGROUND: The pathogenesis of nasopharyngeal carcinoma has been under intense investigation, especially of its peculiar predominance in southern China. The authors previously reported consistent loss of genetic material on the short arm of chromosome 3 in a few nasopharyngeal carcinoma cases. In this study, the authors examined the genetic changes as well as the presence of Epstein-Barr virus (EBV) genome on 36 nasopharyngeal carcinoma primary biopsy specimens of the undifferentiated type and the correlation of the findings to patients' clinical status. METHODS: The authors examined the DNA from tumor tissue and from matched blood leukocytes of 36 patients who suffered from nasopharyngeal carcinoma by the restriction fragment length polymorphism analysis. The genotyping for EBV was carried out by polymerase chain reaction using primers complementary to both types of EBV and probes specific to EBNA-2A (EBV-A) or EBNA-2B (EBV-B). RESULTS: A consistent deletion at two specific locus of the short arm of chromosome 3 was observed in all informative cases. The authors also found that EBV genome, especially type A, was present in 35 of 36 cases. In the remaining one case, EBV-B was detected. CONCLUSIONS: As the same tumor tissue was used for both genetic and viral studies in each case, the results may represent sequential genetic lesions in the pathogenesis and/or summation of genetic events. Moreover, 7 of 32 informative tumors were from patients of early staging (Stages I and II), which suggests the genetic changes may occur in the early development of nasopharyngeal carcinoma. Difference in allele frequency in specific locus was also noted between Asian and white patients for the first time.

Adult

Loss of heterozygosity on the short arm of chromosome 3 in nasopharyngeal carcinoma.

A consistent loss of constitutional heterozygosity within a specific chromosome locus in a tumor type is suggestive of a tumor suppressor gene important in the genesis of that tumor. We studied whether such genetic alterations are involved, in the development of nasopharyngeal carcinoma (NPC). Tumor and matched blood leukocytes DNA from eleven Hong Kong Chinese patients with primary NPC stages I to IV were subjected to restriction fragment length polymorphism (RFLP) analysis using chromosome 3-specific polymorphic probes. Such probes are assigned to chromosomal region 3p25 (RAF-1), 3p24-22.1 (ERBA beta), 3p21 (DNF15S2), 3p14 (D3S3), and 3q12 (D3S1). The breakpoint varied among tumors, ranging in extent from 3p21-14. However, 100% frequency of complete loss of heterozygosity was observed at two chromosomal loci: RAF-1 locus (ten of ten cases at 3p25) and D3S3 locus (nine of nine cases at 3p14), in all evaluable NPC patients, suggesting the presence of putative tumor suppressor gene(s) within or close to these defined regions. The observed consistent deletion of alleles on the short arm of chromosome 3 in the NPC cases, which is in line with our previously reported and present cytogenetic findings, may represent a critical event in the multistep genesis of NPC. The present report also identifies defined loci for linkage studies on NPC families.

Carcinoma

Ovarian ablation failures by radiation: a comparison of two dose schedules.

Sixty Chinese breast cancer patients underwent ovarian irradiation with one of two dose schedules: 12 Gy/4 fractions/4-6 days or 14 Gy/4 fractions/4-6 days. The ovarian ablation failure rates were 14% and 0% respectively in patients above 40 years of age. The overall ablation failure rate in younger patients was unacceptably high at 35%. The significance of the findings is discussed.

Adult

Primary mediastinal seminoma.

The records and histopathology of 4 patients with primary mediastinal seminoma were reviewed. All of them were male and at presentation had one or more poor prognostic factors, namely superior vena cava obstruction, hilar lymphadenopathy, bulky tumor, and raised alpha-fetoprotein titers. Their treatment consisted partly or entirely of chemotherapy. Three of them survived free of disease 2-5 years off treatment, 1 of them died of pulmonary fibrosis with no tumor found at postmortem examination. The prognostic factors and treatment of this tumor and the risk of combined radiotherapy and chemotherapy containing bleomycin are discussed.

Adolescent

Nasopharyngeal carcinoma: the significance of neck node involvement in relation to the pattern of distant failure.

The pattern of distant failure of 759 Stage I-IV cases of nasopharyngeal carcinoma was studied. The most common sites of distant metastasis were, in descending order, bone, lung and liver. The N stage, T stage and the characteristics (size and degree of fixation) of the neck nodes involved were found to be significant prognostic factors determining the development of distant metastasis. The bilaterality of neck node involvement, sex, age, haemoglobin and white blood count at diagnosis were not significant. The discriminating effect of N stage holds true in patient groups stratified for the node size and degree of fixation. The superiority of the Ho stage classification was confirmed. The high incidence of distant failure in patients with T3, N3, or bulky or fixed neck node involvement warrants further clinical trials to explore the role of adjuvant chemotherapy.

Adolescent

Seminoma of normally-descended and cryptorchid testis.

The records of 40 patients with seminoma of testis were reviewed; nine had cryptorchidism. The incidence of cryptorchidism among the 36 Chinese patients was 22% (8/36). All Stage I and four Stage II patients were treated by orchidectomy followed by radiotherapy of 30 Gy or more to the pelvic and para-aortic lymphatics, while another seven Stage II patients received pelvic and para-aortic lymphatics plus mediastinal irradiation. For patients with normally-descended testis, the 2-year survival for Stage I was 94% and Stage II, with small and clinically unpalpable abdominal nodal metastases, 86%. For patients with Stage I and II seminoma arising from cryptorchid testis, comparable survival can be achieved by giving similar doses of radiation and adjusting the size of the para-aortic and pelvic radiation fields to cover the known extent of the disease. The prognosis of patients with seminoma arising from cryptorchid testis depends more on the stage and extent of disease than the status of cryptorchid testis. Painful groin mass or abdominal pain were the presenting symptoms in more than half of the patients with cryptorchid testes. The changed symptomatology in this group of patients can result in diagnosis delay.

Abdominal Pain

Fiberoptic endoscopic examination and biopsy in determining the extent of nasopharyngeal carcinoma.

This is a prospective study on the use of flexible endoscope and multiple biopsies in the assessment of nasopharyngeal carcinoma in 72 patients. This study confirmed the presence of submucosal growth pattern in nasopharyngeal carcinoma in 72 patients. This study confirmed the presence of submucosal growth pattern in nasopharyngeal carcinoma and this occurred in 13.8% of patients. Occult microscopic extension of tumor not detectable by fiberoptic endoscopy occurred in another 51.4% of patients. It has also been shown that multiple biopsy is superior to clinical examination in evaluating the extent of disease in nasopharyngeal carcinoma. Multiple biopsies are suggested for the early detection of nasopharyngeal carcinoma in high-risk cases. Although the better-defined tumor extent do not currently influence the treatment policy of nasopharyngeal carcinoma, and it is too early to assess its prognostic significance, it betters our understanding of the behavior of this tumor. Future analysis in correlation with long-term follow-up data may help to improve the stage classification systems and treatment strategy.

Biopsy

Experience with the management of primary endodermal sinus tumor of the mediastinum.

Ten male patients with extensive primary endodermal sinus tumor of the mediastinum were treated with chemotherapy (with or without surgical excision and radiation therapy) between 1977 and 1985. Three patients, treated with cyclophosphamide-vincristine-based chemotherapy, died 1.5, 2.5, and 6.0 months, respectively, after initial diagnosis. Of the seven patients treated with cisplatin-based chemotherapy, one patient died of septicemia at 2.5 months after diagnosis and was disease-free at autopsy examination. Three other patients died of progressive disease at 7.0, 13.0, and 14.0 months, respectively. The three survivors remain alive at 17.0, 31.0, and 40.0 months from diagnosis; all are without evidence of disease. Of the three patients who underwent excision of the residual mediastinal tumor after cisplatin-based chemotherapy, persistent local disease was found in two patients. One of these two patients died of recurrent disease. All surviving patients had surgical resection of the tumor either before or after cisplatin-based chemotherapy, with or without radiotherapy and the timing of therapeutic interventions was guided by changes in the serum alpha-fetoprotein concentrations after initial therapy and during follow-up. Our experience suggests that the optimal management of patients with primary mediastinal endodermal sinus tumor requires an aggressive multidisciplinary approach guided by the extent of the tumor and the serum tumor marker levels.

Adolescent

Primary mediastinal endodermal sinus tumors: CT evaluation.

Five patients with primary mediastinal endodermal sinus tumor have been evaluated by computed tomography (CT). The tumors were all located in the anterior mediastinum. Prechemotherapy CT demonstrated large, irregularly enhancing inhomogeneous masses without fat components. Calcification was visualized in two tumors. Some parts of the pleura-lung interface were irregular in four cases. Obliteration of fat planes to pericardium and chest wall was evident in all cases, and there was infiltration of intercostal muscles in four. Postchemotherapy CT in two patients who responded to chemotherapy showed either newly developed cystic lesions or cystic change of the original mediastinal mass. The cystic masses had more regular borders, a homogeneous hypodense center, and a smooth peripheral rim of contrast-enhancing tissue.

Adolescent

Treatment of persistent and recurrent nasopharyngeal carcinoma by brachytherapy.

The early results of brachytherapy for persistent and recurrent nasopharyngeal carcinoma in 30 patients is presented. Fifteen patients were treated by intracavitary caesium, 12 patients were treated by interstitial gold grain implant using the split-palate approach and three patients were treated by both intracavitary caesium and interstitial gold grain implant for the first and second relapse in the nasopharynx, respectively. The overall tumour control rate for intracavitary caesium was 5/18 (28%) with median follow-up of 25.2 months, and for interstitial gold grain implant it was 9/14 (64%) with median follow-up of 16.5 months. Interstitial gold grain implantation appears to be effective in the treatment of persistent and recurrent nasopharyngeal carcinoma.

Adult

Breast metastasis in adolescents with alveolar rhabdomyosarcoma of the extremities: report of two cases.

We describe two adolescent girls with alveolar rhabdomyosarcoma arising from extremities who developed bilateral breast metastasis in their clinical course. In both cases, there was widespread systemic disease at initial presentation. Although complete remission was achieved on the 25th week post-chemotherapy initiation, the first patient developed breast metastasis in addition to systemic recurrence on the 44th week and expired. For the second patient, breast metastasis was noted in addition to systemic disease at initial presentation. Aggressive chemotherapy with autologous transplant and radiotherapy were given in addition to bilateral subcutaneous total mastectomy. The patient remained in complete remission 3 months post-therapy. We postulate that adolescent females with alveolar rhabdomyosarcoma of the extremities have a high risk of developing breast metastasis in the pubertal period, and aggressive multidisciplinary treatment is indicated.

Adolescent