Biomedical subjects
Publications and source records attributed to D Choy.
Klinefelter's syndrome is known to be associated with various malignancies including male breast cancer and germ cell tumour. We report a patient with Klinefelter's syndrome who developed a primary B-cell lymphoma of the central nervous system (CNS). To the best of our knowledge, this is the first case of primary CNS lymphoma in Klinefelter's syndrome.
We have used probes representing approximately two-thirds of the Epstein-Barr virus (EBV) genome to examine genetic polymorphism of wild-type EBV directly detected in 28 nasopharyngeal carcinoma (NPC) tissues from Southern China. In the hypervariable regions containing reiterated sequences, this analysis showed that while naturally occurring viruses are genetically diverse, only one genotype was detectable in each tumor specimen. Unique variants in NPC were detected in four regions of the EBV genome. Two of these appeared significant in their distribution. The type C variant resulting from loss of a BamHl site between the BamHl W1* and l1* regions was prevalent among isolates from Southern China, but not so common in the United States. An "f" variant having an extra BamHl site in the BamHl F region was almost exclusively detected in only Asian NPC biopsies.
Seventy patients with malignant lymphomas, including the entity known as polymorphic reticulosis (PR), involving the nose, nasal sinuses, nasopharynx, oropharynx (excluding tonsil), and larynx were studied. There were 26 cases of PR, 19 cases of lymphoma with features of PR (ML[PR]) and 25 cases of conventional lymphomas. Fourteen of the 25 conventional lymphomas were due to dissemination from distant sites. For all histologic types of primary lymphoma, the presenting symptoms were similar, and the nasal cavity was more commonly involved than the nasopharynx. Patients with PR were younger, had a higher male:female ratio, and had a better overall survival rate than patients with conventional lymphomas. Cryostat section immunohistochemistry performed on 17 samples from 16 patients showed only one B lymphoma out of 11 primary lesions; the other 10 cases and three recurrent tumors at distant sites showed phenotypic markers of T lymphocytes and natural killer cells. All three secondary tumors were of B-cell type. Of eight patients with sequential biopsies, progression to a more malignant histopathologic type was found in six. In the PR and ML[PR] biopsies, angiocentricity was detected in 11%, and angioinvasion in 22%. We could not confirm identity of PR with other angiocentric immunoproliferative lesions.
A prospective study of 271 consecutive patients with newly diagnosed nasopharyngeal carcinoma was undertaken to assess the pattern of cervical nodal involvement with reference to 10 cervical nodal groups and three levels of neck; 204 (75.3%) patients were found to have cervical lymphadenopathy at presentation. Fifty-four (26.5%) of these patients had right cervical lymphadenopathy, 70 (34.3%) had left cervical lymphadenopathy, and 80 (39.2%) had bilateral cervical lymphadenopathy. The occurrence of lymphadenopathy in the 10 cervical nodal groups and the mean size of nodes in these nodal groups were computed. The subdigastric and upper jugular group was involved in more than 95% of cases. The lower the position in the neck, the less frequently the nodal group was involved. The mean size of nodes was largest in the subdigastric and upper jugular region compared with the other groups. The nodes in the upper neck were generally larger than those in the lower neck. The lower two levels of neck were involved without involvement of the upper level of the ipsilateral neck in fewer than 4% of cases. The present study indicates that neck node involvement by nasopharyngeal carcinoma is by orderly spread down the neck, which explains the adverse prognostic significance of neck node involvement in the lower neck. The orderly involvement of the neck nodes suggests that prophylactic irradiation of the neck should be given at least one level beyond the clinical extent of disease, which for patients with no clinically palpable node would mean prophylactic irradiation of the upper neck.
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.
The records of 759 patients with nasopharyngeal carcinoma were reviewed. Fifteen of them also suffered from another malignant neoplasm. All patients had histological confirmation of the nasopharyngeal carcinoma and the other malignant neoplasm. There was no predilection for the second malignant neoplasms to arise from the bronchus. Although the observed number of second malignant neoplasms was not significantly different from the expected number (p greater than 0.05) computed by the patient-month approach, in 1 patient the second malignant neoplasm may be causally related to the previous treatment of nasopharyngeal carcinoma by radiotherapy.
The records of 759 Stage I to IV nasopharyngeal carcinoma patients seen between January 1976 and December 1983 were reviewed. There were 72 (9.5%), 162 (21.3%), 317 (41.8%) and 208 (27.4%) patients with Stage I, II, III and IV disease, respectively. Ho's stage classification was found to give a reliable prognosis. The actuarial survival at 5 and 10 years for Stage I, II, III and IV disease was 80.8%, 71.5%, 40.7%, 17.7% and 33.4%, 48.4%, 30.0%, 9.5%, respectively. The significant factors affecting survival were found using Cox multivariate analysis, N and T stages, the size and degree of fixation of neck nodes, sex, age, the presence of cranial nerve palsy and ear symptoms at presentation. Bilateral neck node involvement, histology subtypes of tumour, headache and nasal symptoms at presentation, the difference in radiation dose to the primary tumour and the neck, the initial haemoglobin and white blood count were not significant factors in the present study. The N stage was found to be prognostically significant even among patient groups stratified for the size and degree of fixation of the neck nodes involved. Women had a better survival rate than men, and the survival of patients less than 40 years old was better than those who were older at 5 years, although by 10 years the survival for the two groups was comparable.
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.
The records of 153 nasopharyngeal carcinoma patients with skeletal metastases were reviewed. The skeletal system was the most common site of distant metastases. The patients who developed skeletal metastases were significantly younger than those without skeletal metastases, although there was no difference between sexes. The pattern of skeletal involvement conforms to the general pattern, the spine and pelvis being the common sites. The first region of involvement was lumbar spine (28.4%), then dorsal spine (27.7%), sacrum and pelvis (16.3%), femur (9.9%), rib and sternum (7.8%), humerus (5.0%), cervical spine (3.5%) and skull vault (1.4%). Radiologically, the lesions were lytic in 66.0%, mixed lytic and sclerotic in 12.8% and sclerotic in 21.2%. The time to development of symptomatic skeletal metastases of mixed or sclerotic nature was significantly longer than lytic lesions, and patients with mixed or sclerotic metastases also had better survival.
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.
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.
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.
Between January 1982 and January 1983 all patients with advanced cervical cancer were randomized into three groups: radiotherapy only (group I), radiotherapy plus weekly cis-platinum (group II), and radiation plus twice-weekly cis-platinum (group III). Better initial central control was observed in group III patients. Long-term survival was similar in the three groups. Potentiation of radiotherapy with cis-platinum failed to show any significant improvement in long-term survival.
From 1976 to 1986, ten out of 1154 consecutive nasopharyngeal carcinoma (NPC) patients were found to have dermatomyositis (DM). Their clinical features and treatment results were analyzed. The skin manifestation was typical of DM and myopathy occurred in seven patients. All the tumor on presentation were early stage and locoregional control after radiotherapy was satisfactory. All but one patient had DM prior to diagnosis of NPC. The prognosis of NPC was not affected by DM with survival being comparable to contemporary controls. The complication of radiotherapy were unusually severe. Chronic radiation skin ulceration occurred in 2 patients and subcutaneous indurated fibrosis affecting both sides of neck occurred in all patients. Acute radiation mucositis was also prominent.
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.
Cryosections of nasopharyngeal tissue from 9 patients suspected of having nasopharyngeal carcinoma (NPC) were examined for the presence of Epstein-Barr virus (EBV) markers in situ to assess virus infection in the nasopharynx. Viral DNA, EB nuclear antigen, and/or early antigens (EA.D and EA.R) were detected in 5 NPC specimens. EBV infection was not confined to the tumor areas of the biopsy specimens. Lymphoid cells and nontumor areas of these specimens contained EBV markers. In addition, nasopharyngeal tissues obtained from 3 of 4 patients in clinical remission for the disease showed evidence of EBV infection.
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.
Between October 1981 and November 1984, 291 patients with inoperable advanced non-small cell carcinoma of the lung (NSCLC) were randomized to a two-arm study. Eighteen of 291 defaulted treatment and were excluded from the study. Twenty-seven of 273 died during treatment; they were invaluable for treatment response but were included in survival analysis. Without correction for lung attenuation 45 Gy/18 fractions/4 1/2 weeks were given in arm 1 and 31.2 Gy/4 fractions/4 weeks were given in arm 2. One hundred twenty-eight of 273 were included in arm 1 and 145/273 in arm 2. The two arms were comparable in patient age, sex, performance status and symptoms, primary tumor site, histology, stage of the disease, and distribution of metastases and radiation portal size used. Prognosis was poor with an overall median survival of 20 weeks and was similar in both arms. Radiological tumor response was also similar: 53% in arm 1 and 50% in arm 2. However arm 1 was superior than arm 2 in achieving symptom palliation, 71% vs 54%, p less than 0.02. Treatment complications were mild and included mainly radiation oesophagitis and pneumonitis and pulmonary fibrosis. Treatments in both arms were equally well tolerated.