Biomedical subjects

W H Lau

Publications and source records attributed to W H Lau.

At least 37 records · Page 2Linked to original sources

PubMed2000

Total biological effect on late reactive tissues following reirradiation for recurrent nasopharyngeal carcinoma.

PURPOSE: To assess the additional damage of normal tissues attributable to reirradiation and the magnitude of partial recovery following the initial course. METHODS AND MATERIALS: Symptomatic late complication rates (excluding xerostomia) in 3635 patients receiving one course (Group 1) and 487 patients receiving two courses of external radiotherapy (Group 2) for nasopharyngeal carcinoma were retrospectively analyzed and compared. RESULTS: Group 2 had significantly lower actuarial complication-free survival rates than Group 1: 48% versus 81% at 5 years. The post-retreatment incidence was significantly affected by biologically effective dose (BED) (assuming an alpha/beta ratio of 3 Gy) of the first course: hazard ratio (HR) = 1.04 per Gy(3) (p = 0.01), but only marginally by that of the second course: HR = 1.01 per Gy(3) (p = 0.06). If the summated BED was taken as the dose unit, it was estimated that a total BED of 143 Gy(3) would induce a 20% incidence at 5 years, while the corresponding dose projected from Group 1 was 111 Gy(3). The gap effect was insignificant in the overall analyses, but a trend of decreasing risk with increasing interval was observed in patients with gap > or = 2 years: HR = 0.86 per year (p = 0.07). CONCLUSION: The major determinant of post-retreatment complication is the severity of damage during the initial course. The sum of total doses tolerated is higher than that expected with a single-course treatment, suggesting occurrence of partial recovery (particularly in those reirradiated after an interval of 2 years or more).

Adolescent↗

PubMed1999

Staging of nasopharyngeal carcinoma: from Ho's to the new UICC system.

The independent significance of different tumor factors in 4,514 patients with undifferentiated or non-keratinizing carcinoma of the nasopharynx irradiated at the Queen Elizabeth Hospital during 1976-1985 were analyzed retrospectively. Multivariate analyses showed that the most significant primary factors included cranial nerve palsy, erosion of base of skull and oropharynx. For tumors within the nasopharynx, there was no difference in survival between those with involvement of 1 site vs. more than 1 sites. Patients with cranial nerve palsy had significantly worse prognosis than those with bony erosion alone. Although the nodal characteristics (size, level of extension, fixation, laterality and multiplicity) were inter-related, their independent impact all reached statistical significance. However, the criteria used currently could be simplified: laterality should be revised to unilateral vs. bilateral, level to upper-mid vs. lower neck, and size to < or =6 cm vs. >6 cm. Grouping of N2 together with N3 into Stage IV was inappropriate as the former had significantly better prognosis. Our findings, together with review of the publications, provided clinical data for developing the current UICC staging system for nasopharyngeal carcinoma. Such major revision resulted not only in better distinction of hazards, but also more even distribution of cases between different stages.

Adolescent↗

PubMed1999

Recurrent nasopharyngeal carcinoma: the puzzles of long latency.

PURPOSE: To study the peculiar characteristics of relapses with long latency following radical treatment for nasopharyngeal carcinoma. METHODS AND MATERIALS: 847 patients with nasopharyngeal recurrence were retrospectively studied, focusing on the independent effects of latency on different outcome aspects and its relationship with other prognostic factors. RESULTS: The proportion of recurrence with latency <2 years (Group A), 2-<5 years (Group B), and 25 years (Group C) were 52%, 39%, and 9%, respectively. A higher proportion of Group C originated from patients with node-negative early primary, but fewer of them were still confined within the nasopharynx at detection of recurrence. There was no significant difference in the choice of salvage modality, but among those reirradiated, more of Group C were treated with external beams to a higher dose. The difference in local salvage rate was not statistically significant, but the 5-year distant failure-free rates of the 3 groups were 57%, 67%, and 83%, respectively; and the corresponding disease-specific survival (DSS) were 14%, 20%, and 35%. Multivariate analysis confirmed the independent significance of latency in predicting distant failure (hazard ratio = 0.81 per year, p < 0.01) and cancer deaths (hazard ratio = 0.90 per year, p < 0.01). CONCLUSIONS: Nasopharyngeal recurrence with long latency showed different natural behavior: the prognosis was significantly better due to lower risk of distant failure.

Adolescent↗

PubMed1998

Prognostic significance of DNA flow cytometric analysis in patients with nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a prevalent malignant tumor among Southern Chinese. Previously, the authors described the prognostic significance of a serum antibody assay to a recombinant Epstein-Barr virus Bam HI-Z replication activator protein (ZEBRA) in NPC patients with long term follow-up. In this study, the authors further reported the use of DNA flow cytometry (DNA-FCM) as an additional technique for determining the prognosis of NPC patients in the same series. METHODS: One hundred and forty-three archival biopsies from 110 NPC patients were deparaffinized and subjected to DNA-FCM analysis. DNA ploidy state and various proliferative indices (PI) of the tumors were correlated with patient survival and frequency of recurrence. RESULTS: Among the biopsies analyzed, 119 were histologically positive NPC and 24 were negative. Fifty-one tumor biopsies that fulfilled the guideline criteria of the DNA Cytometry Consensus Conference were correlated with the clinical manifestations of the patients. Among them, 43 tumors (84%) were DNA diploid and 8 (16%) were aneuploid. Two PI, S-phase fraction (SPF) and proliferation fraction (PF), appear to be potentially useful prognostic indicators. For example, PF in patients who developed locoregional recurrence (15.1%) and distant recurrence (16.4%) after radiation therapy both were significantly higher than PF in patients who were in complete remission (8.2%) (P = 0.0005 and P = 0.004, respectively). Significant differences in SPF between patients with distant recurrence (10.6%) and those in remission (5.7%) also was found (P = 0.005). Using Kaplan-Meier analysis, patients with high PF, high SPF, and aneuploid tumors had significantly poorer 12-year survival rates (35%, 26%, and 28%, respectively) than those patients with low PF, low SPF, and diploid tumors (77%, 67%, and 59%, respectively) (P < 0.0009, P < 0.004, and P < 0.01, respectively). CONCLUSIONS: Determination of tumor PI and DNA ploidy state by DNA-FCM at diagnosis of NPC can be potentially useful in selecting a poor prognostic subgroup of NPC patients. These parameters may enable oncologists to plan for more stringent treatment strategies such as hyperfractionated and accelerated radiation therapy or concomitant chemoradiotherapy for these patients.

Biopsy↗

PubMed1998

Effect of time, dose, and fractionation on temporal lobe necrosis following radiotherapy for nasopharyngeal carcinoma.

PURPOSE: To study the relative effects of different radiation factors on temporal lobe necrosis (TLN) and predictive accuracy of different biological equivalent models. METHODS AND MATERIALS: Consecutive patients (1008) treated radically with four different fractionation schedules during 1976-1985 for T1 nasopharyngeal carcinoma were retrospectively analyzed. All were irradiated by megavoltage photons using the same technique. Their age ranged from 18-84 years, and 92% of patients had complete follow-up. The fractional dose to inferomedial parts of both temporal lobes ranged from 2.5-4.2 Gy, total dose 45.6-60 Gy, and overall time 38-75 days. RESULTS: Despite a lower total dose of 50.4 Gy, the 621 patients irradiated with 4.2 Gy per fraction had a significantly higher incidence of temporal lobe necrosis than the 320 patients treated to 60 Gy with 2.5 Gy per fraction: the 10-year actuarial incidence being 18.6% vs. 4.6%, p < 0.001. Multivariate survival analysis showed that fractional effect (product of total dose and fractional dose) was the most significant factor: p = 0.0022, hazard ratio (HR) = 1.044 per Gy2. Overall time and age were both insignificant. The alpha/beta ratio calculated from our data was 2.9 Gy (95% CI: -1.8, 7.6 Gy). Biological effective dose (BED(Gy3)), neuret, and brain tolerance unit all showed strongly significant correlation with the necrotic rate (p < 0.001), and gave similar predictions. The hazard of TLN increased by 14% per Gy3, and it was estimated that 64 Gy (at conventional fractionation of 2 Gy daily) would lead to a 5% necrotic rate at 10 years. Not only did the nominal standard dose (NSD) show the lowest value in terms of log likelihood and standardized HR, but its predictions on TLN deviated markedly from clinically observed rates. CONCLUSION: Fractional effect is the most significant factor affecting cerebral necrosis, and overall time has little protective effect. The BED formula, assuming an alpha/beta ratio of 3 Gy, is an appropriate model for predicting late effects on the temporal lobe, and NSD could give seriously misleading predictions.

Adolescent↗

PubMed1998

Primary non-Hodgkin's lymphoma of the nose and nasopharynx: clinical features, tumor immunophenotype, and treatment outcome in 113 patients.

PURPOSE: To study the clinical features and outcome for primary non-Hodgkin's lymphomas of the nose/nasopharynx (NNP-NHLs) according to immunophenotype. PATIENTS AND METHODS: One hundred thirteen Chinese patients with primary NNP-NHLs that belonged to the categories E, F, G, or H according to the Working Formulation (WF), with full immunophenotypic data and complete clinical follow-up data, were analyzed in this retrospective study. RESULTS: Ninety (79.6%) patients had localized (stage I or II) disease, while 23 (20.4%) had stage III or IV disease. The lymphomas in 51 (45.1%), 24 (21.3%), and 38 (33.6%) patients showed natural killer (NK)/T- (CD56-positive), T-cell, and B-cell immunophenotype, respectively. Seventy-three patients (65.8%) achieved a complete remission, of whom 34 (46.6%) subsequently relapsed. The median follow-up time for those alive was 88 months. The 5-year actuarial disease-free and overall survival rates were 34.4% and 37.9%, respectively. Multivariate analysis showed that only stage and immunophenotype were significant for survival. NK/T lymphomas were distinctive among the three immunophenotypes in the following aspects: the highest male-to-female ratio, more frequent involvement of the nasal cavity alone, higher risk of dissemination to the skin, more frequent development of hemophagocytic syndrome, and the worst prognosis (overall median survival, 12.5 months). CONCLUSION: The three immunophenotypes studied are shown to exhibit different clinical patterns. Since the NK/T phenotype carries the worst prognosis, patients who present with NNP-NHL should have their tumors analyzed for CD56 expression.

Adolescent↗

PubMed1998

Nasopharyngeal carcinoma---time lapse before diagnosis and treatment.

This is a descriptive study of 168 patients with nasopharyngeal carcinoma who were referred to public oncology departments for primary treatment between July and September 1996. The mean duration from the onset of the symptoms to histological diagnosis was 5.0 months; the duration ranged from 6.1 months (for patients presenting with nasal symptoms) to 1.8 months (for those with cranial nerve dysfunction). The mean period between the onset of symptoms and the seeking of medical advice was 2.9months. For 54% of the patients, there was a further delay of up to 2.4 months between the initial medical consultation and referral to the appropriate specialist. The majority (84%) of patients attended public institutions for histological confirmation. The mean total time taken from the onset of symptoms to the commencement of radiotherapy was 6.5 months (range, 1.3-74.0 months)---45% of the delay was attributed to the patient, 20% to initial consultations, 14% to diagnostic arrangement, and 21% to preparation for radiotherapy. Concerted efforts are needed to minimise further the time between the onset of symptoms and treatment. A substantial reduction in this delay can be achieved if both public and primary care doctors were made more aware of the significance of relevant symptoms.

Journal Article↗

PubMed1997

Nonnasal lymphoma expressing the natural killer cell marker CD56: a clinicopathologic study of 49 cases of an uncommon aggressive neoplasm.

Expression of the natural killer (NK) cell antigen CD56 is uncommon among lymphomas, and those that do are almost exclusively of non-B-cell lineage and show a predilection for the nasal and nasopharyngeal region. This study analyzes 49 cases of nonnasal CD56+ lymphomas, the largest series to date, to characterize the clinicopathologic spectrum of these rare neoplasms. All patients were Chinese. Four categories could be delineated. (1) Nasal-type NK/T cell lymphoma (n = 34) patients were adults 21 to 76 years of age (median, 50 years), including 25 men and 9 women. They presented with extranodal disease, usually in multiple sites. The commonest sites of involvement were skin, upper aerodigestive tract, testis, soft tissue, gastrointestinal tract, and spleen. Only 7 cases (21%) apparently had stage I disease. The neoplastic cells were often pleomorphic, with irregular nuclei and granular chromatin, and angiocentric growth was common. The characteristic immunophenotype was CD2+ CD3/Leu4- CD3epsilon+ CD56+, and 32 cases (94%) harbored Epstein-Barr virus (EBV). Follow-up information was available in 29 cases: 24 died at a median of 3.5 months; 3 were alive with relapse at 5 months to 2.5 years; and 2 were alive and well at 3 and 5 years, respectively. (2) Aggressive NK cell leukemia/lymphoma (n = 5) patients presented with hepatomegaly and blood/marrow involvement, sometimes accompanied by splenomegaly or lymphadenopathy. The neoplastic cells often had round nuclei and azurophilic granules in the pale cytoplasm. All cases exhibited an immunophenotype of CD2+ CD3/Leu4- CD56+ CD16- CD57- and all were EBV+. All of these patients died within 6 weeks. (3) In blastoid NK cell lymphoma (n = 2), the lymphoma cells resembled those of lymphoblastic or myeloid leukemia. One case studied for CD2 was negative and both cases were EBV-. One patient was alive with disease at 10 months and one was a recent case. (4) Other specific lymphoma types with CD56 expression (n = 8) included one case each of hepatosplenic gammadelta T-cell lymphoma and S100 protein+ T-cell lymphoproliferative disease and two cases each of T-chronic lymphocytic/prolymphocytic leukemia, lymphoblastic lymphoma, and true histiocytic lymphoma. All of these cases were EBV-. Six patients died at a median of 6.5 months. Nonnasal CD56+ lymphomas are heterogeneous, but all pursue a highly aggressive clinical course. The nasal-type NK/T-cell lymphoma and aggressive NK cell leukemia/lymphoma show distinctive clinicopathologic features and a very strong association with EBV. Blastoid NK cell lymphoma appears to be a different entity and shows no association with EBV.

Adolescent↗

PubMed1997

Reirradiation for recurrent nasopharyngeal carcinoma: factors affecting the therapeutic ratio and ways for improvement.

PURPOSE: To identify factors for maximizing local salvage and minimizing damages by reirradiation for recurrent nasopharyngeal carcinoma. METHODS AND MATERIALS: 654 patients with recurrent nasopharyngeal carcinoma treated by reirradiation during 1976-1992 were retrospectively analyzed. Various fractionation schedules had been used during primary treatment with the total dose ranging from 45.6-70 Gy, fractional dose (at different phases) 1.5-4.2 Gy, and overall time 36-101 days. The gap between the two courses ranged from 0.5-10.6 years. Eighty-two percent of patients were reirradiated with teletherapy, 6% brachytherapy, and 12% with both. For those treated with teletherapy alone, the total dose ranged from 7.5-70 Gy, fractional dose 1.8-5 Gy, and overall time 3-89 days. RESULTS: The 5-year actuarial local salvage and complication-free rates were 23% and 52%, respectively. Multivariate analyses showed that the extensiveness of local recurrence was the most significant factor affecting local salvage, while T-stage of primary tumor also influenced prognosis. Choice of method for reirradiation and fractional effect during both courses affected the risk of late complications. For patients treated by teletherapy alone, the hazard of local failure decreased by 1.7% per Biological Effective Dose (assuming alpha/beta ratio = 10) of the second course, while radiation factors during primary radiotherapy had no significant effect. On the other hand, the risk of late complications was predominantly affected by the primary treatment: the hazard increased by 4.2% per Biological Effective Dose (assuming alpha/beta ratio = 3) of the first course, while the corresponding impact of reirradiation failed to reach statistical significance. Length of the gap between the two courses did not affect the outcome. CONCLUSION: Early detection of local recurrence and adequate total dose by reirradiation are crucial for improving the chance of local salvage. Combination of teletherapy and brachytherapy should be considered whenever feasible and large fractional dose avoided to minimize late complications. Optimization of biological dose during primary treatment is important.

Adolescent↗

PubMed1997

Sphenoidal sinus mucocoele and yawning after radiation treatment for nasopharyngeal carcinoma.

The long term complications of radiotherapy in treating patients with nasopharyngeal carcinoma (NPC) are well recognized. Among these, neurological and endocrinological complications are usually considered to be more clinically important. On the other hand, postirradiation sinusitis is often neglected or overlooked because symptoms are usually non-specific or not clinically disturbing. This leads to the under-reporting of this complication. We report the case history of a patient with NPC who developed recurrent and debilitating bouts of yawning attacks 13 years after radiotherapy. The attacks were thought to be due to the compression of the hypothalamus by a large mucocoele in the sphenoidal sinus, which was successfully managed by surgical drainage.

Adult↗

PubMed1997

Germ cell tumours---local perspectives on a curable cancer.

Germ cell tumours are among the most curable solid cancers and have become a model for the multimodality approach in oncology. The experience of two institutions in Hong Kong involving 149 Chinese patients with testicular germ cell tumours and 10 patients with mediastinal germ cell tumours was reviewed and the overall results were found to be comparable with the global experience. Treatment strategies suitable for the local population are discussed. The earlier identification of patients with metastatic non-seminomatous germ cell tumours who have a poor prognosis, may be important in selecting patients for more intensive treatment such as high dose chemotherapy. With mediastinal germ cell tumours, survival is poorer and improved treatment results may only be possible with increased understanding of the biological abnormalities involved. An integrated multimodality approach to the diagnosis and treatment of this disease is vital to attain optimal management. For these reasons, it is recommended that all patients with germ cell tumours be referred to cancer centres where cross-specialty expertise and experience are available to manage these patients.

Journal Article↗

PubMed1997

Nasopharyngeal carcinoma: presenting symptoms and duration before diagnosis.

This is a retrospective analysis of 4768 patients with undifferentiated or non-keratinising carcinoma of the nasopharynx who were treated during 1 January 1976 to 31 December 1985. The mean duration of symptoms before diagnosis was 8 months (range, 1-36 months for 95% of patients). A significant association between the duration of symptoms and the presenting stage was observed (P<0.001); 58% and 39% of stage I and stage V patients, respectively, reported as having had symptoms for less than 6 months. Of the later presenters (those having had symptoms for 6 months or longer), 89% were given a full course of radical megavoltage radiotherapy, but 6% were too advanced for any irradiation attempt. Consequently, the 10-year actuarial disease-specific survival was significantly higher among the early presenters: 48% versus 42% (P<0.001). The importance of early detection is emphasised.

Journal Article↗

PubMed1996

Aggressive T/natural killer cell lymphoma presenting as testicular tumor.

BACKGROUND: Nonnasal CD56+ T/natural killer (NK) cell lymphomas with morphologic and immunogenetic features similar to those of the distinctive nasal T/NK cell lymphoma are uncommon and have been characterized only recently. They show predominantly extranodal presentation, high stage disease, a highly aggressive course, strong association with Epstein-Barr virus (EBV), and lack of T cell receptor gene rearrangement. Only one previously reported case had a testicular presentation, although the testis is not uncommonly involved during the course of disease in both nasal and nonnasal T/NK cell lymphomas. METHODS: Three patients with T/NK cell lymphoma who presented initially with a testicular mass are reported. RESULTS: The three patients underwent orchidectomy for testicular tumor. Histologically, the testes showed diffuse dense infiltration of medium-sized or large lymphoma cells. Antiocentric growth and necrosis were prominent in two cases. The lymphoma had the following immunophenotype: CD2+ CD3 epsilon+ CD56+ compatible with T/NK cell lymphoma; two lacked staining with Leu4 (CD3), and one had weak staining. With immunohistochemical preparations, it was noted that the rete testis stained consistently for CD56, and the Leydig cells and Sertoli cells showed patchy staining. The neoplastic cells harbored EBV, as demonstrated by in-situ hybridization. Additional sites of disease were detected at the time of the diagnosis in one patient (nose) or appeared soon afterwards in all three patients (skin or gastrointestinal tract). All three patients died within 5 months. CONCLUSIONS: This study confirms that testicular CD56+ T/NK cell lymphoma tends to disseminate early, pursues an aggressive course, and is strongly associated with EBV. CD56 recognizes the neural cell adhesion molecule (NCAM), which exhibits homophilic binding properties. The expression of CD56 in the normal testicular constituents can perhaps explain the tendency for T/NK cell lymphoma to localize in this organ.

Aged↗

PubMed1996

N-staging of nasopharyngeal carcinoma: discrepancy between UICC/AJCC and Ho systems. Union Internationale Contre le Cancer. American Joint Committee for Cancer.

To enable clinicians to have a better understanding of the limitations of the UICC/AJCC and Ho N-staging systems for nasopharyngeal carcinoma, 4730 patients without distant metastases at diagnosis were retrospectively analysed. The two systems agreed in 54% (1867/3451) of node-positive patients, and their treatment results were taken as the reference for comparison. To identify the most appropriate N-stage for the discrepant groups, their outcomes were measured against the respective reference. All patients with single, ipsilateral and small nodes, irrespective of their relative position in the upper-mid neck should be classified as N1, while those with multiple, bilateral/contralateral or medium-sized node(s) are effectively N2, even if nodal involvement is confined to the upper neck. All patients with extension to the supraclavicular fossa (irrespective of size) and those with nodes larger than 6 cm at the greatest diameter (irrespective of level) should be classified and treated as N3, especially as, in this group, half of the patients died of distant metastases and trials of adjuvant systemic therapy have to be considered. Areas of inaccurate prognostication by the respective system should be noted to avoid misguiding treatment strategy. The present analyses support our previous suggestions that both the level of extent and the bulk of nodal deposits are important prognostic factors. While supraclavicular involvement is a significant demarcation, there is little justification for further division into upper and mid-levels. The merits of both systems should be duly recognized and combined for the further improvement of prognostic accuracy.

Adolescent↗

PubMed1996

High dose rate intracavitary brachytherapy in the treatment of nasopharyngeal carcinoma.

A retrospective study on 61 patients, with local persistent or recurrent nasopharyngeal carcinoma (NPC), treated during 1990-1992 with high dose rate intracavitary brachytherapy alone or combined with external irradiation, is presented. All 39 patients with persistent disease were treated solely with brachytherapy. The actuarial 3-year local failure-free survival (LFFS) rates of the persistent and recurrent groups were 82% and 45% respectively. The corresponding disease specific survival rates were 82% and 62%. Fifteen patients with recurrence received the combined modality treatment and their 3-year LFFS rate was 65%. Three out of 7 patients treated by brachytherapy could be controlled locally. The total dose given to the floor of sphenoid was an important predictor of local control. Of the 23 patients with persistent disease treated with < 17.5 Gy to this area, 6 failed locally as opposed to none of the 16 patients receiving a higher dose (p = 0.031). For those with recurrence treated by the combined modality, none of the 7 patients given >/= 57.5 Gy recurred while 5 local failures were observed among those receiving a smaller dose (p = 0.041). The general implications of these results for the treatment of NPC recurrence are discussed.

Actuarial Analysis↗

PubMed1995

Basaloid-squamous carcinoma of the nasopharynx. An Epstein-Barr virus-associated neoplasm compared with morphologically identical tumors occurring in other sites.

BACKGROUND: Basaloid-squamous carcinoma is a newly characterized, highly aggressive neoplasm occurring mostly in the base of tongue, hypopharynx, larynx, and esophagus. Its occurrence in the nasopharynx is rare. METHODS: The clinicopathologic features of three cases of basaloid-squamous carcinoma of the nasopharynx are described and were studied for the presence of Epstein-Barr virus (EBV) by in situ hybridization for EBV-encoded small nuclear RNA (EBER). For comparison, basaloid-squamous carcinomas occurring in other sites also were studied for the presence of EBV. RESULTS: EBER was detected in all 3 cases of basaloid-squamous carcinoma occurring in the nasopharynx, but in none of the 13 cases from other sites including the esophagus, larynx, pharynx, hypopharynx, and nasal cavity. The nasopharyngeal basaloid-squamous carcinomas occurred in two male and one female patients with an age range of 48-70 years. The serum immunoglobulin A against the EBV-viral capsid antigen was elevated in all three cases. Two patients developed cervical lymph node involvement during the course of the disease. All three patients were treated by radiotherapy and survived for longer than 34 months compared with the average reported median survival of approximately 2 years for basaloid-squamous carcinomas occurring in the usual sites. CONCLUSION: Based on this limited study, basaloid-squamous carcinoma occurring in the nasopharynx appears to be an EBV-associated neoplasm, whereas the same tumor occurring in other sites is not. The prognosis is potentially better for patients with nasopharyngeal basaloid-squamous carcinoma, which appears to be pathogenetically and biologically more related to the much more common nasopharyngeal undifferentiated carcinoma.

Aged↗

PubMed1995

Detection of Epstein-Barr virus in Hodgkin's disease occurring in an Oriental population.

Like Burkitt's lymphoma, the strength of association of Epstein-Barr virus (EBV) with Hodgkin's disease occurring in different populations and clinical settings is highly variable, being 30% to 50% in Western countries, nearly 100% in Third World countries like Peru and Honduras, and nearly 100% in patients seropositive for human immunodeficiency virus. Data on the Oriental populations are very limited. Therefore, the current study was performed on the Chinese population of Hong Kong, where the incidence of Hodgkin's disease is low and EBV seroconversion occurs early in life. Twenty-three consecutive samples of Hodgkin's disease collected from 18 male and five female patients over a 12-year period were studied. The first age peak occurred in the second decade of life, and the second peak in the seventh decade. Using the sensitive and specific EBV-encoded RNAs (EBERs) in situ localization technique, positive labeling of the Reed-Sternberg cells and their variants was detected in five of five samples (100%) of mixed cellularity, nine of 16 samples (56%) of nodular sclerosing, one of one sample (100%) of lymphocyte depleted, and none of one sample (0%) of nodular lymphocyte predominant Hodgkin's disease. Further analysis of the data by age group yielded the following results: four of five (80%) for age younger than 15 years, three of nine (33%) for age 15 to 49, and eight of nine (89%) for age 50 or higher, confirming the reported strong association of EBV with Hodgkin's disease at the extremes of life. The overall positivity rate was 65%, which was intermediate between that reported in the Western populations and that in the Third World countries. These findings can be explained by the epidemiological pattern of Hodgkin's disease in Hong Kong, in which the first age peak is left-shifted to a younger age compared with that of Western populations (but not as early as that observed in Third World countries), moving the peak toward an age bracket in which Hodgkin's disease shows stronger association with EBV.

Adolescent↗

PubMed1994

A possible prognostic role of immunoglobulin-G antibody against recombinant Epstein-Barr virus BZLF-1 transactivator protein ZEBRA in patients with nasopharyngeal carcinoma.

BACKGROUND: Epstein-Barr virus BZLF-1 replication activator (ZEBRA) is involved in the switch from viral latency to a productive cycle. Previous immunofluorescent study has shown that patients with nasopharyngeal carcinoma (NPC) have elevated immunoglobulin-G (IgG) antibody titres against recombinant ZEBRA protein (ZEBRA/IgG). METHODS: The prognostic role of ZEBRA/IgG was further investigated by enzyme-linked immunosorbent assay (ELISA) in 110 NPC patients under long period of clinical follow-up. RESULTS: Ninety-seven percent (85 of 88) of the patients with NPC had significantly higher ZEBRA/IgG titres (geometrical mean titre, i.e., GMT = 8397) than normal Chinese individuals (GMT = 233 and P < 0.0001). Based on Kaplan-Meier analysis, the actuarial survival in patients with high ZEBRA/IgG titres (25%) after radiotherapy was significantly lower than that of those with low (76%; P = 0.0008) or intermediate titres (62%; P = 0.0036), although the titres taken before treatment did not bear such a relationship. Subdividing the patients into either individual UICC or Ho's stages, those with late-stage disease (UICC Stage 4 and Ho's Stages 3 and 4) and with high ZEBRA/IgG titres also had poorer prognosis than those with disease of the same stages but who had low titres. Poor prognosis in those with high titres could be associated with a high risk of distant metastasis because consistent titre increase was found in the majority of patients who later developed distant metastasis either in the lung or liver. Only a minimal increase was found in patients with recurrence in the cervical lymph nodes. No consistent increase was observed, however, in patients whose disease was in remission or the majority of those with bone metastasis or local recurrence in the nasopharynx. CONCLUSION: The postradiotherapy ZEBRA/IgG titre could be a potentially useful marker for differentiating NPC patients with poor prognosis from those at high risk for the development of distant metastasis to the lung or liver.

Biomarkers, Tumor↗