Descriptive analysis of endemic and travel hepatitis A cases in Ontario, 1998 to 2004.
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Biomedical subjects
Publications and source records attributed to T W Leung.
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AIMS: Tumour control and complication risk have been major concerns in the treatment of cervical carcinoma. A review of dose distribution for intracavitary treatment of cervical carcinoma revealed that modification of the Manchester dosimetry system is necessary for cases of narrow-sized vagina. A revised dosimetry system was introduced in the present study, with the objective of optimising the dose coverage for the parametrium while minimising the bladder and rectum dosage by restricting the rectal dose so as not to exceed 75% of the brachytherapy prescription dose. MATERIALS AND METHODS: A suitable-sized applicator was selected according to the patient's anatomy. The revised system is optimised based on the fixed geometry of the applicator. The system was therefore predefined and the distribution of the treatment dose already determined before application. The revised system was applied to 135 cases, involving 540 applications. The clinical outcome in terms of local tumour control and complication rates is reported. The differences between the revised system and the Manchester system in terms of dose coverage for the parametrium and the rectum dose were compared. RESULTS: The results showed that higher rectal and parametrial dosages were obtained with the Manchester system as compared with the revised system. Our study showed that over 50% of our patients would have received a rectal dose close to 100% of the point A dose if the Manchester system was applied, whereas it was restricted to below 75% using the revised system. Using the revised system, the significance of the parametrial dosage coverage in relation to local control was assessed: the mean dose to the rectum and the bladder as a percentage of point A was 65.7 +/- 5% (range 50-85%) and 66.4 +/- 14% (range 29-116%), respectively. The 5-year actuarial local failure-free survival rates were 90, 92.9, 86.8, 100, 69.7 and 0% for stages IB, IIA, IIB, IIIA, IIIB and IV (P < 0.0001), respectively. The 3-year actuarial complication rates (grade 3/4) for proctitis and cystitis were 1.4 and 0.5%, respectively. The dosage coverage for the parametrium was found to be significant (P = 0.029) in relation to local control for early-stage disease. CONCLUSIONS: The favourable local tumour control and low complication rates shown by our results indicate that the revised system presents an optimal dose distribution, particularly for the application of small ovoids, whereas morbidity was reduced to a lower level without compromising local control.
PURPOSE: This randomized study compared the results achieved by concurrent chemoradiotherapy (CRT) versus radiotherapy (RT) alone for nasopharyngeal carcinoma (NPC) with advanced nodal disease. PATIENTS AND METHODS: Patients with nonkeratinizing/undifferentiated NPC staged T1-4N2-3M0 were randomized to CRT or RT. Both arms were treated with the same RT technique and dose fractionation. The CRT patients were given cisplatin 100 mg/m2 on days 1, 22, and 43, followed by cisplatin 80 mg/m2 and fluorouracil 1,000 mg/m2/d for 96 hours starting on days 71, 99, and 127. RESULTS: From 1999 to January 2004, 348 eligible patients were randomly assigned; the median follow-up was 2.3 years. The two arms were well-balanced in all prognostic factors and RT parameters. The CRT arm achieved significantly higher failure-free survival (72% v 62% at 3-year, P = .027), mostly as a result of an improvement in locoregional control (92% v 82%, P = .005). However, distant control did not improve significantly (76% v 73%, P = .47), and the overall survival rates were almost identical (78% v 78%, P = .97). In addition, the CRT arm had significantly more acute toxicities (84% v 53%, P < .001) and late toxicities (28% v 13% at 3-year, P = .024). CONCLUSION: Preliminary results confirmed that CRT could significantly improve tumor control, particularly at locoregional sites. However, there was significant increase in the risk of toxicities and no early gain in overall survival. Longer follow-up is needed to confirm the ultimate therapeutic ratio.
PURPOSE: To analyze the treatment results achievable for nasopharyngeal carcinoma in the modern era to identify the key failures for future improvement and to provide an updated baseline for future trials. METHODS AND MATERIALS: The results of 2687 consecutive patients treated at all public oncology centers in Hong Kong during 1996-2000 were retrospectively analyzed. The stage distribution (by American Joint Committee on Cancer and International Union Against Cancer staging system, 1997) was 7% Stage I, 41% Stage II, 25% Stage III, and 28% Stage IVA-B. All patients were irradiated with 6-MV photons and the median total dose was 66 Gy. Only 23% of patients had additional treatment with chemotherapy. RESULTS: The 5-year local, nodal, and distant failure-free rates were 85%, 94%, and 81%, respectively; patients with local failure had significantly higher risk of nodal and distant failures. The 5-year progression-free, overall, and cancer-specific survival rates were 63%, 75%, and 80%, respectively. The presenting stage was the most important prognostic factor for all endpoints: with overall survival decreasing from 90% for Stage I to 58% for Stage IVA-B. The results achieved by the 2070 patients treated by radiotherapy alone were almost identical to that of the whole series, the distant failure-free rate among patients with locoregional control was 89% for Stage I-II and 75% for Stage III-IVB. The 860 patients (32%) staged with magnetic resonance imaging achieved significantly better results than those staged by computed tomography, the overall survival being 93% vs. 83% for Stages I-II, and 72% vs. 63% for Stages III-IVB (p = 0.001). CONCLUSIONS: Treatment results for nasopharyngeal carcinoma have substantially improved in the modern era; future trials should be based on updated baseline results. Further reduction of distant failure is important for future breakthrough, particularly for patients with advanced disease.
OBJECTIVE: To evaluate the impact of intimate partner violence on the quality of life in Obstetric/Gynecological (OBGYN) patients. METHOD: A total of 1614 OBGYN patients were classified into four groups (Group 1: requesting termination of pregnancy, n=300; Group 2: infertility patients, n=500; Group 3: other general gynecological patients, n=300; Group 4: obstetric patients, n=514) were successfully interviewed in the absence of their male partners, using a structured questionnaire modified from the Abuse Assessment Screen Questionnaire. Those who reported ever having been abused, together with an equal number of non-abused women as controls, were asked to complete the World Health Organization Quality of Life Measure - Abbreviated version (Hong Kong) Questionnaire. RESULTS: The overall lifetime prevalence of intimate partner violence was 7.2%, with the lifetime prevalence being 12.7%, 1.8%, 4.7%, and 10.9% respectively in Groups 1-4. The mean quality of life domain scores among the abused victims were significantly lower in the physical health domain, social relationship domain, environment domain and psychological health domain. CONCLUSION: The baseline quality of life of the victims of intimate partner violence is significantly impaired compared with the non-abused controls.
OBJECTIVE: To evaluate the effectiveness of an empowerment intervention in reducing intimate partner violence (IPV) and improving health status. DESIGN: Randomised controlled trial. SETTING: Antenatal clinic in a public hospital in Hong Kong. SAMPLE: One hundred and ten Chinese pregnant women with a history of abuse by their intimate partners. METHODS: Women were randomised to the experimental or control group. Experimental group women received empowerment training specially designed for Chinese abused pregnant women while the control group women received standard care for abused women. Data were collected at study entry and six weeks postnatal. MAIN OUTCOMES MEASURES: IPV [on the Conflict Tactics Scale (CTS)], health-related quality of life (SF-36) and postnatal depression [Edinburgh Postnatal Depression Scale (EPDS)]. RESULTS: Following the training, the experimental group had significantly higher physical functioning and had significantly improved role limitation due to physical problems and emotional problems. They also reported less psychological (but not sexual) abuse, minor (but not severe) physical violence and had significantly lower postnatal depression scores. However, they reported more bodily pain. CONCLUSION: An empowerment intervention specially designed for Chinese abused pregnant women was effective in reducing IPV and improving the health status of the women.
AIMS: To evaluate the current UICC/AJCC Staging System for nasopharyngeal carcinoma and to search for ways of improving the system. MATERIALS AND METHODS: This is a retrospective analysis of 2687 consecutive patients treated in five public centres in Hong Kong during the period 1996-2000. All patients were staged by computed tomography, magnetic resonance imaging, or both. The prognostic significance of the current stage assignment on various aspects of tumour control was evaluated. RESULTS: T-category, N-category and stage-group were all significant prognostic factors for major end points (P < 0.01). However, the distinction of prognosis between Stage I and II was insignificant (5-year cancer-specific survival being 92% vs 95%; P = 0.13). Multivariate analyses (corrected for age and sex) revealed lack of significance between T2a and T1 in hazards of local and distant failures, N3a and N2 in distant failure and subgroups of T1-2N0 in cancer-specific deaths. Corresponding down-staging of T2a to T1, N3a to N2, and subgroup T2N0 to stage I, resulted in more even and orderly increase in the hazard ratio of cancer-specific deaths (from 1 for stage I to 1.98 for II, 3.5 for III, 6.08 for IVA and 8.62 for IVB), better hazard consistency among subgroups of the same stage and more balanced stage distribution. CONCLUSIONS: The current UICC/AJCC Staging System could be further improved by the modifications suggested; validation of the current proposal by external data is urgently awaited.
AIMS: To review the treatment results of patients with endometrial carcinoma having positive peritoneal washing (PPW), adnexal involvement, uterine serosal involvement, or all three. MATERIALS AND METHODS: The treatment records of patients who had undergone primary surgery for endometrial cancer without distant metastasis during 1990--2001 at the Department of Clinical Oncology, Tuen Mun Hospital, Hong Kong, were reviewed. Thirty-five patients were found to have involvement of positive PPW, adnexal involvement, uterine serosal involvement, or all three. Seven (20%) of them had gross or microscopic lymph-node metastasis. Thirty-three (94.3%) patients received adjuvant radiotherapy (28 whole-pelvic irradiation [WPI]; five abdominal radiotherapy [WART]). Two patients with solitary ovarian metastasis received chemotherapy, and one with isolated PPW also received adjuvant hormonal therapy. The median follow-up was 50.4 months (range 2.4-151.2 months). Multivariate analysis was carried out using the Cox regression proportional hazards model. RESULTS: Among the 28 patients with clinical or pathological node-negative disease (International Federation of Gynecology and Obstetrics [FIGO] stage IIIA), only two patients with solitary ovarian metastases developed recurrence. The 5-year actuarial disease-free survival (DFS) rates for the whole group and patients without lymph-node involvement were 77.9% and 91.7%, respectively. Five out of the seven patients with lymph-node involvement developed recurrences. Univariate analysis showed that lymph-node involvement (P < 0.0001) and high-grade disease (P = 0.011) were the significant poor prognostic factors. Multivariate analysis showed that lymph-node involvement was the only significant poor prognostic factor to predict poor 5-year DFS (P = 0.0001). Only one patient (3.7%) who had received WART developed grade 4 toxicity. CONCLUSIONS: This study showed that good treatment results could be obtained from patients with stage IIIA endometrial carcinoma without clinical or pathological lymph-node involvement after adjuvant radiotherapy, with acceptable late side-effects. The relative prognostic importance of individual IIIA involvement and the optimal adjuvant treatment remain to be determined.
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BACKGROUND: Alveolar rhabdomyosarcoma (RMS) has a high risk for local and distal failure. Multimodal management of a patient with alveolar RMS of the cervix uteri is outlined. CASE: A 39-year-old woman suffered from alveolar RMS of the cervix without involvement of uterus and parametrium. She was treated with total hysterectomy and left salpingo-oophorectomy. Systemic chemotherapy and pelvic irradiation were also offered. She remains in clinical remission 3 years after presentation. CONCLUSION: Postoperative chemotherapy and irradiation could be effective treatments for alveolar rhabdomyosarcoma of the cervix in adult patients.
AIMS: This study introduces a non-invasive method based on computed tomography (CT) verification to ensure patients are accurately positioned before fractionated stereotactic radiotherapy. It enables quality control of mask positioning with reference to the CT images of the treatment plan. MATERIALS AND METHODS: A mask system, together with a dental impression moulded mouth bite, was used for patient immobilisation. In order to facilitate relevant image comparison, special alignment during CT localisation was discussed in the study. The accuracy of patient set-up was studied by assessing the isocentre position in relation to the patient's anatomical structure. The planning CT images were applied as a reference and the study was applied to 261 cranial applications. RESULTS: The results show that the mean and the maximum overall displacements at the isocentre were 0.7 and 2.5 mm, respectively. The mean and the maximum rotational displacement in the axial plane were 0.56 degrees and 2 degrees, respectively. The mean translational displacement and rotational displacement were close to zero when considering the direction of movement. CONCLUSIONS: The results indicate that the systematic error of the mask system and the verification method are minimal. Advantages of this technique include the simple set-up, three-dimensional quantification and short study time (10-15 min). It is therefore practical to implement on a routine basis. Investigation of the ability to relocate the mask is also recommended to justify the required safety margin between the clinical and planning target volumes.
PURPOSE: Nasopharyngeal carcinoma (NPC) is highly sensitive to both radiotherapy (RT) and chemotherapy. This randomized phase III trial compared concurrent cisplatin-RT (CRT) with RT alone in patients with locoregionally advanced NPC. PATIENTS AND METHODS: Patients with Ho's N2 or N3 stage or N1 stage with nodal size > or = 4 cm were randomized to receive cisplatin 40 mg/m(2) weekly up to 8 weeks concurrently with radical RT (CRT) or RT alone. The primary end point was progression-free survival (PFS). RESULTS: Three hundred fifty eligible patients were randomized. Baseline patient characteristics were comparable in both arms. There were significantly more toxicities, including mucositis, myelosuppression, and weight loss in the CRT arm. There were no treatment-related deaths in the CRT arm, and one patient died during treatment in the RT-alone arm. At a median follow-up of 2.71 years, the 2-year PFS was 76% in the CRT arm and 69% in the RT-alone arm (P =.10) with a hazards ratio of 1.367 (95% confidence interval [CI], 0.93 to 2.00). The treatment effect had a significant covariate interaction with tumor stage, and a subgroup analysis demonstrated a highly significant difference in favor of the CRT arm in Ho's stage T3 (P =.0075) with a hazards ratio of 2.328 (95% CI, 1.26 to 4.28). For T3 stage, the time to first distant failure was statistically significantly different in favor of the CRT arm (P =.016). CONCLUSION: Concurrent CRT is well tolerated in patients with advanced NPC in endemic areas. Although PFS was not significantly different between the concurrent CRT arm and the RT-alone arm in the overall comparison, PFS was significantly prolonged in patients with advanced tumor and node stages.
OBJECTIVES: (1) To determine and compare the prevalence of domestic violence among abortion-seeking patients with other general gynecology patients; (2) to see if a follow-up interview 6 weeks after abortion can improve the abuse disclosure rate; (3) to see if the abused victims accept direct referral to their gynecologists/social workers for help. METHODS: This is a prospective questionnaire survey in a university teaching hospital on patients seeking abortion and an approximately equal number of other general gynecology patients. Participants were interviewed by a designated project nurse in a private setting, using a structured questionnaire (Modified Abuse Assessment Screen Questionnaire) to assess the past and recent history of abuse. The interview was repeated 6 weeks after the abortion for the abortion-seeking group. RESULTS: Five hundred and one participants were interviewed, including 245 seeking abortion (TOP group) and 256 other general gynecology patients (non-TOP group). The lifetime prevalence of abuse in the TOP group (27.3%) was significantly higher than the non-TOP group (8.2%) (P<0.001). Repeating the interview 6 weeks after the abortion did not increase the disclosure rate. Most abused victims were unwilling to disclose their information of abuse to their gynecologists or social workers at the time of interview. CONCLUSIONS: Domestic violence is a significant problem among the gynecology patients, particularly those seeking abortion. A single interview prior to abortion is adequately effective for screening. However, the most effective and acceptable way of helping these victims needs to be explored further.
OBJECTIVES: To study the relationship between domestic violence and postnatal blues/depression in a Chinese community. METHODS: This was a prospective cohort study on 838 women after delivery in a local university teaching hospital. Between October, 2000 and February, 2001, all Chinese speaking women after delivery were invited to be interviewed by a designated research nurse using the Abuse Assessment Screen (AAS) to detect the incidence of domestic violence, the nature of violence and the perpetrator of abuse. Demographic data, pregnancy outcome, Stein's Daily Scoring System (SDSS) scores on day 2 or 3 postdelivery, Edinburgh Postnatal Depression Scale (EPDS) scores on day 2 or 3 postdelivery, 1-2 days after discharge from hospital and at 6 weeks postdelivery were compared between the abused and non-abused groups using Student's t-test, chi(2)-test and Fisher's exact test as appropriate. RESULTS: A total of 139 women (16.6%) had been abused in the last year (the abused group). Of these, 87 (10.4%) had been abused during the current pregnancy. The nature of abuse was mainly verbal. Fourteen women (1.7%) had been sexually abused in the last year. The husband/boyfriend, mother-in-law and employer/colleague were the most common perpetrators of abuse. Socio-demographic factors did not differ between the two groups except that pregnancy was more likely to be unplanned in the abused group (P=0.002). The pregnancy outcome did not differ. However, the abused group had significantly higher SDSS and EPDS scores at all stages of screening (P=0.003, P=0.000, P=0.010 and P=0.001, respectively). CONCLUSION: The findings supported our hypothesis that the effect of domestic violence on Chinese pregnant women is mainly on their psychological well-being.
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FoxM1 (previously named WIN, HFH-11 or Trident) is a Forkhead box (Fox) transcription factor widely expressed in proliferating cells. Various findings, including a recent analysis of FoxM1 knockout mice, suggest that FoxM1 is required for normal S-M coupling during cell cycle progression. To study the regulatory role of FoxM1 and its downstream regulatory targets, three stably transfected HeLa lines that display doxycycline (dox)-inducible FoxM1 expression were established. Over-expression of FoxM1 by dox induction facilitates growth recovery from serum starvation. Quantitation of cyclin B1 and D1 levels using flow cytometric, Western and Northern analyses reveals that elevated FoxM1 levels lead to stimulation of cyclin B1 but not cyclin D1 expression. Transient reporter assays in the dox-inducible lines and upon co-transfection with a constitutive FoxM1 expression plasmid suggest that FoxM1 can activate the cyclin B1 promoter.
To investigate the potential role of somatic mitochondrial DNA (mtDNA) mutations in tumorigenesis, the occurrence of mutations in mtDNA of ovarian carcinomas was studied. We sequenced the D-loop region of mtDNA of 15 primary ovarian carcinomas and their matched normal controls. Somatic mtDNA mutations were detected in 20% (3 of 15) tumor samples carrying single or multiple changes. Complete sequence analysis of the mtDNA genomes of another 10 pairs of primary ovarian carcinomas and control tissues revealed somatic mtDNA mutations in 60% (6 of 10) of tumor samples. Most of these mutations were homoplasmic, and most were T-->C or G-->A transitions, but one represented a differential length within a run of identical C residues. A region of mtDNA sequence including the 16S and 12S rRNA genes, the D-loop and the cytochrome b gene, may represent the zone of preferred mtDNA mutation in ovarian cancer. The high incidence of mtDNA mutations found in ovarian carcinomas and other human cancers suggests that genetic instability of mtDNA might play a significant role in tumorigenesis.
BACKGROUND: In the current study the authors examined the pharmacokinetics of direct intralesional injection of cisplatin/epinephrine/bovine collagen gel in patients with hepatocellular carcinoma and cirrhosis. METHODS: Six patients with cirrhosis and unresectable hepatocellular carcinoma received a direct intralesional injection (range, 6.7-26.7 mg) into their tumors under ultrasonographic guidance. The authors determined the total cisplatin (Pt) concentration in the plasma and urine and nonprotein-bound free Pt in plasma ultrafiltrate using flameless atomic absorption spectrometry. Data from individual patients were analyzed to calculate the pharmacokinetic parameters via a noncompartmental method for constant infusion. To demonstrate that the changes in pharmacokinetics are not related to the underlying cirrhosis, a similar methodology was applied to measure the pharmacokinetic parameters of four similar patients who were treated with cisplatin, 75 mg/m(2), as a 1-hour intravenous infusion. RESULTS: The time to attain maximum concentration of total Pt after intralesional injection was dose-dependent and ranged from 2-13 hours. The concentration-time curve was biphasic in nature. The initial half-life of total Pt in patients who received an intralesional injection varied with the cisplatin dose. The initial half-life for cisplatin doses < 15 mg was approximately 9 hours and the initial half-life at higher cisplatin doses (> 15 mg) was approximately 25 hours. The area under the curve (AUC) was dose-dependent with values ranging from 38-150 microm/mL x hour. Pharmacokinetic parameters for free Pt (ultrafiltrate) were significantly different. The time to attain maximum concentration (t-max) and terminal half-life were shorter and the average AUC was approximately 100-fold lower than total Pt. After the intravenous infusion of cisplatin, the t-max for total and free Pt was 1.3 hours and 1.1 hours, respectively. The terminal half-life and average AUC for total Pt was 194 hours and 247 microg/mL per hour, respectively, and its corresponding parameters for free Pt after intravenous infusion were much lower, similar to the findings for the intralesional injection. CONCLUSIONS: The prolonged t-max and initial half-life noted with the intralesional injection of cisplatin/epinephrine/collagen gel are consistent with its proclaimed ability to retain cisplatin at the tumor and delay its release in systemic circulation. The kinetics of intralesional cisplatin injection also suggest local sequestration of the drug in the injected site. Parameters of intravenous cisplatin infusion in cirrhotic patients are similar to those of patients from the historic control group.