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Biomedical subjects

R Tsang

Publications and source records attributed to R Tsang.

At least 19 recordsLinked to original sources
PubMed2005

Prognostic factors and the effect of treatment with radioactive iodine and external beam radiation on patients with differentiated thyroid cancer seen at a single institution over 40 years.

OBJECTIVES: To assess the prognostic factors and the role of radioactive iodine (RAI) and external beam radiotherapy (RT) in patients with differentiated thyroid cancer. DESIGN: A retrospective review of 729 patients treated between 1958 and 1998. The median follow-up was 11.3 years (range 0.3-39.8 years). Primary outcomes included time to cause-specific survival and time to local-regional relapse. Baseline and treatment variables were assessed for statistical significance using the Cox proportional hazards model. RESULTS: The 10-year cause-specific survival (CSS) was 87.3% and the 10-year local-regional relapse-free rate (LRFR) was 84.9%. In multivariate analysis there was no statistically significant improvement in CSS with more aggressive treatment (i.e. more extensive surgery, the administration of RAI and/or RT). By multivariate analysis the use of RAI resulted in a statistically significant improvement in LRFR (hazard ratio 0.5; 95% confidence interval 0.3-0.8; P = 0.007). In low-risk patients at AJCC stage I < or = 45 years, there was no apparent benefit from RAI. For patients over 60, with extrathyroid extension but no gross residual disease (n = 70), adjuvant external RT resulted in statistically significantly higher CSS (10-year CSS 81.0%vs. 64.6%, P = 0.04) and LRFR (10-year LRFR 86.4%vs. 65.7%, P = 0.01). CONCLUSIONS: The use of RAI was associated with improved LRFR but not in low-risk patients. External beam RT improved LRFR and CSS in high-risk patients.

Adolescent↗
PubMed2004

The role of allogeneic bone marrow transplantation in adult patients below the age of 55 years with acute lymphoblastic leukemia in first complete remission: a donor vs no donor comparison.

The role of allogeneic bone marrow transplantation (alloBMT) in adults with acute lymphoblastic leukemia (ALL) in first complete remission (CR1) remains controversial. At our institution, the policy is to offer alloBMT to ALL patients in CR1 up to the age of 55 years if a related donor is available. In addition, unrelated donor transplants are offered to patients with Philadelphia (Ph+) ALL. We report the results on 92 patients with ALL treated according to this policy from September 1992 to October 2001. Of the 87 patients achieving CR1, the comparison of patients with (n=48) or without donors (n=39) was done using an intention-to-treat approach. Of the 48 patients with donors (39 related and nine unrelated), 35 (73%) received alloBMT in CR1. No significant difference in 3-year event-free survival (EFS) (40 vs 39%, P=0.74) or overall survival (OS) (46 vs 58%, P=0.41) was seen in 'donor' vs 'no-donor' groups. For Ph+ patients, 3-year EFS and OS in 'donor' group were 46 and 57%, respectively, none of the patients in 'no-donor' group survived beyond 3 years. With our treatment strategy, 3-year OS of Ph+ patients was equivalent to Ph-negative (Ph-) patients (51 vs 52%, P=0.77). In conclusion, our data show that the policy of performing alloBMT if a sibling donor is available has not resulted in better outcome in Ph- patients.

Adolescent↗
PubMed2004

Long-term outcome after intensive therapy with etoposide, melphalan, total body irradiation and autotransplant for acute myeloid leukemia.

Intensive therapy and autologous blood and marrow transplantation (ABMT) is an established post-remission treatment for acute myeloid leukemia (AML), although its exact role remains controversial and few data are available regarding longer-term outcomes. We examined the long-term outcome of patients with AML transplanted at a single center using uniform intensive therapy consisting of etoposide, melphalan and TBI. In all, 145 patients with AML underwent ABMT: 117 in first remission, 21 in second remission and seven beyond second remission. EFS and OS were significantly predicted by remission status (P<0.0001). For transplantation in first remission, 8 year EFS and OS were 55% (95% CI, 44-64%) and 62% (95% CI, 50-72%), respectively. By multivariate analysis, only age (P=0.04) and cytogenetic risk group (P=0.006) influenced OS. For patients transplanted in second remission, 8 year EFS and OS were 30% (95% CI, 9-55%) and 36% (95% CI, 13-60%), respectively. No pre-transplant variables significantly predicted outcome. None of the seven patients who underwent ABMT beyond second remission or in early relapse were long-term survivors. ABMT can provide long-term antileukemic control for patients with AML in first remission. For patients in second remission approximately 30% can achieve cure with ABMT, and this option may be preferable to alternate donor allogeneic stem cell transplantation.

Acute Disease↗
PubMed2002

'Relative' chemotherapy sensitivity: the impact of number of salvage regimens prior to autologous stem cell transplant for relapsed and refractory aggressive non-Hodgkin's lymphoma.

The purpose of the study was to assess the impact of number of salvage regimens needed to demonstrate chemotherapy sensitivity on relapse rates, survival, and toxicity following high-dose therapy and autologous bone marrow transplantation (ABMT) in relapsed or refractory non-Hodgkin's lymphoma. We retrospectively reviewed 136 patients with intermediate-grade lymphoma who underwent ABMT. All patients were treated with salvage therapy to maximum tumor reduction. Three quarters (102/136) of the patients received one salvage regimen, while 31 (23%) patients received two or more regimens. When compared to patients requiring >or= two regimens, patients requiring only one salvage regimen to demonstrate chemosensitivity were more likely to have a longer previous CR from initial therapy (CR >or=12 months in 47% vs 26%; P = 0.04) and to have attained CR with salvage (54% vs 16%; P = 0.001). Both median relapse-free survival (RFS) and overall survival (OS) have not yet been reached in patients receiving one salvage regimen (median follow-up 50.6 months). This is superior to the median RFS of 9.1 months (P = 0.004) and OS of 11.1 months in patients requiring >or=two regimens to demonstrate chemosensitivity (P = 0.002). Time to engraftment, toxic deaths and incidence of myelodysplasia were similar in the groups. The survival rate observed in patients requiring >or=two salvage regimens, although inferior to that of patients receiving a single salvage regimen, are still generally superior to results in the literature for patients treated with chemotherapy alone without ABMT. We conclude that high-dose therapy with ABMT is appropriate for lymphoma patients even when disease reduction requires repeated numbers of salvage regimens.

Adult↗
PubMed2002

Effect of mycophenolate mofetil on severity of nephritis and nitric oxide production in lupus-prone MRL/lpr mice.

Mycophenolate mofetil (MMF), an immunosuppressive drug commonly used in organ transplantation, is increasingly being used to treat autoimmune diseases including systemic lupus erythematosus (SLE). Excessive production of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) has been implicated in the pathogenesis of lupus nephritis. We evaluated the effect of MMF on the severity of nephritis and the production of NO in lupus-prone MRL/lpr mice. Eight-week-old female MRL/lpr mice (n = 20) were treated with MMF (100 mg/kg/day) by oral gavage for 12 weeks. Control mice (n = 20) received vehicle on the same schedule. The mice were killed after 12 weeks of treatment. Treatment with MMF significantly decreased the amount of proteinuria, prolonged survival and reduced the histological severity of glomerulonephritis. Urinary nitrite/nitrate excretion in the MMF-treated mice was significantly reduced during the first 8 weeks of treatment. However, by the end of the 12 weeks' treatment period, there was no significant difference between vehicle and MMF-treated mice in terms of urinary nitrite/nitrate excretion, intra-renal production of NO, expression of iNOS protein and induction of iNOS mRNA. We conclude that MMF is effective in attenuating the severity of nephritis in MRL/lpr mice. The beneficial effects of MMF on lupus nephritis during the early phase of the disease might be partly attributed to the inhibition of NO production. The inhibitory effect of MMF on NO production diminishes as the disease progresses. MMF probably has additional, as yet undefined mode of actions to fully account for its beneficial effects on lupus nephritis.

Animals↗
PubMed2002

Single-centre experience with allogeneic bone marrow transplantation for acute lymphoblastic leukaemia in childhood: similar survival after matched-related and matched-unrelated donor transplants.

Seventy percent of children with acute lymphoblastic leukaemia (ALL) who may benefit from bone marrow transplant (BMT) lack a human leucocyte antigen (HLA)-matched related donor (MRD). For these children, BMT from a matched unrelated donor (MUD) represents a therapeutic option. We reviewed the course of 62 children with ALL who received fully matched marrow allografts at our institution between 1990 and 1998: 36 with MRDs and 26 with MUDs. Clinical characteristics were similar in the two groups. The interval from attainment of pre-BMT complete remission to transplant was significantly longer in the MUD group. Conditioning (etoposide/total body irradiation) and graft-versus-host disease (GVHD) prophylaxis regimens were the same for all patients, and all received T cell-replete bone marrow. There was no significant difference in probability of engraftment, or time to engraftment, in the two groups. MUD BMT recipients had a significantly greater incidence of grade II-IV acute GVHD (58% versus 24% in the MRD group; P = 0.02), and demonstrated a trend towards more chronic GVHD (39% versus 15%; P = 0.06). Three years post BMT, the probabilities of transplant-related mortality were 33 +/- 11% and 20 +/- 8% in MUD and MRD groups respectively (P = 0.38); the probabilities of relapse were 28 +/- 12% and 41 +/- 9% respectively (P = 0.19). Lansky or Karnofsky performance scores in event-free survivors were 90-100 in 87% of the MUD group and 83% of the MRD group. With a median follow up of 38 months (range, 3-97), 3-year event-free survival was 49 +/- 11% and 47 +/- 9% in the MUD and MRD BMT groups respectively (P = 0.71). These results suggest that MUD BMT is a valuable therapy for children with ALL in whom BMT is indicated, and underscore the importance of efforts aimed at expediting unrelated donor searches for patients lacking a MRD.

Adolescent↗
PubMed2001

Radiation-associated pneumonitis following autologous stem cell transplantation: predictive factors, disease characteristics and treatment outcomes.

High-dose therapy followed by autologous stem cell transplantation (ASCT) prolongs survival in patients with multiple myeloma and is relatively safe with treatment-related mortality rates of only 1-5%. Interstitial pneumonitis (IP) is normally an infrequent complication of ASCT with a reported incidence of 0-16%. Between 1992 and 1998, 94 myeloma patients at our center underwent ASCT using a high-dose regimen of etoposide (60 mg/kg), melphalan (160 mg/m2) and fractionated TBI 12 Gy. An unusually high incidence of IP (29/94 (31%)) was noted. Mortality in the IP patients was high at 45%. Patients developing IP were more frequently anemic than those who did not have pulmonary complications (hemoglobin <100 g/l) prior to transplant (P = 0.03) but no other pre-transplant factors were predictive (ie age, gender, smoking history, CMV status, pulmonary function, creatinine, beta2-microglobulin or C-reactive protein, prior cumulative chemotherapy or chest irradiation). A significantly lower IP rate was noted in 32 contemporaneous myeloma control patients conditioned with BU-CY without TBI at our center (3/32 (9%); P=0.03) and in 32 lymphoma control patients conditioned with the same melphalan and etoposide regimen minus the TBI (2/32 (6%); P = 0.003). In contrast, when using the same TBI-containing regimen in 32 concurrently treated lymphoma patients, an increase in IP similar to that seen in our myeloma cohort (7/32 (22%); P = 0.3) was noted. This strongly suggests that TBI is the predominant factor contributing to lung toxicity. We conclude that radiation-associated pneumonitis cannot be easily predicted by pretransplant variables. Therefore surveillance, early recognition and prompt therapy are recommended.

Adult↗
PubMed2001

Autotransplants for histologically transformed follicular non-Hodgkin's lymphoma.

Histological transformation from a follicular non-Hodgkin's lymphoma (NHL) to a higher grade lymphoma carries a poor prognosis despite treatment with aggressive anthracycline-based chemotherapy. We retrospectively analysed 35 patients with histologically transformed NHL who underwent high-dose therapy and autotransplantation at our centre. Patients up to 65 years old were eligible for autotransplant at the time of transformation or with subsequent relapses, provided that chemosensitivity to a salvage regimen could be demonstrated. All patients received high-dose therapy [etoposide 60 mg/kg, melphalan 160 mg/m2 and fractionated total body irradiation (TBI) 12 Gy] followed by unpurged autologous bone marrow or blood stem cell rescue. Most patients (69%) had advanced stage disease (stages 3--4) at transformation and bone marrow involvement was common (49%). Twenty-six (74%) patients were in partial remission (PR) and nine (26%) in complete remission (CR) at the time of transplant. Median duration from transformation to transplant was 10.9 months (range, 5.2 months--4.6 years). At a median follow up of 52 months after autotransplant, 19 (54%) patients had died. Causes of death were progressive lymphoma in nine patients (26%), treatment-related mortality (TRM) in seven (20%) and myelodysplasia in three (8%). Only five patients in our cohort were > 60 years old, but all died as a result of treatment-related causes (mostly pulmonary infections). Five-year overall survival and progression-free survival from time of transplant were 37% and 36% respectively. Using multivariate analysis of factors including gender, age, stage, extranodal disease, disease bulk, B symptoms, number of prior therapies, relapse status and CR/PR status at transplant, only advanced age significantly predicted for survival from autotransplant (P = 0.002). Our survival data are comparable to previous reports of autotransplantation for transformed NHL and suggest a benefit over standard chemotherapy alone in selected patients. However, our high TRM cautions the use of aggressive therapy, including TBI, in patients over 60 years old.

Adult↗
PubMed2001

Malignant lymphoma of mucosa-associated lymphoid tissue of the lacrimal gland: case report and review of literature.

Mucosa-associated lymphoid tissue (MALT) lymphomas are increasingly recognized as a distinct clinical-pathologic entity among the non-Hodgkin's lymphomas. It usually presents as a localized disease process in extranodal tissues or organs such as stomach, salivary gland, thyroid gland, and not infrequently in orbital adnexa. Radiotherapy has an important role in the management, although long-term clinical results specifically addressing localized MALT lymphomas are lacking. We report a case of localized MALT lymphoma of the lacrimal gland, with successful treatment by radiation therapy (total dose 25 Gy) with 3 years of clinical follow-up. A review of the published literature was undertaken to assess the role of radiotherapy in the treatment of this disease involving orbital tissues, specifically, the lacrimal gland. Based on previous reports of patients with orbital lymphomas (low grade) and pseudolymphomas, of which many will now be recognized as MALT lymphomas, radiotherapy has an excellent local control rate and would be the treatment of choice. However, long-term results of pathologically confirmed cases of MALT lymphomas need further study because occasional relapses at distant sites can occur.

Eye Neoplasms↗
PubMed2001

Increased risk for nonmedullary thyroid cancer in the first degree relatives of prevalent cases of nonmedullary thyroid cancer: a hospital-based study.

The genetic basis for nonmedullary forms of thyroid cancer (NMTC) is less well established than that of medullary thyroid cancer. However, epidemiological and family studies suggest that a proportion of NMTC may be due to inherited predisposition. To estimate the familial risk of thyroid cancer, we conducted a hospital-based case-control study at the Princess Margaret Hospital in Toronto, Ontario, Canada, and at 2 university hospitals in Montréal, Québec, Canada. We obtained pedigrees from 339 unselected patients diagnosed with NMTC and from 319 unaffected ethnically matched controls. Family histories of cancer were obtained from the cases and controls for 3292 first degree relatives of cases and controls. Seventeen cases (5.0%) and 2 controls (0.6%) reported at least one first degree relative with thyroid cancer. In relatives of patients with thyroid cancer, the incidence of any type of cancer (including NMTC) was 38% higher than in relatives of controls (incidence rate ratio, 1.4; 95% confidence interval, 1.1-1.7). The relative risk for thyroid cancer was 10-fold higher in relatives of cancer patients than in controls (incidence rate ratio, 10.3; 95% confidence interval, 2.2-47.6). Our findings suggest that hereditary or other familial factors are important in a small proportion of NMTC. Molecular studies are needed to determine the genetic basis of cancer susceptibility in these families.

Adolescent↗
PubMed2000

Radiolabeling brachytherapy sources with Re-188 through chelating microfilms: stents.

Rhenium-188 (Re-188, T(1/2) = 17 h) emits beta particles (E(max) = 2. 12 MeV) having an ideal range for intravascular brachytherapy and certain cancer brachytherapies. Re-188 was attached to metal wafers and stents via a chelating microfilm, and these brachytherapy sources characterized in vitro and in vivo. To prepare the sources, a siloxane film containing reactive amines was plasma deposited on the metal, a chelating microfilm conjugated to the amines, and the chelating microfilm used to attach Re-188. Re-188 was selectively bound to materials coated with the chelating microfilm. Binding correlated with the amount of radionuclide used. Wafers (1 cm(2)) bound up to 62.9 MBq (1.7 mCi) of Re-188 with yields generally near 30%. Stents bound up to 26.6 MBq (720 microCi). Typically, stents were labeled to bind 4-12 MBq and deposit 10-30 Gy at 2 mm in the arterial wall. In phantom studies, the longer nitinol stents deposited doses of 2.3 Gy/MBq (0.085 Gy/microCi), while shorter stainless steel stents deposited 4.62 Gy/MBq (0.171 Gy/microCi). After placement in arteries of pigs, only the Re-188-stents were detected by scintigraphy at times up to 24 h. Scintigraphy did not detect activity in other organs. Blood sampling (0.1-24 h) detected maximum radioactivity (up to 388 cpm/mL/100micro Ci) at 6 h. We conclude that on-demand radiolabeling of stents and other brachytherapy sources with Re-188 can be performed routinely.

Biocompatible Materials↗
PubMed2000

Primary gastric lymphoma: brief overview of the recent Princess Margaret Hospital experience.

Primary gastric lymphoma is the commonest form of presentation for gastrointestinal lymphomas and the stomach is one of the most frequent sites of extranodal lymphoma. We present a review of the Princess Margaret Hospital (PMH) experience to illustrate the favorable prognosis and examine the long-term outcomes in this disease. Between 1967 and 1996, 149 consecutive patients with gastric lymphoma were treated at the PMH. The majority (122 patients) presented with diffuse large-cell lymphoma and 78 had stage I disease. In the past, the standard treatment was surgery (partial gastrectomy) followed by post-operative radiation therapy (RT; 78 patients). The overall 10-year survival was 62%. For patients who were treated with surgery and post-operative RT (operable disease) between 1967 and 1985, the 10-year rates of overall survival and cause-specific survival were 66.2% and 88%, respectively. In the past decade, combined-modality therapy with chemotherapy followed by RT was introduced for large-cell lymphoma, while RT alone was used for mucosa-associated lymphoid tissue (MALT) lymphoma. In 45 patients treated in the past decade, the overall 5-year survival was 86%, the cause-specific survival was 95.5%, and the relapse-free rate was 87.3%. These results support the view that primary gastric lymphoma is a highly curable disease. Future efforts should focus on reducing treatment morbidity, while preserving excellent results.

Adult↗
PubMed2000

Mucosa-associated lymphoid tissue lymphomas.

Mucosa-associated lymphoid tissue (MALT) lymphoma has attracted attention because its concept has amalgamated the study of etiology and pathogenesis in an intriguing group of lymphomas. MALT lymphomas are a B-cell malignancy with characteristic lymphoepithelial lesions; cells are CD20-positive and CD5- and CD10-negative. The molecular changes observed include trisomy 3, t(11;18), and t(1;14) translocations. They commonly occur in the stomach, orbit, salivary glands, and thyroid. Localized disease is present in 60% to 70% of patients. Involvement of multiple extranodal sites has been observed at presentation or during the course of disease. Lymphocyte homing has been implicated in gastrointestinal MALT and may be involved in other MALT lymphomas. Local therapy, either through surgery or radiotherapy, is curative in a high proportion of patients. MALT lymphomas respond to chemotherapy, but there is no evidence that cure can be achieved, although prolonged survival is common. Long-term follow-up is essential for study of the outcomes in this disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Intensification of the stem cell transplant induction regimen results in increased treatment-related mortality without improved outcome in multiple myeloma.

Randomized trials conducted by the Intergroupe Française du Myelome (IFM) demonstrate that the use of high-dose chemotherapy (HDCT) and stem cell transplantation (SCT) improves event-free (EFS) and overall survival (OS) in younger patients with multiple myeloma (MM). Nevertheless, current HDCT regimens remain inadequate as all patients ultimately relapse following SCT. In an attempt to improve the OS of MM patients post-SCT we used an escalated HDCT regimen incorporating both intensified melphalan (160 mg/m2) and fractionated total body irradiation (12 Gy) to maximize the dose response of myeloma cells to these agents and included infusional etoposide 60 mg/kg in an attempt to eradicate clonal B cells potentially contributing to the myeloma clone. One hundred patients with MM received this intensified SCT regimen. The 100-day treatment-related mortality was 12% predominantly reflecting the development of interstitial pneumonitis (IP) in 28% of patients of whom 7/28 (25%) died. The predicted 5-year OS and EFS following the diagnosis of MM were 60% and 35%, respectively. The median OS from the time of transplant is 41 months and the median EFS is 28 months. More than two prior chemotherapy regimens, previous radiation therapy (RT) and the presence of an abnormal karyotype involving chromosomes 11 or 13 were significantly predictive of poor outcome. Interferon maintenance was not associated with improved outcome. Intensification of the HDCT regimen utilizing etoposide together with escalated melphalan and TBI increases morbidity and mortality without increasing OS beyond that reported with less toxic regimens.

Adult↗
PubMed1999

Evaluation of a long-chain polyunsaturated fatty acid supplemented formula on growth, tolerance, and plasma lipids in preterm infants up to 48 weeks postconceptional age.

BACKGROUND: The last trimester of pregnancy is a period of rapid accretion of long-chain polyunsaturated fatty acids, both in the central nervous system and the body as a whole. Human milk contains these fatty acids, whereas some preterm infant formulas do not. Infants fed formulas without these fatty acids have lower plasma and erythrocyte concentrations than infants fed human milk. Preclinical and clinical studies have demonstrated that single-cell sources (algal and fungal) of long-chain polyunsaturated fatty acids are bioavailable. A balanced addition of fatty acids from these oils to preterm formula results in blood fatty acid concentrations in low birth weight infants comparable to those of infants fed human milk. METHODS: In the present study the growth, acceptance (overall incidence of discontinuation, reasons for discontinuation, overall incidence and type of individual adverse events), and plasma fatty acid concentrations were compared in three groups of infants fed a long-chain polyunsaturated fatty acid-supplemented preterm infant formula, an unsupplemented control formula, or human milk. The study was prospective, double-blind (formula groups only), and randomized (formula groups only). Two hundred eighty-eight infants were enrolled (supplemented formula group, n = 77; control formula group, n = 78; human milk group, n = 133). RESULTS: Anthropometric measurements at enrollment, at first day of full oral feeding, and at both 40 and 48 weeks postconceptional age did not differ between the formula groups, whereas the human milk-fed group initially grew at a lower rate. The incidence of severe adverse events was rare and not significantly different between formula groups. The groups fed either human milk or supplemented formula had long-chain polyunsaturated fatty acid concentrations higher than those in the control formula group. CONCLUSIONS: The results of this study demonstrate the safety and efficacy of a preterm formula supplemented with long-chain polyunsaturated fatty acids from single-cell oils.

Aging↗
PubMed1998

Late effects of treatment for early-stage Hodgkin's disease.

A comprehensive survey of late effects (physical, social and reproductive) following treatment at a single institution for early stage Hodgkin's disease (HD) was performed. A total of 611 patients with stage I and II HD treated between 1973 and 1984 were reviewed; 460 were alive and were mailed a self-reported questionnaire. A total of 363 (79%) replies were received. Twenty patients died of second malignancy, 14 of heart disease and nine from respiratory disease. There were 37 cases of second malignancy [relative risk (RR) 2.2, absolute excess risk (AR) 35.8]. The 15-year incidence of heart disease was 11% and there were nine myocardial infarction deaths (RR 1.55, AR 5.4). Twenty-eight (8%) respondents stated that their career had been greatly interfered with, 53 (14.5%) perceived financial loss. Sexual activity was disrupted in 25.8%. In total, 56 men had fathered 112 pregnancies. Of 171 women, 40.3% became pregnant, resulting in 92 live births. A total of 43 men and 16 women had sought medical advice with regard to infertility.

Acute Disease↗