Epidemiology and prognostic factors for mycosis fungoides and Sézary syndrome in a multi-ethnic Asian cohort: a 12-year review.

BACKGROUND: Limited information exists regarding survival of Asian patients with mycosis fungoides (MF) and Sézary syndrome (SS). OBJECTIVE: To evaluate the epidemiology, outcome and prognostic factors of these patients. METHODS: A retrospective review of MF/SS cases diagnosed from 2000 to 2011 at a tertiary referral dermatology centre in Singapore was performed. RESULTS: Of 246 patients, 63% were male and the median age at diagnosis was 49 years. 73.2% were Chinese, 12.6% Indian, 6.9% Malay and 7.3% Caucasian. A total of 239 patients (97.2%) had MF and seven had SS. Median follow-up duration was 6.3 years, and median duration of symptoms at diagnosis was 13 months. For patients with MF, the majority had early disease (92.8% stage IA-IIA). 3.8% were stage IIB, 1.7% stage III and 1.7% stage IV. Complete response to treatment occurred in 78.2%, partial response in 9.6%, persistent but non-progressive disease in 10.0% and disease progression in 4.1% of patients. Large cell transformation occurred in 4.1% of patients. Mean overall survival during this study was 12.7 years, with death occurring in 2.5% of patients (all ≥stage IIB at diagnosis). For patients with SS, 71.4% presented with stage IVA disease, 28.6% stage IVB. Complete response to treatment occurred in 14.2%, persistent but non-progressive disease in 28.6% and disease progression in 57.2% of patients. Mean overall survival was 3.3 years within this study, with death occurring in 42.9% of SS patients. Prognostic factors associated with favourable recurrence-free survival were male gender (P = 0.008), early disease stage (T1) at diagnosis (P < 0.001) and absence of maintenance treatment after remission (P = 0.01). CONCLUSION: Compared to Caucasian and East Asian cohorts, MF in South-East Asians was diagnosed at a younger age and associated with lower mortality, largely due to greater prevalence of hypopigmented MF.

Prevalence of smoking and its associated factors with smoking among elderly smokers in Malaysia: findings from a nationwide population-based study.

BACKGROUND: The determination of smoking prevalence and its associated factors among the elderly could provide evidence-based findings to guide the planning and implementation of policy in order to will help in reducing the morbidity and mortality of smoking-related diseases, thus increase their quality of life. This paper describes the rate of smoking and identifies the factor(s) associated with smoking among the elderly in Malaysia. METHODS: A representative sample of 2674 respondents was obtained via a two-stage sampling method in proportion to population size. Face-to-face interviews were conducted using a set of standardized validated questionnaire. Data was weighted by taking into consideration the complex sampling design and non-response rate prior to data analysis. Univariable and multivariable logistic regression were used to determine the factor/s associated with smoking. RESULTS: The prevalence of non-smokers, ex-smokers and current smokers among Malaysians aged 60 years and above were 36.3 % (95 % CI = 32.7-39.8), 24.4 % (95 % CI = 21.2-27.5) and 11.9 % (95 % CI = 9.5-14.3), respectively. Current smokers were significantly more prevalent in men (28.1 %) than in women (2.9 %), but the prevalence declined with advancing age, higher educational attainment, and among respondents with known diabetes, hypertension and hypercholesterolemia. Multivariable analysis revealed that males (aOR, 18.6, 95 % CI 10.9-31.9) and other Bumiputras (aOR 2.58, 95 % CI 1.29-5.15) were more likely to smoke. in addition, elderly with lower educational attainment (aOR, 1.70, 95 % CI 1.24-7.41) and those without/unknown hypertension also reported higher likelihood to be current smokers (aOR 1.98, 95 % CI 1.35-2.83). However, there were no significant associations between respondents with no/unknown diabetes or hypercholesterolemia with smoking. CONCLUSIONS: In short, smoking is common among elderly men in Malaysia. Therefore, intervention programs should integrate the present findings to reduce the smoking rate and increase the smoking cessation rate among the elderly in Malaysia and subsequently to reduce the burden of smoking-related disease.

Experimental study of the potential hazards of surgical smoke from powered instruments.

BACKGROUND: Many surgical instruments have been replaced with powered devices in open gastrointestinal and laparoscopic surgery. The production of smoke as a result of vaporization of surgical tissue is inevitable, and exposure to surgical smoke is a long-standing concern. These vapours are potentially hazardous to patients and surgical teams. The present research was designed to compare various surgical devices to determine whether viable cells exist in their surgical smoke. METHODS: The search for viable cells in surgical smoke was conducted using both in vitro and in vivo experiments. Various cancers were cauterized with electrocautery, radiofrequency ablation and ultrasonic scalpels, and the resulting surgical smoke was aspirated with Transwell(®) membrane; viable cells were sought in the surgical smoke. In an in vivo experiment, samples of SCC7 were cauterized with an ultrasonic scalpel and the sediment from the rinsed Transwell(®) membrane liquid after centrifugation was injected subcutaneously into the lower back of mice. RESULTS: Viable cells were found only in the smoke from ultrasonic scalpels (in all 25 samples taken 5 cm from the cautery; 2 of 25 samples at 10 cm). Viable cells in the surgical smoke from ultrasonic scalpels implanted in mice grew in 16 of 40 injection sites. Histological and biochemical analyses revealed that these cancer cells were identical to the cancer cells cauterized by the ultrasonic scalpel. CONCLUSION: Viable tumour cells are produced in the surgical smoke from tumour dissection by ultrasonic scalpel. Surgical relevance Surgical smoke is a byproduct of dissection using a number of powered devices. Hazards to operating room personnel and patients are unclear. This study has shown that use of an ultrasonic dissection device can produce smoke that contains viable tumour cells. Although the model is somewhat artificial, a theoretical risk exists, and measures to evacuate surgical smoke efficiently are important.

Comparison of clinical with pathological nodal staging from systematic mediastinal lymph node dissection in early resectable non-small cell lung cancer.

INTRODUCTION: We compared the accuracy of clinical nodal (cN) status N0-1 with that of pathological nodal (pN) status obtained from systematic mediastinal lymph node dissection (SMLD) in primary non-small cell lung cancer. METHODS: Data from 22 consecutive patients, who underwent lung cancer resection and SMLD of at least three mediastinal lymph node stations, from November 2001 to May 2003, were ana1ysed retrospectively. Only patients with cN0-1 status on computed tomography (CT) referred for surgery, were included in this study. RESULTS: Mean age of patients was 66.6 +/- 8.1 years with a male to female ratio of 17:5. Mean number of lymph node stations dissected was 5.8 +/- 1.8. 41 percent had squamous cell carcinoma, 45.5 percent had adenocarcinoma, and 4.5 percent each had large cell carcinoma, bronchioalveolar carcinoma or a lymphoepithelial carcinoma. pN2 metastases were found in 27.3 percent of patients. The sensitivity of cN0-1 was only 12.5 percent, with a specificity of 92.9 percent and an area under the receiver operating characteristics curve of 0.53. The positive and negative predictive values of cN0-1 status were 50 percent and 65 percent, respectively, with an accuracy of 59 percent. 41 percent of patients were understaged with 27.3 percent in pathological stage III. Curative resections were achieved in 59 percent of patients. CONCLUSION: The sensitivity of cN0-1 status based on CT alone is extremely poor when compared with pN status from SMLD. Based on cN0-1 status alone without SMLD, 27.3 percent of patients in pN2 would have been understaged. We recommend that all patients with cN0-1 status should undergo SMLD of at least three appropriate mediastinal node stations, for more accurate staging.

A multicentre randomised phase II study of carboplatin in combination with gemcitabine at standard rate or fixed dose rate infusion in patients with advanced stage non-small-cell lung cancer.

BACKGROUND: Intracellular gemcitabine triphosphate (dFdCTP) levels can be optimised by administering gemcitabine at a fixed dose rate infusion. PATIENTS AND METHODS: Patients with chemonaive advanced non-small cell lung cancer (NSCLC) were randomised to receive gemcitabine at a fixed dose rate gemcitabine 750 mg/m(2) over 75 min (arm A) or gemcitabine 1000 mg/m(2) over 30 min (arm B) on days 1 and 8 every three week cycle. Carboplatin at AUC of 5 was administered in both treatment arms on day 1 of each cycle. End points were activity, tolerability and pharmacokinetics of plasma and intracellular gemcitabine. RESULTS: 76 patients were randomised. Response rate was 34% in arm A and 42% in arm B. Toxicity and quality of life scores were similar for both treatment arms. Mean plasma Cmax(gemcitabine) and mean dFdCTP AUC in arm A was 20.8 microM +/- 17.2 microM and 35,079 +/- 18,216 microM*min respectively and in arm B, 41.2 +/- 13.9 microM and 32 249 +/- 11 267 microM*min respectively. dFdCTP saturation was reached in Arm B but not in Arm A. CONCLUSION: The saturability of dFdCTP accumulation in Arm A suggests optimal delivery of gemcitabine is achieved using fixed rate infusion compared to 30-min infusion. Fixed dose rate gemcitabine is active and feasible, supporting the concept of fixed dosing rate of gemcitabine in advanced NSCLC. However, this entails a longer infusion time with associated higher costs involved.

Paclitaxel, 5-fluorouracil and hydroxyurea concurrent with radiation in locally advanced nasopharyngeal carcinoma.

BACKGROUND: Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced nasopharyngeal carcinoma (NPC). We conducted a phase II trial using paclitaxel, 5-fluorouracil and hydroxyurea concurrent with radiation (TFHX). PATIENTS AND METHODS: Fifty-nine patients with locally advanced NPC were treated with CRT consisting of 4-day continuous infusions of paclitaxel (20 mg/m(2)/d) and 5-fluorouracil (600 mg/m(2)/d), and oral hydroxyurea 500 mg bid for nine doses, every 3 weeks concurrent with radiotherapy (RT). RT consisted of once daily 200cGy fractions 5 times per week to a total of 7000cGy. RESULTS: Complete response was seen in 86% and 71% of patients at 4 and 12 months after CRT. The median follow-up was 34 months. Twenty-three patients experienced relapse. Sixteen deaths occurred: 13 from progressive disease. Three-year overall survival and progression-free survival were 72% and 54% respectively, with locoregional and distant control rates of 83% and 64% at 3 years respectively. Grade 3 to 4 acute toxicities included oropharyngeal mucositis in 81% of patients treated, dermatitis in 63%, weight loss in 32%, and neutropenia in 22%. Neutropenic fever was seen in 14%. There were no treatment-related deaths from acute toxicity. CONCLUSIONS: TFHX is shown to be feasible in NPC. Non-cross resistant induction chemotherapy should be further studied with this regimen.

Phase II trial of docetaxel in Asian patients with inoperable stage III non-small cell lung cancer.

Docetaxel has a response rate of greater than 30% in first-line treatment of Western patients with advanced non-small cell lung cancer (NSCLC). The goal of this open-label. phase II study was to evaluate the activity and safety profile of docetaxel in Asian patients with inoperable untreated stage III NSCLC. Docetaxel was given at 100 mg/m2 as a 1-h infusion every 3 weeks. Prophylactic dexamethasone was given to reduce hypersensitivity reactions and edema. Thirty-five patients were enrolled in the study. The response rate was 34% (95% CI, 19%-50%) according to intent-to-treat analysis. No complete response was observed. Twenty-four patients (69%) had grade 3 or 4 neutropenia in cycle 1, and febrile neutropenia was seen in 12 patients. Six patients (17%) experienced mild fluid retention. Docetaxel is an active agent in first-line treatment of Asian patients with locally advanced NSCLC, with the main toxicity being neutropenia. Fluid retention was a minor problem in this study.

Immunoglobulin D multiple myeloma in our hospital--a rare occurrence.

Immunoglobulin (Ig) D multiple myeloma is a rare presentation, usually with an aggressive course and a poorer prognosis. It accounts for about 1-2% of newly diagnosed mulitple myeloma patients. Due to its rarity, reports on Ig D multiple myeloma are limited in the literature. We therefore present 4 cases of Ig D multiple myeloma in our hospital over a period of 8 years between 1990 to 1998. The average age of presentation of our patients was 44 years old with a female preponderance. Common presenting symptoms were appetite and weight loss and bone pain. Two patients presented with neurological symptoms and 2 with renal impairment. Three patients had an associated lambda paraproteinaemia and the fourth had a kappa paraproteinaemia. A common finding in Ig D myeloma is a small or no spike seen on serum electrophoresis together with heavy Bence Jones proteinuria. A review of the literature on Ig D myeloma is also presented.

L-asparaginase induced intracranial haemorrhage in acute lymphoblastic leukemia.

A 20-year-old national serviceman with acute lymphoblastic leukaemia, developed a large left parieto-occipital haemorrhage 7 days after completion of induction chemotherapy. Severe hypofibrinogenemia had been noted while he was receiving L-asparaginase. The haemorrhage could not be attributed to thrombocytopenia, disseminated intravascular coagulopathy, arterio-venous malformation, berry aneurysm or leukaemic infiltration because each of these causes was carefully investigated into and excluded. We conclude that the intracranial haemorrhage was likely L-asparaginase induced, an uncommon but recognised complication associated with L-asparaginase therapy.

Activation of tumor necrosis factor-alpha system in chronic hepatitis C virus infection.

Tumor necrosis factor-alpha (TNF-alpha) plays a central role in the host's immunomodulatory response to infective agents. To evaluate the TNF-alpha system in patients with chronic hepatitis C virus (HCV) infection, plasma, serum, and peripheral blood mononuclear cells (PBMC) were prospectively collected from 53 patients and 33 healthy control subjects. Circulating TNF-alpha and TNF receptors were assayed by their respective enzyme immunoassays. In addition, TNF-alpha mRNA was quantitated in PBMC using a branched DNA assay, and production of TNF-alpha by PBMC with and without lipopolysaccharide was also assessed. Patients with chronic HCV infection had a higher level of circulating TNF-alpha compared to healthy control subjects (9.62 +/- 6.01 vs 3.66 +/- 1.23 pg/ml, P < 0.001). They also had higher circulating levels of TNF receptors compared to control (CD120a: 3323 +/- 1267, pg/ml, N = 49 vs 1855 +/- 422 pg/ml, N = 33, P < 0.001; CD120b: 1290 +/- 650 pg/ml, N = 51, vs 863 +/- 207 pg/ml, N = 33, P < 0.001). Plasma TNF-alpha level correlated with circulating CD120a (r = 0.52, N = 49, P < 0.001) and weakly with CD120b (r = 0.32, N = 51, P = 0.02). Plasma TNF-alpha also correlated with markers of hepatocellular injury, including ALT (r = 0.34, N = 53, P = 0.01) and alpha-GST (r = 0.31, N = 43, P = 0.042), but not with serum HCV RNA levels. There was no difference in the TNF-alpha mRNA levels in PBMC between patients with chronic HCV infection (1.4 +/- 1.9 units/10[6] cells, N = 8) and healthy control subjects (2.1 +/- 1.4 units/10[6] cells, N = 8, P = NS). There was also no difference in the spontaneous production of TNF-alpha by PBMC (1 x 10[6] cells/ml) between patients with chronic HCV infection (14.2 +/- 36.5 pg/ml, N = 11) and healthy subjects (11.9 +/- 14.0 pg/ml, N = 14, P = NS). However, patients with chronic HCV infection produced more TNF-alpha upon stimulation with lipopolysaccharide compared to healthy control subjects (1278 +/- 693 pg/ml, N = 11, vs 629 +/- 689 pg/ml, N = 14, P < 0.05). These data indicate that the TNF-alpha system is activated in patients with chronic HCV infection.

alpha-Glutathione S-transferase as a marker of hepatocellular damage in chronic hepatitis C virus infection.

alpha-Glutathione S-transferase (alpha GST) may be a good serologic marker of hepatocellular damage because of its low molecular weight, uniform hepatic distribution, high cytosolic concentration, and short half-life. To determine the clinical utility of alpha GST in patients with chronic hepatitis C virus (HCV) infection, serum alpha GST levels were measured in 96 patients with chronic HCV infection, of whom 47 subsequently underwent interferon-alpha therapy. Patients were simultaneously evaluated with conventional liver biochemistry, serum HCV RNA levels, and liver histology. Different methods of serum collection did not affect alpha GST values, indicating that this was a stable serum marker. In 93% of patients with chronic HCV infection, alpha GST was elevated and showed an excellent correlation with serum aminotransferases. Histologic analysis revealed a correlation of alpha GST with both lobular inflammation and bile duct lesions. There was no correlation between serum alpha GST levels and the demographic features, mode of transmission, virologic, other histologic parameters, or subsequent response to interferon-alpha. During serial monitoring in patients undergoing interferon-alpha therapy, elevation of serum alpha GST correlated with biochemical relapse and in some patients virologic relapse in the presence of normal liver biochemistry. alpha GST was persistently elevated in all nonresponders. Four of six of those patients who responded completely followed by early relapse had elevated alpha GST intermittently or continuously during therapy despite normalization of serum aminotransferases. Two of five of those with a complete and sustained response had elevated alpha GST during treatment and follow-up, and both were also seropositive for HCV RNA during follow-up. These data demonstrate that alpha GST is a stable marker, has similar diagnostic utility as serum aminotransferases, and may have a role in the monitoring of patients undergoing interferon-alpha therapy.

Plasma glutathione concentration in patients with chronic hepatitis C virus infection.

It has recently been proposed that a depletion of glutathione (GSH) may be a contributing factor to viral persistence and resistance to interferon-alpha (IFN-alpha) therapy in chronic hepatitis C virus (HC) infection. The aim of this study was: (1) to compare plasma GSH levels in patients with chronic HCV infection and normal healthy controls; and (2) to correlate GSH levels with liver histology and serum HCV RNA levels. Twenty-four patients with compensated chronic hepatitis C and 27 healthy subjects were studied. Serum and heparinized plasma were prospectively prepared and frozen within 1 h of collection. Plasma glutathione and glutathione peroxidase (GP) levels were measured spectrophotometrically. The serum HCV RNA level was quantitated by the branched chain DNA signal-amplification assay. Plasma GSH levels were not decreased in patients with chronic HCV infection but were actually greater than in controls (control 1.27 +/- 0.12 micrograms ml-1, HCV 1.62 +/- 0.11 micrograms ml-1, P < 0.05). There was also no difference in plasma GP activity between these two groups (control 0.233 +/- 0.007 U ml-1, HCV 0.230 +/- 0.007 U ml-1). Among the patients with chronic HCV infection, there was no correlation between either plasma GSH or GP levels and the serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST), serum HCV RNA level, or liver histology. This study demonstrates that chronic HCV infection does not decrease the plasma GSH and GP levels.

Treatment of acute promyelocytic leukaemia in first relapse with all-trans retinoic acid.

A 27-year-old Chinese woman with acute promyelocytic leukaemia in first relapse after the initial conventional induction chemotherapy 18 months earlier was treated with all-trans retinoic acid (ATRA) at an initial dose of 45 mg/m2 and subsequently increased to 65 mg/m2 on day 15. Complete remission was achieved after a total of 40 days of ATRA alone. Serial marrow examinations during induction showed progressive maturation of myelopoiesis without bone marrow hypoplasia. There was a significant reduction in number of cells with the t(15;17) translocation when complete remission was achieved. ATRA was very well-tolerated. The symptoms of dry skin and intermittent headache were self-limiting.

Therapy for chronic hepatitis C.

Hepatitis C is the silent epidemic of the 1970s and 1980s. Interferon alfa is currently the only effective treatment. Enthusiasm for interferon therapy must be tempered because advanced disease usually requires years or even decades to develop and does not occur in all patients. Few patients with chronic hepatitis C derive long-term improvement from a single 6-month course of interferon therapy. Most initial responders relapse and require long-term interferon treatment to suppress the virus. Obviously, the initial goals and expectations for interferon therapy require rethinking. Therapy should not be undertaken by physician or patient with the idea that therapy will be limited to 6 months. The most appropriate goal of therapy now appears to be the long-term control of the biochemical, virologic, and histologic activity of the disease. Unfortunately, the most effective therapeutic regimen for achieving this goal is not yet known and will require continued clinical research.

Multiple myeloma: the National University Hospital (NUH) experience.

The aim of this retrospective study was to define the characteristics of local patients with multiple myeloma. Twenty-nine de novo cases were accrued from October 1986 to January 1992 at the National University Hospital of Singapore. Features like median age of presentation, sex distribution, the incidence of IgG, IgA and light chain subtypes were similar to published data. However IgD myeloma appeared to be more common here and it tended to be more advanced at presentation. Objective response rate to treatment with the melphalan-prednisolone combination was about 40% with a median survival of 18 months.