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Biomedical subjects

C Varghese

Publications and source records attributed to C Varghese.

At least 19 recordsLinked to original sources

Childhood cancer in the south Asian population of England (1990-1992).

Cancer incidence in 1990-92 among English south Asian (residents with ethnic origins in India, Pakistan or Bangladesh) and non-south Asian children is compared. Standardized incidence ratios show significant overall excesses in south Asians (131), largely due to higher rates in south Asian boys, and specific excesses for leukaemia (141), lymphoid leukaemia (141), lymphoma (172) and hepatic tumours (375). Aetiological investigation is required.

Adolescent↗

Proliferating cell nuclear antigen and epidermal growth factor receptor (EGFr) status in renal cell carcinoma patients with polysomy of chromosome 7.

We investigated 40 cases of renal cell carcinoma (RCC) to study the polysomy 7 status in papillary and clear-cell types (nonpapillary RCC) and relationship with clinical, pathological, and biological features such as grade, stage, tumor proliferation rate (PCNA expression) and epidermal growth factor receptor (EGFr) expression and thereby to understand the prognostic significance of polysomy 7 and EGFr expression. In a prospective study, chromosome 7 copy number was analyzed in tumor cells by using fluorescence in situ hybridization (FISH) with an alpha-satellite DNA probe for chromosome 7. Both proliferating cell nuclear antigen (PCNA) and EGFr expression were examined in paraffin sections by immunostaining. The relationship between clinicopathological and clinicobiological parameters was evaluated by appropriate statistical methods. Polysomy 7 was present in 100% of papillary and 56.2% of clear-cell types RCC. In clear-cell RCC, in comparison with polysomy 7-dominant (D) category (20-50% polysomy-7 cells), polysomy 7-major (M) category (>50% polysomy 7 cells) was associated with higher tumor grade (P = 0.05). Polysomy 7 was also correlated with stage of the disease (P = 0.006). The PCNA index ranged between 12.8-89.6% and was comparatively high in high-grade tumors (P = 0.001). The PCNA index was also correlated with polysomy 7 (P = 0.002), and the association was stronger in tumors with polysomy M versus polysomy D category (P = 0.02). The EGFr expression did not correlate with either grade, stage, PCNA, or polysomy 7. The correlation of polysomy 7 with less favorable prognostic factors such as higher tumor grade, stage, and higher proliferative index in the present study indicates that polysomy 7 might be used as a prognostic predictor in clear-cell RCC. Evaluation of clinical end points will confirm the prognostic potential of the genetic marker polysomy 7 in our study.

Adenocarcinoma, Clear Cell↗

Diet and stomach cancer: a case-control study in South India.

A prospective case-control study was conducted in Trivandrum, India, to evaluate the dietary risk factors for stomach cancer. One hundred and ninety-four patients with stomach cancer registered at the Regional Cancer Centre (RCC), Trivandrum, Kerala, India, during the period 1988-1991 were considered as cases. A minimum of one control (n = 305), matched for age (+/- 5 years), sex, religion and residential area was selected from the visitors to RCC during the same period. Interviews were carried out using a predetermined structured food frequency questionnaire. The information collected also included socio-demographic/economic background, tobacco chewing, tobacco smoking and alcohol habits. Data were analysed using a multiple logistic regression model. Odds ratios for all dietary variables were estimated. Increased risks were observed with higher consumption of rice (OR 3.9; 95% CI 1.6-10.0). Risk was high for those consuming spicy food (OR 2.3; 95% CI 1.1-5.0), high consumption of chilli (OR 7.4; 95% CI 4.0-13.5) and consumption of high-temperature food (OR 7.0; 95% CI 3.7-12.9). On multivariate analysis, high consumption of rice, high consumption of chilli and consumption of high-temperature food were found to be independent risk factors.

Adult↗

Hyperfractionation in carcinoma of the cervix: tumor control and late bowel complications.

PURPOSE: Hyperfractionation has been advocated to improve local tumor control by increasing radiation dose without increasing late normal tissue complications. The aim of this study was to determine if hyperfractionation decreased late bowel complications. METHODS AND MATERIALS: Thirty patients with Stage II and III cervical cancer were randomized to receive either hyperfractionation or conventional fractionation. Patients were followed for 5 years and monitored for tumor control, recurrence, and bowel complications. The relative risks of tumor control and bowel complications were computed at 1 year and 5 years of follow-up. Kaplan-Meier survival curves were plotted to determine probabilities of being tumor-free and bowel complication-free. RESULTS: There were 15 patients in each group. At 1 year of follow-up, 2 patients in the hyperfractionation group (13%) and 7 patients in the conventional treatment group (45%) had tumor (relative risk [RR] 0.3; 95% confidence interval [CI] 0.1, 1.1; p = 0.054). Delayed bowel complications were seen in 8 patients in the hyperfractionation group and 1 patient in the conventional treatment group (RR 7.5; 95% CI 1.1, 52; p = 0.014). At 5 years, 2 patients in the hyperfractionation group and 8 patients in the conventional treatment group had tumor (RR 0.3; 95% CI 0.1, 1.1; p = 0.04). Delayed bowel complications (Grades 2 and 3) occurred in 9 women in the hyperfractionation group and 2 patients in the conventional group (RR 5.4; 95% CI 1.5, 19.5; p = 0.0006). Kaplan-Meier analysis showed that the hyperfractionation group had significantly more bowel complications over the 5 years of follow-up (p = 0.024). CONCLUSION: Hyperfractionation may result in better tumor control both at 1 year and at 5 years following treatment of cervical cancer. However, hyperfractionation could lead to increased late bowel complications and must be used judiciously in the treatment of cervical cancer.

Adult↗

Clinical significance of cytogenetic findings at diagnosis and in remission in childhood and adult acute lymphoblastic leukemia: experience from India.

We report cytogenetic findings in 114 patients of acute lymphoblastic leukemia (ALL), which includes 78 children (< or = 15 years) and 36 adults (16-60 years). Chromosome aberrations were detected in 109 (95%) cases. A lower frequency of hyperdiploidy (15%) in children and a higher frequency of hypodiploidy both in children (38.4%) and adults (44.4%) were found, in contrast to literature. Translocations were detected in one third of adult and pediatric cases. The incidence of t(9;22) was comparatively low in adults (7.7%). Frequency of t(1:19) was also low in overall ALL cases. Various other recurrent abnormalities such as del(6q), abn(11q23), i(9p), abn(12q13), del(7q), and i(17q) were seen in our cases; a striking difference in the incidence of del(6q) (41%) and abn(11q23) (30%) was found in our series versus reported literature. Ploidy distribution indicated association of pseudo- and hypodiploidy with B-lineage, and hypodiploidy with T-lineage in children. The occurrence of del(6q) was more frequent in pediatric ALL with highly aberrant pattern and also with lymphadenopathy. Abn(11q23) was found to be early-B and pre-B specific. Kaplan-Meier analysis of overall survival revealed prognostic value of sex, FAB, immunophenotype, and cytogenetic findings. Females and T-ALL patients had a better prognosis, whereas males and B-ALL patients had poor outcome in overall and pediatric age groups. Prognostic evaluation of cytogenetics indicated translocations as an independent high-risk predictor in childhood (P < 0.008) and adult ALL (P < 0.01). Childhood ALL with t(8;14) and t(4;11) and adults with t(9;22) had poor survival. Cytogenetics of remission marrows demonstrated disappearance of abnormal clones in 31.4%, and expansion in normal clones in 50% of patients. Persistence of original clones and development of new clones were observed in 20% and 33% of patients, respectively; whereas karyotype evolution was identified in 10% of patients. The prognostic significance of cytogenetic findings at diagnosis, and differential cytogenetic response in so-called clinical remission in our study indicated the utmost need for more intensive therapy for eradication of resistant clones, and necessity of sequential cytogenetic follow-up in these patients for identification of minimal residual disease.

Adolescent↗

Cancer incidence in the south Asian population of England (1990-92).

Cancer incidence among English south Asians (residents in England with ethnic origins in India, Pakistan or Bangladesh) is described and compared with non-south Asian and Indian subcontinent rates. The setting for the study was areas covered by Thames, Trent, West Midlands and Yorkshire cancer registries. The study identified 356 555 cases of incident cancer (ICD9:140-208) registered between 1990 and 1992, including 3845 classified as English south Asian. The main outcome measures were age specific and directly standardized incidence rates for all cancer sites (ICD9:140-208). English south Asian incidence rates for all sites combined were significantly lower than non-south Asian rates but higher than Indian subcontinent rates. English south Asian rates were substantially higher than Indian subcontinent rates for a number of common sites including lung cancer in males, breast cancer in females and lymphoma in both sexes. English south Asian rates for childhood and early adult cancer (0-29 years) were similar or higher than non-south Asian rates. English south Asian rates were significantly higher than non-south Asian rates for Hodgkin's disease in males, cancer of the tongue, mouth, oesophagus, thyroid gland and myeloid leukaemia in females, and cancer of the hypopharynx, liver and gall bladder in both sexes. The results are consistent with a transition from the lower cancer risk of the country of ethnic origin to that of the country of residence. They suggest that detrimental changes in lifestyle and other exposures have occurred in the migrant south Asian population.

Adolescent↗

Malignancy load on general surgeons: the need to change the general surgical training curriculum.

AIMS: With the advent of newer diagnostic modalities more and more cancer patients are being diagnosed each year. The rising detection rate and greater public awareness have immensely increased the load on already overburdened and increasingly fewer surgical oncology units. As a result a large number of these cases are being dealt with by general surgeons. METHODS: We have used a retrospective case count from a single surgical unit, based at the University Hospital, Varanasi, and data from the Hospital Based Cancer Registry (HBCR), Regional Cancer Centre (RCC), Trivandrum, from 1990 to 1994, to define the malignancy load on general surgical units and to define the number and sites of malignancies commonly encountered by general surgeons. RESULTS: A total of 28,136 patients were registered at the RCC, the commonest malignancy being oral cavity (16.35%), followed by lung (12.7%) and breast (23.8%) among men and women, respectively. On the other hand, in the 2123 patients with malignancy who were treated at the Medical College (MCH) in Trivandrum, the commonest sites encountered were stomach (11.68%), thyroid (10.31%) and colorectal (9.5%). This was quite similar to the frequencies observed at Varanasi, where colorectal cancer constituted 10.26% and stomach 6.98%. Only 13.6% of the patients reporting to RCC were treated by surgery alone or in combination, while this figure was 48. 1% for MCH. Similarly 2056 (7.3%) patients presenting to RCC had completed treatment prior to being referred to RCC; almost all of these patients were treated by surgery at referral institutions by general surgeons. CONCLUSIONS: The results clearly indicate an increased demand on the surgical oncology units, or alternatively an urgent need to redefine the postgraduate curriculum for the better training of general surgeons in understanding malignant disease, especially in the developing countries. We recommend a minimum of 6 months training in surgical oncology for each general surgery postgraduate.

Cancer Care Facilities↗

An assessment of the Nam Pehchan computer program for the identification of names of south Asian ethnic origin.

BACKGROUND: An assessment was made of the usefulness and accuracy of a computer program for the identification of the south Asian population through the classification of names on a disease register. METHODS: The computer program, Nam Pehchan, was used to classify names as either south Asian or non south Asian. The results were compared with a reference standard, which combined use of the program with visual inspection. The latter was facilitated by a computer-generated dictionary of common non south Asian names. The data set consisted of 356,555 cases of incident cancer (ICD9: 140-208) registered between 1990 and 1992 by Thames, Trent, West Midlands and Yorkshire cancer registries. RESULTS: Nam Pehchan classified 5506 cases as south Asian. Visual inspection identified 2024 false positives (36.8 per cent of all cases identified as south Asian by Nam Pehchan) and 363 false negatives (9.5 per cent of those identified by the reference standard). Compared with the reference standard, Nam Pehchan had a sensitivity of 90.5 per cent and a positive predictive value of 63.2 per cent. CONCLUSION: The Nam Pehchan program quickly identified a high proportion of the names classified as south Asian by the reference standard, but the high false positive rate means that the program alone is not an adequate single strategy. The time-consuming process of inspection of program negatives for large data sets can be substantially reduced by comparison with dictionaries of common non south Asian names.

Asia↗

Risk factors for cervical dysplasia in Kerala, India.

A study in Kerala, India, confirmed the importance of genital hygiene in the fight against infections that have a role in the development of cervical dysplasia and cancer. Many women cannot afford sanitary pads, while adequate facilities for washing after coitus are often unavailable. Health education, satisfactory living standards, and the empowerment of women are prerequisites for reducing the incidence of cervical dysplasia.

Adult↗

Cutaneous malignant melanoma--clinical epidemiology and survival.

Melanoma of the skin is rare in the Asian population. However, this malignancy results in a high mortality due to the inadequacies in the referral pattern and management. India is one of the low incidence regions of the world. Cancer registries in India report that the age specific incidence rates for cutaneous malignant melanoma (CMM) are less than 0.5 per 1,000,000. There are only few reports in the literature on CMM in the Asian population. The Regional Cancer Centre at Trivandrum registers about 6000 new cancer cases per year and CMM forms 0.5% of them. This paper presents the clinical epidemiology and survival of 79 cases of CMM registered in the hospital cancer registry during the period 1985-90. The peak age frequency was in the 7th decade. The male:female ratio was 1.6:1. All cases had undergone a surgical manipulation in a peripheral centre, before being referred to this centre. This has posed limitation in staging and in deciding the extends of surgical excision. The overall 5-year survival rate was 25.2% (95% confidence intervals, or, CI, 14%-38%). CMM in the low incidence regions may have a different aetiology and needs to be addressed in epidemiological studies.

Adult↗

Radiotherapy in the treatment of verrucous carcinoma of the oral cavity.

Verrucous carcinomas are considered to have poor radioresponsiveness and radiotherapy has been reported to induce anaplastic transformation. Surgery has been considered to be the primary mode of treatment for these tumours. The clinical features, response to radiotherapy, survival and prognostic factors of a group of 53 patients with oral verrucous cancers, were studied and compared to patients with oral well-differentiated, squamous cancers, treated during the same time period. The buccal mucosa was the commonest primary site in both groups. 42 patients with verrucous cancer underwent primary radiotherapy and 11 underwent primary surgery. Complete response to radiotherapy was achieved in 76% of patients with verrucous cancer and partial response in 24%. Patients with verrucous cancer had a five year actuarial disease-free survival of 66% and overall survival of 86%. The corresponding survival figures were 43% and 56% in well-differentiated squamous cancers (P = 0.004). Composite stage of disease was a significant predictor of disease-free survival in both groups. None of the 16 patients with verrucous cancers that recurred after radiotherapy, had features of anaplastic transformation. Oral verrucous carcinoma appears to have similar radioresponsiveness and improved disease-free survival, compared to well-differentiated squamous cancers. The treatment policies for other oral squamous cancers are applicable to these tumours.

Adult↗

Chemoprevention of oral leukoplakia with vitamin A and beta carotene: an assessment.

We conducted a double-blind placebo-controlled trial to evaluate the chemopreventive potential of either vitamin A alone or beta carotene alone in subjects with oral leukoplakia in Kerala, India. We randomised 160 fishermen and women with oral precancerous lesions to receive oral vitamin A (retinyl acetate 300,000 IU/week x 12 months, n = 50), or beta carotene (360 mg/week x 12 months, n = 55), or placebo (n = 55). Blood, saliva and urine samples were collected at baseline and at exit to study serum micronutrients and mutagenicity assays. Biopsies of the mucosal lesions at entry were performed for histopathological exclusion of malignancy. The subjects were examined once every 2 months to establish clinical response of lesions and toxicity, if any. The results are based on 43 complaint subjects on placebo, 42 on vitamin A and 46 on beta carotene. The complete regression rates were: 10% in the placebo arm, 52% with vitamin A and 33% with beta carotene (P < 0.0001). Homogeneous leukoplakias and smaller lesions responded better than non-homogeneous and larger lesions. No major toxicities were observed. Half of the responders with beta carotene and two thirds with vitamin A relapsed after stopping supplementation. Serum beta carotene concentration increased substantially with beta carotene administration while with vitamin A supplementation there was no change in serum retinol levels. In the vitamin A treated group there was a significant decrease in serum alpha tocopherol. Vitamin A administration resulted in a significant remission of oral leukoplakia without any side effects of prolonged vitamin A supplementation. The results of this study, as well as those from previous studies, appear to provide strong supporting evidence to justify long term trials with vitamin A in subjects with high-risk leukoplakias with oral cancer as an endpoint.

Adult↗

Efficacy of vitamin A in the prevention of loco-regional recurrence and second primaries in head and neck cancer.

Chemoprevention with retinoids is currently an experimental approach to prevent local relapses and second primaries in treated head and neck cancer patients. We evaluated the effectiveness of vitamin A in preventing the above events in a randomised trial involving 106 head and neck cancer patients who had achieved complete regression of their disease with radiotherapy and/or surgery. They were randomised to receive retinyl palmitate (200,000 IU per week for 1 year) or placebo. 50 subjects on vitamin A and 43 on placebo completed 1 year supplementation; 49 in the former group and 42 in the latter could be evaluated over a 3 year period from the initiation of the study. One fifth (11/56) of patients in the vitamin A group and one tenth (5/50) in the placebo group had loco-regional recurrence. The frequency of recurrences in stage I patients in the vitamin A group was higher compared to the placebo group, although it was not statistically significant. No second primaries were observed in the vitamin A group; 2 patients in the placebo group had second primaries. No clinically obvious side effects were observed with vitamin A. The higher frequency of recurrences in the vitamin A group is of concern although it may be a chance finding given the small size of the trial. The effect on second primaries is consistent with other observations reported in literature.

Anticarcinogenic Agents↗

High risk of lymphomas in children of Asian origin: ethnicity or confounding by socioeconomic status?

To examine the role of ethnic origin as a risk factor for paediatric lymphoma, a cancer registry-based analysis was undertaken in Yorkshire, UK. Children of Asian ethnic origin were found to have an odds ratio for lymphomas of 1.60 (CI 0.98-2.62), after adjusting for age and sex. After adjusting also for 'super profile group' as an indicator of socioeconomic status, the estimate became 1.99 (CI 1.08-3.68). Hodgkin's disease and non-Hodgkin's lymphomas were analysed separately with similar results. Super profile group is an area-based measure and may not reflect the individual variation in living standards, especially among the Asian immigrants. Our results indicate that socioeconomic status does not confound the relationship between lymphomas and ethnic origin. However, there is a need for studies of ethnicity that include indicators of individual living standards or socioeconomic status.

Adolescent↗

Cervical cancer in Kerala: a hospital registry-based study on survival and prognostic factors.

The survival experience of 452 cervical cancer patients registered during 1984 by the hospital registry of the Regional Cancer Centre, Trivandrum, Kerala, India, is described in this paper. Eighty per cent of the patients completed the prescribed treatment, which was predominantly radiotherapy. The vital status of each patient was established by scrutiny of case records and by reply-paid postal enquiries. The observed survival rates were estimated by the Kaplan-Meier method and prognostic factors were assessed using Cox's proportional hazards regression analysis. The overall 5 year observed survival rate was 47.4% (95% CI, 41.6-52.9%). Socioeconomic status, performance status and the clinical stage of disease emerged as independent predictors of survival. Low survival was associated with advanced stages of disease, low socioeconomic status and poor performance status. The problems in studying survival from cancer in developing countries and the strategies used to improve follow-up rates in India are discussed. It is stressed that trends in survival rates may be used to evaluate cancer control programmes in developing countries in the absence of reliable mortality statistics and, even when mortality data are available, survival rates are valuable comparative statistics. Earlier detection by improving the awareness of the population and the physicians will improve survival rates, but a more effective and prudent approach would be to prevent invasive cervical cancer, and thereby reduce mortality, by implementing feasible and effective screening programmes in India.

Adult↗

Evaluation of chemoprevention of oral cancer with Spirulina fusiformis.

The blue-green microalgae Spirulina, used in daily diets of natives in Africa and America, have been found to be a rich natural source of proteins, carotenoids, and other micronutrients. Experimental studies in animal models have demonstrated an inhibitory effect of Spirulina algae on oral carcinogenesis. Studies among preschool children in India have demonstrated Spirulina fusiformis (SF) to be an effective source of dietary vitamin A. We evaluated the chemopreventive activity of SF (1 g/day for 12 mos) in reversing oral leukoplakia in pan tobacco chewers in Kerala, India. Complete regression of lesions was observed in 20 of 44 (45%) evaluable subjects supplemented with SF, as opposed to 3 of 43 (7%) in the placebo arm (p < 0.0001). When stratified by type of leukoplakia, the response was more pronounced in homogeneous lesions: complete regression was seen in 16 of 28 (57%) subjects with homogeneous leukoplakia, 2 of 8 with erythroplakia, 2 of 4 with verrucous leukoplakia, and 0 of 4 with ulcerated and nodular lesions. Within one year of discontinuing supplements, 9 of 20 (45%) complete responders with SF developed recurrent lesions. Supplementation with SF did not result in increased serum concentration of retinol or beta-carotene, nor was it associated with toxicity. This is the first human study evaluating the chemopreventive potential of SF. More studies in different settings and different populations are needed for further evaluation.

Adult↗