Efficacy of a herbal mouthwash for management of periodontitis and radiation-induced mucositis - A consolidated report of two randomized controlled clinical trials.

BACKGROUND: Oral diseases like periodontitis and mucositis often require home care using topical agents in the form of mouthwashes. Many herbal mouthwashes are found to be beneficial; however lack proper scientific evidence to support their use. OBJECTIVES: Study 1 evaluated clinical efficacy of herbal mouthwash in the management of chronic periodontitis in comparison with chlorhexidine mouthwash. Study 2 aimed at assessment of herbal mouthwash in patients of radiation-induced mucosititis. METHODS: The novel herbal mouthwash used in the present study wa prepared from extracts of five plants namely Emblica Officinalis, Terminalia chebula, Terminalia bellerica, Glycyrrhiza glabra, and Azadirachta indica. 50 periodontitis patients were randomly allocated to two groups. As per allocation, they were instructed to use either herbal mouthwash or chlorhexidine mouthwash twice daily for two weeks after nonsurgical periodontal therapy. Similarly, patients with radiation-induced mucositis were randomly given herbal mouthwash and soda saline mouthwash. Intergroup and intragroup comparisons of continuous variables were conducted using paired and unpaired t-tests. Categorical variables were compared using the chi-square test. RESULTS: Significant reductions in gingival bleeding, plaque accumulation, and pocket depth were noticed in periodontitis patients in both groups. Patients reported acceptable taste, freshness, and satisfaction after the use of herbal mouthwash. The herbal mouthwash group noticed a significant reduction in the severity of radiation-induced mucositis and analgesic requirements. The intensity of pain, dryness of mouth, oral hygiene, and need for the use of antibiotic and antifungal during radiotherapy was not significant among the groups. CONCLUSION: The results of this preliminary clinical trial support the use of the tested herbal formulation mouthwash as an adjunct in the treatment of periodontitis as well as radiation-induced mucositis. CLINICAL TRIAL REGISTRATION NUMBER: For Study 1: CTRI/2019/10/021574, Study 2: CTRI/2020/04/024851.

A Survey of Current Practice of Supraglottic Airway Devices in Pediatric Anesthesia from India.

BACKGROUND AND OBJECTIVES: Supraglottic airway devices (SADs) have revolutionized the pediatric anesthetic practice and got a key role in difficult airway (DA) management. Several modifications of SADs design had come up to improve their safety. AIM: The aim of this survey was to determine the current usage of SADs in pediatric anesthetic practice, their availability, and to know any difficulties noted in practice. METHODS: It was a questionnaire survey among the anesthesiologists who attended the National Pediatric Anesthesia Conference-2016. The questionnaire assessed the current practice preferences of SADs in routine pediatric cases and DA management, availability of various devices, and any difficulties noted in their usage. RESULTS: First-generation SADs were widely available (97%), and 64% of respondents preferred to use it for pediatric short cases. 64% felt the use of SADs free their hands from holding the facemask and 58% found better airway maintenance with it. Intraoperative displacement (55%) was the common problem reported and only 11% felt aspiration as a problem. Most of the respondents (73%) accepted its use as rescue device in airway emergency, and 84% felt the need of further randomized controlled studies on safety of SADs in children. The majority were not confident to use SADs in neonates. INTERPRETATION AND CONCLUSIONS: The key role of SADs in DA management was well accepted, and aspiration was not a major problem with the use of SADs. Although many newer versions of SADs are available, classic laryngeal mask remains the preferred SAD for the current practitioner. Further, RCTs to ensure the safety of SADs in children are warranted.

Comparative Study of Constant Dose Intrathecal Hypobaric Levobupivacaine with Varying Baricities in Lower Limb Surgeries.

BACKGROUND: Hypobaric spinal anesthesia is advantageous for unilateral lower extremity fractures as it obviates pain of lying on fractured limb for performing subarachnoid block. AIMS: This study compares block characteristics and complications of three different baricities of constant dose intrathecal hypobaric levobupivacaine to determine an optimum baricity. SETTINGS AND DESIGN: One-twenty American Society of Anesthesiologists Physical Status 1 and 2 patients aged 18-65 years undergoing unilateral lower limb surgeries were divided into three equal groups for this prospective cohort study. MATERIALS AND METHODS: To 2 mL intrathecal 0.5% isobaric levobupivacaine (10 mg), 0.4 mL, 0.6 mL, and 0.8 mL of distilled water were added in Groups A, B, and C, respectively. Baricities of Groups A, B, and C are 0.999294, 0.998945, and 0.998806, respectively. Development of sensory and motor block was assessed by the pinprick method and Bromage scale, respectively. The total duration of analgesia and complications were noted. STATISTICAL ANALYSIS USED: Mean, standard error, one-way ANOVA, and Bonferroni were used to analyze quantitative variables; proportions and Chi-square tests for qualitative variables. RESULTS: Demographic parameters, motor block of operated limb, and complications were comparable. Group C had the fastest onset of sensory block (10.10 min) and maximum duration of analgesia (478.97 min; P < 0.001); but high sensory levels in 48.7%. Group B had T10 sensory level in 92.5%; onset comparable to Group C (P = 0.248), and reasonable duration of analgesia (332.50 min). Group A had inadequate sensory levels, slow onset, and early regression. CONCLUSIONS: Group B (baricity - 0.998945) has better block characteristics among three groups compared.

Financial Implications of Intravenous Anesthetic Drug Wastage in Operation Room.

BACKGROUND AND OBJECTIVES: Anesthetic drugs and material wastage are common in operation rooms (ORs). In this era of escalating health-care expenditure, cost reduction strategies are highly relevant. The aim of this study was to assess the amount of daily intravenous anesthetic drug wastage from major ORs and to estimate its financial burden. Any preventive measures to minimize drug wastage are also looked for. METHODS: It was a prospective study conducted at the major ORs of a tertiary care hospital after getting the Institutional Research Committee approval. The total amount of all drugs wasted at the end of a surgical day from each major OR was audited for five nonconsecutive weeks. Drug wasted includes the drugs leftover in the syringes unutilized and opened vials/ampoules. The total cost of the wasted drugs and average daily loss were estimated. RESULTS: The drugs wasted in large quantities included propofol, thiopentone sodium, vecuronium, mephentermine, lignocaine, midazolam, atropine, succinylcholine, and atracurium in that order. The total cost of the wasted drugs during the study period was Rs. 59,631.49, and the average daily loss was Rs. 1987.67. The average daily cost of wasted drug was maximum for vecuronium (Rs. 699.93) followed by propofol (Rs. 662.26). INTERPRETATION AND CONCLUSIONS: Financial implications of anesthetic drug wastage can be significant. Propofol and vecuronium contributed maximum to the financial burden. Suggestions for preventive measures to minimize the wastage include education of staff and residents about the cost of drugs, emphasizing on the judicial use of costly drugs.

Barriers to the universal adoption of bilateral internal mammary artery grafting.

The left internal mammary artery (LIMA) graft is considered the "gold standard" of coronary artery bypass grafting (CABG). This conduit provides increased survival, symptomatic relief, increased freedom from myocardial infarction, and increased freedom from re-intervention when compared to saphenous venous grafting. It has a remarkable long term patency rate with clinical and angiographic outcomes that are unmatched by other conduits. Given the fact that patients often require more than one graft during a coronary revascularization procedure, the prospect of bilateral internal mammary artery (BIMA) grafting has been very appealing to some surgeons. BIMA grafting has been extensively studied via multiple retrospective and prospective cohort studies and findings have indicated that BIMA grafting can have an increased survival benefit when compared to LIMA grafting alone. As a result, this technique has accrued increasing popularity over the course of the last decade. Yet, questions still remain on whether BIMA grafting is the optimal treatment modality for patients in terms of long-term prognosis. There is limited data at the present time from randomized controlled trials and only 4-12% of CABGs performed today utilize BIMA grafting. Concerns regarding perioperative complications, which patient subsets are at higher risks for complications from the technique, and the technical challenges involved in utilizing and teaching the technique have limited its widespread use.

Clinical trials of cancer screening in the developing world and their impact on cancer healthcare.

Several research and training initiatives were organized by the International Agency for Research on Cancer (IARC) in collaboration with national institutions in countries such as Angola, Brazil, Burkina Faso, China, Republic of Congo, Guinea, India, Mali, Mauritania, Nepal, Niger, Peru, Tanzania and Thailand among others, to address feasible and effective means of early detection and prevention of cervical, breast and oral cancers. The impact of these activities, that involved over 600 000 participants and more than 1200 healthcare personnel trained on strengthening the local health services in terms of infrastructure, human resources and service delivery aspects in host countries and other regions, is addressed here. These studies, inbuilt in appropriate health services platforms, have resulted in the development and sustenance of several continuing point of care services of screening and treatment in most host countries, particularly in sub-Saharan Africa, and have catalysed regional early detection programmes in India, China and Thailand. The IARC collaborative studies have evolved into major focal points of training and extending services in many countries. The large evidence base, resulting from ours and other studies is likely, in due course, to facilitate much wider scaling up of screening and treatment services through organised programmes.

Prognosis criteria of casual systolic and diastolic blood pressure values in a prospective study in India.

BACKGROUND: In India, cardiovascular events are often diagnosed at lower blood pressures (BP) than in Western countries, questioning whether the actual World Health Organization cut-off points for hypertension (systolic BP (SBP) >or=140 mm Hg and/or diastolic BP (DBP) >or=90 mm Hg) are appropriate in low resource countries. METHODS: A large population-based cohort study including 167 331 adults aged 35-90 years, living in a rural area, was followed up during a 7-year mean duration for all-cause mortality and cardiovascular disease (CVD) deaths. At baseline, casual BP was measured, and lifestyle was assessed through a questionnaire. Death rates were calculated according to SBP and DBP, and their association was examined in a multivariate analysis, among all subjects, then stratified by sex and age groups. RESULTS: Forty-five per cent of the study subjects had hypertension. The nadir of CVD death rates was observed at 110 mm Hg for casual SBP and 75-80 mm Hg for casual DBP. In the multivariate analysis, SBP from 120 mm Hg and DBP from 90 mm Hg were significantly associated with risks of ischaemic heart disease and stroke. High SBP and DBP values were greater predictors of mortality in the young age group (34-44 years) than in the old age group (65+ years). SBP was a stronger independent predictor of CVD than DBP. CONCLUSIONS: SBP and DBP were associated with CVD mortality at thresholds lower than the current hypertension definition. Measurement limited to SBP alone would be effective in screening for CVD risk in large populations.

Completed suicide in adults of rural Kerala: rates and determinants.

BACKGROUND: India has witnessed a dramatic increase in suicide rates during the past few decades. The southern state of Kerala has been reporting the highest rates of suicide. Since suicide rates are estimated from death registries, they are likely to be under-reported because the civil registration system is incomplete and suicide deaths are poorly reported. METHODS: A cohort of 132 000 participants (age 35 years and above) in Thiruvananthapuram (erstwhile Trivandrum) district, Kerala was followed up for mortality from 1996 to 2005, after having filled-in a lifestyle questionnaire at baseline. The cause of death was based on verbal autopsy. Suicide methods were recorded and rates were estimated, and suicide risks were calculated according to several socioeconomic factors. RESULTS: During the follow up period, a total of 11 608 deaths, of which 385 were suicides (3.3% of total deaths), were registered. The overall suicide rate was 39.3/100 000 person-years among adults 35-90 years of age (men: 78/ 100000; women: 16.5/100000). The predominant methods of suicide were hanging, followed by poisoning and drowning. The suicide determinants were male gender, middle-age (40-60 years), Hindu, alcohol drinkers and secondary education level (< or = 7 years). Neither low socioeconomic level, living alone, nor being a married woman was associated with suicide risk. CONCLUSION: Suicide rates were consistent with the official rates of Thiruvananthapuram district (37/100 000). However, our study population did not include the 14-34-year-old age-group which represents more than 37% of all suicides and hence it is more likely that the official rates are under-reported. Determinants of suicide were in line with previous studies.

Which socio-demographic factors are associated with participation in oral cancer screening in the developing world? Results from a population-based screening project in India.

BACKGROUND: This study examines socio-demographic determinants of participation in a population-based randomized controlled trial that proved that oral visual inspection was effective in reducing oral cancer mortality in high-risk individuals in India. METHODS: Multivariate logistic regression was used to establish socio-demographic characteristics of participants versus non-participants in the intervention arm. Compliance with referral was analysed according to the socio-demographic characteristics of screen-positives. RESULTS: Of 96,517 eligible subjects, 87,655 were screened, 8688 individuals never received the invitation and 174 refused screening. Compared to the non-screened, a higher proportion of screened individuals were women (OR=4.51; CI: 4.28-4.75), lived in better housing (OR=1.35; CI: 1.25-1.41), had television/radio (OR=1.50; CI: 1.43-1.58) and were tobacco and alcohol users (OR=2.75; CI: 2.57-2.95). Being 65 and older decreased the chances of screening (OR=0.39; CI: 0.37-0.42), as well as living in high-size households (OR=0.73; CI: 0.68-0.78). Sixty-three percent of 5143 screen-positives complied with referral. Controlling for all other factors, individuals older than 44, and those with more advanced lesions were more likely to comply with referral (p<0.001). Individuals living in better housing were less likely to comply with referral (OR=0.79; CI: 0.65-0.95). CONCLUSIONS: In summary, adequate coverage can be obtained in population-based oral screening in developing countries. The study underscores the important role of patient-provider communication in assuring high compliance with referral.

High expression levels of nuclear factor kappa B and gelatinases in the tumorigenesis of oral squamous cell carcinoma.

BACKGROUND: The cellular mechanisms involved in transformation of a premalignant/potentially malignant oral lesion to a malignant one remain unclear. Previous studies have documented a direct involvement of matrix metalloproteinase (MMP) overexpression in the development and progression of head and neck squamous cell carcinoma (HNSCC). MMP activation, particularly MMP2 and MMP9, observed in different cancers, has been shown to be mediated via the transcription factor nuclear factor kappa B (NF-kappaB). The present study analyzes the clinical significance of gelatinases and NF-kappaB in various histologic phases of human oral tumor progression. METHODS: Methodology included immunohistochemistry for MMP2, MMP9, p50, and p65 components of NF-kappaB and IkappaBalpha (inhibitor kappaBalpha). Gelatin zymography was carried out to determine the extent of gelatinolytic activity. Western blotting was used to confirm the gelatinolytic bands of zymogram, and electrophoretic mobility shift assay (EMSA) was carried out to confirm NF-kappaB activation. RESULTS: A gradual increase was evident in the intensity of the expression and gelatinolytic activity of gelatinase paralleling the histologic progression of malignancy. This finding supports the histologic evidence of tumor invasion occurring in the transition between premalignancy and invasive cancer. Nuclear translocation of NF-kappaB (p50-p65 form) gradually progresses through the premalignant phase of oral tissue to the invasive phase, showing NF-kappaB activation during oral tumorigenesis. NF-kappaB activation correlatively paralleled the pattern of expression of gelatinases. CONCLUSIONS: The results of this study suggest a regulatory role for NF-kappaB on activation of gelatinases during malignant transformation in the oral mucosa.

Association between diabetes mellitus and pre-malignant oral diseases: a cross sectional study in Kerala, India.

Recent studies have suggested role of diabetes mellitus in the development of periodontal diseases, oral inflammatory and neoplastic lesions. We analysed data from randomised oral cancer screening trial in Kerala, India, to study the association between chronic diseases in general, diabetes mellitus in particular, and pre-malignant oral lesions and conditions. A total of 927 subjects with oral leukoplakia, 170 with oral submucous fibrosis, 100 with erythroplakia lesions and 47,773 apparently healthy subjects constituted the cases and controls respectively for our present study. The odds ratio (OR) for oral leukoplakia among women with a history of diabetes mellitus was found to be 2.0 (95% confidence interval (CI) = 1.4-2.9) whereas that for erythroplakia was 3.2 (95% CI = 1.3-7.9), after adjusting for potential confounders. No statistically significant association between diabetes mellitus and oral submucous fibrosis and pre-cancerous lesions/conditions in men was found. An association between diabetes mellitus and pre-malignant oral lesions among women has been observed in our study, although the underlying mechanisms are not clear. This needs to be further evaluated in other settings.

Single nucleotide polymorphisms of DNA repair genes XRCC1 and XPD and its molecular mapping in Indian oral cancer.

Tobacco users with diminished ability to repair somatic mutations may be more susceptible to tobacco attributable cancers. The distribution of single nucleotide polymorphisms (SNPs) in DNA repair genes XRCC1 and XPD in 110 oral carcinoma cases, 84 leukoplakia and 110 controls belonging to the Travancore South Indian population were examined. SNPs investigated included Arg194Trp, Arg280His, and Arg399Gln of the XRCC1 gene and Lys751Gln of the XPD gene. In addition, one of the variants positions, A399G, was mapped onto the BRCT I domain model built by comparative modeling (threading). Presence of the polymorphic variant of XRCC1 codon 194 and 399 and XPD was associated with increased risk of oral cancer compared to the wild genotype. Smokers and betel quid chewers with the variant allele of XRCC1 399 codon and XPD also exhibited increased risk of oral cancer. The A399G variant position mapped onto the surface of the BRCT I domain provides a possible rationale for altered XRCC1 function. These results suggest that polymorphisms in functionally important repair genes, specifically, those that map onto the protein surface may alter protein function without significantly affecting its structure.

Socioeconomic status, lifestyle factors and oral premalignant lesions.

Several studies have suggested that low socioeconomic status (SES) is associated with a higher risk of oral cancer, but the association with oral premalignant lesions has not yet been explored. The aim of this study was to examine the association of education, occupation, income and SES index with oral premalignant lesions. A case-control study was conducted with data from the baseline screening of a randomized oral cancer screening trial in Kerala, India. There were a total of 927 oral leukoplakia, 170 oral submucous fibrosis, 100 erythroplakia and 115 multiple oral premalignant lesion cases and 47,773 controls. Subjects with high SES index had protective ORs for oral premalignant lesions, ranging from 0.6 to 0.7, after adjustment for age, sex, BMI, tobacco chewing, smoking, drinking and fruit/vegetable intake. Higher education levels were also associated with decreased risk of all four oral premalignant lesions. Protective ORs for income were observed for oral leukoplakia and possibly oral submucous fibrosis and erythroplakia. SES may be associated with oral premalignant lesions because of access to medical care, health related behaviors, living environment or psychosocial factors. Though the mechanism for the association is not clear, higher SES index, education and income were associated with decreased risk of oral premalignant lesions in our study.

Interim results from a cluster randomized controlled oral cancer screening trial in Kerala, India.

A cluster randomized controlled oral cancer screening trial is on-going in the Trivandrum district, India, to evaluate the efficacy of screening in reducing oral cancer mortality. Subjects, aged 35 years and above, in 13 clusters in the Trivandrum district, India, were randomized to the intervention (screening) group (7 clusters, 78969 subjects) to receive three rounds of screening by oral visual inspection by trained health workers at 3-year intervals or to a control group (6 clusters, 74739 subjects). Two rounds of screening were completed between 1995 and 2002 during which 69896 (88.5%) subjects were screened at least once, and 59.7% of the 4408 screen-positive subjects were further investigated. In the intervention group, 344404 person-years were accrued and 329326 person-years were in the control group. In the intervention group, 149 incident oral cancer cases and 65 deaths from oral cancer were observed, and 106 incident cases and 62 deaths from oral cancer were observed in the control group. The programme sensitivity for detection of oral precancerous lesions and cancer was 81.5% and the programme specificity was 84.8%; the programme positive predictive value was 39.6%. In the intervention group 37.6% of the cases were in stages I-II, as opposed to 18.9% in the control group. The 3 year survival rate was 57.5% in the intervention and 38.8% in the control group (P<0.05). The age standardized oral cancer mortality rates were 21.2/100000 person-years in the intervention and 21.3/100000 in the control group. After completing two rounds of screening, oral cancer mortality rates were similar in both study groups.

Genetic polymorphism of CYP1A1, GSTM1 and GSTT1 genes in Indian oral cancer.

Oral cancer ranks first among all cancers in males and is the third most common among females in India. Tobacco-derived carcinogens are involved in the development of oral cancer. Environment-gene interaction in oral carcinogenesis is well demonstrated by phase I and II enzymes that are involved in the metabolism of carcinogens. This study looked at the significance of genetic polymorphisms in CYP1A1, GSTM1 and GSTT1 genes in patients with oral cancer. The study included 98 oral cancer patients and 60 age and sex matched healthy controls. Genotypes of CYP1A1, GSTM1 and GSTT1 were determined by PCR-RFLP. GSTM1 null deletion was observed in 49% of oral cancer cases and 33% of control subjects. For GSTT1, 18% of carcinomas and 8% of controls had the null genotype. In the case of CYP1A1 m2 allele, 51% of oral cancers and 17% of normal controls, respectively, had one or both alleles with the isoleucine-->valine substitution. Digestion of the PCR products with enzyme Nco1 revealed polymorphism for CYP1A1 m2 with bands at 263 bp. There was no association between genotypes with tumor size, stage, grade, and age. Since null genotype individuals may possibly be poor detoxifiers with reduced ability to neutralise the reactive carcinogenic intermediates, they may be a high risk category. The frequency distribution of CYP1A1 m2 (Ile/val) genotypes among oral cancer patients was significantly different that from normal controls. The risk of CYP1A1 can be supported by the functional difference between presence of valine and isoleucine; valine type has higher catalytic and mutagenic activity towards benzo[a] pyrene than the isoleucine type. In conclusion, our results suggest that polymorphism in CYP1A1 m2 gene and/or GSTM1 and GSTT1 null genotype may confer an increased risk for oral cancer.

Apoptosis, angiogenesis and proliferation: trifunctional measure of tumour response to radiotherapy for oral cancer.

Local recurrence is a significant problem following radiotherapy in oral carcinoma and hence there is a paramount need for predictive markers. This study therefore analysed the predictive value of pre-treatment status of angiogenesis, apoptosis, expression of apoptosis regulatory p53, bax and bcl-2 proteins as well as tissue proliferation in relation to tumour response to radiotherapy. Sixty-nine histologically defined invasive carcinoma lesions were included in the study. Extent of apoptosis was defined morphologically and by the TUNEL (Tdt-mediated dUTP biotin nick end labelling) assay. Expression of apoptosis regulatory p53, bax and bcl-2 proteins were evaluated by immunocytochemistry. Mutant p53 protein was detected using a mutant p53-specific ELISA. The extent of tissue proliferation was evaluated by cyclin D1 expression. Angiogenesis was evaluated by CD34 antigen expression. All patients were treated with radical radiotherapy and followed up for 36 months. High levels of p53 protein detected by immunocytochemistry were found to be associated with poor response to treatment or disease relapse. Detection of mutant p53 protein also showed significant association with poor prognosis. Low levels of angiogenesis had a correlation with recurrence status. Tumours showing less vascularisation as well as increased apoptosis had a poor prognosis. Expression of p53 and bcl-2 proteins showed direct correlation with angiogenesis. There was no correlation between clinical status and any of the experimental parameters with histopathological grades of invasive lesions. Presence of mutant p53 protein is suggestive of poor tumour response to radiotherapy. Expression of p53 and increased apoptosis in less vascularised tumours is associated with treatment resistance. A predictive assay based on these results designed to analyse individual tumour samples showed presence of apoptotic cells near the vasculature to be indicative of good prognosis, while absence of apoptotic cells or highly proliferative cells and/or expression of bcl-2 protein in cells around the vasculature to be an indicator of poor prognosis.

Sarcoma of the oral and maxillofacial soft tissue in adults.

AIMS: Sarcoma occurring in oral and maxillofacial soft tissue is rare. This study was carried out to evaluate the prevalence of oral soft tissue sarcoma and to record its natural history and survival. METHODS: Retrospective analysis of the patients with histologically proven oral and maxillofacial soft tissue sarcoma treated at the Regional Cancer Centre (RCC), Trivandrum, betweeen 1990-1998 was carried out. RESULTS: During this period, ten cases of oral and maxillofacial sarcomas were registered. Three lesions were located on the cheek mucosa, two on the tongue and two on the mandibular alveolus, while there was one lesion each in the parotid region, maxilla and face (NOS). Mean age at presentation was 31.3+/-14.1 years (range 15-54 years). Seven of the patients (70%) were males. There were three cases of rhabdomyosarcoma (RMS), three cases of spindle cell sarcoma and one case each of angiosarcoma, haemangioendothelioma, malignant schwannoma and malignant fibrous histiocytoma (MFH). All the patients were treated with surgery as a primary modality. Median follow-up time was 30 months (range 5-94 months). An overall srvival of 87.5% at 5 years was observed; however, 5-year disease free survival was 60.0% (95% CI 19.5-85.2). CONCLUSIONS: Soft tissue sarcomas are of comparatively less frequent occurrence in oral and maxillofacial soft tissue than in other tissues. A good survival rate can be achieved by multimodality treatment.

Early findings from a community-based, cluster-randomized, controlled oral cancer screening trial in Kerala, India. The Trivandrum Oral Cancer Screening Study Group.

BACKGROUND: Oral cancer satisfies the criteria for a suitable disease for screening, and oral visual inspection is a suitable test for oral cancer screening. The efficacy of screening in reducing mortality from oral cancer has not yet been evaluated. The authors describe a cluster-randomized, controlled oral cancer screening trial in southern India and its early results. METHODS: Apparently healthy subjects age 35 years or older in 13 clusters called panchayaths were randomized to either an intervention group (n = 7) or a control group (n = 6). Subjects in the intervention group will receive 3 rounds of screening consisting of oral visual inspection by trained health workers at 3-year intervals. The first round of screening was carried out between October 1995 and May 1998. Participants were visited in their homes and interviewed for sociodemographic details, tobacco-smoking and alcohol-drinking habits, and personal medical history. Those with tobacco or alcohol habits were advised to stop those habits. Subjects in the intervention group were offered screening, and those with lesions suggestive of oral leukoplakia, submucous fibrosis, or oral cancer were referred for examination by physicians. Confirmed leukoplakias were excised whenever possible, others were kept on follow-up, and those with confirmed oral cancers were referred for treatment. Data on oral cancer incidence, stage distribution, survival, and mortality in the study groups are obtained by record linkage with the Trivandrum population-based cancer registry and municipal death registration systems. RESULTS: There were 59,894 eligible subjects in the intervention group and 54,707 in the control group; 31.4% of the former group reported no tobacco or alcohol habits, compared with 44.1% of the latter. The distribution of age, education, occupation, income, and socioeconomic status were similar in the two groups. Of 3585 subjects in the intervention group referred, 52.4% were examined by physicians; 36 subjects with oral cancers and 1310 with oral precancers were diagnosed. Of the 63 oral cancers recorded in the cancer registry, 47 were in the intervention group and 16 were in the control group, yielding incidence rates of 56.1 and 20.3 per 100,000 person-years in the intervention and control groups, respectively. The program sensitivity for detection of oral cancer was 76.6% and the specificity 76.2%; the positive predictive value was 1.0% for oral cancer. In the intervention group, 72.3% of the cases were in Stages I-II, as opposed to 12.5% in the control group. The 3-year case fatality rates were 14.9% (7 of 47 patients) in the intervention group and 56.3% (9 of 16 patients) in the control group. CONCLUSIONS: Though compliance with referral for confirmatory examination in the first round was lower than the 70% anticipated, intermediate end points, such as stage at diagnosis and case fatality, indicate that the trial is making fairly satisfactory progress.

De novo programmed cell death in oral cancer.

AIM: The importance of programmed cell death or apoptosis in the maintenance of tissue homoeostasis and the pathogenesis of oral cancer was analysed in relation to apoptosis regulatory proteins, tissue proliferation and tumour histology. METHODS AND RESULTS: The extent of apoptosis was defined by morphological criteria and the TUNEL (terminal deoxy nucleotidyl transferase-mediated dUTP biotin nick end labelling) assay. p53, bax, bcl-2 and cyclin D1 expression was evaluated by immunocytochemistry. The presence of mutant p53 was analysed using a mutant p53-specific ELISA. An inverse correlation was observed between TUNEL reactivity and histology of the lesion (r = -0.555, P = 0.0001). There was also correlation between TUNEL reactivity and immunoreactivity of apoptosis regulatory proteins. p53 (r = 0.641, P = 0.00023), bcl-2 (r = -0.642, P = 0.00014) and bax (r = 0.651, P = 0.00002). The presence of mutant p53 protein showed an inverse correlation to the extent of apoptosis (r = - 0.301, P = 0.00063). Significant correlation was evident between the bax/bcl-2 ratio and TUNEL (r = 0.652, P = 0.00001) as well as between cyclin D1 and TUNEL reactivity (r = 0.577, P = 0.00001). CONCLUSIONS: Results from this study suggest that apoptosis decreases as histological abnormality increases. Apoptotic regulatory proteins are also altered in a histologically dependent manner. Deregulated proliferation occurs simultaneously with decreased apoptosis during tumour progression in the oral mucosa.