Radical External-Beam Radiotherapy in Combination With Intracavitary Brachytherapy for Localized Carcinoma of the Cervix in Sri Lanka: Is Treatment Delayed Treatment Denied?

PURPOSE: Radical external-beam radiotherapy (EBRT) followed by intracavitary brachytherapy is standard of care for patients with localized carcinoma of the cervix unsuitable for radical surgery. However, outcome data are scarce in resource-limited settings. We conducted a retrospective analysis of survival in a cohort of patients treated with this strategy in Sri Lanka. PATIENTS AND METHODS: All patients with localized cervical cancer treated with primary EBRT and intracavitary brachytherapy from 2014 to 2015 were included in the study. Primary end point was disease-free survival (DFS), defined as time to local or systemic recurrence or death. Univariable analysis was performed to determine the prognostic significance of the following variables: age, stage, use of concurrent chemotherapy, EBRT dose, brachytherapy dose, and time to completion of treatment (dichotomized at 60 days). Factors significant on univariable analysis were included in a multivariable model. RESULTS: A total of 113 patients with available data were included in the analysis. Mean age was 58 years (range, 35-85 years), and most patients (n = 103 of 113) presented with stage ≥ IIB disease. Median time to delivery of brachytherapy from commencement of EBRT was 110 days (range, 34-215 days), with only 12 (11%) of 113 patients completing treatment within 60 days. Median follow-up was 28 months (range, 5-60 months), and 2-year DFS was 63.7% (95% CI, 55.4% to 73.2%). Treatment delay was the only significant factor associated with inferior DFS on univariable analysis (log-rank P = .03), and therefore, multivariable analysis was not performed. CONCLUSION: There are significant delays in receiving intracavitary brachytherapy after completing EBRT for cervical cancer in Sri Lanka, which is associated with inferior DFS. Increasing brachytherapy resources is an urgent priority to improve outcomes of patients with cervical cancer.

Promoter Hypermethylation of Tumor-Suppressor Genes p16INK4a,RASSF1A,TIMP3, and PCQAP/MED15 in Salivary DNA as a Quadruple Biomarker Panel for Early Detection of Oral and Oropharyngeal Cancers.

Silencing of tumor-suppressor genes (TSGs) by DNA promoter hypermethylation is an early event in carcinogenesis; hence, TSGs may serve as early tumor biomarkers. We determined the promoter methylation levels of p16INK4a, RASSF1A, TIMP3, and PCQAP/MED15 TSGs in salivary DNA from oral cancer (OC) and oropharyngeal cancer (OPC) patients, using methylation-specific PCR coupled with densitometry analysis. We assessed the association between DNA methylation of individual TSGs with OC and OPC risk factors. The performance and the clinical validity of this quadruple-methylation marker panel were evaluated in discriminating OC and OPC patients from healthy controls using the CombiROC web tool. Our study reports that RASSF1A, TIMP3, and PCQAP/MED15 TSGs were significantly hypermethylated in OC and OPC cases compared to healthy controls. DNA methylation levels of TSGs were significantly augmented by smoking, alcohol use, and betel quid chewing, indicating the fact that frequent exposure to risk factors may drive oral and oropharyngeal carcinogenesis through TSG promoter hypermethylation. Also, this quadruple-methylation marker panel of p16INK4a, RASSF1A, TIMP3, and PCQAP/MED15 TSGs demonstrated excellent diagnostic accuracy in the early detection of OC at 91.7% sensitivity and 92.3% specificity and of OPC at 99.8% sensitivity and 92.1% specificity from healthy controls.

Characteristics and sequelae of erupted supernumerary teeth: A study of 218 cases among Sri Lankan children.

AIM: In the present study, we investigated the characteristics and sequelae of erupted supernumerary teeth (ST) in a sample of Sri Lankan children. METHODS: Data were recorded from patients' clinical records, radiographs, models, and extracted teeth. RESULTS: The sample consisted of 239 ST from 218 patients. The mean age of the sample was 9.08 ± 2.47 years. The male-to-female ratio was 2.8:1. The majority (42.66%) of patients with ST were in aged 8-10 years. Many (94.94%) of the ST were located in the premaxilla (incisor), followed by the canine (4.22%), premolar (0.42%), and molar (0.42%) regions. The most common shape of ST teeth was conical. Malocclusion (59.83%) was the major problem associated with ST, and the clinical impact was highest on the 8-10-year age group. A strong association was observed between patients' age and clinical impact to the dentition (χ2 =42.09, P=.000). CONCLUSION: Because the majority of ST can lead to malocclusion, especially in mixed dentition, awareness, early detection, and timely clinical intervention of ST are recommended.

A shifting paradigm in the aetiology of oral and pharyngeal cancer in Sri Lanka: a case-control study providing serologic evidence for the role of oncogenic HPV types 16 and 18.

BACKGROUND: Oral and pharyngeal cancer (OPC) of multifactorial aetiology is a major health problem globally. Ranking first in all cancers, OPC poses a significant impact on the Sri Lankan male population. As Human Papillomavirus (HPV) high risk (HR) types are found to be significant risk factors for OPC globally, the current study was undertaken to examine the association between HR-HPV16 and 18 types with OPC in Sri Lanka. MATERIALS AND METHODS: Serum samples of 78 OPC patients and 51 non-cancer controls were assayed for the presence of anti-HPV16 and anti-HPV18 IgG antibodies using in-house established Enzyme Linked Immunosorbent Assays (ELISAs). The association between OPC and its risk factors i.e. HPV, smoking, alcohol, betel quid, poor dentition, was established using Chi-square test. Logistic regression was used to calculate odds ratios (OR), adjusted for the influence of other risk factors. RESULTS: This prototype study in Sri Lanka showed a significant risk of 15 fold in developing OPC due to HPV16/18 seropositivity after removing variability due to other factors. Oncogenic HPV18 showed a higher rate of seropositivity being detected in 32% of OPC patients, and also in 2% of non-cancer control subjects. HR-HPV16 was detected in 23% of OPC patients and in 5.88% of controls. Moreover, seven OPC patients were detected with both anti-HPV16 and anti-HPV18 antibodies. According to the logistic regression models HPV18 seropositivity was associated with a 28 fold risk in developing OPC while that of HPV16 was associated with a 6 fold increase in risk for the development of OPC. A 5 fold risk of developing OPC was also pronounced among smokers while alcohol, betel and poor dentition was not significantly associated with OPC. Statistically significant differences with regard to age, gender, smoking, alcohol, betel use, poor dentition and site specificity of the tumour was not observed between HPV seropositive and seronegative OPC patients. CONCLUSIONS: Both in-house developed ELISAs detected significant proportions of HPV seropositives within the OPC study population suggestive of HPV as a strong risk factor for oral and pharyngeal carcinogenesis in Sri Lanka.

Haematinic deficiency and macrocytosis in middle-aged and older adults.

OBJECTIVE: To assess the prevalence and determinants of haematinic deficiency (lack of B12 folate or iron) and macrocytosis in blood from a national population-based study of middle-aged and older adults. METHODS: A cross-sectional study involving 1,207 adults aged ≥45 years, recruited from a sub-study of the Irish National Survey of Lifestyle Attitudes and Nutrition (SLÁN 2007). Participants completed a health and lifestyle questionnaire and a standard food frequency questionnaire. Non-fasting blood samples were obtained for measurement of full blood count and expert morphological assessment, serum ferritin, soluble transferrin receptor assay (sTfR), B12, folate and coeliac antibodies. Blood samples were also assayed for thyroid function (T4, TSH), liver function, aminotransferase (AST) and gamma-glutamyl transferase (GGT). RESULTS: The overall prevalence (95% C.I.) of anaemia (Hb <13.5 g/dl men and 11.3 g/dl women) was 4.6% (2.9%-6.4%) in men and 1.0% (0.2%-1.9%) in women. Iron deficiency (ferritin <17 ng/ml men and <11 ng/ml in women) was detected in 6.3% of participants (3.7% in males and 8.7% in females, p<0.001). Based on both low ferritin and raised sTfR (>21 nmol/ml) only 2.3% were iron-deficient. 3.0% and 2.7% were found to have low levels of serum folate (<2.3 ng/ml) and serum B12 (<120 ng/l) respectively. Clinically significant macrocytosis (MCV>99fl) was detected in 8.4% of subjects. Strong, significant and independent associations with macrocytosis were observed for lower social status, current smoking status, moderate to heavy alcohol intake, elevated GGT levels, deficiency of folate and vitamin B12, hypothyroidism and coeliac disease. The population attributable fraction (PAF) for macrocytosis associated with elevated GGT (25.0%) and smoking (24.6%) was higher than for excess alcohol intake (6.3%), folate deficiency (10.5%) or vitamin B12 (3.4%). CONCLUSIONS: Haematinic deficiency and macrocytosis are common in middle-aged/older adults in Ireland. Macrocytosis is more likely to be attributable to an elevated GGT and smoking than vitamin B12 or folate deficiency.

Chronic Myeloid Leukemia with e19a2 BCR-ABL1 Transcripts and Marked Thrombocytosis: The Role of Molecular Monitoring.

While most patients with chronic myeloid leukemia (CML) express either e13a2 or e14a2 BCR-ABL1 transcripts, a significant minority expresses variant transcripts, of which e19a2 is the most common. Although considered to have a relatively favourable outcome, reported responses to tyrosine kinase inhibitor (TKI) therapy are variable with molecular monitoring in CML patients with e19a2 BCR-ABL1 transcripts rarely reported. A case of e19a2 BCR-ABL1 CML with marked thrombocytosis is described in which the value of molecular monitoring is emphasised during treatment interruptions, dose reductions, and changes. This case serves to demonstrate the requirement for prospective real-time quantitative PCR (RQ-PCR) assays for patients with variant BCR-ABL1 transcript types and standardisation of such assays to enable modern patient management.

Evaluation of bone marrow examinations performed by an advanced nurse practitioner: an extended role within a haematology service.

PURPOSE: Traditionally, medical personnel have undertaken bone marrow (BM) examination. However, specially trained nurses in advanced practice roles are increasingly undertaking this role. This paper presents the findings from an audit of BM examinations undertaken by an advanced nurse practitioner (ANP) at a regional haematology specialist centre. METHODS: The audit evaluated the quality of BM examinations performed by the ANP over the past two years (September 2007-September 2009). Over the two year period, 324 BM examinations were performed at the centre of which 156 (48.1%) were performed by the ANP. A random sample of 30 BM examinations undertaken by the ANP were analysed by the consultant haematologist. RESULTS: All 30 BM examinations undertaken by the ANP were sufficient for diagnosis. CONCLUSIONS: The ANP is capable and competent to obtain BM samples which are of a sufficient quality to permit diagnosis.

A statewide evaluation system for early psychosis.

OBJECTIVE: We describe a system of outcome evaluation for early psychosis programmes and present preliminary data. The Early Psychosis Outcome Evaluation System (EPOES) was designed for use in a naturalistic, prospective study of a cohort of early-episode psychosis patients. We describe patients in terms of symptoms, substance use, social functioning and family burden, and examine the effectiveness of treatment programmes. METHOD: Four sites in Perth, Western Australia, participated. Outcome was evaluated from three sources: case manager (CM), patient (P) and family member (FM). Seven clinical outcome measures were used: the Brief Psychiatric Rating Scale (CM), Brief Symptom Inventory (P), Substance Use (CM); Social Functioning Scale (P); Global Assessment Scale (CM); Burden Assessment Scale (FM), and the General Health Questionnaire-12 (FM). Measures were collected at intake (baseline) into a specialist early psychosis service and thereafter every 6 months until discharge from the service. RESULTS: After the first year of data capture, 84 baseline assessments have been completed, and 23 patients have been followed up at 6 months. Clinicians and patients reported significantly less psychopathology at 6 months. Sixty per cent of patients reported marijuana use within 3 months of baseline assessment, and 30% amphetamine, ecstasy or cocaine use. Increased levels of psychopathology were recorded for substance-using patients. Family members (59%) reported psychological distress at baseline; this was reduced at 6 months. Patient social functioning and family burden did not improve measurably. CONCLUSIONS: The EPOES is an effective system that provides feedback on the clinical status of early-episode psychosis patients. Both observed and self-rated psycho-pathology and family psychological distress, is improved after 6 months of intervention. Family burden and patient social functioning did not demonstrate improvement. Patient social functioning is an important area for treatment. Substance use is associated with poorer psychopathology. EPOES provides a feasible system of measuring outcome in early psychosis intervention.