Choice of baseline hazards in joint modeling of longitudinal and time-to-event cancer survival data.

Longitudinal time-to-event analysis is a statistical method to analyze data where covariates are measured repeatedly. In survival studies, the risk for an event is estimated using Cox-proportional hazard model or extended Cox-model for exogenous time-dependent covariates. However, these models are inappropriate for endogenous time-dependent covariates like longitudinally measured biomarkers, Carcinoembryonic Antigen (CEA). Joint models that can simultaneously model the longitudinal covariates and time-to-event data have been proposed as an alternative. The present study highlights the importance of choosing the baseline hazards to get more accurate risk estimation. The study used colon cancer patient data to illustrate and compare four different joint models which differs based on the choice of baseline hazards [piecewise-constant Gauss-Hermite (GH), piecewise-constant pseudo-adaptive GH, Weibull Accelerated Failure time model with GH & B-spline GH]. We conducted simulation study to assess the model consistency with varying sample size (N = 100, 250, 500) and censoring (20 %, 50 %, 70 %) proportions. In colon cancer patient data, based on Akaike information criteria (AIC) and Bayesian information criteria (BIC), piecewise-constant pseudo-adaptive GH was found to be the best fitted model. Despite differences in model fit, the hazards obtained from the four models were similar. The study identified composite stage as a prognostic factor for time-to-event and the longitudinal outcome, CEA as a dynamic predictor for overall survival in colon cancer patients. Based on the simulation study Piecewise-PH-aGH was found to be the best model with least AIC and BIC values, and highest coverage probability(CP). While the Bias, and RMSE for all the models showed a competitive performance. However, Piecewise-PH-aGH has shown least bias and RMSE in most of the combinations and has taken the shortest computation time, which shows its computational efficiency. This study is the first of its kind to discuss on the choice of baseline hazards.

Breast cancer survival in India across 11 geographic areas under the National Cancer Registry Programme.

BACKGROUND: Population-based cancer survival is a key indicator for assessing the effectiveness of cancer control by a health care system in a specific geographic area. Breast cancer is the most common cancer among women in India, accounting for over one quarter of all female cancers. The objective of this study was to estimate the 5-year survival of female patients who were diagnosed with breast cancer between 2012 and 2015 from the existing Population-Based Cancer Registries (PBCRs) in India. METHODS: In total, 17,331 patients who had breast cancer diagnosed between 2012 and 2015 from 11 PBCRs were followed until June 30, 2021. Active methods were used to track the vital status of registered breast cancer cases. The study conducted survival analysis by calculating the difference between the date of first diagnosis and the date of death or censoring to estimate observed survival and relative survival using the actuarial survival approach and the Ederer-II approach, respectively. RESULTS: The 5-year age-standardized relative survival (95% confidence interval [CI]) of patients with breast cancer was 66.4% (95% CI, 65.5%-67.3%). Mizoram (74.9%; 95% CI, 68.1%-80.8%), Ahmedabad urban (72.7%; 95% CI, 70.3%-74.9%), Kollam (71.5%; 95% CI, 69.2%-73.6%), and Thiruvananthapuram (69.1%; 95% CI, 67.0%-71.2%) had higher survival rates than the national average. Conversely, Pasighat had the lowest survival rate (41.9%; 95% CI, 14.7%-68.6%). The 5-year observed survival rates for localized, regional, and distant metastasis in the pooled PBCRs were 81.0%, 65.5%, and 18.3%, respectively. CONCLUSIONS: The overall disparity in survival rates was observed across 11 PBCRs, with lower survival rates reported in Manipur, Tripura, and Pasighat. Therefore, it is imperative to implement comprehensive cancer control strategies widely throughout the country.

Assessment of spatial variation in lung cancer incidence and air pollutants: spatial regression modeling approach.

A notable finding is that Kerala's capital Thiruvananthapuram has shown an increasing trend in lung cancer (LC) incidence. Long-term exposure to air pollution is a significant environmental risk factor for LC. This study investigated the spatial association between LC and exposure to air pollutants in Thiruvananthapuram, using Spatial Lag Model (SLM), Spatial Error Model (SEM), and Geographically Weighted Regression (GWR). The results showed that overall LC incidence rate was 111 per 105 males (age >60 years), whereas spatial distribution map revealed that 48% of the area had an incidence rate greater than 150. The results revealed a significant association between PM2.5 and LC. SLM was identified as the best model that predicted 62% variation in LC. GWR model improved model performance and made better local predictions in the southeastern parts of the study area. This study explores the effectiveness of spatial regression techniques for dealing spatial effects and pinpointing high-risk areas.

Spatiotemporal pattern of thyroid cancer incidence in South Kerala: A population-based study.

Background: Thyroid cancer (TC) is the most common endocrine cancer and has been increasing over the past decades worldwide. A notable finding is that Kerala's capital Thiruvananthapuram ranks the first among men and the second highest among women in the incidence of TC in India. Reasons for this increase have not been established. Objectives: Here, we investigated the spatiotemporal pattern of TC incidence in Thiruvananthapuram. Materials and Methods: TC incidence data (n = 1937) of Population Based Cancer Registry Thiruvananthapuram, Kerala, India, between 2012 and 2016, were analyzed for identifying geographical patterns by spatial methods, temporal methods for studying spatial variation in TC incidence, distribution of age, gender, and histology in lowland (coastal), midland, and highland. Results: Spatial clustering of TC incidence was identified consistently near the coastal region based on all geospatial analyses. 56.9%, 23.9%, and 19.2% of TC cases were observed in the coastal, midland, and highland areas, respectively. A significant clustered pattern of TC incidence was revealed by Moran's index I (0.49), high-high clusters by local Moran's, hotspot by Getis-Ord-Gi* (P < 0.05), point pattern analysis by nearest neighbor ratio and kernel density estimation. The relative risk of the significant cluster was obtained as 1.60 (95% confidence interval: 1.03-1.84) by SaTScan analysis. Conclusion: This study identified spatial variations in the pattern of TC cases with significant clusters near the coastal region of Thiruvananthapuram. This would help to pinpoint the high-risk geographical areas of TC and for more effective cancer control programs.

Open to robotic right donor hepatectomy: A tectonic shift in surgical technique.

Robotic right live donor hepatectomy (r-LDRH) has been reported with reduced morbidity compared to open donor right hepatectomy (o-LDRH) in few recent series. Nevertheless, its routine use is debated. We present a large series comparing pure r-LDRH with o-LDRH. Consecutive r-LDRH performed from June 2018 to June 2020 (n = 102) were compared with consecutive donors undergoing o-LDRH (n = 152) from February 2016 to February 2018, a period when r-LDRH was not available at this center. Propensity score matched (PSM) analysis of 89 case-control pairs was additionally performed. Primary endpoints were length of high dependency unit (HDU) and hospital stay and Clavien-Dindo graded complications among donors. Although r-LDRH took longer to perform (540 vs. 462 min, P < .001), the postoperative peak transaminases levels (P < .001), the length of HDU (3 vs. 4 days, P < .001), and hospital stay (8 vs. 9 days, P < .001) were lower in in donors undergoing r-LDRH. Clavien-Dindo graded complications were similar (16.67% in r-LDRH and 13.16% in o-LDRH). The rates of early allograft dysfunction (1.6% vs. 3.3%), bile leak (14.7% vs. 10.7%), and 1-year mortality (13.7% vs. 11.8%) were comparable between r-LDRH and o-LDRH recipients. PSM analysis yielded similar results between the groups. These data support the safety and feasibility of r-LDRH in select donors.

Validation of Malayalam Translation of the European Organization for the Research and Treatment of Cancer Quality of Life Instrument OG25 for Esophagogastric Junction Cancers.

BACKGROUND: Quality of life questionnaire (QLQ) OG25 is the questionnaire used for measuring quality of life (QOL) of patients with esophago-gastric junction (OG) cancers. QLQ-OG 25 is a disease-specific tool to capture the QOL parameters of patients with OG junction cancers. OG 25 was developed by the European Organization for the Research and Treatment of Cancer (EORTC) using inspiration from their questionnaires for carcinoma stomach (STO22) and carcinoma esophagus (OES18). It is usually used along with QLQ-C30, which is a general tool applicable for all cancers. This questionnaire is in the English language. In order to use this questionnaire in a non-English speaking population, the English questionnaire has to be initially translated to the local languages. Malayalam is the language spoken by 38.5 million people residing in the South Indian state, Kerala, India. We have translated and validated the QLQ-OG 25 to Malayalam language in an attempt of enabling it to be used for future studies at this geographic region. METHODS: The translation was done by the standard protocol adopted by EORTC. QLQ-C30 and QLQ-OG25 questionnaires were then filled in by patients with OG junction cancers. These patients had cancers of various subsites of the OG junction and were at different stages of treatment, at the time of interview. The interview was done twice, at an interval ranging from 48 h to 1 week between the two interviews. RESULTS: A total of 46 patients with OG junction tumors at varying stages of treatment completed the questionnaire. There were no missing data. The average time to finish the interview was 12.12 min. The Cronbach's alpha, which signifies the internal consistency of the questionnaire, was found to be >0.7 in all the domains studied, except in cognitive function. The intraclass correlation coefficients varied from 0.63 to 0.93. CONCLUSION: The Malayalam translation of the QOL tool QLQ-OG25 has been found to be an acceptable and valid tool in assessing the QOL parameters of patients with OG junction cancers.

The City of Hope Quality of Life Stoma Questionnaire: Malayalam Translation and Validation.

BACKGROUND: Malayalam is the language spoken by 38.5 million people worldwide. There is no specific instrument to measure stoma-related quality of life (QOL) in Malayalam language. AIM: This study was designed to translate and validate the city of hope QOL (COH-QOL) Ostomy Questionnaire, which is a robust tool developed in English language. MATERIALS AND METHODS: The instrument was translated to Malayalam, abiding by internationally accepted translation methodology. Trained interviewer (first author) administered the questionnaire to patients with stoma, who were visiting the stoma clinic. The reliability of the subscales and the total scores were established by calculating correlation coefficients. Convergent and divergent validity were evaluated by calculating Pearson's correlations of each item with its own scale and other scales. RESULTS: Cronbach's alpha coefficients for all subscales were 0.70 or more. Similarly, split-half coefficients also were more than 0.70, which were acceptable. All subscales met the minimum acceptable standards of convergent and discriminant validity. Discriminant validity of all scores was less than convergent validity which suggests that there was no overlap between various constructs in measuring the same traits. The validation study of Malayalam translation of COH stoma questionnaire has shown that the tool is valid and reliable. CONCLUSION: The validation study of Malayalam translation of City of Hope Stoma questionnaire has shown the tool is valid and reliable.

Development of a field-friendly automated dietary assessment tool and nutrient database for India.

Studies of diet and disease risk in India and among other Asian-Indian populations are hindered by the need for a comprehensive dietary assessment tool to capture data on the wide variety of food and nutrient intakes across different regions and ethnic groups. The nutritional component of the India Health Study, a multicentre pilot cohort study, included 3908 men and women, aged 35-69 years, residing in three regions of India (New Delhi in the north, Mumbai in the west and Trivandrum in the south). We developed a computer-based, interviewer-administered dietary assessment software known as the 'NINA-DISH (New Interactive Nutrition Assistant - Diet in India Study of Health)', which consisted of four sections: (1) a diet history questionnaire with defined questions on frequency and portion size; (2) an open-ended section for each mealtime; (3) a food-preparer questionnaire; (4) a 24 h dietary recall. Using the preferred meal-based approach, frequency of intake and portion size were recorded and linked to a nutrient database that we developed and modified from a set of existing international databases containing data on Indian foods and recipes. The NINA-DISH software was designed to be easily adaptable and was well accepted by the interviewers and participants in the field. A predominant three-meal eating pattern emerged; however, patterns in the number of foods reported and the primary contributors to macro- and micronutrient intakes differed by region and demographic factors. The newly developed NINA-DISH software provides a much-needed tool for measuring diet and nutrient profiles across the diverse populations of India with the potential for application in other South Asian populations living throughout the world.

Survival of patients with cervical cancer in India - findings from 11 population based cancer registries under National Cancer Registry Programme.

Background: Cancer survival data from Population Based Cancer Registries (PBCR) reflect the average outcome of patients in the population, which is critical for cancer control efforts. Despite decreasing incidence rates, cervical cancer is the second most common female cancer in India, accounting for 10% of all female cancers. The objective of the study is to estimate the five-year survival of patients with cervical cancer diagnosed between 2012 and 2015 from the PBCRs in India. Methods: A single primary incidence of cervical cancer cases of 11 PBCRs (2012-2015) was followed till June 30, 2021 (n = 5591). Active follow-ups were conducted through hospital visits, telephone calls, home or field visits, and public databases. Five-year Observed Survival (OS) and Age Standardised Relative Survival (ASRS) was calculated. OS was measured by age and clinical extent of disease for cervical cancers. Findings: The five-year ASRS (95% CI) of cervical cancer was 51.7% (50.2%-53.3%). Ahmedabad urban (61.5%; 57.4%-65.4%) had a higher survival followed by Thiruvananthapuram (58.8%; 53.1%-64.3%) and Kollam (56.1%; 50.7%-61.3%). Tripura had the lowest overall survival rate (31.6%; 27.2%-36.1%). The five-year OS% for pooled PBCRs was 65.9%, 53.5%, and 18.0% for localised, regional, and distant metastasis, respectively. Interpretation: We observed a wide variation in cervical cancer survival within India. The findings of this study would help the policymakers to identify and address inequities in the health system. We re-emphasise the importance of awareness, early detection, and increase the improvement of the health care system. Funding: The National Cancer Registry Programme is funded through intra-mural funding by Indian Council of Medical Research, Department of Health Research, India, Ministry of Health & Family Welfare.

Trained Army Nurses in Colonial India: Early Experiences and Challenges.

The paper examines the introduction of trained female nurses for the British army men in colonial India between 1888 and 1920. It discusses the genesis of the Indian Nursing Service (INS), including the background and negotiations leading up to its formation, terms of employment, duties and working conditions of the nursing sisters. The memoir of Catharine Grace Loch, who served as the first Chief Lady Superintendent of the service is used extensively to trace the early experiences and challenges of the nursing sisters. The paper primarily argues that the INS being a new service, the colonial government maintained tight control over its functioning, and extreme conservatism in spending, thus retarding the growth of professional army nursing in India. Secondly, in examining the relations between the sisters and the (male) nursing orderlies, sub-medical and medical officers, the paper argues that the inadequate delineation of the nursing sisters' position in the military medical hierarchy was an important reason for the undermining of their expertise and status. Thirdly, the paper contends that as an all-women service, nursing constituted an important avenue of female agency within the patriarchal colonial establishment, which subjected the sisters to scrutiny both professionally and socially. The paper analyses the resultant conditions and regulations imposed on the sisters - most of them determined by gender and class notions. Finally, the paper discusses the gradual establishment and recognition of the service as an important cornerstone for the health of the army, while highlighting the shortcomings that yet persisted up until 1920.

Treatment Outcomes of Adenoid Cystic Carcinomas of the Head and Neck Region-A Single-Institution Experience.

Malu RafiObjectives This study was undertaken to evaluate the characteristics and treatment outcomes of patients with adenoid cystic carcinomas of the head and neck region treated at a tertiary cancer center in south India. Materials and Methods This was a retrospective study done on patients treated at the institute between 2004 and 2011. Clinicopathological details and treatment outcomes were captured from the treatment records to estimate the treatment outcomes and factors affecting them. Results There were a total of 140 patients with mean age of presentation of 46 years and a median follow-up of 65 months. The most common single site of presentation was the oral cavity. One-hundred eighteen patients (84.3%) underwent primary surgical resection in which 38% had negative surgical margins. Ninety-nine patients were given adjuvant radiotherapy and 18 patients received radical radiotherapy, mostly for surgically inaccessible and inoperable tumors. Median time to recurrence and distant metastasis was 37 and 34 months, respectively. The overall survival and disease-free survival estimate using the Kaplan-Meier method were 92.3 and 71.9%, respectively, at 5 years. Surgical removal of the primary tumor and the nodal stage had the most significant impact on the overall survival outcomes of these patients. Conclusion Surgery remains the most impactful treatment modality in the management of these rare epithelial tumors. The use of adjuvant radiotherapy may help to tackle the issues of perineural spread and inadequate surgical margins in technically difficult sites. Radical radiotherapy also has impressive response rates.

A Comparison Between Sequential Conventional and Hypofractionated Boost Following Whole-Breast Radiotherapy: A Propensity Score-Matched Analysis.

BACKGROUND: The majority of local relapses after breast conservation therapy occur in the proximity of the primary lesion. Studies have shown that boost radiotherapy (RT) following conventional whole-breast radiotherapy (WBRT) of 50 Gy in five weeks improves outcomes. Boost RT also increases the risk of moderate skin reactions and fibrosis. The ideal boost RT dose and timing (sequential versus simultaneous) after hypofractionated radiotherapy schedules remain unclear. This retrospective propensity score-matched analysis assessed the outcome of sequential hypofractionated boost compared to conventional fractionated boost. METHODS: The study was approved by the Institutional Review Board of the Regional Cancer Centre, Thiruvananthapuram, India. Patients with stage I-III breast cancer who have received adjuvant radiotherapy with a sequential boost of either hypofractionated RT (8 Gy in three fractions) or conventional fractionated RT (10 Gy in five fractions) after conservative breast surgery were identified from the radiotherapy planning records and included in this study. A 1:1 case matching was performed using a propensity score incorporating four known prognostic factors, namely, clinical and pathological composite stage, tumor grade, tumor biology (based on estrogen and/or progesterone and HER2 neu expression), and boost technique, which may have an impact on acute toxicity to make the two boost groups more homogenous. RESULTS: After propensity score matching (PSM), there were a total of 166 patients, with 83 patients each in both conventional and hypofractionated boost RT groups. The median follow-up period was 30.7 months. At two years, locoregional recurrence-free survival (LRFS) was 98.8% in both groups. Disease-free survival (DFS) at two years for the hypofractionated group and conventional group was 91.5% and 96.3% (hazard ratio (HR): 2.5, 95% confidence interval (CI): 0.664-9.4, p = 0.161), respectively, with no statistically significant difference. Patients with grade 3 tumors who received hypofractionated boost had a statistically significant increased risk of recurrence (DFS: 88.9% versus 100%, HR: 60.559, 95% CI: 0.138-26613.2, p = 0.011). The overall survival (OS) at two years was 100% in both groups. There was no difference in acute skin toxicity between the two groups. CONCLUSION: The present interim analysis shows similar locoregional recurrence-free survival, overall survival, and disease-free survival and acute skin toxicity for hypofractionated boost RT of 8 Gy in three fractions compared to the conventional boost of 10 Gy in five fractions. Hypofractionated boost is a feasible alternative option following hypofractionated whole-breast radiotherapy for women with breast conservation treatment. However, longer follow-up is required before forming definite conclusions.

Carcinoma buccal mucosa treated with definitive hypofractionated accelerated radiotherapy: a retrospective analysis of treatment outcomes.

Introduction: Oral cancer is a major public health concern in India. Both conventional and altered fractionation radiotherapy schedules have been used in curative treatment of oral cancer. This study aimed to retrospectively evaluate the clinical profile and treatment outcomes of patients with carcinoma buccal mucosa who underwent treatment with definitive hypofractionated accelerated radiotherapy. Methods: A total of 517 patients treated from January 2011 to December 2016 were eligible for the analysis. All patients were treated with definitive hypofractionated accelerated radiotherapy schedule of 5,250 cGy in 15 fractions over 3 weeks. Survival estimates were generated using the Kaplan-Meier method. Results: At a median follow-up of 77.4 months, 473 (91.5%) patients attained complete remission with radiation therapy. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 69% and 80.5%, respectively. The 5-year OS for stage I, II, III and IVa tumours was 80.3%, 84.4%, 81.4% and 73.7%, respectively, and the DFS was 75.7%, 73.2%, 69.6% and 60.2%, respectively. Age >50 years was found to be a significant factor affecting DFS (P = 0.026) and OS (P = 0.048) in multivariate analysis. Fifty-three (10.3%) patients developed osteoradionecrosis of the mandible. Conclusion: Excellent outcome could be achieved in less-aggressive, low-volume carcinoma of the buccal mucosa with radical accelerated hypofractionated radiotherapy. A radiotherapy schedule over a 3-week period is useful in high-volume centres.

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.

Outcomes of organ preservation treatment in advanced laryngeal carcinoma: A retrospective analysis from a single institution.

Chemoradiation is the standard treatment for patients with locally advanced laryngeal carcinoma with intact cartilage and functional larynx. The aim of this retrospective study was to assess overall survival (OS) and disease-free survival (DFS) of patients with locally advanced (stage III and stage IV) squamous cell carcinoma of the larynx who have been treated with definitive radical radiotherapy (RT) with or without chemotherapy in a tertiary cancer center in India between January 1, 2006 and December 31, 2015. Data were collected using structured proforma. The patients were treated with RT alone, induction chemotherapy (IC) followed by RT, concurrent chemoradiation therapy (CCRT) or IC followed by CCRT. Response assessment was conducted at 3-4 months post-treatment. Patient-, tumor- and treatment-related factors were documented and were associated with DFS and OS. Survival curves were generated using the Kaplan-Meier method and the statistical significance of survival curves was assessed using the log-rank test. Prognostic factors were assessed using the Cox proportional hazards regression model. A total of 630 patients were included in the present study. The most common age group at presentation was 50-70 years (n=477; 75.7%) and 95.4% (n=601) patients were male. The most common stage at presentation was stage III (n=367, 58.1%). The median follow-up period for the entire group of was 59 months (range, 2-175 months). A complete response after treatment was seen in 549 patients (87.1%). Salvage surgery was performed for 11 patients with residual disease. A total of 134 patients (21.3%) had developed locoregional and distant relapses, and salvage surgery was performed for 31 out of 102 patients with locoregional relapse. The 5-year OS was 48.7% and the 5-year DFS was 45.7%. The stage-wise OS rates were 58.9, 34.9 and 30.4% (P=0.001) and the stage-wise DFS rates were 56.3, 32.0 and 21.7 (P=0.001) for stage III, IVa and IVb, respectively. Results from the present study demonstrated the feasibility of delivery of chemoradiation protocols with good results in a developing country.

Treatment outcomes of squamous cell carcinoma of the lip: A retrospective study.

Oral and lip cancer is the most common type of cancer among males in India. Early stage tumours of the lip (stages I and II) are treated with single modality treatment, using either radiotherapy [external beam radiotherapy (EBRT) or brachytherapy] or surgery. Locally advanced tumours (stages III and IVa) are treated with surgery followed by adjuvant treatment. The aim of the present study was to retrospectively evaluate the clinical profile and treatment outcomes of patients with squamous cell carcinoma of the lip who were treated with radical intent at the Regional Cancer Centre (Thiruvananthapuram, India). For this purpose, a total of 120 patients treated with radical radiotherapy (brachytherapy or EBRT) or surgery with or without adjuvant treatment between January 2010 and December 2016 were eligible for the analysis. Kaplan-Meier analysis was used to generate the survival outcomes. Univariate and multivariate analyses were performed to determine the impact of various patient- and tumour-related factors and treatment modality on outcomes. At a median follow-up time of 67.6 months, the disease-free survival (DFS) and overall survival (OS) rates at 4 years for the entire cohort were 69.1 and 86.7%, respectively. The 4-year OS rates for patients with stage I, II, III and IV disease were 88.9, 95.2, 86.8 and 75.3%, respectively, and the DFS rates were 83.6, 69.5, 78.8 and 42.9%, respectively. Primary tumour (P=0.025), nodal (P=0.005) and composite clinical (P=0.006) stage were found to be significant factors affecting DFS rates in the univariate analysis. However, only the nodal stage (P=0.005) was found to be a significant factor affecting DFS rates in the multivariate analysis. On the whole, the present study demonstrates that the outcomes of patients with lip carcinoma are favourable when treated at the early stages, and the results from this series are in line with those already published.

Angiotensin-(1-7) via the mas receptor alleviates the diabetes-induced decrease in GFAP and GAP-43 immunoreactivity with concomitant reduction in the COX-2 in hippocampal formation: an immunohistochemical study.

We have previously shown that chronic treatment with angiotensin-(1-7) [Ang-(1-7)] can prevent diabetes-induced cardiovascular dysfunction. However, effect of Ang-(1-7) treatment on diabetes-induced alterations in the CNS is unknown. The aim of this study was to test the hypothesis that treatment with Ang-(1-7) can produce protection against diabetes-induced CNS changes. We examined the effect of Ang-(1-7) on the number of cyclooxygenase-2 (COX-2) immunoreactive neurons and the glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes and assessed the changes in the neuronal growth-associated protein-43 (GAP-43) of the hippocampal formation in streptozotocin-induced diabetes in rats. Animals were sacrificed 30 days after induction of diabetes and/or treatment with Ang-(1-7). Ang-(1-7) treatment significantly prevented diabetes-induced decrease in the number of GFAP immunoreactive astrocytes and GAP-43 positive neurons in all hippocampal regions. Co-administration of A779, a selective Ang-(1-7) receptor antagonist, inhibited Ang-(1-7)-mediated protective effects indicating that Ang-(1-7) produces its effects through activation of receptor Mas. Further, Ang-(1-7) treatment through activation of Mas significantly prevented diabetes-induced increase in the number of the COX-2 immunolabeled neurons in all sub-regions of the hippocampus examined. These results show that Ang-(1-7) has a protective role against diabetes-induced changes in the CNS.

Developmental trauma: Conceptual framework, associated risks and comorbidities, and evaluation and treatment.

Children exposed to adverse childhood experiences (ACEs) and pervasive interpersonal traumas may go on to develop PTSD and, in most cases, will further undergo a significant shift in their developmental trajectory. This paper examines contemporary research on Developmental Trauma (DT), which is inextricably linked to disruptions in social cognition, physiological and behavioral regulation, and parent-child attachments. Developmental trauma associated with early experiences of abuse or neglect leads to multi-faceted and longstanding consequences and underscores critical periods of development, complex stress-mediated adaptations, and multilevel, trans-theoretical influences in the diagnostic formulation and treatment of traumatized children, adolescents, and adults. Psychological and medical correlates of Developmental Trauma Disorder are considered, and directions for future research are discussed.

Epstein-Barr virus dynamics and its prognostic impact on nasopharyngeal cancers in a non-endemic region.

Background: Epstein-Barr virus (EBV) DNA quantification in nasopharyngeal cancer (NPC) is an indicator of the tumour burden, stage and survival. Although EBV dynamics in endemic regions has been extensively studied and reported, the data from non-endemic regions is sparse. This study attempts to investigate the EBV dynamics in NPC patients from a non-endemic region and also to identify the factors impacting the outcomes. Materials and methods: This was a prospective observational study conducted at a tertiary care centre in South India and enrolled patients with non-metastatic, biopsy proven NPC, who were suitable for radical chemo-radiotherapy with or without induction chemotherapy. Two blood samples, one prior to initiation of any anticancer treatment, and second at 6 weeks post treatment, were collected to quantify EBV DNA using real-time quantitative polymerase chain reaction. Antibodies against EBV viral capsid antigen (EBV VCA IgM), EBV Early Antigen (EBV EA IgG) and EBV Nuclear Antigen (EBV EBNA IgG) were also measured in the sample. The impact of EBV dynamics on the outcomes was then analysed. Results: The study included a total of 35 patients. Thirty-three had identifiable EBV DNA (94.3%) and a histological diagnosis of non-keratinising undifferentiated type of squamous cell carcinoma. There was no correlation between the EBV DNA and anti-EBV antibodies. There was a significant association between composite stage and pre-treatment DNA titre (p = 0.030). The mean EBV DNA titre was lower for patients with no clinically demonstrable disease at last follow-up and the reduction in EBV DNA titres was significant (p = 0.020) for those patients who remained disease free. Conclusion: Plasma EBV DNA is an accurate and reliable biomarker for NPC for WHO type 2 and 3 tumours even in non-endemic regions.

Effects of Revision Surgery and Surgical Margins on Outcome of Peripheral Soft Tissue Sarcomas: Experience from a Tertiary Cancer Care Centre.

INTRODUCTION: The purpose of this study is to assess the impact of revision surgery, after unplanned excision, on oncological outcome and surgical morbidity in soft tissue sarcomas and also to assess the relation between margin status and oncologic outcome. MATERIALS AND METHODS: We undertook a retrospective analysis of prospectively maintained database of 153 patients with peripheral soft tissue sarcomas treated in our institute from 2006-2010. RESULTS: Postoperatively, 111(72.5%) patients had negative margins, 20(13.1%) had close margins and 22(14.4%) had planned positive margins. Local recurrence rate was 19.8% in patients with negative margins and 28.6% for patients with close or positive margins (p= 0.007). There was no statistically significant difference in rates of distant metastases (18.9% vs 21.4%, p value 0.56) and five-year overall survival (82.5% Vs 79.8%, p value 0.41) between margin negative and close/positive groups. The five-year overall survival rates were 80.4 vs 77.8% (p =0.42) and five-year disease-free survival rates were 72.4% vs 70.2% (p=0.3), in the revision surgery group and primary surgery group respectively. CONCLUSION: Margin status after excision of soft tissue sarcoma is not a direct predictor for overall survival or distant metastasis. Revision surgery after an unplanned excision does not carry worse survival compared to primary surgery group.