A National Cancer Grid pooled procurement initiative, India.

In health systems with little public funding and decentralized procurement processes, the pricing and quality of anti-cancer medicines directly affects access to effective anti-cancer therapy. Factors such as differential pricing, volume-dependent negotiation and reliance on low-priced generics without any evaluation of their quality can lead to supply and demand lags, high out-of-pocket expenditures for patients and poor treatment outcomes. While pooled procurement of medicines can help address some of these challenges, monitoring of the procurement process requires considerable administrative investment. Group negotiation to fix prices, issuing of uniform contracts with standardized terms and conditions, and procurement by individual hospitals also reduce costs and improve quality without significant investment. The National Cancer Grid, a network of more than 250 cancer centres in India, piloted pooled procurement to improve negotiability of high-value oncology and supportive care medicines. A total of 40 drugs were included in this pilot. The pooled demand for the drugs from 23 centres was equivalent to 15.6 billion Indian rupees (197 million United States dollars (US$)) based on maximum retail prices. The process included technical and financial evaluation followed by contracts between individual centres and the selected vendors. Savings of 13.2 billion Indian Rupees (US$ 166.7million) were made compared to the maximum retail prices. The savings ranged from 23% to 99% (median: 82%) and were more with generics than innovator and newly patented medicines. This study reveals the advantages of group negotiation in pooled procurement for high-value medicines, an approach that can be applied to other health systems.

Lorsque les systèmes de santé reçoivent peu de fonds publics et que leurs processus d'achat sont décentralisés, le prix et la qualité des médicaments contre le cancer ont un impact direct sur l'accès aux traitements efficaces contre la maladie. Des facteurs tels que l'application de prix différenciés, les négociations en fonction des volumes ainsi que la confiance placée dans des génériques bon marché dont la qualité n'a pas été évaluée peuvent entraîner des décalages entre l'offre et la demande, d'énormes dépenses non remboursables pour les patients et de piètres résultats thérapeutiques. Bien que les acquisitions groupées de médicaments puissent contribuer à résoudre certains de ces problèmes, le suivi du processus d'achat requiert un engagement considérable au niveau administratif. Les négociations collectives en vue de fixer les tarifs, l'établissement de contrats types assortis de conditions générales standardisées, mais aussi les achats effectués par des hôpitaux en particulier peuvent également faire baisser les coûts et améliorer la qualité sans nécessiter d'importants investissements. Le National Cancer Grid, un réseau réunissant plus de 250 centres d'oncologie en Inde, a testé un dispositif d'achat groupé visant à assurer une meilleure négociabilité pour des médicaments et soins de soutien essentiels contre le cancer. Au total, 40 substances ont été prises en compte dans ce projet pilote. La demande groupée en médicaments émise par 23 centres équivalait à 15,6 milliards de roupies indiennes (197 millions de dollars américains) d'après le prix maximal de vente au détail. Ce processus prévoyait une évaluation technique et financière, puis des contrats entre chaque centre et les distributeurs sélectionnés. Des économies de 13,2 milliards de roupies indiennes (166,7 millions de dollars américains) ont pu être réalisées par rapport au prix maximal de vente au détail. Ces économies étaient comprises entre 23 et 99% (médiane: 82%) et concernaient davantage les médicaments génériques que les marques et les médicaments récemment brevetés. La présente étude révèle les avantages que représentent les négociations collectives lors des achats groupés de médicaments essentiels, une approche applicable à d'autres systèmes de santé.

En los sistemas sanitarios con escasa financiación pública y procesos de adquisición descentralizados, el sistema de fijación de precios y la calidad de los medicamentos contra el cáncer afectan directamente al acceso a una terapia eficaz contra dicha enfermedad. Factores como los diferentes sistemas de determinación de precios, la negociación en función del volumen y la dependencia de genéricos de bajo precio sin evaluación de su calidad pueden generar retrasos en la oferta y la demanda, elevados gastos para los pacientes y malos resultados en el tratamiento. Aunque la adquisición conjunta de medicamentos puede ayudar a abordar algunos de estos retos, el seguimiento del proceso de adquisición requiere una inversión administrativa considerable. La negociación colectiva a la hora de determinar los precios, la emisión de contratos unificados con términos y condiciones estandarizados y la adquisición por parte de algunos hospitales también reducen los costes y mejoran la calidad sin necesidad de realizar una gran inversión. La Red Nacional de Cáncer, una red que cuenta con más de 250 centros oncológicos en la India, puso a prueba la adquisición conjunta con el fin de mejorar la negociabilidad de medicamentos oncológicos y de tratamiento complementario que resultaban costosos. En esta prueba piloto se incluyó un total de 40 medicamentos. La demanda conjunta de medicamentos por parte de 23 centros fue equivalente a 15 600 millones de rupias indias (197 millones USD) según los precios minoristas máximos. El proceso incluyó una evaluación técnica y financiera, así como contratos entre centros independientes y proveedores seleccionados. Se logró un ahorro de 13 200 millones de rupias indias (166,7 millones USD) en comparación con los precios minoristas máximos. El ahorro osciló entre el 23 y el 99% (media: 82%) y fue más alto con los medicamentos genéricos que con los de marca y los recién patentados. Este estudio pone de manifiesto las ventajas de la negociación colectiva en lo que respecta a la adquisición conjunta de medicamentos costosos, un enfoque que se puede aplicar a otros sistemas sanitarios.

Management of compound odontoma with 70 denticles and impacted lateral incisor over an 8-year follow-up.

Odontomas are benign developmental tumors formed by the improper growth of completely differentiated epithelial and mesenchymal cells of odontogenic origin. The etiology of odontoma is unknown and it is detected during routine radiographic examination. The ideal management is early detection and surgical enucleation. The commonly associated clinical problems of odontomas are delayed exfoliation of primary teeth, delayed eruption or impaction of permanent teeth, displacement of teeth, root resorption, congenital missing, and widening of follicular space. Here, we describe a unique case of compound odontoma with a high number of denticles managed based on a definite decision support system over 8 years. An 8-year-old boy with 70 denticles in the left maxillary region underwent enucleation. On periodic follow-up, the associated impacted lateral incisor was extruded orthodontically.

Polymorphous Adenocarcinoma: A Rare Case Report with Unique Radiographic Appearance on CBCT.

BACKGROUND: Polymorphous low-grade adenocarcinoma (PLGA) is a slow growing malignant tumor of minor salivary glands and is generally of indolent nature. However, according to the most recent WHO Classification of Salivary Gland Tumors (2017), the cancer is classified as Polymorphous AdenoCarcinoma (PAC). PAC presents as a less aggressive tumor, though it could on rare occasions demonstrate distant metastasis. Case Presentation. A 47-year-old man who was referred by a private practitioner for a CBCT scan in reference to a proliferative soft-tissue growth in the hard palate. The growth was mild and tender and there was Grade III mobility in relation to all the maxillary teeth. Panoramic radiograph taken previously had revealed evidence of alveolar bone loss in relation to the maxillary teeth and was inconclusive of any other findings. The CBCT scan revealed evidence of moth-eaten appearance of maxilla with destruction of medial and lateral walls and floor of maxillary sinus. There was also evidence of involvement of right eustachian tube, ethmoidal wall, and nasopalatine canal. An intraosseous malignancy of the palate was suspected, and a total maxillectomy was performed. The tissue sample was sent for histopathological assessment wherein changes diagnostic for polymorphous low-grade adenocarcinoma of the palate were observed. CONCLUSION: PAC is a distinct, yet commonly occurring, minor salivary gland tumor with varied clinical and histologic appearance. This case report highlights the importance of CBCT in diagnosing the intraosseous involvement of such tumors which can help shed some light in enhancing our knowledge about the minor salivary gland malignancies like PAC.

Efficacy and Safety of Lateral Approach-Video Endoscopic Inguinal Lymphadenectomy (L-VEIL) over Open Inguinal Block Dissection: a Retrospective Study.

This retrospective study compared the immediate post-operative short-term outcomes of Lateral Approach-Video Endoscopic Inguinal Lymphadenectomy (L-VEIL) and open surgery approach in patients with TNM stage N0 and N1 tumors. Inguinal lymphadenectomies performed for various TNM stage N0 and N1 cancers between January 2011 and December 2015 at a single center were analyzed by collecting data from operation theater records and case files. Mean blood loss, operative time, drain output, nodal yield, nodal positivity, and complications were analyzed as post-procedural outcomes. Among the 116 surgeries performed, 92 were open surgery and 24 were L-VEIL. Compared with open surgery, L-VEIL led to significantly lower blood loss (64.8 mL vs. 23.3 mL; p = 0.002), mean nodal yield (11.04 vs. 8.38; p = 0.001), and mean hospital stay (3.08 vs. 8 days; p < 0.001). However, the operative time was similar for both the groups (94.5 vs. 68.1 min; p = 0.08). Complications that were significantly low in L-VEIL were flap necrosis [RR 1.29; 95% CI (1.03-1.72); p < 0.001], wound dehiscence [RR 1.25; 95% CI (1.19-1.51); p = 0.005), wound infection [RR 1.34; 95% CI (1.19-1.51); p = 0.003], readmission [RR 1.3; 95% CI (1.17-1.44); p = 0.005], and re-surgery [p = 0.014]. Occurrence of complications such as lymphocele [RR 1.25; 95% CI (0.33-4.78); p = 0.5], lymphorrhea [RR 1.27; 95% CI (1.15-1.40); p = 0.5], and pedal edema [p = 0.2] were similar for both the approaches. L-VEIL was effective and safe compared with open inguinal block dissection in treatment of various TNM stage N0 and N1 urogenital and skin cancers.

Vitamin E TPGS Emulsified Vinorelbine Bitartrate Loaded Solid Lipid Nanoparticles (SLN): Formulation Development, Optimization and In vitro Characterization.

BACKGROUND: Vinorelbine bitartrate (VRL), a semi synthetic vinca alkaloid approved for breast cancer, has been proven to be beneficial as first line and subsequent therapies. However, its hydrophilic and thermo labile nature provides hindrance to oral clinical translation. OBJECTIVES: The current work focused on the application of DOE a modern statistical optimization tool for the development and optimization of a solid lipid nanoparticle (SLN) formulation that can encapsulate hydrophilic and thermolabile Vinorelbine bitartrate (VRL) to a maximum extent without compromising integrity and anticancer activity of the drug. METHODS: SLNs were prepared by solvent diffusion technique employing Taguchi orthogonal array design with optimized formulation and process variables. The emulsifying nature and low melting point of glyceryl mono-oleate (GMO) were exploited to enhance entrapment and minimizing temperature associated degradation, respectively. Moreover, two types of surfactants, Vitamin E TPGS (TPGS) and Poloxamer-188 were utilized to obtain TPGS-VRL-SLNs and PL-VRL-SLNs, respectively. The SLNs were characterized for various physicochemical properties, in-vitro drug release kinetics and anticancer activity by MTT assay on MCF-7 cancer cell lines. RESULTS: The SLNs were found to be spherical in shape with entrapment efficiency (EE) up to 58 %. Invitro release studies showed biphasic release pattern following Korsemeyer peppas model with fickian release kinetics. Results of MTT assay revealed that TPGS-VRL-SLNs and PL-VRL-SLNs were 39.5 and 18.5 fold more effective, respectively, compared to the pristine VRL. CONCLUSION: DOE approach was successfully applied for the development of VRL-SLNs. Enhanced entrapment and anticancer efficacy of TPGS-VRL-SLN can be attributed to emulsifying nature of GMO and inherent cytotoxic nature of TPGS, respectively, which synergizes with VRL. Therefore, TPGS associated SLNs may be potential carrier in cancer chemotherapeutics.

Expression of tripartite motif-containing protein 28 in primary breast carcinoma predicts metastasis and is involved in the stemness, chemoresistance, and tumor growth.

The prediction of who develops metastasis has been the most difficult aspect in the management of breast cancer patients. The lymph node metastasis has been the most useful predictor of prognosis and patient management. However, a good proportion of patients with lymph node positivity remain disease free for 5 years or more, while about a third of those who were lymph node negative develop distant metastasis within the same period. This warrants a robust biomarker(s), preferably gene expression based. In order to elucidate gene-based biomarkers for prognosis of breast cancers, gene expression profiling of primary tumors and follow-up for over 5 years has been performed. The analysis revealed a network of genes centered around the tripartite motif-containing protein 28 as an important indicator of disease progression. Short hairpin RNA-mediated knockdown of tripartite motif-containing protein 28 in breast cancer cells revealed a decreased expression of epithelial-to-mesenchymal transition markers and increased expression of epithelial markers, decreased migration and invasion, and increased chemosensitivity to doxorubicin, 5-fluorouracil, and methotrexate. Furthermore, knockdown of tripartite motif-containing protein 28 resulted in the decrease of stemness as revealed by sphere formation assay as well as decreased expression of CD44 and Bmi1. Moreover, tripartite motif-containing protein 28 knockdown significantly reduced the tumor size and lung metastasis in orthotopic tumor xenograft assay in immunocompromised mice. The tumor size was further reduced when these mice were treated with doxorubicin. These data provide evidence for tripartite motif-containing protein 28 as a biomarker and a potential therapeutic target for breast cancer.

Global trends in esophageal cancer.

BACKGROUND AND OBJECTIVES: Esophageal Cancer (EC) is a lethal malignancy with poor prognosis and significant variations in the incidence, mortality, and histopathology based on geographic regions. The aim of this study was to quantitatively analyze these variations to identify patterns and areas for further research. METHODS: We utilized the GLOBOCAN 2012, and Cancer Incidence in five Continents, Volume X (CI5X) database to analyze variations in EC incidence and mortality. RESULTS: We found the EC incidence and mortality is geographically varied with a particularly high burden in East Asia and Eastern/Southern Africa where esophageal squamous cell carcinoma (SCC) predominates over adenocarcinoma (AC). Interestingly, there is a dichotomy between the high incidence of esophageal SCC in East Africa and low incidence in West Africa. The global incidence and mortality from EC is expected to rise in the coming decades. Asia, and China in particular, will continue to be the areas most burdened by EC, while Africa is expected to surpass the incidence and mortality rates of Europe. CONCLUSIONS: The global burden of EC is expected to rise in the coming years. Understanding the geographic, environmental, and genetic contributors to the development of EC will be essential in combating its prevalence.

Prevalence and correlates of malnutrition among elderly in an urban area in Coimbatore.

BACKGROUND: Different studies in India have shown that more than 50% of elderly population of India are suffering from malnutrition and more than 90% have less than recommended intake. OBJECTIVES: The aim of this study is to estimate the prevalence and correlates of malnutrition among elderly aged 60 years and above in an urban area in Coimbatore using Mini Nutritional Assessment (MNA). METHODS: A cross-sectional study was conducted on 154 households and 190 elderly were interviewed. Nutritional status was assessed using the MNA questionnaire. RESULTS: Mean (standard deviation) age of the total population (n = 190) was 71.09 (7.93) years and 30% was male. In this population, 37 (19.47%) was malnourished (MNA <17.0) and 47 (24.73%) were at risk for malnutrition (MNA 17.0-23.5). No significant association was observed between smoking, current alcohol consumption, higher medication use, higher comorbidity, and use of walk aid with malnutrition. Among the social factors studied, lower socioeconomic status compared to higher socioeconomic status (adjusted odds ratio [OR] =5.031, P < 0.001), single/widowed/divorced compared to married (adjusted OR = 3.323, P < 0.05), and no pension compared to those having pension (adjusted OR = 3.239, P < 0.05) were significantly associated with malnutrition. CONCLUSION: The prevalence of malnutrition observed in the aged people is unacceptably high. The increasing total number of lifestyle, somatic, functional, and social factors was associated with lower MNA scores. The findings of the present study clearly indicate that malnutrition is a multifactorial condition associated with sociodemographic, somatic, and functional status. Hence, we recommend that the treatment of malnutrition should be multifactorial, and the treatment team should be multidisciplinary. Further research is needed to develop appropriate guidelines for nutritional screening and interventional programs among geriatric population.

Comparison of Epidural Bupivacaine, Levobupivacaine and Dexmedetomidine in Patients Undergoing Vascular Surgery.

INTRODUCTION: Levobupivacaine is the s-isomer of racemic Bupivacaine. It is less cardio, neurotoxic and equally potent local anaesthetic compared to its racemate. It is known to cause less Depression of myocardial contractility. Dexmeditomidine when used via epidural route has synergistic effect with local anaesthetics. Majority of patients presenting for vascular surgery are elderly and have associated co-morbidities like diabetes, hypertension, and coronary artery disease. We intend to study safety and efficacy of epidural Levoupivacaine and Dexmedetomidine in this group of patients. MATERIALS AND METHODS: Sixty adult patients undergoing lower limb vascular surgery under lumbar epidural anaesthesia were randomly allocated to three groups. All groups were preloaded with 10ml/kg of crystalloid solution. B group was scheduled to receive 15 ml of racemic Bupivacaine, L-group was scheduled to receive 15ml of Levobupivacaine and LD-group received 15ml of Levobupivacaine with 0.5 mics/kg Dexmeditomedine. Time to onset of sensory block to T-10, maximum sensory level achieved, Bromage scale, time to two segment regression, time to total regression, sedation level achieved and patients assessment of quality of anaesthesia were assessed. Haemodynamic parameters were monitored throughout study period. Adverse effects were noted and treated appropriately. RESULTS: Baseline parameters were comparable among all the groups. Time to onset of sensory block to T-10 and maximum level of block achieved, was comparable among the groups. Time to two segment regression and time to total regression was significantly prolonged in LD group compared to other two groups. There was significant bradycardia noted in LD group which required treatment. CONCLUSION: Levobupivacaine can be safely used in elderly high risk patients undergoing vascular surgery. Addition of dexmedetomidine prolongs the duration of anaesthesia and postoperative analgesia.

Report from a symposium on catalyzing primary and secondary prevention of cancer in India.

PURPOSE: Oral, breast, and cervical cancers are amenable to early detection and account for a third of India's cancer burden. We convened a symposium of diverse stakeholders to identify gaps in evidence, policy, and advocacy for the primary and secondary prevention of these cancers and recommendations to accelerate these efforts. METHODS: Indian and global experts from government, academia, private sector (health care, media), donor organizations, and civil society (including cancer survivors and patient advocates) presented and discussed challenges and solutions related to strategic communication and implementation of prevention, early detection, and treatment linkages. RESULTS: Innovative approaches to implementing and scaling up primary and secondary prevention were discussed using examples from India and elsewhere in the world. Participants also reflected on existing global guidelines and national cancer prevention policies and experiences. CONCLUSIONS: Symposium participants proposed implementation-focused research, advocacy, and policy/program priorities to strengthen primary and secondary prevention efforts in India to address the burden of oral, breast, and cervical cancers and improve survival.

LC-MS-based serum metabolomic analysis reveals dysregulation of phosphatidylcholines in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers with poor prognosis. Here, we carried out liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS)-based untargeted metabolomic analysis of ESCC serum samples. Statistical analysis resulted in the identification of 652 significantly dysregulated molecular features in serum from ESCC patients as compared to the healthy subjects. Phosphatidylcholines were identified as a major class of dysregulated metabolites in this study suggesting potential perturbation of phosphocholine metabolism in ESCC. By using a targeted MS/MS approach both in positive and negative mode, we were able to characterize and confirm the structure of seven metabolites. Our study describes a quantitative LC-MS approach for characterizing dysregulated lipid metabolism in ESCC. BIOLOGICAL SIGNIFICANCE: Altered metabolism is a hallmark of cancer. We carried out (LC-MS)-based untargeted metabolomic profiling of serum from esophageal squamous cell carcinoma (ESCC) patients to characterize dysregulated metabolites. Phosphatidylcholine metabolism was found to be significantly altered in ESCC. Our study illustrates the use of mass spectrometry-based metabolomic analysis to characterize molecular alterations associated with ESCC. This article is part of a Special Issue entitled: Proteomics in India.

Identification of differentially expressed serum proteins in gastric adenocarcinoma.

Gastric adenocarcinoma is an aggressive cancer with poor prognosis. Blood based biomarkers of gastric cancer have the potential to improve diagnosis and monitoring of these tumors. Proteins that show altered levels in the circulation of gastric cancer patients could prove useful as putative biomarkers. We used an iTRAQ-based quantitative proteomic approach to identify proteins that show altered levels in the sera of patients with gastric cancer. Our study resulted in identification of 643 proteins, of which 48 proteins showed increased levels and 11 proteins showed decreased levels in serum from gastric cancer patients compared to age and sex matched healthy controls. Proteins that showed increased expression in gastric cancer included inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4), Mannose-binding protein C (MBL2), sex hormone-binding globulin (SHBG), insulin-like growth factor-binding protein 2 (IGFBP2), serum amyloid A protein (SAA1), Orosomucoid 1 (ORM1) and extracellular superoxide dismutase [Cu-Zn] (SOD3). We used multiple reaction monitoring assays and validated elevated levels of ITIH4 and SAA1 proteins in serum from gastric cancer patients. BIOLOGICAL SIGNIFICANCE: Gastric cancer is a highly aggressive cancer associated with high mortality. Serum-based biomarkers are of considerable interest in diagnosis and monitoring of various diseases including cancers. Gastric cancer is often diagnosed at advanced stages resulting in poor prognosis and high mortality. Pathological diagnosis using biopsy specimens remains the gold standard for diagnosis of gastric cancer. Serum-based biomarkers are of considerable importance as they are minimally invasive. In this study, we carried out quantitative proteomic profiling of serum from gastric cancer patients to identify proteins that show altered levels in gastric cancer patients. We identified more than 50 proteins that showed altered levels in gastric cancer patient sera. Validation in a large cohort of well classified patient samples would prove useful in identifying novel blood based biomarkers for gastric cancers. This article is part of a Special Issue entitled: Proteomics in India.

Downregulation of S100 Calcium Binding Protein A9 in Esophageal Squamous Cell Carcinoma.

The development of esophageal squamous cell carcinoma (ESCC) is poorly understood and the major regulatory molecules involved in the process of tumorigenesis have not yet been identified. We had previously employed a quantitative proteomic approach to identify differentially expressed proteins in ESCC tumors. A total of 238 differentially expressed proteins were identified in that study including S100 calcium binding protein A9 (S100A9) as one of the major downregulated proteins. In the present study, we carried out immunohistochemical validation of S100A9 in a large cohort of ESCC patients to determine the expression and subcellular localization of S100A9 in tumors and adjacent normal esophageal epithelia. Downregulation of S100A9 was observed in 67% (n = 192) of 288 different ESCC tumors, with the most dramatic downregulation observed in the poorly differentiated tumors (99/111). Expression of S100A9 was restricted to the prickle and functional layers of normal esophageal mucosa and localized predominantly in the cytoplasm and nucleus whereas virtually no expression was observed in the tumor and stromal cells. This suggests the important role that S100A9 plays in maintaining the differentiated state of epithelium and suggests that its downregulation may be associated with increased susceptibility to tumor formation.

Cyathula prostrata: a potent source of anticancer agent against daltons ascites in Swiss albino mice.

OBJECTIVE: To evaluate the anticancer activity of the methanolic extract of Cyathula prostrata in Ehrlich ascites carcinoma (EAC)-bearing mice with methotrexate as positive control in the advanced stage of tumorigenesis. METHODS: EAC was induced in swiss albino mice by injecting 10(6) cell/mL of tumor cell suspension intraperitoneal. The methanolic extract of Cyathula prostrata effect on the tumor cell viability, DNA fragmentation and MTT assay were carried out. RESULTS: Methanolic extract attenuated percentage increased in the cell survival time when compared to control group. However, the effect was less than that of methotrexat. Methotrexat and the extracts reversed the tumor-induced alterations in DNA fragmentation and MTT assay. CONCLUSIONS: The present study suggests that the methanol extract of Cyathula prostrata has significant anticancer activity and that is comparable to that of methotrexate.

Trends in oesophagus and Stomach cancer incidence in Bangalore, India.

BACKGROUND: During recent decades, an increase in the incidence of certain oesophago-gastric cancer has been reported in some countries and in India. This study sought to analyze oesophageal and gastric cancer incidence trends in Bangalore by sex and morphology for the period 1982-2007. PATIENTS AND METHODS: Oesophageal and gastric cancer cases were drawn from Bangalore population-based cancer registry locating in Kidwai memorial Institute of Oncology started in 1982 under national cancer Registry Programme funded by Indian Council of Medical Research. Time trends in sex- and age-standardized cancer incidence rates were analyzed by site and histology over the study period, using relative change. RESULTS: Age-standardised oesophageal cancer incidence rates increased in males, in females failed to register a significant trend over the study period. Overall, gastric cancer decreased from 9.81 and 5.48 rates per 100 000 person-years in 1982-86 to 9.45 and 5.25 in 2002-07, among men and women, respectively. Where as oesophageal adenocarcinomas increased sharply in both sex, among men, oesophageal squamous cell cancer rates increased steadily from the mid-1982s onwards a bit decline was observed from 1997, the same trend observed in females. The gastric cancer decreased over the study period. There was a marked decrease in the incidence of oesophago-gastric cancer presenting with unknown and unspecified morphology reported. KEYWORDS: adenocarcinoma, Oesophageal and stomach, incidence, age specific rate, age adjusted rate, population-based registry, trends.

Evaluation of chemopreventive effect of Fumaria indica against N-nitrosodiethylamine and CCl4-induced hepatocellular carcinoma in Wistar rats.

OBJECTIVE: To investigation the chemopreventive potential of Fumaria indica (F. indica) extract (FIE) on N-nitrosodiethylamine and CCl(4)-induced hepatocarcinogenesis in Wistar rats. METHODS: The experimental animals were divided into six groups (n=6). Hepatocellular carcinoma was induced by single intraperitoneal injection of N-nitrosodiethylamine (NDEA) in normal saline at a dose of 200 mg/kg body weight followed by weekly subcutaneous injections of CCl(4)(3 mL/kg/week) for 6 weeks, as the promoter of carcinogenic effect. After administration of the carcinogen, 200 and 400 mg/kg of FIE were administered orally once a day throughout the study. At the end of 20 weeks, the body weight, liver weight and relative liver weight were measured. The percentage of nodule incidence and liver cancer markers such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), γ-glutamyl transferase (γ-GT), total bilirubin level (TBL), α-feto protein (AFP) and carcinoembryonic antigen were estimated along with histopathological investigation in experimental groups of rats. RESULTS: Obtained results demonstrated that the cotreatment with FIE significantly prevented the decrease of the body weight and also increased in relative liver weight caused by NDEA. The treatment with FIE significantly reduced the nodule incidence and nodule multiplicity in the rats after NDEA administration. The levels of liver cancer markers such as AST, ALT, ALP, γ-glutamyl transferase, TBL, AFP and carcinoembryonic antigen were substantially increased by NDEA treatment. However, FIE treatment significantly reduced the liver injury and restored the entire liver cancer markers. Histological observations of liver tissues too correlated with the biochemical observations. CONCLUSIONS: These finding powerfully supports that F. indica exert chemopreventive effect by suppressing the tumor burden and restoring the activities of hepatic cancer marker enzymes on NDEA and CCl(4)-induced hepatocarcinogenesis in Wistar rats.

Modulatory effect of polyphenolic extracts of Ichnocarpus frutescens on oxidative stress in rats with experimentally induced diabetes.

BACKGROUND & OBJECTIVES: The role of oxidative stress in the development of diabetes mellitus and its vascular complications are extensively studied. Hyperglycaemia causes oxidative damage by generation of reactive oxygen species and results in the development of complications. The present study was undertaken with the objective of exploring the anti-hyperglycaemic potential of polyphenolic enriched extract of Ichnocarpus frutescens in streptozotocin induced (n-STZ) neonatal diabetic rats (pups) for six weeks and to study oxidative stress and antioxidant status. METHODS: Two days old pups were rendered diabetic by single injection of streptozotocin (90 mg/kg body wt, ip). At the end of the treatment period, the level of blood glucose, serum biochemical markers, serum lipid levels and liver malondialdehyde, tissue antioxidant levels were measured. RESULTS: A marked rise was observed in the levels of fasting blood glucose (230.33 mg/dl), lipid profiles, lipid peroxidative products and a significant decrease in tissue antioxidants (superoxide dismuatase, catalase and reduced glutathione) and serum high density lipoprotein cholesterol levels in STZ treated rats. Oral administration of polyphenolic extract (150 and 300 mg/kg body wt, po) decreased fasting blood glucose levels (187.66 and 170.50 mg/dl, respectively) of STZ-treated diabetic rats significantly (P<0.01), when compared with control rats. In addition, the polyphenolic extract showed favourable effect (P<0.01) on the reduced tissues antioxidants level, liver glycogen level, high density lipoprotein level, with significant (P<0.01) reduction of elevated lipid peroxidation products. Histopathological study of the pancreas showed the protective role of polyphenolic extract. INTERPRETATION & CONCLUSIONS: Our study showed the antioxidant of effect polyphenolic extract of I. frutescens in STZ induced experimental diabetes. The results also suggested that this polyphenolic rich extract could be potentially useful for hyperglycaemia treatment to correct the diabetic state.

Protective effect of Lagenaria siceraria (Mol) against membrane-bound enzyme alterations in isoproterenol-induced cardiac damage in rats.

This study was aimed at evaluating the preventive role of the ethanolic extract of Lagenaria siceraria (Mol) fruit on membrane-bound enzymes, such as sodium potassium-dependent adenosine triphosphatase (Na(+)/K(+) ATPase), calcium-dependent adenosine triphosphatase (Ca(2+) ATPase) and magnesium-dependent adenosine triphosphatase (Mg(2+) ATPase) on isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Male albino Wistar rats were pretreated with the ethanolic extract of L. siceraria (Mol) fruit (125, 250 and 500 mg kg(-1) body weight) for a period of 30 days. After the treatment period, ISO (85mg kg(-1) body weight) was subcutaneously injected into rats at 24-h intervals for 2 days. ISO-induced rats showed a significant (p < 0.05) decrease in the activity of Na(+)/K(+) ATPase and an increase in the activities of Ca(2+) and Mg(2+) ATPases in the heart tissues. Pre-treatment with the ethanolic extract of L. siceraria (Mol) fruit for a period of 30 days exhibited a significant (p < 0.05) effect in ISO-induced rats. Thus, our study shows that the ethanolic extract of L. siceraria (Mol) fruit has membrane-stabilising role in ISO-induced MI in rats.