186 results on '"Srirajaskanthan, Rajaventhan"'
Search Results
152. Iodine Nutrition: Salt Fortification with Iodine
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Hussein, Izzeldin S., Preedy, Victor R., editor, Srirajaskanthan, Rajaventhan, editor, and Patel, Vinood B., editor
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- 2013
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153. The Stability of Water-Soluble Vitamins and Issues in the Fortification of Foods
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Bui, Lan T. T., Small, Darryl M., Coad, Ross, Preedy, Victor R., editor, Srirajaskanthan, Rajaventhan, editor, and Patel, Vinood B., editor
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- 2013
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154. Fortification of Milk with Mineral Elements
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Ocak, Elvan, Rajendram, Rajkumar, Preedy, Victor R., editor, Srirajaskanthan, Rajaventhan, editor, and Patel, Vinood B., editor
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- 2013
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155. Calcium-Fortified Soymilk
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Pathomrungsiyounggul, Pattavara, Lewis, Michael J., Grandison, Alistair S., Preedy, Victor R., editor, Srirajaskanthan, Rajaventhan, editor, and Patel, Vinood B., editor
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- 2013
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156. Commercial Conjugated Linoleic Acid (CLA) Fortified Dairy Products
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Rodríguez-Alcalá, Luis Miguel, Villar-Tajadura, Antonia, Juarez, Manuela, Fontecha, Javier, Preedy, Victor R., editor, Srirajaskanthan, Rajaventhan, editor, and Patel, Vinood B., editor
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- 2013
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157. Fortification of Corn Flour-Derived Products
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Dichi, Isaias, Miglioranza, Lucia Helena Silva, Preedy, Victor R., editor, Srirajaskanthan, Rajaventhan, editor, and Patel, Vinood B., editor
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- 2013
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158. Fortified Margarine and Fat Spreads
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Sioen, Isabelle, Preedy, Victor R., editor, Srirajaskanthan, Rajaventhan, editor, and Patel, Vinood B., editor
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- 2013
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159. Iron-Fortified Drinking Water
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Amancio, Olga Maria Silverio, Braga, Josefina Aparecida Pellegrini, Preedy, Victor R., editor, Srirajaskanthan, Rajaventhan, editor, and Patel, Vinood B., editor
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- 2013
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160. Middle East Perspectives of Food Fortification: Implementation Dynamics and Policy Factors
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Alasfoor, Deena, Preedy, Victor R., editor, Srirajaskanthan, Rajaventhan, editor, and Patel, Vinood B., editor
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- 2013
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161. Heme Iron as Source of Iron in Food Fortification
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Polo, Javier, Rodríguez, Carmen, Preedy, Victor R., editor, Srirajaskanthan, Rajaventhan, editor, and Patel, Vinood B., editor
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- 2013
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162. Millet Flours as a Vehicle for Fortification with Iron and Zinc
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Platel, Kalpana, Preedy, Victor R., editor, Srirajaskanthan, Rajaventhan, editor, and Patel, Vinood B., editor
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- 2013
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163. Iron- and Zinc-Fortified Parboiled Rice
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Prom-u-thai, Chanakan, Rerkasem, Benjavan, Preedy, Victor R., editor, Srirajaskanthan, Rajaventhan, editor, and Patel, Vinood B., editor
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- 2013
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164. Ferric Pyrophosphate as an Alternative Iron Source for Food Fortification
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Salgueiro, María Jimena, Boccio, José, Preedy, Victor R., editor, Srirajaskanthan, Rajaventhan, editor, and Patel, Vinood B., editor
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- 2013
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165. Iron Fortification of Milk and Dairy Products
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Cayot, Philippe, Guzun-Cojocaru, Tatiana, Cayot, Nathalie, Preedy, Victor R., editor, Srirajaskanthan, Rajaventhan, editor, and Patel, Vinood B., editor
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- 2013
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166. Food Fortification Policy in Canada
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Sacco, Jocelyn, Preedy, Victor R., editor, Srirajaskanthan, Rajaventhan, editor, and Patel, Vinood B., editor
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- 2013
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167. Fortified Humanitarian Food-Aid Commodities
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Dunn, Michael L., Preedy, Victor R., editor, Srirajaskanthan, Rajaventhan, editor, and Patel, Vinood B., editor
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- 2013
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168. Current Mandatory Fortificants in Developed Nations Compared to Developing Nations
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Ewen, Scarlett, Vatanparast, Hassan, Preedy, Victor R., editor, Srirajaskanthan, Rajaventhan, editor, and Patel, Vinood B., editor
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- 2013
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169. The Link Between Organizational Bodies and Fortification Strategies and Practice: The Role of the Flour Fortification Initiative
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Zimmerman, Sarah, Baldwin, Robert J., Preedy, Victor R., editor, Srirajaskanthan, Rajaventhan, editor, and Patel, Vinood B., editor
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- 2013
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170. Iodine Fortification and Hyperthyroidism
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Charlotte Cerqueira, Nils Knudsen, Inge Bülow Pedersen, Hans Perrild, Torben Jørgensen, Lars Ovesen, Peter Laurberg, Allan Carlé, Preedy, Victor R., Srirajaskanthan, Rajaventhan, and Patel, Vinood B.
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business.industry ,Offspring ,Thyroid ,Fortification ,Physiology ,chemistry.chemical_element ,Iodine ,medicine.anatomical_structure ,Fetal Stage ,chemistry ,Thyroid hormones ,Medicine ,business ,Iodine intake ,Hormone - Abstract
Iodine is a necessary substrate for the synthesis of thyroid hormones, which are involved in the regulation of almost all metabolic processes in the human body. In the adult, a sufficient production of thyroid hormone is essential to sustain health. In the offspring, a sufficient production is vital for normal development and growth and the most critical stage of iodine requirement is during fetal stage and early childhood.
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- 2013
171. Use and perceived utility of [ 18 F]FDG PET/CT in neuroendocrine neoplasms: A consensus report from the European Neuroendocrine Tumor Society (ENETS) Advisory Board Meeting 2022.
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Ambrosini V, Caplin M, Castaño JP, Christ E, Denecke T, Deroose CM, Dromain C, Falconi M, Grozinsky-Glasberg S, Hicks RJ, Hofland J, Kjaer A, Knigge UP, Kos-Kudla B, Koumarianou A, Krishna B, Lamarca A, Pavel M, Reed NS, Scarpa A, Srirajaskanthan R, Sundin A, Toumpanakis C, and Prasad V
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- Humans, Fluorodeoxyglucose F18, Consensus, Positron-Emission Tomography, Positron Emission Tomography Computed Tomography methods, Neuroendocrine Tumors diagnostic imaging, Neuroendocrine Tumors therapy, Neuroendocrine Tumors pathology
- Abstract
Somatostatin receptor (SST) PET/CT is the gold standard for well-differentiated neuroendocrine tumours (NET) imaging. Higher grades of neuroendocrine neoplasms (NEN) show preferential [18F]FDG (FDG) uptake, and even low-grade NET may de-differentiate over time. FDG PET/CT's prognostic role is widely accepted; however, its impact on clinical decision-making remains controversial and its use varies widely. A questionnaire-based survey on FDG PET/CT use and perceived decision-making utility in NEN was submitted to the ENETS Advisory Board Meeting attendees (November 2022, response rate = 70%). In 3/15 statements, agreement was higher than 75%: (i) FDG was considered useful in NET, irrespective of grade, in case of mis-matched lesions (detectable on diagnostic CT but negative/faintly positive on SST PET/CT), especially if PRRT is contemplated (80%); (ii) in NET G3 if curative surgery is considered (82%); and (iii) in NEC prior to surgery with curative intent (98%). FDG use in NET G3, even in the presence of matched lesions, as a baseline for response assessment was favoured by 74%. Four statements obtained more than 60% consensus: (i) FDG use in NET G3 if locoregional therapy is considered (65%); (ii) in neuroendocrine carcinoma before initiating active therapy as a baseline for response assessment (61%); (iii) biopsy to re-assess tumour grade prior to a change in therapeutic management (68%) upon detection of FDG-positivity on the background of a prior G1-2 NET; (iv) 67% were in favour to reconsider PRRT to treat residual SST-positive lesions after achieving complete remission on FDG of the SST-negative disease component. Multidisciplinary opinion broadly supports the use of FDG PET/CT for characterisation of disease biology and to guide treatment selection across a range of indications, despite the lack of full consensus in many situations. This may reflect existing clinical access due to lack of reimbursement or experience with this investigation, which should be addressed by further research., (© 2023 British Society for Neuroendocrinology.)
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- 2024
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172. Incidence and survival of neuroendocrine neoplasia in England 1995-2018: A retrospective, population-based study.
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White BE, Rous B, Chandrakumaran K, Wong K, Bouvier C, Van Hemelrijck M, George G, Russell B, Srirajaskanthan R, and Ramage JK
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Background: Neuroendocrine neoplasia (NEN) incidence is rising internationally. We aimed to evaluate the epidemiology of NEN in England and examine changes in survival over time., Methods: A retrospective, population-based study using nationally representative data between 1995 and 2018 from the National Cancer Registry and Analysis Service (NCRAS) in England was conducted on 63,949 tumours. Age-standardized incidence was calculated using Office for National Statistics (ONS) data. Overall survival (OS) was calculated using the Kaplan-Meier estimator. Multivariable analysis was performed using an accelerated failure time model., Findings: Of 63,949 cases, 50.5% (32,309) were female. Age-adjusted incidence increased 3.7-fold between 1995 and 2018 from 2.35 to 8.61 per 100,000. In 2018, highest incidence occurred in lung (1.47 per 100,000), small intestine (1.46 per 100,000), pancreas (1.00 per 100,000) and appendix (0.95 per 100,000). In multivariable analysis, age, sex, morphology, stage, site and deprivation were independent predictors of survival ( p < 0.001). Survival of the entire cohort, and by primary site, is improving over time., Interpretation: NEN incidence continues to rise in England with survival improving over time. Relatively high survival compared to other cancers is an issue for long-term outcomes and funding of care., Funding: Data were extracted and transferred using a grant from Neuroendocrine cancer UK., Competing Interests: JKR supervised securing funding for the grant from Neuroendocrine Cancer UK (NCUK) to process the data in the initial planning of the work. CB states that NCUK receives donation, grant and sponsorship money from patients, businesses and not-for-profit organisations. CB is a board member of the International Neuroendocrine Cancer Alliance (INCA). The other authors declare no conflict of interest., (© 2022 The Authors.)
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- 2022
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173. Symptom Diaries of Patients with Midgut Neuroendocrine Tumors Treated with 177 Lu-DOTATATE.
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Strosberg JR, Srirajaskanthan R, El-Haddad G, Wolin EM, Chasen BR, Kulke MH, Bushnell DL, Caplin ME, Baum RP, Hendifar AE, Öberg K, Ruszniewski P, Santoro P, Broberg P, Leeuwenkamp OR, and Krenning EP
- Abstract
We report the impact of
177 Lu DOTATATE treatment on abdominal pain, diarrhea, and flushing, symptoms that patients with advanced midgut neuroendocrine tumors (NETs) often find burdensome. Methods: All patients enrolled in the international randomized phase 3 Neuroendocrine Tumors Therapy (NETTER-1) trial (177 Lu-DOTATATE plus standard-dose octreotide long-acting repeatable [LAR], n = 117; high-dose octreotide LAR, n = 114) were asked to record the occurrence of predefined symptoms in a daily diary. Change from baseline in symptom scores (mean number of days with a symptom) was analyzed using a mixed model for repeated measures. Results: Patients (intent-to-treat) who received177 Lu-DOTATATE experienced a significantly greater decline from baseline in symptom scores than patients who received high-dose octreotide LAR. For177 Lu-DOTATATE, the mean decline in days with abdominal pain, diarrhea, and flushing was 4.10, 4.55, and 4.52 days per 4 weeks, respectively, compared with 0.99, 1.44, and 2.54 days for high-dose octreotide LAR. The mean differences were 3.11 days (95% confidence interval, 1.35-4.88; P = 0.0007) for abdominal pain, 3.11 days (1.18-5.04; P = 0.0017) for diarrhea, and 1.98 days (0.08-3.88; P = 0.0413) for flushing, favoring177 Lu-DOTATATE. A positive repeated measures correlation was found between diary-recorded symptom scores and questionnaire-recorded pain, diarrhea, and flushing. Conclusion: In addition to efficacy and quality of life benefits, symptom diaries from NETTER-1 demonstrated that treatment with177 Lu DOTATATE was associated with statistically significant reductions in abdominal pain, diarrhea, and flushing, constituting the core symptoms of patients with progressive midgut NETs, compared with high-dose octreotide LAR, supporting a beneficial effect of177 Lu DOTATATE on HRQoL., (Copyright © 2021 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)- Published
- 2021
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174. The effect of prophylactic surgery in survival and HRQoL in appendiceal NEN.
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Alexandraki KI, Kaltsas G, Grozinsky-Glasberg S, Oleinikov K, Kos-Kudła B, Kogut A, Srirajaskanthan R, Pizanias M, Poulia KA, Ferreira C, Weickert MO, and Daskalakis K
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- Female, Humans, Neoplasm Recurrence, Local, Surveys and Questionnaires, Appendiceal Neoplasms surgery, Neuroendocrine Tumors surgery, Quality of Life
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Background/aims: Long-term outcomes are understudied in patients with well-differentiated appendiceal neuroendocrine neoplasms (WD-ANENs). We aimed to evaluate the validity of currently applied criteria for completion prophylactic right hemicolectomy (pRHC) and determine its association with patient outcomes, including health-related quality of life (HRQoL)., Methods: Eligible patients from five European referral centers were divided between those who underwent appendectomy alone and those who underwent completion pRHC. HRQoL EORTC-QLC-C30 questionnaires and cross-sectional imaging data were prospectively collected. Age- and sex-matched healthy controls were recruited for HRQoL analysis' validation., Results: We included 166 patients (119 women [71.2%]: mean age at baseline: 31 ± 16 years). Mean follow-up was 50.9 ± 54 months. Most patients (152 [92%]) had tumors ≤20 mm in size. Fifty-eight patients (34.9%) underwent pRHC that in final analysis was regarded as an overtreatment in 38/58 (65.5%). In multivariable analysis, tumor size >20 mm was the only independent predictor for lymph node (LN) involvement (p = 0.002). No mortality was reported, whereas 2-, 5- and 10-year recurrence-free survival in patients subjected to postoperative cross-sectional imaging (n = 136) was 98.5%, 97.8%, and 97.8%, respectively. Global HRQoL was not significantly impaired in patients with WD-ANEN compared with age- and sex-matched healthy individuals (median scores 0.83[0.08-1] vs 0.83[0.4-1], respectively; p = 0.929). Among patients with WD-ANEN impaired social functioning (p = 0.016), diarrhea (p = 0.003) and financial difficulties (0.024) were more frequently reported in the pRHC group., Conclusions: WD-ANEN is a low-malignant neoplasm with unconfirmed associated mortality, low recurrence rate, and overall preserved HRQoL. pRHC comes at a price of excessive surgery, functional HRQoL issues, and diarrhea. The value per se of a prophylactic surgical approach to patients with WD-ANENs <20 mm is challenged.
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- 2020
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175. Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177 Lu-Dotatate: an analysis of the NETTER-1 study.
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Strosberg J, Kunz PL, Hendifar A, Yao J, Bushnell D, Kulke MH, Baum RP, Caplin M, Ruszniewski P, Delpassand E, Hobday T, Verslype C, Benson A, Srirajaskanthan R, Pavel M, Mora J, Berlin J, Grande E, Reed N, Seregni E, Paganelli G, Severi S, Morse M, Metz DC, Ansquer C, Courbon F, Al-Nahhas A, Baudin E, Giammarile F, Taïeb D, Mittra E, Wolin E, O'Dorisio TM, Lebtahi R, Deroose CM, Grana CM, Bodei L, Öberg K, Polack BD, He B, Mariani MF, Gericke G, Santoro P, Erion JL, Ravasi L, and Krenning E
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- Alkaline Phosphatase, Humans, Octreotide adverse effects, Treatment Outcome, Liver Neoplasms radiotherapy, Neuroendocrine Tumors radiotherapy, Organometallic Compounds therapeutic use
- Abstract
Purpose: To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with
177 Lu-Dotatate., Methods: In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression., Results: Significantly prolonged median PFS occurred with177 Lu-Dotatate versus octreotide LAR 60 mg in patients with low (< 25%), moderate (25-50%), and high (> 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the177 Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden., Conclusions:177 Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov : NCT01578239, EudraCT: 2011-005049-11.- Published
- 2020
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176. Quality of life in patients with gastroenteropancreatic tumours: A systematic literature review.
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Watson C, Tallentire CW, Ramage JK, Srirajaskanthan R, Leeuwenkamp OR, and Fountain D
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- Aged, Female, Humans, Middle Aged, Quality of Life, Intestinal Neoplasms therapy, Neuroendocrine Tumors therapy, Pancreatic Neoplasms therapy, Stomach Neoplasms therapy
- Abstract
Background: Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are slow-growing cancers that arise from diffuse endocrine cells in the gastrointestinal tract (GI-NETs) or the pancreas (P-NETs). They are relatively uncommon, accounting for 2% of all gastrointestinal malignancies. The usual treatment options in advanced GEP-NET patients with metastatic disease include chemotherapy, biological therapies, and peptide receptor radionuclide therapy. Understanding the impact of treatment on GEP-NET patients is paramount given the nature of the disease. Health-related quality of life (HRQoL) is increasingly important as a concept reflecting the patients' perspective in conjunction with the disease presentation, severity and treatment., Aim: To conduct a systematic literature review to identify literature reporting HRQoL data in patients with GEP-NETs between January 1985 and November 2019., Methods: The PRISMA guiding principles were applied. MEDLINE, Embase and the Cochrane library were searched. Data extracted from the publications included type of study, patient population data (mid-gut/hind-gut/GI-NET/P-NET), sample size, intervention/comparators, HRQoL instruments, average and data spread of overall and sub-scores, and follow-up time for data collection., Results: Forty-three publications met the inclusion criteria. The heterogeneous nature of the different study populations was evident; the percentage of female participants ranged between 30%-60%, whilst average age ranged from 53.8 to 67.0 years. Eight studies investigated GI-NET patients only, six studies focused exclusively on P-NET patients and the remaining studies involved both patient populations or did not report the location of the primary tumour. The most commonly used instrument was the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 ( n = 28) with consistent results across studies; the GI-NET-specific module Quality of Life Questionnaire-GINET21 was used in six of these studies. A number of randomised trials demonstrated no HRQoL changes between active treatment and placebo arms. The Phase III NETTER-1 study provides the best data available for advanced GEP-NET patients; it shows that peptide receptor radionuclide therapy can significantly improve GEP-NET patients' HRQoL., Conclusion: HRQoL instruments offer a means to monitor patients' general disease condition, disease progression and their physical and mental well-being. Instruments including the commonly used European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and GINET21 lack, however, validation and a defined minimal clinical important difference specifically for GI-NET and P-NET patients., Competing Interests: Conflict-of-interest statement: All the authors declare that they have no competing interests., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)
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- 2020
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177. Health-related quality of life in neuroendocrine neoplasia: a critical review.
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White BE, Druce MR, Grozinsky-Glasberg S, Srirajaskanthan R, Gamper EM, Gray D, Mujica-Mota R, and Ramage JK
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- Humans, Neuroendocrine Tumors psychology, Quality of Life psychology
- Abstract
Incidence of neuroendocrine neoplasia (NEN) is increasing, as is use of health-related quality of life (HRQoL) measurement in clinical trials. Following development of validated questionnaires, HRQoL is widely used to assess outcomes. This review is intended for healthcare professionals and is based on a selection of data published in the last decade. HRQoL is on par with other clinical endpoints such as performance status. Assessments in clinical trials have been particularly useful for monitoring the symptom burden of NEN, for the effects of treatments on patients' lives, and have provided new data allied to the usual clinical endpoints. QoL expressed as quality-adjusted life years (QALYs) have become the most important primary outcome to establish cost-effectiveness in health economic evaluation. From looking at clinical trials over the last 10 years, we see that the quality of HRQoL evidence reported in published studies has improved and, in general, recent studies are likely to be more methodologically robust. Assessment of HRQoL in clinical trials is likely to become a standard part of clinical practice in NEN, as in other cancers. However, clear methods for calculating the clinical meaningfulness of changes in scores are needed. Other limitations of HRQoL measurement include lack of specificity to certain symptom sets and ease of completion and administration. An international group taking a lead on developing HRQoL research specifically in NEN patients is needed to address limitations of the evidence base. In order for greater weight to be placed on HRQoL data, agreement on optimal, validated scoring systems is needed.
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- 2020
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178. Impact of neuroendocrine morphology on cancer outcomes and stage at diagnosis: a UK nationwide cohort study 2013-2015.
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Genus TSE, Bouvier C, Wong KF, Srirajaskanthan R, Rous BA, Talbot DC, Valle JW, Khan M, Pearce N, Elshafie M, Reed NS, Morgan E, Deas A, White C, Huws D, and Ramage J
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- Adult, Aged, Aged, 80 and over, Female, Follow-Up Studies, Humans, Incidence, Intestinal Neoplasms mortality, Intestinal Neoplasms pathology, Lung Neoplasms mortality, Lung Neoplasms pathology, Male, Middle Aged, Mortality, Neoplasm Staging, Neuroendocrine Tumors mortality, Neuroendocrine Tumors pathology, Prognosis, United Kingdom epidemiology, Intestinal Neoplasms diagnosis, Intestinal Neoplasms epidemiology, Lung Neoplasms diagnosis, Lung Neoplasms epidemiology, Neuroendocrine Tumors diagnosis, Neuroendocrine Tumors epidemiology
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Background: The diagnosis of neuroendocrine neoplasms (NENs) is often delayed. This first UK population-based epidemiological study of NENs compares outcomes with non-NENs to identify any inequalities., Methods: Age-standardised incidence rate (ASR), 1-year overall survival, hazard ratios and standardised mortality rates (SMRs) were calculated for all malignant NENs diagnosed 2013-2015 from UK national Public Health records. Comparison with non-NENs assessed 1-year overall survival (1YS) and association between diagnosis at stage IV and morphology., Results: A total of 15,222 NENs were identified, with an ASR (2013-2015 combined) of 8.6 per 100,000 (95% CI 8.5-8.7); 4.6 per 100 000 (95% CI, 4.5-4.7) for gastro-entero-pancreatic (GEP) NENs. The 1YS was 75% (95% CI, 73.9-75.4) varying significantly by sex. Site and morphology were prognostic. NENs (predominantly small cell carcinomas) in the oesophagus, bladder, prostate, and female reproductive organs had a poorer outcome and were three times more likely to be diagnosed at stage IV than non-NENs., Conclusion: Advanced stage at diagnosis with significantly poorer outcomes of some NENs compared with non-NENs at the same anatomical site, highlight the need for improved access to specialist services and targeted service improvement.
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- 2019
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179. The prognosis and management of neuroendocrine neoplasms-related metastatic bone disease: lessons from clinical practice.
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Alexandraki KI, Pizanias M, Uri I, Thomas D, Page T, Kolomodi D, Low CS, Adesanya O, Tsoli M, Gross DJ, Randeva H, Srirajaskanthan R, Grozinsky-Glasberg S, Kaltsas G, and Weickert MO
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- Adult, Aged, Aged, 80 and over, Bone Neoplasms diagnostic imaging, Bone Neoplasms secondary, Disease Management, Female, Humans, Intestinal Neoplasms diagnostic imaging, Intestinal Neoplasms pathology, Male, Middle Aged, Neuroendocrine Tumors diagnostic imaging, Neuroendocrine Tumors secondary, Pancreatic Neoplasms diagnostic imaging, Pancreatic Neoplasms pathology, Prognosis, Tomography, X-Ray Computed, Young Adult, Bone Neoplasms therapy, Diphosphonates therapeutic use, Intestinal Neoplasms therapy, Neuroendocrine Tumors therapy, Pancreatic Neoplasms therapy
- Abstract
Purpose: To study the evolution and optimal management of metastatic bone disease (mBD) in patients with neuroendocrine neoplasms (NENs)., Methods: Seventy-four patients were recruited from four NEN centers in this observational multicenter study., Results: Pancreas and small bowel were the most common primaries (30 and 27%, respectively). Almost all gastrointestinal (GI)-NENs were grades 1 and 2, whereas bronchopulmonary-thymic were atypical carcinoids. Thirty-two (43%) patients had synchronous metastatic bone disease (mBD) and three patients reported bone-specific symptoms; metachronous mBD developed at a median of 35 (range: 4-395) months. Thirty-six (86%) of patients with metachronous mBD had stage IV disease at diagnosis. Somatostatin receptor functional imaging and computed tomography were the modalities mostly used for mBD identification. Fifty-two patients received assessable bone-related therapy (bisphosphonates, denosumab, local radiotherapy, and radionuclide treatment). Improvement in mBD was seen in 5, stable disease in 22, and deterioration in 25 patients. The presence of synchronous mBD and the negative outcome of bone-related therapy negatively affected overall survival (OS). In the multivariate analysis, the stronger predictor of OS was the outcome of bone-related therapy (HR: 4.753; 95% CI: 1.589-14.213). Bisphosphonates therapy was the mostly used bone-specific treatment but its monthly administration did not affect OS. At last follow-up, 39 patients were alive with OS 50 (14-463) months., Conclusions: Early investigation for mBD offers a prognostic marker of patients with NENs, since synchronous mBD has a negative impact on survival. The outcome of bone-related therapy affects OS but the monthly administration of bisphosphonates did not show a benefit over less intense schemes.
- Published
- 2019
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180. Phase 3 Trial of 177 Lu-Dotatate for Midgut Neuroendocrine Tumors.
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Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, Mittra E, Kunz PL, Kulke MH, Jacene H, Bushnell D, O'Dorisio TM, Baum RP, Kulkarni HR, Caplin M, Lebtahi R, Hobday T, Delpassand E, Van Cutsem E, Benson A, Srirajaskanthan R, Pavel M, Mora J, Berlin J, Grande E, Reed N, Seregni E, Öberg K, Lopera Sierra M, Santoro P, Thevenet T, Erion JL, Ruszniewski P, Kwekkeboom D, and Krenning E
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- Aged, Antineoplastic Agents administration & dosage, Antineoplastic Agents adverse effects, Delayed-Action Preparations, Disease-Free Survival, Drug Administration Schedule, Female, Gastrointestinal Neoplasms mortality, Humans, Infusions, Intravenous, Kaplan-Meier Estimate, Male, Middle Aged, Nausea chemically induced, Neuroendocrine Tumors mortality, Octreotide adverse effects, Octreotide therapeutic use, Organometallic Compounds adverse effects, Antineoplastic Agents therapeutic use, Gastrointestinal Neoplasms drug therapy, Neuroendocrine Tumors drug therapy, Octreotide administration & dosage, Octreotide analogs & derivatives, Organometallic Compounds therapeutic use
- Abstract
Background: Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 (
177 Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors., Methods: We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either177 Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) (177 Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here., Results: At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the177 Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the177 Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the177 Lu-Dotatate group and 26 in the control group (P=0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the177 Lu-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame., Conclusions: Treatment with177 Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the177 Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11 .).- Published
- 2017
- Full Text
- View/download PDF
181. Rectal neuroendocrine tumor.
- Author
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Wu J, Srirajaskanthan R, and Ramage J
- Subjects
- Female, Humans, Male, Endoscopy, Gastrointestinal methods, Intestinal Mucosa surgery, Neuroendocrine Tumors surgery, Rectal Neoplasms surgery
- Published
- 2014
- Full Text
- View/download PDF
182. Long-term safety and efficacy of renin-angiotensin blockade in atherosclerotic renal artery stenosis.
- Author
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Sofroniadou S, Kassimatis T, Srirajaskanthan R, Reidy J, and Goldsmith D
- Subjects
- Adult, Aged, Aged, 80 and over, Angioplasty, Angiotensin Receptor Antagonists adverse effects, Angiotensin-Converting Enzyme Inhibitors adverse effects, Cardiovascular Diseases etiology, Disease Progression, Female, Follow-Up Studies, Glomerular Filtration Rate drug effects, Humans, Kaplan-Meier Estimate, Kidney Failure, Chronic etiology, Male, Middle Aged, Proportional Hazards Models, Prospective Studies, Renal Artery Obstruction complications, Renin-Angiotensin System drug effects, Time Factors, Angiotensin Receptor Antagonists therapeutic use, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Atherosclerosis complications, Blood Pressure drug effects, Renal Artery Obstruction physiopathology, Renal Artery Obstruction therapy
- Abstract
Purpose: The activation of the renin-angiotensin-aldosterone system caused by renal ischaemia in atherosclerotic renal artery stenosis (ARAS) may be responsible for serious cardiovascular and renal consequences. The aim of the study was to assess the long-term safety, tolerability and outcomes of the use of angiotensin I-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) in patients with ARAS., Methods: Thirty-six patients with angiographically defined ARAS (managed either with revascularization or only with medical treatment) were prospectively assessed for the safety, tolerability and outcomes of the use of ACEis or ARBs., Results: The mean period of follow-up was 88.9 ± 37.8 months. A statistically significant reduction in systolic and diastolic blood pressure was recorded over time (P < 0.001). While estimated glomerular filtration rate remained almost stable during the study period (0.816), nuclear EDTA-GFR showed a significant reduction over time (P = 0.03). Mean time from diagnosis/intervention to end-stage renal disease for the cohort of 36 patients was 165.38 ± 13.62 months. Mean overall patient survival was 135.36 ± 15.25 months, with fourteen deaths (38.8%) occurring during the observational period. ACEi/ARB therapy was discontinued transiently in only 4 subjects., Conclusions: The use of ACEis/ARBs is safe and effective in patients with ARAS independently of any parameters.
- Published
- 2012
- Full Text
- View/download PDF
183. Novel techniques for imaging and diagnosing neuroendocrine tumours.
- Author
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Srirajaskanthan R and Easdale S
- Subjects
- Humans, Diagnostic Imaging instrumentation, Diagnostic Imaging methods, Neuroendocrine Tumors diagnosis
- Published
- 2011
- Full Text
- View/download PDF
184. An urgent call to the magnetic resonance scanner: potential dangers of capsule endoscopy.
- Author
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Berry PA, Srirajaskanthan R, and Anderson SH
- Subjects
- Adult, Female, Humans, Magnetic Resonance Imaging, Radiography, Abdominal, Capsule Endoscopy, Foreign Bodies diagnosis
- Published
- 2010
- Full Text
- View/download PDF
185. Expression of the HER-1-4 family of receptor tyrosine kinases in neuroendocrine tumours.
- Author
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Srirajaskanthan R, Shah T, Watkins J, Marelli L, Khan K, and Caplin ME
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers, Tumor analysis, Female, Humans, Immunohistochemistry, Male, Middle Aged, Neuroendocrine Tumors mortality, Neuroendocrine Tumors pathology, Prognosis, Receptor, ErbB-4, ErbB Receptors biosynthesis, Neuroendocrine Tumors metabolism, Receptor, ErbB-2 biosynthesis, Receptor, ErbB-3 biosynthesis
- Abstract
The type I receptor tyrosine kinase family comprises four homologous members: Epidermal growth factor receptor (EGFR), HER-2, HER-3 and HER-4. Studies have shown that EGFR and HER-2 play a critical role in oncogenesis. In this study we sought to determine the pattern of expression and the prognostic significance of EGFR, HER-2, HER-3 and HER-4 in a variety of neuroendocrine tumours using immunohistochemistry. HER family receptor expression in 82 paraffin-embedded specimens of neuroendocrine tumours using immunohistochemistry was examined. The pattern and protein expression levels for each receptor were correlated with clinical and pathological parameters. EGFR expression was identified in 86.6% samples, HER-2 was not expressed in any samples, HER-3 was expressed in 8.5% samples and HER-4 was expressed 91.5%. EGFR and HER-4 were co-expressed in 79.3% of cases. HER-3 was correlated with better survival. EGFR was not associated with poor prognosis. This study has demonstrated EGFR, HER-2 and HER-4 expression is not associated with poorer survival. HER-3 expression is correlated with better prognosis. Overexpression of EGFR and HER-4 may offer potential new therapeutic targets.
- Published
- 2010
- Full Text
- View/download PDF
186. The role of 99mTc-depreotide in the management of neuroendocrine tumours.
- Author
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Shah T, Kulakiene I, Quigley AM, Warbey VS, Srirajaskanthan R, Toumpanakis C, Hochhauser D, Buscombe J, and Caplin ME
- Subjects
- Adult, Female, Humans, Male, Middle Aged, Radionuclide Imaging, Radiopharmaceuticals, Reproducibility of Results, Sensitivity and Specificity, Neuroendocrine Tumors diagnostic imaging, Somatostatin analogs & derivatives
- Abstract
Background: In-pentetreotide scan (OctreoScan) is a widely available agent with high sensitivity for imaging neuroendocrine tumours. Negative In-pentetreotide poses diagnostic as well as therapeutic problems in terms of staging and consideration of targeted radionuclide therapy., Aim: To assess the role of Tc-depreotide in patients with negative or weakly positive OctreoScan (Krenning score< or =1; measured on a scale range 0-4). To determine the usefulness of Tc-depreotide scintigraphy for highlighting lesions that may be missed by OctreoScan and/or CT/MRI imaging., Study Design: Prospective analysis of 25 patients with neuroendocrine tumours, with negative or weakly positive In-pentetreotide scans, who were consecutively enrolled to undergo In-pentetreotide and Tc-depreotide imaging. The results were compared with either CT or MRI scans., Results: Histology was available for 20 of 25 patients: of these 40% had high-grade tumours (cellular proliferation marker Ki-67 score >20%), a further 35% had intermediate-grade tumours (Ki-67 2-20%), and the remaining 25% had low-grade tumours (Ki-67 <2%). Fifty-two percent of patients had completely negative and 48% had weakly positive OctreoScan results. Thirty-two percent of these same patients had significantly positive Tc-depreotide scans (Krenning score> or =2), with the histology demonstrating intermediate-grade or high-grade tumours., Conclusion: Tc-depreotide imaging has low sensitivity but is useful in a one-third of OctreoScan-negative patients, displaying significantly better uptake than In-pentetreotide in this patient group. It aids diagnosis by highlighting lesions not seen by OctreoScan and/or CT/MRI imaging, and can possibly identify a group of patients amenable to therapy with radionuclide agents, such as SOM230, targeting somatostatin receptor subtypes 2, 3 and 5.
- Published
- 2008
- Full Text
- View/download PDF
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