262 results on '"M. Caplin"'
Search Results
202. ENETS Consensus Guidelines for the management of patients with digestive neuroendocrine neoplasms: colorectal neuroendocrine neoplasms.
- Author
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Caplin M, Sundin A, Nillson O, Baum RP, Klose KJ, Kelestimur F, Plöckinger U, Papotti M, Salazar R, and Pascher A
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- Humans, Colorectal Neoplasms diagnosis, Colorectal Neoplasms epidemiology, Colorectal Neoplasms therapy, Neuroendocrine Tumors diagnosis, Neuroendocrine Tumors epidemiology, Neuroendocrine Tumors therapy
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- 2012
- Full Text
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203. mTOR inhibitor therapy for patients with carcinoid.
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Rindi G and Caplin M
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- Everolimus, Female, Humans, Male, Sirolimus therapeutic use, Antineoplastic Agents, Hormonal therapeutic use, Carcinoid Tumor drug therapy, Immunosuppressive Agents therapeutic use, Malignant Carcinoid Syndrome drug therapy, Octreotide therapeutic use, Sirolimus analogs & derivatives
- Published
- 2011
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204. Circulating tumor cells and EpCAM expression in neuroendocrine tumors.
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Khan MS, Tsigani T, Rashid M, Rabouhans JS, Yu D, Luong TV, Caplin M, and Meyer T
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- Adult, Aged, Aged, 80 and over, Disease Progression, Epithelial Cell Adhesion Molecule, Female, Humans, Male, Middle Aged, Neuroendocrine Tumors diagnostic imaging, Neuroendocrine Tumors metabolism, Paraffin Embedding, Radiography, Antigens, Neoplasm metabolism, Cell Adhesion Molecules metabolism, Neoplastic Cells, Circulating metabolism, Neuroendocrine Tumors blood
- Abstract
Purpose: Neuroendocrine tumors (NET) are heterogeneous tumors with widely variable survival. It is unknown whether they express EpCAM (epithelial cell adhesion molecule) and thus whether NET circulating tumor cells (CTC) are detectable. We systematically investigated EpCAM expression and CTC detection in patients with metastatic NETs and evaluated the potential of CTCs to predict radiological progression., Experimental Design: EpCAM protein expression was evaluated in 74 samples of formalin-fixed, paraffin-embedded NET tissue by immunohistochemistry. Seventy-nine patients with metastatic NETs (42 midgut, 5 unknown primary, 19 pancreatic, 13 bronchopulmonary) had blood samples drawn for CTC isolation and enumeration utilizing the CellSearch platform. Patients were classified as having progressive or nonprogressive disease on the basis of serial imaging., Results: Strong homogeneous, membranous EpCAM expression was observed in all ileal (n = 26) and pancreatic NETs (n = 16), whereas variable EpCAM expression was observed in bronchopulmonary NETs (n = 13). Forty-three percent of midgut and 21% of pancreatic NETs had CTCs detected with a range of 0-62 and 0-11, respectively. The absence of CTCs was strongly associated with stable disease (P < 0.001). There was a moderate correlation between CTC levels and urinary 5-hydroxyindole acetic acid (r = 0.5, P = 0.007) and between CTC levels and burden of liver metastases (B = 8.91, P < 0.001). There was no or low correlation between CTC levels and Ki-67 (r = 0.08, P = 0.59) and serum chromogranin A (r = 0.246, P = 0.03)., Conclusions: This is the first systematic analysis showing EpCAM expression and CTC detection in NETs. CTCs seem to be associated with progressive disease and may provide useful prognostic information given the variable survival rates in these tumors., (©2011 AACR.)
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- 2011
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205. Use of molecular imaging to differentiate liver metastasis of colorectal cancer metastasis from neuroendocrine tumor origin.
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Desai K, Watkins J, Woodward N, Quigley AM, Toumpanakis C, Bomanji J, and Caplin M
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- Biopsy, Colorectal Neoplasms diagnosis, Diagnosis, Differential, Fluorodeoxyglucose F18, Humans, Liver Neoplasms diagnosis, Male, Middle Aged, Neoplasms, Multiple Primary diagnosis, Neoplasms, Multiple Primary pathology, Neuroendocrine Tumors diagnosis, Organometallic Compounds, Pancreatic Neoplasms diagnosis, Positron-Emission Tomography methods, Colorectal Neoplasms pathology, Liver Neoplasms secondary, Neuroendocrine Tumors pathology, Pancreatic Neoplasms pathology
- Abstract
Synchronous malignant neoplasms in a single patient are well documented in the literature. It is also recognized that there is increasing incidence of synchronous non-neuroendocrine neoplasm in patients with neuroendocrine tumor (NET). We present a case, of a patient with synchronous colorectal cancer and pancreatic NET, both cancers presenting with liver metastasis. By using 18F-FDG PET and 68Ga-DOTATATE PET imaging, we showed 2 different tumor types within the liver, which was subsequently confirmed on liver biopsy. This case report shows the utility of molecular imaging using different PET peptides. These newer modalities are useful in understanding the biology of the NET and in determining the best patient management.
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- 2011
- Full Text
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206. Distribution pattern of 68Ga-DOTATATE in disease-free patients.
- Author
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Shastry M, Kayani I, Wild D, Caplin M, Visvikis D, Gacinovic S, Reubi JC, and Bomanji JB
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- Adolescent, Adult, Aged, Aged, 80 and over, Biological Transport, Female, Health, Humans, Male, Middle Aged, Positron-Emission Tomography, Receptors, Somatostatin metabolism, Reference Values, Tomography, X-Ray Computed, Young Adult, Organometallic Compounds pharmacokinetics
- Abstract
Purpose: 68Ga-DOTA-DPhe1,Tyr3-octreotate (68Ga-DOTATATE) is a somatostatin analogue that shows high affinity for somatostatin receptor subtype 2 (sst2) and has been used for imaging neuroendocrine tumours. However, normal uptake patterns and potential pitfalls have not been described with this high-sensitivity radiotracer. The aim of this study was therefore to outline the normal distribution pattern of 68Ga-DOTATATE in disease-free patients, to provide standardized uptake values (SUVs) of various organs and to compare our results with the current knowledge on sst2 receptor expression in vitro., Methods: 68Ga-DOTATATE PET/computed tomography was performed in 42 patients (15 men and 27 women). Approximately 145 MBq of tracer was injected intravenously and imaging was performed using a GE Discovery ST PET/computed tomography scanner. SUVs were calculated on the reconstructed images for various organs., Results: 68Ga-DOTATATE uptake was noted in the sst2-expressing organs such as pituitary, thyroid, stomach wall, spleen, adrenals, kidneys, pancreas and prostate and in the liver and salivary glands, with excreted activity in the bowel and in the pelvicalyceal system of the kidneys and urinary bladder. The SUVs ranged from 0.1 to 48.8 in the organs considered. Potential pitfalls in interpreting the 68Ga-DOTATATE uptake in organs such as thyroid, pancreas lymph nodes and bowel were identified., Conclusion: This study shows the distribution pattern of 68Ga-DOTATATE outlines the range of SUVs for various organs in disease-free patients and identifies some of the potential pitfalls encountered during imaging.
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- 2010
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207. NANETS consensus guidelines for the diagnosis of neuroendocrine tumor.
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Vinik AI, Woltering EA, Warner RR, Caplin M, O'Dorisio TM, Wiseman GA, Coppola D, and Go VL
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- Biomarkers, Tumor blood, Biomarkers, Tumor urine, Chromogranin A blood, Humans, Hydroxyindoleacetic Acid urine, Neuroendocrine Tumors diagnosis
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- 2010
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208. ENETS consensus guidelines for the management of bone and lung metastases from neuroendocrine tumors.
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Kos-Kudła B, O'Toole D, Falconi M, Gross D, Klöppel G, Sundin A, Ramage J, Oberg K, Wiedenmann B, Komminoth P, Van Custem E, Mallath M, Papotti M, and Caplin M
- Subjects
- Bone Neoplasms therapy, Humans, Lung Neoplasms therapy, Bone Neoplasms secondary, Digestive System Neoplasms pathology, Lung Neoplasms secondary, Neuroendocrine Tumors pathology
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- 2010
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209. Comparison of (68)Ga-DOTATATE and (18)F-fluorodeoxyglucose PET/CT in the detection of recurrent medullary thyroid carcinoma.
- Author
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Conry BG, Papathanasiou ND, Prakash V, Kayani I, Caplin M, Mahmood S, and Bomanji JB
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- Adult, Aged, Female, Humans, Male, Middle Aged, Radiopharmaceuticals, Reproducibility of Results, Sensitivity and Specificity, Subtraction Technique, Thyroid Gland diagnostic imaging, Carcinoma, Medullary diagnosis, Fluorodeoxyglucose F18, Neoplasm Recurrence, Local diagnosis, Organometallic Compounds, Positron-Emission Tomography methods, Thyroid Neoplasms diagnosis, Tomography, X-Ray Computed methods
- Abstract
Purpose: This was a retrospective study to detect and map the extent of disease in recurrent medullary thyroid carcinoma (MTC) using the novel PET somatostatin analogue (68)Ga-DOTATATE and conventional (18)F-FDG positron emission tomography/computed tomography (PET/CT)., Methods: Eighteen patients (13 men, 5 women, median age: 54 years) who had previously been operated on for MTC and presented with biochemical (raised calcitonin levels) and/or imaging evidence of recurrence underwent both (68)Ga-DOTATATE and (18)F-FDG PET/CT within a maximum interval of 4 weeks (median interval of 1 week). (68)Ga-DOTATATE- and (18)F-FDG-avid lesions were recorded per patient as well as per region in six distinct regions: (1) thyroid bed-local recurrence, (2) cervical lymph nodes, (3) mediastinum, (4) lungs, (5) liver and (6) bones. The (68)Ga-DOTATATE and (18)F-FDG PET/CT findings were classified as positive or negative on visual interpretation. These findings were further characterised as concordant or discordant, depending on whether there was agreement or discrepancy in imaging with the two radiotracers. A separate analysis of the unenhanced CT component of the examination was performed. Verification of the lesions was achieved by histopathological analysis, further imaging studies and clinical follow-up., Results: (68)Ga-DOTATATE PET/CT imaging achieved disease detection in 13 of 18 and (18)F-FDG PET/CT in 14 of 18 patients. These results corresponded to per-patient sensitivities of 72.2% [95% confidence interval (CI): 46.4-89.3%] for (68)Ga-DOTATATE versus 77.8% (95% CI: 51.9-92.6%) for (18)F-FDG (non-significant difference). (18)F-FDG revealed a total of 28 metastatic MTC regions and (68)Ga-DOTATATE 23 regions. In ten patients a discordant tracer pattern of per-region and/or per-lesion distribution of recurrent disease was observed, while in four patients a concordant pattern was noted (no lesions were detected by either modality in the remaining four patients)., Conclusion: Neither (18)F-FDG nor (68)Ga-DOTATATE PET/CT can fully map the extent of disease in patients with recurrent MTC, although (18)F-FDG PET/CT may identify more lesions. However, (68)Ga-DOTATATE PET/CT can be a useful complementary imaging tool and may identify patients suitable for consideration of targeted radionuclide somatostatin analogue therapy.
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- 2010
- Full Text
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210. A comparison of 68Ga-DOTATATE and 18F-FDG PET/CT in pulmonary neuroendocrine tumors.
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Kayani I, Conry BG, Groves AM, Win T, Dickson J, Caplin M, and Bomanji JB
- Subjects
- Adult, Aged, Aged, 80 and over, Biological Transport, Female, Humans, Lung Neoplasms metabolism, Lung Neoplasms pathology, Male, Middle Aged, Neuroendocrine Tumors metabolism, Neuroendocrine Tumors pathology, Positron-Emission Tomography, Receptors, Somatostatin metabolism, Retrospective Studies, Tomography, X-Ray Computed, Fluorodeoxyglucose F18 metabolism, Lung Neoplasms diagnostic imaging, Neuroendocrine Tumors diagnostic imaging, Organometallic Compounds metabolism
- Abstract
Unlabelled: Our purpose was to compare the performance of (68)Ga-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-d-Phe(1),Tyr(3)-octreotate (DOTATATE), a novel selective somatostatin receptor 2 PET ligand, and (18)F-FDG in the detection of pulmonary neuroendocrine tumors using PET/CT, with correlation of uptake and tumor grade on histology., Methods: The imaging findings of the first 18 consecutive patients (8 men and 10 women) with pulmonary neuroendocrine tumors (11 typical carcinoids, 2 atypical carcinoids, 1 large cell neuroendocrine tumor, 1 small cell neuroendocrine carcinoma, 1 non-small cell lung cancer with neuroendocrine differentiation, and 2 cases of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia) who underwent (68)Ga-DOTATATE and (18)F-FDG PET/CT were reviewed. In all cases, the diagnosis was established on histology., Results: Of 18 patients, 15 had primary tumors (median size, 2.7 cm; range, 0.5-8 cm) and 3 had recurrent tumors. All typical carcinoids showed high uptake of (68)Ga-DOTATATE (maximum standardized uptake value [SUV(max)] >or= 8.2), but 4 of 11 showed negative or minimal (18)F-FDG uptake (SUV(max) = 1.7-2.9). All tumors of higher grade showed high uptake of (18)F-FDG (SUV(max) >or= 11.7), but 3 of 5 showed only minimal accumulation of (68)Ga-DOTATATE (SUV(max) = 2.2-2.8). Neither case of diffuse idiopathic pulmonary neuroendocrine cell hyperplasia showed uptake of (68)Ga-DOTATATE or (18)F-FDG. Typical carcinoids showed significantly higher uptake of (68)Ga-DOTATATE and significantly less uptake of (18)F-FDG than did tumors of higher grade (P = 0.002 and 0.005). There was no instance of false-positive uptake of (68)Ga-DOTATATE, but there were 3 sites of (18)F-FDG uptake secondary to inflammation. (68)Ga-DOTATATE was superior to (18)F-FDG in discriminating endobronchial tumor from distal collapsed lung (P = 0.02)., Conclusion: Typical bronchial carcinoids showed higher and more selective uptake of (68)Ga-DOTATATE than of (18)F-FDG. Atypical carcinoids and higher grades had less (68)Ga-DOTATATE avidity but were (18)F-FDG-avid.
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- 2009
- Full Text
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211. Biochemical testing for neuroendocrine tumors.
- Author
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Vinik AI, Silva MP, Woltering EA, Go VL, Warner R, and Caplin M
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- Chromogranin A analysis, Disease Progression, Humans, Neuroendocrine Tumors pathology, Neurokinin A analysis, Pancreatic Hormones analysis, Predictive Value of Tests, Prognosis, Biomarkers, Tumor analysis, Neuroendocrine Tumors diagnosis, Neuroendocrine Tumors metabolism
- Abstract
In this review, we focus on the use of biochemical markers for the diagnosis of neuroendocrine tumors and exclusion of conditions that masquerade as neuroendocrine tumors. In addition, we outline the use of biochemical markers for follow-up, response to intervention, and determination of prognosis. Previous publications have focused only on markers specific to certain tumor types, but the uniqueness of this chapter is that it presents a new approach ranging from biochemical markers that relate to symptoms to the use of markers that facilitate decision making with regard to optimizing the choices of therapy from the complex arrays of intervention, The sequence of presentation in this chapter is first to provide the usual view, that is, biochemical markers of each tumor type and thereafter the diagnosis of the underlying condition or exclusion thereof and finally the algorithm for their use from the clinical presentation to the suspected diagnosis and the biochemical markers to monitor progression and therapeutic choice. There is also a specific description of the properties of the most important biochemical markers and 2 complications, bone metastasis and carcinoid heart disease, from the biochemical point of view.
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- 2009
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212. Midgut neuroendocrine tumours with liver metastases: results of the UKINETS study.
- Author
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Ahmed A, Turner G, King B, Jones L, Culliford D, McCance D, Ardill J, Johnston BT, Poston G, Rees M, Buxton-Thomas M, Caplin M, and Ramage JK
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- Adolescent, Adult, Aged, Aged, 80 and over, Cause of Death, Female, Follow-Up Studies, Humans, Intestinal Neoplasms diagnosis, Intestinal Neoplasms therapy, Ireland, Liver Neoplasms diagnosis, Liver Neoplasms therapy, Male, Middle Aged, Neuroendocrine Tumors diagnosis, Neuroendocrine Tumors therapy, Prognosis, Retrospective Studies, Survival Analysis, Treatment Outcome, United Kingdom, Young Adult, Intestinal Neoplasms mortality, Intestinal Neoplasms pathology, Liver Neoplasms mortality, Liver Neoplasms secondary, Neuroendocrine Tumors mortality, Neuroendocrine Tumors pathology
- Abstract
We intended to identify the prognostic factors and the results of interventions on patients with liver metastatic midgut carcinoids. Five institutions that are part of United Kingdom and Ireland neuroendocrine tumour (NET) group took part in this study. Patients were included if they had histology proven NET of midgut origin and liver metastases at the time of the study. Clinical and biochemical data were collected retrospectively from hospital charts, pathology reports, radiology reports and biochemistry records for each patient. Three hundred and sixty patients were included in the study. The median survival from date of diagnosis was 7.69 years (confidence interval (CI) 6.40-8.99) and 5.95 years (CI 5.02-6.88) from date of diagnosis of liver metastases. On univariate analysis, increasing age at diagnosis, increasing urinary hydroxyindole acetic acid levels, increasing plasma chromogranin A levels, high Ki67, high tumour volume and treatment with chemotherapy were identified as factors associated with a significantly poorer outcome. Resection of liver metastases, resection of small bowel primary, treatment with somatostatin analogue therapy and treatment with peptide receptor therapy were associated with improved prognosis. Multivariate analysis revealed that age at diagnosis (P=0.014), Ki67 level (P=0.039) and resection of primary (P=0.015) were independent predictors of survival. This is the largest study to our knowledge looking specifically at the prognosis and clinical course of patients with liver metastatic midgut NETs. For the first time, we have shown that Ki67 and resection of primary are independent predictors of survival for this group of patients.
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- 2009
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213. Proceedings of the IASLC International Workshop on Advances in Pulmonary Neuroendocrine Tumors 2007.
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Lim E, Goldstraw P, Nicholson AG, Travis WD, Jett JR, Ferolla P, Bomanji J, Rusch VW, Asamura H, Skogseid B, Baudin E, Caplin M, Kwekkeboom D, Brambilla E, and Crowley J
- Subjects
- Humans, Lung Neoplasms diagnosis, Lung Neoplasms therapy, Neuroendocrine Tumors diagnosis, Neuroendocrine Tumors therapy
- Abstract
The International Association for the Study of Lung Cancer, (IASLC) International Congress on Advances in Pulmonary Neuroendocrine Tumors was a two-day meeting held at the Royal Brompton Hospital in London, United Kingdom on the thirteenth and forteenth of December 2007. The meeting was led by 14 member international faculty-in the disciplines of pathology, surgery, medicine, oncology, endocrinology, nuclear medicine, diagnostic imaging, and biostatistics. The aims were twofold, as an educational meeting, and to develop the IASLC International Pulmonary Neuroendocrine Tumors Registry. The meeting highlighted the difference in presentation of the tumors, management options for early and advanced stage disease including the use of novel agents and approaches. The need, process, and approach to an International Registry of Pulmonary Neuroendocrine Tumors were emphasized. International collaboration to develop a retrospective registry, prospective data collection, virtual tissue bank, and collaborative clinical trials were universally agreed as the best way to advance our understanding and treatment of these rare tumors.
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- 2008
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214. Functional imaging of neuroendocrine tumors with combined PET/CT using 68Ga-DOTATATE (DOTA-DPhe1,Tyr3-octreotate) and 18F-FDG.
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Kayani I, Bomanji JB, Groves A, Conway G, Gacinovic S, Win T, Dickson J, Caplin M, and Ell PJ
- Subjects
- Adolescent, Adult, Aged, Female, Gallium, Humans, Male, Middle Aged, Positron-Emission Tomography, Prognosis, Retrospective Studies, Survival Rate, Tomography, X-Ray Computed, Fluorodeoxyglucose F18, Neuroendocrine Tumors diagnostic imaging, Organometallic Compounds, Radiopharmaceuticals
- Abstract
Background: The aim was to assess the relevant distribution of the novel PET tracer (68)Ga-DOTATATE in neuroendocrine tumors (NETs) with combined positron emission tomography / computed tomography (PET/CT) and compare its performance with that of (18)F-FDG PET/CT., Methods: The imaging findings with (68)Ga-DOTATATE and (18)F-FDG on 38 consecutive patients with a diagnosis of primary or recurrent NET were compared and correlated with tumor grade on histology based on ki67 and mitotic index., Results: The sensitivity of (68)Ga-DOTATATE PET/CT was 82% (31 of 38) and that of (18)F-FDG PET/CT was 66% (25 of 38). The sensitivity of combined (68)Ga-DOTATATE and (18)F-FDG PET/CT was 92% (35 of 38). There was greater uptake of (68)Ga-DOTATATE than (18)F-FDG in low-grade NET (median SUV 29 vs 2.9, P < .001). In high-grade NET there was higher uptake of (18)F-FDG over (68)Ga-DOTATATE (median SUV 11.7 vs 4.4, P = .03). There was a significant correlation with predominant tumor uptake of (68)Ga-DOTATATE or (18)F-FDG and tumor grade on histology (P < .0001)., Conclusions: (68)Ga-DOTATATE PET/CT is a useful novel imaging modality for NETs and is superior to (18)F-FDG for imaging well-differentiated NET. Functional imaging with both (68)Ga-DOTATATE and (18)F-FDG has potential for a more comprehensive tumor assessment in intermediate- and high-grade tumors., ((c) 2008 American Cancer Society.)
- Published
- 2008
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215. Gastroenteropancreatic neuroendocrine tumours.
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Modlin IM, Oberg K, Chung DC, Jensen RT, de Herder WW, Thakker RV, Caplin M, Delle Fave G, Kaltsas GA, Krenning EP, Moss SF, Nilsson O, Rindi G, Salazar R, Ruszniewski P, and Sundin A
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- Animals, Biomarkers, Tumor, Humans, Molecular Biology, Protein-Tyrosine Kinases antagonists & inhibitors, Somatostatin analogs & derivatives, Somatostatin metabolism, Somatostatin therapeutic use, Carcinoma, Neuroendocrine classification, Carcinoma, Neuroendocrine metabolism, Carcinoma, Neuroendocrine pathology, Gastrointestinal Neoplasms metabolism, Gastrointestinal Neoplasms physiopathology, Gastrointestinal Neoplasms therapy, Pancreatic Neoplasms metabolism, Pancreatic Neoplasms physiopathology, Pancreatic Neoplasms therapy
- Abstract
Gastroenteropancreatic (GEP) neuroendocrine tumours (NETs) are fairly rare neoplasms that present many clinical challenges. They secrete peptides and neuroamines that cause distinct clinical syndromes, including carcinoid syndrome. However, many are clinically silent until late presentation with mass effects. Investigation and management should be highly individualised for a patient, taking into consideration the likely natural history of the tumour and general health of the patient. Management strategies include surgery for cure (which is achieved rarely) or for cytoreduction, radiological intervention (by chemoembolisation and radiofrequency ablation), chemotherapy, and somatostatin analogues to control symptoms that result from release of peptides and neuroamines. New biological agents and somatostatin-tagged radionuclides are under investigation. The complexity, heterogeneity, and rarity of GEP NETs have contributed to a paucity of relevant randomised trials and little or no survival increase over the past 30 years. To improve outcome from GEP NETs, a better understanding of their biology is needed, with emphasis on molecular genetics and disease modeling. More-reliable serum markers, better tumour localisation and identification of small lesions, and histological grading systems and classifications with prognostic application are needed. Comparison between treatments is currently very difficult. Progress is unlikely to occur without development of centers of excellence, with dedicated combined clinical teams to coordinate multicentre studies, maintain clinical and tissue databases, and refine molecularly targeted therapeutics.
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- 2008
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216. TNM staging of foregut (neuro)endocrine tumors: a consensus proposal including a grading system.
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Rindi G, Klöppel G, Alhman H, Caplin M, Couvelard A, de Herder WW, Erikssson B, Falchetti A, Falconi M, Komminoth P, Körner M, Lopes JM, McNicol AM, Nilsson O, Perren A, Scarpa A, Scoazec JY, and Wiedenmann B
- Subjects
- Biomarkers, Tumor analysis, Digestive System Neoplasms chemistry, Digestive System Neoplasms classification, Humans, Lymph Nodes chemistry, Lymph Nodes pathology, Mitotic Index, Neoplasm Metastasis diagnosis, Neoplasm Staging standards, Neuroendocrine Tumors chemistry, Neuroendocrine Tumors classification, Digestive System Neoplasms diagnosis, Neoplasm Staging methods, Neuroendocrine Tumors diagnosis
- Abstract
The need for standards in the management of patients with endocrine tumors of the digestive system prompted the European Neuroendocrine Tumor Society (ENETS) to organize a first Consensus Conference, which was held in Frascati (Rome) and was based on the recently published ENETS guidelines on the diagnosis and treatment of digestive neuroendocrine tumors (NET). Here, we report the tumor-node-metastasis proposal for foregut NETs of the stomach, duodenum, and pancreas that was designed, discussed, and consensually approved at this conference. In addition, we report the proposal for a working formulation for the grading of digestive NETs based on mitotic count and Ki-67 index. This proposal, which needs to be validated, is meant to help clinicians in the stratification, treatment, and follow-up of patients.
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- 2006
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217. Novel markers of cell kinetics to evaluate progression from cirrhosis to hepatocellular carcinoma.
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Quaglia A, McStay M, Stoeber K, Loddo M, Caplin M, Fanshawe T, Williams G, and Dhillon A
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- Adult, Biomarkers, Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular metabolism, Cell Cycle Proteins genetics, Cell Cycle Proteins metabolism, Cell Transformation, Neoplastic, Disease Progression, Geminin, Gene Expression Regulation, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, Ki-67 Antigen genetics, Ki-67 Antigen metabolism, Kinetics, Liver Cirrhosis genetics, Liver Cirrhosis metabolism, Liver Neoplasms genetics, Liver Neoplasms metabolism, Male, Middle Aged, Minichromosome Maintenance Complex Component 2, Nuclear Proteins genetics, Nuclear Proteins metabolism, Carcinoma, Hepatocellular physiopathology, Cell Cycle, Liver Cirrhosis physiopathology, Liver Neoplasms physiopathology
- Abstract
Background: We investigated cell cycle kinetics of nodular lesions in cirrhosis to differentiate hepatocellular carcinoma (HCC) from its precursor lesions., Methods: Twelve small HCC, 10 regenerative (RN), six large regenerative (LRN), and five dysplastic nodules (DN), identified in explant cirrhotic livers of five consecutive patients transplanted at Royal Free Hospital in 2002. Immunoperoxidase for MCM2, geminin and Ki67 was performed and the percentage of positive cells counted., Results: The proportion of cells expressing MCM2 was more than those expressing Ki67, which in turn was more than those expressing geminin (overall median=16%, 2% and 0.5%, respectively, P<0.001). There was a statistically significant trend of increasing Ki67 expression (P=0.006), from RN to HCC; this trend was not statistically significant for geminin (P=0.18) or MCM2 (P=0.51). The median percentage of cells expressing Ki67 was 1% in RN, 0.5% in LRN, 2.2% in DN and 5.4% in HCC. The combination of these markers identified four different cell kinetics patterns: 'resting' (G0 cells: MCM2 -ve, Ki67 -ve, geminin -ve); 'licensed' (MCM2 +ve, Ki67 -ve, geminin -ve); 'slowly growing' (G1 phase arrest, MCM2 +ve, Ki67 +ve, low (0.4%) geminin) and expanding (MCM2 +ve, Ki67 +ve, geminin +ve) nodules., Conclusions: The combination of MCM2, geminin and Ki67 could represent a valuable tool in the understanding of HCC progression in cirrhosis.
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- 2006
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218. Interaction of the epidermal growth factor receptor and the DNA-dependent protein kinase pathway following gefitinib treatment.
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Friedmann BJ, Caplin M, Savic B, Shah T, Lord CJ, Ashworth A, Hartley JA, and Hochhauser D
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- Androstadienes pharmacology, Androstadienes therapeutic use, Animals, Antineoplastic Combined Chemotherapy Protocols, Cell Line, Tumor, Cell Nucleus enzymology, Cytosol enzymology, DNA metabolism, DNA-Activated Protein Kinase genetics, Etoposide therapeutic use, Gefitinib, Humans, Protein Kinase Inhibitors pharmacology, RNA, Small Interfering genetics, RNA, Small Interfering pharmacology, Rats, Wortmannin, Antineoplastic Agents therapeutic use, Cisplatin therapeutic use, DNA-Activated Protein Kinase antagonists & inhibitors, DNA-Activated Protein Kinase metabolism, ErbB Receptors metabolism, Neoplasms drug therapy, Protein Kinase Inhibitors therapeutic use, Quinazolines therapeutic use
- Abstract
The epidermal growth factor receptor (EGFR) is an important target for cancer therapy. We previously showed that the EGFR inhibitor gefitinib modulated repair of DNA damage following exposure to cisplatin and etoposide involving the DNA-dependent protein kinase (DNA-PK) pathway. In this study, we specifically investigated the effect of EGFR inhibition by gefitinib on functional activity of DNA-PK in cancer cell lines and the interaction between EGFR and DNA-PK. The effects of DNA-PK inhibition by wortmannin and small interfering RNA to the catalytic subunit of DNA-PK (DNA-PK(CS)) on cell proliferation and DNA interstrand cross-link repair were investigated in the human MCF-7 breast cancer cell line and compared with the effects of gefitinib. DNA-PK activity was quantitated and expression measured by immunoblotting following gefitinib treatment. Immunoprecipitation experiments were done with and without gefitinib in MCF-7 cells, the AR42J pancreas cell line with high EGFR, and the human MDA-453 breast cancer cell line expressing low EGFR. Nuclear and cytoplasmic extracts were immunoblotted with antibody to DNA-PK(CS) to determine if gefitinib treatment altered cellular expression. Reduction of DNA-PK activity by wortmannin and expression by small interfering RNA to DNA-PK(CS) sensitized cells to cisplatin and inhibited repair of cisplatin-induced interstrand cross-links. Gefitinib treatment reduced DNA-PK activity in MCF-7 and AR42J but not MDA-453 cells. Immunoprecipitation experiments showed interaction between EGFR and DNA-PK(CS) in a dose-dependent and time-dependent manner following gefitinib treatment in MCF-7 and AR42J but not MDA-453 cells. Gefitinib treatment reduced nuclear expression and increased cytosolic expression of DNA-PK(CS) in MCF-7 and AR42J but not MDA-453 cells. Treatment with gefitinib modulates association of EGFR and DNA-PK(CS). This is correlated with decreased function of DNA-PK(CS). Inhibition of DNA-PK(CS) may be an important factor in sensitization to chemotherapy and radiation following treatment with inhibitors of the EGFR pathway.
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- 2006
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219. Primary mucinous carcinoid tumour of the ovary: a case report.
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Karavolos S, Caplin M, Benjamin E, Crow J, and Mould T
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- Adenocarcinoma, Mucinous diagnosis, Adenocarcinoma, Mucinous pathology, Adult, Carcinoid Tumor diagnosis, Carcinoid Tumor pathology, Diagnosis, Differential, Female, Humans, Leiomyoma diagnosis, Ovarian Neoplasms diagnosis, Ovarian Neoplasms pathology, Prognosis, Treatment Outcome, Adenocarcinoma, Mucinous surgery, Carcinoid Tumor surgery, Ovarian Neoplasms surgery
- Abstract
Primary ovarian carcinoid tumours of the ovary are rare and represent less than 0.1% of ovarian malignancy. The evidence to guide treatment and prognosis of these tumours is limited. We report a case of primary ovarian mucinous carcinoid tumour, of the atypical category, in a 34-year-old nulliparous woman. Only three such cases have previously been reported. At four years from presentation, she has no signs of metastatic disease, despite delayed primary surgery and then initial conservative management. At present surgical excision with close follow-up appears to be the management of choice. This case adds to the body of evidence and demonstrates a possible good prognosis with non-aggressive behaviour in the atypical mucinous carcinoid group.
- Published
- 2006
220. Rare functioning pancreatic endocrine tumors.
- Author
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O'Toole D, Salazar R, Falconi M, Kaltsas G, Couvelard A, de Herder WW, Hyrdel R, Nikou G, Krenning E, Vullierme MP, Caplin M, Jensen R, and Eriksson B
- Subjects
- Humans, Neuroendocrine Tumors epidemiology, Neuroendocrine Tumors genetics, Pancreatic Neoplasms epidemiology, Pancreatic Neoplasms physiopathology, Pancreatic Neoplasms therapy, Neuroendocrine Tumors diagnosis, Neuroendocrine Tumors therapy, Pancreatic Neoplasms diagnosis
- Published
- 2006
- Full Text
- View/download PDF
221. Endocrine tumours of the gastrointestinal tract. Biotherapy for metastatic endocrine tumours.
- Author
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Shah T and Caplin M
- Subjects
- Antineoplastic Agents, Hormonal administration & dosage, Antineoplastic Agents, Hormonal adverse effects, Antineoplastic Agents, Hormonal therapeutic use, Drug Therapy, Combination, Gastrointestinal Agents administration & dosage, Gastrointestinal Agents therapeutic use, Gels, Humans, Interferon-alpha therapeutic use, Octreotide administration & dosage, Octreotide adverse effects, Octreotide therapeutic use, Peptides, Cyclic administration & dosage, Peptides, Cyclic therapeutic use, Quality of Life, Somatostatin administration & dosage, Somatostatin therapeutic use, Carcinoma, Neuroendocrine drug therapy, Carcinoma, Neuroendocrine secondary, Gastrointestinal Neoplasms drug therapy, Gastrointestinal Neoplasms pathology, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms pathology, Somatostatin analogs & derivatives
- Abstract
Somatostatin analogues have been the mainstay of symptomatic management of patients with neuroendocrine tumours (NETs) for two decades with the main mechanism of action being inhibition of peptide release. Evidence base for interferon use is perhaps less clear. It may contribute to symptom control by abrogating peptide release, and there is some evidence that it has an anti-proliferative action. Combination of somatostatin analogues and interferon provides symptom control, mainly by effecting a reduction in the amount of circulating, physiologically active, peptide hormones. Treatment can also provide disease stabilisation in a proportion of patients. In a minority of patients treatment may lead to partial response.
- Published
- 2005
- Full Text
- View/download PDF
222. Guidelines for the management of gastroenteropancreatic neuroendocrine (including carcinoid) tumours.
- Author
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Ramage JK, Davies AH, Ardill J, Bax N, Caplin M, Grossman A, Hawkins R, McNicol AM, Reed N, Sutton R, Thakker R, Aylwin S, Breen D, Britton K, Buchanan K, Corrie P, Gillams A, Lewington V, McCance D, Meeran K, and Watkinson A
- Subjects
- Algorithms, Antineoplastic Agents therapeutic use, Carcinoid Tumor diagnosis, Carcinoid Tumor etiology, Catheter Ablation methods, Clinical Protocols, Diagnostic Imaging methods, Embolization, Therapeutic methods, Gastrointestinal Neoplasms diagnosis, Gastrointestinal Neoplasms etiology, Humans, Neoplasm Metastasis diagnosis, Neoplasm Metastasis therapy, Neuroendocrine Tumors diagnosis, Neuroendocrine Tumors etiology, Pancreatic Neoplasms diagnosis, Pancreatic Neoplasms etiology, Prognosis, Quality of Life, Specimen Handling, Survival Analysis, Treatment Outcome, Carcinoid Tumor therapy, Gastrointestinal Neoplasms therapy, Neuroendocrine Tumors therapy, Pancreatic Neoplasms therapy
- Published
- 2005
- Full Text
- View/download PDF
223. Modulation of DNA repair in vitro after treatment with chemotherapeutic agents by the epidermal growth factor receptor inhibitor gefitinib (ZD1839).
- Author
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Friedmann B, Caplin M, Hartley JA, and Hochhauser D
- Subjects
- Cell Division drug effects, Cell Line, Tumor, Chromones pharmacology, Cisplatin pharmacology, Comet Assay, DNA Damage, DNA, Neoplasm analysis, DNA, Neoplasm genetics, Dose-Response Relationship, Drug, Drug Synergism, Enzyme Inhibitors pharmacology, ErbB Receptors metabolism, Etoposide pharmacology, Gefitinib, Humans, Melphalan pharmacology, Morpholines pharmacology, Phosphatidylinositol 3-Kinases metabolism, Phosphoinositide-3 Kinase Inhibitors, Signal Transduction drug effects, Time Factors, Antineoplastic Agents pharmacology, DNA Repair drug effects, ErbB Receptors antagonists & inhibitors, Quinazolines pharmacology
- Abstract
Purpose: The epidermal growth factor receptor (EGFR) is commonly expressed in human tumors and provides a target for therapy. Gefitinib (Iressa, ZD1839) is a quinazoline derivative that inhibits EGFR tyrosine kinase activity. Gefitinib demonstrated anticancer efficacy in vivo, and although experiments in vitro have suggested that inhibition of EGFR modulates the activity of chemotherapeutic agents, the mechanism of this interaction is unclear. We investigated mechanisms for this modulation., Experimental Design: The antiproliferative effect of gefitinib alone or combined with cisplatin, melphalan, and etoposide was determined in a human breast (MCF-7) cancer cell line. Using the alkaline single-cell gel electrophoresis (comet) assay, we investigated kinetics of DNA damage and repair after treatment with the chemotherapeutic drugs combined with gefitinib. To investigate whether the phosphatidylinositol 3'-kinase pathway was contributing to repair-inhibition produced by gefitinib, cells were exposed to chemotherapy in combination with the phosphatidylinositol 3'-kinase inhibitor LY294002., Results: A superadditive (synergistic) increase in growth inhibition for combined treatment with gefitinib was found for cisplatin and etoposide, but not with melphalan. There was delayed repair of DNA strand breaks after treatment with etoposide combined with gefitinib, and repair of DNA interstrand cross-links produced by cisplatin is delayed in combination with gefitinib. Inhibition of cell proliferation and DNA repair was identical in cells treated with LY294002. Immunoprecipitation of cell extracts demonstrated that after exposure to gefitinib, there was an association between EGFR and DNA-PK(CS)., Conclusion: Gefitinib acts through inhibition of repair of cisplatin and etoposide-induced DNA damage; this effect is mimicked by inhibitors of the phosphatidylinositol 3'-kinase suggesting similar mechanisms of action.
- Published
- 2004
- Full Text
- View/download PDF
224. Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system.
- Author
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Oberg K, Kvols L, Caplin M, Delle Fave G, de Herder W, Rindi G, Ruszniewski P, Woltering EA, and Wiedenmann B
- Subjects
- Digestive System Neoplasms diagnosis, Digestive System Neoplasms metabolism, Digestive System Neoplasms therapy, Digestive System Surgical Procedures methods, Humans, Neuroendocrine Tumors diagnosis, Neuroendocrine Tumors metabolism, Neuroendocrine Tumors therapy, Receptors, Somatostatin metabolism, Somatostatin analogs & derivatives, Somatostatin metabolism, Antineoplastic Agents, Hormonal therapeutic use, Digestive System Neoplasms drug therapy, Neuroendocrine Tumors drug therapy, Octreotide therapeutic use, Somatostatin therapeutic use
- Abstract
This consensus report gives a detailed description of the use of somatostatin analogs in the management of neuroendocrine tumors of the gastroenteropancreatic system. As background information we have outlined critical aspects of the pathology, the use of tumor markers, a definition of functional and non-functional digestive neuroendocrine tumors, different imaging modalities, surgical considerations, liver embolization and the use of cytotoxic drugs as well as interferon. Included in the report is an overview of somatostatin, somatostatin analogs and its receptor expression in different neuroendocrine tumors. It will also define the binding affinities of different somatostatin analogs to the five different subtypes of somatostatin receptor. We compare the efficacy of octreotide and lanreotide in reducing diarrhea and flushing. Side-effects are described and we provide practical information on somatostatin analog treatment.
- Published
- 2004
- Full Text
- View/download PDF
225. Guidelines for the diagnosis and treatment of neuroendocrine gastrointestinal tumours. A consensus statement on behalf of the European Neuroendocrine Tumour Society (ENETS).
- Author
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Plöckinger U, Rindi G, Arnold R, Eriksson B, Krenning EP, de Herder WW, Goede A, Caplin M, Oberg K, Reubi JC, Nilsson O, Delle Fave G, Ruszniewski P, Ahlman H, and Wiedenmann B
- Subjects
- Humans, Gastrointestinal Neoplasms diagnosis, Gastrointestinal Neoplasms therapy, Neuroendocrine Tumors diagnosis, Neuroendocrine Tumors therapy
- Published
- 2004
- Full Text
- View/download PDF
226. Rapid and sustained relief from the symptoms of carcinoid syndrome: results from an open 6-month study of the 28-day prolonged-release formulation of lanreotide.
- Author
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Ruszniewski P, Ish-Shalom S, Wymenga M, O'Toole D, Arnold R, Tomassetti P, Bax N, Caplin M, Eriksson B, Glaser B, Ducreux M, Lombard-Bohas C, de Herder WW, Delle Fave G, Reed N, Seitz JF, Van Cutsem E, Grossman A, Rougier P, Schmidt W, and Wiedenmann B
- Subjects
- Adult, Aged, Aged, 80 and over, Chromogranins blood, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug Evaluation methods, Female, Flushing drug therapy, Flushing physiopathology, Humans, Hydroxyindoleacetic Acid urine, Male, Malignant Carcinoid Syndrome complications, Malignant Carcinoid Syndrome metabolism, Middle Aged, Peptides, Cyclic blood, Quality of Life, Somatostatin blood, Time Factors, Treatment Outcome, Vipoma drug therapy, Vipoma physiopathology, Delayed-Action Preparations therapeutic use, Malignant Carcinoid Syndrome drug therapy, Peptides, Cyclic therapeutic use, Somatostatin analogs & derivatives, Somatostatin therapeutic use
- Abstract
This 6-month, open, non-controlled, multicenter, dose-titration study evaluated the efficacy and safety of 28-day prolonged-release (PR) lanreotide in the treatment of carcinoid syndrome. Eligible patients had a carcinoid tumor with > or =3 stools/day and/or > or =1 moderate/severe flushing episodes/day. Six treatments of 28-day PR lanreotide were administered by deep subcutaneous injection. The dose for the first two injections was 90 mg. Subsequent doses could be titrated (60, 90, 120 mg) according to symptom response. Seventy-one patients were treated. Flushing decreased from a mean of 3.0 at baseline to 2.3 on day 1, and 2.0 on day 2, with a daily mean of 2.1 for the first week post-treatment (p < 0.05). Diarrhea decreased from a mean of 5.0 at baseline to 4.3 on day 1 (p < 0.05), and 4.5 on day 2, with a daily mean of 4.4 for the first week post-treatment (p < 0.001). Symptom frequency decreased further after the second and third injections, and reached a plateau after the fourth injection. By month 6, flushing and diarrhea had significantly decreased from baseline by a mean of 1.3 and 1.1 episodes/day, respectively (both p < or = 0.001); 65% of patients with flushing as the target symptom and 18% of diarrhea-target patients achieved > or =50% reduction from baseline. Median urinary 5-hydroxyindoleacetic acid and chromogranin A levels decreased by 24 and 38%, respectively. Treatment was well tolerated. 28-day PR lanreotide was effective in reducing the symptoms and biochemical markers associated with carcinoid syndrome.
- Published
- 2004
- Full Text
- View/download PDF
227. The management of patients with neuroendocrine tumours.
- Author
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Caplin M and Wiedenmann B
- Subjects
- Endocrine Gland Neoplasms therapy, Humans, Nervous System Neoplasms therapy, Neuroendocrine Tumors therapy
- Published
- 2003
- Full Text
- View/download PDF
228. Use of stents in the palliative treatment of malignant gastric outlet and duodenal obstruction.
- Author
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Aviv RI, Shyamalan G, Khan FH, Watkinson AF, Tibballs J, Caplin M, and Winslett M
- Subjects
- Adult, Aged, Duodenal Obstruction etiology, Female, Gastric Outlet Obstruction etiology, Humans, Middle Aged, Prospective Studies, Retrospective Studies, Treatment Outcome, Duodenal Obstruction therapy, Gastric Outlet Obstruction therapy, Gastrointestinal Neoplasms complications, Palliative Care methods, Stents
- Abstract
Aim: To evaluate the efficacy of stenting in the palliation of malignant duodenal and gastric outlet obstruction., Materials and Methods: We retrospectively reviewed our series of patients who underwent stenting for malignant upper gastrointestinal obstruction between March 1998 and December 1999. From January 2000 data have been acquired prospectively. Our series comprises 21 stents successfully deployed in 15 patients., Results: The technical and clinical success was 93% (14/15 patients). One patient required endoscopic negotiation of recurrent gastric carcinoma at the gastrojejunostomy site after failure to cross the lesion fluroscopically. Two patients required re-intervention 2 and 5 weeks after initial stent placement, for migration and ingrowth respectively. Eighteen stents were placed transorally, two stents transhepatically and one via a transgastric approach. Early complications (pain < 3 days) occurred in two patients (13%) and late complications (ingrowth, overgrowth and migration) occurred in three patients (20%). The median survival was 2.4 months (range 2-4 months)., Conclusion: Stenting provides a less invasive palliative option than surgery with the advantage of lower morbidity and complication rates. It has the advantage of high technical and clinical success rates facilitated by alternative routes of access into the upper gastrointestinal tract via transgastric and transhepatic routes in addition to the traditional peroral route., (Copyright 2002 The Royal College of Radiologists.)
- Published
- 2002
- Full Text
- View/download PDF
229. Correspondence re: Weinberg et al., Cholecystokinin and gastrin levels are not elevated in pancreatic carcinoma. Cancer Epidemiol. Biomark. Prev., 10: 721-722, 2001.
- Author
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Watson SA and Caplin M
- Subjects
- Humans, Cholecystokinin metabolism, Gastrins metabolism, Pancreatic Neoplasms metabolism
- Published
- 2002
230. Effect of gastrin and anti-gastrin antibodies on proliferation of hepatocyte cell lines.
- Author
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Caplin M, Khan K, Grimes S, Michaeli D, Savage K, Pounder R, and Dhillon A
- Subjects
- Animals, Cell Division drug effects, Cell Line, Hepatocytes drug effects, Indoles pharmacology, Liver Neoplasms, Experimental pathology, Meglumine analogs & derivatives, Meglumine pharmacology, Receptor, Cholecystokinin B, Receptors, Cholecystokinin antagonists & inhibitors, Receptors, Cholecystokinin drug effects, Antibodies pharmacology, Gastrins immunology, Gastrins pharmacology, Hepatocytes cytology
- Abstract
Gastrin (G-17) and its precursor glycine-extended gastrin (G-17-gly) have been shown to be trophic to some gastrointestinal tumors. This in vitro study assessed the effect of G-17, G-17-gly, anti-gastrin antibodies (anti-G-17), and the CCK-B receptor antagonist PD135,158 on three hepatoma cell lines (PLC/PRF/5, HepG2 and MCA-RH7777) and an embryonic liver cell line (WRL68). The pancreatic adenocarcinoma cell line AR42J was used as a positive control. G-17 and G-17-gly caused significant proliferation of AR42J and WRL68 cell lines. G-17-gly but not G-17 induced significant proliferation of the PLC/PRF/5 cell line. Anti-G-17 and PD135,158 significantly inhibited unstimulated AR42J and WRL68 cell lines. Anti-G-17 also inhibited the proliferative effects of G-17 and G-17-gly on AR42J, WRL68, and PLC/PRF/5 cell lines, whereas PD135,158 inhibited the proliferative effect of G-17 only. G-17 and G-17-gly as well as anti-G-17 and PD135,158 had no effect on HepG2 and MCA-RH77777 cell lines. It is concluded that G-17-stimulated proliferation is mediated via the CCK-B receptor and G-17-gly via a separate, as yet uncharacterized, receptor. There may therefore be a role for gastrin in embryonic hepatocellular proliferation and perhaps also in the proliferation of some hepatocellular tumors.
- Published
- 2001
- Full Text
- View/download PDF
231. New therapeutic options of carcinoid syndrome metastatic to the liver.
- Author
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Wardyn KA, Zycińska K, Oledzka-Oreziak M, Ostrowski K, Krawczyk M, Królicki L, and Caplin M
- Subjects
- 3-Iodobenzylguanidine pharmacology, Antineoplastic Agents pharmacology, Carcinoid Tumor surgery, Humans, Interferon-alpha pharmacology, Neoplasm Metastasis, Somatostatin pharmacology, Carcinoid Tumor pathology, Carcinoid Tumor therapy, Liver pathology, Liver Neoplasms secondary
- Abstract
Carcinoid syndrome is a relatively rare disease, generally associated with poor prognosis. Conventional diagnostic and therapeutic methods often prove inadequate and ineffective. New therapeutic options have recently been provided by Radiolabeled long-acting somatostatin analogs (Octreotide), alpha interferon, 131 MIBG and non-pharmacological methods--embolization of the hepatic artery, gene therapy, and combined therapies.
- Published
- 2001
232. Expression and processing of gastrin in pancreatic adenocarcinoma.
- Author
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Caplin M, Savage K, Khan K, Brett B, Rode J, Varro A, and Dhillon A
- Subjects
- Humans, Immunohistochemistry, Receptors, Cholecystokinin metabolism, Adenocarcinoma metabolism, Gastrins metabolism, Neoplasm Proteins metabolism, Pancreatic Neoplasms metabolism
- Abstract
Background: Gastrin is a trophic hormone and promotes growth of gastrointestinal and non-gastrointestinal cancers. Studies both in vitro and in vivo have suggested that pancreatic cancer cells not only have the ability to respond to circulating forms of gastrin but also to respond to the autocrine production of gastrin and its precursors. The aim of this study was to identify the expression of CCK-B/gastrin receptor, progastrin, glycine-extended gastrin and amidated gastrin in both normal pancreas and pancreatic adenocarcinoma., Methods: Tissue sections from patients with normal pancreas (n = 10) and pancreatic cancer (n = 22) were assessed using immunohistochemical methods for CCK-B/gastrin receptor, progastrin, glycine-extended gastrin and amidated gastrin expression., Results: Normal pancreas showed no expression of receptor or gastrin isoforms except for occasional cells in the islets. Definite expression of CCK-B/gastrin receptor, progastrin, glycine-extended gastrin and amidated gastrin was observed in 95, 91, 55 and 23 per cent of sections from patients with pancreatic cancer respectively., Conclusion: Pancreatic cancer cells express CCK-B/gastrin receptor and gastrin precursor forms in most patients. Expression of the gastrin precursor forms is probably related to autocrine production. New therapeutic strategies need to be developed for the management of pancreatic cancer. Targeting gastrin and its receptor may provide a novel treatment option.
- Published
- 2000
- Full Text
- View/download PDF
233. Expression and processing of gastrin in hepatocellular carcinoma, fibrolamellar carcinoma and cholangiocarcinoma.
- Author
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Caplin M, Khan K, Savage K, Rode J, Varro A, Michaeli D, Grimes S, Brett B, Pounder R, and Dhillon A
- Subjects
- Humans, Immunohistochemistry, Liver metabolism, Liver pathology, Protein Processing, Post-Translational, Bile Duct Neoplasms metabolism, Bile Ducts, Intrahepatic metabolism, Carcinoma, Hepatocellular metabolism, Cholangiocarcinoma metabolism, Gastrins biosynthesis, Liver Neoplasms metabolism
- Abstract
Background/aims: Gastrin is a trophic factor within the normal gastrointestinal tract and is also a mitogen for a number of gastrointestinal and non-gastrointestinal tumours. Precursor forms of gastrin including progastrin (proG) and glycine-extended gastrin (G-gly) as well as the fully processed amidated gastrin (G-NH2) are expressed by tumours. There has been little study of the role of gastrin in either normal liver or liver tumours. The aim of this study was to identify the expression of CCK-B/gastrin receptor (CCK-BR), proG, G-gly and G-NH2 in normal liver and liver tumours., Methods: Tissue sections from patients with hepatocellular carcinoma, fibrolamellar carcinoma, cholangiocarcinoma as well as normal liver biopsies were assessed for expression of CCK-BR and gastrin isoforms., Results: Most liver tumours express CCK-BR and are able to process gastrin as far as proG and G-gly, although not as far as the amidated form. There appears to be little expression of the receptor and no expression of precursor forms of gastrin in normal liver., Conclusions: Liver tumours express the CCK-BR and precursor forms of gastrin. This expression may be associated with tumour proliferation.
- Published
- 1999
- Full Text
- View/download PDF
234. Gastric carcinoid expresses the gastrin autocrine pathway.
- Author
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Smith AM, Watson SA, Caplin M, Clarke P, Griffin N, Varro A, and Hardcastle JD
- Subjects
- Adult, Aged, Cholecystokinin metabolism, Female, Gastric Acid metabolism, Humans, Immunohistochemistry, Male, Middle Aged, Carcinoid Tumor metabolism, Gastrins metabolism, Stomach Neoplasms metabolism
- Abstract
Background: In gastric adenocarcinoma the gastrin autocrine-paracrine pathway is activated. As enterochromaffin-like (ECL) cells originate from the same stem as epithelial cells, the aim of this study was to determine if the gastrin autocrine pathway is present in gastric carcinoid., Methods: Samples from ten patients with gastric carcinoid were assessed by immunocytochemistry using primary antibodies directed against gastrin precursors and the gastrin/cholecystokinin B receptor and detected using the avidin-biotin immunoperoxidase system., Results: A high level of expression of precursor and mature gastrin peptides, together with the gastrin receptor, was seen in all carcinoids screened., Conclusion: In common with the glandular epithelium of the stomach the gastrin gene is activated during the neoplastic process in ECL cells. This finding may explain why some carcinoids do not regress after surgical procedures that lower serum gastrin. Antigastrin agents may be a useful treatment for carcinoid either in their own right or as an adjunct to surgery.
- Published
- 1998
- Full Text
- View/download PDF
235. Expression of CCKB/gastrin receptor isoforms in gastro-intestinal tumour cells.
- Author
-
Watson SA, Clarke PA, Smith AM, Varro A, Michaeli D, Grimes S, Caplin M, and Hardcastle JD
- Subjects
- 3T3 Cells chemistry, Animals, Blotting, Western, Humans, Mice, Molecular Weight, Neoplasm Proteins genetics, Receptors, Cholecystokinin genetics, Transfection, Gastrointestinal Neoplasms chemistry, Neoplasm Proteins analysis, Receptors, Cholecystokinin analysis
- Abstract
Anti-serum raised against the human cholecystokinin B (CCKB)/gastrin receptor was used in Western blotting to differentiate the cellular locations of receptor isoforms expressed by human gastro-intestinal (GI) tumour cell lines. Using anti-serum directed against the amino-terminal extracellular tail of the CCKB/gastrin receptor, 8/9 cell lines were shown to express immunoreactive proteins of either m.w. 70 or 40 kDa, or both. Both isoforms were found to be associated with intracellular, non-nuclear membranes, whereas only the 70 kDa protein was expressed in the plasma membrane. Receptor expression was related to gastrin production and secretion. Both progastrin and glycine-extended gastrin-17 were produced and secreted by the tumour cell lines; however, carboxy amidated gastrin was not detected by radioimmunoassay. A CCKB/gastrin receptor transfectant NIH3T3 cell line did not produce detectable gastrin and showed exclusive expression of the 70 kDa receptor on the plasma membrane. One cell line had <50 pg/ml cell-associated progastrin and no detectable receptor form. Cell lines expressing 50-150 pg/ml had both 40 and 70 kDa receptor forms. Those expressing >150 pg/ml progastrin had only the 40 kDa isoform, which was shown to be exclusively expressed on intracellular, non-nuclear membranes, in one of the cell lines. Of the 4 cell lines exclusively expressing the lower m.w. receptor, 3 had gastrin present within the cell, which was not secreted. Thus, if cell-associated gastrin induces a proliferative effect, it may be by an intracrine pathway. Our study has identified the presence of CCKB/gastrin receptor isoforms in different cellular locations and may help toward understanding the complex autocrine and intracrine pathways mediated by gastrin peptides.
- Published
- 1998
- Full Text
- View/download PDF
236. Antituberculous therapy and acute liver failure.
- Author
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Caplin M, Thompson N, Hamilton M, McIntyre N, and Burroughs A
- Subjects
- Antitubercular Agents therapeutic use, Chemical and Drug Induced Liver Injury prevention & control, Clinical Protocols, Humans, Liver Function Tests, Risk, Tuberculosis diagnosis, Tuberculosis drug therapy, Antitubercular Agents adverse effects, Chemical and Drug Induced Liver Injury etiology
- Published
- 1995
237. Inexpensive apparatus for the measurement of the temperature dependence of gas phase fluorescence spectra.
- Author
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Swords MD, Caplin M, and Phillips D
- Subjects
- Equipment Design, Equipment Failure Analysis, Temperature, Flow Injection Analysis instrumentation, Gases analysis, Gases chemistry, Heating instrumentation, Specimen Handling instrumentation, Spectrometry, Fluorescence instrumentation
- Abstract
An inexpensive and easily constructed cell is reported which allows the observation of gaseous fluorescence spectra over a wide temperature range.
- Published
- 1978
- Full Text
- View/download PDF
238. Relationship between radiological classification and the serological and haematological features of untreated pulmonary tuberculosis in Indonesia.
- Author
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Caplin M, Grange JM, Morley S, Brown RA, Kemp M, Gibson JA, Kardjito T, Hoeppner V, and Beck JS
- Subjects
- Acute-Phase Proteins analysis, Adolescent, Adult, Aged, Antibodies, Viral analysis, Female, Humans, Immunoglobulins analysis, Male, Middle Aged, Mycobacterium bovis immunology, Mycobacterium tuberculosis immunology, Radiography, Tuberculin Test, Tuberculosis, Pulmonary blood, Lung diagnostic imaging, Tuberculosis, Pulmonary diagnostic imaging
- Abstract
Immunological and metabolic responses were studied in 110 patients with newly diagnosed pulmonary tuberculosis and 32 healthy controls from similar socioeconomic backgrounds. The severity of lung involvement was assessed radiologically, but this was not related to the current features of cell mediated immunity or to those of many aspects of the serological response to Mycobacterium tuberculosis. However, the patients with more extensive pulmonary tuberculosis showed higher titres of IgG2 antibody to whole killed M. tuberculosis and to the ML34 epitope shared by many species of mycobacteria. The patients with more extensive pulmonary tuberculosis showed a more marked metabolic response to infection as manifested by changes in serum levels of acute phase reactant proteins. Accordingly, the metabolic responses are considered to be more likely to prove of value in clinical monitoring of patients for severity of infection, or of reactivation of infection with M. tuberculosis, than immunological responses.
- Published
- 1989
- Full Text
- View/download PDF
239. Relation between lung cancer, chronic bronchitis, and airways obstruction.
- Author
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Caplin M and Festenstein F
- Subjects
- Adult, Age Factors, Aged, Chronic Disease, Female, Forced Expiratory Volume, Humans, Lung Neoplasms mortality, Male, Middle Aged, Smoking, Airway Obstruction complications, Bronchitis complications, Lung Neoplasms complications
- Abstract
Since cigarette smoking is an important cause of lung cancer and chronic bronchitis both conditions should occur together more often in cigarette smokers than would result from chance. If they do commonly occur together then severe airways obstruction, which is often associated with chronic bronchitis, should also be often associated with lung cancer. To discover whether this were so three groups of patients were studied at the London Chest Hospital. Two hundred men and 43 women who presented with lung cancer provided information on the prevalence of defined chronic bronchitis and airways obstruction in those suffering from lung cancer. The third group consisted of 233 men presenting with defined chronic bronchitis who were kept under observation to discover how many would die from lung cancer. The results suggested that simple bronchitis and lung cancer often occur together but that obstructive bronchitis and lung cancer do not often occur together. The lack of association between lung cancer and severe airways obstruction requires an explanation.
- Published
- 1975
- Full Text
- View/download PDF
240. Disseminated intravascular coagulation: a multisystem problem.
- Author
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Caplin M
- Subjects
- Blood Coagulation, Disseminated Intravascular Coagulation physiopathology, Heparin administration & dosage, Humans, Nursing Assessment, Disseminated Intravascular Coagulation nursing
- Published
- 1984
- Full Text
- View/download PDF
241. Choice of treatment in operable lung cancer.
- Author
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Belcher JR and Caplin M
- Subjects
- Attitude of Health Personnel, Decision Making, Humans, Lung Neoplasms radiotherapy, Lung Neoplasms surgery
- Published
- 1979
- Full Text
- View/download PDF
242. Early mobilization of uncomplicated myocardial infarct patients.
- Author
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Caplin M
- Subjects
- Aged, Bed Rest adverse effects, Female, Humans, Male, Middle Aged, Early Ambulation, Myocardial Infarction rehabilitation
- Published
- 1986
243. Restriction of cold fluids in myocardial infarction patients: myth or fact?
- Author
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Caplin M
- Subjects
- Humans, Myocardial Infarction nursing, Posture, Cold Temperature adverse effects, Drinking, Heart Rate, Myocardial Infarction physiopathology
- Published
- 1984
244. Letter: Solitary pulmonary nodules.
- Author
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Belcher JR and Caplin M
- Subjects
- Biopsy, Needle, Fiber Optic Technology, Humans, Lung Neoplasms diagnosis, Solitary Pulmonary Nodule diagnosis
- Published
- 1975
- Full Text
- View/download PDF
245. Pulmonary necrobiotic nodules without rheumatoid arthritis.
- Author
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Eraut D, Evans J, and Caplin M
- Subjects
- Adult, Aged, Arthritis, Rheumatoid complications, Female, Follow-Up Studies, Humans, Male, Middle Aged, Rheumatoid Factor analysis, Rheumatoid Nodule complications, Solitary Pulmonary Nodule pathology, Time Factors, Rheumatoid Nodule pathology, Solitary Pulmonary Nodule etiology
- Abstract
Pulmonary necrobiotic nodules are the least common of the pulmonary lesions associated with rheumatoid arthritis. Histologically they are identical to subcutaneous rheumatoid nodules. Systemic rheumatoid arthritis usually precedes the development of pulmonary nodules. Seven cases where the pulmonary nodule appeared before or without the development of systemic rheumatoid arthritis are described. The typical histological and radiological features of necrobiotic nodules were found in each. In five of the seven the nodules were in more than one site and in five there were cavitating nodules. Spontaneous improvement occurred in one case. Pulmonary nodules preceded systemic rheumatoid arthritis in three cases and in the remaining four cases systemic rheumatoid arthritis has not yet appeared despite prolonged follow-up. In all patients, tests for rheumatoid factor have remained negative. The absence of circulating rheumatoid factor and systemic rheumatoid arthritis cannot exclude the diagnosis in these cases if the histological diagnosis is accepted as conclusive.
- Published
- 1978
246. Pleural calcification.
- Author
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Kendall B and Caplin M
- Subjects
- Asbestosis complications, Calcinosis diagnostic imaging, Calcinosis etiology, Diagnosis, Differential, Humans, Pleural Effusion, Pneumothorax, Artificial adverse effects, Radiography, Tuberculosis, Pulmonary, Pleural Diseases diagnostic imaging, Pleural Diseases etiology
- Published
- 1967
- Full Text
- View/download PDF
247. HUMAN CANCER MATERIALS.
- Author
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CAPLIN M, CAPEL LH, and WHEELER WF
- Subjects
- Humans, Male, Biopsy, Neoplasms
- Published
- 1965
248. A BRONCHITIS REGISTRY IN EAST LONDON. A REPORT ON THE FIRST YEAR'S WORK. I. ESTABLISHMENT OF THE REGISTRY AND CLINICAL FINDINGS.
- Author
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CAPLIN M, CAPEL LH, and WHEELER WF
- Subjects
- England, London, Biometry, Bronchitis, Registries, Statistics as Topic
- Published
- 1964
- Full Text
- View/download PDF
249. Tuberculin sensitivity in the middle-aged and elderly.
- Author
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CAPLIN M, SILVER CP, and WHEELER WF
- Subjects
- Aged, Humans, Middle Aged, Immune System Phenomena, Tuberculin, Tuberculin Test statistics & numerical data
- Published
- 1958
- Full Text
- View/download PDF
250. PROCAINE AMIDE AND S.L.E.
- Author
-
CAPLIN M, CAPEL LH, and WHEELER WF
- Subjects
- Drug Therapy, Procainamide
- Published
- 1965
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