Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Δευτέρα 5 Ιουνίου 2017
Meta-analysis of pre-operative magnetic resonance imaging (MRI) and surgical treatment for breast cancer
Abstract
Background
Although there is no consensus on whether pre-operative MRI in women with breast cancer (BC) benefits surgical treatment, MRI continues to be used pre-operatively in practice. This meta-analysis examines the association between pre-operative MRI and surgical outcomes in BC.
Methods
A systematic review was performed to identify studies reporting quantitative data on pre-operative MRI and surgical outcomes (without restriction by type of surgery received or type of BC) and using a controlled design. Random-effects logistic regression calculated the pooled odds ratio (OR) for each surgical outcome (MRI vs. no-MRI groups), and estimated ORs stratified by study-level age. Subgroup analysis was performed for invasive lobular cancer (ILC).
Results
Nineteen studies met eligibility criteria: 3 RCTs and 16 comparative studies that included newly diagnosed BC of any type except for three studies restricted to ILC. Primary analysis (85,975 subjects) showed that pre-operative MRI was associated with increased odds of receiving mastectomy [OR 1.39 (1.23, 1.57); p < 0.001]; similar findings were shown in analyses stratified by study-level median age. Secondary analyses did not find statistical evidence of an effect of MRI on the rates of re-excision, re-operation, or positive margins; however, MRI was significantly associated with increased odds of receiving contralateral prophylactic mastectomy [OR 1.91 (1.25, 2.91); p = 0.003]. Subgroup analysis for ILC did not find any association between MRI and the odds of receiving mastectomy [OR 1.00 (0.75, 1.33); p = 0.988] or the odds of re-excision [OR 0.65 (0.35, 1.24); p = 0.192].
Conclusions
Pre-operative MRI is associated with increased odds of receiving ipsilateral mastectomy and contralateral prophylactic mastectomy as surgical treatment in newly diagnosed BC patients.
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Rationale and protocol of MetNET-2 trial: Lanreotide Autogel plus metformin in advanced gastrointestinal or lung neuroendocrine tumors
Future Oncology Ahead of Print.
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Rationale and protocol of MetNET-2 trial: Lanreotide Autogel plus metformin in advanced gastrointestinal or lung neuroendocrine tumors
Future Oncology Ahead of Print.
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Salvage Strategies for Management of Testicular Tumors
Abstract
Testicular germ cell tumors (GCTs) comprise 2% of all human male malignancies and are the most common solid tumors in men between ages 15 and 35 years. Risk of contralateral testicular GCT is between 1 and 5%. Partial orchidectomy (PO) was originally described in 1984 by Richie. The evolving indications include metachronous tumors and tumor in solitary testicles. Also, small non-palpable lesions detected only by ultrasonography (USG) in asymptomatic patients is another indication. Salvagability is only chosen for tumors less than 2 cm in size. The key feature of PO is an inguinal approach with early vascular control using a rubber tourniquet before testicular mobilization into the field to avoid systemic tumor seeding. After, mass excision with a margin mandatory frozen section is done to assess adequacy of resection. Intra-op USG may be beneficial in small non-palpable lesions. Post op tumor markers are assessed and patients are taught self-examination of testis. Recent series shows that PO is safe and gives adequate oncological control. Carcinoma in situ (CIS) in the affected testis at PO or after testicular sparing surgery remains a challenge. At most centers, 20 Gy is recommended when adjuvant local radiation treatment is chosen to treat CIS. But this dose may hamper Androgen production. Radical orchiectomy remains the gold standard and should be discussed as part of informed consent. It is mandatory to highlight the risks of local recurrence and CIS, and treatment (observation, radiation, or completion orchiectomy) as well as the need for androgen supplementation and fertility risks before choosing testicular salvage procedures.
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Current Concepts in the Management of Non-Muscle Invasive Bladder Cancer
Abstract
Non-muscle invasive bladder cancer, despite advances in the field of medicine, remains an enigmatic problem with no tangible solution of one-time treatment as it needs an invasive surveillance in the form of cystoscopy. There are issues related to diagnosis, ideal resection technique, BCG treatment, and follow-up. In this article, we review the recent developments in the diagnosis of the disease and describe optimal management strategies.
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Rationale and protocol of MetNET-2 trial: Lanreotide Autogel plus metformin in advanced gastrointestinal or lung neuroendocrine tumors
Future Oncology Ahead of Print.
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Salvage Strategies for Management of Testicular Tumors
Abstract
Testicular germ cell tumors (GCTs) comprise 2% of all human male malignancies and are the most common solid tumors in men between ages 15 and 35 years. Risk of contralateral testicular GCT is between 1 and 5%. Partial orchidectomy (PO) was originally described in 1984 by Richie. The evolving indications include metachronous tumors and tumor in solitary testicles. Also, small non-palpable lesions detected only by ultrasonography (USG) in asymptomatic patients is another indication. Salvagability is only chosen for tumors less than 2 cm in size. The key feature of PO is an inguinal approach with early vascular control using a rubber tourniquet before testicular mobilization into the field to avoid systemic tumor seeding. After, mass excision with a margin mandatory frozen section is done to assess adequacy of resection. Intra-op USG may be beneficial in small non-palpable lesions. Post op tumor markers are assessed and patients are taught self-examination of testis. Recent series shows that PO is safe and gives adequate oncological control. Carcinoma in situ (CIS) in the affected testis at PO or after testicular sparing surgery remains a challenge. At most centers, 20 Gy is recommended when adjuvant local radiation treatment is chosen to treat CIS. But this dose may hamper Androgen production. Radical orchiectomy remains the gold standard and should be discussed as part of informed consent. It is mandatory to highlight the risks of local recurrence and CIS, and treatment (observation, radiation, or completion orchiectomy) as well as the need for androgen supplementation and fertility risks before choosing testicular salvage procedures.
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Current Concepts in the Management of Non-Muscle Invasive Bladder Cancer
Abstract
Non-muscle invasive bladder cancer, despite advances in the field of medicine, remains an enigmatic problem with no tangible solution of one-time treatment as it needs an invasive surveillance in the form of cystoscopy. There are issues related to diagnosis, ideal resection technique, BCG treatment, and follow-up. In this article, we review the recent developments in the diagnosis of the disease and describe optimal management strategies.
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Dramatic Responses Seen with TRK Inhibitor [News in Brief]
Treatment with larotrectinib yielded responses in 76% of patients—pediatric and adult—regardless of tumor type.
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Olaparib Keeps Hereditary Breast Tumors in Check [News in Brief]
For metastatic breast cancer with BRCA mutations, PARP inhibitor beats chemo in phase III trial for the first time.
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First Tissue-Agnostic Drug Approval Issued [News in Brief]
Pembrolizumab OK'd for mismatch repair–deficient or microsatellite instability–high solid tumors.
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Emory's Winship Earns Comprehensive Status [News in Brief]
Cancer center receives NCI kudos for its clinical trials program and population-based research initiatives.
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Human Subjects Protection and Cancer Surveillance Research: Revised Regulations, Expanded Opportunities
On January 19, 2017, the United States federal government issued revisions to the Common Rule under which scientists who receive federal funding conduct research involving human subjects. The revised Common Rule expressly addresses public health surveillance in relation to scientific research and the protection of human subjects, and its impacts are anticipated to contribute to the efficiency of activities, including cancer registration and surveillance, and research that uses cancer registry data. Cancer Res; 77(12); 1–4. ©2017 AACR.
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FOXM1 in Cancer: Interactions and Vulnerabilities
FOXM1 is a transcription factor of the Forkhead family that is required for cell proliferation of normal cells. However, FOXM1 is repeatedly overexpressed in a variety of human cancers, and it has been implicated in all major hallmarks of cancer delineated by Hanahan and Weinberg. It has been postulated that the oncogenic potential of FOXM1 is determined by its capacity to transactivate target genes that are implicated in different phases of cancer development. However, FOXM1 may also play an oncogenic role by interacting with other proteins, such as β-catenin or SMAD3 to induce oncogenic WNT and TGFβ signaling pathways, respectively. In this review, I will discuss the protein–protein interactions of FOXM1 that are critical for cancer development and may represent novel targets for anticancer drugs. Cancer Res; 77(12); 1–5. ©2017 AACR.
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Nature and Nurture: What Determines Tumor Metabolic Phenotypes?
Understanding the genetic basis of cancer has led to therapies that target driver mutations and has helped match patients with more personalized drugs. Oncogenic mutations influence tumor metabolism, but other tumor characteristics can also contribute to their metabolic phenotypes. Comparison of isogenic lung and pancreas tumor models suggests that use of some metabolic pathways is defined by lineage rather than by driver mutation. Lung tumors catabolize circulating branched chain amino acids (BCAA) to extract nitrogen for nonessential amino acid and nucleotide synthesis, whereas pancreatic cancer obtains amino acids from catabolism of extracellular protein. These differences in amino acid metabolism translate into distinct pathway dependencies, as genetic disruption of the enzymes responsible for utilization of BCAA nitrogen limits the growth of lung tumors, but not pancreatic tumors. These data argue that some cancer metabolic phenotypes are defined by cancer tissue-of-origin and environment and that these features constrain the influence of genetic mutations on metabolism. A better understanding of the factors defining tumor nutrient utilization could be exploited to help improve cancer therapy. Cancer Res; 77(12); 1–4. ©2017 AACR.
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Level of cystatin C in functional thyroid disorders and its relation to GFR
Abstract
Thyroid hormones affect the development and physiology of the kidneys. Hypothyroidism and hyperthyroidism affect glomerular filtration rate (GFR), tubular function, renal blood flow, and structure of the kidney. Cystatin C is a non-glycosylated neuroendocrine protein. It is freely filtered at the glomerulus and completely reabsorbed and catabolized by cells of tubules. Cystatin C levels, affected by the thyroid state, is being increased in hyperthyroidism and decreased in hypothyroidism. The current study was conducted on 66 patients of thyroid disorder and 21 healthy control subjects. Total T3, total T4, and TSH were measured by cobas e 411. Human Cystatin C was measured using ELISA kit based on sandwich enzyme-linked immunosorbent assay. Cystatin C was significantly increased in both total hyperthyroid and clinical hyperthyroid groups as compared to control (p < 0.001). eGFRCys C and eGFRCr-Cys C were significantly decreased in hyperthyroid and clinical hyperthyroid (p < 0.001). Cystatin C was significantly reduced in hypothyroid group and subgroups comparing to control group (p < 0.001, p < 0.001, and p = 0.004, respectively). As regard to eGFRCys C, it was significantly an overestimate clearance in hypothyroid group and subgroups when compared to normal subjects (p < 0.001, p < 0.001, and p = 0.002, respectively). Thyroid dysfunction affects cystatin C level as well as cystatin-based eGFR so it is not suitable in thyroid dysfunction specially in clinical dysfunction.
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Human Subjects Protection and Cancer Surveillance Research: Revised Regulations, Expanded Opportunities
On January 19, 2017, the United States federal government issued revisions to the Common Rule under which scientists who receive federal funding conduct research involving human subjects. The revised Common Rule expressly addresses public health surveillance in relation to scientific research and the protection of human subjects, and its impacts are anticipated to contribute to the efficiency of activities, including cancer registration and surveillance, and research that uses cancer registry data. Cancer Res; 77(12); 1–4. ©2017 AACR.
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FOXM1 in Cancer: Interactions and Vulnerabilities
FOXM1 is a transcription factor of the Forkhead family that is required for cell proliferation of normal cells. However, FOXM1 is repeatedly overexpressed in a variety of human cancers, and it has been implicated in all major hallmarks of cancer delineated by Hanahan and Weinberg. It has been postulated that the oncogenic potential of FOXM1 is determined by its capacity to transactivate target genes that are implicated in different phases of cancer development. However, FOXM1 may also play an oncogenic role by interacting with other proteins, such as β-catenin or SMAD3 to induce oncogenic WNT and TGFβ signaling pathways, respectively. In this review, I will discuss the protein–protein interactions of FOXM1 that are critical for cancer development and may represent novel targets for anticancer drugs. Cancer Res; 77(12); 1–5. ©2017 AACR.
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Nature and Nurture: What Determines Tumor Metabolic Phenotypes?
Understanding the genetic basis of cancer has led to therapies that target driver mutations and has helped match patients with more personalized drugs. Oncogenic mutations influence tumor metabolism, but other tumor characteristics can also contribute to their metabolic phenotypes. Comparison of isogenic lung and pancreas tumor models suggests that use of some metabolic pathways is defined by lineage rather than by driver mutation. Lung tumors catabolize circulating branched chain amino acids (BCAA) to extract nitrogen for nonessential amino acid and nucleotide synthesis, whereas pancreatic cancer obtains amino acids from catabolism of extracellular protein. These differences in amino acid metabolism translate into distinct pathway dependencies, as genetic disruption of the enzymes responsible for utilization of BCAA nitrogen limits the growth of lung tumors, but not pancreatic tumors. These data argue that some cancer metabolic phenotypes are defined by cancer tissue-of-origin and environment and that these features constrain the influence of genetic mutations on metabolism. A better understanding of the factors defining tumor nutrient utilization could be exploited to help improve cancer therapy. Cancer Res; 77(12); 1–4. ©2017 AACR.
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Improved outcome of 131I-mIBG treatment through combination with external beam radiotherapy in the SK-N-SH mouse model of neuroblastoma
To assess the efficacy of different schedules for combining external beam radiotherapy (EBRT) with molecular radiotherapy (MRT) using 131I-mIBG in the management of neuroblastoma.
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Prévention médicale et traitement des complications pulmonaires secondaires à la radiothérapie
Source:Cancer/Radiothérapie
Author(s): A. Vallard, C. Rancoule, H. Le Floch, J.-B. Guy, S. Espenel, C. Le Péchoux, É. Deutsch, N. Magné, C. Chargari
Les complications pulmonaires pouvant être induites par la radiothérapie se composent essentiellement de la pneumopathie radique (aiguë ou subaiguë), de la fibrose pulmonaire, et de la bronchiolite oblitérante avec pneumopathie organisée (abrégée en « pneumopathie organisée » chez les francophones, « BOOP » chez les anglo-saxons). Cet article est une synthèse de la littérature portant sur ces pathologies, faisant une mise au point sur la démarche diagnostique, sur les connaissances physiopathologiques actuelles, et sur les moyens non dosimétriques de prévention et de traitement. Puisqu'aucun signe clinique ou paraclinique n'est pathognomonique de ces phénomènes, le diagnostic doit être porté par élimination. Les examens paracliniques absolument nécessaires sont la scanographie thoracique en coupes fines et les épreuves fonctionnelles respiratoires avec mesure de la diffusion libre du CO. Par ailleurs, aucun traitement n'a vraiment montré d'efficacité dans la prévention des complications pulmonaires radio-induites et dans le traitement de la fibrose. Les molécules les plus avancées et les plus prometteuses concernant la prévention des complications pulmonaires de la radiothérapie sont l'amifostine, les inhibiteurs de l'enzyme de conversion de l'angiotensine et la pentoxifylline. Des inhibiteurs de la synthèse du collagène sont en cours de développement préclinique, afin de limiter la fibrose radio-induite. Dans le cas du traitement de la pneumopathie radique, les corticoïdes tiennent une place centrale, sans qu'il n'existe un protocole standardisé. Des alternatives (immunosuppresseurs) existent, sur la foi de résultats issus de cas cliniques. Ces données mettent en lumière le rôle primordial de la protection dosimétrique des poumons dans la prévention de la toxicité pulmonaire radio-induite.Radiation-induced lung injuries mainly include the (acute or sub-acute) radiation pneumonitis, the lung fibrosis and the bronchiolitis obliterans organizing pneumonia (BOOP). The present review aims at describing the diagnostic process, the current physiopathological knowledge, and the available (non dosimetric) preventive and curative treatments. Radiation-induced lung injury is a diagnosis of exclusion, since clinical, radiological, or biological pathognomonic evidences do not exist. Investigations should necessarily include a thoracic high resolution CT-scan and lung function tests with a diffusing capacity of the lung for carbon monoxide. No treatment ever really showed efficacy to prevent acute radiation-induced lung injury, or to treat radiation-induced lung fibrosis. The most promising drugs in order to prevent radiation-induced lung injury are amifostine, angiotensin-converting-enzyme inhibitors and pentoxifylline. Inhibitors of collagen synthesis are currently tested at a pre-clinical stage to limit the radiation-induced lung fibrosis. Regarding available treatments of radiation-induced pneumonitis, corticoids can be considered the cornerstone. However, no standardized program or guidelines concerning the initial dose and the gradual tapering have been scientifically established. Alternative treatments can be prescribed, based on clinical cases reporting on the efficacy of immunosuppressive drugs. Such data highlight the major role of the lung dosimetric protection in order to efficiently prevent radiation-induced lung injury.
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Prévention médicale et traitement des complications pulmonaires secondaires à la radiothérapie
Source:Cancer/Radiothérapie
Author(s): A. Vallard, C. Rancoule, H. Le Floch, J.-B. Guy, S. Espenel, C. Le Péchoux, É. Deutsch, N. Magné, C. Chargari
Les complications pulmonaires pouvant être induites par la radiothérapie se composent essentiellement de la pneumopathie radique (aiguë ou subaiguë), de la fibrose pulmonaire, et de la bronchiolite oblitérante avec pneumopathie organisée (abrégée en « pneumopathie organisée » chez les francophones, « BOOP » chez les anglo-saxons). Cet article est une synthèse de la littérature portant sur ces pathologies, faisant une mise au point sur la démarche diagnostique, sur les connaissances physiopathologiques actuelles, et sur les moyens non dosimétriques de prévention et de traitement. Puisqu'aucun signe clinique ou paraclinique n'est pathognomonique de ces phénomènes, le diagnostic doit être porté par élimination. Les examens paracliniques absolument nécessaires sont la scanographie thoracique en coupes fines et les épreuves fonctionnelles respiratoires avec mesure de la diffusion libre du CO. Par ailleurs, aucun traitement n'a vraiment montré d'efficacité dans la prévention des complications pulmonaires radio-induites et dans le traitement de la fibrose. Les molécules les plus avancées et les plus prometteuses concernant la prévention des complications pulmonaires de la radiothérapie sont l'amifostine, les inhibiteurs de l'enzyme de conversion de l'angiotensine et la pentoxifylline. Des inhibiteurs de la synthèse du collagène sont en cours de développement préclinique, afin de limiter la fibrose radio-induite. Dans le cas du traitement de la pneumopathie radique, les corticoïdes tiennent une place centrale, sans qu'il n'existe un protocole standardisé. Des alternatives (immunosuppresseurs) existent, sur la foi de résultats issus de cas cliniques. Ces données mettent en lumière le rôle primordial de la protection dosimétrique des poumons dans la prévention de la toxicité pulmonaire radio-induite.Radiation-induced lung injuries mainly include the (acute or sub-acute) radiation pneumonitis, the lung fibrosis and the bronchiolitis obliterans organizing pneumonia (BOOP). The present review aims at describing the diagnostic process, the current physiopathological knowledge, and the available (non dosimetric) preventive and curative treatments. Radiation-induced lung injury is a diagnosis of exclusion, since clinical, radiological, or biological pathognomonic evidences do not exist. Investigations should necessarily include a thoracic high resolution CT-scan and lung function tests with a diffusing capacity of the lung for carbon monoxide. No treatment ever really showed efficacy to prevent acute radiation-induced lung injury, or to treat radiation-induced lung fibrosis. The most promising drugs in order to prevent radiation-induced lung injury are amifostine, angiotensin-converting-enzyme inhibitors and pentoxifylline. Inhibitors of collagen synthesis are currently tested at a pre-clinical stage to limit the radiation-induced lung fibrosis. Regarding available treatments of radiation-induced pneumonitis, corticoids can be considered the cornerstone. However, no standardized program or guidelines concerning the initial dose and the gradual tapering have been scientifically established. Alternative treatments can be prescribed, based on clinical cases reporting on the efficacy of immunosuppressive drugs. Such data highlight the major role of the lung dosimetric protection in order to efficiently prevent radiation-induced lung injury.
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Acute psychoactive and toxic effects of D. metel on mice explained by 1 H NMR based metabolomics approach
Abstract
Datura metel L. (D. metel) is one well-known folk medical herb with wide application and also the most abused plants all over the world, mainly for spiritual or religious purpose, over-dosing of which often produces poisonous effects. In this study, mice were orally administered with the extract of D. metel once a day at doses for 10 mg/kg and 40 mg/kg for consecutive 4 days, 1H NMR based metabolomics approach aided with histopathological inspection and biochemical assays were used for the first time to study the psychoactive and toxic effects of D. metel. Histopathological inspection revealed obvious hypertrophy of hepatocytes, karyolysis and karyorrhexis in livers as well as distinct nerve cell edema, chromatolysis and lower nuclear density in brains. The increased tissue level of methane dicarboxylic aldehyde (MDA) and superoxide dismutase (SOD), decreased tissue level of glutathione (GSH) along with increased serum level of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) suggested brain and liver injury induced by D. metel. Orthogonal signal correction–partial least squares–discriminant analysis (OSC–PLS–DA) of NMR profiles supplemented with correlation network analysis revealed significant altered metabolites and related pathway that contributed to oxidative stress, energy metabolism disturbances, neurotransmitter imbalance and amino acid metabolism disorders.
http://ift.tt/2rLZPxN
Acute psychoactive and toxic effects of D. metel on mice explained by 1 H NMR based metabolomics approach
Abstract
Datura metel L. (D. metel) is one well-known folk medical herb with wide application and also the most abused plants all over the world, mainly for spiritual or religious purpose, over-dosing of which often produces poisonous effects. In this study, mice were orally administered with the extract of D. metel once a day at doses for 10 mg/kg and 40 mg/kg for consecutive 4 days, 1H NMR based metabolomics approach aided with histopathological inspection and biochemical assays were used for the first time to study the psychoactive and toxic effects of D. metel. Histopathological inspection revealed obvious hypertrophy of hepatocytes, karyolysis and karyorrhexis in livers as well as distinct nerve cell edema, chromatolysis and lower nuclear density in brains. The increased tissue level of methane dicarboxylic aldehyde (MDA) and superoxide dismutase (SOD), decreased tissue level of glutathione (GSH) along with increased serum level of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) suggested brain and liver injury induced by D. metel. Orthogonal signal correction–partial least squares–discriminant analysis (OSC–PLS–DA) of NMR profiles supplemented with correlation network analysis revealed significant altered metabolites and related pathway that contributed to oxidative stress, energy metabolism disturbances, neurotransmitter imbalance and amino acid metabolism disorders.
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Secondary breast carcinoma after completely remitted chronic myeloid leukemia following targeted tyrosine kinase inhibitor therapy
Abstract
We describe a rare case of secondary breast carcinoma after chronic myeloid leukemia (CML) in a 56-year-old woman. The patient was treated with hydroxyurea and imatinib for CML and achieved complete remission (she has since been taking imatinib as the maintenance therapy). Four years later, the patient noticed a firm and painless lump in the left breast, which was diagnosed as ductal carcinoma in situ based on a percutaneous biopsy of the mass. Simple resection and sentinel lymph node biopsy of the left breast were then performed. Pathological studies revealed a medium-grade intraductal carcinoma, with local infiltration associated with invasive micropapillary carcinoma. She received adjuvant endocrine therapy with imatinib after surgery. Breast cancer secondary to CML (treated with imatinib and completely remitted) is extremely rare. This report provides evidence to assist in the diagnosis and treatment for this rare manifestation.
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Subtype-specific prognostic impact of different immune signatures in node-negative breast cancer
Abstract
Background
The role of different subtypes of immune cells is still a matter of debate.
Methods
We compared the prognostic relevance for metastasis-free survival (MFS) of a B-cell signature (BS), a T-cell signature (TS), and an immune checkpoint signature (CPS) in node-negative breast cancer (BC) using mRNA expression. Microarray-based gene-expression data were analyzed in six previously published cohorts of node-negative breast cancer patients not treated with adjuvant therapy (n = 824). The prognostic relevance of the individual immune markers was assessed using univariate analysis. The amount of independent prognostic information provided by each immune signature was then compared using a likelihood ratio statistic in the whole cohort as well as in different molecular subtypes.
Results
Univariate Cox regression in the whole cohort revealed prognostic significance of CD4 (HR 0.66, CI 0.50–0.87, p = 0.004), CXCL13 (HR 0.86, CI 0.81–0.92, p < 0.001), CD20 (HR 0.76, CI 0.64–0.89, p = 0.001), IgκC (HR 0.81, CI 0.75–0.88, p < 0.001), and CTLA-4 (HR 0.67, CI 0.46–0.97, p = 0.032). Multivariate analyses of the immune signatures showed that both TS (p < 0.001) and BS (p < 0.001) showed a significant prognostic information in the whole cohort. After accounting for clinical-pathological variables, TS (p < 0.001), BS (p < 0.05), and CPS (p < 0.05) had an independent effect for MFS. In subgroup analyses, the prognostic effect of immune cells was most pronounced in HER2+ BC: BS as well as TS showed a strong association with MFS when included first in the model (p < 0.001).
Conclusion
Immune signatures provide subtype-specific additional prognostic information over clinical-pathological variables in node-negative breast cancer.
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The peripheral monocyte count is associated with the density of tumor-associated macrophages in the tumor microenvironment of colorectal cancer: a retrospective study
Abstract
Background
Inflammation is widely recognized to play an important role in cancer progression, and the peripheral monocyte count has been reported to correlate with the prognosis in patients with colorectal cancer. This is based on the hypothesis that the peripheral monocyte level and the density of tumor-associated macrophages (TAMs) in the cancer microenvironment correlate with each other. However, the influence of TAMs on the prognosis and the correlation between the peripheral monocyte count and the density of TAMs have not yet been elucidated.
Methods
A total of 168 patients with stage II/III colorectal cancer were enrolled in this study. Preoperative blood samples were obtained at the time of the diagnosis before surgery. The expression of TAMs in the cancer microenvironment was assessed by immunohistochemistry.
Results
The progression-free and overall survival rate were significantly worse in the high-TAMs group than in the low-TAMs group (p = 0.0012 and p = 0.0207, respectively). The peripheral monocyte count was significantly associated with the number of TAMs (correlation coefficients: 0.202, p = 0.047).
Conclusions
The peripheral monocyte count was associated with the density of the TAMs, which created a microenvironment favorable for cancer development and were correlated with a poor prognosis. Therefore, the peripheral monocyte count is a useful prognostic marker reflecting the status of the tumor microenvironment.
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The peripheral monocyte count is associated with the density of tumor-associated macrophages in the tumor microenvironment of colorectal cancer: a retrospective study
Abstract
Background
Inflammation is widely recognized to play an important role in cancer progression, and the peripheral monocyte count has been reported to correlate with the prognosis in patients with colorectal cancer. This is based on the hypothesis that the peripheral monocyte level and the density of tumor-associated macrophages (TAMs) in the cancer microenvironment correlate with each other. However, the influence of TAMs on the prognosis and the correlation between the peripheral monocyte count and the density of TAMs have not yet been elucidated.
Methods
A total of 168 patients with stage II/III colorectal cancer were enrolled in this study. Preoperative blood samples were obtained at the time of the diagnosis before surgery. The expression of TAMs in the cancer microenvironment was assessed by immunohistochemistry.
Results
The progression-free and overall survival rate were significantly worse in the high-TAMs group than in the low-TAMs group (p = 0.0012 and p = 0.0207, respectively). The peripheral monocyte count was significantly associated with the number of TAMs (correlation coefficients: 0.202, p = 0.047).
Conclusions
The peripheral monocyte count was associated with the density of the TAMs, which created a microenvironment favorable for cancer development and were correlated with a poor prognosis. Therefore, the peripheral monocyte count is a useful prognostic marker reflecting the status of the tumor microenvironment.
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ERβ1 inhibits metastasis of androgen receptor-positive triple-negative breast cancer by suppressing ZEB1
Abstract
Background
Increasing evidence has indicated an important role for estrogen receptor beta 1 (ERβ1) in breast cancer. However, the role of ERβ1 in the metastasis of androgen receptor (AR)-positive triple-negative breast cancer (TNBC) and the underlying mechanisms are still unknown.
Methods
Stable ERβ1-expressing TNBC cell lines were generated for this study. We detected the abilities of cell migration and invasion by wound-healing and transwell assays and the expression of E-cadherin and N-cadherin by quantitative RT-PCR (qRT-PCR) and western blotting assays in TNBC cell lines. Chromatin immunoprecipitation (ChIP) analysis was performed to assess the effect of AR on ERβ1 promoter. Tumor metastasis was evaluated in vivo using a lung metastasis mouse model. Lastly, immunohistochemical expression of ERβ1 in TNBC tissues was analyzed and correlated with clinicopathological features.
Results
ERβ1 suppressed the invasion and migration abilities of AR-positive TNBC cells and induced the downregulation of ZEB1. ZEB1 overexpression abrogated the increase in E-cadherin expression and the decrease in N-cadherin expression modulated by ERβ1. A lung metastasis mouse model showed that the incidence of metastasis was lower in ERβ1-expressing TNBC cells. Further, AR activation increased the anti-metastatic effect of ERβ1 in AR-positive TNBC cells, which accelerated ERβ1 transcription by functioning as a transcription factor that bound to the promoter of ERβ1. No significant change was observed in AR expression induced by ERβ1. Immunohistochemistry (IHC) analysis of TNBC clinical samples showed that ERβ1 and AR were positive in 31.7% and 23.2% of samples, respectively. ERβ1 expression was negatively correlated with ZEB1 expression and lymph node metastasis, and positively correlated with the expression of AR and E-cadherin.
Conclusion
Our findings suggested a potential role of ERβ1 in metastasis of AR-positive TNBC and provided novel insights into the mechanism of action of ERβ1 and the possible relationship between ERβ1 and AR.
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Outcome of HIV-associated lymphoma in a resource-limited setting of Jos, Nigeria
Abstract
Background
Lymphoma is a leading cause of cancer-related death among human immunodeficiency virus (HIV)-infected individuals in the current era of potent anti-retroviral therapy (ART). Globally, mortality after HIV-associated lymphoma has profound regional variation. Little is known about HIV-associated lymphoma mortality in Nigeria and other resource-limited setting in sub-Saharan Africa. Therefore, we evaluated the all-cause mortality after lymphoma and associated risk factors including HIV at the Jos University Teaching Hospital (JUTH) Nigeria.
Methods
We conducted a ten-year retrospective cohort study of lymphoma patients managed in JUTH. The main outcome measured was all-cause mortality and HIV infection was the main exposure variable. Overall death rate was estimated using the total number of death events and cumulative follow up time from lymphoma diagnosis to death. Cox proportional hazard regression was used to assess factors associated with mortality after lymphoma diagnosis.
Results
Out of 40 lymphoma patients evaluated, 8(20.0%) were HIV positive and 32(80.0%) were HIV negative. After 127.63 person- years of follow-up, there were 16 deaths leading to a crude mortality rate of 40.0 per 100 person-years. The 2-year probability of survival was 30% for HIV-infected patients and 74% for HIV-uninfected. Median survival probability for HIV-infected patients was 2.1 years and 7.6 years for those without HIV. Unadjusted hazard of death was associated with late stage, HR 11.33(95% CI 2.55, 50.26,p = 0.001); low cumulative cycles of chemotherapy, HR 6.43(95% CI 1.80, 22.89,p = 0.004); greater age, HR 5.12(95% CI 1.45,18.08,p = 0.01); presence of comorbidity, HR 3.43(95% CI 1.10,10.78,p = 0.03); and HIV-infection, HR 3.32(95% CI 1.05, 10.51,p = 0.04). In an adjusted model only stage was significantly associated with death, AHR 5.45(1.14–26.06, p = 0.03).
Conclusion
Our findings suggest that HIV- infection accounted for three times probability of death in lymphoma patients compared to their HIV-uninfected counterparts due to late stage of lymphoma presentation in this population. Also initiation of chemotherapy was associated with lower probability of death among lymphoma patients managed at JUTH, Nigeria. Earlier stage at lymphoma diagnosis and prompt therapeutic intervention is likely to improve survival in these patients. Future research should undertake collaborative studies to obtain comprehensive regional data and identify unique risk factors of poor outcomes among HIV-infected patients with lymphoma in Nigeria.
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ERβ1 inhibits metastasis of androgen receptor-positive triple-negative breast cancer by suppressing ZEB1
Abstract
Background
Increasing evidence has indicated an important role for estrogen receptor beta 1 (ERβ1) in breast cancer. However, the role of ERβ1 in the metastasis of androgen receptor (AR)-positive triple-negative breast cancer (TNBC) and the underlying mechanisms are still unknown.
Methods
Stable ERβ1-expressing TNBC cell lines were generated for this study. We detected the abilities of cell migration and invasion by wound-healing and transwell assays and the expression of E-cadherin and N-cadherin by quantitative RT-PCR (qRT-PCR) and western blotting assays in TNBC cell lines. Chromatin immunoprecipitation (ChIP) analysis was performed to assess the effect of AR on ERβ1 promoter. Tumor metastasis was evaluated in vivo using a lung metastasis mouse model. Lastly, immunohistochemical expression of ERβ1 in TNBC tissues was analyzed and correlated with clinicopathological features.
Results
ERβ1 suppressed the invasion and migration abilities of AR-positive TNBC cells and induced the downregulation of ZEB1. ZEB1 overexpression abrogated the increase in E-cadherin expression and the decrease in N-cadherin expression modulated by ERβ1. A lung metastasis mouse model showed that the incidence of metastasis was lower in ERβ1-expressing TNBC cells. Further, AR activation increased the anti-metastatic effect of ERβ1 in AR-positive TNBC cells, which accelerated ERβ1 transcription by functioning as a transcription factor that bound to the promoter of ERβ1. No significant change was observed in AR expression induced by ERβ1. Immunohistochemistry (IHC) analysis of TNBC clinical samples showed that ERβ1 and AR were positive in 31.7% and 23.2% of samples, respectively. ERβ1 expression was negatively correlated with ZEB1 expression and lymph node metastasis, and positively correlated with the expression of AR and E-cadherin.
Conclusion
Our findings suggested a potential role of ERβ1 in metastasis of AR-positive TNBC and provided novel insights into the mechanism of action of ERβ1 and the possible relationship between ERβ1 and AR.
http://ift.tt/2rXbfja
Outcome of HIV-associated lymphoma in a resource-limited setting of Jos, Nigeria
Abstract
Background
Lymphoma is a leading cause of cancer-related death among human immunodeficiency virus (HIV)-infected individuals in the current era of potent anti-retroviral therapy (ART). Globally, mortality after HIV-associated lymphoma has profound regional variation. Little is known about HIV-associated lymphoma mortality in Nigeria and other resource-limited setting in sub-Saharan Africa. Therefore, we evaluated the all-cause mortality after lymphoma and associated risk factors including HIV at the Jos University Teaching Hospital (JUTH) Nigeria.
Methods
We conducted a ten-year retrospective cohort study of lymphoma patients managed in JUTH. The main outcome measured was all-cause mortality and HIV infection was the main exposure variable. Overall death rate was estimated using the total number of death events and cumulative follow up time from lymphoma diagnosis to death. Cox proportional hazard regression was used to assess factors associated with mortality after lymphoma diagnosis.
Results
Out of 40 lymphoma patients evaluated, 8(20.0%) were HIV positive and 32(80.0%) were HIV negative. After 127.63 person- years of follow-up, there were 16 deaths leading to a crude mortality rate of 40.0 per 100 person-years. The 2-year probability of survival was 30% for HIV-infected patients and 74% for HIV-uninfected. Median survival probability for HIV-infected patients was 2.1 years and 7.6 years for those without HIV. Unadjusted hazard of death was associated with late stage, HR 11.33(95% CI 2.55, 50.26,p = 0.001); low cumulative cycles of chemotherapy, HR 6.43(95% CI 1.80, 22.89,p = 0.004); greater age, HR 5.12(95% CI 1.45,18.08,p = 0.01); presence of comorbidity, HR 3.43(95% CI 1.10,10.78,p = 0.03); and HIV-infection, HR 3.32(95% CI 1.05, 10.51,p = 0.04). In an adjusted model only stage was significantly associated with death, AHR 5.45(1.14–26.06, p = 0.03).
Conclusion
Our findings suggest that HIV- infection accounted for three times probability of death in lymphoma patients compared to their HIV-uninfected counterparts due to late stage of lymphoma presentation in this population. Also initiation of chemotherapy was associated with lower probability of death among lymphoma patients managed at JUTH, Nigeria. Earlier stage at lymphoma diagnosis and prompt therapeutic intervention is likely to improve survival in these patients. Future research should undertake collaborative studies to obtain comprehensive regional data and identify unique risk factors of poor outcomes among HIV-infected patients with lymphoma in Nigeria.
http://ift.tt/2rLNPMQ
Phase 2 study of intrabone single unit cord blood transplantation for hematological malignancies
Abstract
The outcomes of cord blood transplantation with non-irradiated reduced-intensity conditioning for hematological malignancies need to be improved because of graft failure and delayed engraftment. Intrabone infusion of cord blood cells has the potential to resolve the problems. In this phase 2 study, twenty-one adult patients with hematological malignancy received intrabone transplantation of serological HLA-A, B, and DR ≥4/6 matched single cord blood with a median number of cryopreserved total nucleated cells of 2.7 × 107/kg (range, 2.0-4.9 × 107/kg) following non-irradiated fludarabine-based reduced-intensity conditioning. Short-term methotrexate and tacrolimus were given as graft-versus-host disease prophylaxis, and granulocyte colony-stimulating factor was administered after transplantation. No severe adverse events related to intrabone injection were observed. The cumulative incidences of neutrophils ≥0.5 × 109/L, reticulocytes ≥1%, and platelets ≥20 × 109/L recoveries were 76.2%, 71.4%, and 76.2%, respectively, with median time to recoveries of 17, 28, and 32 days after transplantation, respectively. The probability of survival with neutrophil engraftment on day 60 was 71.4%, and overall survival at 1 year after transplantation was 52.4%. The incidences of grade II-IV and III-IV acute graft-versus-host disease were 44% and 19%, respectively, with no cases of chronic graft-versus-host disease. The present study demonstrated the safety of direct intrabone infusion of cord blood. Further analysis is required to confirm the efficacy of intrabone single cord blood transplantation with non-irradiated reduced-intensity conditioning for adult patients with hematological malignancy.
This article is protected by copyright. All rights reserved.
http://ift.tt/2rDDSif
Phase 2 study of intrabone single unit cord blood transplantation for hematological malignancies
Abstract
The outcomes of cord blood transplantation with non-irradiated reduced-intensity conditioning for hematological malignancies need to be improved because of graft failure and delayed engraftment. Intrabone infusion of cord blood cells has the potential to resolve the problems. In this phase 2 study, twenty-one adult patients with hematological malignancy received intrabone transplantation of serological HLA-A, B, and DR ≥4/6 matched single cord blood with a median number of cryopreserved total nucleated cells of 2.7 × 107/kg (range, 2.0-4.9 × 107/kg) following non-irradiated fludarabine-based reduced-intensity conditioning. Short-term methotrexate and tacrolimus were given as graft-versus-host disease prophylaxis, and granulocyte colony-stimulating factor was administered after transplantation. No severe adverse events related to intrabone injection were observed. The cumulative incidences of neutrophils ≥0.5 × 109/L, reticulocytes ≥1%, and platelets ≥20 × 109/L recoveries were 76.2%, 71.4%, and 76.2%, respectively, with median time to recoveries of 17, 28, and 32 days after transplantation, respectively. The probability of survival with neutrophil engraftment on day 60 was 71.4%, and overall survival at 1 year after transplantation was 52.4%. The incidences of grade II-IV and III-IV acute graft-versus-host disease were 44% and 19%, respectively, with no cases of chronic graft-versus-host disease. The present study demonstrated the safety of direct intrabone infusion of cord blood. Further analysis is required to confirm the efficacy of intrabone single cord blood transplantation with non-irradiated reduced-intensity conditioning for adult patients with hematological malignancy.
This article is protected by copyright. All rights reserved.
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Differential expression pattern of protein markers for predicting chemosensitivity of dexamethasone-based chemotherapy of B cell acute lymphoblastic leukemia
Abstract
Dexamethasone is considered as a direct chemotherapeutic agent in the treatment of pediatric acute lymphoblastic leukemia (ALL). Beside the advantages of the drug, some problems arising from the dose-related side effects are challenging issues during the treatment. Accordingly, the classification of patients to dexamethasone sensitive and resistance groups can help to select optimizing the therapeutic dose with the lowest adverse effects particularly in sensitive cases. For this purpose, we investigated inhibited proliferation and induced cytotoxicity in NALM-6 cells, as sensitive cells, after dexamethasone treatment. In addition, comparative protein expression analysis using the 2DE–MALDI–TOF MS technique was performed to identify the specific altered proteins. In addition, we evaluated mRNA expression levels of the identified proteins in bone-marrow samples from pediatric ALL patients using the real-time q-PCR method. Eventually, proteomic analysis revealed a combination of biomarkers, including capping proteins (CAPZA1 and CAPZB), chloride channel (CLIC1), purine nucleoside phosphorylase (PNP), and proteasome activator (PSME1), in response to the dexamethasone treatment. In addition, our results indicated low expression of identified proteins at both the mRNA and protein expression levels after drug treatment. Moreover, quantitative real-time PCR data analysis indicated that independent of the molecular subtypes of the leukemia, CAPZA1, CAPZB, CLIC1, and PNP expression levels were lower in ALL samples than normal samples, although PSME1 expression level was higher in ALL samples than normal samples. Furthermore, the expression level of all proteins (except PSME1) was different between high-risk and standard-risk patients that suggesting the prognostic value of them. In conclusion, our study suggests a panel of biomarkers comprising CAPZA1, CAPZB, CLIC1, PNP, and PSME1 as early diagnosis and treatment evaluation markers that may differentiate cancer cells which are presumably to benefit from dexamethasone-based chemotherapy and may facilitate the prediction of clinical outcome.
http://ift.tt/2rDiXfr
Differential expression pattern of protein markers for predicting chemosensitivity of dexamethasone-based chemotherapy of B cell acute lymphoblastic leukemia
Abstract
Dexamethasone is considered as a direct chemotherapeutic agent in the treatment of pediatric acute lymphoblastic leukemia (ALL). Beside the advantages of the drug, some problems arising from the dose-related side effects are challenging issues during the treatment. Accordingly, the classification of patients to dexamethasone sensitive and resistance groups can help to select optimizing the therapeutic dose with the lowest adverse effects particularly in sensitive cases. For this purpose, we investigated inhibited proliferation and induced cytotoxicity in NALM-6 cells, as sensitive cells, after dexamethasone treatment. In addition, comparative protein expression analysis using the 2DE–MALDI–TOF MS technique was performed to identify the specific altered proteins. In addition, we evaluated mRNA expression levels of the identified proteins in bone-marrow samples from pediatric ALL patients using the real-time q-PCR method. Eventually, proteomic analysis revealed a combination of biomarkers, including capping proteins (CAPZA1 and CAPZB), chloride channel (CLIC1), purine nucleoside phosphorylase (PNP), and proteasome activator (PSME1), in response to the dexamethasone treatment. In addition, our results indicated low expression of identified proteins at both the mRNA and protein expression levels after drug treatment. Moreover, quantitative real-time PCR data analysis indicated that independent of the molecular subtypes of the leukemia, CAPZA1, CAPZB, CLIC1, and PNP expression levels were lower in ALL samples than normal samples, although PSME1 expression level was higher in ALL samples than normal samples. Furthermore, the expression level of all proteins (except PSME1) was different between high-risk and standard-risk patients that suggesting the prognostic value of them. In conclusion, our study suggests a panel of biomarkers comprising CAPZA1, CAPZB, CLIC1, PNP, and PSME1 as early diagnosis and treatment evaluation markers that may differentiate cancer cells which are presumably to benefit from dexamethasone-based chemotherapy and may facilitate the prediction of clinical outcome.
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PET/CT scanning with 3D acquisition is feasible for quantifying myocardial blood flow when diagnosing coronary artery disease
Abstract
Background
The quantification of myocardial blood flow (MBF) and coronary flow reserve (CFR) are useful approaches for evaluating the functional severity of coronary artery disease (CAD). 15O-water positron emission tomography (PET) is considered the gold standard method for MBF quantification. However, MBF measurements in 15O-water PET with three-dimensional (3D) data acquisition, attenuation correction using computed tomography (CT), and time of flight have not been investigated in detail or validated. We conducted this study to evaluate the diagnostic potential of MBF measurements using PET/CT for a comparison of a control group and patients suspected of having CAD.
Results
Twenty-four patients with known or suspected CAD and eight age-matched healthy volunteers underwent rest and pharmacological stress perfusion studies with 15O-water PET/CT. The whole and three regional (left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA) territory) MBF values were estimated. The CFR was computed as the ratio of the MBF during adenosine triphosphate-induced stress to the MBF at rest. The inter-observer variability was assessed by two independent observers. PET/CT using a 15O-water dose of 500 MBq and 3D data acquisition showed good image quality. A strong inter-observer correlation was detected in both the whole MBF analysis and the regional analysis with high intra-class correlation coefficients (r > 0.90, p < 0.001). Regional MBF at rest (LAD, 0.82 ± 0.15 ml/min/g; LCX, 0.83 ± 0.17 ml/min/g; RCA, 0.71 ± 0.20 ml/min/g; p = 0.74), MBF at stress (LAD, 3.77 ± 1.00 ml/min/g; LCX, 3.56 ± 1.01 ml/min/g; RCA, 3.27 ± 1.04 ml/min/g; p = 0.62), and CFR (LAD, 4.64 ± 0.90; LCX, 4.30 ± 0.64; RCA, 4.64 ± 0.96; p = 0.66) of the healthy volunteers showed no significant difference among the three regions. The global CFR of the patients was significantly lower than that of the volunteers (2.75 ± 0.81 vs. 4.54 ± 0.66, p = 0.0002). The regional analysis of the patients demonstrated that the CFR tended to be lower in the stenotic region compared to the non-stenotic region (2.43 ± 0.81 vs. 2.95 ± 0.92, p = 0.052).
Conclusions
15O-water PET/CT with 3D data acquisition can be reliably used for the quantification of functional MBF and CFR in CAD patients.
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PET/CT scanning with 3D acquisition is feasible for quantifying myocardial blood flow when diagnosing coronary artery disease
Abstract
Background
The quantification of myocardial blood flow (MBF) and coronary flow reserve (CFR) are useful approaches for evaluating the functional severity of coronary artery disease (CAD). 15O-water positron emission tomography (PET) is considered the gold standard method for MBF quantification. However, MBF measurements in 15O-water PET with three-dimensional (3D) data acquisition, attenuation correction using computed tomography (CT), and time of flight have not been investigated in detail or validated. We conducted this study to evaluate the diagnostic potential of MBF measurements using PET/CT for a comparison of a control group and patients suspected of having CAD.
Results
Twenty-four patients with known or suspected CAD and eight age-matched healthy volunteers underwent rest and pharmacological stress perfusion studies with 15O-water PET/CT. The whole and three regional (left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA) territory) MBF values were estimated. The CFR was computed as the ratio of the MBF during adenosine triphosphate-induced stress to the MBF at rest. The inter-observer variability was assessed by two independent observers. PET/CT using a 15O-water dose of 500 MBq and 3D data acquisition showed good image quality. A strong inter-observer correlation was detected in both the whole MBF analysis and the regional analysis with high intra-class correlation coefficients (r > 0.90, p < 0.001). Regional MBF at rest (LAD, 0.82 ± 0.15 ml/min/g; LCX, 0.83 ± 0.17 ml/min/g; RCA, 0.71 ± 0.20 ml/min/g; p = 0.74), MBF at stress (LAD, 3.77 ± 1.00 ml/min/g; LCX, 3.56 ± 1.01 ml/min/g; RCA, 3.27 ± 1.04 ml/min/g; p = 0.62), and CFR (LAD, 4.64 ± 0.90; LCX, 4.30 ± 0.64; RCA, 4.64 ± 0.96; p = 0.66) of the healthy volunteers showed no significant difference among the three regions. The global CFR of the patients was significantly lower than that of the volunteers (2.75 ± 0.81 vs. 4.54 ± 0.66, p = 0.0002). The regional analysis of the patients demonstrated that the CFR tended to be lower in the stenotic region compared to the non-stenotic region (2.43 ± 0.81 vs. 2.95 ± 0.92, p = 0.052).
Conclusions
15O-water PET/CT with 3D data acquisition can be reliably used for the quantification of functional MBF and CFR in CAD patients.
http://ift.tt/2swy7mT
HPV Vaccination Linked to Decreased Oral HPV Infections
A study of more than 2,600 young adults found that the prevalence of oral infection with four HPV types, including two cancer-causing types, was 88% lower in those who reported receiving at least one dose of an HPV vaccine than in those not vaccinated.
http://ift.tt/2qTWFJ2
HPV Vaccination Linked to Decreased Oral HPV Infections
A study of more than 2,600 young adults found that the prevalence of oral infection with four HPV types, including two cancer-causing types, was 88% lower in those who reported receiving at least one dose of an HPV vaccine than in those not vaccinated.
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The prognostic significance of KRAS and BRAF mutation status in Korean colorectal cancer patients
Abstract
Background
BRAF and KRAS mutations are well-established biomarkers in anti-EGFR therapy. However, the prognostic significance of these mutations is still being examined. We determined the prognostic value of BRAF and KRAS mutations in Korean colorectal cancer (CRC) patients.
Methods
From July 2010 to September 2013, 1096 patients who underwent surgery for CRC at Seoul St. Mary's Hospital were included in the analysis. Resected specimens were examined for BRAF, KRAS, and microsatellite instability (MSI) status. All data were reviewed retrospectively.
Results
Among 1096 patients, 401 (36.7%) had KRAS mutations and 44 (4.0%) had BRAF mutations. Of 83 patients, 77 (92.8%) had microsatellite stable (MSS) or MSI low (MSI-L) status while 6 (7.2%) patients had MSI high (MSI-H) status. Patients with BRAF mutation demonstrated a worse disease-free survival (DFS, HR 1.990, CI 1.080–3.660, P = 0.02) and overall survival (OS, HR 3.470, CI 1.900–6.330, P < 0.0001). Regarding KRAS status, no significant difference was noted in DFS (P = 0.0548) or OS (P = 0.107). Comparing the MSS/MSI-L and MSI-H groups there were no significant differences in either DFS (P = 0.294) or OS (P = 0.557).
Conclusions
BRAF mutation, rather than KRAS, was a significant prognostic factor in Korean CRC patients at both early and advanced stages. The subgroup analysis for MSI did not show significant differences in clinical outcome. BRAF should be included in future larger prospective biomarker studies on CRC.
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The prognostic significance of KRAS and BRAF mutation status in Korean colorectal cancer patients
Abstract
Background
BRAF and KRAS mutations are well-established biomarkers in anti-EGFR therapy. However, the prognostic significance of these mutations is still being examined. We determined the prognostic value of BRAF and KRAS mutations in Korean colorectal cancer (CRC) patients.
Methods
From July 2010 to September 2013, 1096 patients who underwent surgery for CRC at Seoul St. Mary's Hospital were included in the analysis. Resected specimens were examined for BRAF, KRAS, and microsatellite instability (MSI) status. All data were reviewed retrospectively.
Results
Among 1096 patients, 401 (36.7%) had KRAS mutations and 44 (4.0%) had BRAF mutations. Of 83 patients, 77 (92.8%) had microsatellite stable (MSS) or MSI low (MSI-L) status while 6 (7.2%) patients had MSI high (MSI-H) status. Patients with BRAF mutation demonstrated a worse disease-free survival (DFS, HR 1.990, CI 1.080–3.660, P = 0.02) and overall survival (OS, HR 3.470, CI 1.900–6.330, P < 0.0001). Regarding KRAS status, no significant difference was noted in DFS (P = 0.0548) or OS (P = 0.107). Comparing the MSS/MSI-L and MSI-H groups there were no significant differences in either DFS (P = 0.294) or OS (P = 0.557).
Conclusions
BRAF mutation, rather than KRAS, was a significant prognostic factor in Korean CRC patients at both early and advanced stages. The subgroup analysis for MSI did not show significant differences in clinical outcome. BRAF should be included in future larger prospective biomarker studies on CRC.
http://ift.tt/2rWKUBK
Differential expression pattern of protein markers for predicting chemosensitivity of dexamethasone-based chemotherapy of B cell acute lymphoblastic leukemia
Abstract
Dexamethasone is considered as a direct chemotherapeutic agent in the treatment of pediatric acute lymphoblastic leukemia (ALL). Beside the advantages of the drug, some problems arising from the dose-related side effects are challenging issues during the treatment. Accordingly, the classification of patients to dexamethasone sensitive and resistance groups can help to select optimizing the therapeutic dose with the lowest adverse effects particularly in sensitive cases. For this purpose, we investigated inhibited proliferation and induced cytotoxicity in NALM-6 cells, as sensitive cells, after dexamethasone treatment. In addition, comparative protein expression analysis using the 2DE–MALDI–TOF MS technique was performed to identify the specific altered proteins. In addition, we evaluated mRNA expression levels of the identified proteins in bone-marrow samples from pediatric ALL patients using the real-time q-PCR method. Eventually, proteomic analysis revealed a combination of biomarkers, including capping proteins (CAPZA1 and CAPZB), chloride channel (CLIC1), purine nucleoside phosphorylase (PNP), and proteasome activator (PSME1), in response to the dexamethasone treatment. In addition, our results indicated low expression of identified proteins at both the mRNA and protein expression levels after drug treatment. Moreover, quantitative real-time PCR data analysis indicated that independent of the molecular subtypes of the leukemia, CAPZA1, CAPZB, CLIC1, and PNP expression levels were lower in ALL samples than normal samples, although PSME1 expression level was higher in ALL samples than normal samples. Furthermore, the expression level of all proteins (except PSME1) was different between high-risk and standard-risk patients that suggesting the prognostic value of them. In conclusion, our study suggests a panel of biomarkers comprising CAPZA1, CAPZB, CLIC1, PNP, and PSME1 as early diagnosis and treatment evaluation markers that may differentiate cancer cells which are presumably to benefit from dexamethasone-based chemotherapy and may facilitate the prediction of clinical outcome.
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Comprehensive genomic profiling of different subtypes of nasopharyngeal carcinoma reveals similarities and differences to guide targeted therapy
BACKGROUND
To date, no targeted therapy has been approved for nasopharyngeal carcinoma (NPC), and this underscores the need for an in-depth understanding of clinically relevant genomic alterations (CRGAs).
METHODS
Comprehensive genomic profiling was performed for 190 NPC patients, including 20 patients with nasopharyngeal adenocarcinoma (NPAC), 62 patients with nasopharyngeal squamous cell carcinoma (NPSCC), and 108 patients with nasopharyngeal undifferentiated carcinoma (NPUC). The associations of genes and pathways with subtypes, Epstein-Barr virus (EBV) infections, and the tumor mutation burden (TMB) were statistically evaluated.
RESULTS
Although the overall rates of genomic alterations were similar, the 3 NPC subtypes exhibited different mutational landscapes. Notably, mutations in a proven-treatable target gene, isocitrate dehydrogenase 2 (IDH2), were significantly associated with NPUC but not with NPAC or NPSCC. The top 5 ranked CRGAs included CDKN2A (29%), IDH2 (16%), SMARCB1 (7%), PIK3CA (6%), and NF1 (5%) in NPUC; CDKN2A (27%), PIK3CA (23%), FBXW7 (11%), PTEN (11%), and EGFR (8%) in NPSCC; and CDKN2A (20%), KRAS (15%), CCND1 (10%), MAP3K1 (10%), and NOTCH1 (10%) in NPAC. The incidence of EBV infections significantly correlated with the subtypes and with TP53, CDKN2A, and CDKN2B. The TMB status correlated with the subtypes and with LRP1B, FBXW7, and PIK3CA mutations as well as DNA repair, phosphoinositide 3-kinase/mammalian target of rapamycin, and mitogen-activated protein kinase pathways.
CONCLUSIONS
These results indicate that different NPC subtypes harbor different CRGAs. Both EBV infections and the TMB are associated with the NPC subtypes as well as the alterations of individual genes and pathways. The high frequency of IDH2 mutations in NPUC may facilitate potential targeted therapy and will ultimately point to new therapeutic strategies. Cancer 2017. © 2017 American Cancer Society.
http://ift.tt/2rWKjQt
Concurrent chemotherapy is associated with improved survival in elderly patients with bladder cancer undergoing radiotherapy
BACKGROUND
The current study was conducted to compare the overall survival (OS) of concurrent chemoradiotherapy (CCRT) versus radiotherapy (RT) alone in elderly patients (those aged ≥80 years) with muscle-invasive bladder cancer (MIBC).
METHODS
Patients aged ≥80 years with cT2-4, N0-3, M0 transitional cell MIBC who were treated with curative RT (60-70 Gray) or CCRT were identified in the National Cancer Data Base. Univariable and multivariable frailty survival analyses, as well as 1-to-1 propensity score matching, were used to isolate the association between CCRT and OS.
RESULTS
A total of 1369 patients who were treated with RT from 2004 through 2013 met eligibility criteria: 739 patients (54%) received RT alone and 630 patients (46%) received CCRT. The median age of the patients was 84 years (range, 80-90 years). The median follow-up was 21 months. The 2-year OS rate was 48%. When comparing CCRT with RT alone, the 2-year OS rate was 56% versus 42% (P<.0001), respectively. Multivariable analysis demonstrated that CCRT (hazard ratio [HR], 0.74; 95% confidence interval [95% CI], 0.65-0.84 [P<.0001]) and a higher RT dose (HR, 0.78; 95% CI, 0.67-0.90 [P<.001]) were associated with improved OS. T4 disease was associated with worse OS (HR, 1.42; 95% CI, 1.15-1.76 [P = .001]). After using 1-to-1 propensity score matching, there remained an OS benefit for the use of CCRT (HR, 0.77; 95% CI, 0.67-0.90 [P<.001]).
CONCLUSIONS
CCRT is associated with improved OS compared with the use of RT alone in elderly patients with MIBC, independent of Charlson-Deyo comorbidity score, suggesting that CCRT should be used in this population. Cancer 2017. © 2017 American Cancer Society.
http://ift.tt/2swcKSu
Voices of children and adolescents on phase 1 or phase 2 cancer trials: A new trial endpoint?
BACKGROUND
Pediatric participants on phase 1 or phase 2 clinical trials for incurable cancer are at risk of experiencing toxicities (adverse events [AEs]) related to trial participation. Multiple AEs are subjective; thus, the real impact of trial treatment cannot be known unless patient subjective reports are solicited.
METHODS
The authors assessed the feasibility and acceptability of soliciting symptom, function, and quality of life (QOL) reports from participants aged 8 to 18 years who were enrolled on phase 1/2 clinical trials at 4 cancer centers during the first course of chemotherapy. The authors also assessed the reliability and validity of 6 self-report Patient-Reported Outcomes Measurement Information System (PROMIS) pediatric measures and 4 open-ended interview questions at 2 time points (at the time of trial enrollment [T1] and 3 to 4 weeks later [T2]).
RESULTS
The enrollment rate of 75.9% (20 participants) exceeded the feasibility criterion, and missingness of measures by person, measure, and items at T1 and T2 were lower than the acceptability criteria. New QOL themes were limited to the impact of treatment on families and being away from home, family, and friends for treatment. All but one measure at T1 met the reliability criterion and all measures did so at T2. Validity support was limited however because as theorized, mobility decreased and fatigue increased as AEs increased.
CONCLUSIONS
Soliciting and documenting symptom, function, and QOL reports from patients aged 8 to 18 years who are enrolled on a phase 1/2 clinical trial is feasible and acceptable to participants, particularly when embedded in trials. Reliable and valid findings can result, making patient self-reported outcomes a possible new trial endpoint. Cancer 2017. © 2017 American Cancer Society.
http://ift.tt/2rWUVyY
Voices of children and adolescents on phase 1 or phase 2 cancer trials: A new trial endpoint?
BACKGROUND
Pediatric participants on phase 1 or phase 2 clinical trials for incurable cancer are at risk of experiencing toxicities (adverse events [AEs]) related to trial participation. Multiple AEs are subjective; thus, the real impact of trial treatment cannot be known unless patient subjective reports are solicited.
METHODS
The authors assessed the feasibility and acceptability of soliciting symptom, function, and quality of life (QOL) reports from participants aged 8 to 18 years who were enrolled on phase 1/2 clinical trials at 4 cancer centers during the first course of chemotherapy. The authors also assessed the reliability and validity of 6 self-report Patient-Reported Outcomes Measurement Information System (PROMIS) pediatric measures and 4 open-ended interview questions at 2 time points (at the time of trial enrollment [T1] and 3 to 4 weeks later [T2]).
RESULTS
The enrollment rate of 75.9% (20 participants) exceeded the feasibility criterion, and missingness of measures by person, measure, and items at T1 and T2 were lower than the acceptability criteria. New QOL themes were limited to the impact of treatment on families and being away from home, family, and friends for treatment. All but one measure at T1 met the reliability criterion and all measures did so at T2. Validity support was limited however because as theorized, mobility decreased and fatigue increased as AEs increased.
CONCLUSIONS
Soliciting and documenting symptom, function, and QOL reports from patients aged 8 to 18 years who are enrolled on a phase 1/2 clinical trial is feasible and acceptable to participants, particularly when embedded in trials. Reliable and valid findings can result, making patient self-reported outcomes a possible new trial endpoint. Cancer 2017. © 2017 American Cancer Society.
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Comprehensive genomic profiling of different subtypes of nasopharyngeal carcinoma reveals similarities and differences to guide targeted therapy
BACKGROUND
To date, no targeted therapy has been approved for nasopharyngeal carcinoma (NPC), and this underscores the need for an in-depth understanding of clinically relevant genomic alterations (CRGAs).
METHODS
Comprehensive genomic profiling was performed for 190 NPC patients, including 20 patients with nasopharyngeal adenocarcinoma (NPAC), 62 patients with nasopharyngeal squamous cell carcinoma (NPSCC), and 108 patients with nasopharyngeal undifferentiated carcinoma (NPUC). The associations of genes and pathways with subtypes, Epstein-Barr virus (EBV) infections, and the tumor mutation burden (TMB) were statistically evaluated.
RESULTS
Although the overall rates of genomic alterations were similar, the 3 NPC subtypes exhibited different mutational landscapes. Notably, mutations in a proven-treatable target gene, isocitrate dehydrogenase 2 (IDH2), were significantly associated with NPUC but not with NPAC or NPSCC. The top 5 ranked CRGAs included CDKN2A (29%), IDH2 (16%), SMARCB1 (7%), PIK3CA (6%), and NF1 (5%) in NPUC; CDKN2A (27%), PIK3CA (23%), FBXW7 (11%), PTEN (11%), and EGFR (8%) in NPSCC; and CDKN2A (20%), KRAS (15%), CCND1 (10%), MAP3K1 (10%), and NOTCH1 (10%) in NPAC. The incidence of EBV infections significantly correlated with the subtypes and with TP53, CDKN2A, and CDKN2B. The TMB status correlated with the subtypes and with LRP1B, FBXW7, and PIK3CA mutations as well as DNA repair, phosphoinositide 3-kinase/mammalian target of rapamycin, and mitogen-activated protein kinase pathways.
CONCLUSIONS
These results indicate that different NPC subtypes harbor different CRGAs. Both EBV infections and the TMB are associated with the NPC subtypes as well as the alterations of individual genes and pathways. The high frequency of IDH2 mutations in NPUC may facilitate potential targeted therapy and will ultimately point to new therapeutic strategies. Cancer 2017. © 2017 American Cancer Society.
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Concurrent chemotherapy is associated with improved survival in elderly patients with bladder cancer undergoing radiotherapy
BACKGROUND
The current study was conducted to compare the overall survival (OS) of concurrent chemoradiotherapy (CCRT) versus radiotherapy (RT) alone in elderly patients (those aged ≥80 years) with muscle-invasive bladder cancer (MIBC).
METHODS
Patients aged ≥80 years with cT2-4, N0-3, M0 transitional cell MIBC who were treated with curative RT (60-70 Gray) or CCRT were identified in the National Cancer Data Base. Univariable and multivariable frailty survival analyses, as well as 1-to-1 propensity score matching, were used to isolate the association between CCRT and OS.
RESULTS
A total of 1369 patients who were treated with RT from 2004 through 2013 met eligibility criteria: 739 patients (54%) received RT alone and 630 patients (46%) received CCRT. The median age of the patients was 84 years (range, 80-90 years). The median follow-up was 21 months. The 2-year OS rate was 48%. When comparing CCRT with RT alone, the 2-year OS rate was 56% versus 42% (P<.0001), respectively. Multivariable analysis demonstrated that CCRT (hazard ratio [HR], 0.74; 95% confidence interval [95% CI], 0.65-0.84 [P<.0001]) and a higher RT dose (HR, 0.78; 95% CI, 0.67-0.90 [P<.001]) were associated with improved OS. T4 disease was associated with worse OS (HR, 1.42; 95% CI, 1.15-1.76 [P = .001]). After using 1-to-1 propensity score matching, there remained an OS benefit for the use of CCRT (HR, 0.77; 95% CI, 0.67-0.90 [P<.001]).
CONCLUSIONS
CCRT is associated with improved OS compared with the use of RT alone in elderly patients with MIBC, independent of Charlson-Deyo comorbidity score, suggesting that CCRT should be used in this population. Cancer 2017. © 2017 American Cancer Society.
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The role of thyroid FNA cytology in pediatric malignant lesions: An overview of the literature
When one is dealing with pediatric thyroid lesions, fine-needle aspiration is the first diagnostic tool for the correct characterization of these nodules. Despite the apparent infrequency of thyroid cancers in children, recent data from the National Cancer Institute prove that the incidence has been increasing, especially in adolescents. With the same data, a higher prevalence of well-differentiated cancers can be estimated, with 90% diagnosed as papillary thyroid cancer. Nonetheless, some publications have demonstrated that some specific malignant variants are more frequent in children and have a more aggressive behavior that justifies the increased number of surgical procedures. For this reason, the American Thyroid Association recommends the performance of neck ultrasonography and fine-needle aspiration cytology (FNAC) for the evaluation of pediatric thyroid nodules. Accordingly, as reported in adult thyroid series, several authors have documented the high sensitivity and diagnostic accuracy of FNAC in pediatric series; they have also shared the same problematic issues encountered in adult populations, mostly in the diagnosis of indeterminate lesions. To provide precise clinical and/or surgical management, the correct cytological identification of specific malignant histotypes/entities should be mandatory because lymph nodes, distant metastases, and extrathyroidal infiltration are more frequent within specific histotypes. A perusal of the literature shows that their identification has not been extensively studied and investigated in cytological samples. This review focuses on the analysis of data from the literature on the evaluation of malignancies and specific morphological features in pediatric thyroid lesions. Cancer (Cancer Cytopathol) 2017. © 2017 American Cancer Society.
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Digital image analysis supports a nuclear-to-cytoplasmic ratio cutoff value of 0.5 for atypical urothelial cells
BACKGROUND
An elevated nuclear-to-cytoplasmic (N:C) ratio of ≥0.5 is a required criterion for the diagnosis of atypical urothelial cells (AUC) in The Paris System for Reporting Urinary Cytology.
METHODS
To validate the N:C ratio cutoff value and its predictive power for high-grade urothelial carcinoma (HGUC), the authors retrospectively reviewed the urinary tract cytology specimens of 15 cases of AUC with HGUC on follow-up (AUC-HGUC) and 33 cases of AUC without HGUC on follow-up (AUC-N-HGUC). The number of atypical cells in each case was recorded, and each atypical cell was photographed and digitally examined to calculate the nuclear size and N:C ratio.
RESULTS
On average, the maximum N:C ratios of atypical cells were significantly different between the AUC-HGUC and AUC-N-HGUC cohorts (0.53 vs 0.43; P =.00009), whereas the maximum nuclear sizes of atypical cells (153.43 μM2 vs 201.47 μM2; P = .69) and the number of atypical cells per case (10.13 vs 7.88; P = .12) were not found to be significantly different. Receiver operating characteristic analysis demonstrated that the maximum N:C ratio alone had high discriminatory capacity (area under the curve, 79.19%; 95% confidence interval, 64.19%-94.19%). The optimal maximum N:C ratio threshold was 0.486, giving a sensitivity of 73.3% and a specificity of 84.8% for predicting HGUC on follow-up.
CONCLUSIONS
The identification of AUC with an N:C ratio >0.486 has a high predictive power for HGUC on follow-up in AUC specimens. This justifies using the N:C ratio as a required criterion for the AUC category. Individual laboratories using different cytopreparation methods may require independent validation of the N:C ratio cutoff value. Cancer (Cancer Cytopathol) 2017. © 2017 American Cancer Society.
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The role of thyroid FNA cytology in pediatric malignant lesions: An overview of the literature
When one is dealing with pediatric thyroid lesions, fine-needle aspiration is the first diagnostic tool for the correct characterization of these nodules. Despite the apparent infrequency of thyroid cancers in children, recent data from the National Cancer Institute prove that the incidence has been increasing, especially in adolescents. With the same data, a higher prevalence of well-differentiated cancers can be estimated, with 90% diagnosed as papillary thyroid cancer. Nonetheless, some publications have demonstrated that some specific malignant variants are more frequent in children and have a more aggressive behavior that justifies the increased number of surgical procedures. For this reason, the American Thyroid Association recommends the performance of neck ultrasonography and fine-needle aspiration cytology (FNAC) for the evaluation of pediatric thyroid nodules. Accordingly, as reported in adult thyroid series, several authors have documented the high sensitivity and diagnostic accuracy of FNAC in pediatric series; they have also shared the same problematic issues encountered in adult populations, mostly in the diagnosis of indeterminate lesions. To provide precise clinical and/or surgical management, the correct cytological identification of specific malignant histotypes/entities should be mandatory because lymph nodes, distant metastases, and extrathyroidal infiltration are more frequent within specific histotypes. A perusal of the literature shows that their identification has not been extensively studied and investigated in cytological samples. This review focuses on the analysis of data from the literature on the evaluation of malignancies and specific morphological features in pediatric thyroid lesions. Cancer (Cancer Cytopathol) 2017. © 2017 American Cancer Society.
http://ift.tt/2qY6WPB
Digital image analysis supports a nuclear-to-cytoplasmic ratio cutoff value of 0.5 for atypical urothelial cells
BACKGROUND
An elevated nuclear-to-cytoplasmic (N:C) ratio of ≥0.5 is a required criterion for the diagnosis of atypical urothelial cells (AUC) in The Paris System for Reporting Urinary Cytology.
METHODS
To validate the N:C ratio cutoff value and its predictive power for high-grade urothelial carcinoma (HGUC), the authors retrospectively reviewed the urinary tract cytology specimens of 15 cases of AUC with HGUC on follow-up (AUC-HGUC) and 33 cases of AUC without HGUC on follow-up (AUC-N-HGUC). The number of atypical cells in each case was recorded, and each atypical cell was photographed and digitally examined to calculate the nuclear size and N:C ratio.
RESULTS
On average, the maximum N:C ratios of atypical cells were significantly different between the AUC-HGUC and AUC-N-HGUC cohorts (0.53 vs 0.43; P =.00009), whereas the maximum nuclear sizes of atypical cells (153.43 μM2 vs 201.47 μM2; P = .69) and the number of atypical cells per case (10.13 vs 7.88; P = .12) were not found to be significantly different. Receiver operating characteristic analysis demonstrated that the maximum N:C ratio alone had high discriminatory capacity (area under the curve, 79.19%; 95% confidence interval, 64.19%-94.19%). The optimal maximum N:C ratio threshold was 0.486, giving a sensitivity of 73.3% and a specificity of 84.8% for predicting HGUC on follow-up.
CONCLUSIONS
The identification of AUC with an N:C ratio >0.486 has a high predictive power for HGUC on follow-up in AUC specimens. This justifies using the N:C ratio as a required criterion for the AUC category. Individual laboratories using different cytopreparation methods may require independent validation of the N:C ratio cutoff value. Cancer (Cancer Cytopathol) 2017. © 2017 American Cancer Society.
http://ift.tt/2rtehdv
Clinical Impact of Mismatch Repair Protein Testing on Outcome of Early Staged Colorectal Carcinomas
Abstract
Introduction
Colorectal cancer is the third most common cancer in men and second most common in women globally. In the present study, we aimed to analyse the proportion of patients with loss of immunostaining for mismatch repair (MMR) proteins in all newly diagnosed stage II cases of colorectal cancer for the purpose of prognostication, for determination of further chemotherapeutic strategy and for familial screening.
Method
From January 2014 to December 2015, 62 consecutive newly diagnosed cases of stage II colorectal cancer were included in the study. Details of each patient related to their demographic profile and tumour profile were recorded. All the cases were grossed and staged according to College of American Pathologist (CAP) guidelines. The expression of MMR proteins (which was earlier validated on normal as well as tumour tissue) in FFPE tumour tissue using IHC for mut L homologue 1 (MLH1), mut S homologue 2 (MSH2), mut S homologue 6 (MSH6) and post-meiotic segregation increased 2 (PMS2) was studied. Information regarding stage, treatment, clinical outcome and overall survival was retrieved when available.
Results
Out of a total of 371 cases, 62 (16.7%) cases were of stage II CRC, out of which 43 (12%) were treatment naive. Among the selected 62 cases, 26 (41.9%) demonstrated loss of MMR proteins and 36 (58.0%) cases had intact nuclear expression. Out of the cases with MMR loss, 38.4% showed loss of MLH1 and PMS2, 30.7% showed loss of MSH2 and MSH6, 26.9% showed isolated loss of PMS2 and 3.8% showed isolated loss of MSH6. Right-sided location (57.6%) was more common than left-sided (19.2%) and transverse colon (23.0%). Majority of the cases were moderately differentiated (65.3%) in morphology. There was no intratumoural infiltrate in most of the cases (53.8%), and only 3.8% cases showed marked intratumoural infiltrate. Also, peritumoural lymphocytic infiltrate was mild to moderate in most of the cases (26.9%) and marked Crohn's-like infiltrate was seen in only 7.6% cases.
Conclusion
Our study shows that the routine evaluation of MMR proteins is achievable and essential for the purpose of prognostication, planning of treatment strategies and ascertaining a hereditary basis of CRC. The incidence of MMR protein loss was quite high in our study compared to other studies probably due to a difference in ethnicity. Though a right-sided predominance was supported, none of the typical morphological features of microsatellite instability (MSI) tumours were substantiated by our study, highlighting the lack of importance of histology for predicting MSI, and emphasising the point that MSI testing should be done as a routine procedure in all stage II CRC. A short follow-up was done for all our cases and comparison between the survival of the chemotherapy treated MSI cases versus those which were treatment naïve was performed and revealed that chemotherapy (CT) did not provide additional benefit to survival; MSI tumours in general are a better prognostic category and do not require additional chemotherapy.
http://ift.tt/2rWGye9
Clinical Impact of Mismatch Repair Protein Testing on Outcome of Early Staged Colorectal Carcinomas
Abstract
Introduction
Colorectal cancer is the third most common cancer in men and second most common in women globally. In the present study, we aimed to analyse the proportion of patients with loss of immunostaining for mismatch repair (MMR) proteins in all newly diagnosed stage II cases of colorectal cancer for the purpose of prognostication, for determination of further chemotherapeutic strategy and for familial screening.
Method
From January 2014 to December 2015, 62 consecutive newly diagnosed cases of stage II colorectal cancer were included in the study. Details of each patient related to their demographic profile and tumour profile were recorded. All the cases were grossed and staged according to College of American Pathologist (CAP) guidelines. The expression of MMR proteins (which was earlier validated on normal as well as tumour tissue) in FFPE tumour tissue using IHC for mut L homologue 1 (MLH1), mut S homologue 2 (MSH2), mut S homologue 6 (MSH6) and post-meiotic segregation increased 2 (PMS2) was studied. Information regarding stage, treatment, clinical outcome and overall survival was retrieved when available.
Results
Out of a total of 371 cases, 62 (16.7%) cases were of stage II CRC, out of which 43 (12%) were treatment naive. Among the selected 62 cases, 26 (41.9%) demonstrated loss of MMR proteins and 36 (58.0%) cases had intact nuclear expression. Out of the cases with MMR loss, 38.4% showed loss of MLH1 and PMS2, 30.7% showed loss of MSH2 and MSH6, 26.9% showed isolated loss of PMS2 and 3.8% showed isolated loss of MSH6. Right-sided location (57.6%) was more common than left-sided (19.2%) and transverse colon (23.0%). Majority of the cases were moderately differentiated (65.3%) in morphology. There was no intratumoural infiltrate in most of the cases (53.8%), and only 3.8% cases showed marked intratumoural infiltrate. Also, peritumoural lymphocytic infiltrate was mild to moderate in most of the cases (26.9%) and marked Crohn's-like infiltrate was seen in only 7.6% cases.
Conclusion
Our study shows that the routine evaluation of MMR proteins is achievable and essential for the purpose of prognostication, planning of treatment strategies and ascertaining a hereditary basis of CRC. The incidence of MMR protein loss was quite high in our study compared to other studies probably due to a difference in ethnicity. Though a right-sided predominance was supported, none of the typical morphological features of microsatellite instability (MSI) tumours were substantiated by our study, highlighting the lack of importance of histology for predicting MSI, and emphasising the point that MSI testing should be done as a routine procedure in all stage II CRC. A short follow-up was done for all our cases and comparison between the survival of the chemotherapy treated MSI cases versus those which were treatment naïve was performed and revealed that chemotherapy (CT) did not provide additional benefit to survival; MSI tumours in general are a better prognostic category and do not require additional chemotherapy.
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The vicious circle of treatment-induced toxicities in locally advanced head and neck cancer and the impact on treatment intensity
Publication date: Available online 4 June 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Bossi Paolo, Cossu Rocca Maria, Corvò Renzo, Depenni Roberta, Guardamagna Vittorio, Marinangeli Franco, Miccichè Francesco, Trippa Fabio
The intensity of the available treatment approaches for locally-advanced head and neck cancer (HNC) is at the upper limit of tolerance of acute toxicities. Several factors including breakthrough cancer pain, mucositis, dysphagia, local and systemic infections, and nutritional problems are related to treatment intensity. Particularly, pain, as symptom directly associated with the disease or combined with other treatment-related factors, has a major impact on quality of life of HNC patients and ultimately can influence the efficacy of treatments in HNC. Here, a Multidisciplinary Board of Italian Experts has addressed these issues, with the aim to identify the unmet need and appropriate strategies for the maintenance of optimal treatment intensity in HNC.
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The vicious circle of treatment-induced toxicities in locally advanced head and neck cancer and the impact on treatment intensity
Publication date: Available online 4 June 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Bossi Paolo, Cossu Rocca Maria, Corvò Renzo, Depenni Roberta, Guardamagna Vittorio, Marinangeli Franco, Miccichè Francesco, Trippa Fabio
The intensity of the available treatment approaches for locally-advanced head and neck cancer (HNC) is at the upper limit of tolerance of acute toxicities. Several factors including breakthrough cancer pain, mucositis, dysphagia, local and systemic infections, and nutritional problems are related to treatment intensity. Particularly, pain, as symptom directly associated with the disease or combined with other treatment-related factors, has a major impact on quality of life of HNC patients and ultimately can influence the efficacy of treatments in HNC. Here, a Multidisciplinary Board of Italian Experts has addressed these issues, with the aim to identify the unmet need and appropriate strategies for the maintenance of optimal treatment intensity in HNC.
http://ift.tt/2sw065S
Intussusception reduction: Effect of air vs. liquid enema on radiation dose
Abstract
Background
Both air and radiopaque liquid contrast are used to reduce ileocolic intussusception under fluoroscopy. Some suggest air lowers radiation dose due to shorter procedure times. However, air enema likely lowers radiation dose regardless of fluoroscopy time due to less density over the automatic exposure control cells.
Objectives
We test the hypothesis that air enema reduction of ileocolic intussusception results in lower radiation dose than liquid contrast enema independent of fluoroscopy time. We describe a role for automatic exposure control in this dose difference.
Materials and methods
We retrospectively evaluated air and liquid intussusception reductions performed on a single digital fluoroscopic unit during a 26-month period. We compared patient age, weight, gender, exam time of day and year, performing radiologist(s), radiographic image acquisitions, grid and magnification use, fluoroscopy time and dose area product. We compared categorical and continuous variables statistically using chi-square and Mann-Whitney U tests, respectively.
Results
The mean dose area product was 2.7-fold lower for air enema, 1.3 ± 0.9 dGy·cm2, than for liquid, 3.5 ± 2.5 dGy·cm2 (P<0.005). The mean fluoroscopy time was similar between techniques. The mean dose area product/min was 2.3-fold lower for air, 0.6 ± 0.2 dGy·cm2/min, than for liquid, 1.4 ± 0.5 dGy·cm2/min (P<0.001). No group differences were identified in other measured dose parameters.
Conclusion
Fluoroscopic intussusception reduction using air enema uses less than half the radiation dose of liquid contrast enema. Dose savings are independent of fluoroscopy time and are likely due to automatic exposure control interaction.
http://ift.tt/2rWJ8kf
Most children with cancer are not enrolled on a clinical trial in Canada: a population-based study
Abstract
Background
Primary objective was to describe the proportion of children newly diagnosed with cancer enrolled on a therapeutic clinical trial. Secondary objectives were to describe reasons for non-enrollment and factors associated with enrollment on trials.
Methods
In this retrospective cohort study, we included children newly diagnosed with cancer between 0 and 14 years of age and diagnosed from 2001 to 2012. We used data from the Cancer in Young People in Canada (CYP-C) national pediatric cancer population-based database. CYP-C captures all cases of pediatric cancer (0–14 years) diagnosed and treated at one of the 17 tertiary pediatric oncology centers in Canada. Non-enrollment was evaluated using univariate and multiple logistic regression analysis.
Results
There were 9204 children with cancer included, of whom 2533 (27.5%) were enrolled on a clinical trial. The most common reasons cited for non-enrollment were lack of an available trial (52.2%) and physician choice (11.2%). In multiple regression, Asian and Arab/west Asian race were associated with lower enrollment (P = 0.006 and P = 0.032 respectively). All cancer diagnoses were more likely to be enrolled compared to astrocytoma and children with acute lymphoblastic leukemia had an almost 18-fold increased odds of enrollment compared to astrocytoma (P < 0.0001). Greater distance from the tertiary care center was independently associated with non-enrollment (P < 0.0001).
Conclusions
In Canada, 27.5% of children with cancer are enrolled onto therapeutic clinical trials and lack of an available trial is the most common reason contributing to non-enrollment. Future research should better understand reasons for lack of trial availability and physician preferences to not offer trials.
http://ift.tt/2rCZyLH
Intussusception reduction: Effect of air vs. liquid enema on radiation dose
Abstract
Background
Both air and radiopaque liquid contrast are used to reduce ileocolic intussusception under fluoroscopy. Some suggest air lowers radiation dose due to shorter procedure times. However, air enema likely lowers radiation dose regardless of fluoroscopy time due to less density over the automatic exposure control cells.
Objectives
We test the hypothesis that air enema reduction of ileocolic intussusception results in lower radiation dose than liquid contrast enema independent of fluoroscopy time. We describe a role for automatic exposure control in this dose difference.
Materials and methods
We retrospectively evaluated air and liquid intussusception reductions performed on a single digital fluoroscopic unit during a 26-month period. We compared patient age, weight, gender, exam time of day and year, performing radiologist(s), radiographic image acquisitions, grid and magnification use, fluoroscopy time and dose area product. We compared categorical and continuous variables statistically using chi-square and Mann-Whitney U tests, respectively.
Results
The mean dose area product was 2.7-fold lower for air enema, 1.3 ± 0.9 dGy·cm2, than for liquid, 3.5 ± 2.5 dGy·cm2 (P<0.005). The mean fluoroscopy time was similar between techniques. The mean dose area product/min was 2.3-fold lower for air, 0.6 ± 0.2 dGy·cm2/min, than for liquid, 1.4 ± 0.5 dGy·cm2/min (P<0.001). No group differences were identified in other measured dose parameters.
Conclusion
Fluoroscopic intussusception reduction using air enema uses less than half the radiation dose of liquid contrast enema. Dose savings are independent of fluoroscopy time and are likely due to automatic exposure control interaction.
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Most children with cancer are not enrolled on a clinical trial in Canada: a population-based study
Abstract
Background
Primary objective was to describe the proportion of children newly diagnosed with cancer enrolled on a therapeutic clinical trial. Secondary objectives were to describe reasons for non-enrollment and factors associated with enrollment on trials.
Methods
In this retrospective cohort study, we included children newly diagnosed with cancer between 0 and 14 years of age and diagnosed from 2001 to 2012. We used data from the Cancer in Young People in Canada (CYP-C) national pediatric cancer population-based database. CYP-C captures all cases of pediatric cancer (0–14 years) diagnosed and treated at one of the 17 tertiary pediatric oncology centers in Canada. Non-enrollment was evaluated using univariate and multiple logistic regression analysis.
Results
There were 9204 children with cancer included, of whom 2533 (27.5%) were enrolled on a clinical trial. The most common reasons cited for non-enrollment were lack of an available trial (52.2%) and physician choice (11.2%). In multiple regression, Asian and Arab/west Asian race were associated with lower enrollment (P = 0.006 and P = 0.032 respectively). All cancer diagnoses were more likely to be enrolled compared to astrocytoma and children with acute lymphoblastic leukemia had an almost 18-fold increased odds of enrollment compared to astrocytoma (P < 0.0001). Greater distance from the tertiary care center was independently associated with non-enrollment (P < 0.0001).
Conclusions
In Canada, 27.5% of children with cancer are enrolled onto therapeutic clinical trials and lack of an available trial is the most common reason contributing to non-enrollment. Future research should better understand reasons for lack of trial availability and physician preferences to not offer trials.
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