The etiology of scrotal pain is clinically classified in terms of the necessity for emergency surgery. Lately, color Doppler ultrasonography has reduced unnecessary surgeries, but there are still some cases that require immediate exploration because of an uncertain diagnosis. Here, we describe the case of a 14-month-old boy, who could not deliver his complaint accurately, presenting with a grumpy mood and a red swollen scrotum. Emergency surgery revealed that the cause was intense inflammation of the hydrocele wall, which typically does not cause acute scrotum. We also reviewed rare etiologies of scrotal pain for general physicians to develop the differential diagnosis.
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Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Τετάρτη 7 Φεβρουαρίου 2018
Unusual Cause of Acute Scrotal Pain-Inflammatory Noncommunicating Hydrocele: A Pediatric Case Report
Nicotinamide N-methyltransferase: potential involvement in cutaneous malignant melanoma
Nicotinamide N-methyltransferase (NNMT) is an enzyme that catalyzes the N-methylation of nicotinamide and pyridine compounds, participating in xenobiotic and drug metabolism. Data on literature have evidenced a possible role of NNMT in many solid cancers, but no data are currently available in cutaneous melanoma. Recent important advances have been achieved in the treatment of advanced melanoma with targeted therapy and immunotherapy. However, the identification of biomarkers that can be used for the detection of early stage disease as well as for monitoring the therapeutic response during treatment is of utmost importance. The aim of this study was to study the possible role of NNMT in melanoma. In the present study, we carried out immunohistochemical analyses to evaluate the expression of the enzyme NNMT in 34 melanomas and 34 nevi. Moreover, we explored the relationship between NNMT levels and the prognostic parameters of patients with melanoma. The results obtained showed significantly (P
http://ift.tt/2EbzUHe
http://ift.tt/2EbzUHe
Clinical and Novel Biomarkers in the Management of Prostate Cancer
Opinion statement
Clinical outcomes in prostate cancer after initial screening and treatment for organ-confined disease and in advanced stage after drug intervention can be heterogeneous. Serum prostate-specific antigen which has a modest value as a screening biomarker while widely used in practice in all subsequent stages has limitations for prognostication or prediction of drug efficacy. Recent advances in genomic sciences and the identification of the mutational landscape of organ-confined and advanced-stage disease have contributed to the development of molecular biomarker profiling in addition to serum prostate-specific antigen. Genomic biomarkers are in development for application to screening for lethal disease subtypes, monitoring of disease recurrence after initial treatments, prognostication, as well as for prediction of drug efficacy. The application of translational molecular profiling in prostate cancer has the potential to enhance clinical management and outcomes in the future. Molecular biomarkers in development in organ-confined disease include both DNA- and RNA-based candidate and pathway-based biomarkers. In advanced-stage disease, molecular biomarker profiling has emerged for identifying therapeutic targets, prediction of drug efficacy, and for prognostication of survival that includes germline single nucleotide profiling and somatic aberrations including copy number variation and mutations and RNA-based profiling. This review summarizes the current state of clinical biomarkers used in practice, their limitations, and novel molecular biomarkers being developed for several clinical endpoints in early- and late-stage cancer.
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Options for Adjuvant Therapy for Uterine Leiomyosarcoma
Opinion statement
Uterine leiomyosarcoma (uLMS) is a rare disease; in the data from the SEER database, 3165 cases of uLMS were diagnosed between January 2000 and December 2012. While a majority of patients (60%) are diagnosed with early stage disease, recurrence rates are high. Five-year disease-specific survival is 76% for patients with FIGO stage I and 60% for patients with FIGO stage II disease. Adjuvant treatments, including radiation therapy, chemotherapy, and combined modality approaches, have been explored with the goal of demonstrating improved survival. However, heterogeneous patient populations, small sample sizes, and lack of no-treatment control arms have limited the interpretation and reliability of the results from these studies. A randomized trial of adjuvant pelvic radiation compared to no additional treatment showed that adjuvant radiation did not improve recurrence or survival outcomes for early-stage uterine LMS. To date, no prospective, randomized trial has been completed comparing adjuvant chemotherapy to observation. A recent well-designed retrospective study showed that women treated with adjuvant gemcitabine-docetaxel had no improvement in progression-free or overall survival compared to women who received no additional treatment. Thus, current data support our recommendation against adjuvant radiation or chemotherapy treatment for patients with non-morcellated, completely resected, and uterine-confined leiomyosarcoma. We recommend that these patients be observed with periodic surveillance imaging and physical examinations.
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Second Malignancies after Hematopoietic Stem Cell Transplantation
Opinion statement
Second malignancies are a rare but well-defined late complication after autologous and allogeneic hematopoietic stem-cell transplantation (SCT). Solid malignancies occur in up to 15% of patients 15 years after SCT with myeloablative conditioning, with no plateau in the incidence rates. They are responsible for 5–10% of late deaths after SCT. The incidence is increased with advanced age at SCT. The major risk factors are the use of total body irradiation, which is associated with adenocarcinomas and with chronic graft-versus-host disease which is associated with squamous cell cancers. There is less data on the incidence of second malignancies after reduced-intensity conditioning, but it may not be lower. The types of solid tumors reported in excess include melanoma and other skin cancers; cancers of the oral cavity and head and neck, brain, liver, uterine cervix, thyroid, breast, lung; and possibly gastrointestinal cancers. Therapy-related myeloid neoplasms (t-MN) are more common after autologous SCT and may be related mostly to pre-transplant therapies. Post-transplant lymphoproliferative disease is donor-cell-derived lymphoma that is more common after allogeneic SCT with T-cell depletion or intensive immune-suppression state. Second malignancies are most often treated similarly to the standard therapy for similar malignancies. Lifelong cancer screening and prevention interventions are required for all transplantation survivors.
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Novel Therapies for Older Adults With Acute Lymphoblastic Leukemia
Abstract
Purpose of Review
Older adults with acute lymphoblastic leukemia (ALL) have worse survival compared to their younger counterparts. Here, we review the reasons for the poorer outcomes of older patients with ALL and also summarize the current and future therapeutic approaches to ALL in the elderly population.
Recent Findings
The poor outcomes of older adults with ALL are driven largely by lack of tolerance to standard-dose chemotherapy, which leads to unacceptably high rates of myelosuppression-related deaths. Recent studies have shown promising results with the use of low-intensity or chemotherapy-free regimens in older patients with ALL, which are able to retain efficacy without excess toxicity.
Summary
Novel antibody constructs such as inotuzumab ozogamicin and blinatumomab as well as potent later-generation tyrosine kinase inhibitors such as ponatinib hold significant promise in the management of ALL in the older adult. Innovative combination strategies may further improve the outcomes of these patients.
from Cancer via ola Kala on Inoreader http://ift.tt/2FUWbW9
via IFTTT
Clinical and Novel Biomarkers in the Management of Prostate Cancer
Opinion statement
Clinical outcomes in prostate cancer after initial screening and treatment for organ-confined disease and in advanced stage after drug intervention can be heterogeneous. Serum prostate-specific antigen which has a modest value as a screening biomarker while widely used in practice in all subsequent stages has limitations for prognostication or prediction of drug efficacy. Recent advances in genomic sciences and the identification of the mutational landscape of organ-confined and advanced-stage disease have contributed to the development of molecular biomarker profiling in addition to serum prostate-specific antigen. Genomic biomarkers are in development for application to screening for lethal disease subtypes, monitoring of disease recurrence after initial treatments, prognostication, as well as for prediction of drug efficacy. The application of translational molecular profiling in prostate cancer has the potential to enhance clinical management and outcomes in the future. Molecular biomarkers in development in organ-confined disease include both DNA- and RNA-based candidate and pathway-based biomarkers. In advanced-stage disease, molecular biomarker profiling has emerged for identifying therapeutic targets, prediction of drug efficacy, and for prognostication of survival that includes germline single nucleotide profiling and somatic aberrations including copy number variation and mutations and RNA-based profiling. This review summarizes the current state of clinical biomarkers used in practice, their limitations, and novel molecular biomarkers being developed for several clinical endpoints in early- and late-stage cancer.
http://ift.tt/2GUO9ho
Options for Adjuvant Therapy for Uterine Leiomyosarcoma
Opinion statement
Uterine leiomyosarcoma (uLMS) is a rare disease; in the data from the SEER database, 3165 cases of uLMS were diagnosed between January 2000 and December 2012. While a majority of patients (60%) are diagnosed with early stage disease, recurrence rates are high. Five-year disease-specific survival is 76% for patients with FIGO stage I and 60% for patients with FIGO stage II disease. Adjuvant treatments, including radiation therapy, chemotherapy, and combined modality approaches, have been explored with the goal of demonstrating improved survival. However, heterogeneous patient populations, small sample sizes, and lack of no-treatment control arms have limited the interpretation and reliability of the results from these studies. A randomized trial of adjuvant pelvic radiation compared to no additional treatment showed that adjuvant radiation did not improve recurrence or survival outcomes for early-stage uterine LMS. To date, no prospective, randomized trial has been completed comparing adjuvant chemotherapy to observation. A recent well-designed retrospective study showed that women treated with adjuvant gemcitabine-docetaxel had no improvement in progression-free or overall survival compared to women who received no additional treatment. Thus, current data support our recommendation against adjuvant radiation or chemotherapy treatment for patients with non-morcellated, completely resected, and uterine-confined leiomyosarcoma. We recommend that these patients be observed with periodic surveillance imaging and physical examinations.
http://ift.tt/2FYC35z
Second Malignancies after Hematopoietic Stem Cell Transplantation
Opinion statement
Second malignancies are a rare but well-defined late complication after autologous and allogeneic hematopoietic stem-cell transplantation (SCT). Solid malignancies occur in up to 15% of patients 15 years after SCT with myeloablative conditioning, with no plateau in the incidence rates. They are responsible for 5–10% of late deaths after SCT. The incidence is increased with advanced age at SCT. The major risk factors are the use of total body irradiation, which is associated with adenocarcinomas and with chronic graft-versus-host disease which is associated with squamous cell cancers. There is less data on the incidence of second malignancies after reduced-intensity conditioning, but it may not be lower. The types of solid tumors reported in excess include melanoma and other skin cancers; cancers of the oral cavity and head and neck, brain, liver, uterine cervix, thyroid, breast, lung; and possibly gastrointestinal cancers. Therapy-related myeloid neoplasms (t-MN) are more common after autologous SCT and may be related mostly to pre-transplant therapies. Post-transplant lymphoproliferative disease is donor-cell-derived lymphoma that is more common after allogeneic SCT with T-cell depletion or intensive immune-suppression state. Second malignancies are most often treated similarly to the standard therapy for similar malignancies. Lifelong cancer screening and prevention interventions are required for all transplantation survivors.
http://ift.tt/2GZ9k1G
Novel Therapies for Older Adults With Acute Lymphoblastic Leukemia
Abstract
Purpose of Review
Older adults with acute lymphoblastic leukemia (ALL) have worse survival compared to their younger counterparts. Here, we review the reasons for the poorer outcomes of older patients with ALL and also summarize the current and future therapeutic approaches to ALL in the elderly population.
Recent Findings
The poor outcomes of older adults with ALL are driven largely by lack of tolerance to standard-dose chemotherapy, which leads to unacceptably high rates of myelosuppression-related deaths. Recent studies have shown promising results with the use of low-intensity or chemotherapy-free regimens in older patients with ALL, which are able to retain efficacy without excess toxicity.
Summary
Novel antibody constructs such as inotuzumab ozogamicin and blinatumomab as well as potent later-generation tyrosine kinase inhibitors such as ponatinib hold significant promise in the management of ALL in the older adult. Innovative combination strategies may further improve the outcomes of these patients.
http://ift.tt/2FUWbW9
Final Validation of the ProMisE Molecular Classifier for Endometrial Carcinoma in a Large Population-based Case Series.
Abstract
Introduction
Based on The Cancer Genome Atlas, we previously developed and confirmed a pragmatic molecular classifier for endometrial cancers; ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer). ProMisE identifies four prognostically distinct molecular subtypes, and can be applied to diagnostic specimens (biopsy/curettings), enabling earlier informed decision-making. We have strictly adhered to the Institute of Medicine (IOM) guidelines for the development of genomic biomarkers, and herein present the final validation step of a locked-down classifier prior to clinical application. Patients and Methods
We assessed a retrospective cohort of women from the Tübingen University Women's Hospital treated for endometrial carcinoma between 2003-13. Primary outcomes of overall, disease-specific and progression-free survival were evaluated for clinical, pathological, and molecular features. Results
Complete clinical and molecular data were evaluable from 452 women. Patient age ranged from 29 – 93 (median 65) years, and 87.8% cases were endometrioid histotype. Grade distribution included 282 (62.4%) G1, 75 (16.6%) G2, and 95 (21.0%) G3 tumors. 276 (61.1%) patients had stage IA disease, with the remaining stage IB (89 (19.7%)), stage II (26 (5.8%)), and stage III/IV (61 (13.5%)). ProMisE molecular classification yielded 127 (28.1%) MMR-D, 42 (9.3%) POLE, 55 (12.2%) p53abn, and 228 (50.4%) p53wt. ProMisE was a prognostic marker for progression-free (P=0.001) and disease-specific (P=0.03) survival even after adjusting for known risk factors. Concordance between diagnostic and surgical specimens was highly favorable; accuracy 0.91, kappa 0.88. Discussion
We have developed, confirmed and now validated a pragmatic molecular classification tool (ProMisE) that provides consistent categorization of tumors and identifies four distinct prognostic molecular subtypes. ProMisE can be applied to diagnostic samples and thus could be used to inform surgical procedure(s) and/or need for adjuvant therapy. Based on the IOM guidelines this classifier is now ready for clinical evaluation through prospective clinical trials.http://ift.tt/2nQTAVT
Epigenetic modifiers as new immunomodulatory therapies in solid tumours
Abstract
Background
Immune therapies have revolutionized cancer treatment over the last few years by allowing improvements in overall survival. However, the majority of patients is still primary or secondary resistant to such therapies, and enhancing sensitivity to immune therapies is therefore crucial to improve patient outcome. Several recent lines of evidence suggest that epigenetic modifiers have intrinsic immunomodulatory properties, which could be of therapeutic interest. Material and Methods
We reviewed preclinical evidence and clinical studies which describe or exploit immunomodulatory properties of epigenetic agents. Experimental approaches, clinical applicability and corresponding ongoing clinical trials are described. Results
Several epigenetic modifiers, such as histone deacetylase inhibitors, DNA methyl transferase inhibitors, bromodomain inhibitors, lysine-specific histone demethylase 1 inhibitors and enhancer of zeste homolog 2 inhibitors, display intrinsic immunomodulatory properties. The latter can be achieved through the action of these drugs either on cancer cells (e.g. presentation and generation of neoantigens, induction of immunogenic cell death, modulation of cytokine secretion), on immune cells (e.g. linage, differentiation, activation status and antitumor capability), or on components of the microenvironment (e.g. regulatory T cells and macrophages). Several promising combinations, notably with immune checkpoint blockers or adoptive T cell therapy, can be envisioned. Dedicated clinically-relevant approaches for patient selection and trial design will be required to optimally develop such combinations. Conclusion
In an era where immune therapies are becoming a treatment backbone in many tumour types, epigenetic modifiers could play a crucial role in modulating tumours' immunogenicity and sensitivity to immune agents. Optimal trial design, including window of opportunity trials, will be key in the success of this approach, and clinical evaluation is ongoing.http://ift.tt/2nKoH6g
Final Validation of the ProMisE Molecular Classifier for Endometrial Carcinoma in a Large Population-based Case Series.
Abstract
Introduction
Based on The Cancer Genome Atlas, we previously developed and confirmed a pragmatic molecular classifier for endometrial cancers; ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer). ProMisE identifies four prognostically distinct molecular subtypes, and can be applied to diagnostic specimens (biopsy/curettings), enabling earlier informed decision-making. We have strictly adhered to the Institute of Medicine (IOM) guidelines for the development of genomic biomarkers, and herein present the final validation step of a locked-down classifier prior to clinical application. Patients and Methods
We assessed a retrospective cohort of women from the Tübingen University Women's Hospital treated for endometrial carcinoma between 2003-13. Primary outcomes of overall, disease-specific and progression-free survival were evaluated for clinical, pathological, and molecular features. Results
Complete clinical and molecular data were evaluable from 452 women. Patient age ranged from 29 – 93 (median 65) years, and 87.8% cases were endometrioid histotype. Grade distribution included 282 (62.4%) G1, 75 (16.6%) G2, and 95 (21.0%) G3 tumors. 276 (61.1%) patients had stage IA disease, with the remaining stage IB (89 (19.7%)), stage II (26 (5.8%)), and stage III/IV (61 (13.5%)). ProMisE molecular classification yielded 127 (28.1%) MMR-D, 42 (9.3%) POLE, 55 (12.2%) p53abn, and 228 (50.4%) p53wt. ProMisE was a prognostic marker for progression-free (P=0.001) and disease-specific (P=0.03) survival even after adjusting for known risk factors. Concordance between diagnostic and surgical specimens was highly favorable; accuracy 0.91, kappa 0.88. Discussion
We have developed, confirmed and now validated a pragmatic molecular classification tool (ProMisE) that provides consistent categorization of tumors and identifies four distinct prognostic molecular subtypes. ProMisE can be applied to diagnostic samples and thus could be used to inform surgical procedure(s) and/or need for adjuvant therapy. Based on the IOM guidelines this classifier is now ready for clinical evaluation through prospective clinical trials.from Cancer via ola Kala on Inoreader http://ift.tt/2nQTAVT
via IFTTT
Epigenetic modifiers as new immunomodulatory therapies in solid tumours
Abstract
Background
Immune therapies have revolutionized cancer treatment over the last few years by allowing improvements in overall survival. However, the majority of patients is still primary or secondary resistant to such therapies, and enhancing sensitivity to immune therapies is therefore crucial to improve patient outcome. Several recent lines of evidence suggest that epigenetic modifiers have intrinsic immunomodulatory properties, which could be of therapeutic interest. Material and Methods
We reviewed preclinical evidence and clinical studies which describe or exploit immunomodulatory properties of epigenetic agents. Experimental approaches, clinical applicability and corresponding ongoing clinical trials are described. Results
Several epigenetic modifiers, such as histone deacetylase inhibitors, DNA methyl transferase inhibitors, bromodomain inhibitors, lysine-specific histone demethylase 1 inhibitors and enhancer of zeste homolog 2 inhibitors, display intrinsic immunomodulatory properties. The latter can be achieved through the action of these drugs either on cancer cells (e.g. presentation and generation of neoantigens, induction of immunogenic cell death, modulation of cytokine secretion), on immune cells (e.g. linage, differentiation, activation status and antitumor capability), or on components of the microenvironment (e.g. regulatory T cells and macrophages). Several promising combinations, notably with immune checkpoint blockers or adoptive T cell therapy, can be envisioned. Dedicated clinically-relevant approaches for patient selection and trial design will be required to optimally develop such combinations. Conclusion
In an era where immune therapies are becoming a treatment backbone in many tumour types, epigenetic modifiers could play a crucial role in modulating tumours' immunogenicity and sensitivity to immune agents. Optimal trial design, including window of opportunity trials, will be key in the success of this approach, and clinical evaluation is ongoing.from Cancer via ola Kala on Inoreader http://ift.tt/2nKoH6g
via IFTTT
Tumor necrosis and >20 mitoses per 50 high-power fields can distinguish ‘very high-risk’ and ‘highest-risk’ within ‘high-risk’ gastric gastrointestinal stromal tumor
Future Oncology, Ahead of Print.
http://ift.tt/2nRMGj4
Why does a high-fat diet increase cancer risk?
Future Oncology, Ahead of Print.
http://ift.tt/2nLHy0H
High-fat diet and colorectal cancer: myths and facts
Future Oncology, Ahead of Print.
http://ift.tt/2nSjF78
Tumor necrosis and >20 mitoses per 50 high-power fields can distinguish ‘very high-risk’ and ‘highest-risk’ within ‘high-risk’ gastric gastrointestinal stromal tumor
Future Oncology, Ahead of Print.
from Cancer via ola Kala on Inoreader http://ift.tt/2nRMGj4
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Why does a high-fat diet increase cancer risk?
Future Oncology, Ahead of Print.
from Cancer via ola Kala on Inoreader http://ift.tt/2nLHy0H
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High-fat diet and colorectal cancer: myths and facts
Future Oncology, Ahead of Print.
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The impact of anaemia, transfusion dependency, comorbidities and polypharmacy in elderly patients with low-risk myelodysplastic syndromes
Abstract
Myelodysplastic syndromes (MDS) are heterogeneous clonal disorders ranging from indolent conditions with a near-normal life expectancy to forms approaching acute myeloid leukaemia. Comorbid conditions have rarely been systematically studied among patients with MDS. Older age per se has a negative impact on survival of MDS patients, in particular of those with lower risk. However, age indirectly affects also the survival of higher-risk patients by limiting their eligibility to intensive treatments. In addition, ageing is associated with an increasingly high risk of developing comorbidity, and a high prevalence of comorbid diseases has indeed been reported in MDS patients. The impact of multi-morbidities/comorbidities and polypharmacy in patients with low-risk MDS patients is a poorly explored topic. We focused on medications, multi-morbidities and comorbidities of 155 low-risk MDS patients followed in the haematological outpatients clinics or in medical/oncology wards of our University Hospital. One or more comorbidities were present at diagnosis in 24 younger patients with MDS syndromes (31%), whereas 56 older patients with MDS (75%) presented 1 or more comorbidities (P < 0.001).The most frequent comorbidity was cardiac comorbidity 18% in younger patients and 25% in older patients. With no statistical significance between older and younger patients, congestive heart failure was the most frequent observed disease. Our study has shown a statistical correlation between transfusion dependency and polypathology (P = 0.0014). These data were also confirmed in a subanalysis of the younger group of patients. Our study has shown that comorbidity is very common among patients with MDS, potentially affecting the clinical course and outcome of MDS patients.
http://ift.tt/2nSEsr8
The impact of anaemia, transfusion dependency, comorbidities and polypharmacy in elderly patients with low-risk myelodysplastic syndromes
Abstract
Myelodysplastic syndromes (MDS) are heterogeneous clonal disorders ranging from indolent conditions with a near-normal life expectancy to forms approaching acute myeloid leukaemia. Comorbid conditions have rarely been systematically studied among patients with MDS. Older age per se has a negative impact on survival of MDS patients, in particular of those with lower risk. However, age indirectly affects also the survival of higher-risk patients by limiting their eligibility to intensive treatments. In addition, ageing is associated with an increasingly high risk of developing comorbidity, and a high prevalence of comorbid diseases has indeed been reported in MDS patients. The impact of multi-morbidities/comorbidities and polypharmacy in patients with low-risk MDS patients is a poorly explored topic. We focused on medications, multi-morbidities and comorbidities of 155 low-risk MDS patients followed in the haematological outpatients clinics or in medical/oncology wards of our University Hospital. One or more comorbidities were present at diagnosis in 24 younger patients with MDS syndromes (31%), whereas 56 older patients with MDS (75%) presented 1 or more comorbidities (P < 0.001).The most frequent comorbidity was cardiac comorbidity 18% in younger patients and 25% in older patients. With no statistical significance between older and younger patients, congestive heart failure was the most frequent observed disease. Our study has shown a statistical correlation between transfusion dependency and polypathology (P = 0.0014). These data were also confirmed in a subanalysis of the younger group of patients. Our study has shown that comorbidity is very common among patients with MDS, potentially affecting the clinical course and outcome of MDS patients.
from Cancer via ola Kala on Inoreader http://ift.tt/2nSEsr8
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First international TNBC conference meeting report
Abstract
Recently, Georgia State University's Centennial Hall was the premier location for the 2017 International Conference on Triple Negative Breast Cancer (TNBC): Illuminating Actionable Biology, which was held from Sept. 18 to 20, 2017, in Atlanta, USA. The conference featured a stellar line-up of domestic and international speakers and diverse participants including TNBC survivors, luminaries in breast cancer research, medical students and fellows, clinicians, translational researchers, epidemiologists, biostatisticians, bioinformaticians, and representatives from the industry. This report distills the burning questions that spiked the event and summarizes key themes, findings, unique opportunities and future directions that emerged from this confluence of thought leaders.
http://ift.tt/2EcIGon
Clinical relevance of oncologic prognostic factors in the decision-making of pre-hepatectomy chemotherapy for colorectal cancer hepatic metastasis: the priority of hepatectomy
Abstract
Background
Although liver resection (LR) provides the best chance of long-term survival for patients with colorectal cancer (CRC) hepatic metastasis, concerns regarding chemotherapy before liver resection remain unresolved.
Methods
A retrospective review of patients who underwent curative LR for CRC hepatic metastasis between January 2008 and February 2016 was performed. Outcome relevance based on oncologic prognostic factors and chemotherapy prior to liver resection was assessed.
Results
Patients who had received pre-hepatectomy chemotherapy for CRC hepatic metastasis and delayed liver resection had a worse outcome in terms of CRC recurrence following liver resection. The hazard ratio (HR) of pre-hepatectomy chemotherapy in patients with minor oncologic prognostic factors was 1.55 (confidence interval, CI = 1.07–2.26, p = 0.021) for CRC recurrence after liver resection for hepatic metastasis, whereas the HR of pre-hepatectomy chemotherapy was 1.34 (CI = 0.99–1.81, p = 0.062) for CRC recurrence in patients with multiple oncologic prognostic factors.
Conclusion
The administration of pre-hepatectomy chemotherapy and delaying liver resection seems not to be an optimal strategy to provide a clinical benefit for patients with CRC hepatic metastasis. Hence, liver resection should be attempted without delay at the initial detection of CRC hepatic metastasis whenever possible.
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Clinical relevance of oncologic prognostic factors in the decision-making of pre-hepatectomy chemotherapy for colorectal cancer hepatic metastasis: the priority of hepatectomy
Abstract
Background
Although liver resection (LR) provides the best chance of long-term survival for patients with colorectal cancer (CRC) hepatic metastasis, concerns regarding chemotherapy before liver resection remain unresolved.
Methods
A retrospective review of patients who underwent curative LR for CRC hepatic metastasis between January 2008 and February 2016 was performed. Outcome relevance based on oncologic prognostic factors and chemotherapy prior to liver resection was assessed.
Results
Patients who had received pre-hepatectomy chemotherapy for CRC hepatic metastasis and delayed liver resection had a worse outcome in terms of CRC recurrence following liver resection. The hazard ratio (HR) of pre-hepatectomy chemotherapy in patients with minor oncologic prognostic factors was 1.55 (confidence interval, CI = 1.07–2.26, p = 0.021) for CRC recurrence after liver resection for hepatic metastasis, whereas the HR of pre-hepatectomy chemotherapy was 1.34 (CI = 0.99–1.81, p = 0.062) for CRC recurrence in patients with multiple oncologic prognostic factors.
Conclusion
The administration of pre-hepatectomy chemotherapy and delaying liver resection seems not to be an optimal strategy to provide a clinical benefit for patients with CRC hepatic metastasis. Hence, liver resection should be attempted without delay at the initial detection of CRC hepatic metastasis whenever possible.
http://ift.tt/2Eole78
The Impact of Fellowship in Dietetics on Clinical Practice
Abstract
Medical nutrition therapy (MNT) in pediatric cancer treatment is essential. The Nutrition Department and the International Outreach Program at St. Jude Children's Research Hospital in Memphis, TN have worked together from 2005 to 2013 to develop and implement a training program for international dietitians working with pediatric oncology patients. During that time, St. Jude hosted 15 dietitians from various countries for this 3-week-long program. The curriculum provided experience in nutrition risk screening, nutrition care process, nutrition for cancer prevention, palliative care, and exposure to nutrition support. Monthly online meetings were established through the Cure4Kids website to continue collaboration and training. Learning outcomes were developed, and the impact of the program was evaluated based on changes made by former fellows in clinical practice, research, management, and food service upon return to their country. In addition, the program was evaluated based on recognition by the medical team, professional growth/networking, and personal growth. The survey return rate was 100%: responses revealed that 80% of participants continued working in pediatric oncology, 67% participated in monthly meetings, 47% collaborated on research, 100% advanced their competency in clinical practice, 93% broadened their competency in research, 67% became increasingly competent in management, 60% implemented changes in food service, 100% were recognized for participating in the program, and 100 and 93% noted that participation in the fellowship program helped their professional and personal growth, respectively. The psychological impact of the training on healthcare providers was as important as the impact of the program on patient care.
http://ift.tt/2sk3MvG
The Impact of Fellowship in Dietetics on Clinical Practice
Abstract
Medical nutrition therapy (MNT) in pediatric cancer treatment is essential. The Nutrition Department and the International Outreach Program at St. Jude Children's Research Hospital in Memphis, TN have worked together from 2005 to 2013 to develop and implement a training program for international dietitians working with pediatric oncology patients. During that time, St. Jude hosted 15 dietitians from various countries for this 3-week-long program. The curriculum provided experience in nutrition risk screening, nutrition care process, nutrition for cancer prevention, palliative care, and exposure to nutrition support. Monthly online meetings were established through the Cure4Kids website to continue collaboration and training. Learning outcomes were developed, and the impact of the program was evaluated based on changes made by former fellows in clinical practice, research, management, and food service upon return to their country. In addition, the program was evaluated based on recognition by the medical team, professional growth/networking, and personal growth. The survey return rate was 100%: responses revealed that 80% of participants continued working in pediatric oncology, 67% participated in monthly meetings, 47% collaborated on research, 100% advanced their competency in clinical practice, 93% broadened their competency in research, 67% became increasingly competent in management, 60% implemented changes in food service, 100% were recognized for participating in the program, and 100 and 93% noted that participation in the fellowship program helped their professional and personal growth, respectively. The psychological impact of the training on healthcare providers was as important as the impact of the program on patient care.
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The influence of tissue composition uncertainty on dose distributions in brachytherapy
Model-based dose calculation algorithms (MBDCAs) have evolved from serving as a research tool into clinical practice in brachytherapy. This study investigates primary sources of tissue elemental compositions used as input to MBDCAs and the impact of their variability on MBDCA-based dosimetry.
http://ift.tt/2GVFfQV
The first clinical implementation of real-time image-guided adaptive radiotherapy using a standard linear accelerator
Until now, real-time image guided adaptive radiation therapy (IGART) has been the domain of dedicated cancer radiotherapy systems. The purpose of this study was to clinically implement and investigate real-time IGART using a standard linear accelerator.
http://ift.tt/2FUXAfp
Diffusion pseudonormalization and clinical outcome in term neonates with hypoxic–ischemic encephalopathy
Abstract
Background
Pseudonormalization of diffusion-weighted magnetic resonance imaging (MRI) can lead to underestimation of brain injury in newborns with hypoxic–ischemic encephalopathy (HIE), posing a significant problem. We have noticed that some neonates show pseudonormalization negativity on diffusion-weighted imaging.
Objective
To compare pseudonormalization negativity with clinical outcomes.
Materials and methods
Seventeen term neonates with moderate or severe HIE underwent therapeutic hypothermia. They were examined by MRI twice at mean ages of 3 days and 10 days. We evaluated the presence of restricted diffusion, and also the presence or absence of pseudonormalization, by diffusion-weighted imaging at the time of the second MRI, and correlated the results with clinical outcome.
Results
DWI demonstrated no abnormality in seven neonates. Among the 10 neonates with abnormal diffusion-weighted imaging findings, 2 were positive for pseudonormalization and 8 were negative. Among neonates with normal diffusion-weighted imaging findings and with positivity for pseudonormalization, none had major disability. Among the eight neonates with pseudonormalization negativity, all but one, who was lost to follow-up, had major disability.
Conclusion
Abnormal diffusion-weighted imaging with pseudonormalization negativity might be predictive of severe brain injury and major disability. The second-week MRI is important for the judgment of pseudonormalization.
http://ift.tt/2BKGH97
Diffusion pseudonormalization and clinical outcome in term neonates with hypoxic–ischemic encephalopathy
Abstract
Background
Pseudonormalization of diffusion-weighted magnetic resonance imaging (MRI) can lead to underestimation of brain injury in newborns with hypoxic–ischemic encephalopathy (HIE), posing a significant problem. We have noticed that some neonates show pseudonormalization negativity on diffusion-weighted imaging.
Objective
To compare pseudonormalization negativity with clinical outcomes.
Materials and methods
Seventeen term neonates with moderate or severe HIE underwent therapeutic hypothermia. They were examined by MRI twice at mean ages of 3 days and 10 days. We evaluated the presence of restricted diffusion, and also the presence or absence of pseudonormalization, by diffusion-weighted imaging at the time of the second MRI, and correlated the results with clinical outcome.
Results
DWI demonstrated no abnormality in seven neonates. Among the 10 neonates with abnormal diffusion-weighted imaging findings, 2 were positive for pseudonormalization and 8 were negative. Among neonates with normal diffusion-weighted imaging findings and with positivity for pseudonormalization, none had major disability. Among the eight neonates with pseudonormalization negativity, all but one, who was lost to follow-up, had major disability.
Conclusion
Abnormal diffusion-weighted imaging with pseudonormalization negativity might be predictive of severe brain injury and major disability. The second-week MRI is important for the judgment of pseudonormalization.
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Flavagline analog FL3 induces cell cycle arrest in urothelial carcinoma cell of the bladder by inhibiting the Akt/PHB interaction to activate the GADD45α pathway
Prohibitin 1 (PHB) is a potential target for the treatment of urothelial carcinoma of the bladder (UCB). FL3 is a newly synthesized agent that inhibits cancer cell proliferation by targeting the PHB protein; h...
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Urban Neighborhood and Residential Factors Associated with Breast Cancer in African American Women: a Systematic Review
Abstract
Residential characteristics in urban neighborhoods impact health and might be important factors contributing to health disparities, especially in the African American population. The purpose of this systematic review is to understand the relationship between urban neighborhood and residential factors and breast cancer incidence and prognosis in African American women. Using PubMed and Web of Science, the existing literature was reviewed. Observational, cross-sectional, cohort, and prospective studies until February 2017 were examined. Studies including populations of African American women, setting in "urban" areas, and a measure of a neighborhood or residential factor were reviewed. Four parameters related to neighborhood or residential factors were extracted including: neighborhood socioeconomic status (nSES), residential segregation, spatial access to mammography, and residential pollution. Our analysis showed that African American women living in low nSES have greater odds of late stage diagnosis and mortality. Furthermore, African American women living in segregated areas (higher percentage of Blacks) have higher odds of late stage diagnosis and mortality compared to White and Hispanic women living in less segregated areas (lower percentage of Blacks). Late stage diagnosis was also shown to be significantly higher in areas with poor mammography access and areas with higher Black residential segregation. Lastly, residential pollution did not affect breast cancer risk in African American women. Overall, this systematic review provides a qualitative synthesis of major neighborhood and residential factors on breast cancer outcomes in African American women.
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Urban Neighborhood and Residential Factors Associated with Breast Cancer in African American Women: a Systematic Review
Abstract
Residential characteristics in urban neighborhoods impact health and might be important factors contributing to health disparities, especially in the African American population. The purpose of this systematic review is to understand the relationship between urban neighborhood and residential factors and breast cancer incidence and prognosis in African American women. Using PubMed and Web of Science, the existing literature was reviewed. Observational, cross-sectional, cohort, and prospective studies until February 2017 were examined. Studies including populations of African American women, setting in "urban" areas, and a measure of a neighborhood or residential factor were reviewed. Four parameters related to neighborhood or residential factors were extracted including: neighborhood socioeconomic status (nSES), residential segregation, spatial access to mammography, and residential pollution. Our analysis showed that African American women living in low nSES have greater odds of late stage diagnosis and mortality. Furthermore, African American women living in segregated areas (higher percentage of Blacks) have higher odds of late stage diagnosis and mortality compared to White and Hispanic women living in less segregated areas (lower percentage of Blacks). Late stage diagnosis was also shown to be significantly higher in areas with poor mammography access and areas with higher Black residential segregation. Lastly, residential pollution did not affect breast cancer risk in African American women. Overall, this systematic review provides a qualitative synthesis of major neighborhood and residential factors on breast cancer outcomes in African American women.
http://ift.tt/2ENRWfD
Two Cases of Hepatoblastoma in Young Adults
Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.
http://ift.tt/2EaGi1H
Two Cases of Hepatoblastoma in Young Adults
Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.
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Tobacco smoking and the risk of sudden cardiac death: a systematic review and meta-analysis of prospective studies
Abstract
Smoking is an established risk factor for cardiovascular disease including coronary heart disease and stroke, however, data regarding smoking and sudden cardiac death have not been summarized in a meta-analysis previously. We therefore conducted a systematic review and meta-analysis to clarify this association. We searched the PubMed and Embase databases for studies of smoking and sudden cardiac death up to July 20th 2017. Prospective studies were included if they reported adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for smoking and sudden cardiac death. Summary RRs were estimated by use of a random effects model. Twelve prospective studies were included. The summary RR was 3.06 (95% CI 2.46–3.82, I2 = 41%, pheterogeneity = 0.12, n = 7) for current smokers and 1.38 (95% CI 1.20–1.60, I2 = 0%, pheterogeneity = 0.55, n = 7) for former smokers compared to never smokers. For four studies using non-current (never + former) smokers as the reference category the summary RR among current smokers was 2.08 (95% CI 1.70–2.53, I2 = 18%, pheterogeneity = 0.30). The results persisted in most of the subgroup analyses. There was no evidence of publication bias. These results confirm that smoking increases the risk of sudden cardiac death. Any further studies should investigate in more detail the effects of duration of smoking, number of cigarettes per day, pack-years, and time since quitting smoking and sudden cardiac death.
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A statewide program providing colorectal cancer screening to the uninsured of South Carolina
BACKGROUND
Cancer screening rates are lowest in those without insurance or a regular provider. Since 2008, the Colorectal Cancer Prevention Network (CCPN) has provided open access colonoscopy to uninsured residents of South Carolina through established, statewide partnerships and patient navigation. Herein, we describe the structure, implementation, and clinical outcomes of this program.
METHODS
The CCPN provides access to colonoscopy screening at no cost to uninsured, asymptomatic patients aged 50-64 years (African Americans age 45-64 years are eligible) who live at or below 150% of the poverty line and seek medical care in free medical clinics, federally qualified health centers, or hospital-based indigent practices in South Carolina. Screening is performed by board-certified gastroenterologists. Descriptive statistics and regression analysis are used to describe the population screened, and to assess compliance rates and colonoscopy quality metrics.
RESULTS
Out of >4000 patients referred to the program, 1854 were deemed eligible, 1144 attended an in-person navigation visit, and 1030 completed a colonoscopy; 909 were included in the final sample. Nearly 90% of participants exhibited good-to-excellent bowel preparation. An overall cecal intubation rate of 99% was measured. The polyp detection rate and adenoma detection rate were 63% and 36%, respectively, with male sex and urban residence positively associated with adenoma detection. Over 13% of participants had an advanced polyp, and 1% had a cancer diagnosis or surgical intervention.
CONCLUSION
The CCPN program is characterized by strong collaboration with clinicians statewide, low no-show rates, and high colonoscopy quality. Future work will assess the effectiveness of the navigation approach and will explore the mechanisms driving higher adenoma detection in urban participants. Cancer 2018. © 2018 American Cancer Society.
http://ift.tt/2E6JsU1
Factors affecting early versus late remission in acromegaly following stereotactic radiosurgery
Abstract
Stereotactic radiosurgery (SRS) is a well-established treatment modality for patients with acromegaly. Our previously published study demonstrated a median time to remission of 29 months. This study aims to identify factors affecting the timing of remission and also to quantify the rate of late remission. This is a retrospective analysis of acromegaly patients who underwent SRS between 1988 and 2016. Early and late remissions were defined based on our prior median remission time of 29 months. The median imaging and endocrine follow-ups are 66 and 104.8 months, respectively. Multivariate analysis was conducted to analyze factors leading to late remission. A total number of 157 patients, of those 102 (64.9%) patients achieved remission. of those 102 patients, 62 patients (60.7%) had remission in less than 29 months (early remission) whereas 40 patients (39.3%) achieved remission later than (late remission) 29 months. The two groups differed significantly in the time interval between the last resection and the first SRS (p = 0.040) whole sella radiosurgery (p = 0.025) or radiosurgery to the cavernous sinus (p = 0.041). Competing risk analysis showed the interval between resection and SRS was significantly longer in the late remission group (HR 1.013, 95% CI 1.004–1.02; p = 0.007). Fifty-one of 157 patients (32.5%) developed a new endocrine deficiency following SRS. Those with shorter time between resection and SRS were more likely to achieve early remission. While most patients achieve remission in less than 4 years, the latency of effect with SRS yields a small percentage of patients achieving remission beyond that time point.
http://ift.tt/2BfOQBm
A statewide program providing colorectal cancer screening to the uninsured of South Carolina
BACKGROUND
Cancer screening rates are lowest in those without insurance or a regular provider. Since 2008, the Colorectal Cancer Prevention Network (CCPN) has provided open access colonoscopy to uninsured residents of South Carolina through established, statewide partnerships and patient navigation. Herein, we describe the structure, implementation, and clinical outcomes of this program.
METHODS
The CCPN provides access to colonoscopy screening at no cost to uninsured, asymptomatic patients aged 50-64 years (African Americans age 45-64 years are eligible) who live at or below 150% of the poverty line and seek medical care in free medical clinics, federally qualified health centers, or hospital-based indigent practices in South Carolina. Screening is performed by board-certified gastroenterologists. Descriptive statistics and regression analysis are used to describe the population screened, and to assess compliance rates and colonoscopy quality metrics.
RESULTS
Out of >4000 patients referred to the program, 1854 were deemed eligible, 1144 attended an in-person navigation visit, and 1030 completed a colonoscopy; 909 were included in the final sample. Nearly 90% of participants exhibited good-to-excellent bowel preparation. An overall cecal intubation rate of 99% was measured. The polyp detection rate and adenoma detection rate were 63% and 36%, respectively, with male sex and urban residence positively associated with adenoma detection. Over 13% of participants had an advanced polyp, and 1% had a cancer diagnosis or surgical intervention.
CONCLUSION
The CCPN program is characterized by strong collaboration with clinicians statewide, low no-show rates, and high colonoscopy quality. Future work will assess the effectiveness of the navigation approach and will explore the mechanisms driving higher adenoma detection in urban participants. Cancer 2018. © 2018 American Cancer Society.
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Factors affecting early versus late remission in acromegaly following stereotactic radiosurgery
Abstract
Stereotactic radiosurgery (SRS) is a well-established treatment modality for patients with acromegaly. Our previously published study demonstrated a median time to remission of 29 months. This study aims to identify factors affecting the timing of remission and also to quantify the rate of late remission. This is a retrospective analysis of acromegaly patients who underwent SRS between 1988 and 2016. Early and late remissions were defined based on our prior median remission time of 29 months. The median imaging and endocrine follow-ups are 66 and 104.8 months, respectively. Multivariate analysis was conducted to analyze factors leading to late remission. A total number of 157 patients, of those 102 (64.9%) patients achieved remission. of those 102 patients, 62 patients (60.7%) had remission in less than 29 months (early remission) whereas 40 patients (39.3%) achieved remission later than (late remission) 29 months. The two groups differed significantly in the time interval between the last resection and the first SRS (p = 0.040) whole sella radiosurgery (p = 0.025) or radiosurgery to the cavernous sinus (p = 0.041). Competing risk analysis showed the interval between resection and SRS was significantly longer in the late remission group (HR 1.013, 95% CI 1.004–1.02; p = 0.007). Fifty-one of 157 patients (32.5%) developed a new endocrine deficiency following SRS. Those with shorter time between resection and SRS were more likely to achieve early remission. While most patients achieve remission in less than 4 years, the latency of effect with SRS yields a small percentage of patients achieving remission beyond that time point.
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Changes in signal intensity in the dentate nucleus at unenhanced T1-weighted magnetic resonance imaging depending on class of previously used gadolinium-based contrast agent
Abstract
Background
Signal increase on T1-weighted magnetic resonance imaging (MRI) in the dentate nucleus has been reported in adults after multiple injections of gadolinium-based contrast agents. Linear contrast agents are more prone to cause this increase. Studies in children are still rare and focus mostly on the analysis of one single agent.
Objective
To compare signal intensity chances in children after more than four injections of either only linear or only macrocyclic contrast agents.
Materials and methods
Seventy children (examined from October 2001 to February 2016) were included in this retrospective study. Signal intensities in the dentate nucleus and pons were measured on non-enhanced T1-weighted images from the first and last MRI scans. A two-sample t-test compared the dentate nucleus-to-pons signal intensity ratio differences for linear versus macrocyclic gadolinium-based contrast agent applications and also the number of applications (4-8, 9-12 or >12). Patients' charts were analysed to evaluate potentially associated neurological symptoms.
Results
Patients had contrast-enhanced MRI using either only linear (n=16) or only macrocyclic (n=54) gadolinium-based contrast agents. In patients with >12 injections, dentate nucleus-to-pons signal intensity ratio was statistically different concerning the contrast agent class (0.16±0.125 for macrocyclic vs. 0.0005±0.13 for linear agents). For linear agents, a statistically significant increase was found between 4-8 injections (-0.051±0.087) and >12 injections (0.16±0.125). No neurological symptoms were recorded in patients with signal changes.
Conclusion
Multiple injections of linear gadolinium-based contrast agents lead to a signal increase of the dentate nucleus in children. Signal intensity increases depend on the number of injections of linear contrast agents.
http://ift.tt/2GTy8IF
Changes in signal intensity in the dentate nucleus at unenhanced T1-weighted magnetic resonance imaging depending on class of previously used gadolinium-based contrast agent
Abstract
Background
Signal increase on T1-weighted magnetic resonance imaging (MRI) in the dentate nucleus has been reported in adults after multiple injections of gadolinium-based contrast agents. Linear contrast agents are more prone to cause this increase. Studies in children are still rare and focus mostly on the analysis of one single agent.
Objective
To compare signal intensity chances in children after more than four injections of either only linear or only macrocyclic contrast agents.
Materials and methods
Seventy children (examined from October 2001 to February 2016) were included in this retrospective study. Signal intensities in the dentate nucleus and pons were measured on non-enhanced T1-weighted images from the first and last MRI scans. A two-sample t-test compared the dentate nucleus-to-pons signal intensity ratio differences for linear versus macrocyclic gadolinium-based contrast agent applications and also the number of applications (4-8, 9-12 or >12). Patients' charts were analysed to evaluate potentially associated neurological symptoms.
Results
Patients had contrast-enhanced MRI using either only linear (n=16) or only macrocyclic (n=54) gadolinium-based contrast agents. In patients with >12 injections, dentate nucleus-to-pons signal intensity ratio was statistically different concerning the contrast agent class (0.16±0.125 for macrocyclic vs. 0.0005±0.13 for linear agents). For linear agents, a statistically significant increase was found between 4-8 injections (-0.051±0.087) and >12 injections (0.16±0.125). No neurological symptoms were recorded in patients with signal changes.
Conclusion
Multiple injections of linear gadolinium-based contrast agents lead to a signal increase of the dentate nucleus in children. Signal intensity increases depend on the number of injections of linear contrast agents.
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miR-155 Affects Osteosarcoma MG-63 Cell Autophagy Induced by Adriamycin Through Regulating PTEN-PI3K/AKT/mTOR Signaling Pathway
Cancer Biotherapy & Radiopharmaceuticals , Vol. 0, No. 0.
http://ift.tt/2GVdUy7
Generation of erythroid cells from polyploid giant cancer cells: re-thinking about tumor blood supply
Abstract
Introduction
During development and tumor progression, cells need a sufficient blood supply to maintain development and rapid growth. It is reported that there are three patterns of blood supply for tumor growth: endothelium-dependent vessels, mosaic vessels, and vasculogenic mimicry (VM). VM was first reported in highly aggressive uveal melanomas, with tumor cells mimicking the presence and function of endothelial cells forming the walls of VM vessels. The walls of mosaic vessels are randomly lined with both endothelial cells and tumor cells. We previously proposed a three-stage process, beginning with VM, progressing to mosaic vessels, and eventually leading to endothelium-dependent vessels. However, many phenomena unique to VM channel formation remain to be elucidated, such as the origin of erythrocytes before VM vessels connect with endothelium-dependent vessels.
Results
In adults, erythroid cells are generally believed to be generated from hematopoietic stem cells in the bone marrow. In contrast, embryonic tissue obtains oxygen through formation of blood islands, which are largely composed of embryonic hemoglobin with a higher affinity with oxygen, in the absence of mature erythrocytes. Recent data from our laboratory suggest that embryonic blood-forming mechanisms also exist in cancer tissue, particularly when these tissues are under environmental stress such as hypoxia. We review the evidence from induced pluripotent stem cells in vitro and in vivo to support this previously underappreciated cell functionality in normal and cancer cells, including the ability to generate erythroid cells. We will also summarize the current understanding of tumor angiogenesis, VM, and our recent work on polyploid giant cancer cells, with emphasis on their ability to generate erythroid cells and their association with tumor growth under hypoxia.
Conclusion
An alternative embryonic pathway to obtain oxygen in cancer cells exists, particularly when they are under hypoxic conditions.
http://ift.tt/2EaiRBz
Generation of erythroid cells from polyploid giant cancer cells: re-thinking about tumor blood supply
Abstract
Introduction
During development and tumor progression, cells need a sufficient blood supply to maintain development and rapid growth. It is reported that there are three patterns of blood supply for tumor growth: endothelium-dependent vessels, mosaic vessels, and vasculogenic mimicry (VM). VM was first reported in highly aggressive uveal melanomas, with tumor cells mimicking the presence and function of endothelial cells forming the walls of VM vessels. The walls of mosaic vessels are randomly lined with both endothelial cells and tumor cells. We previously proposed a three-stage process, beginning with VM, progressing to mosaic vessels, and eventually leading to endothelium-dependent vessels. However, many phenomena unique to VM channel formation remain to be elucidated, such as the origin of erythrocytes before VM vessels connect with endothelium-dependent vessels.
Results
In adults, erythroid cells are generally believed to be generated from hematopoietic stem cells in the bone marrow. In contrast, embryonic tissue obtains oxygen through formation of blood islands, which are largely composed of embryonic hemoglobin with a higher affinity with oxygen, in the absence of mature erythrocytes. Recent data from our laboratory suggest that embryonic blood-forming mechanisms also exist in cancer tissue, particularly when these tissues are under environmental stress such as hypoxia. We review the evidence from induced pluripotent stem cells in vitro and in vivo to support this previously underappreciated cell functionality in normal and cancer cells, including the ability to generate erythroid cells. We will also summarize the current understanding of tumor angiogenesis, VM, and our recent work on polyploid giant cancer cells, with emphasis on their ability to generate erythroid cells and their association with tumor growth under hypoxia.
Conclusion
An alternative embryonic pathway to obtain oxygen in cancer cells exists, particularly when they are under hypoxic conditions.
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The concentration of programmed cell death-ligand 1 in the peripheral blood is a useful biomarker for esophageal squamous cell carcinoma
Abstract
Background
We determined the serum concentrations of Programmed cell death-1 (PD-1) and its ligands (PD-L1 and PD-L2) in patients with esophageal squamous cell carcinoma (ESCC).
Methods
Blood samples were collected from 85 patients with histologically proved ESCC. Serum levels of PD-1, PD-L1, and PD-L2 were measured using enzyme linked immunosorbent assays. Correlations between serum PD-1, PD-L1, and PD-L2 concentration and tumor depth, number of lymph node metastases, organ metastasis status, or disease stage were assessed and five-year survival rates according to clinicopathological characteristics were calculated.
Results
The concentration of PD-1 was not differed according to tumor progression. On the other hand, the average concentration of PD-L1 in patients with T3/T4 disease was 15.6 (12.2–18.3) pg/mL (25–75%), and this was significantly higher than that in patients with Tis/T1/T2 disease (p = 0.020). Similarly, PD-L1 levels were significantly higher in patients with positive lymph nodes than in cases with negative lymph node involvement (p = 0.006) and were higher in patients with organ metastasis (p = 0.123) and in more advanced stage (p = 0.006). Similar tendency was observed regarding PD-L2 concentrations. PD-L2 concentration was higher in T3, T4 cases (p = 0.008), in LN positive cases (p = 0.032), and in more advanced stage (p = 0.024).
Conclusion
Our data showed that a concentration of PD-L1 in peripheral blood was high in advanced cancer and high concentration of PD-L1 predicted disease progression and also poor survival in patients with ESCC.
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The concentration of programmed cell death-ligand 1 in the peripheral blood is a useful biomarker for esophageal squamous cell carcinoma
Abstract
Background
We determined the serum concentrations of Programmed cell death-1 (PD-1) and its ligands (PD-L1 and PD-L2) in patients with esophageal squamous cell carcinoma (ESCC).
Methods
Blood samples were collected from 85 patients with histologically proved ESCC. Serum levels of PD-1, PD-L1, and PD-L2 were measured using enzyme linked immunosorbent assays. Correlations between serum PD-1, PD-L1, and PD-L2 concentration and tumor depth, number of lymph node metastases, organ metastasis status, or disease stage were assessed and five-year survival rates according to clinicopathological characteristics were calculated.
Results
The concentration of PD-1 was not differed according to tumor progression. On the other hand, the average concentration of PD-L1 in patients with T3/T4 disease was 15.6 (12.2–18.3) pg/mL (25–75%), and this was significantly higher than that in patients with Tis/T1/T2 disease (p = 0.020). Similarly, PD-L1 levels were significantly higher in patients with positive lymph nodes than in cases with negative lymph node involvement (p = 0.006) and were higher in patients with organ metastasis (p = 0.123) and in more advanced stage (p = 0.006). Similar tendency was observed regarding PD-L2 concentrations. PD-L2 concentration was higher in T3, T4 cases (p = 0.008), in LN positive cases (p = 0.032), and in more advanced stage (p = 0.024).
Conclusion
Our data showed that a concentration of PD-L1 in peripheral blood was high in advanced cancer and high concentration of PD-L1 predicted disease progression and also poor survival in patients with ESCC.
http://ift.tt/2Et047W
Body mass index, abdominal fatness, and the risk of sudden cardiac death: a systematic review and dose–response meta-analysis of prospective studies
Abstract
Although overweight and obesity are established risk factors for some types of heart disease including ischemic heart disease, heart failure and atrial fibrillation, less is known about the association between adiposity and sudden cardiac death. We conducted a systematic review and meta-analysis of prospective studies to clarify the association between adiposity and risk of sudden cardiac death. PubMed and Embase databases were searched up to July 20th 2017. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random effects models. The summary RR was 1.16 (95% CI 1.05–1.28, I2 = 68%, n = 14) per 5 unit increment in BMI, and 1.82 (95% CI 1.61–2.07, I2 = 0%, n = 3) per 0.1 unit increase in waist-to-hip ratio, and 1.03 (95% CI 0.93–1.15, I2 = 0%, n = 2) per 10 cm increase in waist circumference. The heterogeneity in the analysis of BMI and sudden cardiac death persisted across most subgroup analyses. The association was stronger among studies with longer follow-up compared to short follow-up and was observed in the European and American studies, but not in the Asian studies. There was a J-shaped association between BMI and sudden cardiac death and the lowest risk was observed in the normal weight range, however, the increased risk with a low BMI was attenuated among studies with a longer duration of follow-up. This meta-analysis suggest an increased risk of sudden cardiac death with increasing BMI and waist-to-hip ratio, however, further studies with stratification for smoking status are needed of waist circumference, weight changes and adiposity at younger ages.
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Correction to: SEOM clinical guidelines for endometrial cancer (2017)
In the original version of this article Figure 1 was shown incorrectly. The correct Figure 1 is shown here:
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Correction to: SEOM clinical guidelines for endometrial cancer (2017)
In the original version of this article Figure 1 was shown incorrectly. The correct Figure 1 is shown here:
http://ift.tt/2Bf0jBj
Visualization of endothelial cell cycle dynamics in mouse using the Flt-1/eGFP-anillin system
Abstract
Endothelial cell proliferation is a key process during vascular growth but its kinetics could only be assessed in vitro or ex vivo so far. To enable the monitoring and quantification of cell cycle kinetics in vivo, we have generated transgenic mice expressing an eGFP-anillin construct under control of the endothelial-specific Flt-1 promoter. This construct labels the nuclei of endothelial cells in late G1, S and G2 phase and changes its localization during the different stages of M phase, thereby enabling the monitoring of EC proliferation and cytokinesis. In Flt-1/eGFP-anillin mice, we found eGFP+ signals specifically in Ki67+/PECAM+ endothelial cells during vascular development. Quantification using this cell cycle reporter in embryos revealed a decline in endothelial cell proliferation between E9.5 to E12.5. By time-lapse microscopy, we determined the length of different cell cycle phases in embryonic endothelial cells in vivo and found a M phase duration of about 80 min with 2/3 covering karyokinesis and 1/3 cytokinesis. Thus, we have generated a versatile transgenic system for the accurate assessment of endothelial cell cycle dynamics in vitro and in vivo.
http://ift.tt/2FWscgO
Visualization of endothelial cell cycle dynamics in mouse using the Flt-1/eGFP-anillin system
Abstract
Endothelial cell proliferation is a key process during vascular growth but its kinetics could only be assessed in vitro or ex vivo so far. To enable the monitoring and quantification of cell cycle kinetics in vivo, we have generated transgenic mice expressing an eGFP-anillin construct under control of the endothelial-specific Flt-1 promoter. This construct labels the nuclei of endothelial cells in late G1, S and G2 phase and changes its localization during the different stages of M phase, thereby enabling the monitoring of EC proliferation and cytokinesis. In Flt-1/eGFP-anillin mice, we found eGFP+ signals specifically in Ki67+/PECAM+ endothelial cells during vascular development. Quantification using this cell cycle reporter in embryos revealed a decline in endothelial cell proliferation between E9.5 to E12.5. By time-lapse microscopy, we determined the length of different cell cycle phases in embryonic endothelial cells in vivo and found a M phase duration of about 80 min with 2/3 covering karyokinesis and 1/3 cytokinesis. Thus, we have generated a versatile transgenic system for the accurate assessment of endothelial cell cycle dynamics in vitro and in vivo.
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Associations Between Serum Bone Biomarkers in Early Breast Cancer and Development of Bone Metastasis: Results From the AZURE (BIG01/04) Trial
Abstract
Background
Adjuvant therapies can prevent/delay bone metastasis development in breast cancer. We investigated whether serum bone turnover markers in early disease have clinical utility in identifying patients with a high risk of developing bone metastasis. Methods
Markers of bone formation (N-terminal propeptide of type-1 collagen [P1NP]) and bone resorption (C-telopeptide of type-1 collagen [CTX], pyridinoline cross-linked carboxy-terminal telopeptide of type-1 collagen [1-CTP]) were measured in baseline (pretreatment blood samples from 872 patients from a large randomized trial of adjuvant zoledronic acid (AZURE-ISRCTN79831382) in early breast cancer. Cox proportional hazards regression and cumulative incidence functions (adjusted for factors having a statistically significant effect on outcome) were used to investigate prognostic and predictive associations between recurrence events, bone marker levels, and clinical variables. All statistical tests were two-sided. Results
When considered as continuous variables (log transformed), P1NP, CTX, and 1-CTP were each prognostic for future bone recurrence at any time (P = .006, P = .009, P = .008, respectively). Harrell's c-indices were a P1NP of 0.57 (95% confidence interval [CI] = 0.51 to 0.63), CTX of 0.57 (95% CI = 0.51 to 0.62), and 1-CTP of 0.57 (95% CI = 0.52 to 0.63). In categorical analyses based on the normal range, high baseline P1NP (>70 ng/mL) and CTX (>0.299 ng/mL), but not 1-CTP (>4.2 ng/mL), were also prognostic for future bone recurrence (P = .03, P = .03, P = .10, respectively). None of the markers were prognostic for overall distant recurrence; that is, they were bone metastasis specific, and none of the markers were predictive of treatment benefit from zoledronic acid. Conclusions
Serum P1NP, CTX, and 1-CTP are clinically useful, easily measured markers that show good prognostic ability (though low-to-moderate discrimination) for bone-specific recurrence and are worthy of further study.http://ift.tt/2BfxFQp
Complete resection of a rectus abdominis muscle invaded by desmoid tumors and subsequent management with an abdominal binder: a case report
Desmoid-type fibromatosis is characterized by desmoid tumors, which are benign soft tissue tumors that can be locally aggressive but typically do not metastasize. Desmoid tumors can manifest anywhere in the bo...
http://ift.tt/2C05FwV
Eribulin therapy for the treatment of patients with advanced soft tissue sarcoma
Future Oncology, Ahead of Print.
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Eribulin therapy for the treatment of patients with advanced soft tissue sarcoma
Future Oncology, Ahead of Print.
http://ift.tt/2nQazHM
Ethnic density and cancer: A review of the evidence
Accumulating data suggest that factors in the social environment may be associated with cancer-related outcomes. Ethnic density, defined as the proportion of racial/ethnic minority individuals residing in a given geographic area, is 1 of the most frequently studied social environment factors, but studies on ethnic density and cancer have yielded inconsistent findings. Thus, the objective of the current review was to summarize the extant data on ethnic density and cancer-related outcomes (cancer risk, stage at diagnosis, and mortality) with the aim of identifying pathways by which ethnic density may contribute to outcomes across populations. In general, the findings indicated an association between ethnic density and increased risk for cancers of infectious origin (eg, liver, cervical) but lower risk for breast and colorectal cancers, particularly among Hispanic and Asian Americans. Hispanic ethnic density was associated with greater odds of late-stage cancer diagnosis, whereas black ethnic density was associated with greater mortality. In addition, this review highlights several methodological and conceptual issues surrounding the measurement of ethnic neighborhoods and their available resources. Clarifying the role of neighborhood ethnic density is critical to developing a greater understanding of the health risks and benefits accompanying these environments and how they may affect racial and ethnic disparities in cancer-related outcomes. Cancer 2018. © 2018 American Cancer Society.
http://ift.tt/2GWJOdM
Ethnic density and cancer: A review of the evidence
Accumulating data suggest that factors in the social environment may be associated with cancer-related outcomes. Ethnic density, defined as the proportion of racial/ethnic minority individuals residing in a given geographic area, is 1 of the most frequently studied social environment factors, but studies on ethnic density and cancer have yielded inconsistent findings. Thus, the objective of the current review was to summarize the extant data on ethnic density and cancer-related outcomes (cancer risk, stage at diagnosis, and mortality) with the aim of identifying pathways by which ethnic density may contribute to outcomes across populations. In general, the findings indicated an association between ethnic density and increased risk for cancers of infectious origin (eg, liver, cervical) but lower risk for breast and colorectal cancers, particularly among Hispanic and Asian Americans. Hispanic ethnic density was associated with greater odds of late-stage cancer diagnosis, whereas black ethnic density was associated with greater mortality. In addition, this review highlights several methodological and conceptual issues surrounding the measurement of ethnic neighborhoods and their available resources. Clarifying the role of neighborhood ethnic density is critical to developing a greater understanding of the health risks and benefits accompanying these environments and how they may affect racial and ethnic disparities in cancer-related outcomes. Cancer 2018. © 2018 American Cancer Society.
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A vaccine targeting basic fibroblast growth factor elicits a protective immune response against murine melanoma.
A vaccine targeting basic fibroblast growth factor elicits a protective immune response against murine melanoma.
Cancer Biol Ther. 2018 Feb 06;:0
Authors: Zhang X, Li NL, Guo C, Li YD, Luo LL, Liu YQ, Duan YY, Li ZD, Xie XR, Song HX, Yang PL, An FY
Abstract
Tumor growth and metastasis are closely related to angiogenesis. Basic fibroblast growth factor(bFGF) is an angiogenic factor, and up-regulated expression of bFGF plays a crucial role in the development and metastasis of melanoma. Therefore, in this study, we sought to achieve antitumor activity by immunity targeting bFGF which would inhibit tumor angiogenesis and simultaneously induce bFGF specific cytotoxic T lymphocytes to kill melanoma cells. A human bFGF protein was used as exogenous antigen, coupled with a saponin-liposome adjuvant formulation to enhance CTL response. The results showed that the immunity induced strong immune response and produced prominent anti-cancer activities. CD31 immunohistochemistry and alginate-encapsulated tumor cell assay displayed that tumor angiogenesis was effectively inhibited. Further, the higher production of IFN-γ and cytotoxic T lymphocyte killing assay suggested that the anti-cancer activities may mainly depend on cellular immune response, which could cause the inhibition of tumor angiogenesis and specific killing of tumor cells by bFGF-specific cytotoxic T lymphocytes. We concluded that immunotherapy targeting bFGF may be a prominent strategy for melanoma, and that the adjuvant formulation of saponin-liposome is very desirable in enhancing cytotoxic T lymphocytes response.
PMID: 29405828 [PubMed - as supplied by publisher]
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The irreversible ERBB1/2/4 inhibitor neratinib interacts with the PARP1 inhibitor niraparib to kill ovarian cancer cells.
The irreversible ERBB1/2/4 inhibitor neratinib interacts with the PARP1 inhibitor niraparib to kill ovarian cancer cells.
Cancer Biol Ther. 2018 Feb 06;:0
Authors: Booth L, Roberts JL, Samuel P, Avogadri-Connors F, Cutler RE, Lalani AS, Poklepovic A, Dent P
Abstract
The irreversible ERBB1/2/4 inhibitor neratinib has been shown to rapidly down-regulate the expression of ERBB1/2/4 as well as the levels of c-MET, PDGFRα and mutant RAS proteins via autophagic degradation. Neratinib interacted in an additive to synergistic fashion with the approved PARP1 inhibitor niraparib to kill ovarian cancer cells. Neratinib and niraparib caused the ATM-dependent activation of AMPK which in turn was required to cause mTOR inactivation, ULK-1 activation and ATG13 phosphorylation. The drug combination initially increased autophagosome levels followed later by autolysosome levels. Preventing autophagosome formation by expressing activated mTOR or knocking down of Beclin1, or knock down of the autolysosome protein cathepsin B, reduced drug combination lethality. The drug combination caused an endoplasmic reticulum stress response as judged by enhanced eIF2α phosphorylation that was responsible for reducing MCL-1 and BCL-XL levels and increasing ATG5 and Beclin1 expression. Knock down of BIM, but not of BAX or BAK, reduced cell killing. Expression of activated MEK1 prevented the drug combination increasing BIM expression and reduced cell killing. Downstream of the mitochondrion, drug lethality was partially reduced by knock down of AIF, but expression of dominant negative caspase 9 was not protective. Our data demonstrate that neratinib and niraparib interact to kill ovarian cancer cells through convergent DNA damage and endoplasmic reticulum stress signaling. Cell killing required the induction of autophagy and was cathepsin B and AIF -dependent, and effector caspase independent.
PMID: 29405820 [PubMed - as supplied by publisher]
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Giant colonic diverticulum—a rare cause of acute abdomen
Abstract
Giant colonic diverticulum (GCD), defined as diverticulum larger than 4 cm, is a rare entity. It is generally a manifestation of colonic diverticular disease and can have dramatic complications such as perforation, abscess, volvulus, infarction and adenocarcinoma. This report documents the case of a 63-year-old man coming to the Emergency Department with acute abdomen due to a perforation of a GCD. In the plain abdominal X-ray the 'Balloon-sign' was revealed, computed tomography scan and Hartmann's procedure were performed. Acute abdomen can occur as a manifestation of a complication of a GCD, and this report highlights the fact that GCD should be considered for patients with a high risk of diverticular disease and abdominal pain.http://ift.tt/2ENHvZL
Medullary-like hepatocellular carcinoma
Abstract
Hepatocellular carcinoma (HCC) is the most frequent primary hepatic cancer. Pathological features can define the biological behavior and prognosis. Medullary-like HCC is a very rare variant that has been described only twice in literature. In the present study, we report the case of a non-cirrhotic 72-year-old man, who presented two HCC lesions on routine screening for hepatitis C virus liver disease. Radiological imaging and biopsy showed two different subtypes: one classic HCC, which was treated with chemoembolization, and a second PET/CT-positive carcinoma with a PET/CT-positive metastatic coeliac lymph node, which was resected laparoscopically with a left lateral sectionectomy and extended lymphadenectomy. Histopathology revealed a medullary-like HCC; lymph node analysis confirmed the metastatic nature of the PET/CT-positive coeliac node and showed an incidental B-cell lymphoma in the hepatic pedicle lymph nodes. To the best of our knowledge this is the third case of medullary-like HCC described in the literature, and the first associated to a concomitant typical HCC.http://ift.tt/2E89geq
After a punch: recurrence of compartment syndrome following minor trauma
Abstract
Acute compartment syndrome (ACS) is a diagnosis that requires high-clinical suspicion especially in cases when the initial causal event could be considered insignificant. We present a novel case presentation of ACS associated with minor trauma in a patient with a previous history of compartment syndrome in the same extremity from a motor vehicle accident 10 years prior to presentation. To the best of our knowledge, this is the first reported case of recurrent ACS. Due to the possibility of significant morbidity, including loss of limb, it is imperative to recognize the presentation quickly so proper surgical intervention can occur. This case shows compartment syndrome can occur after a low impact mechanism of injury and previous compartment syndrome may be a risk factor, lowering the threshold for a re-occurrence. Serial exams and compartment pressure measurements should be used to aid recognition in ambiguous clinical presentations.http://ift.tt/2EJRWgN
A vaccine targeting basic fibroblast growth factor elicits a protective immune response against murine melanoma.
A vaccine targeting basic fibroblast growth factor elicits a protective immune response against murine melanoma.
Cancer Biol Ther. 2018 Feb 06;:0
Authors: Zhang X, Li NL, Guo C, Li YD, Luo LL, Liu YQ, Duan YY, Li ZD, Xie XR, Song HX, Yang PL, An FY
Abstract
Tumor growth and metastasis are closely related to angiogenesis. Basic fibroblast growth factor(bFGF) is an angiogenic factor, and up-regulated expression of bFGF plays a crucial role in the development and metastasis of melanoma. Therefore, in this study, we sought to achieve antitumor activity by immunity targeting bFGF which would inhibit tumor angiogenesis and simultaneously induce bFGF specific cytotoxic T lymphocytes to kill melanoma cells. A human bFGF protein was used as exogenous antigen, coupled with a saponin-liposome adjuvant formulation to enhance CTL response. The results showed that the immunity induced strong immune response and produced prominent anti-cancer activities. CD31 immunohistochemistry and alginate-encapsulated tumor cell assay displayed that tumor angiogenesis was effectively inhibited. Further, the higher production of IFN-γ and cytotoxic T lymphocyte killing assay suggested that the anti-cancer activities may mainly depend on cellular immune response, which could cause the inhibition of tumor angiogenesis and specific killing of tumor cells by bFGF-specific cytotoxic T lymphocytes. We concluded that immunotherapy targeting bFGF may be a prominent strategy for melanoma, and that the adjuvant formulation of saponin-liposome is very desirable in enhancing cytotoxic T lymphocytes response.
PMID: 29405828 [PubMed - as supplied by publisher]
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The irreversible ERBB1/2/4 inhibitor neratinib interacts with the PARP1 inhibitor niraparib to kill ovarian cancer cells.
The irreversible ERBB1/2/4 inhibitor neratinib interacts with the PARP1 inhibitor niraparib to kill ovarian cancer cells.
Cancer Biol Ther. 2018 Feb 06;:0
Authors: Booth L, Roberts JL, Samuel P, Avogadri-Connors F, Cutler RE, Lalani AS, Poklepovic A, Dent P
Abstract
The irreversible ERBB1/2/4 inhibitor neratinib has been shown to rapidly down-regulate the expression of ERBB1/2/4 as well as the levels of c-MET, PDGFRα and mutant RAS proteins via autophagic degradation. Neratinib interacted in an additive to synergistic fashion with the approved PARP1 inhibitor niraparib to kill ovarian cancer cells. Neratinib and niraparib caused the ATM-dependent activation of AMPK which in turn was required to cause mTOR inactivation, ULK-1 activation and ATG13 phosphorylation. The drug combination initially increased autophagosome levels followed later by autolysosome levels. Preventing autophagosome formation by expressing activated mTOR or knocking down of Beclin1, or knock down of the autolysosome protein cathepsin B, reduced drug combination lethality. The drug combination caused an endoplasmic reticulum stress response as judged by enhanced eIF2α phosphorylation that was responsible for reducing MCL-1 and BCL-XL levels and increasing ATG5 and Beclin1 expression. Knock down of BIM, but not of BAX or BAK, reduced cell killing. Expression of activated MEK1 prevented the drug combination increasing BIM expression and reduced cell killing. Downstream of the mitochondrion, drug lethality was partially reduced by knock down of AIF, but expression of dominant negative caspase 9 was not protective. Our data demonstrate that neratinib and niraparib interact to kill ovarian cancer cells through convergent DNA damage and endoplasmic reticulum stress signaling. Cell killing required the induction of autophagy and was cathepsin B and AIF -dependent, and effector caspase independent.
PMID: 29405820 [PubMed - as supplied by publisher]
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[Can medical oncologists talk about cure to their patient after localized breast cancer treatment?]
[Can medical oncologists talk about cure to their patient after localized breast cancer treatment?]
Bull Cancer. 2018 Feb 02;:
Authors: Torregrosa C, Coutu-Nadeau LP, Rodrigues MJ, Mamzer-Bruneel MF
Abstract
INTRODUCTION: Despite ongoing therapeutic advances in oncology, the use of the term cure in front of patients remains controversial. The word remission is often preferred in clinical practice. The purpose of this research is to explore how oncologists vary in their usage and definition of the word cure when talking to patients.
METHODS: Qualitative and exploratory pilot study conducted by semi structured interviews with a group of French oncologists about a clinical vignette of localized breast cancer treated by surgery and complete adjuvant treatment.
RESULTS: Thirteen oncologists participated in this study between January and March 2016. They were divided into two groups according to whether or not they use the term cure in their clinical practice. A first group of five doctors define the word cure as the lasting absence of relapse of the disease. Because of their duty of transparency and the uncertainty of post-therapeutic relapse, these five doctors tend to never use the word cure. The analysis of the second group of eight doctors, who do use of the word cure in their practice, highlighted an absence of consensus on its definition. However, all of them justify their use of it with the importance of expressing positive emotions such as hope to patients.
DISCUSSION: Our findings confirm that there are divergent understandings of the concept of cure between oncologists and how they manage prognosis uncertainty. Medical language is thus influenced by scientific knowledge, but also by doctors' personal values and ways of thinking, perhaps influencing the doctor-patient relationship in turn. This exploratory study will be extended on a wider scale to explore the coexistence of other elements of diversity.
PMID: 29402398 [PubMed - as supplied by publisher]
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Immunotherapy, an evolving approach for the management of triple negative breast cancer: Converting non-responders to responders
Source:Critical Reviews in Oncology/Hematology
Author(s): Mai F. Tolba, Hany A. Omar
Immunotherapy comprises a promising new era in cancer therapy. Immune checkpoint inhibitors targeting either the programmed death (PD)-1 receptor or its ligand PD-L1 were first approved by the Food and Drug Administration (FDA) for the management of metastatic melanoma in 2011. The approval of this class is being extended to include other types of immunogenic tumors. Although breast cancer (BC) was first categorized as non-immunogenic tumor type, there are certain subsets of BC that showed a high level of tumor infiltrating lymphocytes (TILs). Those subsets include the triple negative breast cancer (TNBC) and HER-2 positive breast tumors. Preliminary data from clinical trials presented promising outcomes for patients with advanced stage/metastatic TNBC. While the objective response rate (ORR) was relatively low, it is still promising because of the observation that the patients who respond to the treatment with immune checkpoint blockade have favorable prognosis and often show a significant increase in the overall survival. Therefore, the main challenge is to find ways to enhance the tumor response to such therapy and to convert the non-responders to responders. This will consequently bring new hopes for patients with advanced stage metastatic TNBC and help to decrease death tolls from this devastating disease. In the current review, we are highlighting and discussing the up-to-date strategies adopted at either the preclinical or the clinical settings to enhance tumor responsiveness to immunotherapy.
http://ift.tt/2DaMPI1
Global comparison of targeted alpha vs targeted beta therapy for cancer: In vitro, in vivo and clinical trials
Source:Critical Reviews in Oncology/Hematology, Volume 123
Author(s): Loredana Marcu, Eva Bezak, Barry J. Allen
Targeted therapy for cancer is a rapidly expanding and successful approach to the management of many intractable cancers. However, many immunotherapies fail in the longer term and there continues to be a need for improved targeted cancer cell toxicity, which can be achieved by radiolabelling the targeting vector with a radioisotope.Such constructs are successful in using a gamma ray emitter for imaging. However, traditionally, a beta emitter is used for therapeutic applications. The new approach is to use the short range and highly cytotoxic alpha radiation from alpha emitters to achieve improved efficacy and therapeutic gain.This paper sets out to review all experimental and theoretical comparisons of efficacy and therapeutic gain for alpha and beta emitters labelling the same targeting vector. The overall conclusion is that targeted alpha therapy is superior to targeted beta therapy, such that the use of alpha therapy in clinical settings should be expanded.
http://ift.tt/2E798eV
A systematic review of the influence of radiation-induced lymphopenia on survival outcomes in solid tumors
Source:Critical Reviews in Oncology/Hematology, Volume 123
Author(s): Bhanu Prasad Venkatesulu, Supriya Mallick, Steven H. Lin, Sunil Krishnan
Lymphopenia is a common accompaniment of multimodal cancer therapy. As the most radiosensitive cells of the hematopoietic system, lymphocytes residing within or circulating through a radiation portal are frequently depleted by radiation therapy. The recognition that radiation-induced reduction of circulating lymphocyte counts and eventual lymphocyte infiltration of tumors have a tangible impact on overall survival outcomes has revived the interest in understanding the causes of treatment-associated lymphopenia and developing strategies to predict, prevent and ameliorate this well-documented phenomenon. In this systematic review, we have performed a comprehensive search of the literature to elucidate the studies that document a correlation between radiation-associated lymphopenia and survival outcomes in solid malignancies. We also summarize potential unifying paradigms that account for radiation-induced lymphopenia across studies and lay the groundwork for attempting to explain and/or counter this phenomenon.
http://ift.tt/2ENMBoW
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