Ascaris lumbricoides is one of the most common intestinal infections in developing countries, including Kosovo. In contrast to migration to the bile duct, migration of the worm to the gallbladder, due to the narr...
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Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Σάββατο 13 Ιανουαρίου 2018
Gallbladder ascariasis in Kosovo – focus on ultrasound and conservative therapy: a case series
Selective IKK2 inhibitor IMD0354 disrupts NF-κB signaling to suppress corneal inflammation and angiogenesis
Abstract
Corneal neovascularization is a sight-threatening condition caused by angiogenesis in the normally avascular cornea. Neovascularization of the cornea is often associated with an inflammatory response, thus targeting VEGF-A alone yields only a limited efficacy. The NF-κB signaling pathway plays important roles in inflammation and angiogenesis. Here, we study consequences of the inhibition of NF-κB activation through selective blockade of the IKK complex IκB kinase β (IKK2) using the compound IMD0354, focusing on the effects of inflammation and pathological angiogenesis in the cornea. In vitro, IMD0354 treatment diminished HUVEC migration and tube formation without an increase in cell death and arrested rat aortic ring sprouting. In HUVEC, the IMD0354 treatment caused a dose-dependent reduction in VEGF-A expression, suppressed TNFα-stimulated expression of chemokines CCL2 and CXCL5, and diminished actin filament fibers and cell filopodia formation. In developing zebrafish embryos, IMD0354 treatment reduced expression of Vegf-a and disrupted retinal angiogenesis. In inflammation-induced angiogenesis in the rat cornea, systemic selective IKK2 inhibition decreased inflammatory cell invasion, suppressed CCL2, CXCL5, Cxcr2, and TNF-α expression and exhibited anti-angiogenic effects such as reduced limbal vessel dilation, reduced VEGF-A expression and reduced angiogenic sprouting, without noticeable toxic effect. In summary, targeting NF-κB by selective IKK2 inhibition dampened the inflammatory and angiogenic responses in vivo by modulating the endothelial cell expression profile and motility, thus indicating an important role of NF-κB signaling in the development of pathologic corneal neovascularization.
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Selective IKK2 inhibitor IMD0354 disrupts NF-κB signaling to suppress corneal inflammation and angiogenesis
Abstract
Corneal neovascularization is a sight-threatening condition caused by angiogenesis in the normally avascular cornea. Neovascularization of the cornea is often associated with an inflammatory response, thus targeting VEGF-A alone yields only a limited efficacy. The NF-κB signaling pathway plays important roles in inflammation and angiogenesis. Here, we study consequences of the inhibition of NF-κB activation through selective blockade of the IKK complex IκB kinase β (IKK2) using the compound IMD0354, focusing on the effects of inflammation and pathological angiogenesis in the cornea. In vitro, IMD0354 treatment diminished HUVEC migration and tube formation without an increase in cell death and arrested rat aortic ring sprouting. In HUVEC, the IMD0354 treatment caused a dose-dependent reduction in VEGF-A expression, suppressed TNFα-stimulated expression of chemokines CCL2 and CXCL5, and diminished actin filament fibers and cell filopodia formation. In developing zebrafish embryos, IMD0354 treatment reduced expression of Vegf-a and disrupted retinal angiogenesis. In inflammation-induced angiogenesis in the rat cornea, systemic selective IKK2 inhibition decreased inflammatory cell invasion, suppressed CCL2, CXCL5, Cxcr2, and TNF-α expression and exhibited anti-angiogenic effects such as reduced limbal vessel dilation, reduced VEGF-A expression and reduced angiogenic sprouting, without noticeable toxic effect. In summary, targeting NF-κB by selective IKK2 inhibition dampened the inflammatory and angiogenic responses in vivo by modulating the endothelial cell expression profile and motility, thus indicating an important role of NF-κB signaling in the development of pathologic corneal neovascularization.
http://ift.tt/2EBLgQH
Smoking, Sex, and Non–Small Cell Lung Cancer: Steroid Hormone Receptors in Tumor Tissue (S0424)
Abstract
Background
To what extent steroid hormones contribute to lung cancer in male and female never smokers and smokers is unclear. We examined expression of hormone receptors in lung tumors by sex and smoking. Methods
Patients with primary non–small cell lung cancer were recruited into an Intergroup study in the United States and Canada, led by SWOG (S0424). Tumors from 813 cases (450 women and 363 men) were assayed using immunohistochemistry for estrogen receptor (ER)–α, ER-β, progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Linear regression was used to examine differences in expression by sex and smoking status. Cox proportional hazard models were used to estimate survival associated with the receptors. All statistical tests were two-sided. Results
In ever smokers, postmenopause and oral contraceptive use were associated with lower nuclear ER-β (P = .02) and total (nuclear + cytoplasmic) PR expression (P = .02), respectively. Women had lower cytoplasmic ER-α (regression coefficient [β], or differences in H-scores = –15.8, P = .003) and nuclear ER-β (β = –12.8, P = .04) expression than men, adjusting for age, race, and smoking. Ever smokers had both higher cytoplasmic ER-α (β = 45.0, P < .001) and ER-β (β = 25.9, P < .001) but lower total PR (β = –42.1, P < .001) than never smokers. Higher cytoplasmic ER-α and ER-β were associated with worse survival (hazard ratio = 1.73, 95% confidence interval [CI] = 1.15 to 2.58, and HR = 1.59, 95% CI = 1.08 to 2.33, respectively; quartiles 4 vs 1). Conclusions
Lower expression of nuclear ER-β in women supports the estrogen hypothesis in lung cancer etiology. Increasing cytoplasmic ER-α and ER-β and decreasing PR protein expression may be mechanisms whereby smoking disrupts hormone pathways.http://ift.tt/2CZ7eMU
Variation in guideline-concordant care for elderly patients with metastatic breast cancer in the United States
Abstract
Purpose
Prior studies have identified shortcomings in the quality of care for early-stage breast cancer. Guidelines recommend systemic therapy for metastatic breast cancer (MBC), but few studies have examined guideline concordance for these patients.
Methods
We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data to identify patients aged ≥ 66 diagnosed in 2010–2011 with de novo MBC who were continuously enrolled in fee-for-service Medicare. We described initial care (within 6 months of diagnosis) for hormone receptor (HR)-positive/human epidermal receptor-2 (HER2)-negative, HER2-positive, and triple-negative (TN) tumors. We identified factors independently associated with receiving no initial systemic therapy, and compared hospice and hospital utilization for treated versus untreated patients.
Results
Among 446 patients, 65% were HR-positive, 21% were HER2-positive, and 14% were TN. Most patients (76.9%) received initial systemic treatment. Among treated HR-positive patients, 15% received chemotherapy as initial treatment; among treated HER2-positive patients, 34% did not receive HER2-targeted initial therapy. Factors independently associated with receiving no initial systemic therapy included older age (ORage continuous/year = 1.08, 95% CI 1.04–1.11), being not married (ORnot married vs. married = 2.87, 95% CI 1.42–5.81), and subtype (ORTN vs. HR+ = 4.95, 95% CI 2.53–9.71). Of patients who did not receive initial systemic therapy, 41.1% did not receive hospice services.
Conclusions
In this population-based MBC cohort, almost one quarter did not receive initial systemic therapy and a substantial proportion of treated patients did not receive guideline-concordant first-line therapy. Further research should explore underuse of chemotherapy and HER2-targeted therapies, investigate whether patterns of care are consistent with patient preferences, and identify opportunities to optimize hospice utilization for patients not receiving treatment.
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Oncological outcomes after cytoreductive nephrectomy for patients with metastatic renal cell carcinoma with inferior vena caval tumor thrombus
Abstract
Background
To evaluate the oncological outcomes of patients with metastatic renal cell carcinoma (mRCC) involving the inferior vena cava (IVC) who received cytoreductive nephrectomy.
Methods
This study included 75 consecutive metastatis renal cell carcinoma (mRCC) patients with inferior vena cava (IVC) tumor thrombus undergoing cytoreductive nephrectomy and tumor thrombectomy followed by systemic therapy.
Results
Of the 75 patients, 11, 33, 24 and 7 had level I, II, III and IV IVC thrombus, respectively. Following surgical treatment, 25 (group A), 27 (group B) and 23 (group C) received cytokine therapy alone, molecular-targeted therapy alone and both therapies, respectively, as management for metastatic diseases. The median overall survival (OS) of the 75 patients was 16.2 months. No significant differences in OS were noted according to the level of the IVC tumor thrombus. There were no significant differences in OS among groups A, B and C; however, OS in groups B and C was significantly superior to that in group A. Furthermore, multivariate analysis of several parameters identified the following independent predictors of poor OS—elevated C-reactive protein, liver metastasis and postoperative treatment with cytokine therapy alone.
Conclusions
The prognosis of mRCC patients with IVC thrombus undergoing cytoreductive nephrectomy may be significantly affected by the type of postoperative systemic therapy rather than the level of the IVC tumor thrombus. Accordingly, cytoreductive nephrectomy should be considered as a major therapeutic option for patients with mRCC involving the IVC, particularly in the era of targeted therapy.
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Oncological outcomes after cytoreductive nephrectomy for patients with metastatic renal cell carcinoma with inferior vena caval tumor thrombus
Abstract
Background
To evaluate the oncological outcomes of patients with metastatic renal cell carcinoma (mRCC) involving the inferior vena cava (IVC) who received cytoreductive nephrectomy.
Methods
This study included 75 consecutive metastatis renal cell carcinoma (mRCC) patients with inferior vena cava (IVC) tumor thrombus undergoing cytoreductive nephrectomy and tumor thrombectomy followed by systemic therapy.
Results
Of the 75 patients, 11, 33, 24 and 7 had level I, II, III and IV IVC thrombus, respectively. Following surgical treatment, 25 (group A), 27 (group B) and 23 (group C) received cytokine therapy alone, molecular-targeted therapy alone and both therapies, respectively, as management for metastatic diseases. The median overall survival (OS) of the 75 patients was 16.2 months. No significant differences in OS were noted according to the level of the IVC tumor thrombus. There were no significant differences in OS among groups A, B and C; however, OS in groups B and C was significantly superior to that in group A. Furthermore, multivariate analysis of several parameters identified the following independent predictors of poor OS—elevated C-reactive protein, liver metastasis and postoperative treatment with cytokine therapy alone.
Conclusions
The prognosis of mRCC patients with IVC thrombus undergoing cytoreductive nephrectomy may be significantly affected by the type of postoperative systemic therapy rather than the level of the IVC tumor thrombus. Accordingly, cytoreductive nephrectomy should be considered as a major therapeutic option for patients with mRCC involving the IVC, particularly in the era of targeted therapy.
http://ift.tt/2Fz9Fra
Combined sublethal irradiation and agonist anti-CD40 enhance donor T cell accumulation and control of autochthonous murine pancreatic tumors
Abstract
Tumor-reactive T lymphocytes can promote the regression of established tumors. However, their efficacy is often limited by immunosuppressive mechanisms that block T cell accumulation or function. ACT provides the opportunity to ameliorate immune suppression prior to transfer of tumor-reactive T cells to improve the therapeutic benefit. We evaluated the combination of lymphodepleting whole body irradiation (WBI) and agonist anti-CD40 (αCD40) antibody on control of established autochthonous murine neuroendocrine pancreatic tumors following the transfer of naïve tumor-specific CD8 T cells. Sublethal WBI had little impact on disease outcome but did promote T cell persistence in the lymphoid organs. Host conditioning with αCD40, an approach known to enhance APC function and T cell expansion, transiently increased donor T cell accumulation in the lymphoid organs and pancreas, but failed to control tumor progression. In contrast, combined WBI and αCD40 prolonged T cell proliferation and dramatically enhanced accumulation of donor T cells in both the lymphoid organs and pancreas. This dual conditioning approach also promoted high levels of inflammation in the pancreas and tumor, induced histological regression of established tumors, and extended the lifespan of treated mice. Prolonged survival was entirely dependent upon adoptive transfer, but only partially dependent upon IFNγ production by donor T cells. Our results identify the novel combination of two clinically relevant host conditioning approaches that synergize to overcome immune suppression and drive strong tumor-specific T cell accumulation within well-established tumors.
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Combined sublethal irradiation and agonist anti-CD40 enhance donor T cell accumulation and control of autochthonous murine pancreatic tumors
Abstract
Tumor-reactive T lymphocytes can promote the regression of established tumors. However, their efficacy is often limited by immunosuppressive mechanisms that block T cell accumulation or function. ACT provides the opportunity to ameliorate immune suppression prior to transfer of tumor-reactive T cells to improve the therapeutic benefit. We evaluated the combination of lymphodepleting whole body irradiation (WBI) and agonist anti-CD40 (αCD40) antibody on control of established autochthonous murine neuroendocrine pancreatic tumors following the transfer of naïve tumor-specific CD8 T cells. Sublethal WBI had little impact on disease outcome but did promote T cell persistence in the lymphoid organs. Host conditioning with αCD40, an approach known to enhance APC function and T cell expansion, transiently increased donor T cell accumulation in the lymphoid organs and pancreas, but failed to control tumor progression. In contrast, combined WBI and αCD40 prolonged T cell proliferation and dramatically enhanced accumulation of donor T cells in both the lymphoid organs and pancreas. This dual conditioning approach also promoted high levels of inflammation in the pancreas and tumor, induced histological regression of established tumors, and extended the lifespan of treated mice. Prolonged survival was entirely dependent upon adoptive transfer, but only partially dependent upon IFNγ production by donor T cells. Our results identify the novel combination of two clinically relevant host conditioning approaches that synergize to overcome immune suppression and drive strong tumor-specific T cell accumulation within well-established tumors.
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Eighty-five-year-old man with mosaic attenuation on chest imaging
Description
An 85-year-old man presented with worsening dyspnea and non-productive cough ongoing for 3 days prior to the admission. The patient denied any fever, chills, chest pain, palpitations, orthopnoea or paroxysmal nocturnal dyspnoea. Physical examination was remarkable for mild respiratory distress without any additional findings on auscultation. Social history was significant for >20 pack-year history of smoking. Vitals on admission: blood pressure 138/85, heart rate 92 bpm, respiratory rate 22, pO2 94% on room air. EKG was noticeable for normal sinus rhythm with ventricular rate of 87, without any ST-T wave changes.
A chest X-ray (CXR) was significant for hyperlucent lungs (figure 1). CT of chest without Intravenous contrast was performed to evaluate for possible atypical infection that could have been missed on the CXR.1 Areas of hypoattenuation are visible on the scan (figure 2A).
Figure 1
Chest X-ray showing hyperlucent lungs.
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Torsion and rupture of a non-communicating rudimentary horn in a 17-week gestation in a 16-year-old girl: lessons learnt
A unicornuate uterus with non-communicating rudimentary horn has always been notorious and poses threat to continuation of pregnancy with dismal consequences. We are reporting an interesting case of uterine malformation with a 90° rotation of uterine axis which ultimately ruptured during termination of pregnancy. The rarity in our case was not only conception in non-communicating horn but also the complete twisting of axis which made the pregnant horn come in front of the non-gravid unicornuate uterus, mimicking normal pregnancy. The most important lesson learnt is that if induction does not lead to cervical changes and uterine contractions, one must consider atypical presentations of an anomalous uterus as a possible differential before proceeding further.
http://ift.tt/2qX22ri
Correction: A rare case of dual diagnosis in a 16-year-old girl with shortness of breath
de Vere F, House R, Gokdogan Y. A rare case of dual diagnosis in a 16-year-old girl with shortness of breath. BMJ Case Reports 2017. doi:10.1136/bcr-2017-221939.
There was an error in the published version of this article, in that the following statement was missed from the publication:
FDV and RH are joint first authors and contributed equally to this paper.
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Relevance of enlarged cardiophrenic lymph nodes in determining prognosis of patients with advanced ovarian cancer
Ovarian cancer often presents at an advanced stage with widespread peritoneal and/or extra-abdominal metastases. Complete cytoreduction is the mainstay of treatment for disease confined to peritoneum. But in patients with distant metastases, the role and rationale is less obvious. One of the the most common sites of extra-abdominal disease is the cardiophrenic lymph node (CPLN). In this paper, we described the management of a patient with International Federation of Gynecology and Obstetrics (FIGO) stage IVB epithelial ovarian carcinoma and widespread peritoneal and extra-abdominal metastases to the CPLN, who underwent complete cytoreduction including excision of enlarged CPLN, following neoadjuvant chemotherapy. We examined the literature to determine the prognostic value of enlarged CPLN and their relevance in managing patients with advanced ovarian cancer and found it as an adverse prognostic factor. Transdiaphragmatic excision of CPLN is feasible without major complications. But as its correlation with overall or progression-free survival is not yet evident, large-scale prospective studies are warranted.
http://ift.tt/2r2KtGj
Combined sublethal irradiation and agonist anti-CD40 enhance donor T cell accumulation and control of autochthonous murine pancreatic tumors
Abstract
Tumor-reactive T lymphocytes can promote the regression of established tumors. However, their efficacy is often limited by immunosuppressive mechanisms that block T cell accumulation or function. ACT provides the opportunity to ameliorate immune suppression prior to transfer of tumor-reactive T cells to improve the therapeutic benefit. We evaluated the combination of lymphodepleting whole body irradiation (WBI) and agonist anti-CD40 (αCD40) antibody on control of established autochthonous murine neuroendocrine pancreatic tumors following the transfer of naïve tumor-specific CD8 T cells. Sublethal WBI had little impact on disease outcome but did promote T cell persistence in the lymphoid organs. Host conditioning with αCD40, an approach known to enhance APC function and T cell expansion, transiently increased donor T cell accumulation in the lymphoid organs and pancreas, but failed to control tumor progression. In contrast, combined WBI and αCD40 prolonged T cell proliferation and dramatically enhanced accumulation of donor T cells in both the lymphoid organs and pancreas. This dual conditioning approach also promoted high levels of inflammation in the pancreas and tumor, induced histological regression of established tumors, and extended the lifespan of treated mice. Prolonged survival was entirely dependent upon adoptive transfer, but only partially dependent upon IFNγ production by donor T cells. Our results identify the novel combination of two clinically relevant host conditioning approaches that synergize to overcome immune suppression and drive strong tumor-specific T cell accumulation within well-established tumors.
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Combined sublethal irradiation and agonist anti-CD40 enhance donor T cell accumulation and control of autochthonous murine pancreatic tumors
Abstract
Tumor-reactive T lymphocytes can promote the regression of established tumors. However, their efficacy is often limited by immunosuppressive mechanisms that block T cell accumulation or function. ACT provides the opportunity to ameliorate immune suppression prior to transfer of tumor-reactive T cells to improve the therapeutic benefit. We evaluated the combination of lymphodepleting whole body irradiation (WBI) and agonist anti-CD40 (αCD40) antibody on control of established autochthonous murine neuroendocrine pancreatic tumors following the transfer of naïve tumor-specific CD8 T cells. Sublethal WBI had little impact on disease outcome but did promote T cell persistence in the lymphoid organs. Host conditioning with αCD40, an approach known to enhance APC function and T cell expansion, transiently increased donor T cell accumulation in the lymphoid organs and pancreas, but failed to control tumor progression. In contrast, combined WBI and αCD40 prolonged T cell proliferation and dramatically enhanced accumulation of donor T cells in both the lymphoid organs and pancreas. This dual conditioning approach also promoted high levels of inflammation in the pancreas and tumor, induced histological regression of established tumors, and extended the lifespan of treated mice. Prolonged survival was entirely dependent upon adoptive transfer, but only partially dependent upon IFNγ production by donor T cells. Our results identify the novel combination of two clinically relevant host conditioning approaches that synergize to overcome immune suppression and drive strong tumor-specific T cell accumulation within well-established tumors.
http://ift.tt/2D9xuHQ
Handedness and the risk of glioma
Abstract
Gliomas are the most common type of malignant primary brain tumor and few risk factors have been linked to their development. Handedness has been associated with several pathologic neurological conditions such as schizophrenia, autism, and epilepsy, but few studies have evaluated a connection between handedness and risk of glioma. In this study, we examined the relationship between handedness and glioma risk in a large case–control study (1849 glioma cases and 1354 healthy controls) and a prospective cohort study (326,475 subjects with 375 incident gliomas). In the case–control study, we found a significant inverse association between left handedness and glioma risk, with left-handed persons exhibiting a 35% reduction in the risk of developing glioma [odds ratio (OR) = 0.65, 95% confidence interval (CI) 0.51–0.83] after adjustment for age, gender, race, education, and state of residence; similar inverse associations were observed for GBM (OR = 0.69, 95% CI 0.52–0.91), and non-GBM (OR = 0.59, 95% CI 0.42–0.82) subgroups. The association was consistent in both males and females, and across age strata, and was observed in both glioblastoma and in lower grade tumors. In the prospective cohort study, we found no association between handedness and glioma risk (hazards ratio = 0.92, 95% CI 0.67–1.28) adjusting for age, gender, and race. Further studies on this association may help to elucidate mechanisms of pathogenesis in glioma.
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Handedness and the risk of glioma
Abstract
Gliomas are the most common type of malignant primary brain tumor and few risk factors have been linked to their development. Handedness has been associated with several pathologic neurological conditions such as schizophrenia, autism, and epilepsy, but few studies have evaluated a connection between handedness and risk of glioma. In this study, we examined the relationship between handedness and glioma risk in a large case–control study (1849 glioma cases and 1354 healthy controls) and a prospective cohort study (326,475 subjects with 375 incident gliomas). In the case–control study, we found a significant inverse association between left handedness and glioma risk, with left-handed persons exhibiting a 35% reduction in the risk of developing glioma [odds ratio (OR) = 0.65, 95% confidence interval (CI) 0.51–0.83] after adjustment for age, gender, race, education, and state of residence; similar inverse associations were observed for GBM (OR = 0.69, 95% CI 0.52–0.91), and non-GBM (OR = 0.59, 95% CI 0.42–0.82) subgroups. The association was consistent in both males and females, and across age strata, and was observed in both glioblastoma and in lower grade tumors. In the prospective cohort study, we found no association between handedness and glioma risk (hazards ratio = 0.92, 95% CI 0.67–1.28) adjusting for age, gender, and race. Further studies on this association may help to elucidate mechanisms of pathogenesis in glioma.
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Long term exposure to cell phone frequencies (900 and 1800 MHz) induces apoptosis, mitochondrial oxidative stress and TRPV1 channel activation in the hippocampus and dorsal root ganglion of rats
Abstract
Mobile phone providers use electromagnetic radiation (EMR) with frequencies ranging from 900 to 1800 MHz. The increasing use of mobile phones has been accompanied by several potentially pathological consequences, such as neurological diseases related to hippocampal (HIPPON) and dorsal root ganglion neuron (DRGN). The TRPV1 channel is activated different stimuli, including CapN, high temperature and oxidative stress. We investigated the contribution TRPV1 to mitochondrial oxidative stress and apoptosis in HIPPON and DRGN following long term exposure to 900 and 1800 MHz in a rat model. Twenty-four adult rats were equally divided into the following groups: (1) control, (2) 900 MHz, and (3) 1800 MHz exposure. Each experimental group was exposed to EMR for 60 min/ 5 days of the week during the one year. The 900 and 1800 MHz EMR exposure induced increases in TRPV1 currents, intracellular free calcium influx (Ca2+), reactive oxygen species (ROS) production, mitochondrial membrane depolarization (JC-1), apoptosis, and caspase 3 and 9 activities in the HIPPON and DRGN. These deleterious processes were further increased in the 1800 MHz experimental group compared to the 900 MHz exposure group. In conclusion, mitochondrial oxidative stress, programmed cell death and Ca2+ entry pathway through TRPV1 activation in the HIPPON and DRGN of rats were increased in the rat model following exposure to 900 and 1800 MHz cell frequencies. Our results suggest that exposure to 900 and 1800 MHz EMR may induce a dose-associated, TRPV1-mediated stress response.
http://ift.tt/2AVuFVL
Long term exposure to cell phone frequencies (900 and 1800 MHz) induces apoptosis, mitochondrial oxidative stress and TRPV1 channel activation in the hippocampus and dorsal root ganglion of rats
Abstract
Mobile phone providers use electromagnetic radiation (EMR) with frequencies ranging from 900 to 1800 MHz. The increasing use of mobile phones has been accompanied by several potentially pathological consequences, such as neurological diseases related to hippocampal (HIPPON) and dorsal root ganglion neuron (DRGN). The TRPV1 channel is activated different stimuli, including CapN, high temperature and oxidative stress. We investigated the contribution TRPV1 to mitochondrial oxidative stress and apoptosis in HIPPON and DRGN following long term exposure to 900 and 1800 MHz in a rat model. Twenty-four adult rats were equally divided into the following groups: (1) control, (2) 900 MHz, and (3) 1800 MHz exposure. Each experimental group was exposed to EMR for 60 min/ 5 days of the week during the one year. The 900 and 1800 MHz EMR exposure induced increases in TRPV1 currents, intracellular free calcium influx (Ca2+), reactive oxygen species (ROS) production, mitochondrial membrane depolarization (JC-1), apoptosis, and caspase 3 and 9 activities in the HIPPON and DRGN. These deleterious processes were further increased in the 1800 MHz experimental group compared to the 900 MHz exposure group. In conclusion, mitochondrial oxidative stress, programmed cell death and Ca2+ entry pathway through TRPV1 activation in the HIPPON and DRGN of rats were increased in the rat model following exposure to 900 and 1800 MHz cell frequencies. Our results suggest that exposure to 900 and 1800 MHz EMR may induce a dose-associated, TRPV1-mediated stress response.
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Survivorship care plan outcomes for primary care physicians, cancer survivors, and systems: a scoping review
Abstract
Purpose
With the focus on survivorship care-coordination between oncology and primary care providers (PCPs), there is a need to assess the research regarding the use of survivorship care plans (SCPs) and determine emerging research areas. We sought to find out how primary care physicians have been involved in the use of SCPs and determine SCP's effectiveness in improving care for cancer survivors. In this scoping review, we aimed to identify gaps in the current research and reveal opportunities for further research.
Methods
We followed the methodology for scoping studies which consists of identifying the research question, locating relevant studies, selecting studies, charting the data, and collating, summarizing, and reporting the results.
Results
Out of 5375 original articles identified in the literature search, 25 met the inclusion/exclusion criteria. Eight articles examined PCP-only related outcomes, eight examined survivor-only related outcomes, eight examined mixed outcomes between both groups, and one examined system-based outcomes. Findings highlighted several areas where SCPs may provide benefits, including increased confidence among PCPs in managing the care of survivors and increased quality of life and well-being for survivors. This research also highlighted the need for careful consideration of SCP mode of delivery and content in order to maximize their utility to patients and providers.
Conclusions
Based on the findings of this review, SCPs may benefit providers and health care systems, but the benefits to patients remain unclear. Further research on the potential benefits of SCPs to particular patient populations is warranted.
Implications for Cancer Survivors
SCPs appear to be beneficial to PCPs in improving overall quality of care. However, more work needs to be done to understand the direct impact on cancer survivors.
http://ift.tt/2AWk9O7
Survivorship care plan outcomes for primary care physicians, cancer survivors, and systems: a scoping review
Abstract
Purpose
With the focus on survivorship care-coordination between oncology and primary care providers (PCPs), there is a need to assess the research regarding the use of survivorship care plans (SCPs) and determine emerging research areas. We sought to find out how primary care physicians have been involved in the use of SCPs and determine SCP's effectiveness in improving care for cancer survivors. In this scoping review, we aimed to identify gaps in the current research and reveal opportunities for further research.
Methods
We followed the methodology for scoping studies which consists of identifying the research question, locating relevant studies, selecting studies, charting the data, and collating, summarizing, and reporting the results.
Results
Out of 5375 original articles identified in the literature search, 25 met the inclusion/exclusion criteria. Eight articles examined PCP-only related outcomes, eight examined survivor-only related outcomes, eight examined mixed outcomes between both groups, and one examined system-based outcomes. Findings highlighted several areas where SCPs may provide benefits, including increased confidence among PCPs in managing the care of survivors and increased quality of life and well-being for survivors. This research also highlighted the need for careful consideration of SCP mode of delivery and content in order to maximize their utility to patients and providers.
Conclusions
Based on the findings of this review, SCPs may benefit providers and health care systems, but the benefits to patients remain unclear. Further research on the potential benefits of SCPs to particular patient populations is warranted.
Implications for Cancer Survivors
SCPs appear to be beneficial to PCPs in improving overall quality of care. However, more work needs to be done to understand the direct impact on cancer survivors.
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The Roles of Adjuvant Supplements in Colorectal Cancer Patients on Chemotherapy - Reaping Benefits from Metabolic Crosstalk.
| Related Articles |
The Roles of Adjuvant Supplements in Colorectal Cancer Patients on Chemotherapy - Reaping Benefits from Metabolic Crosstalk.
Nutr Cancer. 2018 Jan 11;:1-8
Authors: Golkhalkhali B, Paliany AS, Chin KF, Rajandram R
Abstract
The prevalence of colorectal cancer (CRC) is on a steady rise over the years, with the World Health Organization (WHO) reporting CRC as the fourth leading cause of cancer-related death worldwide. While treatment modalities may differ in accordance to the staging and severity of the disease itself, chemotherapy is almost unavoidable in most cases. Though effective in its mode of action, chemotherapy is commonly associated with undesirable side effects that negatively affects the patient in terms of quality of life, and in some cases may actually interfere with their treatment regimens, thus escalating to poor prognosis. Gastrointestinal disturbances is a major side effect of chemotherapy and in CRC, gastrointestinal disturbances may be further aggravated and grave in nature mainly due to the affected site, being the gastrointestinal tract. The use of complementary therapies as adjuncts to alleviate the side effects of chemotherapy in CRC patients is gaining prominence with dietary supplements being the most commonly employed adjunct. Some of the frequently used dietary supplements for CRC patients are probiotics, omega-3 fatty acid and glutamine. The successful crosstalk between these dietary supplements with important metabolic pathways is crucial in the alleviation of chemotherapy side effects.
PMID: 29324050 [PubMed - as supplied by publisher]
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The Prediction of Deterioration of Nutritional Status during Chemoradiation Therapy in Patients with Esophageal Cancer.
| Related Articles |
The Prediction of Deterioration of Nutritional Status during Chemoradiation Therapy in Patients with Esophageal Cancer.
Nutr Cancer. 2018 Jan 11;:1-7
Authors: Rietveld SCM, Witvliet-van Nierop JE, Ottens-Oussoren K, van der Peet DL, de van der Schueren MAE
Abstract
Patients with esophageal cancer are at high risk of developing malnutrition during neoadjuvant chemoradiation therapy (CRT), which in turn is associated with postoperative morbidity. The aim of the study is to explore whether parameters of a complete pre-treatment nutritional status may predict deterioration of nutritional status during CRT in patients with esophageal cancer. In this prospective cohort study, 101 patients with esophageal cancer treated with CRT were included. Data of patient characteristics, tumor classification, performance score, %weight change, body mass index, fat (free) mass index, phase angle, handgrip strength, energy- and protein intake, and use of (additional) dietary supplements were collected. A prediction model was constructed to identify predictive parameters for deterioration in nutritional status (defined as weight loss of >5% and/or decline in fat free mass of ≥1.4 kg) during CRT. Nutritional status deteriorated in 49 patients (49%) during CRT. The only predictor for deterioration in nutritional status was fat free mass index (OR 1.21 (90% CI: 1.03 - 1.42)). Patients with a higher fat free mass index are at increased risk of deterioration in nutrition status during CRT. Results suggest that all patients should be carefully supervised during CRT, regardless of their nutritional status before start of CRT.
PMID: 29324061 [PubMed - as supplied by publisher]
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The Roles of Adjuvant Supplements in Colorectal Cancer Patients on Chemotherapy - Reaping Benefits from Metabolic Crosstalk.
| Related Articles |
The Roles of Adjuvant Supplements in Colorectal Cancer Patients on Chemotherapy - Reaping Benefits from Metabolic Crosstalk.
Nutr Cancer. 2018 Jan 11;:1-8
Authors: Golkhalkhali B, Paliany AS, Chin KF, Rajandram R
Abstract
The prevalence of colorectal cancer (CRC) is on a steady rise over the years, with the World Health Organization (WHO) reporting CRC as the fourth leading cause of cancer-related death worldwide. While treatment modalities may differ in accordance to the staging and severity of the disease itself, chemotherapy is almost unavoidable in most cases. Though effective in its mode of action, chemotherapy is commonly associated with undesirable side effects that negatively affects the patient in terms of quality of life, and in some cases may actually interfere with their treatment regimens, thus escalating to poor prognosis. Gastrointestinal disturbances is a major side effect of chemotherapy and in CRC, gastrointestinal disturbances may be further aggravated and grave in nature mainly due to the affected site, being the gastrointestinal tract. The use of complementary therapies as adjuncts to alleviate the side effects of chemotherapy in CRC patients is gaining prominence with dietary supplements being the most commonly employed adjunct. Some of the frequently used dietary supplements for CRC patients are probiotics, omega-3 fatty acid and glutamine. The successful crosstalk between these dietary supplements with important metabolic pathways is crucial in the alleviation of chemotherapy side effects.
PMID: 29324050 [PubMed - as supplied by publisher]
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Combined sublethal irradiation and agonist anti-CD40 enhance donor T cell accumulation and control of autochthonous murine pancreatic tumors
Abstract
Tumor-reactive T lymphocytes can promote the regression of established tumors. However, their efficacy is often limited by immunosuppressive mechanisms that block T cell accumulation or function. ACT provides the opportunity to ameliorate immune suppression prior to transfer of tumor-reactive T cells to improve the therapeutic benefit. We evaluated the combination of lymphodepleting whole body irradiation (WBI) and agonist anti-CD40 (αCD40) antibody on control of established autochthonous murine neuroendocrine pancreatic tumors following the transfer of naïve tumor-specific CD8 T cells. Sublethal WBI had little impact on disease outcome but did promote T cell persistence in the lymphoid organs. Host conditioning with αCD40, an approach known to enhance APC function and T cell expansion, transiently increased donor T cell accumulation in the lymphoid organs and pancreas, but failed to control tumor progression. In contrast, combined WBI and αCD40 prolonged T cell proliferation and dramatically enhanced accumulation of donor T cells in both the lymphoid organs and pancreas. This dual conditioning approach also promoted high levels of inflammation in the pancreas and tumor, induced histological regression of established tumors, and extended the lifespan of treated mice. Prolonged survival was entirely dependent upon adoptive transfer, but only partially dependent upon IFNγ production by donor T cells. Our results identify the novel combination of two clinically relevant host conditioning approaches that synergize to overcome immune suppression and drive strong tumor-specific T cell accumulation within well-established tumors.
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The Prediction of Deterioration of Nutritional Status during Chemoradiation Therapy in Patients with Esophageal Cancer.
| Related Articles |
The Prediction of Deterioration of Nutritional Status during Chemoradiation Therapy in Patients with Esophageal Cancer.
Nutr Cancer. 2018 Jan 11;:1-7
Authors: Rietveld SCM, Witvliet-van Nierop JE, Ottens-Oussoren K, van der Peet DL, de van der Schueren MAE
Abstract
Patients with esophageal cancer are at high risk of developing malnutrition during neoadjuvant chemoradiation therapy (CRT), which in turn is associated with postoperative morbidity. The aim of the study is to explore whether parameters of a complete pre-treatment nutritional status may predict deterioration of nutritional status during CRT in patients with esophageal cancer. In this prospective cohort study, 101 patients with esophageal cancer treated with CRT were included. Data of patient characteristics, tumor classification, performance score, %weight change, body mass index, fat (free) mass index, phase angle, handgrip strength, energy- and protein intake, and use of (additional) dietary supplements were collected. A prediction model was constructed to identify predictive parameters for deterioration in nutritional status (defined as weight loss of >5% and/or decline in fat free mass of ≥1.4 kg) during CRT. Nutritional status deteriorated in 49 patients (49%) during CRT. The only predictor for deterioration in nutritional status was fat free mass index (OR 1.21 (90% CI: 1.03 - 1.42)). Patients with a higher fat free mass index are at increased risk of deterioration in nutrition status during CRT. Results suggest that all patients should be carefully supervised during CRT, regardless of their nutritional status before start of CRT.
PMID: 29324061 [PubMed - as supplied by publisher]
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Vasoactive-inotropic score as a predictor of morbidity and mortality in adults after cardiac surgery with cardiopulmonary bypass
Abstract
Purpose
The vasoactive-inotropic score (VIS) is a scale showing the amount of vasoactive and inotropic support. Recently, it was suggested that the VIS after cardiac surgery predicts morbidity and mortality in infants. The purpose of this study was to evaluate the VIS at the end of surgery as a predictor of morbidity and mortality in adult cardiac surgery.
Methods
A retrospective cohort study of 129 adult cardiac surgery patients was performed at a university hospital. The primary outcome was termed "poor outcome", which was a composite of morbidity and mortality. The secondary outcomes were the duration of intensive care unit (ICU) stay and time to first extubation. Multivariate logistic regression analysis was performed to evaluate the association between the VIS and poor outcomes. A proportional hazards model was used to evaluate the duration of the ICU stay and time to first extubation.
Results
After adjusting for the EuroSCORE, preoperative ejection fraction, and bypass time, a high VIS at the end of surgery was associated with a poor outcome with an adjusted odds ratio of 4.87 (95% confidence interval 1.51–18.94; p = 0.007). After controlling for the EuroSCORE and bypass time, patients with a high VIS experienced longer ICU stay (hazard ratio 1.62; 95% confidence interval 1.10–2.39; p = 0.015) and needed longer ventilation (hazard ration 1.87; 95% confidence interval 1.28–2.74, p = 0.001).
Conclusions
The amount of cardiovascular support at the end of cardiac surgery may predict morbidity and mortality in adults.
http://ift.tt/2D6Ugkl
Tumor expression of survivin, p53, cyclin D1, osteopontin and fibronectin in predicting the response to neo-adjuvant chemotherapy in children with advanced malignant peripheral nerve sheath tumor
Abstract
Purpose
Selected cell-cycle regulators and extracellular matrix proteins were found to play roles in malignant peripheral nerve sheath tumor (MPNST) biology. We aimed to analyze whether initial tumor tissue expressions of survivin, p53, cyclin D1, osteopontin (OPN) and fibronectin (FN) correlate with the response to neo-adjuvant CHT (naCHT) in children with advanced inoperable MPNST.
Methods
The study included 26 children with MPNST (M/F 14/12, median age 130 months) treated in Polish centers of pediatric oncology between 1992 and 2013. Tissue expression of markers was studied immunohistochemically in the manually performed tissue microarrays and assessed semi-quantitatively as low and high, based on the rate of positive cells and staining intensity.
Results
Good response to naCHT was noted in 47.6%, while poor—in 52.4% of patients. The response to naCHT was influenced negatively by the presence of neurofibromatosis NF1 and high initial tumor tissue expression of OPN, survivin, p53 and cyclin D1. Patients with high tumor expression of either OPN, survivin or p53 and those with simultaneous high expression of ≥ 3 of the markers, responded significantly worse to naCHT, than patients, in whom expression of ≤ 2 markers were detected at diagnosis. Nearly, 85% of patients expressing ≥ 3 markers, responded poor to CHT; while 87.5% of children, expressing ≤ 2 markers, were good responders.
Conclusion
The initial tumor tissue expression of OPN, survivin, p53 and cyclin D1 may serve as markers to predict response to naCHT in pediatric advanced MPNST. Future studies in more numerous group of patients are needed to confirm these preliminary results.
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Tumor expression of survivin, p53, cyclin D1, osteopontin and fibronectin in predicting the response to neo-adjuvant chemotherapy in children with advanced malignant peripheral nerve sheath tumor
Abstract
Purpose
Selected cell-cycle regulators and extracellular matrix proteins were found to play roles in malignant peripheral nerve sheath tumor (MPNST) biology. We aimed to analyze whether initial tumor tissue expressions of survivin, p53, cyclin D1, osteopontin (OPN) and fibronectin (FN) correlate with the response to neo-adjuvant CHT (naCHT) in children with advanced inoperable MPNST.
Methods
The study included 26 children with MPNST (M/F 14/12, median age 130 months) treated in Polish centers of pediatric oncology between 1992 and 2013. Tissue expression of markers was studied immunohistochemically in the manually performed tissue microarrays and assessed semi-quantitatively as low and high, based on the rate of positive cells and staining intensity.
Results
Good response to naCHT was noted in 47.6%, while poor—in 52.4% of patients. The response to naCHT was influenced negatively by the presence of neurofibromatosis NF1 and high initial tumor tissue expression of OPN, survivin, p53 and cyclin D1. Patients with high tumor expression of either OPN, survivin or p53 and those with simultaneous high expression of ≥ 3 of the markers, responded significantly worse to naCHT, than patients, in whom expression of ≤ 2 markers were detected at diagnosis. Nearly, 85% of patients expressing ≥ 3 markers, responded poor to CHT; while 87.5% of children, expressing ≤ 2 markers, were good responders.
Conclusion
The initial tumor tissue expression of OPN, survivin, p53 and cyclin D1 may serve as markers to predict response to naCHT in pediatric advanced MPNST. Future studies in more numerous group of patients are needed to confirm these preliminary results.
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Imaging in juvenile idiopathic arthritis — international initiatives and ongoing work
Abstract
Imaging is increasingly being integrated into clinical practice to improve diagnosis, disease control and outcome in children with juvenile idiopathic arthritis. Over the last decades several international groups have been launched to standardize and validate different imaging techniques. To enhance transparency and facilitate collaboration, we present an overview of ongoing initiatives.
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Neurologic complications of immune checkpoint inhibitors
Abstract
Immune checkpoint inhibitors (ICPIs) have recently emerged as a novel treatment for cancer. These agents, transforming the field of oncology, are not devoid of toxicity and cause immune-related side effects which can involve any organ including the nervous system. In this study, we present 9 patients (7 men and 2 women) with neurologic complications secondary to ICPI treatment. These included meningoencephalitis, limbic encephalitis, polyradiculitis, cranial polyneuropathy, myasthenic syndrome and myositis. Four patients received dual ICPI therapy comprised of programmed cell death-1 and cytotoxic lymphocyte associated protein-4 blocking antibodies. Median time to onset of neurologic adverse event during immune checkpoint inhibitor treatment was 8 weeks (range 5 days–19 weeks). In all patients ICPIs were stopped and corticosteroids were initiated, resulting in a marked improvement in seven out of nine patients. Two patients, one with myositis and one with myasthenic syndrome, died. In two patients ICPI therapy was resumed after resolution of the neurological adverse event with no additional neurologic complications. This series highlights the very broad spectrum of neurological complications of ICPIs, emphasizes the need for expedited diagnosis and suggests that withholding treatment early, accompanied with steroid therapy, carries the potential of complete resolution of the neurological immune-mediated condition. Thus, a high level of suspicion and rapid initiation of corticosteroids are mandatory to prevent uncontrolled clinical deterioration, which might be fatal.
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Imaging in juvenile idiopathic arthritis — international initiatives and ongoing work
Abstract
Imaging is increasingly being integrated into clinical practice to improve diagnosis, disease control and outcome in children with juvenile idiopathic arthritis. Over the last decades several international groups have been launched to standardize and validate different imaging techniques. To enhance transparency and facilitate collaboration, we present an overview of ongoing initiatives.
http://ift.tt/2EFJXjQ
Neurologic complications of immune checkpoint inhibitors
Abstract
Immune checkpoint inhibitors (ICPIs) have recently emerged as a novel treatment for cancer. These agents, transforming the field of oncology, are not devoid of toxicity and cause immune-related side effects which can involve any organ including the nervous system. In this study, we present 9 patients (7 men and 2 women) with neurologic complications secondary to ICPI treatment. These included meningoencephalitis, limbic encephalitis, polyradiculitis, cranial polyneuropathy, myasthenic syndrome and myositis. Four patients received dual ICPI therapy comprised of programmed cell death-1 and cytotoxic lymphocyte associated protein-4 blocking antibodies. Median time to onset of neurologic adverse event during immune checkpoint inhibitor treatment was 8 weeks (range 5 days–19 weeks). In all patients ICPIs were stopped and corticosteroids were initiated, resulting in a marked improvement in seven out of nine patients. Two patients, one with myositis and one with myasthenic syndrome, died. In two patients ICPI therapy was resumed after resolution of the neurological adverse event with no additional neurologic complications. This series highlights the very broad spectrum of neurological complications of ICPIs, emphasizes the need for expedited diagnosis and suggests that withholding treatment early, accompanied with steroid therapy, carries the potential of complete resolution of the neurological immune-mediated condition. Thus, a high level of suspicion and rapid initiation of corticosteroids are mandatory to prevent uncontrolled clinical deterioration, which might be fatal.
http://ift.tt/2D7uUD1
The association between smoking and cancer incidence in BRCA1 and BRCA2 mutation carriers
Abstract
Tobacco smoke is an established carcinogen, but the association between tobacco smoking and cancer risk in BRCA mutation carriers is not clear. The aim of this study was to evaluate prospectively the association between tobacco smoking and cancer incidence in a cohort of BRCA1 and BRCA2 mutation carriers. The study population consisted of unaffected BRCA mutation carriers. Information on lifestyle including smoking histories, reproductive factors, and past medical histories was obtained through questionnaires. Incident cancers were updated biennially via follow-up questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using time-dependent Cox regression models. There were 700 incident cancers diagnosed over 26,711 person-years of follow-up. The most frequent cancers seen in BRCA mutation carriers were breast (n = 428; 61%) and ovarian (n = 109; 15%) cancer. Compared to non-smokers, (ever) smoking was associated with a modest increased risk of all cancers combined (HR = 1.17; 95%CI 1.01-1.37). Women in the highest group of total pack-years (4.3-9.8) had an increased risk of developing any cancer (HR = 1.27; 95%CI 1.04-1.56), breast cancer (HR=1.33, 95%CI 1.02-1.75), and ovarian cancer (HR = 1.68; 95%CI 1.06-2.67) compared to never smokers. The associations between tobacco smoking and cancer did not differ by BRCA mutation type or by age at diagnosis. This prospective study suggests that tobacco smoking is associated with a modest increase in the risks of breast and ovarian cancer among women with BRCA1 or BRCA2 mutation. This article is protected by copyright. All rights reserved.
http://ift.tt/2ECKCT2
Reproductive history, breast-feeding and risk of triple negative breast cancer: The Breast Cancer Etiology in Minorities (BEM) Study
Abstract
Few risk factors have been identified for triple negative breast cancer (TNBC) which lacks expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). This more aggressive subtype disproportionately affects some racial/ethnic minorities and is associated with lower survival. We pooled data from three population-based studies (558 TNBC and 5,111 controls) and examined associations of TNBC risk with reproductive history and breast-feeding. We estimated odds ratios (OR) and 95% confidence intervals (CI) using multivariable logistic regression. For younger women, aged <50 years, TNBC risk was increased two-fold for parous women who never breast-fed compared to nulliparous women (OR=2.02, 95% CI=1.12-3.63). For younger parous women, longer duration of lifetime breast-feeding was associated with a borderline reduced risk (≥24 vs. 0 months: OR=0.52, 95% CI=0.26-1.04, P trend=0.06). Considering the joint effect of parity and breast-feeding, risk was increased two-fold for women with ≥3 full-term pregnancies (FTPs) and no or short-term (<12 months) breast-feeding compared to women with 1-2 FTPs and breast-feeding ≥12 months (OR=2.56, 95% CI=1.22-5.35). None of these associations were observed among older women (≥50 years). Differences in reproductive patterns possibly contribute to the racial/ethnic differences in TNBC incidence. Among controls aged <50 years, the prevalence of no or short-term breast-feeding and ≥3 FTPs was highest for Hispanics (22%), followed by African Americans (18%), Asian Americans (15%), and non-Hispanic whites (6%). Breast-feeding is a modifiable behavioral factor that may lower TNBC risk and mitigate the effect of full-term pregnancies in women under age 50 years. This article is protected by copyright. All rights reserved.
http://ift.tt/2FwJ527
The association between smoking and cancer incidence in BRCA1 and BRCA2 mutation carriers
Abstract
Tobacco smoke is an established carcinogen, but the association between tobacco smoking and cancer risk in BRCA mutation carriers is not clear. The aim of this study was to evaluate prospectively the association between tobacco smoking and cancer incidence in a cohort of BRCA1 and BRCA2 mutation carriers. The study population consisted of unaffected BRCA mutation carriers. Information on lifestyle including smoking histories, reproductive factors, and past medical histories was obtained through questionnaires. Incident cancers were updated biennially via follow-up questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using time-dependent Cox regression models. There were 700 incident cancers diagnosed over 26,711 person-years of follow-up. The most frequent cancers seen in BRCA mutation carriers were breast (n = 428; 61%) and ovarian (n = 109; 15%) cancer. Compared to non-smokers, (ever) smoking was associated with a modest increased risk of all cancers combined (HR = 1.17; 95%CI 1.01-1.37). Women in the highest group of total pack-years (4.3-9.8) had an increased risk of developing any cancer (HR = 1.27; 95%CI 1.04-1.56), breast cancer (HR=1.33, 95%CI 1.02-1.75), and ovarian cancer (HR = 1.68; 95%CI 1.06-2.67) compared to never smokers. The associations between tobacco smoking and cancer did not differ by BRCA mutation type or by age at diagnosis. This prospective study suggests that tobacco smoking is associated with a modest increase in the risks of breast and ovarian cancer among women with BRCA1 or BRCA2 mutation. This article is protected by copyright. All rights reserved.
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Reproductive history, breast-feeding and risk of triple negative breast cancer: The Breast Cancer Etiology in Minorities (BEM) Study
Abstract
Few risk factors have been identified for triple negative breast cancer (TNBC) which lacks expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). This more aggressive subtype disproportionately affects some racial/ethnic minorities and is associated with lower survival. We pooled data from three population-based studies (558 TNBC and 5,111 controls) and examined associations of TNBC risk with reproductive history and breast-feeding. We estimated odds ratios (OR) and 95% confidence intervals (CI) using multivariable logistic regression. For younger women, aged <50 years, TNBC risk was increased two-fold for parous women who never breast-fed compared to nulliparous women (OR=2.02, 95% CI=1.12-3.63). For younger parous women, longer duration of lifetime breast-feeding was associated with a borderline reduced risk (≥24 vs. 0 months: OR=0.52, 95% CI=0.26-1.04, P trend=0.06). Considering the joint effect of parity and breast-feeding, risk was increased two-fold for women with ≥3 full-term pregnancies (FTPs) and no or short-term (<12 months) breast-feeding compared to women with 1-2 FTPs and breast-feeding ≥12 months (OR=2.56, 95% CI=1.22-5.35). None of these associations were observed among older women (≥50 years). Differences in reproductive patterns possibly contribute to the racial/ethnic differences in TNBC incidence. Among controls aged <50 years, the prevalence of no or short-term breast-feeding and ≥3 FTPs was highest for Hispanics (22%), followed by African Americans (18%), Asian Americans (15%), and non-Hispanic whites (6%). Breast-feeding is a modifiable behavioral factor that may lower TNBC risk and mitigate the effect of full-term pregnancies in women under age 50 years. This article is protected by copyright. All rights reserved.
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Sequential versus simultaneous use of chemotherapy and gonadotropin-releasing hormone agonist (GnRHa) among estrogen receptor (ER)-positive premenopausal breast cancer patients: effects on ovarian function, disease-free survival, and overall survival
Abstract
Objective
To investigate ovarian function and therapeutic efficacy among estrogen receptor (ER)-positive, premenopausal breast cancer patients treated with gonadotropin-releasing hormone agonist (GnRHa) and chemotherapy simultaneously or sequentially.
Method
This study was a phase 3, open-label, parallel, randomized controlled trial (NCT01712893). Two hundred sixteen premenopausal patients (under 45 years) diagnosed with invasive ER-positive breast cancer were enrolled from July 2009 to May 2013 and randomized at a 1:1 ratio to receive (neo)adjuvant chemotherapy combined with sequential or simultaneous GnRHa treatment. All patients were advised to receive GnRHa for at least 2 years. The primary outcome was the incidence of early menopause, defined as amenorrhea lasting longer than 12 months after the last chemotherapy or GnRHa dose, with postmenopausal or unknown follicle-stimulating hormone and estradiol levels. The menstrual resumption period and survivals were the secondary endpoints.
Result
The median follow-up time was 56.9 months (IQR 49.5–72.4 months). One hundred and eight patients were enrolled in each group. Among them, 92 and 78 patients had complete primary endpoint data in the sequential and simultaneous groups, respectively. The rates of early menopause were 22.8% (21/92) in the sequential group and 23.1% (18/78) in the simultaneous group [simultaneous vs. sequential: OR 1.01 (95% CI 0.50–2.08); p = 0.969; age-adjusted OR 1.13; (95% CI 0.54–2.37); p = 0.737]. The median menstruation resumption period was 12.0 (95% CI 9.3–14.7) months and 10.3 (95% CI 8.2–12.4) months for the sequential and simultaneous groups, respectively [HR 0.83 (95% CI 0.59–1.16); p = 0.274; age-adjusted HR 0.90 (95%CI 0.64–1.27); p = 0.567]. No significant differences were evident for disease-free survival (p = 0.290) or overall survival (p = 0.514) between the two groups.
Conclusion
For ER-positive premenopausal patients, the sequential use of GnRHa and chemotherapy showed ovarian preservation and survival outcomes that were no worse than simultaneous use. The application of GnRHa can probably be delayed until menstruation resumption after chemotherapy.
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