Assessing the Feasibility of an Electronic Patient-Reported Outcome (ePRO) Collection System in Caregivers of Cancer Patients

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Assessing the Feasibility of an Electronic Patient-Reported Outcome (ePRO) Collection System in Caregivers of Cancer Patients

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Cancers, Vol. 10, Pages 44: Integrin Inhibitors in Prostate Cancer

Cancers, Vol. 10, Pages 44: Integrin Inhibitors in Prostate Cancer

Cancers doi: 10.3390/cancers10020044

Authors: Maylein Juan-Rivera Magaly Martínez-Ferrer

Prostate cancer (PCa) is the most frequently diagnosed cancer and the third highest cause of cancer-related deaths in men in the U.S. The development of chemotherapeutic agents that can bind PCa tumor cells with high specificity is critical in order to increase treatment effectiveness. Integrin receptors and their corresponding ligands have different expression patterns in PCa cells. They have been identified as promising targets to inhibit pathways involved in PCa progression. Currently, several compounds have proven to target specific integrins and their subunits in PCa cells. In this article, we review the role of integrins inhibitors in PCa and their potential as therapeutic targets for PCa treatments. We have discussed the following: natural compounds, monoclonal antibodies, statins, campothecins analog, aptamers, d-aminoacid, and snake venom. Recent studies have shown that their mechanisms of action result in decrease cell migration, cell invasion, cell proliferation, and metastasis of PCa cells.

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Cancers, Vol. 10, Pages 44: Integrin Inhibitors in Prostate Cancer

Cancers, Vol. 10, Pages 44: Integrin Inhibitors in Prostate Cancer

Cancers doi: 10.3390/cancers10020044

Authors: Maylein Juan-Rivera Magaly Martínez-Ferrer

Prostate cancer (PCa) is the most frequently diagnosed cancer and the third highest cause of cancer-related deaths in men in the U.S. The development of chemotherapeutic agents that can bind PCa tumor cells with high specificity is critical in order to increase treatment effectiveness. Integrin receptors and their corresponding ligands have different expression patterns in PCa cells. They have been identified as promising targets to inhibit pathways involved in PCa progression. Currently, several compounds have proven to target specific integrins and their subunits in PCa cells. In this article, we review the role of integrins inhibitors in PCa and their potential as therapeutic targets for PCa treatments. We have discussed the following: natural compounds, monoclonal antibodies, statins, campothecins analog, aptamers, d-aminoacid, and snake venom. Recent studies have shown that their mechanisms of action result in decrease cell migration, cell invasion, cell proliferation, and metastasis of PCa cells.

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Enhanced Recovery After Surgery (ERAS®) in thoracic surgical oncology

Future Oncology, Ahead of Print.


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Is it appropriate to perform video-assisted thoracoscopic surgery for advanced lung cancer?

Future Oncology, Ahead of Print.


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Enhanced Recovery After Surgery (ERAS®) in thoracic surgical oncology

Future Oncology, Ahead of Print.


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Is it appropriate to perform video-assisted thoracoscopic surgery for advanced lung cancer?

Future Oncology, Ahead of Print.


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Title page / Editorial Board

Publication date: February 2018
Source:Cancer Epidemiology, Volume 52





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Table of contents

Publication date: February 2018
Source:Cancer Epidemiology, Volume 52





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Title page / Editorial Board

Publication date: February 2018
Source:Cancer Epidemiology, Volume 52





http://ift.tt/2sdT2Pe

Table of contents

Publication date: February 2018
Source:Cancer Epidemiology, Volume 52





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In Vitro and In Vivo Characterization of a Preclinical Radiation-Adapted Model for Ewing Sarcoma

Publication date: Available online 5 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Mary Carroll Shapiro, Tien Tang, Atreyi Dasgupta, Lyazat Kurenbekova, Ryan Shuck, M. Waleed Gaber, Jason T. Yustein
PurposeRadiation therapy (RT) is a viable therapeutic option for Ewing sarcoma (ES) patients. However, little progress has been made to elucidate mechanisms of radioresistance. This study establishes a novel ES radiation-adapted model designed to assess molecular and fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) alterations secondary RT.Methods and MaterialsRadiation-adapted cell lines (RACL) were created in vitro by exposing ES human cell lines to fractionated doses of radiation. Assays to assess migration/invasion potential and RNA expression were performed on the RACL. Orthotopic intra-tibial in vivo investigations were performed with radiation-sensitive and radiation-adapted ES cells to generate tumors. Transplanted mice were imaged using ¹⁸F-FDG-PET followed by fractionated RT directed at the primary tumor. Mice were monitored for tumor regression and change in metabolic activity using ¹⁸F-FDG PET imaging. Protein expression analyses were performed on the RACL and orthotopic tumors.ResultsExposure to fractionated doses of radiation caused a significant increase in migratory and invasive properties in the RACL when compared to non-irradiated wild type ES cells. RACL transcriptomic and proteomic analysis suggests enhanced activation of the mTOR-AKT pathway when compared to wild type ES cells. Radiation-adapted tumors demonstrated significantly less tumor regression (p = 0.03) compared to wild type tumors. Wild type tumors also had decreased expression of lactate dehydrogenase A (LDHA) protein and significantly lower metabolic activity after RT compared to radiation-adapted tumors (p = 0.03).ConclusionsWe developed novel in vitro and in vivo radiation-adapted ES models. In vitro investigations revealed increased migratory and invasive phenotypes in the RACL. In vivo investigations demonstrated increased metabolic activity and significantly decreased sensitivity to RT in the radiation-adapted tumors as demonstrated by growth response curves and ¹⁸F-FDG PET activity. Investigations of the RACL identified possible radiosensitizing-dependent targets in LDHA and mTOR-AKT pathway.

Teaser

Ewing sarcoma (ES) is the second most common pediatric bone cancer, and patients with relapsed/resistant disease have a five-year overall survival rate of only 15-20%. Front-line standard of care treatment for patients with ES includes chemotherapy and local control with surgery and/or radiation. We have developed novel in vitro and in vivo radiation-adapted ES models that demonstrate a relationship between metabolism and radioresistance as well as identify several candidate biomarkers for radioresistant disease in ES.


http://ift.tt/2BKwWb8

Does Prophylactic Radiotherapy to avoid Gynecomastia in Patients with Prostate Cancer increase the risk of Breast Cancer?

Publication date: Available online 5 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Bjørg Y. Aksnessæther, Arne Solberg, Olbjørn H. Klepp, Tor Åge Myklebust, Eva Skovlund, Solveig Roth Hoff, Lars J. Vatten, Jo-Åsmund Lund
PurposeProstate cancer (PC) patients treated with antiandrogen monotherapy are offered prophylactic radiotherapy to the breast buds (PRT) to avoid gynecomastia. The aim of this study was to evaluate whether the risk of breast cancer (BC) in men with PC as their first cancer diagnosis, was influenced by PRT.Methods and MaterialsFrom the Norwegian Cancer Registry we collected data on all patients with PC as their first cancer diagnosis diagnosed between 1997- 2014. We registered all radiotherapy given to the patients in the same period, and the occurrence of BC diagnosed 3 months or more following the PC diagnosis. The histopathological diagnoses of all BC cases were collected. Subdistribution hazard ratios (SHR) for the risk of BC in PRT and non-PRT treated patients were estimated. A standardized incidence ratio (SIR) for BC was calculated by comparing our cohort to the standard male population.ResultsWe analyzed 59 169 patients with PC, whom 7864 (13.3%) had received PRT. Median follow-up time was 4 years. Three of 12 men diagnosed with BC had received PRT, and two of three were phyllodes tumors. The risk of BC was not statistically significantly different in patients given RT as compared to the non-RT patients, SHR 1.62 95% CI 0.41-5.62, adjusted for age and time of diagnosis. SIR was 0.996 95 % CI 0.57-1.75.ConclusionsIn this registry based study, we did not find an increased risk of BC in PC patients treated with PRT. The number of BC cases in our study was low, and the risk of secondary breast cancer following PRT seems to be negligible. The incidence of BC may, however rise with additional follow-up. It is noteworthy that two patients who had been treated with PRT were diagnosed with malignant phyllodes tumor, an extremely rare type of BC associated with gynecomastia.

Teaser

Nordic patients with prostate cancer receive prophylactic radiotherapy to the breast buds to avoid gynecomastia when treated with antiandrogen monotherapy. In this study with data from the Norwegian Cancer Registry, we did not find increased risk of breast cancer (BC) in irradiated patients compared to non-irradiated patients. It is noteworthy that in the RT group, there were two cases of malignant phyllodes breast tumor, an extremely rare type of BC associated with gynecomastia.


http://ift.tt/2BcjeN5

In Vitro and In Vivo Characterization of a Preclinical Radiation-Adapted Model for Ewing Sarcoma

Publication date: Available online 5 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Mary Carroll Shapiro, Tien Tang, Atreyi Dasgupta, Lyazat Kurenbekova, Ryan Shuck, M. Waleed Gaber, Jason T. Yustein
PurposeRadiation therapy (RT) is a viable therapeutic option for Ewing sarcoma (ES) patients. However, little progress has been made to elucidate mechanisms of radioresistance. This study establishes a novel ES radiation-adapted model designed to assess molecular and fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET) alterations secondary RT.Methods and MaterialsRadiation-adapted cell lines (RACL) were created in vitro by exposing ES human cell lines to fractionated doses of radiation. Assays to assess migration/invasion potential and RNA expression were performed on the RACL. Orthotopic intra-tibial in vivo investigations were performed with radiation-sensitive and radiation-adapted ES cells to generate tumors. Transplanted mice were imaged using ¹⁸F-FDG-PET followed by fractionated RT directed at the primary tumor. Mice were monitored for tumor regression and change in metabolic activity using ¹⁸F-FDG PET imaging. Protein expression analyses were performed on the RACL and orthotopic tumors.ResultsExposure to fractionated doses of radiation caused a significant increase in migratory and invasive properties in the RACL when compared to non-irradiated wild type ES cells. RACL transcriptomic and proteomic analysis suggests enhanced activation of the mTOR-AKT pathway when compared to wild type ES cells. Radiation-adapted tumors demonstrated significantly less tumor regression (p = 0.03) compared to wild type tumors. Wild type tumors also had decreased expression of lactate dehydrogenase A (LDHA) protein and significantly lower metabolic activity after RT compared to radiation-adapted tumors (p = 0.03).ConclusionsWe developed novel in vitro and in vivo radiation-adapted ES models. In vitro investigations revealed increased migratory and invasive phenotypes in the RACL. In vivo investigations demonstrated increased metabolic activity and significantly decreased sensitivity to RT in the radiation-adapted tumors as demonstrated by growth response curves and ¹⁸F-FDG PET activity. Investigations of the RACL identified possible radiosensitizing-dependent targets in LDHA and mTOR-AKT pathway.

Teaser

Ewing sarcoma (ES) is the second most common pediatric bone cancer, and patients with relapsed/resistant disease have a five-year overall survival rate of only 15-20%. Front-line standard of care treatment for patients with ES includes chemotherapy and local control with surgery and/or radiation. We have developed novel in vitro and in vivo radiation-adapted ES models that demonstrate a relationship between metabolism and radioresistance as well as identify several candidate biomarkers for radioresistant disease in ES.


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Does Prophylactic Radiotherapy to avoid Gynecomastia in Patients with Prostate Cancer increase the risk of Breast Cancer?

Publication date: Available online 5 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Bjørg Y. Aksnessæther, Arne Solberg, Olbjørn H. Klepp, Tor Åge Myklebust, Eva Skovlund, Solveig Roth Hoff, Lars J. Vatten, Jo-Åsmund Lund
PurposeProstate cancer (PC) patients treated with antiandrogen monotherapy are offered prophylactic radiotherapy to the breast buds (PRT) to avoid gynecomastia. The aim of this study was to evaluate whether the risk of breast cancer (BC) in men with PC as their first cancer diagnosis, was influenced by PRT.Methods and MaterialsFrom the Norwegian Cancer Registry we collected data on all patients with PC as their first cancer diagnosis diagnosed between 1997- 2014. We registered all radiotherapy given to the patients in the same period, and the occurrence of BC diagnosed 3 months or more following the PC diagnosis. The histopathological diagnoses of all BC cases were collected. Subdistribution hazard ratios (SHR) for the risk of BC in PRT and non-PRT treated patients were estimated. A standardized incidence ratio (SIR) for BC was calculated by comparing our cohort to the standard male population.ResultsWe analyzed 59 169 patients with PC, whom 7864 (13.3%) had received PRT. Median follow-up time was 4 years. Three of 12 men diagnosed with BC had received PRT, and two of three were phyllodes tumors. The risk of BC was not statistically significantly different in patients given RT as compared to the non-RT patients, SHR 1.62 95% CI 0.41-5.62, adjusted for age and time of diagnosis. SIR was 0.996 95 % CI 0.57-1.75.ConclusionsIn this registry based study, we did not find an increased risk of BC in PC patients treated with PRT. The number of BC cases in our study was low, and the risk of secondary breast cancer following PRT seems to be negligible. The incidence of BC may, however rise with additional follow-up. It is noteworthy that two patients who had been treated with PRT were diagnosed with malignant phyllodes tumor, an extremely rare type of BC associated with gynecomastia.

Teaser

Nordic patients with prostate cancer receive prophylactic radiotherapy to the breast buds to avoid gynecomastia when treated with antiandrogen monotherapy. In this study with data from the Norwegian Cancer Registry, we did not find increased risk of breast cancer (BC) in irradiated patients compared to non-irradiated patients. It is noteworthy that in the RT group, there were two cases of malignant phyllodes breast tumor, an extremely rare type of BC associated with gynecomastia.


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Clinical implementation of contrast-enhanced four-dimensional dual-energy computed tomography for target delineation of pancreatic cancer

The accurate delineation of pancreatic tumor with respiratory motion is challenging. This study demonstrates the application of contrast-enhanced four-dimensional dual-energy computed tomography (CE-4D-DECT) for tumor delineation and assesses the objective and subjective image quality.

http://ift.tt/2FP5Iyd

Pancreatic cyst biopsy: Improvement in diagnosis with micro forceps biopsy

Clinician's Corner represents the opinions and views of the author and does not reflect any policy or opinion of the American Cancer Society, Cancer Cytopathology, or Wiley unless this is clearly specified. Cancer Cytopathol 2018. © 2018 American Cancer Society.

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Cytologic-histologic correlation of programmed death-ligand 1 immunohistochemistry in lung carcinomas

BACKGROUND

Programmed cell death protein 1 inhibitors increasingly are being used to treat patients with advanced lung carcinomas. Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) in tumor cells (TCs) and tumor-infiltrating immune cells (ICs) is used to select patients for programmed cell death protein 1 inhibition, but few studies have evaluated PD-L1 IHC in cytology specimens. The objective of the current study was to compare PD-L1 IHC in cytology cell blocks and matched surgical specimens.

METHODS

A total of 56 cytology specimens obtained between 2013 and 2016 with matching surgical specimens were stained with anti-PD-L1. Membranous positivity was scored as a percentage of the TCs and ICs by 2 pathologists. Results were compared between cytology and surgical specimens, and interobserver concordance was assessed.

RESULTS

The average PD-L1 positivity rate was 28% in TCs and 5% in ICs in surgical specimens (standard deviations of 37% and 7%, respectively), and 21% in TCs and 8% in ICs in cytology specimens (standard deviations of 33% and 15%, respectively). Interobserver concordance was high for TCs in surgical and cytology specimens (intraclass correlation coefficients of 0.96 and 0.96, respectively), and was moderate for ICs in surgical and cytology specimens (intraclass correlation coefficients of 0.47 and 0.67, respectively). There was moderate to high correlation between PD-L1 positivity in TCs between surgical and cytology specimens (Spearman correlation coefficient [Spearman r], 0.69), particularly among fine-needle aspiration specimens (Spearman r, 0.78), but not between PD-L1 positivity in ICs in surgical and cytology specimens (Spearman r, 0.14), including among fine-needle aspiration specimens (Spearman r, 0.23).

CONCLUSIONS

Tumor PD-L1 IHC positivity in cytology specimens appears to correlate strongly with results obtained from matching surgical specimens. PD-L1 IHC in ICs within cytology specimens does not reflect results in matched surgical specimens and should not be used in clinical decision making. Cancer Cytopathol 2018. © 2018 American Cancer Society.

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Pancreatic cyst biopsy: Improvement in diagnosis with micro forceps biopsy

Clinician's Corner represents the opinions and views of the author and does not reflect any policy or opinion of the American Cancer Society, Cancer Cytopathology, or Wiley unless this is clearly specified. Cancer Cytopathol 2018. © 2018 American Cancer Society.

http://ift.tt/2ElYB31

Cytologic-histologic correlation of programmed death-ligand 1 immunohistochemistry in lung carcinomas

BACKGROUND

Programmed cell death protein 1 inhibitors increasingly are being used to treat patients with advanced lung carcinomas. Programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) in tumor cells (TCs) and tumor-infiltrating immune cells (ICs) is used to select patients for programmed cell death protein 1 inhibition, but few studies have evaluated PD-L1 IHC in cytology specimens. The objective of the current study was to compare PD-L1 IHC in cytology cell blocks and matched surgical specimens.

METHODS

A total of 56 cytology specimens obtained between 2013 and 2016 with matching surgical specimens were stained with anti-PD-L1. Membranous positivity was scored as a percentage of the TCs and ICs by 2 pathologists. Results were compared between cytology and surgical specimens, and interobserver concordance was assessed.

RESULTS

The average PD-L1 positivity rate was 28% in TCs and 5% in ICs in surgical specimens (standard deviations of 37% and 7%, respectively), and 21% in TCs and 8% in ICs in cytology specimens (standard deviations of 33% and 15%, respectively). Interobserver concordance was high for TCs in surgical and cytology specimens (intraclass correlation coefficients of 0.96 and 0.96, respectively), and was moderate for ICs in surgical and cytology specimens (intraclass correlation coefficients of 0.47 and 0.67, respectively). There was moderate to high correlation between PD-L1 positivity in TCs between surgical and cytology specimens (Spearman correlation coefficient [Spearman r], 0.69), particularly among fine-needle aspiration specimens (Spearman r, 0.78), but not between PD-L1 positivity in ICs in surgical and cytology specimens (Spearman r, 0.14), including among fine-needle aspiration specimens (Spearman r, 0.23).

CONCLUSIONS

Tumor PD-L1 IHC positivity in cytology specimens appears to correlate strongly with results obtained from matching surgical specimens. PD-L1 IHC in ICs within cytology specimens does not reflect results in matched surgical specimens and should not be used in clinical decision making. Cancer Cytopathol 2018. © 2018 American Cancer Society.

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Germline promoter hypermethylation in BRCA1 and BRCA2 genes is not present in hereditary breast cancer patients

Abstract

Purpose

Germline promoter hypermethylation of BRCA1 and BRCA2 genes is an alternative event of gene silencing that has not been widely investigated in hereditary breast and ovarian cancer (HBOC) syndrome.

Methods

We analyzed germline BRCA promoter hypermethylation in HBOC patients with and without BRCA mutations and control subjects, using a recently developed BRCA methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay.

Results

Neither the patients tested nor the control subjects showed germline hypermethylation of the BRCA1 and BRCA2 promoter regions analyzed.

Conclusions

Despite the results achieved at somatic levels by other researchers, these were not confirmed in our study at the germline level. Our results show the need to establish more predictive CpG sites in the BRCA promoter regions to optimize the MS-MLPA assay for the detection of germline hypermethylation as an effective pre-screening tool for whole-BRCA genetic analysis in HBOC, because we can not rule out the existence of germline promoter hypermethylation in BRCA.

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Germline promoter hypermethylation in BRCA1 and BRCA2 genes is not present in hereditary breast cancer patients

Abstract

Purpose

Germline promoter hypermethylation of BRCA1 and BRCA2 genes is an alternative event of gene silencing that has not been widely investigated in hereditary breast and ovarian cancer (HBOC) syndrome.

Methods

We analyzed germline BRCA promoter hypermethylation in HBOC patients with and without BRCA mutations and control subjects, using a recently developed BRCA methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) assay.

Results

Neither the patients tested nor the control subjects showed germline hypermethylation of the BRCA1 and BRCA2 promoter regions analyzed.

Conclusions

Despite the results achieved at somatic levels by other researchers, these were not confirmed in our study at the germline level. Our results show the need to establish more predictive CpG sites in the BRCA promoter regions to optimize the MS-MLPA assay for the detection of germline hypermethylation as an effective pre-screening tool for whole-BRCA genetic analysis in HBOC, because we can not rule out the existence of germline promoter hypermethylation in BRCA.

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Kombination aus perkutaner Strahlentherapie, Brachytherapie und Androgendeprivation gleichwertige Alternative zur radikalen Prostatektomie beim Prostatakarzinom

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Direct dose correlation of MRI morphologic alterations of healthy liver tissue after robotic liver SBRT

Abstract

Purpose

For assessing healthy liver reactions after robotic SBRT (stereotactic body radiotherapy), we investigated early morphologic alterations on MRI (magnetic resonance imaging) with respect to patient and treatment plan parameters.

Patients and methods

MRI data at 6–17 weeks post-treatment from 22 patients with 42 liver metastases were analyzed retrospectively. Median prescription dose was 40 Gy delivered in 3–5 fractions. T2- and T1-weighted MRI were registered to the treatment plan. Absolute doses were converted to EQD2 (Equivalent dose in 2Gy fractions) with α/β-ratios of 2 and 3 Gy for healthy, and 8 Gy for modelling pre-damaged liver tissue.

Results

Sharply defined, centroid-shaped morphologic alterations were observed outside the high-dose volume surrounding the GTV. On T2-w MRI, hyperintensity at EQD2 isodoses of 113.3 ± 66.1 Gy₂, 97.5 ± 54.7 Gy₃, and 66.5 ± 32.0 Gy₈ significantly depended on PTV dimension (p = 0.02) and healthy liver EQD2 (p = 0.05). On T1-w non-contrast MRI, hypointensity at EQD2 isodoses of 113.3 ± 49.3 Gy₂, 97.4 ± 41.0 Gy₃, and 65.7 ± 24.2 Gy₈ significantly depended on prior chemotherapy (p = 0.01) and total liver volume (p = 0.05). On T1-w gadolinium-contrast delayed MRI, hypointensity at EQD2 isodoses of 90.6 ± 42.5 Gy₂, 79.3 ± 35.3 Gy₃, and 56.6 ± 20.9 Gy₈ significantly depended on total (p = 0.04) and healthy (p = 0.01) liver EQD2.

Conclusions

Early post-treatment changes in healthy liver tissue after robotic SBRT could spatially be correlated to respective isodoses. Median nominal doses of 10.1–11.3 Gy per fraction (EQD2 79–97 Gy₃) induce characteristic morphologic alterations surrounding the lesions, potentially allowing for dosimetric in-vivo accuracy assessments. Comparison to other techniques and investigations of the short- and long-term clinical impact require further research.

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Cytoplasmic collagen XIαI as a prognostic biomarker in esophageal squamous cell carcinoma

.


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Cytoplasmic collagen XIαI as a prognostic biomarker in esophageal squamous cell carcinoma

.


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Single-institution experience of intensity-modulated radiotherapy for malignant pleural mesothelioma at University of Catania

Future Oncology, Ahead of Print.


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Single-institution experience of intensity-modulated radiotherapy for malignant pleural mesothelioma at University of Catania

Future Oncology, Ahead of Print.


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Gut Bacteria Influence Effectiveness of a Type of Immunotherapy

Using mouse models of cancer, researchers found that altering gut microbiome could affect whether tumors responded to checkpoint inhibition.

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Feasibility of 15 O-water PET studies of auditory system activation during general anesthesia in children

Abstract

Background

¹⁵O-Water positron emission tomography (PET) enables functional imaging of the auditory system during stimulation via a promontory electrode or cochlear implant, which is not possible using functional magnetic resonance imaging (fMRI). Although PET has been introduced in this context decades ago, its feasibility when performed during general anesthesia has not yet been explored. However, due to a shift to earlier (and bilateral) auditory implantation, the need to study children during general anesthesia appeared, since they are not able to cooperate during scanning. Therefore, we evaluated retrospectively results of individual SPM (statistical parametric mapping) analysis of ¹⁵O-water PET in 17 children studied during general anesthesia and compared them to those in 9 adults studied while awake. Specifically, the influence of scan duration, smoothing filter kernel employed during preprocessing, and cut-off value used for statistical inferences were evaluated. Frequencies, peak heights, and extents of activations in auditory and extra-auditory brain regions (AR and eAR) were registered.

Results

It was possible to demonstrate activations in auditory brain regions during general anesthesia; however, the frequency and markedness of positive findings were dependent on some of the abovementioned influence factors. Scan duration (60 vs. 90 s) had no significant influence on peak height of auditory cortex activations. To achieve a similar frequency and extent of AR activations during general anesthesia compared to waking state, a lower cut-off for statistical inferences (p < 0.05 or p < 0.01 vs. p < 0.001) had to be applied. However, this lower cut-off was frequently associated with unexpected, "artificial" activations in eAR. These activations in eAR could be slightly reduced by the use of a stronger smoothing filter kernel during preprocessing of the data (e.g., [30 mm]³).

Conclusions

Our data indicate that it is feasible to detect auditory cortex activations in ¹⁵O-water PET during general anesthesia. Combined with the improved signal to noise ratios of modern PET scanners, this suggests reasonable prospects for further evaluation of the method for clinical use in auditory implant users. Adapted parameters for data analysis seem to be helpful to improve the proportion of signals in AR versus eAR.

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Solid pseudopapillary tumor of pancreas: A case report and review of genetic features

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Gut Bacteria Influence Effectiveness of a Type of Immunotherapy

Using mouse models of cancer, researchers found that altering gut microbiome could affect whether tumors responded to checkpoint inhibition.

http://ift.tt/2E3dBj0

Feasibility of 15 O-water PET studies of auditory system activation during general anesthesia in children

Abstract

Background

¹⁵O-Water positron emission tomography (PET) enables functional imaging of the auditory system during stimulation via a promontory electrode or cochlear implant, which is not possible using functional magnetic resonance imaging (fMRI). Although PET has been introduced in this context decades ago, its feasibility when performed during general anesthesia has not yet been explored. However, due to a shift to earlier (and bilateral) auditory implantation, the need to study children during general anesthesia appeared, since they are not able to cooperate during scanning. Therefore, we evaluated retrospectively results of individual SPM (statistical parametric mapping) analysis of ¹⁵O-water PET in 17 children studied during general anesthesia and compared them to those in 9 adults studied while awake. Specifically, the influence of scan duration, smoothing filter kernel employed during preprocessing, and cut-off value used for statistical inferences were evaluated. Frequencies, peak heights, and extents of activations in auditory and extra-auditory brain regions (AR and eAR) were registered.

Results

It was possible to demonstrate activations in auditory brain regions during general anesthesia; however, the frequency and markedness of positive findings were dependent on some of the abovementioned influence factors. Scan duration (60 vs. 90 s) had no significant influence on peak height of auditory cortex activations. To achieve a similar frequency and extent of AR activations during general anesthesia compared to waking state, a lower cut-off for statistical inferences (p < 0.05 or p < 0.01 vs. p < 0.001) had to be applied. However, this lower cut-off was frequently associated with unexpected, "artificial" activations in eAR. These activations in eAR could be slightly reduced by the use of a stronger smoothing filter kernel during preprocessing of the data (e.g., [30 mm]³).

Conclusions

Our data indicate that it is feasible to detect auditory cortex activations in ¹⁵O-water PET during general anesthesia. Combined with the improved signal to noise ratios of modern PET scanners, this suggests reasonable prospects for further evaluation of the method for clinical use in auditory implant users. Adapted parameters for data analysis seem to be helpful to improve the proportion of signals in AR versus eAR.

http://ift.tt/2E4tABt

Solid pseudopapillary tumor of pancreas: A case report and review of genetic features

http://ift.tt/2nLfoSD

NRG oncology RTOG 9006: a phase III randomized trial of hyperfractionated radiotherapy (RT) and BCNU versus standard RT and BCNU for malignant glioma patients

Abstract

From 1990 to 1994, patients with newly diagnosed malignant gliomas were enrolled and randomized between hyperfractionated radiation (HFX) of 72.0 Gy in 60 fractions given twice daily and 60.0 Gy in 30 fractions given once daily. All patients received 80 mg/m² of 1,3 bis(2 chloroethyl)-1 nitrosourea on days 1–3 q8 weeks for 1 year. Patients were stratified by age, KPS, and histology. The primary endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS) and toxicity. Out of the 712 patients accrued, 694 (97.5%) were analyzable cases (350 HFX, 344 standard arm). There was no significant difference between the arms on overall acute or late treatment-related toxicity. No statistically significant effect for HFX, as compared to standard therapy, was found on either OS, with a median survival time (MST) of 11.3 versus 13.1 months (p = 0.20) or PFS, with a median PFS time of 5.7 versus 6.9 months (p = 0.18). The treatment effect on OS remained insignificant based on the multivariate analysis (hazard ratio 1.16; p = 0.0682). When OS was analyzed by histology subgroup there was also no significant difference between the two arms for patients with glioblastoma multiforme (MST: 10.3 vs. 11.2 months; p = 0.34), anaplastic astrocytoma (MST: 69.8 vs. 50.0 months; p = 0.91) or anaplastic oligodendroglioma (MST: 92.1 vs. 66.5 months; p = 0.33). Though this trial provided many invaluable secondary analyses, there was no trend or indication of a benefit to HFX radiation to 72.0 Gy in any subset of malignant glioma patients.

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NRG oncology RTOG 9006: a phase III randomized trial of hyperfractionated radiotherapy (RT) and BCNU versus standard RT and BCNU for malignant glioma patients

Abstract

From 1990 to 1994, patients with newly diagnosed malignant gliomas were enrolled and randomized between hyperfractionated radiation (HFX) of 72.0 Gy in 60 fractions given twice daily and 60.0 Gy in 30 fractions given once daily. All patients received 80 mg/m² of 1,3 bis(2 chloroethyl)-1 nitrosourea on days 1–3 q8 weeks for 1 year. Patients were stratified by age, KPS, and histology. The primary endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS) and toxicity. Out of the 712 patients accrued, 694 (97.5%) were analyzable cases (350 HFX, 344 standard arm). There was no significant difference between the arms on overall acute or late treatment-related toxicity. No statistically significant effect for HFX, as compared to standard therapy, was found on either OS, with a median survival time (MST) of 11.3 versus 13.1 months (p = 0.20) or PFS, with a median PFS time of 5.7 versus 6.9 months (p = 0.18). The treatment effect on OS remained insignificant based on the multivariate analysis (hazard ratio 1.16; p = 0.0682). When OS was analyzed by histology subgroup there was also no significant difference between the two arms for patients with glioblastoma multiforme (MST: 10.3 vs. 11.2 months; p = 0.34), anaplastic astrocytoma (MST: 69.8 vs. 50.0 months; p = 0.91) or anaplastic oligodendroglioma (MST: 92.1 vs. 66.5 months; p = 0.33). Though this trial provided many invaluable secondary analyses, there was no trend or indication of a benefit to HFX radiation to 72.0 Gy in any subset of malignant glioma patients.

http://ift.tt/2DYKMUH

Role of RPLND and Metastasectomy in the Management of Oligometastatic Renal Cell Carcinoma

Abstract

Although lymphadenectomy is currently accepted as most accurate and reliable staging procedure for lymph node metastases, its therapeutic benefit in renal cell carcinoma (RCC) still remains controversial. Although the new, targeted therapy paradigms have changed the treatment of patients with advanced RCC and offer prolonged survival, cure is extremely uncommon in the absence of surgical resections. In this paper, the current role of metastasectomy is reviewed. Review the available literature concerning the role of retroperitoneal lymph node dissection and metastasectomy in outcome of oligometastatic RCC. A PubMed search was conducted to identify original articles, review articles, and editorials addressing the role of retroperitoneal lymph node dissection and metastasectomy in outcome of oligometastatic RCC. Keywords included renal tumors, renal cell cancer, kidney cancer, lymphadenectomy, metastasectomy, and oligometastases. While there is no randomized study available, recent large observational studies have better defined the prognosis of patients with metastatic RCC with or without metastasectomy and RPLND. To date, the available evidence suggests that RPLND and metastasectomy may be beneficial when technically feasible in patients with locally advanced (unfavorable clinical and pathologic characteristics) and oligometastatic disease. A proportion of patients will achieve long-term survival with aggressive surgical resection.

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Role of RPLND and Metastasectomy in the Management of Oligometastatic Renal Cell Carcinoma

Abstract

Although lymphadenectomy is currently accepted as most accurate and reliable staging procedure for lymph node metastases, its therapeutic benefit in renal cell carcinoma (RCC) still remains controversial. Although the new, targeted therapy paradigms have changed the treatment of patients with advanced RCC and offer prolonged survival, cure is extremely uncommon in the absence of surgical resections. In this paper, the current role of metastasectomy is reviewed. Review the available literature concerning the role of retroperitoneal lymph node dissection and metastasectomy in outcome of oligometastatic RCC. A PubMed search was conducted to identify original articles, review articles, and editorials addressing the role of retroperitoneal lymph node dissection and metastasectomy in outcome of oligometastatic RCC. Keywords included renal tumors, renal cell cancer, kidney cancer, lymphadenectomy, metastasectomy, and oligometastases. While there is no randomized study available, recent large observational studies have better defined the prognosis of patients with metastatic RCC with or without metastasectomy and RPLND. To date, the available evidence suggests that RPLND and metastasectomy may be beneficial when technically feasible in patients with locally advanced (unfavorable clinical and pathologic characteristics) and oligometastatic disease. A proportion of patients will achieve long-term survival with aggressive surgical resection.

http://ift.tt/2BVo7ae

Statistical Controversies in Clinical Research: Limitations of open-label studies assessing antiangiogenic therapies with regard to evaluation of vascular adverse drug events. A meta-analysis

Abstract

Background

Previous meta-analyses have shown paradoxical increased risk of bleeding and thrombotic events in patients receiving antiangiogenics (AA) that may be simply explained by the studies design included. By a meta-epidemiological approach, we aim to investigate the impact of double-blind (DB) and open-label study designs on the risks of bleeding, venous thrombotic events (VTE) and arterial thrombotic events (ATE) in cancer patients treated with AA.

Materials and Methods

We searched Medline, Cochrane, ClinicalTrials.gov databases, and proceedings of major oncology congresses for clinical trials published from January 2003 to January 2016. Randomized clinical trials that assigned patients with solid cancers to AA or control groups were eligible for inclusion. Combined odds ratios (OR) for the risks of bleeding events, VTE and ATE were calculated for open and DB trials. Estimation bias of the treatment effect was determined by the ratio of odds ratio (ROR), by dividing the OR values obtained in open-label trials by those obtained in DB trials.

Results

The literature-based meta-analysis included 166 trials (72,024 patients). For bleeding events, comparison of AA versus control yielded an overall OR of 2.41 (95% CI 2.12-2.73; P <0.001), but this risk was overestimated by 1.68 (95% CI 1.33-2.13) in open-label studies. Concerning VTE, the OR was 1.19 (95% CI 1.04-1.35; P =0.012) overall with AA, but this effect disappears when considering only DB trials (OR 0.99, 95% CI, 0.83-1.17). The corresponding ROR showed a significant overestimation of 1.53 (95% CI 1.19-1.96) in open-label trials. For ATE, an OR of 1.59 (95% CI 1.30-1.94; P <0.001) was observed, associated with a significant overestimation of 1.65 (95% CI 1.13-2.43) in open-label trials.

Conclusions

Open-label studies overestimated the risk of vascular adverse events with AA by at least 50%. Meta-analyses assessing adverse drug events should therefore be restricted to DB randomized trials.

http://ift.tt/2GMLTsm

EXPRESSION III: Patient´s Expectations and Preferences regarding Physician–Patient Relationship and Clinical Management. Results of the International NOGGO/ENGOT-ov4-GCIG study in 1,830 Ovarian Cancer Patients from European countries.

Abstract

Backround

The primary aim of this study was to investigate information needs and treatment preferences of patients with ovarian cancer, focusing especially on physician-patient relationship and treatment

Patients and methods

A questionnaire was developed based on the experiences of the national German survey Expression II, and was provided to patients with ovarian cancer either at initial diagnosis or with recurrent disease via Internet (online-version) or as print-out-version.

Results

From December 2009 to October 2012, a total of 1,830 patients with ovarian cancer from eight European countries (Austria, Belgium, France, Germany, Italy, Poland, Romania, Spain) participated, 902 (49.3%) after initial diagnosis and 731 (39.9%) with recurrent ovarian cancer. The median age was 58 years (range 17–89). Nearly all patients (96.2%) had experienced upfront surgery followed by first-line chemotherapy (91.8%). The majority of patients were satisfied with the completeness and comprehensibility of the explanation about the diagnosis and treatment options. The 3 most important aspects, identified by patients to improve the treatment for ovarian cancer included: "the therapy should not induce alopecia" (42%), "there must be more done to counter fatigue" (34.5%), and "the therapy should be more effective" (29.7%). Out of 659 (36%) patients, who were offered participation in a clinical trial, 476 (26%) were included.

Conclusion

This study underlines the high need of patients with ovarian cancer for all details concerning treatment options irrespective of their cultural background, the stage of disease and the patient's age. Increased information requirements regarding potential side effects and treatment alternatives were recorded. Besides the need for more effective therapy, alopecia and fatigue are the most important side effects of concern to patients.

http://ift.tt/2sadiBm

Developing Androgen Receptor Targeting for Salivary Gland Cancers

http://ift.tt/2GMLRAK

Phase 1-2 trial designs: how early should efficacy guide the dose recommendation process?

http://ift.tt/2GOjP84

Nivolumab versus docetaxel in previously treated advanced non-small cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases

Abstract

Background

Long-term data with immune checkpoint inhibitors in non-small cell lung cancer (NSCLC) are limited. Two phase III trials demonstrated improved overall survival (OS) and a favorable safety profile with the anti–programmed death-1 antibody nivolumab versus docetaxel in patients with previously treated advanced squamous (CheckMate 017) and non-squamous (CheckMate 057) NSCLC. We report results from ≥3 years' follow-up, including subgroup analyses of patients with liver metastases, who historically have poorer prognosis among patients with NSCLC.

Patients and methods

Patients were randomized 1:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m² every 3 weeks) until progression or discontinuation. The primary endpoint of each study was OS. Patients with baseline liver metastases were pooled across studies by treatment for subgroup analyses.

Results

After 40.3 months' minimum follow-up in CheckMate 017 and 057, nivolumab continued to show an OS benefit versus docetaxel: estimated 3-year OS rates were 17% (95% confidence interval [CI], 14–21%) versus 8% (95% CI, 6–11%) in the pooled population with squamous or non-squamous NSCLC. Nivolumab was generally well tolerated, with no new safety concerns identified. Of 854 randomized patients across both studies, 193 had baseline liver metastases. Nivolumab resulted in improved OS compared with docetaxel in patients with liver metastases (hazard ratio, 0.68; 95% CI, 0.50–0.91), consistent with findings from the overall pooled study population (hazard ratio, 0.70; 95% CI, 0.61–0.81). Rates of treatment-related hepatic adverse events (primarily grade 1–2 liver enzyme elevations) were slightly higher in nivolumab-treated patients with liver metastases (10%) than in the overall pooled population (6%).

Conclusions

After 3 years' minimum follow-up, nivolumab continued to demonstrate an OS benefit versus docetaxel in patients with advanced NSCLC. Similarly, nivolumab demonstrated an OS benefit versus docetaxel in patients with liver metastases, and remained well tolerated.

Clinical trial registration

CheckMate 017: NCT01642004; CheckMate 057: NCT01673867

http://ift.tt/2sdtXEm

CHK1 Inhibition in Soft-Tissue Sarcomas: Biological and Clinical Implications

Abstract

Background

Inhibition of ChK1 appears as a promising strategy for selectively potentiate the efficacy of chemotherapeutic agents in G1 checkpoint-defective tumor cells such as those that lack functional p53 protein. The p53 pathway is commonly dysregulated in soft-tissue sarcomas (STS) through mutations affecting TP53 or MDM2 amplification. GDC-0575 is a selective ATP-competitive inhibitor of CHK1.

Methods

We have performed a systematic screening of a panel of 10 STS cell lines by combining the treatment of GDC-0575 with chemotherapy. Cell proliferation, cell death and cell cycle analysis were evaluated with high throughput assay. In vivo experiments were performed by using TP53-mutated and TP53 wild-type patient-derived xenograft models of STS. Clinical activity of GDC-0575 combined with chemotherapy in patients with TP53-mutated and TP53 wild-type STS was also assessed.

Results

We found that GDC-0575 abrogated DNA damage-induced S and G2–M checkpoints, exacerbated DNA double-strand breaks and induced apoptosis in STS cells. Moreover, we observed a synergistic or additive effect of GDC-0575 together with gemcitabine in vitro and in vivo in TP53-proficient but not TP53-deficient sarcoma models. In a phase 1 study of GDC-0575 in combination with gemcitabine, two patients with metastatic TP53-mutated STS had an exceptional, long-lasting response despite administration of a very low dose of gemcitabine whereas one patient with wild-type TP53 STS had no clinical benefit. Genetic profiling of samples from a patient displaying secondary resistance after 1 year showed loss of one preexisting loss-of-function mutation in the helical domain of DNA2.

Conclusion

We provide the first pre-clinical and clinical evidence that potentiation of chemotherapy activity with a CHK1 inhibitor is a promising strategy in TP53-deficient STS and deserves further investigation in the phase 2 setting.

http://ift.tt/2GM48yl

Statistical Controversies in Clinical Research: Limitations of open-label studies assessing antiangiogenic therapies with regard to evaluation of vascular adverse drug events. A meta-analysis

Abstract

Background

Previous meta-analyses have shown paradoxical increased risk of bleeding and thrombotic events in patients receiving antiangiogenics (AA) that may be simply explained by the studies design included. By a meta-epidemiological approach, we aim to investigate the impact of double-blind (DB) and open-label study designs on the risks of bleeding, venous thrombotic events (VTE) and arterial thrombotic events (ATE) in cancer patients treated with AA.

Materials and Methods

We searched Medline, Cochrane, ClinicalTrials.gov databases, and proceedings of major oncology congresses for clinical trials published from January 2003 to January 2016. Randomized clinical trials that assigned patients with solid cancers to AA or control groups were eligible for inclusion. Combined odds ratios (OR) for the risks of bleeding events, VTE and ATE were calculated for open and DB trials. Estimation bias of the treatment effect was determined by the ratio of odds ratio (ROR), by dividing the OR values obtained in open-label trials by those obtained in DB trials.

Results

The literature-based meta-analysis included 166 trials (72,024 patients). For bleeding events, comparison of AA versus control yielded an overall OR of 2.41 (95% CI 2.12-2.73; P <0.001), but this risk was overestimated by 1.68 (95% CI 1.33-2.13) in open-label studies. Concerning VTE, the OR was 1.19 (95% CI 1.04-1.35; P =0.012) overall with AA, but this effect disappears when considering only DB trials (OR 0.99, 95% CI, 0.83-1.17). The corresponding ROR showed a significant overestimation of 1.53 (95% CI 1.19-1.96) in open-label trials. For ATE, an OR of 1.59 (95% CI 1.30-1.94; P <0.001) was observed, associated with a significant overestimation of 1.65 (95% CI 1.13-2.43) in open-label trials.

Conclusions

Open-label studies overestimated the risk of vascular adverse events with AA by at least 50%. Meta-analyses assessing adverse drug events should therefore be restricted to DB randomized trials.

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EXPRESSION III: Patient´s Expectations and Preferences regarding Physician–Patient Relationship and Clinical Management. Results of the International NOGGO/ENGOT-ov4-GCIG study in 1,830 Ovarian Cancer Patients from European countries.

Abstract

Backround

The primary aim of this study was to investigate information needs and treatment preferences of patients with ovarian cancer, focusing especially on physician-patient relationship and treatment

Patients and methods

A questionnaire was developed based on the experiences of the national German survey Expression II, and was provided to patients with ovarian cancer either at initial diagnosis or with recurrent disease via Internet (online-version) or as print-out-version.

Results

From December 2009 to October 2012, a total of 1,830 patients with ovarian cancer from eight European countries (Austria, Belgium, France, Germany, Italy, Poland, Romania, Spain) participated, 902 (49.3%) after initial diagnosis and 731 (39.9%) with recurrent ovarian cancer. The median age was 58 years (range 17–89). Nearly all patients (96.2%) had experienced upfront surgery followed by first-line chemotherapy (91.8%). The majority of patients were satisfied with the completeness and comprehensibility of the explanation about the diagnosis and treatment options. The 3 most important aspects, identified by patients to improve the treatment for ovarian cancer included: "the therapy should not induce alopecia" (42%), "there must be more done to counter fatigue" (34.5%), and "the therapy should be more effective" (29.7%). Out of 659 (36%) patients, who were offered participation in a clinical trial, 476 (26%) were included.

Conclusion

This study underlines the high need of patients with ovarian cancer for all details concerning treatment options irrespective of their cultural background, the stage of disease and the patient's age. Increased information requirements regarding potential side effects and treatment alternatives were recorded. Besides the need for more effective therapy, alopecia and fatigue are the most important side effects of concern to patients.

from Cancer via ola Kala on Inoreader http://ift.tt/2sadiBm
via IFTTT

Developing Androgen Receptor Targeting for Salivary Gland Cancers

from Cancer via ola Kala on Inoreader http://ift.tt/2GMLRAK
via IFTTT

Phase 1-2 trial designs: how early should efficacy guide the dose recommendation process?

from Cancer via ola Kala on Inoreader http://ift.tt/2GOjP84
via IFTTT

Nivolumab versus docetaxel in previously treated advanced non-small cell lung cancer (CheckMate 017 and CheckMate 057): 3-year update and outcomes in patients with liver metastases

Abstract

Background

Long-term data with immune checkpoint inhibitors in non-small cell lung cancer (NSCLC) are limited. Two phase III trials demonstrated improved overall survival (OS) and a favorable safety profile with the anti–programmed death-1 antibody nivolumab versus docetaxel in patients with previously treated advanced squamous (CheckMate 017) and non-squamous (CheckMate 057) NSCLC. We report results from ≥3 years' follow-up, including subgroup analyses of patients with liver metastases, who historically have poorer prognosis among patients with NSCLC.

Patients and methods

Patients were randomized 1:1 to nivolumab (3 mg/kg every 2 weeks) or docetaxel (75 mg/m² every 3 weeks) until progression or discontinuation. The primary endpoint of each study was OS. Patients with baseline liver metastases were pooled across studies by treatment for subgroup analyses.

Results

After 40.3 months' minimum follow-up in CheckMate 017 and 057, nivolumab continued to show an OS benefit versus docetaxel: estimated 3-year OS rates were 17% (95% confidence interval [CI], 14–21%) versus 8% (95% CI, 6–11%) in the pooled population with squamous or non-squamous NSCLC. Nivolumab was generally well tolerated, with no new safety concerns identified. Of 854 randomized patients across both studies, 193 had baseline liver metastases. Nivolumab resulted in improved OS compared with docetaxel in patients with liver metastases (hazard ratio, 0.68; 95% CI, 0.50–0.91), consistent with findings from the overall pooled study population (hazard ratio, 0.70; 95% CI, 0.61–0.81). Rates of treatment-related hepatic adverse events (primarily grade 1–2 liver enzyme elevations) were slightly higher in nivolumab-treated patients with liver metastases (10%) than in the overall pooled population (6%).

Conclusions

After 3 years' minimum follow-up, nivolumab continued to demonstrate an OS benefit versus docetaxel in patients with advanced NSCLC. Similarly, nivolumab demonstrated an OS benefit versus docetaxel in patients with liver metastases, and remained well tolerated.

Clinical trial registration

CheckMate 017: NCT01642004; CheckMate 057: NCT01673867

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CHK1 Inhibition in Soft-Tissue Sarcomas: Biological and Clinical Implications

Abstract

Background

Inhibition of ChK1 appears as a promising strategy for selectively potentiate the efficacy of chemotherapeutic agents in G1 checkpoint-defective tumor cells such as those that lack functional p53 protein. The p53 pathway is commonly dysregulated in soft-tissue sarcomas (STS) through mutations affecting TP53 or MDM2 amplification. GDC-0575 is a selective ATP-competitive inhibitor of CHK1.

Methods

We have performed a systematic screening of a panel of 10 STS cell lines by combining the treatment of GDC-0575 with chemotherapy. Cell proliferation, cell death and cell cycle analysis were evaluated with high throughput assay. In vivo experiments were performed by using TP53-mutated and TP53 wild-type patient-derived xenograft models of STS. Clinical activity of GDC-0575 combined with chemotherapy in patients with TP53-mutated and TP53 wild-type STS was also assessed.

Results

We found that GDC-0575 abrogated DNA damage-induced S and G2–M checkpoints, exacerbated DNA double-strand breaks and induced apoptosis in STS cells. Moreover, we observed a synergistic or additive effect of GDC-0575 together with gemcitabine in vitro and in vivo in TP53-proficient but not TP53-deficient sarcoma models. In a phase 1 study of GDC-0575 in combination with gemcitabine, two patients with metastatic TP53-mutated STS had an exceptional, long-lasting response despite administration of a very low dose of gemcitabine whereas one patient with wild-type TP53 STS had no clinical benefit. Genetic profiling of samples from a patient displaying secondary resistance after 1 year showed loss of one preexisting loss-of-function mutation in the helical domain of DNA2.

Conclusion

We provide the first pre-clinical and clinical evidence that potentiation of chemotherapy activity with a CHK1 inhibitor is a promising strategy in TP53-deficient STS and deserves further investigation in the phase 2 setting.

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Analysis of Iodine Content in Salts and Korean Sauces for Low-Iodine Diet Education in Korean Patients with Thyroid Cancer Preparing for Radioiodine Therapy

Abstract

Purpose

A low-iodine diet is necessary in patients about to undergo radioiodine therapy for thyroid cancer to decrease the competitive absorption of ingested nonradioactive iodine. This study aimed to assess the iodine concentrations in salts and basic Korean sauces, and to provide fundamental data for guidelines on a low-iodine diet before radioiodine therapy.

Methods

The iodine contents of refined salts, solar sea salts, fish sauces, and commonly used Korean sauces with added refined salt were determined by ICP-MS.

Results

The iodine content of refined salts was found to be very low (0.033 ± 0.05 μg/100 g) compared with that of solar sea salts (434 ± 73.6 μg/100 g). The iodine contents of Korean soy sauce, Korean soybean paste, Gochujang seasoned with refined salt were also very low (0.010, 0.044, 0.002 μg/100 g, respectively). However, the mean iodine contents of the shrimp and fish Jeots analyzed in this study were found to be 41.3 ± 4.2 and 24.8 ± 4.5 μg/100 g, respectively.

Conclusion

This study is the first to investigate the iodine contents of the salts and basic sauces used in Korea. The results show that refined salts and Korean traditional sauces seasoned with them can be safely used in low-iodine diets before radioiodine therapy.

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Analysis of Iodine Content in Salts and Korean Sauces for Low-Iodine Diet Education in Korean Patients with Thyroid Cancer Preparing for Radioiodine Therapy

Abstract

Purpose

A low-iodine diet is necessary in patients about to undergo radioiodine therapy for thyroid cancer to decrease the competitive absorption of ingested nonradioactive iodine. This study aimed to assess the iodine concentrations in salts and basic Korean sauces, and to provide fundamental data for guidelines on a low-iodine diet before radioiodine therapy.

Methods

The iodine contents of refined salts, solar sea salts, fish sauces, and commonly used Korean sauces with added refined salt were determined by ICP-MS.

Results

The iodine content of refined salts was found to be very low (0.033 ± 0.05 μg/100 g) compared with that of solar sea salts (434 ± 73.6 μg/100 g). The iodine contents of Korean soy sauce, Korean soybean paste, Gochujang seasoned with refined salt were also very low (0.010, 0.044, 0.002 μg/100 g, respectively). However, the mean iodine contents of the shrimp and fish Jeots analyzed in this study were found to be 41.3 ± 4.2 and 24.8 ± 4.5 μg/100 g, respectively.

Conclusion

This study is the first to investigate the iodine contents of the salts and basic sauces used in Korea. The results show that refined salts and Korean traditional sauces seasoned with them can be safely used in low-iodine diets before radioiodine therapy.

http://ift.tt/2E5tepS

Physical activity during adolescence and young adulthood and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers

Abstract

Background

Physical activity is inversely associated with the risk of breast cancer among women in the general population. It is not clear whether or not physical activity is associated with the risk of BRCA-associated breast cancer.

Methods

We conducted a case–control study of 443 matched pairs of BRCA mutation carriers to evaluate the association between physical activity and breast cancer risk. Moderate and vigorous physical activities at ages 12–13, ages 14–17, ages 18–22, ages 23–29 and ages 30–34 were determined using the Nurses' Health Study II Physical Activity Questionnaire. We estimated mean metabolic equivalent task hours/week for moderate, vigorous and total physical activities overall (ages 12–34), during adolescence (ages 12–17) and during early adulthood (ages 18–34). Logistic regression analysis was used to estimate the odds ratios (OR) and 95% confidence intervals (CI) for total, moderate and strenuous recreational physical activities and breast cancer risk, by menopausal status.

Results

Overall, there was no significant association between total physical activity and subsequent breast cancer risk (OR_{Q4 vs. Q1} = 1.01, 95% CI 0.69–1.47; P-trend = 0.72). Moderate physical activity between ages 12–17 was associated with a 38% decreased risk of premenopausal breast cancer (OR_{Q4 vs. Q1} = 0.62; 95% CI 0.40–0.96; P-trend = 0.01). We found no association between exercise and breast cancer diagnosed after menopause.

Conclusions

These findings suggest that early-life physical activity is associated with a reduced risk of premenopausal breast cancer among BRCA mutation carriers.

Impact

Future prospective analyses, complemented by mechanistic evidence, are warranted in this high-risk population.

http://ift.tt/2nKcf5F

Induction chemotherapy with the EXTREME regimen in frail patients with locally advanced head and neck squamous cell carcinoma

Abstract

Background

Induction chemotherapy (IC) with TPF (docetaxel, cisplatin, 5FU) for locally advanced head and neck squamous cell carcinoma (LAHNSCC) is limited to fit patients.

Objective

We conducted a retrospective cohort study to assess the use of the EXTREME regimen (platinum-based therapy, 5FU, cetuximab) as IC in frail patients with LAHNSCC.

Patients and methods

Retrospective analysis of all consecutive patients with unresectable LAHNSCC treated with the EXTREME regimen, with or without 5FU as IC, from two French centers from 2008 to 2015. We assessed the rate of completed sequence defined as at least two cycles of IC and definitive radiation therapy.

Results

We included 34 patients with a median age of 56 years [44-70]. The primary site of tumor development was the oropharynx (67%, n=23, all HPV negative), hypopharynx (21%, n=7) and the oral cavity (12%, n=4). At inclusion, patients presented: T4 76, 5% (n=26), N2c 41% (n=14), N3 26% (n=9), stage disease IVa 62% (n=21), IVb 38% (n=13), ECOG PS2 38% (n=13), decreased weight (10% in one month or 15% in 6 months) 74% (n=25). The sequence was achieved for 76% (n=26) of patients and 80% (n=27) presented a clinical response after the chemotherapy course with notably increased weight (40%, n=11) or general status (75%, n=26). Median PFS and OS were 5.7 and 15.5 months, respectively. Disease progression at 3 months was significantly associated with decreased median overall survival (13.6 versus 21.9 months, p=0.01).

Conclusion

This is the first study to report the use of the EXTREME regimen as induction chemotherapy, and although this IC was used in a very frail population, the majority completed the sequence with significant clinical benefit.

http://ift.tt/2E43gaE

Cancers, Vol. 10, Pages 43: Elevated Polyamines in Saliva of Pancreatic Cancer

Cancers, Vol. 10, Pages 43: Elevated Polyamines in Saliva of Pancreatic Cancer

Cancers doi: 10.3390/cancers10020043

Authors: Yasutsugu Asai Takao Itoi Masahiro Sugimoto Atsushi Sofuni Takayoshi Tsuchiya Reina Tanaka Ryosuke Tonozuka Mitsuyoshi Honjo Shuntaro Mukai Mitsuru Fujita Kenjiro Yamamoto Yukitoshi Matsunami Takashi Kurosawa Yuichi Nagakawa Miku Kaneko Sana Ota Shigeyuki Kawachi Motohide Shimazu Tomoyoshi Soga Masaru Tomita Makoto Sunamura

Detection of pancreatic cancer (PC) at a resectable stage is still difficult because of the lack of accurate detection tests. The development of accurate biomarkers in low or non-invasive biofluids is essential to enable frequent tests, which would help increase the opportunity of PC detection in early stages. Polyamines have been reported as possible biomarkers in urine and saliva samples in various cancers. Here, we analyzed salivary metabolites, including polyamines, using capillary electrophoresis-mass spectrometry. Salivary samples were collected from patients with PC (n = 39), those with chronic pancreatitis (CP, n = 14), and controls (C, n = 26). Polyamines, such as spermine, N1-acetylspermidine, and N1-acetylspermine, showed a significant difference between patients with PC and those with C, and the combination of four metabolites including N1-acetylspermidine showed high accuracy in discriminating PC from the other two groups. These data show the potential of saliva as a source for tests screening for PC.

http://ift.tt/2E2N2P3

Cancers, Vol. 10, Pages 43: Elevated Polyamines in Saliva of Pancreatic Cancer

Cancers, Vol. 10, Pages 43: Elevated Polyamines in Saliva of Pancreatic Cancer

Cancers doi: 10.3390/cancers10020043

Authors: Yasutsugu Asai Takao Itoi Masahiro Sugimoto Atsushi Sofuni Takayoshi Tsuchiya Reina Tanaka Ryosuke Tonozuka Mitsuyoshi Honjo Shuntaro Mukai Mitsuru Fujita Kenjiro Yamamoto Yukitoshi Matsunami Takashi Kurosawa Yuichi Nagakawa Miku Kaneko Sana Ota Shigeyuki Kawachi Motohide Shimazu Tomoyoshi Soga Masaru Tomita Makoto Sunamura

Detection of pancreatic cancer (PC) at a resectable stage is still difficult because of the lack of accurate detection tests. The development of accurate biomarkers in low or non-invasive biofluids is essential to enable frequent tests, which would help increase the opportunity of PC detection in early stages. Polyamines have been reported as possible biomarkers in urine and saliva samples in various cancers. Here, we analyzed salivary metabolites, including polyamines, using capillary electrophoresis-mass spectrometry. Salivary samples were collected from patients with PC (n = 39), those with chronic pancreatitis (CP, n = 14), and controls (C, n = 26). Polyamines, such as spermine, N1-acetylspermidine, and N1-acetylspermine, showed a significant difference between patients with PC and those with C, and the combination of four metabolites including N1-acetylspermidine showed high accuracy in discriminating PC from the other two groups. These data show the potential of saliva as a source for tests screening for PC.

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High expression of cystine–glutamate antiporter xCT (SLC7A11) is an independent biomarker for epileptic seizures at diagnosis in glioma

Abstract

Epileptic seizures are an important cause of morbidity in glioma patients. Substantial lines of evidence support the concept of the excitatory neurotransmitter glutamate being a crucial mediator of glioma-associated seizures. In gliomas, non-vesicular secretion of glutamate via the cystine–glutamate exchanger (SLC7A11, xCT) constitutes the main mechanism contributing to high extracellular glutamate concentrations. However, a convincing "proof-of-relevance" of this mechanism in patient material is lacking. A cohort of 229 consecutive patients with newly diagnosed glioma was analyzed with respect to presence, time course, and severity of epileptic seizures. 14 patients were excluded due to previous epileptic seizures, insufficient clinical data or insufficient tumor material. The maximal immunohistochemical expression of xCT was determined in 1–3 independent samples from central tumor areas of each tumor using tissue microarrays. In addition to histological grading of the tumors, isocitrate dehydrogenase 1 (IDH1) R132H mutational status was determined by immunohistochemistry. 215 consecutive glioma patients were included in the study (7.4% grade II, 7.0% grade III, 85.6% grade IV). High xCT expression was significantly associated with seizures at onset (p = 0.05) but not with development of seizures or with refractory seizures. Low-grade gliomas (WHO II/III) had lower xCT expression than glioblastoma (p = 0.001), and tumors without IDH1 R132H mutation tended to have higher xCT levels (p = 0.07). In a multivariate analysis, high xCT expression and WHO tumor grade but not IDH1 R132H mutation, were significantly associated with epileptic seizures at diagnosis (odds ratio 2.2, p = 0.02). Further, xCT expression did not correlate with survival (p = 0.27, log-rank test). Thus, high xCT expression is an independent marker for glioma-associated seizures at diagnosis especially in high-grade glioma, but is not associated with worse survival in our cohort.

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High expression of cystine–glutamate antiporter xCT (SLC7A11) is an independent biomarker for epileptic seizures at diagnosis in glioma

Abstract

Epileptic seizures are an important cause of morbidity in glioma patients. Substantial lines of evidence support the concept of the excitatory neurotransmitter glutamate being a crucial mediator of glioma-associated seizures. In gliomas, non-vesicular secretion of glutamate via the cystine–glutamate exchanger (SLC7A11, xCT) constitutes the main mechanism contributing to high extracellular glutamate concentrations. However, a convincing "proof-of-relevance" of this mechanism in patient material is lacking. A cohort of 229 consecutive patients with newly diagnosed glioma was analyzed with respect to presence, time course, and severity of epileptic seizures. 14 patients were excluded due to previous epileptic seizures, insufficient clinical data or insufficient tumor material. The maximal immunohistochemical expression of xCT was determined in 1–3 independent samples from central tumor areas of each tumor using tissue microarrays. In addition to histological grading of the tumors, isocitrate dehydrogenase 1 (IDH1) R132H mutational status was determined by immunohistochemistry. 215 consecutive glioma patients were included in the study (7.4% grade II, 7.0% grade III, 85.6% grade IV). High xCT expression was significantly associated with seizures at onset (p = 0.05) but not with development of seizures or with refractory seizures. Low-grade gliomas (WHO II/III) had lower xCT expression than glioblastoma (p = 0.001), and tumors without IDH1 R132H mutation tended to have higher xCT levels (p = 0.07). In a multivariate analysis, high xCT expression and WHO tumor grade but not IDH1 R132H mutation, were significantly associated with epileptic seizures at diagnosis (odds ratio 2.2, p = 0.02). Further, xCT expression did not correlate with survival (p = 0.27, log-rank test). Thus, high xCT expression is an independent marker for glioma-associated seizures at diagnosis especially in high-grade glioma, but is not associated with worse survival in our cohort.

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Physician turnover effect for in-hospital cardiopulmonary resuscitation: a 10-year experience in a tertiary academic hospital

Abstract

Purpose

Controversy exists as to whether the physician turnover affects patient outcome in academic hospitals. In-hospital cardiopulmonary resuscitation (CPR) is an important indicator of in-hospital mortality. This study aimed to investigate whether the physician turnover is associated with the in-hospital CPR rate.

Methods

This retrospective cohort study was conducted at a single center; all in-hospital CPR cases among in-patients from 1 January 2007 to 31 December 2016 were analyzed. The turnover period was defined as the changeover of the trainee workforce in March, May, and November. The primary outcome was any variation in the monthly in-hospital CPR events (per 1000 admissions). The secondary outcomes were return of spontaneous circulation (ROSC), CPR in intensive care unit (ICU), monthly in-hospital deaths per 1000 admissions, and average length of hospital stay.

Results

A total of 2182 in-hospital CPR cases were included in the analysis. Monthly in-hospital CPR rates were greater during the turnover period when compared to the non-turnover period (4.66 ± 1.02 vs. 4.18 ± 1.56, P = 0.027). There was no significant difference in ROSC rate, CPR in ICU rate, monthly in-hospital deaths per 1000 admissions, or average length of hospital stay between the two periods.

Conclusion

Our findings indicate that physician turnover may be associated with in-hospital CPR rate. However, physician turnover was not associated with ROSC rate, rate of CPR in the ICU, in-hospital death, or length of hospital stay.

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First-line ribociclib plus letrozole in postmenopausal women with HR+ , HER2− advanced breast cancer: Tumor response and pain reduction in the phase 3 MONALEESA-2 trial

Abstract

Purpose

The phase 3 MONALEESA-2 study demonstrated that addition of ribociclib (RIB) to letrozole (LET) significantly improved progression-free survival (PFS) in patients (pts) with hormone receptor-positive (HR+), HER2-negative (HER2−) advanced breast cancer (ABC). Here, we evaluated duration of response (DoR), tumor shrinkage, PFS by treatment-free interval (TFI), and health-related quality of life (HRQoL).

Methods

Postmenopausal women (N = 668) with HR+ , HER2− ABC and no prior systemic therapy for ABC were randomized to RIB (600 mg/day; 3 weeks on/1 week off) plus LET (2.5 mg/day; continuous) or placebo (PBO) plus LET. Primary end point was PFS; HRQoL was the secondary end point; DoR was exploratory end point and PFS by TFI was post hoc analysis.

Results

Of 501 pts with measurable disease and confirmed complete or partial response, median DoR was 26.7 months (95% CI, 24.0–NR) in the RIB arm versus 18.6 months (95% CI, 14.8–23.1) in the PBO arm. At 8 weeks, more pts in the RIB arm (32%) versus the PBO arm (17%) experienced best percentage change ≥ 60%. The average pain reduction was greater in the RIB arm (26%) versus the PBO arm (15%). PFS benefit was seen with RIB vs PBO, irrespective of TFI.

Conclusion

RIB plus LET versus PBO plus LET is associated with earlier and more durable tumor response, greater degree of tumor shrinkage and pain reduction, and PFS benefit irrespective of TFI. These data further support RIB plus LET as a first-line treatment option for postmenopausal women with HR+ , HER2− ABC.

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Waste anesthetic gas exposure and strategies for solution

Abstract

As inhaled anesthetics are widely used, medical staff have inevitably suffered from exposure to anesthetic waste gases (WAGs). Whether chronic exposure to WAGs has an impact on the health of medical staff has long been a common concern, but conclusions are not consistent. Many measures and equipment have been proposed to reduce the concentration of WAGs as far as possible. This review aims to dissect the current exposure to WAGs and its influence on medical staff in the workplace and the environment, and summarize strategies to reduce WAGs.

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SmartTots Update Regarding Anesthetic Neurotoxicity in the Developing Brain

SmartTots (http://smarttots.org/) represents a public–private partnership between the International Anesthesia Research Society and the US Food and Drug Administration. Over the past 7 years, SmartTots has worked in collaboration with various stakeholders to determine whether anesthetic drugs have detrimental effects on the developing brain. SmartTots has funded clinical and preclinical studies, organized meetings, served as a repository of peer-reviewed information, and facilitated the development of consensus-based statements. Here, we report advances in the field of anesthetic neurotoxicity and provide an update on SmartTots' activities. Clinical studies have provided some reassurance that a brief exposure to anesthetic drugs does not cause overt, persistent cognitive deficits. New recommendations aim to increase the reproducibility and "clinical relevance" of data from studies of laboratory animals. Overall, the field has advanced substantially; however, it remains paramount to definitively resolve whether anesthetic drugs are neurotoxic to the immature brain. The results of SmartTots efforts will either ally unwarranted fears or substantially change pediatric anesthetic practice and prompt studies to identify neuroprotective strategies. Accepted for publication November 28, 2017. Funding: None. The authors declare no conflicts of interest. The opinions expressed in this article are those of the authors, not SmartTots or the US Food and Drug Administration (FDA). The authors represent the Board of Trustees of the International Anesthesia Research Society (IARS) on the Executive Council and Scientific Advisory Board of SmartTots. Reprints will not be available from the authors. Address correspondence to Beverley A. Orser, MD, PhD, University of Toronto, Room 3318, Medical Sciences Bldg, 1 King's College Cir, Toronto, Ontario M5S1A8, Canada. Address e-mail to Beverley.Orser@utoronto.ca. © 2018 International Anesthesia Research Society

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Chronic Pain and the Opioid Epidemic: Are We Ignoring the Potential Benefits of Nitrous Oxide?

No abstract available

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Teaching Medical Students Clinical Anesthesia

There are many reasons for evaluating our approach and improving our teaching of America's future doctors, whether they become anesthesiologists (recruitment) or participate in patient management in the perioperative period (general patient care). Teaching medical students the seminal aspects of any medical specialty is a continual challenge. Although no definitive curricula or single clinical approach has been defined, certain key features can be ascertained from clinical experience and the literature. A survey was conducted among US anesthesiology teaching programs regarding the teaching content and approaches currently used to teach US medical students clinical anesthesia. Using the Accreditation Council for Graduate Medical Education website that lists 133 accredited anesthesiology programs, residency directors were contacted via e-mail. Based on those responses and follow-up phone calls, teaching representatives from 125 anesthesiology departments were identified and asked via e-mail to complete a survey. The survey was returned by 85 programs, yielding a response rate of 68% of individuals contacted and 63% of all departments. Ninety-one percent of the responding departments teach medical students, most in the final 2 years of medical school. Medical student exposure to clinical anesthesia occurred as elective only at 42% of the institutions, was requirement only at 16% of responding institutions, and the remainder had both elective and required courses. Anesthesiology faculty at 43% of the responding institutions reported teaching in the preclinical years of medical school, primarily in the departments of pharmacology and physiology. Forty-five percent of programs reported interdisciplinary teaching with other departments teaching classes such as gross anatomy. There is little exposure of anesthesiology faculty to medical students in other general courses. Teaching in the operating room is the primary teaching method in the clinical years. Students are allowed full access to patient care, including performing history and physical examinations, participating in the insertion of IVs and airway management. Simulation-based teaching was used by 82% of programs during medical student anesthesia clerkships. Sixty-eight percent of respondents reported that they have no formal training for their anesthesiology faculty teachers, 51% stated that they do not receive nonclinical time to teach, and 38% of respondents stated that they received some form of remuneration for teaching medical students, primarily nonclinical time. This article presents a summary of these survey results, provides a historical review of previous evaluations of teaching medical students clinical anesthesia, and discusses the contributions of anesthesiologists to medical student education. Accepted for publication December 5, 2017. Funding: Departmental. The author declares no conflicts of interest. Reprints will not be available from the author. Address correspondence to Saundra E. Curry, MD, Department of Anesthesiology, Columbia University, PH 5–133, 622 W 168th St, New York, NY 10032. Address e-mail to sc42@cumc.columbia.edu. © 2018 International Anesthesia Research Society

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Effect-Site Target-Controlled Infusion in the Obese: Model Derivation and Performance Assessment

BACKGROUND: The aim of this study is to derive a propofol pharmacokinetic (PK) pharmacodynamic (PD) model to perform effect-site target-controlled infusion (TCI) in obese patients, and to analyze its performance along with that of other available PK models. METHODS: In the first step of the study, a 3-compartment PK model linked to a sigmoidal inhibitory Emax PD model by a first-order rate constant (keo) was used to fit propofol concentration–bispectral index (BIS) data. Population modeling analysis was performed by nonlinear mixed effects regression in NONMEM (ICON, Dublin, Ireland). PK data from 3 previous studies in obese adult patients (n = 47), including PD (BIS) data from 1 of these studies (n = 20), were pooled and simultaneously analyzed. A decrease in NONMEM objective function (ΔOBJ) of 3.84 points, for an added parameter, was considered significant at the 0.05 level. In the second step of the study, we analyzed the predictive performance (median predictive errors [MDPE] and median absolute predictive errors [MDAPE]) of the current model and of other available models using an independent data set (n = 14). RESULTS: Step 1: The selected PKPD model produced an adequate fit of the data. Total body weight resulted in the best size scalar for volumes and clearances (ΔOBJ, −18.173). Empirical allometric total body weight relationships did not improve model fit (ΔOBJ, 0.309). A lag time parameter for BIS response improved the fit (ΔOBJ, 89.593). No effect of age or gender was observed. Step 2: Current model MDPE and MDAPE were 11.5% (3.7–25.0) and 26.8% (20.7–32.6) in the PK part and 0.4% (−10.39 to 3.85) and 11.9% (20.7–32.6) in the PD part. The PK model developed by Eleveld et al resulted in the lowest PK predictive errors (MDPE =

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The Effect of Intermittent Oxytocin Pretreatment on Oxytocin-Induced Contractility of Human Myometrium In Vitro

BACKGROUND: Prolonged continuous oxytocin administration during labor may induce oxytocin receptor desensitization, which attenuates the response of the myometrium to further oxytocin, increasing the risk of postpartum hemorrhage. The literature comparing pulsatile (intermittent) versus continuous oxytocin administration for induction and augmentation of labor is inconsistent with regard to maternal outcomes. We aimed to determine the effect of intermittent versus continuous oxytocin preexposure on myometrial responsiveness to subsequent oxytocin. We hypothesized that intermittent oxytocin pretreatment would result in superior subsequent oxytocin-induced contractility than continuous oxytocin pretreatment. METHODS: This in vitro study was undertaken using myometrium obtained from women undergoing elective cesarean deliveries. Each myometrial strip was mounted in an individual organ bath with physiological salt solution under homeostatic conditions and allocated to one of 3 groups: (1) control (no pretreatment); (2) continuous (pretreatment with oxytocin 10−5 M for 2 hours); or (3) intermittent (pretreatment with alternating oxytocin 10−5 M and physiological salt solution every 15 minutes, for 2 hours). After pretreatment, dose–response testing to oxytocin 10−10 to 10−5 M was performed and contractile parameters were measured. The primary outcome was motility index (MI, amplitude × frequency) of contractions. RESULTS: Eighteen women were recruited, and 86 successful experiments were performed (control n = 29, continuous n = 28, intermittent n = 29). The means (standard errors) of MI (√g·contractions/10 min) in the control, continuous, and intermittent groups were 2.34 (0.09), 1.78 (0.09), and 2.13 (0.11), respectively. The MI was significantly reduced in the continuous group when compared to the control (estimated difference [95% confidence interval {CI}], −0.56 [−0.81 to −0.31]; P

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In Response

No abstract available

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Adding Dopamine to Proxymetacaine or Oxybuprocaine Solutions Potentiates and Prolongs the Cutaneous Antinociception in Rats

Background: We evaluated the interaction of dopamine–proxymetacaine and dopamine– oxybuprocaine antinociception using isobolograms. Methods: This experiment uses subcutaneous drug (proxymetacaine, oxybuprocaine, and dopamine) injections under the skin of the rat's back, thus simulating infiltration blocks. The dose-related antinociceptive curves of proxymetacaine and oxybuprocaine alone and in combination with dopamine were constructed, and then the antinociceptive interactions between the local anesthetic and dopamine were analyzed using isobolograms. Results: Subcutaneous proxymetacaine, oxybuprocaine, and dopamine produced a sensory block to local skin pinpricks in a dose-dependent fashion. The rank order of potency was proxymetacaine (0.57 [0.52–0.63] μmol/kg) > oxybuprocaine (1.05 [0.96–1.15] μmol/kg) > dopamine (165 [154–177] μmol/kg; P oxybuprocaine > dopamine. Coadministration of proxymetacaine or oxybuprocaine with dopamine produced a synergistic antinociceptive effect. Dopamine prolonged the duration of skin antinociception caused by proxymetacaine or oxybuprocaine. This study tests subcutaneous injections under the hairy skin, thus simulating infiltration blocks that occur during surgery. Reprints will not be available from the authors. Address correspondence to Ching-Hsia Hung, PhD, Department of Physical Therapy, College of Medicine, National Cheng Kung University, No.1 Ta-Hsueh Rd, Tainan, Taiwan. Address e-mail to chhung@mail.ncku.edu.tw. © 2018 International Anesthesia Research Society

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Comparison of Nasal Intubations by GlideScope With and Without a Bougie Guide in Patients Who Underwent Maxillofacial Surgeries: Randomized Clinical Trial

BACKGROUND: Nasotracheal intubation is commonly performed to provide a secure airway for the maintenance of general anesthesia in maxillofacial surgeries. Routine nasotracheal intubation is performed under general anesthesia by direct laryngoscopy, frequently with the aid of Magill forceps. This method can be time-consuming and may cause bleeding in the field of view. A gum elastic bougie (GEB) is a cheap, slender, and flexible device that could expedite nasotracheal intubation. The aim of this study was to evaluate the use of a GEB during nasotracheal intubation to facilitate the procedure and reduce the rate of complications. METHODS: In this randomized clinical trial study, 110 patients with American Society of Anesthesiologists (ASA) physical status I–II from 15 to 65 years of age were randomized into 2 equal groups. In both groups, a GlideScope and armored tube were used. In the GEB group, GEB was used to facilitate nasal intubation while the nasal intubation was performed without the aid of GEB in the routine group. The difficult intubation (defined as >1 attempt for intubation) was the primary outcome, and the duration of the intubation, the presence of traces of bleeding, the need for a tube replacement, and the usage of Magill forceps were the secondary outcomes. RESULTS: The incidence of bleeding in the GEB group was 1.81% vs 43.63% in the routine group (P

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