The Safety Assessment of Toxic Metals in Commonly Used Pharmaceutical Herbal Products and Traditional Herbs for Infants in Jordanian Market

Abstract

The objective of this study was to assess the levels of contamination by toxic metals (Pb, Al, Ni, Cd and As) that may be present in 25 infant pharmaceutical herbal products and 15 traditional herbs in Jordan. Both products and medicinal herbs are currently prescribed by paediatricians. They are available as over-the-counter medicines and are sold the in herbal market, ensuring easy accessibility for parents. Inductively coupled plasma-optical emission spectroscopy (ICP-OES), with limit of detections (LODs) of 0.10, 1.00, 0.20, 0.15 and 2.00 mg.kg⁻¹ for Pb, Al, Ni, Cd and As respectively, was employed to measure the levels of toxic metals in the samples. Pb, Al and Ni were detected in 88, 76 and 4% of the analysed samples of pharmaceutical herbal products and in 93, 87 and 13% of the analysed samples of traditional herbs, respectively. Neither Cd or As were detected in all analysed samples. The data obtained were subsequently compared by referral to the acceptable limits of toxic heavy metals according to World Health Organisation (WHO) standards. Largely, the results showed acceptable toxic metal levels in the finished pharmaceutical products and the traditional medicinal herbs for infants. One exception to this was Persian Thyme (Satureja thymbra) with Pb content of 41.18 mg.kg⁻¹. Also, the daily intake of detected metals through pharmaceutical herbal products was found to be lower than the daily tolerable intake limit set by the regulatory bodies, except of 8% of products that exceeded the tolerable daily intake of Pb set by US FDA, as compared to traditional medicinal herbs, where the tolerable daily intake for Pb, Al and Ni were exceeded in 40, 60 and 8% of the analysed herbs, respectively. The results obtained revealed that the excessive use of medicinal plants as alternative medicine should be used with caution keeping in mind the safety factor in infants.

https://ift.tt/2jv7MCb

The Safety Assessment of Toxic Metals in Commonly Used Pharmaceutical Herbal Products and Traditional Herbs for Infants in Jordanian Market

Abstract

The objective of this study was to assess the levels of contamination by toxic metals (Pb, Al, Ni, Cd and As) that may be present in 25 infant pharmaceutical herbal products and 15 traditional herbs in Jordan. Both products and medicinal herbs are currently prescribed by paediatricians. They are available as over-the-counter medicines and are sold the in herbal market, ensuring easy accessibility for parents. Inductively coupled plasma-optical emission spectroscopy (ICP-OES), with limit of detections (LODs) of 0.10, 1.00, 0.20, 0.15 and 2.00 mg.kg⁻¹ for Pb, Al, Ni, Cd and As respectively, was employed to measure the levels of toxic metals in the samples. Pb, Al and Ni were detected in 88, 76 and 4% of the analysed samples of pharmaceutical herbal products and in 93, 87 and 13% of the analysed samples of traditional herbs, respectively. Neither Cd or As were detected in all analysed samples. The data obtained were subsequently compared by referral to the acceptable limits of toxic heavy metals according to World Health Organisation (WHO) standards. Largely, the results showed acceptable toxic metal levels in the finished pharmaceutical products and the traditional medicinal herbs for infants. One exception to this was Persian Thyme (Satureja thymbra) with Pb content of 41.18 mg.kg⁻¹. Also, the daily intake of detected metals through pharmaceutical herbal products was found to be lower than the daily tolerable intake limit set by the regulatory bodies, except of 8% of products that exceeded the tolerable daily intake of Pb set by US FDA, as compared to traditional medicinal herbs, where the tolerable daily intake for Pb, Al and Ni were exceeded in 40, 60 and 8% of the analysed herbs, respectively. The results obtained revealed that the excessive use of medicinal plants as alternative medicine should be used with caution keeping in mind the safety factor in infants.

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Management and grading of EGFR inhibitor-induced cutaneous toxicity

Future Oncology, Ahead of Print.


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Systematic review on the efficacy and safety of immune checkpoint inhibition in renal cell carcinoma

Future Oncology, Ahead of Print.


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Management and grading of EGFR inhibitor-induced cutaneous toxicity

Future Oncology, Ahead of Print.


https://ift.tt/2FId9Xr

Systematic review on the efficacy and safety of immune checkpoint inhibition in renal cell carcinoma

Future Oncology, Ahead of Print.


https://ift.tt/2KDh3Vd

Student Perspectives on the Impact of an Undergraduate Work-Integrated Learning Program on Admission and Transition to Medical School

Abstract

Work-integrated learning (WIL) is a form of education that integrates academic and workplace study. Such programs provide students the opportunity to concurrently develop cognitive and non-cognitive competencies. The purpose of this study is to explore which experiences and skills learned in a WIL placement are useful in applying to medical school and transitioning into the first year of a Doctor of Medicine program. All individuals who worked in the Rapid Response Radiotherapy Program (RRRP; WIL placement) since 2004 and had completed at least 1 year of medical school were invited to participate. Semi-formal interviews were conducted and transcribed. A thematic analysis was completed to identify recurring concepts, and quotes were selected to represent them. Of 39 eligible individuals, 14 agreed to participate (36%). Students identified the volume of work, achieving a work-life balance, and time management as challenges in first-year medical school. Five themes emerged regarding the impact of the RRRP on applying and transitioning to medical school: time management skills, mentorship opportunities, research experience, clinical experience, and career choice. WIL placements present a unique opportunity for undergraduate students interested in pursuing medicine to acquire skills and experiences that will help them succeed in applying and transitioning to medical school.

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Translational PK-PD modeling analysis of MCLA-128, a HER2/HER3 bispecific monoclonal antibody, to predict clinical efficacious exposure and dose

Summary

Introduction MCLA-128 is a bispecific monoclonal antibody targeting the HER2 and HER3 receptors. Pharmacokinetics (PK) and pharmacodynamics (PD) of MCLA-128 have been evaluated in preclinical studies in cynomolgus monkeys and mice. The aim of this study was to characterize the PK and PD of MCLA-128 and to predict a safe starting dose and efficacious clinical dose for the First-In-Human study. Methods A PK-PD model was developed based on PK data from cynomolgus monkeys and tumor growth data from a mouse JIMT-1 xenograft model. Allometric scaling was used to scale PK parameters between species. Simulations were performed to predict the safe and efficacious clinical dose, based on AUCs, receptor occupancies and PK-PD model simulations. Results MCLA-128 PK in cynomolgus monkeys was described by a two-compartment model with parallel linear and nonlinear clearance. The xenograft tumor growth model consisted of a tumor compartment with a zero-order growth rate and a first-order dying rate, both affected by MCLA-128. Human doses of 10 to 480 mg q3wk were predicted to show a safety margin of >10-fold compared to the cynomolgus monkey AUC at the no-observed-adverse-effect-level (NOAEL). Doses of ≥360 mg resulted in predicted receptor occupancies above 99% (C_max and C_ave). These doses showed anti-tumor efficacy in the PK-PD model. Conclusions This analysis predicts that a flat dose of 10 to 480 mg q3wk is suitable as starting dose for a First-in-Human study with MCLA-128. Flat doses ≥360 mg q3wk are expected to be efficacious in human, based on receptor occupancies and PK-PD model simulations.

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Student Perspectives on the Impact of an Undergraduate Work-Integrated Learning Program on Admission and Transition to Medical School

Abstract

Work-integrated learning (WIL) is a form of education that integrates academic and workplace study. Such programs provide students the opportunity to concurrently develop cognitive and non-cognitive competencies. The purpose of this study is to explore which experiences and skills learned in a WIL placement are useful in applying to medical school and transitioning into the first year of a Doctor of Medicine program. All individuals who worked in the Rapid Response Radiotherapy Program (RRRP; WIL placement) since 2004 and had completed at least 1 year of medical school were invited to participate. Semi-formal interviews were conducted and transcribed. A thematic analysis was completed to identify recurring concepts, and quotes were selected to represent them. Of 39 eligible individuals, 14 agreed to participate (36%). Students identified the volume of work, achieving a work-life balance, and time management as challenges in first-year medical school. Five themes emerged regarding the impact of the RRRP on applying and transitioning to medical school: time management skills, mentorship opportunities, research experience, clinical experience, and career choice. WIL placements present a unique opportunity for undergraduate students interested in pursuing medicine to acquire skills and experiences that will help them succeed in applying and transitioning to medical school.

https://ift.tt/2rlyO2p

Translational PK-PD modeling analysis of MCLA-128, a HER2/HER3 bispecific monoclonal antibody, to predict clinical efficacious exposure and dose

Summary

Introduction MCLA-128 is a bispecific monoclonal antibody targeting the HER2 and HER3 receptors. Pharmacokinetics (PK) and pharmacodynamics (PD) of MCLA-128 have been evaluated in preclinical studies in cynomolgus monkeys and mice. The aim of this study was to characterize the PK and PD of MCLA-128 and to predict a safe starting dose and efficacious clinical dose for the First-In-Human study. Methods A PK-PD model was developed based on PK data from cynomolgus monkeys and tumor growth data from a mouse JIMT-1 xenograft model. Allometric scaling was used to scale PK parameters between species. Simulations were performed to predict the safe and efficacious clinical dose, based on AUCs, receptor occupancies and PK-PD model simulations. Results MCLA-128 PK in cynomolgus monkeys was described by a two-compartment model with parallel linear and nonlinear clearance. The xenograft tumor growth model consisted of a tumor compartment with a zero-order growth rate and a first-order dying rate, both affected by MCLA-128. Human doses of 10 to 480 mg q3wk were predicted to show a safety margin of >10-fold compared to the cynomolgus monkey AUC at the no-observed-adverse-effect-level (NOAEL). Doses of ≥360 mg resulted in predicted receptor occupancies above 99% (C_max and C_ave). These doses showed anti-tumor efficacy in the PK-PD model. Conclusions This analysis predicts that a flat dose of 10 to 480 mg q3wk is suitable as starting dose for a First-in-Human study with MCLA-128. Flat doses ≥360 mg q3wk are expected to be efficacious in human, based on receptor occupancies and PK-PD model simulations.

https://ift.tt/2jwojFO

Aspects of Modern Biobank Activity – Comprehensive Review

Abstract

Biobanks play an increasing role in contemporary research projects. These units meet all requirements to regard them as a one of the most innovative and up-to-date in the field of biomedical research. They enable conducting wide-scale research by the professional collection of biological specimens and correlated clinical data. Pathology units may be perceived roots of biobanking. The review aims at describing the concept of biobanks, their model of function and scientific potential. It comprises the division of biobanks, sample preservation methods and IT solutions as well as guidelines and recommendations for management of a vast number of biological samples and clinical data. Therefore, appropriate standard operating procedures and protocols are outlined. Constant individualization of diagnostic process and treatment procedures creates the niche for translational units. Thus, the role of biobanks in personalized medicine was also specified. The exceptionality of biobanks poses some new ethical-legal issues which have various solutions, in each legal system, amongst the world. Finally, distribution and activity of European biobanks are mentioned.

https://ift.tt/2JU9icp

Aspects of Modern Biobank Activity – Comprehensive Review

Abstract

Biobanks play an increasing role in contemporary research projects. These units meet all requirements to regard them as a one of the most innovative and up-to-date in the field of biomedical research. They enable conducting wide-scale research by the professional collection of biological specimens and correlated clinical data. Pathology units may be perceived roots of biobanking. The review aims at describing the concept of biobanks, their model of function and scientific potential. It comprises the division of biobanks, sample preservation methods and IT solutions as well as guidelines and recommendations for management of a vast number of biological samples and clinical data. Therefore, appropriate standard operating procedures and protocols are outlined. Constant individualization of diagnostic process and treatment procedures creates the niche for translational units. Thus, the role of biobanks in personalized medicine was also specified. The exceptionality of biobanks poses some new ethical-legal issues which have various solutions, in each legal system, amongst the world. Finally, distribution and activity of European biobanks are mentioned.

https://ift.tt/2JU9icp

Student Perspectives on the Impact of an Undergraduate Work-Integrated Learning Program on Admission and Transition to Medical School

Abstract

Work-integrated learning (WIL) is a form of education that integrates academic and workplace study. Such programs provide students the opportunity to concurrently develop cognitive and non-cognitive competencies. The purpose of this study is to explore which experiences and skills learned in a WIL placement are useful in applying to medical school and transitioning into the first year of a Doctor of Medicine program. All individuals who worked in the Rapid Response Radiotherapy Program (RRRP; WIL placement) since 2004 and had completed at least 1 year of medical school were invited to participate. Semi-formal interviews were conducted and transcribed. A thematic analysis was completed to identify recurring concepts, and quotes were selected to represent them. Of 39 eligible individuals, 14 agreed to participate (36%). Students identified the volume of work, achieving a work-life balance, and time management as challenges in first-year medical school. Five themes emerged regarding the impact of the RRRP on applying and transitioning to medical school: time management skills, mentorship opportunities, research experience, clinical experience, and career choice. WIL placements present a unique opportunity for undergraduate students interested in pursuing medicine to acquire skills and experiences that will help them succeed in applying and transitioning to medical school.

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Student Perspectives on the Impact of an Undergraduate Work-Integrated Learning Program on Admission and Transition to Medical School

Abstract

Work-integrated learning (WIL) is a form of education that integrates academic and workplace study. Such programs provide students the opportunity to concurrently develop cognitive and non-cognitive competencies. The purpose of this study is to explore which experiences and skills learned in a WIL placement are useful in applying to medical school and transitioning into the first year of a Doctor of Medicine program. All individuals who worked in the Rapid Response Radiotherapy Program (RRRP; WIL placement) since 2004 and had completed at least 1 year of medical school were invited to participate. Semi-formal interviews were conducted and transcribed. A thematic analysis was completed to identify recurring concepts, and quotes were selected to represent them. Of 39 eligible individuals, 14 agreed to participate (36%). Students identified the volume of work, achieving a work-life balance, and time management as challenges in first-year medical school. Five themes emerged regarding the impact of the RRRP on applying and transitioning to medical school: time management skills, mentorship opportunities, research experience, clinical experience, and career choice. WIL placements present a unique opportunity for undergraduate students interested in pursuing medicine to acquire skills and experiences that will help them succeed in applying and transitioning to medical school.

https://ift.tt/2rlyO2p

Q&A: Ned Sharpless on His Vision for NCI [News in Depth]

Addressing the challenges of the cancer research landscape requires innovative thinking.

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Kelch-Like Protein 6 Negatively Regulates NF-{kappa}B Activation in Lymphoma [Research Watch]

KLHL6 loss promotes NF-B activation to drive DLBCL proliferation.

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CXCR4 Antagonism Has Antitumor Activity in Combination with Eribulin [Research Watch]

The CXCR4 antagonist balixafortide plus eribulin achieves responses in metastatic breast cancer.

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Carboxyamidotriazole Orotate plus TMZ Is Safe and Active in Glioblastoma [Research Watch]

Carboxyamidotriazole orotate (CTO) plus temozolomide (TMZ) was well tolerated in patients with glioma.

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I-Motif DNA Structures May Regulate Promoters and Telomeres [Research Watch]

I-motif DNA structures form in the nuclei of human cells in a cell-cycle and pH dependent manner.

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A Cryo-EM Structure Elucidates the Human Telomerase Holoenzyme [Research Watch]

The bilobal telomerase structure has a catalytic core lobe and a H/ACA ribonucleoprotein lobe.

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Impact of the treatment of pancreatic exocrine insufficiency on survival of patients with unresectable pancreatic cancer: a retrospective analysis

Abstract

Background

Malnutrition and weight loss are commonly observed in patients with pancreatic cancer and contribute to poor survival. Pancreatic exocrine insufficiency (PEI), which can be caused by ductal obstruction by a tumor, causes maldigestion and malabsorption of nutrients, thus contributing to malnutrition in these patients. In this study, we evaluated the effects of pancreatic enzyme replacement therapy (PERT) on survival in patients with unresectable pancreatic cancer.

Methods

A retrospective analysis was conducted on a database of patients with unresectable, pathologically confirmed pancreatic cancer. All patients were evaluated for palliative chemotherapy and received the optimal palliative care. Patients were divided into two groups: Group 1 received standard therapy; Group 2 underwent additional evaluation of the pancreatic function and therapy with PERT, if needed. Survival (median and 95% confidence interval [CI]) was analyzed using Kaplan–Meier and Cox regression; groups were compared using the log-rank test.

Results

Overall, 160 patients with unresectable pancreatic cancer were included in the analysis (mean age: 70.5 years [range 28–100]; gender: 57.5% male; tumor stage: 78.7% Stage IV). Eighty-six patients (53.75%) were in Group 1 and 74 (46.25%) were in Group 2. Age, gender, tumor size, location and stage, weight loss, and serum CA 19–9 were similar between groups. Ninety-three (58.1%) patients received palliative chemotherapy; 46.5% in Group 1 and 71.6% in Group 2 (P < 0.001). Forty-nine (66.2%) patients in Group 2 and none in Group 1 received PERT. Survival in Group 2 (189 days, 95% CI 167.0–211.0 days) was significantly longer than in Group 1 (95.0 days, 95% CI 75.4–114.6 days) (HR 2.117, 95% CI 1.493–3.002; P < 0.001). Chemotherapy and PERT were significantly and independently associated with longer survival in a model controlled by age and tumor stage. In patients with significant weight loss at diagnosis (> 10% bodyweight within 6 months), PERT was associated with longer survival (HR 2.52, 95% CI 1.55–4.11; P < 0.001).

Conclusions

In patients with unresectable pancreatic cancer, PERT in patients with PEI was associated with longer survival compared with those not receiving PERT, especially in those experiencing significant weight loss. This finding should guide future prospective clinical trials of similar interventions.

https://ift.tt/2rmVTT6

Neuropilin-1 promotes the oncogenic Tenascin-C/ integrin β3 pathway and modulates chemoresistance in breast cancer cells

Abstract

Background

Neuropilin-1 (NRP-1), a non-tyrosine kinase glycoprotein receptor, is associated with poor prognosis breast cancer, however transcriptomic changes triggered by NRP-1 overexpression and its association with chemoresistance in breast cancer have not yet been explored.

Methods

BT-474 NRP-1 variant cells were generated by stable overexpression of NRP-1 in the BT-474 breast cancer cell line. RNA sequencing and qRT-PCR were conducted to identify differentially expressed genes. The role of an upregulated oncogene, Tenascin C (TNC) and its associated pathway was investigated by siRNA-mediated knockdown. Resistant variants of the control and BT-474 NRP-1 cells were generated by sequential treatment with four cycles of Adriamycin/Cyclophosphamide (4xAC) followed by four cycles of Paclitaxel (4xAC + 4xPAC).

Results

NRP-1 overexpression increased cellular tumorigenic behavior. RNA sequencing identified upregulation of an oncogene, Tenascin-C (TNC) and downregulation of several tumor suppressors in BT-474 NRP-1 cells. Additionally, protein analysis indicated activation of the TNC-associated integrin β3 (ITGB3) pathway via focal adhesion kinase (FAK), Akt (Ser473) and nuclear factor kappa B (NF-kB) p65. siRNA-mediated TNC knockdown ablated the migratory capacity of BT-474 NRP-1 cells and inactivated FAK/Akt473 signaling. NRP-1 overexpressing cells downregulated breast cancer resistance protein (BCRP/ABCG2). Consequently, sequential treatment with Adriamycin/Cyclophosphamide (AC) cytotoxic drugs to generate resistant cells indicated that BT-474 NRP-1 cells increased sensitivity to treatment by inactivating NRP-1/ITGB3/FAK/Akt/NF-kB p65 signaling compared to wild-type BT-474 resistant cells.

Conclusions

We thus report a novel mechanism correlating high baseline NRP-1 with upregulated TNC/ITGB3 signaling, but decreased ABCG2 expression, which sensitizes BT-474 NRP-1 cells to Adriamycin/Cyclophosphamide. The study emphasizes on the targetability of the NRP-1/ITGB3 axis and its potential as a predictive biomarker for chemotherapy response.

https://ift.tt/2wfy5FP

Metabolomic profiles in breast cancer:a pilot case-control study in the breast cancer family registry

Abstract

Background

Metabolomics is emerging as an important tool for detecting differences between diseased and non-diseased individuals. However, prospective studies are limited.

Methods

We examined the detectability, reliability, and distribution of metabolites measured in pre-diagnostic plasma samples in a pilot study of women enrolled in the Northern California site of the Breast Cancer Family Registry. The study included 45 cases diagnosed with breast cancer at least one year after the blood draw, and 45 controls. Controls were matched on age (within 5 years), family status, BRCA status, and menopausal status. Duplicate samples were included for reliability assessment. We used a liquid chromatography/gas chromatography mass spectrometer platform to measure metabolites. We calculated intraclass correlations (ICCs) among duplicate samples, and coefficients of variation (CVs) across metabolites.

Results

Of the 661 named metabolites detected, 338 (51%) were found in all samples, and 490 (74%) in more than 80% of samples. The median ICC between duplicates was 0.96 (25th – 75th percentile: 0.82–0.99). We observed a greater than 20% case-control difference in 24 metabolites (p < 0.05), although these associations were not significant after adjusting for multiple comparisons.

Conclusions

These data show that assays are reproducible for many metabolites, there is a minimal laboratory variation for the same sample, and a large between-person variation. Despite small sample size, differences between cases and controls in some metabolites suggest that a well-powered large-scale study is likely to detect biological meaningful differences to provide a better understanding of breast cancer etiology.

https://ift.tt/2rnz5mj

Impact of the treatment of pancreatic exocrine insufficiency on survival of patients with unresectable pancreatic cancer: a retrospective analysis

Abstract

Background

Malnutrition and weight loss are commonly observed in patients with pancreatic cancer and contribute to poor survival. Pancreatic exocrine insufficiency (PEI), which can be caused by ductal obstruction by a tumor, causes maldigestion and malabsorption of nutrients, thus contributing to malnutrition in these patients. In this study, we evaluated the effects of pancreatic enzyme replacement therapy (PERT) on survival in patients with unresectable pancreatic cancer.

Methods

A retrospective analysis was conducted on a database of patients with unresectable, pathologically confirmed pancreatic cancer. All patients were evaluated for palliative chemotherapy and received the optimal palliative care. Patients were divided into two groups: Group 1 received standard therapy; Group 2 underwent additional evaluation of the pancreatic function and therapy with PERT, if needed. Survival (median and 95% confidence interval [CI]) was analyzed using Kaplan–Meier and Cox regression; groups were compared using the log-rank test.

Results

Overall, 160 patients with unresectable pancreatic cancer were included in the analysis (mean age: 70.5 years [range 28–100]; gender: 57.5% male; tumor stage: 78.7% Stage IV). Eighty-six patients (53.75%) were in Group 1 and 74 (46.25%) were in Group 2. Age, gender, tumor size, location and stage, weight loss, and serum CA 19–9 were similar between groups. Ninety-three (58.1%) patients received palliative chemotherapy; 46.5% in Group 1 and 71.6% in Group 2 (P < 0.001). Forty-nine (66.2%) patients in Group 2 and none in Group 1 received PERT. Survival in Group 2 (189 days, 95% CI 167.0–211.0 days) was significantly longer than in Group 1 (95.0 days, 95% CI 75.4–114.6 days) (HR 2.117, 95% CI 1.493–3.002; P < 0.001). Chemotherapy and PERT were significantly and independently associated with longer survival in a model controlled by age and tumor stage. In patients with significant weight loss at diagnosis (> 10% bodyweight within 6 months), PERT was associated with longer survival (HR 2.52, 95% CI 1.55–4.11; P < 0.001).

Conclusions

In patients with unresectable pancreatic cancer, PERT in patients with PEI was associated with longer survival compared with those not receiving PERT, especially in those experiencing significant weight loss. This finding should guide future prospective clinical trials of similar interventions.

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Neuropilin-1 promotes the oncogenic Tenascin-C/ integrin β3 pathway and modulates chemoresistance in breast cancer cells

Abstract

Background

Neuropilin-1 (NRP-1), a non-tyrosine kinase glycoprotein receptor, is associated with poor prognosis breast cancer, however transcriptomic changes triggered by NRP-1 overexpression and its association with chemoresistance in breast cancer have not yet been explored.

Methods

BT-474 NRP-1 variant cells were generated by stable overexpression of NRP-1 in the BT-474 breast cancer cell line. RNA sequencing and qRT-PCR were conducted to identify differentially expressed genes. The role of an upregulated oncogene, Tenascin C (TNC) and its associated pathway was investigated by siRNA-mediated knockdown. Resistant variants of the control and BT-474 NRP-1 cells were generated by sequential treatment with four cycles of Adriamycin/Cyclophosphamide (4xAC) followed by four cycles of Paclitaxel (4xAC + 4xPAC).

Results

NRP-1 overexpression increased cellular tumorigenic behavior. RNA sequencing identified upregulation of an oncogene, Tenascin-C (TNC) and downregulation of several tumor suppressors in BT-474 NRP-1 cells. Additionally, protein analysis indicated activation of the TNC-associated integrin β3 (ITGB3) pathway via focal adhesion kinase (FAK), Akt (Ser473) and nuclear factor kappa B (NF-kB) p65. siRNA-mediated TNC knockdown ablated the migratory capacity of BT-474 NRP-1 cells and inactivated FAK/Akt473 signaling. NRP-1 overexpressing cells downregulated breast cancer resistance protein (BCRP/ABCG2). Consequently, sequential treatment with Adriamycin/Cyclophosphamide (AC) cytotoxic drugs to generate resistant cells indicated that BT-474 NRP-1 cells increased sensitivity to treatment by inactivating NRP-1/ITGB3/FAK/Akt/NF-kB p65 signaling compared to wild-type BT-474 resistant cells.

Conclusions

We thus report a novel mechanism correlating high baseline NRP-1 with upregulated TNC/ITGB3 signaling, but decreased ABCG2 expression, which sensitizes BT-474 NRP-1 cells to Adriamycin/Cyclophosphamide. The study emphasizes on the targetability of the NRP-1/ITGB3 axis and its potential as a predictive biomarker for chemotherapy response.

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Metabolomic profiles in breast cancer:a pilot case-control study in the breast cancer family registry

Abstract

Background

Metabolomics is emerging as an important tool for detecting differences between diseased and non-diseased individuals. However, prospective studies are limited.

Methods

We examined the detectability, reliability, and distribution of metabolites measured in pre-diagnostic plasma samples in a pilot study of women enrolled in the Northern California site of the Breast Cancer Family Registry. The study included 45 cases diagnosed with breast cancer at least one year after the blood draw, and 45 controls. Controls were matched on age (within 5 years), family status, BRCA status, and menopausal status. Duplicate samples were included for reliability assessment. We used a liquid chromatography/gas chromatography mass spectrometer platform to measure metabolites. We calculated intraclass correlations (ICCs) among duplicate samples, and coefficients of variation (CVs) across metabolites.

Results

Of the 661 named metabolites detected, 338 (51%) were found in all samples, and 490 (74%) in more than 80% of samples. The median ICC between duplicates was 0.96 (25th – 75th percentile: 0.82–0.99). We observed a greater than 20% case-control difference in 24 metabolites (p < 0.05), although these associations were not significant after adjusting for multiple comparisons.

Conclusions

These data show that assays are reproducible for many metabolites, there is a minimal laboratory variation for the same sample, and a large between-person variation. Despite small sample size, differences between cases and controls in some metabolites suggest that a well-powered large-scale study is likely to detect biological meaningful differences to provide a better understanding of breast cancer etiology.

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Systematic review of self-reported cognitive function in cancer patients following chemotherapy treatment

Abstract

Purpose

Cognitive symptoms are common in cancer patients, with up to 70% reporting cognitive symptoms following chemotherapy. These symptoms can have a major impact on how an individual functions in all aspects of their lives. This review evaluates self-reported cognitive function and its associations with neuropsychological tests and patient-reported outcomes in adult cancer patients who received chemotherapy treatment for a solid cancer.

Methods

A search of multiple databases (Medline, Ovid at Nursing, PsycINFO, Allied and Complementary Medicine) from 1936 to 2017 was conducted, identifying 1563 unique articles, of which 101 met inclusion criteria.

Results

Of the 101 included studies, 48 (47%) were cross-sectional and 38 (38%) longitudinal in design, with 12 (12%) randomised controlled trials. A minority (26%) incorporated a healthy control arm in the study design, whilst the majority (79%) were in women with breast cancer. There was diversity in the assessment of self-reported cognitive symptoms. A total of 43 of 44 studies that sought an association between self-reported cognitive function and patient-reported outcomes found a moderate to strong association. Overall, 31 studies showed a lack of association between self-reported cognitive symptoms and neuropsychological results, whilst 14 studies reported a significant association between the two, but the association was often restricted to limited cognitive domains.

Conclusion

The review found widespread heterogeneity in the assessment of self-reported cognitive symptoms and consistently absent or weak association with neuropsychological test scores.

Implications for Cancer Survivors

This research highlights the need for a standardised approach to measurement of self-reported cognitive symptoms in cancer patients.

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Systematic review of self-reported cognitive function in cancer patients following chemotherapy treatment

Abstract

Purpose

Cognitive symptoms are common in cancer patients, with up to 70% reporting cognitive symptoms following chemotherapy. These symptoms can have a major impact on how an individual functions in all aspects of their lives. This review evaluates self-reported cognitive function and its associations with neuropsychological tests and patient-reported outcomes in adult cancer patients who received chemotherapy treatment for a solid cancer.

Methods

A search of multiple databases (Medline, Ovid at Nursing, PsycINFO, Allied and Complementary Medicine) from 1936 to 2017 was conducted, identifying 1563 unique articles, of which 101 met inclusion criteria.

Results

Of the 101 included studies, 48 (47%) were cross-sectional and 38 (38%) longitudinal in design, with 12 (12%) randomised controlled trials. A minority (26%) incorporated a healthy control arm in the study design, whilst the majority (79%) were in women with breast cancer. There was diversity in the assessment of self-reported cognitive symptoms. A total of 43 of 44 studies that sought an association between self-reported cognitive function and patient-reported outcomes found a moderate to strong association. Overall, 31 studies showed a lack of association between self-reported cognitive symptoms and neuropsychological results, whilst 14 studies reported a significant association between the two, but the association was often restricted to limited cognitive domains.

Conclusion

The review found widespread heterogeneity in the assessment of self-reported cognitive symptoms and consistently absent or weak association with neuropsychological test scores.

Implications for Cancer Survivors

This research highlights the need for a standardised approach to measurement of self-reported cognitive symptoms in cancer patients.

https://ift.tt/2HPLdXl

Comparison of survival and prognostic factors in patients treated with stereotactic body radiotherapy for oligometastases or oligoprogression

Clinical challenges arise in the oligoprogressive (OP) state with little evidence to support the use of ablative strategies. Our aim is to report on outcomes and prognostic variables following stereotactic body radiotherapy (SBRT) for OP and oligometastases (OM).

https://ift.tt/2wdWDyX

Distinct shifts in the oral microbiota are associated with the progression and aggravation of mucositis during radiotherapy

Oral mucositis remains one of the most common complications of radiation therapy for patients with head and neck cancer. This study aimed to investigate the dynamic shifts in the oral mucosal microbiota and their association with the progression and aggravation of mucositis in patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy.

https://ift.tt/2jzLeQZ

Phase II trial of induction chemotherapy of pemetrexed plus split-dose cisplatin followed by pemetrexed maintenance for untreated non-squamous non-small-cell lung cancer

Abstract

Purpose

We conducted a phase II trial to evaluate the efficacy and safety of induction chemotherapy of pemetrexed plus split-dose cisplatin followed by pemetrexed maintenance for advanced non-squamous non-small-cell lung cancer (NSCLC).

Methods

Patients with advanced or recurrent untreated non-squamous NSCLC received split-dose cisplatin (40 mg/m², days 1 and 8) plus pemetrexed (500 mg/m², day 1) tri-weekly. After four cycles of induction, patients without disease progression received pemetrexed maintenance until disease progression or unacceptable toxicity. The primary endpoint was the 1-year survival rate. The secondary endpoints were progression-free survival (PFS), overall survival (OS), response in induction phase, and safety.

Results

From February 2012 to September 2014, 53 assessable patients were enrolled in this study. Thirty-eight (71.7%) patients completed induction therapy, while 35 (66.0%) received maintenance therapy. The 1-year survival rate was 67.7%. The median PFS and OS were 5.3 and 18.6 months, respectively. The response rate and disease control rate (DCR) during the induction phase were 37.7 and 86.8%, respectively. Eight patients (15.1%) discontinued the therapy due to adverse events (AEs) during the induction phase, but both hematological and non-hematological AEs were infrequent.

Conclusions

Treatment with induction chemotherapy of pemetrexed plus split-dose cisplatin showed a promising 1-year survival rate, DCR, and transition rate into maintenance phase. This regimen is feasible and well-tolerated. A phase III study comparing this regimen with conventional tri-weekly regimen is warranted.

https://ift.tt/2KE9nlG

Expression of M2 macrophage markers YKL-39 and CCL18 in breast cancer is associated with the effect of neoadjuvant chemotherapy

Abstract

Purpose

High activity of enzyme TOP2a in tumor cells is known to be associated with sensitivity to anthracycline chemotherapy, but 20% of such patients do not show clinical response. Tumor microenvironment, including tumor-associated macrophages (TAM), is an essential factor defining the efficiency of chemotherapy. In the present study, we analyzed the expression of M2 macrophage markers, YKL-39 and CCL18, in tumors of breast cancer patients received anthracycline-based NAC.

Methods

Patients were divided into two groups according to the level of doxorubicin sensitivity marker TOP2a: DOX-Sense and DOX-Res groups. Expression levels of TOR2a, CD68, YKL-39 and CCL18 genes were analyzed by qPCR, the amplification of TOR2a gene locus was assessed by the microarray assay. Clinical and pathological responses to neoadjuvant chemotherapy were assessed.

Results

We found that the average level of TOP2a expression in patients of DOX-Sense group was almost 10 times higher than in patients of DOX-Res group, and the expression of CD68 was 3 times higher in the DOX-Sense group compared to DOX-Res group. We demonstrated that expression levels of M2-derived cytokines but not the amount of TAM is indicative for clinical and pathological chemotherapy efficacy in breast cancer patients. Out of 8 patients from DOX-Sense group who did not respond to neoadjuvant chemotherapy (NAC), 7 patients had M2+ macrophage phenotype (YKL-39⁺CCL18⁻ or YKL-39⁻CCL18⁺) and only one patient had M2− macrophage phenotype (YKL-39⁻CCL18⁻). In DOX-Res group, out of 14 patients who clinically responded to NAC 9 patients had M2− phenotype and only 5 patients had M2+ macrophage phenotype. Among pathological non-responders in DOX-Sense group, 19 (82%) patients had M2+ tumor phenotype and only 4 (18%) patients had M2− phenotype. In DOX-Res group, all 5 patients who pathologically responded to NAC had M2 phenotype (YKL-39⁻CCL18⁻). Unlike the clinical response to NAC, the differences in the frequency of M2+ and M2− phenotypes between pathologically responding and non-responding patients within DOX-Sense and DOX-Res groups were statistically significant.

Conclusions

Thus, we showed that in patients with breast cancer who received anthracycline-containing NAC the absence of clinical response is associated with the presence of M2+ macrophage phenotype (YKL-39-CCL18 + or YKL-39 + CCL18-) based on TOP2a overexpression data.

https://ift.tt/2FJrtz3

Phase II trial of induction chemotherapy of pemetrexed plus split-dose cisplatin followed by pemetrexed maintenance for untreated non-squamous non-small-cell lung cancer

Abstract

Purpose

We conducted a phase II trial to evaluate the efficacy and safety of induction chemotherapy of pemetrexed plus split-dose cisplatin followed by pemetrexed maintenance for advanced non-squamous non-small-cell lung cancer (NSCLC).

Methods

Patients with advanced or recurrent untreated non-squamous NSCLC received split-dose cisplatin (40 mg/m², days 1 and 8) plus pemetrexed (500 mg/m², day 1) tri-weekly. After four cycles of induction, patients without disease progression received pemetrexed maintenance until disease progression or unacceptable toxicity. The primary endpoint was the 1-year survival rate. The secondary endpoints were progression-free survival (PFS), overall survival (OS), response in induction phase, and safety.

Results

From February 2012 to September 2014, 53 assessable patients were enrolled in this study. Thirty-eight (71.7%) patients completed induction therapy, while 35 (66.0%) received maintenance therapy. The 1-year survival rate was 67.7%. The median PFS and OS were 5.3 and 18.6 months, respectively. The response rate and disease control rate (DCR) during the induction phase were 37.7 and 86.8%, respectively. Eight patients (15.1%) discontinued the therapy due to adverse events (AEs) during the induction phase, but both hematological and non-hematological AEs were infrequent.

Conclusions

Treatment with induction chemotherapy of pemetrexed plus split-dose cisplatin showed a promising 1-year survival rate, DCR, and transition rate into maintenance phase. This regimen is feasible and well-tolerated. A phase III study comparing this regimen with conventional tri-weekly regimen is warranted.

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Expression of M2 macrophage markers YKL-39 and CCL18 in breast cancer is associated with the effect of neoadjuvant chemotherapy

Abstract

Purpose

High activity of enzyme TOP2a in tumor cells is known to be associated with sensitivity to anthracycline chemotherapy, but 20% of such patients do not show clinical response. Tumor microenvironment, including tumor-associated macrophages (TAM), is an essential factor defining the efficiency of chemotherapy. In the present study, we analyzed the expression of M2 macrophage markers, YKL-39 and CCL18, in tumors of breast cancer patients received anthracycline-based NAC.

Methods

Patients were divided into two groups according to the level of doxorubicin sensitivity marker TOP2a: DOX-Sense and DOX-Res groups. Expression levels of TOR2a, CD68, YKL-39 and CCL18 genes were analyzed by qPCR, the amplification of TOR2a gene locus was assessed by the microarray assay. Clinical and pathological responses to neoadjuvant chemotherapy were assessed.

Results

We found that the average level of TOP2a expression in patients of DOX-Sense group was almost 10 times higher than in patients of DOX-Res group, and the expression of CD68 was 3 times higher in the DOX-Sense group compared to DOX-Res group. We demonstrated that expression levels of M2-derived cytokines but not the amount of TAM is indicative for clinical and pathological chemotherapy efficacy in breast cancer patients. Out of 8 patients from DOX-Sense group who did not respond to neoadjuvant chemotherapy (NAC), 7 patients had M2+ macrophage phenotype (YKL-39⁺CCL18⁻ or YKL-39⁻CCL18⁺) and only one patient had M2− macrophage phenotype (YKL-39⁻CCL18⁻). In DOX-Res group, out of 14 patients who clinically responded to NAC 9 patients had M2− phenotype and only 5 patients had M2+ macrophage phenotype. Among pathological non-responders in DOX-Sense group, 19 (82%) patients had M2+ tumor phenotype and only 4 (18%) patients had M2− phenotype. In DOX-Res group, all 5 patients who pathologically responded to NAC had M2 phenotype (YKL-39⁻CCL18⁻). Unlike the clinical response to NAC, the differences in the frequency of M2+ and M2− phenotypes between pathologically responding and non-responding patients within DOX-Sense and DOX-Res groups were statistically significant.

Conclusions

Thus, we showed that in patients with breast cancer who received anthracycline-containing NAC the absence of clinical response is associated with the presence of M2+ macrophage phenotype (YKL-39-CCL18 + or YKL-39 + CCL18-) based on TOP2a overexpression data.

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Identification of aberrantly expressed F-box proteins in squamous-cell lung carcinoma

Abstract

Purpose

F-box proteins, as components of the Skp1-Cullin 1-F-box protein (SCF) E3 ubiquitin ligase, can specifically bind to substrates and regulate multiple tumor behaviors. However, the role of F-box proteins in squamous-cell lung carcinoma (SqCLC) has not been established.

Methods

We identified the differentially expressed F-box protein-encoding genes in SqCLC by analyzing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Prognosis data were evaluated using the Kaplan–Meier (KM) plotter website. The FBXO5 and FBXO45 mRNA levels were analyzed by real time RT-PCR. The impact of the inhibition of these genes with si-RNA on apoptosis and migration was also investigated.

Results

The FBXO45 and FBXO5 genes were significantly up-regulated in SqCLC compared with normal lung (p values = 0.002 and 0.025, respectively). FBXO45 was significantly elevated in each tumorigenic step, including dysplasia, in situ and SqCLC. The RT-PCR analysis results showed that FBXO5 and FBXO45 were elevated in cancer tissues (p values = 0.024 and 0.004, respectively). Overexpression of FBXO5 and FBXO45 was associated with shorter overall survival (OS) in the SqCLC patients from the K–M plotter database [FBXO5 HR: 1.53 (1.03–2.28), p = 0.036]; [FBXO45 HR: 1.47 (1.03–2.08), p = 0.030]. The GO and KEGG pathway analysis showed that FBXO5 and FBXO45 were associated with cell cycle and adhesion, respectively. Knockdown of FBXO5 leads to increased apoptosis, while knockdown of FBXO45 facilitates the process of epithelial–mesenchymal transition (EMT).

Conclusions

Our results provide evidence that FBXO45 and FBXO5 may play a key role in tumorigenesis and prognosis of SqCLC.

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Identification of aberrantly expressed F-box proteins in squamous-cell lung carcinoma

Abstract

Purpose

F-box proteins, as components of the Skp1-Cullin 1-F-box protein (SCF) E3 ubiquitin ligase, can specifically bind to substrates and regulate multiple tumor behaviors. However, the role of F-box proteins in squamous-cell lung carcinoma (SqCLC) has not been established.

Methods

We identified the differentially expressed F-box protein-encoding genes in SqCLC by analyzing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Prognosis data were evaluated using the Kaplan–Meier (KM) plotter website. The FBXO5 and FBXO45 mRNA levels were analyzed by real time RT-PCR. The impact of the inhibition of these genes with si-RNA on apoptosis and migration was also investigated.

Results

The FBXO45 and FBXO5 genes were significantly up-regulated in SqCLC compared with normal lung (p values = 0.002 and 0.025, respectively). FBXO45 was significantly elevated in each tumorigenic step, including dysplasia, in situ and SqCLC. The RT-PCR analysis results showed that FBXO5 and FBXO45 were elevated in cancer tissues (p values = 0.024 and 0.004, respectively). Overexpression of FBXO5 and FBXO45 was associated with shorter overall survival (OS) in the SqCLC patients from the K–M plotter database [FBXO5 HR: 1.53 (1.03–2.28), p = 0.036]; [FBXO45 HR: 1.47 (1.03–2.08), p = 0.030]. The GO and KEGG pathway analysis showed that FBXO5 and FBXO45 were associated with cell cycle and adhesion, respectively. Knockdown of FBXO5 leads to increased apoptosis, while knockdown of FBXO45 facilitates the process of epithelial–mesenchymal transition (EMT).

Conclusions

Our results provide evidence that FBXO45 and FBXO5 may play a key role in tumorigenesis and prognosis of SqCLC.

https://ift.tt/2FJlk5T

Free-breathing quantification of hepatic fat in healthy children and children with nonalcoholic fatty liver disease using a multi-echo 3-D stack-of-radial MRI technique

Abstract

Background

In adults, noninvasive chemical shift encoded Cartesian magnetic resonance imaging (MRI) and single-voxel magnetic resonance (MR) spectroscopy (SVS) accurately quantify hepatic steatosis but require breath-holding. In children, especially young and sick children, breath-holding is often limited or not feasible. Sedation can facilitate breath-holding but is highly undesirable. For these reasons, there is a need to develop free-breathing MRI technology that accurately quantifies steatosis in all children.

Objective

This study aimed to compare non-sedated free-breathing multi-echo 3-D stack-of-radial (radial) MRI versus standard breath-holding MRI and SVS techniques in a group of children for fat quantification with respect to image quality, accuracy and repeatability.

Materials and methods

Healthy children (n=10, median age [±interquartile range]: 10.9 [±3.3] years) and overweight children with nonalcoholic fatty liver disease (NAFLD) (n=9, median age: 15.2 [±3.2] years) were imaged at 3 Tesla using free-breathing radial MRI, breath-holding Cartesian MRI and breath-holding SVS. Acquisitions were performed twice to assess repeatability (within-subject mean difference, MD_within). Images and hepatic proton-density fat fraction (PDFF) maps were scored for image quality. Free-breathing and breath-holding PDFF were compared using linear regression (correlation coefficient, r and concordance correlation coefficient, ρ_c) and Bland-Altman analysis (mean difference). P<0.05 was considered significant.

Results

In patients with NAFLD, free-breathing radial MRI demonstrated significantly less motion artifacts compared to breath-holding Cartesian (P<0.05). Free-breathing radial PDFF demonstrated a linear relationship (P<0.001) versus breath-holding SVS PDFF and breath-holding Cartesian PDFF with r=0.996 and ρ_c=0.994, and r=0.997 and ρ_c=0.995, respectively. The mean difference in PDFF between free-breathing radial MRI, breath-holding Cartesian MRI and breath-holding SVS was <0.7%. Repeated free-breathing radial MRI had MD_within=0.25% for PDFF.

Conclusion

In this pediatric study, non-sedated free-breathing radial MRI provided accurate and repeatable hepatic PDFF measurements and improved image quality, compared to standard breath-holding MR techniques.

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Free-breathing quantification of hepatic fat in healthy children and children with nonalcoholic fatty liver disease using a multi-echo 3-D stack-of-radial MRI technique

Abstract

Background

In adults, noninvasive chemical shift encoded Cartesian magnetic resonance imaging (MRI) and single-voxel magnetic resonance (MR) spectroscopy (SVS) accurately quantify hepatic steatosis but require breath-holding. In children, especially young and sick children, breath-holding is often limited or not feasible. Sedation can facilitate breath-holding but is highly undesirable. For these reasons, there is a need to develop free-breathing MRI technology that accurately quantifies steatosis in all children.

Objective

This study aimed to compare non-sedated free-breathing multi-echo 3-D stack-of-radial (radial) MRI versus standard breath-holding MRI and SVS techniques in a group of children for fat quantification with respect to image quality, accuracy and repeatability.

Materials and methods

Healthy children (n=10, median age [±interquartile range]: 10.9 [±3.3] years) and overweight children with nonalcoholic fatty liver disease (NAFLD) (n=9, median age: 15.2 [±3.2] years) were imaged at 3 Tesla using free-breathing radial MRI, breath-holding Cartesian MRI and breath-holding SVS. Acquisitions were performed twice to assess repeatability (within-subject mean difference, MD_within). Images and hepatic proton-density fat fraction (PDFF) maps were scored for image quality. Free-breathing and breath-holding PDFF were compared using linear regression (correlation coefficient, r and concordance correlation coefficient, ρ_c) and Bland-Altman analysis (mean difference). P<0.05 was considered significant.

Results

In patients with NAFLD, free-breathing radial MRI demonstrated significantly less motion artifacts compared to breath-holding Cartesian (P<0.05). Free-breathing radial PDFF demonstrated a linear relationship (P<0.001) versus breath-holding SVS PDFF and breath-holding Cartesian PDFF with r=0.996 and ρ_c=0.994, and r=0.997 and ρ_c=0.995, respectively. The mean difference in PDFF between free-breathing radial MRI, breath-holding Cartesian MRI and breath-holding SVS was <0.7%. Repeated free-breathing radial MRI had MD_within=0.25% for PDFF.

Conclusion

In this pediatric study, non-sedated free-breathing radial MRI provided accurate and repeatable hepatic PDFF measurements and improved image quality, compared to standard breath-holding MR techniques.

https://ift.tt/2JTmq1r

Potential impact of invasive surgical procedures on primary tumor growth and metastasis

Abstract

Surgical procedures such as tumor resection and biopsy are still the gold standard for diagnosis and (determination of) treatment of solid tumors, and are prognostically beneficial for patients. However, growing evidence suggests that even a minor surgical trauma can influence several (patho) physiological processes that might promote postoperative metastatic spread and tumor recurrence. Local effects include tumor seeding and a wound healing response that can promote tumor cell migration, proliferation, differentiation, extracellular matrix remodeling, angiogenesis and extravasation. In addition, local and systemic immunosuppression impairs antitumor immunity and contributes to tumor cell survival. Surgical manipulation of the tumor can result in cancer cell release into the circulation, thus increasing the chance of tumor cell dissemination. To prevent these undesired effects of surgical interventions, therapeutic strategies targeting immune response exacerbation or alteration have been proposed. This review summarizes the current literature regarding these local, systemic and secondary site effects of surgical interventions on tumor progression and dissemination, and discusses studies that aimed to identify potential therapeutic approaches to prevent these effects in order to further increase the clinical benefit from surgical procedures.

https://ift.tt/2rrfyl9

Potential impact of invasive surgical procedures on primary tumor growth and metastasis

Abstract

Surgical procedures such as tumor resection and biopsy are still the gold standard for diagnosis and (determination of) treatment of solid tumors, and are prognostically beneficial for patients. However, growing evidence suggests that even a minor surgical trauma can influence several (patho) physiological processes that might promote postoperative metastatic spread and tumor recurrence. Local effects include tumor seeding and a wound healing response that can promote tumor cell migration, proliferation, differentiation, extracellular matrix remodeling, angiogenesis and extravasation. In addition, local and systemic immunosuppression impairs antitumor immunity and contributes to tumor cell survival. Surgical manipulation of the tumor can result in cancer cell release into the circulation, thus increasing the chance of tumor cell dissemination. To prevent these undesired effects of surgical interventions, therapeutic strategies targeting immune response exacerbation or alteration have been proposed. This review summarizes the current literature regarding these local, systemic and secondary site effects of surgical interventions on tumor progression and dissemination, and discusses studies that aimed to identify potential therapeutic approaches to prevent these effects in order to further increase the clinical benefit from surgical procedures.

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Detection of alternative subpleural lymph flow pathways using indocyanine green fluorescence

Abstract

Purpose

Pulmonary lymphatic fluid predominately flows along the bronchi. However, there are reports suggesting that an alternative lymphatic pathway exist, which may result in skip metastases. The aim of this study was to evaluate the subpleural lymph flow in vivo using indocyanine green (ICG) fluorescence.

Methods

One hundred cases were enrolled. ICG was injected into the macroscopically healthy subpleural space. Intraoperative fluorescence images were then observed in real time.

Results

ICG fluorescence was observed moving through subpleural channels in 58/100 cases. ICG flowed into adjacent lobes over interlobar lines in 18 cases and flowed from the visceral pleura directly into the mediastinum in 5 cases. The frequency of mediastinal detection without hilar lymph node detection was significantly higher in the left lung compared to the right (p < 0.05). The subpleural lymph flow detection rates were significantly lower in patients with smoking pack-years ≥ 40 than those with < 40 (p < 0.05).

Conclusions

The flow of lymphatic fluid directly into the mediastinum suggests one mechanism of skip metastasis. In addition, the reduction of the subpleural lymph flows in smokers with ≥ 40 pack-years suggests that smoking might modify lymph flow patterns. These findings may assist in selecting the optimal therapy for patients with possible skip metastasis.

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The attenuation value of preoperative computed tomography as a novel predictor for pancreatic fistula after pancreaticoduodenectomy

Abstract

Purpose

Pancreatic fistula (PF) is the most serious complication following pancreaticoduodenectomy (PD). This study was performed to identify new clinical factors that may predict the development of PF after PD to improve perioperative management.

Methods

Seventy-five consecutive patients who underwent PD from 2012 to 2015 were evaluated. The patients' perioperative data including the computed tomography (CT) parameters were collected. The minimum, maximum, and mean CT attenuation values (HU_min, HU_max, and HU_mean, respectively) were extracted from the pancreatic parenchyma (≥ 100 pixels), and the standard deviation of these values (HU_SD) was determined from the slice in which the superior mesenteric and splenic veins were merged. PF was defined as grade B or C according to the International Study Group for Pancreatic Fistula criteria.

Results

The PF occurrence rate (grade B or C) was 25.3% in 75 patients. A multivariate analysis identified a larger HU_SD (odds ratio 3.092; 95% CI 1.018–9.394) and higher amylase concentration in drainage fluid on postoperative day 1 (odds ratio 1.0001; 95% CI 1.00001–1.00022) as significant risk factors for PF.

Conclusions

The HU_SD of preoperative CT attenuation values in the pancreatic parenchyma was found to be an independent predictor for PF after PD and it might therefore positively contribute to the perioperative management of PD.

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Significance of bacterial culturing of prophylactic drainage fluid in the early postoperative period after liver resection for predicting the development of surgical site infections

Abstract

Purposes

The relationship between the results of bacterial drainage fluid cultures in the early postoperative period after liver resection and the development of surgical site infections (SSIs) is unclear. We evaluated the diagnostic value of bacterial cultures of drainage fluid obtained on postoperative day (POD) 1 after liver resection.

Methods

The cases of all consecutive patients who underwent elective liver resection from January 2014 to December 2016 were analyzed. The association between a positive culture result and the development of SSIs was analyzed.

Results

A total of 195 consecutive patients were studied. Positive drainage fluid cultures were obtained in 6 patients (3.1%). A multivariate analysis revealed that a positive drainage fluid culture was an independent risk factor for SSIs (odds ratio: 8.04, P = 0.035), and combined resection of the gastrointestinal tract was a risk factor for a positive drainage fluid culture (P = 0.006). Among the patients who did not undergo procedures involving the gastrointestinal tract, there was no association between drainage fluid culture positivity and SSIs.

Conclusions

The detection of positive culture results for drainage fluid collected on POD 1 after liver resection was associated with SSIs. However, among patients who did not undergo procedures involving the gastrointestinal tract, it was not a predictor of SSIs.

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Postoperative therapy with infliximab for Crohn’s disease: a 2-year prospective randomized multicenter study in Japan

Abstract

Purpose

The prevention of postoperative recurrence is a critical issue in surgery for Crohn's disease. Prospective randomized trials in Western countries have shown that the postoperative use of anti-tumor necrosis factor α-antibodies was effective in reducing the recurrence rate. We investigated the efficacy of infliximab (IFX) for the prevention of postoperative Crohn's disease recurrence.

Methods

We performed a prospective randomized multicenter study. Patients who underwent intestinal resection were assigned to groups treated with or without IFX. Immediately after surgery, patients in the IFX group received IFX at 5 mg/kg at 0, 2, and 6 weeks, followed by every 8 weeks for 2 years. The primary study outcome was the proportion of patients with endoscopic and/or clinical recurrence at 2 years after surgery.

Results

Thirty-eight eligible patients participated in this study: 19 in the IFX group and 19 in the non-IFX group. The disease recurrence rate in the IFX group was 52.6% (10/19), which was significantly lower than that in the non-IFX group (94.7% [18/19]).

Conclusion

The postoperative use of IFX is effective in preventing Crohn's disease recurrence for 2 years.

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The impact of the Charlson comorbidity index on the prognosis of esophageal cancer patients who underwent esophagectomy with curative intent

Abstract

Purpose

The aim of this study was to clarify the influence of Charlson comorbidity index (CCI) on treatment options, and on short- and mid-term outcomes in esophageal cancer patients who underwent esophagectomy.

Methods

Patients who underwent curative-intent esophagectomy from 2009 to 2014 were classified by CCI. A CCI of ≥ 2 was defined as high, while a CCI of 0 or 1 was classified as low. Clinicopathological parameters, including overall survival (OS) and disease-specific survival (DSS), were compared between the groups.

Results

Among 548 patients, the most frequent comorbidity was chronic obstructive pulmonary disease (n = 142, 25.9%), followed by solid tumor (n = 79, 14.4%). A high CCI was significantly correlated with older age (P < 0.001), surgery alone (P = 0.020), a lower number of dissected lymph nodes (P < 0.001), lower rate of R0 resection (P = 0.048), and prolonged hospital stay (P < 0.001). In the low group, OS after surgery was favorable in comparison to the the high group. Although DSS was comparable between the groups, the CCI was significantly associated with a poor prognosis in patients with stage ≥ II disease.

Conclusions

The CCI was significantly correlated with the prognosis of esophageal cancer patients who underwent curative-intent esophagectomy.

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Non-incisional pleurectomy–decortication for malignant pleural mesothelioma

Abstract

Pleurectomy–decortication (P/D) is lung-sparing surgery with curative intent for malignant pleural mesothelioma (MPM). Visceral pleurectomy is the most challenging step in this procedure. At the beginning of pleurectomy, a sharp pleural incision through the tumor is usually made to create the dissection plane between the visceral pleura and the lung parenchyma, which may cause the spread of tumor cells into the operation field. Here, we describe a sophisticated surgical technique of P/D without any pleural incision ("non-incisional P/D") to achieve en bloc removal of the entire pleura and tumor, which may improve postoperative survival by preventing tumor spread.

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A novel suction/coagulation integrated probe for achieving better hemostasis: development and clinical use

Abstract

Purposes

Modern electrosurgical tools have a specific coagulation mode called "soft coagulation". However, soft coagulation has not been widely accepted for surgical operations. To optimize the soft coagulation environment, we developed a novel suction device integrated with an electrosurgical probe, called the "Suction ball coagulator" (SBC). In this study, we aimed to optimize the SBC design with a prototyping process involving a bench test and preclinical study; then, we aimed to demonstrate the feasibility, safety, and potential effectiveness of the SBC for laparoscopic surgery in clinical settings.

Methods

SBC prototyping was performed with a bench test. Device optimization was performed in a preclinical study with a domestic swine bleeding model. Then, SBC was tested in a clinical setting during 17 clinical laparoscopic colorectal surgeries.

Results

In the bench tests, two tip hole sizes and patterns showed a good suction capacity. The preclinical study indicated the best tip shape for accuracy. In clinical use, no device-related adverse event was observed. Moreover, the SBC was feasible for prompt hemostasis and blunt dissections. In addition, SBC could evacuate vapors generated by tissue ablation using electroprobe during laparoscopic surgery.

Conclusions

We successfully developed a novel, integrated suction/coagulation probe for hemostasis and commercialized it.

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National survey of de novo malignancy after solid organ transplantation in Japan

Abstract

Purpose

In Japan, there have been no national surveys on the incidence of de novo malignancy after solid organ transplantation, which is one of the leading causes of death in transplant recipients.

Methods

A questionnaire was distributed to institutions that perform solid organ transplantation in Japan, and clinical information was collected from patients who underwent transplantation between 2001 and 2010 and who exhibited de novo malignancies.

Results

Nine thousand two hundred ten solid organ transplants (kidney, 49.9%; liver, 45.9%; heart, 0.9%; lung, 1.2%; pancreas, 1.9%; small intestine, 0.2%) were performed. Four hundred seventy-nine (5.2%) cases of de novo malignancy were identified. The transplanted organs of the patients included the kidney (n = 479, 54.8%), liver (n = 186, 38.8%), heart (n = 5, 0.1%), lung (n = 18, 3.8%), pancreas (n = 9, 1.9%), and small intestine (n = 1, 0.02%). The most common malignancies were post-transplant lymphoproliferative disorder (n = 87) and cancers of the kidney (n = 43), stomach (n = 41), large intestine (n = 41), and lung (n = 36).

Conclusions

This is the first national survey of the incidence of de novo malignancy in Japan. Further study is required to identify the risk of de novo malignancy in organ transplant recipients in comparison to the general population, namely the standardized incidence ratio.

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Preservation of the nipple–areola complex in skin-sparing mastectomy for early breast cancer

Abstract

Purpose

Skin-sparing mastectomy (SSM) enables a radical cure of breast cancer while overcoming the cosmetic issues related to surgery. We review our experience of performing SSMs and assess whether preservation of the nipple–areola complex (NAC) could have been an option for some patients who underwent SSM.

Methods

The subjects of this retrospective study were women who underwent SSM that utilized four incision types; namely, the so-called tennis racket incision, a periareolar and midaxillary incision, an areola-sparing and midaxillary incision, and a small transverse elliptical incision. We assessed whether preservation of the NAC would have been an option in SSM, based on histologic examination of three serial cut surfaces of the specimen around the nipple, ruling out the option when evidence of the malignant lesion/s was found in at least one of the following locations: in the nipple, within a 1-cm radius from the base of the nipple, or within 1 cm from the surface of the NAC.

Results

We performed 193 SSMs. The cumulative 10-year local disease-free survival rate was 98%, with 89% of patients reporting levels of satisfaction with the reconstructed breast, of excellent, very good, or good. We evaluated that 70 of the 193 procedures could have been performed as nipple-sparing mastectomy (NSM).

Conclusions

The outcomes of SSM in this series were excellent and NSM might have been an option for about one-third of the patients.

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Postoperative adalimumab maintenance therapy for Japanese patients with Crohn’s disease: a single-center, single-arm phase II trial (CCOG-1107 study)

Abstract

Purpose

To investigate the efficacy and safety of planned postoperative adalimumab (ADA) therapy for Japanese patients with Crohn's disease (CD).

Methods

The subjects of this study were 26 patients who underwent bowel resection for CD. All patients received subcutaneous injections of ADA 160/80 mg at the time of surgery and 2 weeks later, followed by 40 mg every 2 weeks thereafter. The primary endpoint of this study was the incidence of endoscopic recurrence, defined by Rutgeerts endoscopic recurrence scale ≥ i2, 1 year after surgery.

Results

After the median follow-up period of 41.3 months, the median number of treatments with ADA was 56 and the median time-to-treatment failure was 25.6 months. Endoscopic recurrence was observed in 34.6% of the patients 1 year after surgery. Univariate analyses showed that preoperative ADA therapy was significantly associated with endoscopic recurrence. Clinical recurrence developed in 16.7% of the patients within 1 year after surgery. Secondary surgery for recurrence was not required. Although adverse events (≥ grade 3) were experienced by 15.4% of patients, none was withdrawn from this study.

Conclusion

Planned postoperative ADA therapy reduced the incidence of endoscopic and clinical recurrence after bowel resection in Japanese patients with CD.

Trial registration

This trial is registered with the University Hospital Medical Information Network (UMIN000007514).

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Identifying risk factors for L’Hermitte’s sign after IMRT for head and neck cancer

Abstract

Background

L'Hermitte's sign (LS) after chemoradiotherapy for head and neck cancer appears related to higher spinal cord doses. IMRT plans limit spinal cord dose, but the incidence of LS remains high.

Methods

One hundred seventeen patients treated with TomoTherapy™ between 2008 and 2015 prospectively completed a side-effect questionnaire (VoxTox Trial Registration: UK CRN ID 13716). Baseline patient and treatment data were collected. Radiotherapy plans were analysed; mean and maximum spinal cord dose and volumes receiving 10, 20, 30 and 40 Gy were recorded. Dose variation across the cord was examined. These data were included in a logistic regression model.

Results

Forty two patients (35.9%) reported LS symptoms. Concurrent weekly cisplatin did not increase LS risk (p = 0.70, OR = 1.23 {95% CI 0.51–2.34}). Of 13 diabetic participants (9 taking metformin), only 1 developed LS (p = 0.025, OR = 0.13 {95% CI 0.051–3.27}). A refined binary logistic regression model showed that patients receiving unilateral radiation (p = 0.019, OR = 2.06 {95% CI 0.15–0.84}) were more likely to develop LS. Higher V_40Gy (p = 0.047, OR = 1.06 {95% CI 1.00–1.12}), and younger age (mean age 56.6 vs 59.7, p = 0.060, OR = 0.96 {95% CI 0.92–1.00}) were associated with elevated risk of LS, with borderline significance.

Conclusions

In this cohort, concomitant cisplatin did not increase risk, and LS incidence was lower in diabetic patients. Patient age and dose gradients across the spinal cord may be important factors.

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Detection of alternative subpleural lymph flow pathways using indocyanine green fluorescence

Abstract

Purpose

Pulmonary lymphatic fluid predominately flows along the bronchi. However, there are reports suggesting that an alternative lymphatic pathway exist, which may result in skip metastases. The aim of this study was to evaluate the subpleural lymph flow in vivo using indocyanine green (ICG) fluorescence.

Methods

One hundred cases were enrolled. ICG was injected into the macroscopically healthy subpleural space. Intraoperative fluorescence images were then observed in real time.

Results

ICG fluorescence was observed moving through subpleural channels in 58/100 cases. ICG flowed into adjacent lobes over interlobar lines in 18 cases and flowed from the visceral pleura directly into the mediastinum in 5 cases. The frequency of mediastinal detection without hilar lymph node detection was significantly higher in the left lung compared to the right (p < 0.05). The subpleural lymph flow detection rates were significantly lower in patients with smoking pack-years ≥ 40 than those with < 40 (p < 0.05).

Conclusions

The flow of lymphatic fluid directly into the mediastinum suggests one mechanism of skip metastasis. In addition, the reduction of the subpleural lymph flows in smokers with ≥ 40 pack-years suggests that smoking might modify lymph flow patterns. These findings may assist in selecting the optimal therapy for patients with possible skip metastasis.

https://ift.tt/2DNyXET

The attenuation value of preoperative computed tomography as a novel predictor for pancreatic fistula after pancreaticoduodenectomy

Abstract

Purpose

Pancreatic fistula (PF) is the most serious complication following pancreaticoduodenectomy (PD). This study was performed to identify new clinical factors that may predict the development of PF after PD to improve perioperative management.

Methods

Seventy-five consecutive patients who underwent PD from 2012 to 2015 were evaluated. The patients' perioperative data including the computed tomography (CT) parameters were collected. The minimum, maximum, and mean CT attenuation values (HU_min, HU_max, and HU_mean, respectively) were extracted from the pancreatic parenchyma (≥ 100 pixels), and the standard deviation of these values (HU_SD) was determined from the slice in which the superior mesenteric and splenic veins were merged. PF was defined as grade B or C according to the International Study Group for Pancreatic Fistula criteria.

Results

The PF occurrence rate (grade B or C) was 25.3% in 75 patients. A multivariate analysis identified a larger HU_SD (odds ratio 3.092; 95% CI 1.018–9.394) and higher amylase concentration in drainage fluid on postoperative day 1 (odds ratio 1.0001; 95% CI 1.00001–1.00022) as significant risk factors for PF.

Conclusions

The HU_SD of preoperative CT attenuation values in the pancreatic parenchyma was found to be an independent predictor for PF after PD and it might therefore positively contribute to the perioperative management of PD.

https://ift.tt/2rke4ZB

Significance of bacterial culturing of prophylactic drainage fluid in the early postoperative period after liver resection for predicting the development of surgical site infections

Abstract

Purposes

The relationship between the results of bacterial drainage fluid cultures in the early postoperative period after liver resection and the development of surgical site infections (SSIs) is unclear. We evaluated the diagnostic value of bacterial cultures of drainage fluid obtained on postoperative day (POD) 1 after liver resection.

Methods

The cases of all consecutive patients who underwent elective liver resection from January 2014 to December 2016 were analyzed. The association between a positive culture result and the development of SSIs was analyzed.

Results

A total of 195 consecutive patients were studied. Positive drainage fluid cultures were obtained in 6 patients (3.1%). A multivariate analysis revealed that a positive drainage fluid culture was an independent risk factor for SSIs (odds ratio: 8.04, P = 0.035), and combined resection of the gastrointestinal tract was a risk factor for a positive drainage fluid culture (P = 0.006). Among the patients who did not undergo procedures involving the gastrointestinal tract, there was no association between drainage fluid culture positivity and SSIs.

Conclusions

The detection of positive culture results for drainage fluid collected on POD 1 after liver resection was associated with SSIs. However, among patients who did not undergo procedures involving the gastrointestinal tract, it was not a predictor of SSIs.

https://ift.tt/2EnKdok

Postoperative therapy with infliximab for Crohn’s disease: a 2-year prospective randomized multicenter study in Japan

Abstract

Purpose

The prevention of postoperative recurrence is a critical issue in surgery for Crohn's disease. Prospective randomized trials in Western countries have shown that the postoperative use of anti-tumor necrosis factor α-antibodies was effective in reducing the recurrence rate. We investigated the efficacy of infliximab (IFX) for the prevention of postoperative Crohn's disease recurrence.

Methods

We performed a prospective randomized multicenter study. Patients who underwent intestinal resection were assigned to groups treated with or without IFX. Immediately after surgery, patients in the IFX group received IFX at 5 mg/kg at 0, 2, and 6 weeks, followed by every 8 weeks for 2 years. The primary study outcome was the proportion of patients with endoscopic and/or clinical recurrence at 2 years after surgery.

Results

Thirty-eight eligible patients participated in this study: 19 in the IFX group and 19 in the non-IFX group. The disease recurrence rate in the IFX group was 52.6% (10/19), which was significantly lower than that in the non-IFX group (94.7% [18/19]).

Conclusion

The postoperative use of IFX is effective in preventing Crohn's disease recurrence for 2 years.

https://ift.tt/2rkdZVN

The impact of the Charlson comorbidity index on the prognosis of esophageal cancer patients who underwent esophagectomy with curative intent

Abstract

Purpose

The aim of this study was to clarify the influence of Charlson comorbidity index (CCI) on treatment options, and on short- and mid-term outcomes in esophageal cancer patients who underwent esophagectomy.

Methods

Patients who underwent curative-intent esophagectomy from 2009 to 2014 were classified by CCI. A CCI of ≥ 2 was defined as high, while a CCI of 0 or 1 was classified as low. Clinicopathological parameters, including overall survival (OS) and disease-specific survival (DSS), were compared between the groups.

Results

Among 548 patients, the most frequent comorbidity was chronic obstructive pulmonary disease (n = 142, 25.9%), followed by solid tumor (n = 79, 14.4%). A high CCI was significantly correlated with older age (P < 0.001), surgery alone (P = 0.020), a lower number of dissected lymph nodes (P < 0.001), lower rate of R0 resection (P = 0.048), and prolonged hospital stay (P < 0.001). In the low group, OS after surgery was favorable in comparison to the the high group. Although DSS was comparable between the groups, the CCI was significantly associated with a poor prognosis in patients with stage ≥ II disease.

Conclusions

The CCI was significantly correlated with the prognosis of esophageal cancer patients who underwent curative-intent esophagectomy.

https://ift.tt/2DL3uyV

Non-incisional pleurectomy–decortication for malignant pleural mesothelioma

Abstract

Pleurectomy–decortication (P/D) is lung-sparing surgery with curative intent for malignant pleural mesothelioma (MPM). Visceral pleurectomy is the most challenging step in this procedure. At the beginning of pleurectomy, a sharp pleural incision through the tumor is usually made to create the dissection plane between the visceral pleura and the lung parenchyma, which may cause the spread of tumor cells into the operation field. Here, we describe a sophisticated surgical technique of P/D without any pleural incision ("non-incisional P/D") to achieve en bloc removal of the entire pleura and tumor, which may improve postoperative survival by preventing tumor spread.

https://ift.tt/2Crdm40

A novel suction/coagulation integrated probe for achieving better hemostasis: development and clinical use

Abstract

Purposes

Modern electrosurgical tools have a specific coagulation mode called "soft coagulation". However, soft coagulation has not been widely accepted for surgical operations. To optimize the soft coagulation environment, we developed a novel suction device integrated with an electrosurgical probe, called the "Suction ball coagulator" (SBC). In this study, we aimed to optimize the SBC design with a prototyping process involving a bench test and preclinical study; then, we aimed to demonstrate the feasibility, safety, and potential effectiveness of the SBC for laparoscopic surgery in clinical settings.

Methods

SBC prototyping was performed with a bench test. Device optimization was performed in a preclinical study with a domestic swine bleeding model. Then, SBC was tested in a clinical setting during 17 clinical laparoscopic colorectal surgeries.

Results

In the bench tests, two tip hole sizes and patterns showed a good suction capacity. The preclinical study indicated the best tip shape for accuracy. In clinical use, no device-related adverse event was observed. Moreover, the SBC was feasible for prompt hemostasis and blunt dissections. In addition, SBC could evacuate vapors generated by tissue ablation using electroprobe during laparoscopic surgery.

Conclusions

We successfully developed a novel, integrated suction/coagulation probe for hemostasis and commercialized it.

https://ift.tt/2Ez8asj

National survey of de novo malignancy after solid organ transplantation in Japan

Abstract

Purpose

In Japan, there have been no national surveys on the incidence of de novo malignancy after solid organ transplantation, which is one of the leading causes of death in transplant recipients.

Methods

A questionnaire was distributed to institutions that perform solid organ transplantation in Japan, and clinical information was collected from patients who underwent transplantation between 2001 and 2010 and who exhibited de novo malignancies.

Results

Nine thousand two hundred ten solid organ transplants (kidney, 49.9%; liver, 45.9%; heart, 0.9%; lung, 1.2%; pancreas, 1.9%; small intestine, 0.2%) were performed. Four hundred seventy-nine (5.2%) cases of de novo malignancy were identified. The transplanted organs of the patients included the kidney (n = 479, 54.8%), liver (n = 186, 38.8%), heart (n = 5, 0.1%), lung (n = 18, 3.8%), pancreas (n = 9, 1.9%), and small intestine (n = 1, 0.02%). The most common malignancies were post-transplant lymphoproliferative disorder (n = 87) and cancers of the kidney (n = 43), stomach (n = 41), large intestine (n = 41), and lung (n = 36).

Conclusions

This is the first national survey of the incidence of de novo malignancy in Japan. Further study is required to identify the risk of de novo malignancy in organ transplant recipients in comparison to the general population, namely the standardized incidence ratio.

https://ift.tt/2DHRxdv

Preservation of the nipple–areola complex in skin-sparing mastectomy for early breast cancer

Abstract

Purpose

Skin-sparing mastectomy (SSM) enables a radical cure of breast cancer while overcoming the cosmetic issues related to surgery. We review our experience of performing SSMs and assess whether preservation of the nipple–areola complex (NAC) could have been an option for some patients who underwent SSM.

Methods

The subjects of this retrospective study were women who underwent SSM that utilized four incision types; namely, the so-called tennis racket incision, a periareolar and midaxillary incision, an areola-sparing and midaxillary incision, and a small transverse elliptical incision. We assessed whether preservation of the NAC would have been an option in SSM, based on histologic examination of three serial cut surfaces of the specimen around the nipple, ruling out the option when evidence of the malignant lesion/s was found in at least one of the following locations: in the nipple, within a 1-cm radius from the base of the nipple, or within 1 cm from the surface of the NAC.

Results

We performed 193 SSMs. The cumulative 10-year local disease-free survival rate was 98%, with 89% of patients reporting levels of satisfaction with the reconstructed breast, of excellent, very good, or good. We evaluated that 70 of the 193 procedures could have been performed as nipple-sparing mastectomy (NSM).

Conclusions

The outcomes of SSM in this series were excellent and NSM might have been an option for about one-third of the patients.

https://ift.tt/2EJvJ5W

Postoperative adalimumab maintenance therapy for Japanese patients with Crohn’s disease: a single-center, single-arm phase II trial (CCOG-1107 study)

Abstract

Purpose

To investigate the efficacy and safety of planned postoperative adalimumab (ADA) therapy for Japanese patients with Crohn's disease (CD).

Methods

The subjects of this study were 26 patients who underwent bowel resection for CD. All patients received subcutaneous injections of ADA 160/80 mg at the time of surgery and 2 weeks later, followed by 40 mg every 2 weeks thereafter. The primary endpoint of this study was the incidence of endoscopic recurrence, defined by Rutgeerts endoscopic recurrence scale ≥ i2, 1 year after surgery.

Results

After the median follow-up period of 41.3 months, the median number of treatments with ADA was 56 and the median time-to-treatment failure was 25.6 months. Endoscopic recurrence was observed in 34.6% of the patients 1 year after surgery. Univariate analyses showed that preoperative ADA therapy was significantly associated with endoscopic recurrence. Clinical recurrence developed in 16.7% of the patients within 1 year after surgery. Secondary surgery for recurrence was not required. Although adverse events (≥ grade 3) were experienced by 15.4% of patients, none was withdrawn from this study.

Conclusion

Planned postoperative ADA therapy reduced the incidence of endoscopic and clinical recurrence after bowel resection in Japanese patients with CD.

Trial registration

This trial is registered with the University Hospital Medical Information Network (UMIN000007514).

https://ift.tt/2osp6Kl

Identifying risk factors for L’Hermitte’s sign after IMRT for head and neck cancer

Abstract

Background

L'Hermitte's sign (LS) after chemoradiotherapy for head and neck cancer appears related to higher spinal cord doses. IMRT plans limit spinal cord dose, but the incidence of LS remains high.

Methods

One hundred seventeen patients treated with TomoTherapy™ between 2008 and 2015 prospectively completed a side-effect questionnaire (VoxTox Trial Registration: UK CRN ID 13716). Baseline patient and treatment data were collected. Radiotherapy plans were analysed; mean and maximum spinal cord dose and volumes receiving 10, 20, 30 and 40 Gy were recorded. Dose variation across the cord was examined. These data were included in a logistic regression model.

Results

Forty two patients (35.9%) reported LS symptoms. Concurrent weekly cisplatin did not increase LS risk (p = 0.70, OR = 1.23 {95% CI 0.51–2.34}). Of 13 diabetic participants (9 taking metformin), only 1 developed LS (p = 0.025, OR = 0.13 {95% CI 0.051–3.27}). A refined binary logistic regression model showed that patients receiving unilateral radiation (p = 0.019, OR = 2.06 {95% CI 0.15–0.84}) were more likely to develop LS. Higher V_40Gy (p = 0.047, OR = 1.06 {95% CI 1.00–1.12}), and younger age (mean age 56.6 vs 59.7, p = 0.060, OR = 0.96 {95% CI 0.92–1.00}) were associated with elevated risk of LS, with borderline significance.

Conclusions

In this cohort, concomitant cisplatin did not increase risk, and LS incidence was lower in diabetic patients. Patient age and dose gradients across the spinal cord may be important factors.

https://ift.tt/2rm7AIT

Neuroendocrine carcinoma of the cervix: a systematic review of the literature

Abstract

Background

Neuroendocrine carcinoma of the cervix (NECC) is a rare variant of cervical cancer. The prognosis of women with NECC is poor and there is no standardized therapy for this type of malignancy based on controlled trials.

Methods

We performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify clinical trials describing the management and outcome of women with NECC.

Results

Three thousand five hundred thirty-eight cases of NECC in 112 studies were identified. The pooled proportion of NECC among women with cervical cancer was 2303/163470 (1.41%). Small cell NECC, large cell NECC, and other histological subtypes were identified in 80.4, 12.0, and 7.6% of cases, respectively. Early and late stage disease presentation were evenly distributed with 1463 (50.6%) and 1428 (49.4%) cases, respectively. Tumors expressed synaptophysin (424/538 cases; 79%), neuron-specific enolase (196/285 cases; 69%), chromogranin (323/486 cases; 66%), and CD56 (162/267; 61%). The most common primary treatment was radical surgery combined with chemotherapy either as neoadjuvant or adjuvant chemotherapy, described in 42/48 studies. Radiotherapy-based primary treatment schemes in the form of radiotherapy, radiochemotherapy, or radiotherapy with concomitant or followed by chemotherapy were also commonly used (15/48 studies). There is no standard chemotherapy regimen for NECC, but cisplatin/carboplatin and etoposide (EP) was the most commonly used treatment scheme (24/40 studies). Overall, the prognosis of women with NECC was poor with a mean recurrence-free survival of 16 months and a mean overall survival of 40 months. Immune checkpoint inhibitors and targeted agents were reported as being active in three case reports.

Conclusion

NECC is a rare variant of cervical cancer with a poor prognosis. Multimodality treatment with radical surgery and neoadjuvant/adjuvant chemotherapy with cisplatin and etoposide with or without radiotherapy is the mainstay of treatment for early stage disease while chemotherapy with cisplatin and etoposide or topotecan, paclitaxel, and bevacizumab is appropriate for women with locally advanced or recurrent NECC. Immune checkpoint inhibitors may be beneficial, but controlled evidence for their efficacy is lacking.

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PET/CT incidental detection of second tumor in patients investigated for pancreatic neoplasms

Abstract

Background

Positron Emission Tomography/computed tomography (PET/CT) is an imaging technique which has a role in the detection and staging malignancies (both in first diagnosis and follow-up). The finding of an unexpected region of FDG (Fluorodeoxyglucose) uptake can occur when performing whole-body FDG-PET, raising the possibility of a second primary tumor. The aim of this study was to evaluate our experience of second primary cancer incidentally discovered during PET/CT examination performed for pancreatic diseases, during the initial work-up or follow-up after surgical resection.

Methods

In this study, a retrospective evaluation of a prospectively collected data base was performed. Three hundred ninety- nine patients with pancreatic pathology were evaluated by whole body PET/CT imaging from January 2004 to December 2014. Among them, 348 patients were scanned before surgical resection and 51 during the course of their follow-up (pancreatic cancer). Median follow-up time was 29 months (range 14-124).

Results

Fifty-six patients (14%) had incidental uptake of FDG in their organs: 31 patients had focal uptake and 25 showed diffuse with or without focal uptake. All patients with focal uptake were investigated, and invasive malignancy was diagnosed in 22 patients: 14 colon, 4 lung, 1 larynx, 1 urothelial, 1 breast cancer, and 1 colon metastasis from pancreatic cancer. Twenty patients underwent resection, and 6 endoscopic removal of colonic polyps. Three patients were not operated for advanced disease, and two patients did not show any pathology (PET/CT false positive). Of the 10 patients investigated for diffuse uptake, no malignancy was found; none of these patients developed a second cancer during the follow-up.

Conclusions

As in other malignancies, unexpected FDG uptake can occur in patients having PET/CT investigation for pancreatic diseases. Focal uptake is likely to be a malignancy and deserves further investigations, although the stage and the poor prognosis of primary pancreatic cancer should be kept in mind. Some selected patients may benefit from the aggressive treatment of incidental lesions and show survival benefit.

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Pancreatic ductal adenocarcinoma can be detected by analysis of volatile organic compounds (VOCs) in alveolar air

Abstract

Background

In the last decade many studies showed that the exhaled breath of subjects suffering from several pathological conditions has a peculiar volatile organic compound (VOC) profile. The objective of the present work was to analyse the VOCs in alveolar air to build a diagnostic tool able to identify the presence of pancreatic ductal adenocarcinoma in patients with histologically confirmed disease.

Methods

The concentration of 92 compounds was measured in the end-tidal breath of 65 cases and 102 controls. VOCs were measured with an ion-molecule reaction mass spectrometry. To distinguish between subjects with pancreatic adenocarcinomas and controls, an iterated Least Absolute Shrinkage and Selection Operator multivariate Logistic Regression model was elaborated.

Results

The final predictive model, based on 10 VOCs, significantly and independently associated with the outcome had a sensitivity and specificity of 100 and 84% respectively, and an area under the ROC curve of 0.99. For further validation, the model was run on 50 other subjects: 24 cases and 26 controls; 23 patients with histological diagnosis of pancreatic adenocarcinomas and 25 controls were correctly identified by the model.

Conclusions

Pancreatic cancer is able to alter the concentration of some molecules in the blood and hence of VOCs in the alveolar air in equilibrium. The detection and statistical rendering of alveolar VOC composition can be useful for the clinical diagnostic approach of pancreatic neoplasms with excellent sensitivity and specificity.

from Cancer via ola Kala on Inoreader https://ift.tt/2KE8dXg
via IFTTT

Neuroendocrine carcinoma of the cervix: a systematic review of the literature

Abstract

Background

Neuroendocrine carcinoma of the cervix (NECC) is a rare variant of cervical cancer. The prognosis of women with NECC is poor and there is no standardized therapy for this type of malignancy based on controlled trials.

Methods

We performed a systematic literature search of the databases PubMed and Cochrane Central Register of Controlled Trials to identify clinical trials describing the management and outcome of women with NECC.

Results

Three thousand five hundred thirty-eight cases of NECC in 112 studies were identified. The pooled proportion of NECC among women with cervical cancer was 2303/163470 (1.41%). Small cell NECC, large cell NECC, and other histological subtypes were identified in 80.4, 12.0, and 7.6% of cases, respectively. Early and late stage disease presentation were evenly distributed with 1463 (50.6%) and 1428 (49.4%) cases, respectively. Tumors expressed synaptophysin (424/538 cases; 79%), neuron-specific enolase (196/285 cases; 69%), chromogranin (323/486 cases; 66%), and CD56 (162/267; 61%). The most common primary treatment was radical surgery combined with chemotherapy either as neoadjuvant or adjuvant chemotherapy, described in 42/48 studies. Radiotherapy-based primary treatment schemes in the form of radiotherapy, radiochemotherapy, or radiotherapy with concomitant or followed by chemotherapy were also commonly used (15/48 studies). There is no standard chemotherapy regimen for NECC, but cisplatin/carboplatin and etoposide (EP) was the most commonly used treatment scheme (24/40 studies). Overall, the prognosis of women with NECC was poor with a mean recurrence-free survival of 16 months and a mean overall survival of 40 months. Immune checkpoint inhibitors and targeted agents were reported as being active in three case reports.

Conclusion

NECC is a rare variant of cervical cancer with a poor prognosis. Multimodality treatment with radical surgery and neoadjuvant/adjuvant chemotherapy with cisplatin and etoposide with or without radiotherapy is the mainstay of treatment for early stage disease while chemotherapy with cisplatin and etoposide or topotecan, paclitaxel, and bevacizumab is appropriate for women with locally advanced or recurrent NECC. Immune checkpoint inhibitors may be beneficial, but controlled evidence for their efficacy is lacking.

https://ift.tt/2juyGKv