Analysis of Carcinogenic Heavy Metals in Gallstones and its Role in Gallbladder Carcinogenesis

Abstract

Purpose

Gallstone is a high-risk factor for gallbladder pre-malignancy or malignancy (GB PM-M) but which substances of gallstones definitely assist to turn out in to GB PM-M, remains unclear. This study aimed to find out the presence of carcinogenic heavy metals in gallstones and to explore the aetiopathogenesis of gallbladder pre-malignancy and malignancy.

Methods

Presence of elements in gallstones was detected by energy dispersive X-ray spectroscopy (EDS) with scanning electron microscopy (SEM) and then level of carcinogenic heavy metals was estimated in gallstones using atomic absorption spectroscopy (AAS). The experiment was carried out in gallstone samples of 46 patients with gallbladder pre-malignant and malignant condition (PM-M group) and 65 sex and age-matched patients with chronic cholecystitis (C-C group). Gallstones were also classified in to three types such as cholesterol stone, mixed stone, and black pigment stone.

Results

EDS analysis detected presence of mercury, lead, and cobalt elements in all types of gallstones of both PM-M and C-C groups. AAS analysis revealed significantly higher amount of mercury (p < 0.001), lead (p < 0.0001), cobalt (p < 0.01), and cadmium (p < 0.01) in the gallstones of PM-M than C-C groups. The presence of these heavy metals also varied among stone types of both groups. EDS phase analysis showed 'dense deposits' of these metals in gallstones.

Conclusions

Presence of significantly higher amount of mercury, lead, cobalt, and cadmium in gallstones may play a pivotal role as risk factors in the development of gallbladder malignancy or pre-malignancy. 'Dense deposits' of these metals in the gallstones which is the first observation, may act as crucial doses of carcinogens.

http://ift.tt/2gub6xp

Small Bowel Adenocarcinoma in Celiac Disease: a Case Report

http://ift.tt/2fAxiSb

What Do We Need to Know About Colonic Polypoid Ganglioneuroma? A Case Report and A Comprehensive Review

http://ift.tt/2gue6dd

Analysis of Carcinogenic Heavy Metals in Gallstones and its Role in Gallbladder Carcinogenesis

Abstract

Purpose

Gallstone is a high-risk factor for gallbladder pre-malignancy or malignancy (GB PM-M) but which substances of gallstones definitely assist to turn out in to GB PM-M, remains unclear. This study aimed to find out the presence of carcinogenic heavy metals in gallstones and to explore the aetiopathogenesis of gallbladder pre-malignancy and malignancy.

Methods

Presence of elements in gallstones was detected by energy dispersive X-ray spectroscopy (EDS) with scanning electron microscopy (SEM) and then level of carcinogenic heavy metals was estimated in gallstones using atomic absorption spectroscopy (AAS). The experiment was carried out in gallstone samples of 46 patients with gallbladder pre-malignant and malignant condition (PM-M group) and 65 sex and age-matched patients with chronic cholecystitis (C-C group). Gallstones were also classified in to three types such as cholesterol stone, mixed stone, and black pigment stone.

Results

EDS analysis detected presence of mercury, lead, and cobalt elements in all types of gallstones of both PM-M and C-C groups. AAS analysis revealed significantly higher amount of mercury (p < 0.001), lead (p < 0.0001), cobalt (p < 0.01), and cadmium (p < 0.01) in the gallstones of PM-M than C-C groups. The presence of these heavy metals also varied among stone types of both groups. EDS phase analysis showed 'dense deposits' of these metals in gallstones.

Conclusions

Presence of significantly higher amount of mercury, lead, cobalt, and cadmium in gallstones may play a pivotal role as risk factors in the development of gallbladder malignancy or pre-malignancy. 'Dense deposits' of these metals in the gallstones which is the first observation, may act as crucial doses of carcinogens.

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Small Bowel Adenocarcinoma in Celiac Disease: a Case Report

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What Do We Need to Know About Colonic Polypoid Ganglioneuroma? A Case Report and A Comprehensive Review

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Design of a randomized controlled trial of Internet-based cognitive behavioral therapy for treatment-induced menopausal symptoms in breast cancer survivors

Abstract

Background

Menopausal symptoms are common and may be particularly severe in younger women who undergo treatment-induced menopause. Medications to reduce menopausal symptoms are either contra-indicated or have bothersome side effects. Previous studies have demonstrated that face-to-face cognitive behavioral therapy (CBT) is effective in alleviating menopausal symptoms in women with breast cancer. However, compliance with face-to-face CBT programs can be problematic. A promising approach is to use the Internet to make this form of CBT more accessible and feasible for patients. This study is evaluating the efficacy and cost-effectiveness of an Internet-based CBT program, with or without therapist guidance, in alleviating or reducing the severity of menopausal symptoms.

Methods/design

In a multicenter, randomized controlled trial we are evaluating the efficacy of two Internet-based CBT programs in alleviating or reducing the impact of menopausal symptoms, and particularly hot flushes and night sweats, in breast cancer survivors who have experienced a treatment-induced menopause. Secondary outcomes include sexual functioning, sleep quality, hot flush frequency, psychological distress, health-related quality of life and cost-effectiveness. We will recruit 248 women who will be randomized to either a therapist guided or a self-management version of the 6-week Internet-based CBT program, or to a usual care, waiting list control group. Self-administered questionnaires are completed at baseline (T0), and at 10 weeks (T1) and 24 weeks (T2) post-randomization.

Discussion

Internet-based CBT is a potentially useful treatment for reducing menopausal symptoms in breast cancer survivors. This study will provide evidence on the efficacy and cost-effectiveness of such an Internet-based CBT program, with or without therapist support. If demonstrated to be efficacious and cost-effective, the availability of such structured supportive intervention programs will be a welcome addition to standard medical treatment offered to cancer patients with treatment-induced menopause.

Trial registration

The study is retrospectively registered at ClinicalTrials.gov on January 26th 2016 (NCT02672189).

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Design of a randomized controlled trial of Internet-based cognitive behavioral therapy for treatment-induced menopausal symptoms in breast cancer survivors

Abstract

Background

Menopausal symptoms are common and may be particularly severe in younger women who undergo treatment-induced menopause. Medications to reduce menopausal symptoms are either contra-indicated or have bothersome side effects. Previous studies have demonstrated that face-to-face cognitive behavioral therapy (CBT) is effective in alleviating menopausal symptoms in women with breast cancer. However, compliance with face-to-face CBT programs can be problematic. A promising approach is to use the Internet to make this form of CBT more accessible and feasible for patients. This study is evaluating the efficacy and cost-effectiveness of an Internet-based CBT program, with or without therapist guidance, in alleviating or reducing the severity of menopausal symptoms.

Methods/design

In a multicenter, randomized controlled trial we are evaluating the efficacy of two Internet-based CBT programs in alleviating or reducing the impact of menopausal symptoms, and particularly hot flushes and night sweats, in breast cancer survivors who have experienced a treatment-induced menopause. Secondary outcomes include sexual functioning, sleep quality, hot flush frequency, psychological distress, health-related quality of life and cost-effectiveness. We will recruit 248 women who will be randomized to either a therapist guided or a self-management version of the 6-week Internet-based CBT program, or to a usual care, waiting list control group. Self-administered questionnaires are completed at baseline (T0), and at 10 weeks (T1) and 24 weeks (T2) post-randomization.

Discussion

Internet-based CBT is a potentially useful treatment for reducing menopausal symptoms in breast cancer survivors. This study will provide evidence on the efficacy and cost-effectiveness of such an Internet-based CBT program, with or without therapist support. If demonstrated to be efficacious and cost-effective, the availability of such structured supportive intervention programs will be a welcome addition to standard medical treatment offered to cancer patients with treatment-induced menopause.

Trial registration

The study is retrospectively registered at ClinicalTrials.gov on January 26th 2016 (NCT02672189).

http://ift.tt/2fRvqoY

List of reviewers 2015–2016

http://ift.tt/2gtLI7x

List of reviewers 2015–2016

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Impact of urgent resuscitative surgery for life-threatening torso trauma

Abstract

Purpose

This study investigated the advantages of performing urgent resuscitative surgery (URS) in the emergency department (ED); namely, our URS policy, to avoid a delay in hemorrhage control for patients with severe torso trauma and unstable vital signs.

Methods

We divided 264 eligible cases into a URS group (n = 97) and a non-URS group (n = 167) to compare, retrospectively, the observed survival rate with the predicted survival using the Trauma and Injury Severity Score (TRISS).

Results

While the revised trauma score and the injury severity score were significantly lower in the URS group than in the non-URS group, the observed survival rate was significantly higher than the predicted rate in the URS (48.5 vs. 40.2%; p = 0.038). URS group patients with a systolic blood pressure (SBP) <90 mmHg and a Glasgow coma scale (GCS) score of ≥9 had significantly higher observed survival rates than predicted survival rates (0.433 vs. 0.309, p = 0.008), (0.795 vs. 0.681, p = 0.004). The implementation of damage control surgery (DCS) was found to be a significant predictor of survival (OR 5.23, 95% CI 0.113–0.526, p < 0.010).

Conclusion

The best indications for the URS policy are an SBP <90 mmHg, a GCS ≥9 on ED arrival, and/or the need for DCS. By implementing our URS policy, satisfactory survival of patients requiring immediate hemostatic surgery was achieved.

http://ift.tt/2g4WbJo

Impact of urgent resuscitative surgery for life-threatening torso trauma

Abstract

Purpose

This study investigated the advantages of performing urgent resuscitative surgery (URS) in the emergency department (ED); namely, our URS policy, to avoid a delay in hemorrhage control for patients with severe torso trauma and unstable vital signs.

Methods

We divided 264 eligible cases into a URS group (n = 97) and a non-URS group (n = 167) to compare, retrospectively, the observed survival rate with the predicted survival using the Trauma and Injury Severity Score (TRISS).

Results

While the revised trauma score and the injury severity score were significantly lower in the URS group than in the non-URS group, the observed survival rate was significantly higher than the predicted rate in the URS (48.5 vs. 40.2%; p = 0.038). URS group patients with a systolic blood pressure (SBP) <90 mmHg and a Glasgow coma scale (GCS) score of ≥9 had significantly higher observed survival rates than predicted survival rates (0.433 vs. 0.309, p = 0.008), (0.795 vs. 0.681, p = 0.004). The implementation of damage control surgery (DCS) was found to be a significant predictor of survival (OR 5.23, 95% CI 0.113–0.526, p < 0.010).

Conclusion

The best indications for the URS policy are an SBP <90 mmHg, a GCS ≥9 on ED arrival, and/or the need for DCS. By implementing our URS policy, satisfactory survival of patients requiring immediate hemostatic surgery was achieved.

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The impact of extended lymph node dissection versus neoadjuvant therapy with limited lymph node dissection on biochemical recurrence in high-risk prostate cancer patients treated with radical prostatectomy: a multi-institutional analysis

Abstract

The optimal treatment for high-risk prostate cancer (Pca) remains to be established. The current guidelines recommend extended pelvic lymph node dissection (e-PLND) for selected intermediate- and high-risk patients treated with RP. However, the indications, optimal extent, and therapeutic benefits of e-PLND remain unclear. The aim of this study was to assess whether e-PLND confers an oncological benefit for high-risk Pca compared to neoadjuvant luteinizing hormone-releasing hormone and estramustine (LHRH + EMP). The Michinoku Urological Cancer Study Group database contained the data of 2403 consecutive Pca patients treated with RP at four institutes between March 2000 and December 2014. In the e-PLND group, we identified 238 high-risk Pca patients who underwent RP and e-PLND, with lymphatic tissue removal around the obturator and the external iliac regions, and hypogastric lymph node dissection. The neoadjuvant therapy with limited PLND (l-PLND) group included 280 high-risk Pca patients who underwent RP and removal of the obturator node chain between September 2005 and June 2014 at Hirosaki University. The outcome measure was BRFS. The 5-year biochemical recurrence-free survival rates for the neoadjuvant therapy with l-PLND group and e-PLND group were 84.9 and 54.7%, respectively (P < 0.0001). The operative time was significantly longer in the e-PLND group compared to that of the neoadjuvant therapy with l-PLND group. Grade 3/4 surgery-related complications were not identified in both groups. Although the present study was not randomized, neoadjuvant LHRH + EMP therapy followed by RP might reduce the risk of biochemical recurrence.

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Identification of reference genes and miRNAs for qRT-PCR in human esophageal squamous cell carcinoma

Abstract

It is important to select an appropriate reference gene and miRNA when using quantitative real-time polymerase chain reaction (qRT-PCR) to analyze gene and miRNA expression. However, many commonly used reference genes and miRNAs are not stably expressed and therefore not suitable for normalization or quantification of qRT-PCR data. This study aims to identify appropriate reference genes and miRNAs for use in human esophageal squamous carcinoma qRT-PCR analysis. Using data provided by The Cancer Genome Atlas, we identified DDX5, LAPTM4A, P4HB, RHOA, miR-28-5p, miR-34a-5p, and miR-186-5p as candidate reference genes and miRNAs. We used qRT-PCR to verify the expression levels of these candidates and another seven commonly used reference genes and miRNAs. A set of 50 paired human normal esophageal tissues and squamous cell carcinoma samples were used in the analysis. We then used geNorm and NormFinder to analyze the results. DDX5, LAPTM4A, RHOA, ACTB, RNU48, miR-28-5p, miR-34a-5p, and miR-186-5p were stably expressed, indicating they are suitable for used as references in qRT-PCR analysis of esophageal squamous cell carcinoma. However, expression levels of 18s rRNA, GAPDH, P4HB, 5s rRNA, U6, and RNU6B varied greatly between esophageal normal and squamous cell carcinoma samples, indicating that they are not suitable for use as references in the qRT-PCR analysis of esophageal squamous cell carcinoma.

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The impact of extended lymph node dissection versus neoadjuvant therapy with limited lymph node dissection on biochemical recurrence in high-risk prostate cancer patients treated with radical prostatectomy: a multi-institutional analysis

Abstract

The optimal treatment for high-risk prostate cancer (Pca) remains to be established. The current guidelines recommend extended pelvic lymph node dissection (e-PLND) for selected intermediate- and high-risk patients treated with RP. However, the indications, optimal extent, and therapeutic benefits of e-PLND remain unclear. The aim of this study was to assess whether e-PLND confers an oncological benefit for high-risk Pca compared to neoadjuvant luteinizing hormone-releasing hormone and estramustine (LHRH + EMP). The Michinoku Urological Cancer Study Group database contained the data of 2403 consecutive Pca patients treated with RP at four institutes between March 2000 and December 2014. In the e-PLND group, we identified 238 high-risk Pca patients who underwent RP and e-PLND, with lymphatic tissue removal around the obturator and the external iliac regions, and hypogastric lymph node dissection. The neoadjuvant therapy with limited PLND (l-PLND) group included 280 high-risk Pca patients who underwent RP and removal of the obturator node chain between September 2005 and June 2014 at Hirosaki University. The outcome measure was BRFS. The 5-year biochemical recurrence-free survival rates for the neoadjuvant therapy with l-PLND group and e-PLND group were 84.9 and 54.7%, respectively (P < 0.0001). The operative time was significantly longer in the e-PLND group compared to that of the neoadjuvant therapy with l-PLND group. Grade 3/4 surgery-related complications were not identified in both groups. Although the present study was not randomized, neoadjuvant LHRH + EMP therapy followed by RP might reduce the risk of biochemical recurrence.

http://ift.tt/2gy2MKT

Identification of reference genes and miRNAs for qRT-PCR in human esophageal squamous cell carcinoma

Abstract

It is important to select an appropriate reference gene and miRNA when using quantitative real-time polymerase chain reaction (qRT-PCR) to analyze gene and miRNA expression. However, many commonly used reference genes and miRNAs are not stably expressed and therefore not suitable for normalization or quantification of qRT-PCR data. This study aims to identify appropriate reference genes and miRNAs for use in human esophageal squamous carcinoma qRT-PCR analysis. Using data provided by The Cancer Genome Atlas, we identified DDX5, LAPTM4A, P4HB, RHOA, miR-28-5p, miR-34a-5p, and miR-186-5p as candidate reference genes and miRNAs. We used qRT-PCR to verify the expression levels of these candidates and another seven commonly used reference genes and miRNAs. A set of 50 paired human normal esophageal tissues and squamous cell carcinoma samples were used in the analysis. We then used geNorm and NormFinder to analyze the results. DDX5, LAPTM4A, RHOA, ACTB, RNU48, miR-28-5p, miR-34a-5p, and miR-186-5p were stably expressed, indicating they are suitable for used as references in qRT-PCR analysis of esophageal squamous cell carcinoma. However, expression levels of 18s rRNA, GAPDH, P4HB, 5s rRNA, U6, and RNU6B varied greatly between esophageal normal and squamous cell carcinoma samples, indicating that they are not suitable for use as references in the qRT-PCR analysis of esophageal squamous cell carcinoma.

http://ift.tt/2gL0cUP

True Incidence of Gleason 6 Pathology in Patients with Metastatic Castration Resistant Prostate Cancer (mCRPC)

Abstract

Introduction

Recent evidence from histology studies regarding random prostate biopsies hint toward a relationship between higher biopsy Gleason score and the development of metastatic castration resistant prostate cancer (mCRPC). However, prostate biopsy underestimates final pathology in about one-third of patients. We evaluated the final whole gland pathology from radical prostatectomy exclusively in order to assess the true risk of progressing to the mCRPC state for patients with confirmed Gleason ≤6 prostate cancer.

Methods

Patients with confirmed mCRPC from our outpatient clinic were retrospectively evaluated with regard to whole gland pathology and the occurrence of Gleason 6 histology from 1995 to 2015. Conversely, patients with confirmed Gleason 6 pathology from our institutional database were followed up for the development of mCRPC from 2001 to 2015. Kaplan–Meier analysis and the log rank test were applied for survival analysis. The binomial test was used to evaluate occurrence rates of Gleason ≤6 pathologies in mCRPC patients.

Results

Out of 62 patients with mCRPC none had confirmed Gleason 6 pathology on whole gland histology of the prostate. Out of 86 patients with confirmed Gleason 6 pathology none developed an mCRPC over the follow-up period.

Conclusion

The development of mCRPC in patients with true Gleason 6 pathology is very rare and could not be confirmed in our series. This finding may have important implications in future treatment planning.

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A Randomized, Clinical Trial to Evaluate Efficacy and Tolerability of Trypsin:Chymotrypsin as Compared to Serratiopeptidase and Trypsin:Bromelain:Rutoside in Wound Management

Abstract

Introduction

Systemic enzyme therapy can play an important role in maintaining normal inflammatory processes within the body and thereby helps support and speed up healing. In the course of the anti-inflammatory action, enzymes degrade damaged cells and necrotic material and, through the inactivation of mediators and toxic products, they restrict the edema and pain.

Method

The study conducted at Grant Medical College, Mumbai, India was a clinical trial comparing the efficacy and tolerability of three oral enzyme treatment groups—oral tablets containing trypsin:chymotrypsin (TC) (Chymoral Forte^®), serratiopeptidase (S) 5 mg oral tablets, and oral enzyme tablets containing trypsin 48 mg, bromelain 90 mg, and rutoside 100 mg (TBR)—to evaluate their healing potential in surgical wounds after orthopedic surgery.

Results

A total of 75 patients were screened, randomized, and divided into three groups in 1:1:1 ratio receiving either of the three treatments. In the TC group, erythema was significantly reduced from 3.44 on day 3 to 1.16 on day 10 (p < 0.01). There was significantly better reduction in erythema scores in the TC group as compared to S and TBR groups (p < 0.05) at each follow-up visit. Similarly reduction in the local irritation, wound discharge, edema, induration, and tenderness score with TC treatment at the end of the study was significantly higher than that observed in the other two groups. In addition TC showed significant reduction in pain on the VAS scale (p < 0.01). Global assessment of response to therapy for efficacy and tolerability was reported to be good to excellent in 88% and 92% of the patients on TC as compared to 12% and 8% with S and 12% and 8% with TBR.

Conclusion

TC provides a better resolution of symptoms of inflammation after orthopedic surgery as compared to S and TBR, thus facilitating better wound healing. Further studies are warranted to confirm the findings.

Trial Registration

Clinical Trial Registry of India (Reg. No. CTRI/2011/07/001920).

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Erratum to: Clinical and Biological Principles of Cold Atmospheric Plasma Application in Skin Cancer

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Estimated Budget Impact of Adopting the Affordable Care Act’s Required Smoking Cessation Coverage on United States Healthcare Payers

Abstract

Introduction

Despite abundant information on the negative impacts of smoking, more than 40 million adult Americans continue to smoke. The Affordable Care Act (ACA) requires tobacco cessation as a preventive service with no patient cost share for all FDA-approved cessation medications. Health plans have a vital role in supporting smoking cessation by managing medication access, but uncertainty remains on the gaps between smoking cessation requirements and what is actually occurring in practice. This study presents current cessation patterns, real-world drug costs and plan benefit design data, and estimates the 1- to 5-year pharmacy budget impact of providing ACA-required coverage for smoking cessation products to understand the fiscal impact to a US healthcare plan.

Methods

A closed cohort budget impact model was developed in Microsoft Excel^® to estimate current and projected costs for US payers (commercial, Medicare, Medicaid) covering smoking cessation medicines, with assumptions for coverage and smoking cessation product utilization based on current, real-world national and state-level trends for hypothetical commercial, Medicare, and Medicaid plans with 1 million covered lives. A Markov methodology with five health states captures quit attempt and relapse patterns. Results include the number of smokers attempting to quit, number of successful quitters, annual costs, and cost per-member per-month (PMPM).

Results

The projected PMPM cost of providing coverage for smoking cessation medications is $0.10 for commercial, $0.06 for Medicare, and $0.07 for Medicaid plans, reflecting a low incremental PMPM impact of covering two attempts ranging from $0.01 for Medicaid to $0.02 for commercial and Medicare payers.

Conclusion

The projected PMPM impact of covering two quit attempts with access to all seven cessation medications at no patient cost share remains low. Results of this study reinforce that the impact of adopting the ACA requirements for smoking cessation coverage will have a limited near-term impact on health plan's budgets.

Funding

Pfizer Inc.

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True Incidence of Gleason 6 Pathology in Patients with Metastatic Castration Resistant Prostate Cancer (mCRPC)

Abstract

Introduction

Recent evidence from histology studies regarding random prostate biopsies hint toward a relationship between higher biopsy Gleason score and the development of metastatic castration resistant prostate cancer (mCRPC). However, prostate biopsy underestimates final pathology in about one-third of patients. We evaluated the final whole gland pathology from radical prostatectomy exclusively in order to assess the true risk of progressing to the mCRPC state for patients with confirmed Gleason ≤6 prostate cancer.

Methods

Patients with confirmed mCRPC from our outpatient clinic were retrospectively evaluated with regard to whole gland pathology and the occurrence of Gleason 6 histology from 1995 to 2015. Conversely, patients with confirmed Gleason 6 pathology from our institutional database were followed up for the development of mCRPC from 2001 to 2015. Kaplan–Meier analysis and the log rank test were applied for survival analysis. The binomial test was used to evaluate occurrence rates of Gleason ≤6 pathologies in mCRPC patients.

Results

Out of 62 patients with mCRPC none had confirmed Gleason 6 pathology on whole gland histology of the prostate. Out of 86 patients with confirmed Gleason 6 pathology none developed an mCRPC over the follow-up period.

Conclusion

The development of mCRPC in patients with true Gleason 6 pathology is very rare and could not be confirmed in our series. This finding may have important implications in future treatment planning.

http://ift.tt/2gsOqh3

A Randomized, Clinical Trial to Evaluate Efficacy and Tolerability of Trypsin:Chymotrypsin as Compared to Serratiopeptidase and Trypsin:Bromelain:Rutoside in Wound Management

Abstract

Introduction

Systemic enzyme therapy can play an important role in maintaining normal inflammatory processes within the body and thereby helps support and speed up healing. In the course of the anti-inflammatory action, enzymes degrade damaged cells and necrotic material and, through the inactivation of mediators and toxic products, they restrict the edema and pain.

Method

The study conducted at Grant Medical College, Mumbai, India was a clinical trial comparing the efficacy and tolerability of three oral enzyme treatment groups—oral tablets containing trypsin:chymotrypsin (TC) (Chymoral Forte^®), serratiopeptidase (S) 5 mg oral tablets, and oral enzyme tablets containing trypsin 48 mg, bromelain 90 mg, and rutoside 100 mg (TBR)—to evaluate their healing potential in surgical wounds after orthopedic surgery.

Results

A total of 75 patients were screened, randomized, and divided into three groups in 1:1:1 ratio receiving either of the three treatments. In the TC group, erythema was significantly reduced from 3.44 on day 3 to 1.16 on day 10 (p < 0.01). There was significantly better reduction in erythema scores in the TC group as compared to S and TBR groups (p < 0.05) at each follow-up visit. Similarly reduction in the local irritation, wound discharge, edema, induration, and tenderness score with TC treatment at the end of the study was significantly higher than that observed in the other two groups. In addition TC showed significant reduction in pain on the VAS scale (p < 0.01). Global assessment of response to therapy for efficacy and tolerability was reported to be good to excellent in 88% and 92% of the patients on TC as compared to 12% and 8% with S and 12% and 8% with TBR.

Conclusion

TC provides a better resolution of symptoms of inflammation after orthopedic surgery as compared to S and TBR, thus facilitating better wound healing. Further studies are warranted to confirm the findings.

Trial Registration

Clinical Trial Registry of India (Reg. No. CTRI/2011/07/001920).

http://ift.tt/2fz6txM

Erratum to: Clinical and Biological Principles of Cold Atmospheric Plasma Application in Skin Cancer

http://ift.tt/2gsPstx

Estimated Budget Impact of Adopting the Affordable Care Act’s Required Smoking Cessation Coverage on United States Healthcare Payers

Abstract

Introduction

Despite abundant information on the negative impacts of smoking, more than 40 million adult Americans continue to smoke. The Affordable Care Act (ACA) requires tobacco cessation as a preventive service with no patient cost share for all FDA-approved cessation medications. Health plans have a vital role in supporting smoking cessation by managing medication access, but uncertainty remains on the gaps between smoking cessation requirements and what is actually occurring in practice. This study presents current cessation patterns, real-world drug costs and plan benefit design data, and estimates the 1- to 5-year pharmacy budget impact of providing ACA-required coverage for smoking cessation products to understand the fiscal impact to a US healthcare plan.

Methods

A closed cohort budget impact model was developed in Microsoft Excel^® to estimate current and projected costs for US payers (commercial, Medicare, Medicaid) covering smoking cessation medicines, with assumptions for coverage and smoking cessation product utilization based on current, real-world national and state-level trends for hypothetical commercial, Medicare, and Medicaid plans with 1 million covered lives. A Markov methodology with five health states captures quit attempt and relapse patterns. Results include the number of smokers attempting to quit, number of successful quitters, annual costs, and cost per-member per-month (PMPM).

Results

The projected PMPM cost of providing coverage for smoking cessation medications is $0.10 for commercial, $0.06 for Medicare, and $0.07 for Medicaid plans, reflecting a low incremental PMPM impact of covering two attempts ranging from $0.01 for Medicaid to $0.02 for commercial and Medicare payers.

Conclusion

The projected PMPM impact of covering two quit attempts with access to all seven cessation medications at no patient cost share remains low. Results of this study reinforce that the impact of adopting the ACA requirements for smoking cessation coverage will have a limited near-term impact on health plan's budgets.

Funding

Pfizer Inc.

http://ift.tt/2fzjFCw

Monte Carlo systems used for treatment planning and dose verification

Abstract

General-purpose radiation transport Monte Carlo codes have been used for estimation of the absorbed dose distribution in external photon and electron beam radiotherapy patients since several decades. Results obtained with these codes are usually more accurate than those provided by treatment planning systems based on non-stochastic methods. Traditionally, absorbed dose computations based on general-purpose Monte Carlo codes have been used only for research, owing to the difficulties associated with setting up a simulation and the long computation time required. To take advantage of radiation transport Monte Carlo codes applied to routine clinical practice, researchers and private companies have developed treatment planning and dose verification systems that are partly or fully based on fast Monte Carlo algorithms. This review presents a comprehensive list of the currently existing Monte Carlo systems that can be used to calculate or verify an external photon and electron beam radiotherapy treatment plan. Particular attention is given to those systems that are distributed, either freely or commercially, and that do not require programming tasks from the end user. These systems are compared in terms of features and the simulation time required to compute a set of benchmark calculations.

http://ift.tt/2gtEFPT

Pediatric Radiology editorial board — acknowledgments and updates

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Pediatric Radiology editorial board — acknowledgments and updates

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Candidate predisposing germline copy number variants in early onset colorectal cancer patients

Abstract

Purpose

A great proportion of the heritability of colorectal cancer (CRC) still remains unexplained, and rare variants, as well as copy number changes, have been proposed as potential candidates to explain the so-called 'missing heritability'. We aimed to identify rare high-to-moderately penetrant copy number variants (CNVs) in patients suspected of having hereditary CRC due to an early onset.

Methods/patients

We have selected for genome-wide copy number analysis, 27 MMR-proficient early onset CRC patients (<50 years) without identifiable germline mutations in Mendelian genes related to this phenotype. Rare CNVs were selected by removing all CNVs detected at MAF >1% in the in-house control CNV database (n = 629 healthy controls). Copy number assignment was checked by duplex real-time quantitative PCR or multiplex ligation probe amplification. Somatic mutation analysis in candidate genes included: loss of heterozygosity studies, point mutation screening, and methylation status of the promoter.

Results

We have identified two rare germline deletions involving the AK3 and SLIT2 genes in two patients. The search for a second somatic mutational event in the corresponding CRC tumors showed loss of heterozygosity in AK3, and promoter hypermethylation in SLIT2. Both genes have been previously related to colorectal carcinogenesis.

Conclusions

These findings suggest that AK3 and SLIT2 may be potential candidates involved in genetic susceptibility to CRC.

http://ift.tt/2gsR2rw

Correlation between status of epidermal growth factor receptor mutation and distant metastases of lung adenocarcinoma upon initial diagnosis based on 1063 patients in China

Abstract

The study aimed to explore the correlations between status of epidermal growth factor receptor (EGFR) mutations and distant metastases. A total of 1063 patients with lung adenocarcinoma indentified with status of EGFR mutations from August 2010 to May 2015 at Shanxi Cancer Hospital were enrolled. 456 patients were confirmed with EGFR mutations. The associations among EGFR mutations, clinical factors, and distant metastases at initial diagnosis were evaluated. Patients harboring EGFR mutation were more likely to be female (P < 0.001), with no smoking history (P < 0.001), brain metastases (P = 0.029), and higher ECOG performance scores (P = 0.025). The correlation between EGFR mutation status and distant metastases showed statistical significance both in univariate (P = 0.022) and in multivariate analysis (OR 1.573, 95 % CI 1.202–2.059, P = 0.001) especially in brain metastases (OR 1.675, 95 % CI 1.132–2.479, P = 0.010) and lung metastases (OR 1.571, 59 % CI 1.101–2.243 P = 0.013). Furthermore, the 19del mutations showed associations with brain metastases (OR 1.586, 95 % CI 1.028–2.447, P = 0.037), and lung metastases (OR 1.587, 95 % CI 1.065–2.346, P = 0.023). The exon 21 point mutations showed statistically significant differences in liver metastases (OR 1.987, 95 % CI 1.094–3.067, P = 0.024). In conclusion, the EGFR mutations in lung adenocarcinoma patients were independently correlated with distant metastases. Subgroup analyses showed that patients harboring 19del mutations presented different distant metastases compared with those harboring 21 point mutaions.

http://ift.tt/2ghSFsS

Comparison of immunophenotypes of primary breast carcinomas and multiple corresponding distant metastases: an autopsy study of 25 patients

Abstract

Phenotypical change in metastatic breast carcinoma has widely been accepted as an inherent biological feature rather than technical fault. We analyzed the immunohistochemical phenotype and histopathological features of 25 primary breast carcinomas and 90 corresponding distant metastases in 23 organs retrospectively. Histological slides were reviewed for prognostic and predictive factors. Overall, metastases were more similar to each other and often differed from the primary tumor. We created a 3-step grouping system based on the localization of metastases. Regions: tumors metastasizing to the abdominal region were likely to lose ER (p = 0.002); we detected loss of PR in metastases to the thorax (p = 0.039) and abdomen (p < 0.001). Organ systems: loss of ER and PR was observed in metastases to the gastrointestinal system (p = 0.026 and p = 0.001, respectively), in the respiratory system only the loss of PR was significant (p = 0.05). Individual organs: the primaries were likely to lose the hormone receptors in liver metastases (ER p = 0.026; PR p = 0.004). In lung metastases only loss of PR was apparent (p = 0.049). We did not observe significant change in HER2 status, regarding Ki67 change occurred only in bone metastases compared to the primary (p = 0.048). 7/25 patients' distant metastases had heterogeneous immunoprofiles. The later the metastasis was discovered the more likely it had a differing IHC profile compared to the primary tumor, patients who had longer OS had a higher chance to develop a discordant metastasis. Immunoprofile of metastases may differ from primary breast cancer and from each other, probably resulting in different response to therapy.

http://ift.tt/2fDugj9

Implications of vessel co-option in sorafenib-resistant hepatocellular carcinoma

Abstract

The reason why tumors generally have a modest or transient response to antiangiogenic therapy is not well understood. This poses a major challenge for sorafenib treatment of advanced hepatocellular carcinoma (HCC) where alternate therapies are lacking. We recently published a paper entitled "Co-option of liver vessels and not sprouting angiogenesis drives acquired sorafenib resistance in hepatocellular carcinoma" in the Journal of the National Cancer Institute, providing a potential explanation for this limited benefit. We found that in mice bearing HCCs that had acquired resistance to sorafenib, tumors had switched from using angiogenesis for growth to co-opting the liver vasculature by becoming more invasive. Accumulating evidence suggests that many human tumor types may use vessel co-option, which has profound implications for the use of anti-angiogenic agents for cancer treatment.

http://ift.tt/2fzPdZi

Development and validation of a nomogram for predicting the survival of patients with non-metastatic nasopharyngeal carcinoma after curative treatment

Abstract

Background

The TNM staging system is far from perfect in predicting the survival of individual cancer patients because only the gross anatomy is considered. The survival rates of the patients who have the same TNM stage disease vary across a wide spectrum. This study aimed to develop a nomogram that incorporates other clinicopathologic factors for predicting the overall survival (OS) of non-metastatic nasopharyngeal carcinoma (NPC) patients after curative treatments.

Methods

We retrospectively collected the clinical data of 1520 NPC patients who were diagnosed histologically between November 2000 and September 2003. The clinical data of a separate cohort of 464 patients who received intensity-modulated radiation therapy (IMRT) between 2001 and 2010 were also retrieved to examine the extensibility of the model. Cox regression analysis was used to identify the prognostic factors for building the nomogram. The predictive accuracy and discriminative ability were measured using the concordance index (c-index).

Results

We identified and incorporated 12 independent clinical factors into the nomogram. The calibration curves showed that the prediction of OS was in good agreement with the actual observation in the internal validation set and IMRT cohort. The c-index of the nomogram was statistically higher than that of the 7th edition TNM staging system for predicting the survival in both the primary cohort (0.69 vs. 0.62) and the IMRT cohort (0.67 vs. 0.63).

Conclusion

We developed and validated a novel nomogram that outperformed the TNM staging system in predicting the OS of non-metastatic NPC patients who underwent curative therapy.

http://ift.tt/2gtwV06

Candidate predisposing germline copy number variants in early onset colorectal cancer patients

Abstract

Purpose

A great proportion of the heritability of colorectal cancer (CRC) still remains unexplained, and rare variants, as well as copy number changes, have been proposed as potential candidates to explain the so-called 'missing heritability'. We aimed to identify rare high-to-moderately penetrant copy number variants (CNVs) in patients suspected of having hereditary CRC due to an early onset.

Methods/patients

We have selected for genome-wide copy number analysis, 27 MMR-proficient early onset CRC patients (<50 years) without identifiable germline mutations in Mendelian genes related to this phenotype. Rare CNVs were selected by removing all CNVs detected at MAF >1% in the in-house control CNV database (n = 629 healthy controls). Copy number assignment was checked by duplex real-time quantitative PCR or multiplex ligation probe amplification. Somatic mutation analysis in candidate genes included: loss of heterozygosity studies, point mutation screening, and methylation status of the promoter.

Results

We have identified two rare germline deletions involving the AK3 and SLIT2 genes in two patients. The search for a second somatic mutational event in the corresponding CRC tumors showed loss of heterozygosity in AK3, and promoter hypermethylation in SLIT2. Both genes have been previously related to colorectal carcinogenesis.

Conclusions

These findings suggest that AK3 and SLIT2 may be potential candidates involved in genetic susceptibility to CRC.

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Correlation between status of epidermal growth factor receptor mutation and distant metastases of lung adenocarcinoma upon initial diagnosis based on 1063 patients in China

Abstract

The study aimed to explore the correlations between status of epidermal growth factor receptor (EGFR) mutations and distant metastases. A total of 1063 patients with lung adenocarcinoma indentified with status of EGFR mutations from August 2010 to May 2015 at Shanxi Cancer Hospital were enrolled. 456 patients were confirmed with EGFR mutations. The associations among EGFR mutations, clinical factors, and distant metastases at initial diagnosis were evaluated. Patients harboring EGFR mutation were more likely to be female (P < 0.001), with no smoking history (P < 0.001), brain metastases (P = 0.029), and higher ECOG performance scores (P = 0.025). The correlation between EGFR mutation status and distant metastases showed statistical significance both in univariate (P = 0.022) and in multivariate analysis (OR 1.573, 95 % CI 1.202–2.059, P = 0.001) especially in brain metastases (OR 1.675, 95 % CI 1.132–2.479, P = 0.010) and lung metastases (OR 1.571, 59 % CI 1.101–2.243 P = 0.013). Furthermore, the 19del mutations showed associations with brain metastases (OR 1.586, 95 % CI 1.028–2.447, P = 0.037), and lung metastases (OR 1.587, 95 % CI 1.065–2.346, P = 0.023). The exon 21 point mutations showed statistically significant differences in liver metastases (OR 1.987, 95 % CI 1.094–3.067, P = 0.024). In conclusion, the EGFR mutations in lung adenocarcinoma patients were independently correlated with distant metastases. Subgroup analyses showed that patients harboring 19del mutations presented different distant metastases compared with those harboring 21 point mutaions.

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Comparison of immunophenotypes of primary breast carcinomas and multiple corresponding distant metastases: an autopsy study of 25 patients

Abstract

Phenotypical change in metastatic breast carcinoma has widely been accepted as an inherent biological feature rather than technical fault. We analyzed the immunohistochemical phenotype and histopathological features of 25 primary breast carcinomas and 90 corresponding distant metastases in 23 organs retrospectively. Histological slides were reviewed for prognostic and predictive factors. Overall, metastases were more similar to each other and often differed from the primary tumor. We created a 3-step grouping system based on the localization of metastases. Regions: tumors metastasizing to the abdominal region were likely to lose ER (p = 0.002); we detected loss of PR in metastases to the thorax (p = 0.039) and abdomen (p < 0.001). Organ systems: loss of ER and PR was observed in metastases to the gastrointestinal system (p = 0.026 and p = 0.001, respectively), in the respiratory system only the loss of PR was significant (p = 0.05). Individual organs: the primaries were likely to lose the hormone receptors in liver metastases (ER p = 0.026; PR p = 0.004). In lung metastases only loss of PR was apparent (p = 0.049). We did not observe significant change in HER2 status, regarding Ki67 change occurred only in bone metastases compared to the primary (p = 0.048). 7/25 patients' distant metastases had heterogeneous immunoprofiles. The later the metastasis was discovered the more likely it had a differing IHC profile compared to the primary tumor, patients who had longer OS had a higher chance to develop a discordant metastasis. Immunoprofile of metastases may differ from primary breast cancer and from each other, probably resulting in different response to therapy.

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Implications of vessel co-option in sorafenib-resistant hepatocellular carcinoma

Abstract

The reason why tumors generally have a modest or transient response to antiangiogenic therapy is not well understood. This poses a major challenge for sorafenib treatment of advanced hepatocellular carcinoma (HCC) where alternate therapies are lacking. We recently published a paper entitled "Co-option of liver vessels and not sprouting angiogenesis drives acquired sorafenib resistance in hepatocellular carcinoma" in the Journal of the National Cancer Institute, providing a potential explanation for this limited benefit. We found that in mice bearing HCCs that had acquired resistance to sorafenib, tumors had switched from using angiogenesis for growth to co-opting the liver vasculature by becoming more invasive. Accumulating evidence suggests that many human tumor types may use vessel co-option, which has profound implications for the use of anti-angiogenic agents for cancer treatment.

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Development and validation of a nomogram for predicting the survival of patients with non-metastatic nasopharyngeal carcinoma after curative treatment

Abstract

Background

The TNM staging system is far from perfect in predicting the survival of individual cancer patients because only the gross anatomy is considered. The survival rates of the patients who have the same TNM stage disease vary across a wide spectrum. This study aimed to develop a nomogram that incorporates other clinicopathologic factors for predicting the overall survival (OS) of non-metastatic nasopharyngeal carcinoma (NPC) patients after curative treatments.

Methods

We retrospectively collected the clinical data of 1520 NPC patients who were diagnosed histologically between November 2000 and September 2003. The clinical data of a separate cohort of 464 patients who received intensity-modulated radiation therapy (IMRT) between 2001 and 2010 were also retrieved to examine the extensibility of the model. Cox regression analysis was used to identify the prognostic factors for building the nomogram. The predictive accuracy and discriminative ability were measured using the concordance index (c-index).

Results

We identified and incorporated 12 independent clinical factors into the nomogram. The calibration curves showed that the prediction of OS was in good agreement with the actual observation in the internal validation set and IMRT cohort. The c-index of the nomogram was statistically higher than that of the 7th edition TNM staging system for predicting the survival in both the primary cohort (0.69 vs. 0.62) and the IMRT cohort (0.67 vs. 0.63).

Conclusion

We developed and validated a novel nomogram that outperformed the TNM staging system in predicting the OS of non-metastatic NPC patients who underwent curative therapy.

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The effect of isoflurane on 18 F-FDG uptake in the rat brain: a fully conscious dynamic PET study using motion compensation

Abstract

Background

In preclinical positron emission tomography (PET) studies an anaesthetic is used to ensure that the animal does not move during the scan. However, anaesthesia may have confounding effects on the drug or tracer kinetics under study, and the nature of these effects is usually not known.

Method

We have implemented a protocol for tracking the rigid motion of the head of a fully conscious rat during a PET scan and performing a motion compensated list-mode reconstruction of the data. Using this technique we have conducted eight rat studies to investigate the effect of isoflurane on the uptake of ¹⁸F-FDG in the brain, by comparing conscious and unconscious scans.

Results

Our results indicate that isoflurane significantly decreases the whole brain uptake, as well as decreasing the relative regional FDG uptake in the cortex, diencephalon, and inferior colliculi, while increasing it in the vestibular nuclei. No statistically significant changes in FDG uptake were observed in the cerebellum and striata.

Conclusion

The applied event-based motion compensation technique allowed for the investigation of the effect of isoflurane on FDG uptake in the rat brain using fully awake and unrestrained rats, scanned dynamically from the moment of injection. A significant effect of the anaesthesia was observed in various regions of the brain.

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The effect of isoflurane on 18 F-FDG uptake in the rat brain: a fully conscious dynamic PET study using motion compensation

Abstract

Background

In preclinical positron emission tomography (PET) studies an anaesthetic is used to ensure that the animal does not move during the scan. However, anaesthesia may have confounding effects on the drug or tracer kinetics under study, and the nature of these effects is usually not known.

Method

We have implemented a protocol for tracking the rigid motion of the head of a fully conscious rat during a PET scan and performing a motion compensated list-mode reconstruction of the data. Using this technique we have conducted eight rat studies to investigate the effect of isoflurane on the uptake of ¹⁸F-FDG in the brain, by comparing conscious and unconscious scans.

Results

Our results indicate that isoflurane significantly decreases the whole brain uptake, as well as decreasing the relative regional FDG uptake in the cortex, diencephalon, and inferior colliculi, while increasing it in the vestibular nuclei. No statistically significant changes in FDG uptake were observed in the cerebellum and striata.

Conclusion

The applied event-based motion compensation technique allowed for the investigation of the effect of isoflurane on FDG uptake in the rat brain using fully awake and unrestrained rats, scanned dynamically from the moment of injection. A significant effect of the anaesthesia was observed in various regions of the brain.

http://ift.tt/2gKE4K7

The regulation of the mitochondrial apoptotic pathway by glucocorticoid receptor in collaboration with Bcl-2 family proteins in developing T cells

Abstract

Glucocorticoids (GC) are important in the regulation of selection and apoptosis of CD4⁺CD8⁺ double-positive (DP) thymocytes. The pronounced GC-sensitivity of DP thymocytes, observed earlier, might be due to the combination of classical (genomic) and alternative (non-genomic) glucocorticoid receptor (GR) signaling events modifying activation or apoptotic pathways. In particular, the previously demonstrated mitochondrial translocation of activated GR in DP thymocytes offered a fascinating explanation for their pronounced GC-induced apoptosis sensitivity. However, the fine molecular details how the mitochondrial translocation of GR might regulate apoptosis remained unclear. Therefore, in the present study, we intended to examine which apoptotic pathways could be involved in GC-induced thymocyte apoptosis. Furthermore we investigated the potential relationship between the GR and Bcl-2 proteins. Using an in vitro test system, thymocytes from 4-week-old BALB/c mice, were treated with the GC-analogue dexamethasone (DX). Bax accumulated in mitochondria upon DX treatment. Mitochondrial GR showed association with members of the Bcl-2 family: Bak, Bim, Bcl-x_L. Elevated Cytochrome C, and active caspase-3, -8, and -9 levels were detected in thymocytes after DX treatment. These results support the hypothesis that in early phases of GC-induced thymocyte apoptosis, the mitochondrial pathway plays a crucial role, confirmed by the release of Cytochrome C and the activation of caspase-9. The activation of caspase-8 was presumably due to cross-talk between apoptotic signaling pathways. We propose that the GC-induced mitochondrial accumulation of Bax and the interaction between the GR and Bim, Bcl-x_L and Bak could play a role in the regulation of thymocyte apoptosis.

http://ift.tt/2fDfRn8

Antitumor activity of TY-011 against gastric cancer by inhibiting Aurora A, Aurora B and VEGFR2 kinases

Overexpression of Aurora A and B has been reported in a wide range of tumor types, including gastric cancer. Anti-angiogenesis has been considered as an important therapeutic modality in advanced gastric cance...

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Candidate predisposing germline copy number variants in early onset colorectal cancer patients

Abstract

Purpose

A great proportion of the heritability of colorectal cancer (CRC) still remains unexplained, and rare variants, as well as copy number changes, have been proposed as potential candidates to explain the so-called 'missing heritability'. We aimed to identify rare high-to-moderately penetrant copy number variants (CNVs) in patients suspected of having hereditary CRC due to an early onset.

Methods/patients

We have selected for genome-wide copy number analysis, 27 MMR-proficient early onset CRC patients (<50 years) without identifiable germline mutations in Mendelian genes related to this phenotype. Rare CNVs were selected by removing all CNVs detected at MAF >1% in the in-house control CNV database (n = 629 healthy controls). Copy number assignment was checked by duplex real-time quantitative PCR or multiplex ligation probe amplification. Somatic mutation analysis in candidate genes included: loss of heterozygosity studies, point mutation screening, and methylation status of the promoter.

Results

We have identified two rare germline deletions involving the AK3 and SLIT2 genes in two patients. The search for a second somatic mutational event in the corresponding CRC tumors showed loss of heterozygosity in AK3, and promoter hypermethylation in SLIT2. Both genes have been previously related to colorectal carcinogenesis.

Conclusions

These findings suggest that AK3 and SLIT2 may be potential candidates involved in genetic susceptibility to CRC.

from Cancer via ola Kala on Inoreader http://ift.tt/2gsR2rw
via IFTTT

Candidate predisposing germline copy number variants in early onset colorectal cancer patients

Abstract

Purpose

A great proportion of the heritability of colorectal cancer (CRC) still remains unexplained, and rare variants, as well as copy number changes, have been proposed as potential candidates to explain the so-called 'missing heritability'. We aimed to identify rare high-to-moderately penetrant copy number variants (CNVs) in patients suspected of having hereditary CRC due to an early onset.

Methods/patients

We have selected for genome-wide copy number analysis, 27 MMR-proficient early onset CRC patients (<50 years) without identifiable germline mutations in Mendelian genes related to this phenotype. Rare CNVs were selected by removing all CNVs detected at MAF >1% in the in-house control CNV database (n = 629 healthy controls). Copy number assignment was checked by duplex real-time quantitative PCR or multiplex ligation probe amplification. Somatic mutation analysis in candidate genes included: loss of heterozygosity studies, point mutation screening, and methylation status of the promoter.

Results

We have identified two rare germline deletions involving the AK3 and SLIT2 genes in two patients. The search for a second somatic mutational event in the corresponding CRC tumors showed loss of heterozygosity in AK3, and promoter hypermethylation in SLIT2. Both genes have been previously related to colorectal carcinogenesis.

Conclusions

These findings suggest that AK3 and SLIT2 may be potential candidates involved in genetic susceptibility to CRC.

http://ift.tt/2gsR2rw

Stereotactic body radiation therapy (SBRT) for centrally located primary and recurrent non-small cell lung cancer (NSCLC): analysis of toxicity and local control

Abstract

Purpose/objectives

Stereotactic body radiation therapy for centrally located lung tumors has been associated with increased risk of toxicity. A current study aims to evaluate tumor control and toxicity in large cohort of centrally located lesions.

Methods

Central location was defined as tumors within 2 cm of the bronchial tree, trachea, major vessels, esophagus, heart, pericardium, brachial plexus, or vertebral body. Tumors were biopsy proven or PET positive and included recurrent or primary non-small cell lung cancer (NSCLC). A dose was prescribed to a non-uniform planning target volume based on the internal tumor volume constructed from a 4D CT scan allowing for tumor motion. The treatment plans consisted of non-coplanar static aperture arcs and non-coplanar static fields. Treatments were delivered using 6MV X-rays with image guidance.

Results

At a median follow-up of 12.3 months, 107 total NSCLC tumors were retrospectively reviewed. A cohort consisted of primary (n = 57) and recurrent (n = 50) NSCLC tumors with subset of recurrent lesions including 27 hilar or mediastinal lymph nodes. Median and most frequent dose were 45 Gy in four fractions treated once weekly. Estimated 2-year Kaplan-Meier survival was 81.7%, with a significant survival advantage between primary and recurrent (p = 0.003). Eleven patients failed locally giving a 2-year actuarial local control rate of 80.7%, with control rates of 82.5 and 79.2% for primary and recurrent tumors, respectively (p = 0.828). Regional control at 2 years was not significantly different for primary (72.6%) and recurrent (62.7%). Analysis of toxicity revealed no grade 4 or 5 events. One grade 3 event was reported as pneumonitis. Grade 2 toxicity occurred in 10 patients, including dyspnea (1), chest wall pain (2), pneumonitis (4), rib fracture (1), and cough (2).

Conclusions

Moderate prescription dosing, treated once weekly, offers acceptable local control rates for centrally located tumors including recurrent mediastinal and hilar lymph nodes. Toxicity was minimal with the majority of patients experiencing no treatment-related adverse events.

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Stereotactic body radiation therapy (SBRT) for centrally located primary and recurrent non-small cell lung cancer (NSCLC): analysis of toxicity and local control

Abstract

Purpose/objectives

Stereotactic body radiation therapy for centrally located lung tumors has been associated with increased risk of toxicity. A current study aims to evaluate tumor control and toxicity in large cohort of centrally located lesions.

Methods

Central location was defined as tumors within 2 cm of the bronchial tree, trachea, major vessels, esophagus, heart, pericardium, brachial plexus, or vertebral body. Tumors were biopsy proven or PET positive and included recurrent or primary non-small cell lung cancer (NSCLC). A dose was prescribed to a non-uniform planning target volume based on the internal tumor volume constructed from a 4D CT scan allowing for tumor motion. The treatment plans consisted of non-coplanar static aperture arcs and non-coplanar static fields. Treatments were delivered using 6MV X-rays with image guidance.

Results

At a median follow-up of 12.3 months, 107 total NSCLC tumors were retrospectively reviewed. A cohort consisted of primary (n = 57) and recurrent (n = 50) NSCLC tumors with subset of recurrent lesions including 27 hilar or mediastinal lymph nodes. Median and most frequent dose were 45 Gy in four fractions treated once weekly. Estimated 2-year Kaplan-Meier survival was 81.7%, with a significant survival advantage between primary and recurrent (p = 0.003). Eleven patients failed locally giving a 2-year actuarial local control rate of 80.7%, with control rates of 82.5 and 79.2% for primary and recurrent tumors, respectively (p = 0.828). Regional control at 2 years was not significantly different for primary (72.6%) and recurrent (62.7%). Analysis of toxicity revealed no grade 4 or 5 events. One grade 3 event was reported as pneumonitis. Grade 2 toxicity occurred in 10 patients, including dyspnea (1), chest wall pain (2), pneumonitis (4), rib fracture (1), and cough (2).

Conclusions

Moderate prescription dosing, treated once weekly, offers acceptable local control rates for centrally located tumors including recurrent mediastinal and hilar lymph nodes. Toxicity was minimal with the majority of patients experiencing no treatment-related adverse events.

http://ift.tt/2gsUExH

Development and validation of a nomogram for predicting the survival of patients with non-metastatic nasopharyngeal carcinoma after curative treatment

The TNM staging system is far from perfect in predicting the survival of individual cancer patients because only the gross anatomy is considered. The survival rates of the patients who have the same TNM stage ...

from Cancer via ola Kala on Inoreader http://ift.tt/2ghbZq9
via IFTTT

Implications of vessel co-option in sorafenib-resistant hepatocellular carcinoma

The reason why tumors generally have a modest or transient response to antiangiogenic therapy is not well understood. This poses a major challenge for sorafenib treatment of advanced hepatocellular carcinoma (...

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

Development and validation of a nomogram for predicting the survival of patients with non-metastatic nasopharyngeal carcinoma after curative treatment

The TNM staging system is far from perfect in predicting the survival of individual cancer patients because only the gross anatomy is considered. The survival rates of the patients who have the same TNM stage ...

http://ift.tt/2ghbZq9

Implications of vessel co-option in sorafenib-resistant hepatocellular carcinoma

The reason why tumors generally have a modest or transient response to antiangiogenic therapy is not well understood. This poses a major challenge for sorafenib treatment of advanced hepatocellular carcinoma (...

http://ift.tt/2fCKVDP

Treatment of the axilla in patients with primary breast cancer and low burden axillary disease: limitations of the evidence from randomised controlled trials

Publication date: Available online 25 November 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): J.F.R. Robertson, P.J.J. Herrod, J. Matthew, L.S. Kilburn, C.E. Coles, I. Bradbury
Invasive breast cancer is the second most common cancer worldwide. It is known to metastasise to the regional axillary lymph nodes but there has been debate over what is the best way to stage and treat the axilla in patients presenting with primary breast cancer. Multiple trials over the last two decades have led to a change in practice from routine axillary lymph node dissection to sentinel lymph node biopsy in patients who are clinically lymph node negative preoperatively. This has resulted in new questions regarding subsequent treatment of some patients. This review will critically appraise the evidence on axillary treatment in patients with low burden axillary disease and highlight limitations of relevant randomised controlled trials.



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Cholangiocarcinoma

Publication date: Available online 25 November 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): Michela Squadroni, Luca Tondulli, Gemma Gatta, Stefania Mosconi, Giordano Beretta, Roberto Labianca
Biliary tract cancer accounts for <1% of all cancers and affects chiefly an elderly population, with predominance in men. We distinguish cholangiocarcinoma (intrahepatic, hilar and distal) and gallbladder cancer, with different pathogenesis and prognosis.The treatment is based on surgery (whenever possible), radiotherapy in selected cases, and chemotherapy. The standard cytotoxic treatment for advanced/metastatic disease is represented by the combination of gemcitabine and cisplatin, whereas fluoropyrimidines are generally administered in second line setting. At the present time, no biologic drug demonstrated a clear efficacy in this cancer, although the molecular characterisation could provide a promising basis for experimental treatments. A good supportive care and an early palliative care are warranted in most patients and should be delivered as a part of a global approach.



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New perspectives in the second-line treatment of non squamous NSCLC patients: Results from a large Italian Lung Cancer Working Group

Publication date: Available online 25 November 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): Diego Cortinovis, Vanesa Gregorc, Maria Rita Migliorino, Maria Ida Abate, Anna Manzo, Umberto Malapelle, Alessandro Morabito
Lung cancer is still considered a big killer among cancer diseases, due to high incidence and mortality rates. The newer frontiers of therapeutic development regard the discovery of oncogene driven tumours: however, the majority of NSCLC patients are wild type and they cannot be treated with targeted based agents. The recent positive results obtained with immunotherapy and with the combination of angiogenesis inhibitors and docetaxel, changed the therapeutic scenario of the second line therapy of non squamous NSCLC without actionable mutations. A major issue is currently the lack of predictive biomarkers that could help the oncologists in the choice of the best second-line treatment. Aim of this project was to define an optimal therapeutic pathway for patients with non-squamous NSCLC, through a working group of a large number of Italian lung cancer oncologists. Panellists have identified and discussed the more significant criteria in the second-line setting for a therapeutic decision between the combination of angiogenesis inhibitors plus chemotherapy or immunotherapy. Finally, they expressed their preference on each criterion, building a proposal of a decision-making tree for a second-line treatment of non-squamous NSCLC.



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Tumor infiltrating lymphocytes in gastrointestinal tumors: controversies and future clinical implications

Publication date: Available online 25 November 2016
Source:Critical Reviews in Oncology/Hematology
Author(s): Cinzia Solinas, Grazia Pusole, Laura Demurtas, Marco Puzzoni, Roberta Mascia, Gilberto Morgan, Riccardo Giampieri, Mario Scartozzi
Chronic inflammation following infections, autoimmune diseases or exposure to environmental irritants plays a crucial role in tumor development and influences the host immune response to neoplastic cells. The presence of an anti-tumor immune infiltrate is often associated with better outcomes in gastro-intestinal primary cancers, particularly in those with high microsatellite instability (MSI-H). Immunotherapeutic drugs inhibiting the PD-1 and PD-L1 pathway showed promising results in the treatment of these patients in the metastatic setting. The aim of this review is to resume the role tumor infiltrating lymphocytes (TILs) play in gastrointestinal tumors, underlining their potential value as a prognostic and predictive biomarker. TILs assessment could identify subsets of patients with high extent of TILs and better prognosis, that could be spared from adjuvant systemic treatments. Immune infiltration parameters might be additional predictors of a greater benefit from the immunotherapy with the immune checkpoint blockade.



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Monitoring the effects of doxorubicin on 3D-spheroid tumor cells in real-time

http://ift.tt/2fjgPXb