No abstract availablehttp://ift.tt/2DughJr
Cancer Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Σάββατο 20 Ιανουαρίου 2018
Intratidal Analysis of Intraoperative Respiratory System Mechanics: Keep it Simple
No abstract availablehttp://ift.tt/2DughJr
A Novel Approach to Synthesize the Evidence on Analgesic Adjuvants for Postoperative Pain
No abstract availablehttp://ift.tt/2DR2bQc
Alkalinized Lidocaine Preloaded Endotracheal Tube Cuffs Reduce Emergence Cough After Brief Surgery: A Prospective Randomized Trial
BACKGROUND: Alkalinized lidocaine in the endotracheal tube (ETT) cuff decreases the incidence of cough and throat pain on emergence after surgery lasting more than 2 hours. However, alkalinized lidocaine needs 60–120 minutes to cross the ETT cuff membrane; therefore, its usefulness in shorter duration surgery is unknown. This prospective double-blind randomized controlled trial tested the hypothesis that alkalinized lidocaine would reduce the incidence of emergence cough after surgeries lasting 90 minutes before intubation with either 2 mL of 2% lidocaine and 8 mL of 8.4% bicarbonate (group AL) or 10 mL of normal saline (group S). Cuffs were emptied immediately before intubation. After intubation, either 2 mL of 2% lidocaine (AL) or 2 mL of saline (S) were injected into the cuff. Additional 8.4% bicarbonate (AL) or saline (S) was injected into the cuff until there was no air leak. Anesthesia was maintained using desflurane, rocuronium, and either fentanyl or sufentanil to maintain vital signs within 20% of baseline values. Opioids administered in prophylaxis of extubation cough were proscribed. A standardized "no touch" emergence technique was used. A blinded assessor noted any cough above 0.2 minimum alveolar concentration (MAC) of expired desflurane. At 0.2 MAC, once every 30 seconds, the patient was instructed to open his eyes and extubation occurred once a directed response was noted. RESULTS: A total of 213 patients were randomized and 100 patients in each group completed the experimental protocol. The incidence of extubation cough in group AL was 12%, significantly lower (1-sided P = .045) than the 22% incidence in group S. The 1-tailed risk ratio for cough in group AL was 0.55 (0–0.94, P = .045). Total amount of opioids administered (P = .194), ETT cuff preloading times (P = .259), and extubation times (P = .331) were not significantly different between groups. The average duration of surgery was 59 ± 28 minutes in group AL and 52 ± 29 minutes in group S (P = .057). CONCLUSIONS: Alkalinized lidocaine in the ETT cuff significantly decreased general anesthesia emergence cough after surgeries with an average duration of slightlyhttp://ift.tt/2F17QCf
MicroRNAs as Clinical Biomarkers and Therapeutic Tools in Perioperative Medicine
Over the past decade, evolutionarily conserved, noncoding small RNAs—so-called microRNAs (miRNAs)—have emerged as important regulators of virtually all cellular processes. miRNAs influence gene expression by binding to the 3′-untranslated region of protein-coding RNA, leading to its degradation and translational repression. In medicine, miRNAs have been revealed as novel, highly promising biomarkers and as attractive tools and targets for novel therapeutic approaches. miRNAs are currently entering the field of perioperative medicine, and they may open up new perspectives in anesthesia, critical care, and pain medicine. In this review, we provide an overview of the biology of miRNAs and their potential role in human disease. We highlight current paradigms of miRNA-mediated effects in perioperative medicine and provide a survey of miRNA biomarkers in the field known so far. Finally, we provide a perspective on miRNA-based therapeutic opportunities and perspectives.http://ift.tt/2F18Wy1
Pediatric Anesthesiology Fellows’ Perception of Quality of Attending Supervision and Medical Errors
BACKGROUND: Appropriate supervision has been shown to reduce medical errors in anesthesiology residents and other trainees across various specialties. Nonetheless, supervision of pediatric anesthesiology fellows has yet to be evaluated. The main objective of this survey investigation was to evaluate supervision of pediatric anesthesiology fellows in the United States. We hypothesized that there was an indirect association between perceived quality of faculty supervision of pediatric anesthesiology fellow trainees and the frequency of medical errors reported. METHODS: A survey of pediatric fellows from 53 pediatric anesthesiology fellowship programs in the United States was performed. The primary outcome was the frequency of self-reported errors by fellows, and the primary independent variable was supervision scores. Questions also assessed barriers for effective faculty supervision. RESULTS: One hundred seventy-six pediatric anesthesiology fellows were invited to participate, and 104 (59%) responded to the survey. Nine of 103 (9%, 95% confidence interval [CI], 4%–16%) respondents reported performing procedures, on >1 occasion, for which they were not properly trained for. Thirteen of 101 (13%, 95% CI, 7%–21%) reported making >1 mistake with negative consequence to patients, and 23 of 104 (22%, 95% CI, 15%–31%) reported >1 medication error in the last year. There were no differences in median (interquartile range) supervision scores between fellows who reported >1 medication error compared to those reporting ≤1 errors (3.4 [3.0–3.7] vs 3.4 [3.1–3.7]; median difference, 0; 99% CI, −0.3 to 0.3; P = .96). Similarly, there were no differences in those who reported >1 mistake with negative patient consequences, 3.3 (3.0–3.7), compared with those who did not report mistakes with negative patient consequences (3.4 [3.3–3.7]; median difference, 0.1; 99% CI, −0.2 to 0.6; P = .35). CONCLUSIONS: We detected a high rate of self-reported medication errors in pediatric anesthesiology fellows in the United States. Interestingly, fellows' perception of quality of faculty supervision was not associated with the frequency of reported errors. The current results with a narrow CI suggest the need to evaluate other potential factors that can be associated with the high frequency of reported errors by pediatric fellows (eg, fatigue, burnout). The identification of factors that lead to medical errors by pediatric anesthesiology fellows should be a main research priority to improve both trainee education and best practices of pediatric anesthesia.http://ift.tt/2F17HPd
Ischemic Preconditioning and the Role of Antifibrinolytic Drugs: Translation From Bench to Bedside
No abstract availablehttp://ift.tt/2DRYI3R
New Diabetes Medications Raise New Perioperative Concerns for the Anesthesiologist
No abstract availablehttp://ift.tt/2DQiIn7
Informed Consent and Cognitive Dysfunction After Noncardiac Surgery in the Elderly
Cognitive dysfunction 3 months after noncardiac surgery in the elderly satisfies informed consent thresholds of foreseeability in 10%–15% of patients, and materiality with new deficits observed in memory and executive function in patients with normal test performance beforehand. At present, the only safety step to avoid cognitive dysfunction after surgery is to forego surgery, thereby precluding the benefits of surgery with removal of pain and inflammation, and resumption of normal nutrition, physical activity, and sleep. To assure that consent for surgery is properly informed, risks of both cognitive dysfunction and alternative management strategies must be discussed with patients by the surgery team before a procedure is scheduled.
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http://ift.tt/2EWYnfy
Sonic hedgehog and Wnt/β-catenin pathways mediate curcumin inhibition of breast cancer stem cells
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Sonic hedgehog and Wnt/β-catenin pathways mediate curcumin inhibition of breast cancer stem cells
http://ift.tt/2rsfUu2
Antitumor effects of histone deacetylase inhibitor suberoylanilide hydroxamic acid in epidermal growth factor receptor-mutant non-small-cell lung cancer lines in vitro and in vivo
Histone acetylation is one of the most abundant post-translational modifications in eukaryotic cells; aberrant histone acetylation is related to a range of cancer types because of the dysregulation of histone deacetylases (HDACs). Inhibition of HDACs leads to suppression of tumor growth in multiple cancers, whereas the inhibitory effects of HDAC inhibitors remain incompletely understood in epidermal growth factor receptor (EGFR)-mutant lung cancers. In this study, the antitumor effects of HDACs inhibitor suberoylanilide hydroxamic acid (SAHA, vorinostat) were examined in EGFR-mutant lung cancer cell lines. The results of the present work showed that SAHA markedly inhibited cell viability and proliferation, induced cell apoptosis by arresting the cell cycle in the G2/M phase, and significantly reduced tumor growth in a xenograft model. Further study confirmed that the suppression function of SAHA might be mediated by regulating the ERK-dependent and/or the AKT-dependent pathway; meanwhile, angiogenesis abrogation induced by SAHA exerted effects on tumor regression in vivo. Taken together, our results identify the antitumor effects of HDACs inhibitor SAHA as an alternative therapeutic application for the epigenetic treatment of EGFR-mutant non-small-cell lung cancer. * Ye Wei and Fangzheng Zhou contributed equally to the writing of this article. Correspondence to Dandan Yu, MD, Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China Tel/fax: +86 027 6565 9931; e-mail: yudan7088@hotmail.com or Correspondence to Gang Wu, PhD, Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China Tel/fax: +86 027 6565 9931; e-mail: xhzlwg@163.com Received August 29, 2017 Accepted January 3, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2FYB8Db
http://ift.tt/2FYB8Db
Antitumor effects of histone deacetylase inhibitor suberoylanilide hydroxamic acid in epidermal growth factor receptor-mutant non-small-cell lung cancer lines in vitro and in vivo
Histone acetylation is one of the most abundant post-translational modifications in eukaryotic cells; aberrant histone acetylation is related to a range of cancer types because of the dysregulation of histone deacetylases (HDACs). Inhibition of HDACs leads to suppression of tumor growth in multiple cancers, whereas the inhibitory effects of HDAC inhibitors remain incompletely understood in epidermal growth factor receptor (EGFR)-mutant lung cancers. In this study, the antitumor effects of HDACs inhibitor suberoylanilide hydroxamic acid (SAHA, vorinostat) were examined in EGFR-mutant lung cancer cell lines. The results of the present work showed that SAHA markedly inhibited cell viability and proliferation, induced cell apoptosis by arresting the cell cycle in the G2/M phase, and significantly reduced tumor growth in a xenograft model. Further study confirmed that the suppression function of SAHA might be mediated by regulating the ERK-dependent and/or the AKT-dependent pathway; meanwhile, angiogenesis abrogation induced by SAHA exerted effects on tumor regression in vivo. Taken together, our results identify the antitumor effects of HDACs inhibitor SAHA as an alternative therapeutic application for the epigenetic treatment of EGFR-mutant non-small-cell lung cancer. * Ye Wei and Fangzheng Zhou contributed equally to the writing of this article. Correspondence to Dandan Yu, MD, Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China Tel/fax: +86 027 6565 9931; e-mail: yudan7088@hotmail.com or Correspondence to Gang Wu, PhD, Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China Tel/fax: +86 027 6565 9931; e-mail: xhzlwg@163.com Received August 29, 2017 Accepted January 3, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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Patterns of age-specific socioeconomic inequalities in net survival for common cancers in Taiwan, a country with universal health coverage
Source:Cancer Epidemiology, Volume 53
Author(s): Li-Hsin Chien, Tzu-Jui Tseng, Fang-Yu Tsai, Jie-Huei Wang, Chao A. Hsiung, Tsang-Wu Liu, I-Shou Chang
IntroductionIn high-income countries, advances in early diagnosis and treatment have improved cancer survival. However, socioeconomic inequalities in survival have persisted or increased for some adult cancers.Materials and methodsWe assessed net survival for the 20 most common adult cancers in Taiwan. They were stratified into six age groups and three socioeconomic groups.ResultsOut of 120 cancer site and age group combinations, 49 showed improvements in 5-year net survival from 2000–2004 to 2005–2010. Only cervix uteri cancer in the 35–49-year age group showed a deterioration. During 2000–2010, 13 of the 20 cancer cases experienced socioeconomic inequalities for all age groups combined, and the deprivation gaps varied with cancer site and age at diagnosis. For the five most common cancers – liver, colon and rectum, lung, breast, and oral – there were socioeconomic inequalities, and 5-year net survival improved for most or all of the six age groups from 2000–2004 to 2005–2010.ConclusionReducing socioeconomic inequality in survival may lead to improvements in survival overall. We should focus on the age groups with large deprivation gaps. Our results are useful for prioritizing cancer sites and age groups for in-depth socioeconomic disparity studies and for proposing interventions for health disparity reductions and net cancer survival improvements.
http://ift.tt/2DrF2H4
Patterns of age-specific socioeconomic inequalities in net survival for common cancers in Taiwan, a country with universal health coverage
Source:Cancer Epidemiology, Volume 53
Author(s): Li-Hsin Chien, Tzu-Jui Tseng, Fang-Yu Tsai, Jie-Huei Wang, Chao A. Hsiung, Tsang-Wu Liu, I-Shou Chang
IntroductionIn high-income countries, advances in early diagnosis and treatment have improved cancer survival. However, socioeconomic inequalities in survival have persisted or increased for some adult cancers.Materials and methodsWe assessed net survival for the 20 most common adult cancers in Taiwan. They were stratified into six age groups and three socioeconomic groups.ResultsOut of 120 cancer site and age group combinations, 49 showed improvements in 5-year net survival from 2000–2004 to 2005–2010. Only cervix uteri cancer in the 35–49-year age group showed a deterioration. During 2000–2010, 13 of the 20 cancer cases experienced socioeconomic inequalities for all age groups combined, and the deprivation gaps varied with cancer site and age at diagnosis. For the five most common cancers – liver, colon and rectum, lung, breast, and oral – there were socioeconomic inequalities, and 5-year net survival improved for most or all of the six age groups from 2000–2004 to 2005–2010.ConclusionReducing socioeconomic inequality in survival may lead to improvements in survival overall. We should focus on the age groups with large deprivation gaps. Our results are useful for prioritizing cancer sites and age groups for in-depth socioeconomic disparity studies and for proposing interventions for health disparity reductions and net cancer survival improvements.
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Cardiopulmonary Aerobic Fitness Assessment During Maximal and Submaximal Exercise Testing in Pediatric Oncology Patients After Chemotherapy
Purpose: The cardiopulmonary exercise test (CPET) is a valuable tool to assess cardiopulmonary exercise capacity in pediatric oncology patients after chemotherapy. In addition, few studies on the utility of submaximal testing have been performed, which could be important as some patients are unable to complete a maximal effort test secondary to deconditioning by both disease and treatment. Materials and Methods: We performed a retrospective chart review of pediatric cancer patients exposed to chemotherapy from 1992 to 2013 who underwent CPET with cycle ergometry (n=27). The study patients were compared with age-matched, sex-matched, and size-matched normal controls. The submaximal measure recorded was the oxygen consumption (VO2)@respiratory exchange ratio (RER) 1.0 during a maximal effort test. Results: The chemotherapy group demonstrated significantly lower exercise time (9.2±3.6 vs. 11.4±3.8; P=0.008), total work capacity (4914.4±3290.3 vs. 7664.4±4289.5; P=0.004), systolic blood pressure at peak exercise (162.9±23.2 vs. 177.3±23.8; P=0.01), indexed peak VO2 (33.9±6.9 vs. 40.0±6.3; P=0.001), and indexed peak oxygen pulse (6.1±1.3 vs. 7.0±1.5; P=0.004)). For the submaximal outcome measured, 11/27 of the chemotherapy patients had VO2@RER 1.0 values
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Clinical and radiological response of BRAF inhibition and MEK inhibition in patients with brain metastases from BRAF-mutated melanoma
Patients with brain metastases (BM) from melanoma have an overall survival (OS) of 2–6 months after whole-brain radiotherapy. Targeted therapy (TT) is an effective treatment for BRAF-mutated metastatic melanoma. Moreover, recent studies indicate intracranial responses of TT in patients with BM. We analyzed 146 patients with BM from BRAF-mutated melanoma treated with vemurafenib, dabrafenib, or dabrafenib+trametinib between 2010 and 2016. We determined clinical and radiological response, progression-free survival (PFS), and OS. Median OS of patients treated with dabrafenib+trametinib was 11.2 months [n=30; 95% confidence interval (CI): 6.8–15.7], 8.8 months for dabrafenib alone (n=31; 95% CI: 3.9–13.7), and 5.7 months for vemurafenib (n=85; 95% CI: 4.6–6.8). A significantly longer OS was observed in the dabrafenib+trametinib group than in the vemurafenib group (hazard ratio for death, 0.52; 95% CI: 0.30–0.89; P=0.02). Median intracranial PFS of all patients was 4.1 months. Median intracranial PFS for patients treated with dabrafenib+trametinib was 5.8 months (95% CI: 3.2–8.5), 5.7 months (95% CI: 3.0–8.4) for dabrafenib, and 3.6 months (95% CI: 3.5–3.8) for vemurafenib (P=0.54). A total of 63 (43%) patients had symptomatic BM. Intracranial disease control rate at 8 weeks in these patients was 65 versus 70% extracranially. Neurological symptoms improved in 46% of patients with symptomatic BM, whereas in 21%, they remained stable. Median OS in patients with BM from BRAF-mutated melanoma treated with dabrafenib+trametinib was significantly longer than for vemurafenib. Improvement of neurological symptoms was seen in almost half of the patients with symptomatic BM treated with TT. Correspondence to Dieta Brandsma, MD, PhD, Department of Neuro-Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands Tel: +31 20 512 2570; fax: +31 20 512 2572; e-mail: d.brandsma@nki.nl Received August 13, 2017 Accepted December 15, 2017 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
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http://ift.tt/2rn3vrf
Tolerance and outcomes of stereotactic radiosurgery combined with anti-programmed cell death-1 (pembrolizumab) for melanoma brain metastases
Anti-programmed cell death-1 (anti-PD1) antibodies are currently the first-line treatment for patients with metastatic BRAF wild-type melanoma, alone or combined with the anti-CTLA4 monoclonal antibody, ipilimumab. To date, data on safety and the outcomes of patients treated with the anti-PD1 monoclonal antibodies, pembrolizumab (PB), or nivolumab, combined with stereotactic radiosurgery (SRS), for melanoma brain metastases (MBM) are scarce. We retrospectively reviewed all patients with MBM treated with PB combined with SRS between 2012 and 2015. The primary endpoint was neurotoxicity. The secondary endpoints were local, distant intracranial controls and overall survival (OS). Among 74 patients with MBM treated with SRS, 25 patients with a total of 58 MBM treated with PB combined with SRS within 6 months were included. Radiation necrosis, occurring within a median time of 6.5 months, was observed for four MBM (6.8%) in four patients. No other significant SRS-related adverse event was observed. After a median follow-up of 8.4 months, local control was achieved in 46 (80%) metastases and 17 (68%) patients. Perilesional oedema and intratumour haemorrhage appearing or increasing after SRS were associated with local progression (P
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http://ift.tt/2G0hmHs
Success of rechallenging dabrafenib and trametinib combination therapy after trametinib-induced rhabdomyolysis: a case report
The mitogen-activated protein kinase pathway regulates cell growth and differentiation and is activated by BRAF mutations. BRAF mutations are present in about 40–50% of cutaneous melanomas. More than 90% of BRAF mutations are the V600E type. BRAF inhibitor (dabrafenib or vemurafenib) and MEK inhibitor (trametinib or cobimetinib) combination therapies are effective for BRAF-mutant advanced melanomas. A variety of side effects have been observed with combination therapy including pyrexia, fatigue, nausea, and vomiting. Rhabdomyolysis is one of the most severe adverse events, but it is very rare. Only two cases of rhabdomyolysis have been reported in clinical trials. A 41-year-old Japanese woman with cutaneous melanoma was started on a combination of dabrafenib and trametinib therapy after failure of immune checkpoint therapy. One month later, she complained of myalgia and fatigue and was shifted to our hospital. She was diagnosed with trametinib-induced rhabdomyolysis and showed improvement only with a high volume of fluid infusion. We stopped combination therapy, but there were no useful treatment options for her. After resuming dabrafenib, followed by trametinib, she did not have any problems. This is the first case of a patient with metastatic cutaneous melanoma who could recommence combination therapy after trametinib-associated rhabdomyolysis. We assume that not all patients experience recurrence of rhabdomyolysis in trametinib-induced rhabdomyolysis. As few cases have been reported, more information is needed. We have to evaluate safety carefully if rechallenging combination therapy. Correspondence to Yusuke Muto, MD, Department of Dermatologic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan Tel: +81 033 542 2511; fax: +81 033 545 3567; e-mail: ymuto@ncc.go.jp Received May 8, 2017 Accepted November 19, 2017 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2roMeOr
http://ift.tt/2roMeOr
Cardiopulmonary Aerobic Fitness Assessment During Maximal and Submaximal Exercise Testing in Pediatric Oncology Patients After Chemotherapy
Purpose: The cardiopulmonary exercise test (CPET) is a valuable tool to assess cardiopulmonary exercise capacity in pediatric oncology patients after chemotherapy. In addition, few studies on the utility of submaximal testing have been performed, which could be important as some patients are unable to complete a maximal effort test secondary to deconditioning by both disease and treatment. Materials and Methods: We performed a retrospective chart review of pediatric cancer patients exposed to chemotherapy from 1992 to 2013 who underwent CPET with cycle ergometry (n=27). The study patients were compared with age-matched, sex-matched, and size-matched normal controls. The submaximal measure recorded was the oxygen consumption (VO2)@respiratory exchange ratio (RER) 1.0 during a maximal effort test. Results: The chemotherapy group demonstrated significantly lower exercise time (9.2±3.6 vs. 11.4±3.8; P=0.008), total work capacity (4914.4±3290.3 vs. 7664.4±4289.5; P=0.004), systolic blood pressure at peak exercise (162.9±23.2 vs. 177.3±23.8; P=0.01), indexed peak VO2 (33.9±6.9 vs. 40.0±6.3; P=0.001), and indexed peak oxygen pulse (6.1±1.3 vs. 7.0±1.5; P=0.004)). For the submaximal outcome measured, 11/27 of the chemotherapy patients had VO2@RER 1.0 values
http://ift.tt/2EY6rwB
http://ift.tt/2EY6rwB
The combined pN stage and breast cancer subtypes in breast cancer: a better discriminator of outcome can be used to refine the 8th AJCC staging manual
Abstract
Background
pN stage and breast cancer subtypes (BCS) are both well-recognized prognostic indicators. Our previous work has highlighted that patients even with the same pN stage exhibited a significant survival difference in different BCS. Given this achievement, we hypothesized that a statistical interaction might exist between pN stage and BCS. The aim of this retrospective cohort study was to compare the prognostic value of the combined pN stage and BCS (pNnew stage) with either pN stage or BCS alone, and to determine if this combined new stage could serve as an alternative discriminator of outcome.
Methods
We combined pN stage and BCS to create a new variable named pNnew stage and then divided it into four groups: pN0new, pN1new, pN2new, and pN3new. Survival analysis was performed with the use of the Kaplan–Meier method and the log-rank test was used for univariate analysis. For multivariate analysis, cox proportional hazard models were applied, allowing for the estimation of disease-free survival (DFS). To assess discriminatory accuracy of the models, we compared the area under the receiver-operating characteristic curve (AUROC), the Akaike information criterion (AIC), and the Bayesian information criterion (BIC) values. Then, we used this pNnew stage to generate a TNnewM staging system according to the 7th AJCC staging system.
Results
A statistical interaction between pN stage and BCS was found. In multivariate survival analysis, the pNnew stage has been confirmed as an independent prognostic variable of 5-year DFS. The pNnew stage, with a smaller AIC or BIC value and larger AUROC, was a more powerful predictor of DFS than either pN stage or BCS alone. Results were validated in a separate cohort of patients. The TNnewM stage proposed in our present study was found comparable to the new 8th AJCC edition which includes anatomic T, N, and M plus tumor grade and the status of the biomarkers Her-2, ER, and PR with respect to prognostic value for breast cancer patients.
Conclusions
The pNnew stage (combined pN stage and BCS) appears to be a more powerful predictor and discriminator for the outcome of breast cancer, as compared to pN stage or BCS alone, and the TNnewM stage may serve as a simple, easy-to-use alternative to the 8th AJCC edition staging manual.
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Biomarker-Driven Therapy in Metastatic Gastric and Esophageal Cancer: Real-Life Clinical Experience
Abstract
Background
Precision treatment of cancer uses biomarker-driven therapy to individualize and optimize patient care.
Objective
To evaluate real-life clinical experience with biomarker-driven therapy in metastatic gastric and esophageal cancer in Israel.
Patients and Methods
This multicenter retrospective cohort study included patients with metastatic gastric or esophageal cancer who were treated in the participating institutions and underwent biomarker-driven therapy. Treatment was considered to have a benefit if the ratio between the longest progression-free survival (PFS) post biomarker-driven therapy and the last PFS before the biomarker-driven therapy was ≥1.3. The null hypothesis was that ≤15% of patients gain such benefit.
Results
The analysis included 46 patients (61% men; median age, 58 years; 57% with poorly-differentiated tumors). At least one actionable (i.e., predictive of response to a specific therapy) biomarker was identified for each patient. Immunohistochemistry was performed on all samples and identified 1–8 (median: 3) biomarkers per patient (most commonly: low TS, high TOPO1, high TOP2A). Twenty-eight patients received therapy after the biomarker analysis (1–4 lines). In the 1st line after biomarker analysis, five patients (18%) achieved a partial response and five (18%) stable disease; the median (range) PFS was 129 (12–1155) days. Twenty-four patients were evaluable for PFS ratio analysis; in seven (29.2%), the ratio was ≥1.3. In a one-sided exact binomial test vs. the null hypothesis, p = 0.019; therefore, the null hypothesis was rejected.
Conclusions
Our findings demonstrated that implementing biomarker-driven analysis is feasible and could provide clinical benefit for a considerable proportion (~30%) of patients with metastatic gastric or esophageal cancer. 
http://ift.tt/2EZACTP
A retrospective analysis of 5-fluorouracil plus cisplatin as first-line chemotherapy in the recent treatment strategy for patients with metastatic or recurrent esophageal squamous cell carcinoma
Abstract
Background
Patients with metastatic or recurrent esophageal squamous cell carcinoma (ESCC) have a poor prognosis. For decades, the most widely used first-line chemotherapy regimen for these patients has been the combination of 5-fluorouracil + cisplatin (CF). However, prognostic factors of CF as first-line chemotherapy for ESCC have not been clarified.
Methods
A total of 187 patients with metastatic or recurrent esophageal ESCC treated with CF at the National Cancer Center Hospital between January 2001 and December 2012 were enrolled in the study. The CF regimen comprised cisplatin (80 mg/m2) administered on day 1 and 5-fluorouracil (800 mg/m2) administered continuously on days 1–5, every 4 weeks. Multivariate Cox regression analysis was used to determine the potential prognostic factors.
Results
The median age of the patients was 62 (range 34–84) years. Metastasis and recurrence occurred in 116 and 71 of these patients, respectively. The overall response rate was 37.2%, with median progression-free and overall survival times of 4.8 and 10.4 months, respectively. In the multivariate analysis, higher serum C-reactive protein level and lower serum albumin level at the time of CF treatment initiation and number of metastatic sites were identified as independent prognostic factors for survival.
Conclusions
The results of this study corroborate previous findings on the efficacy of CF and will aid physicians in clinical decision-making and individual patient risk stratification, as well as in the further development of chemotherapy regimens.
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A retrospective analysis of 5-fluorouracil plus cisplatin as first-line chemotherapy in the recent treatment strategy for patients with metastatic or recurrent esophageal squamous cell carcinoma
Abstract
Background
Patients with metastatic or recurrent esophageal squamous cell carcinoma (ESCC) have a poor prognosis. For decades, the most widely used first-line chemotherapy regimen for these patients has been the combination of 5-fluorouracil + cisplatin (CF). However, prognostic factors of CF as first-line chemotherapy for ESCC have not been clarified.
Methods
A total of 187 patients with metastatic or recurrent esophageal ESCC treated with CF at the National Cancer Center Hospital between January 2001 and December 2012 were enrolled in the study. The CF regimen comprised cisplatin (80 mg/m2) administered on day 1 and 5-fluorouracil (800 mg/m2) administered continuously on days 1–5, every 4 weeks. Multivariate Cox regression analysis was used to determine the potential prognostic factors.
Results
The median age of the patients was 62 (range 34–84) years. Metastasis and recurrence occurred in 116 and 71 of these patients, respectively. The overall response rate was 37.2%, with median progression-free and overall survival times of 4.8 and 10.4 months, respectively. In the multivariate analysis, higher serum C-reactive protein level and lower serum albumin level at the time of CF treatment initiation and number of metastatic sites were identified as independent prognostic factors for survival.
Conclusions
The results of this study corroborate previous findings on the efficacy of CF and will aid physicians in clinical decision-making and individual patient risk stratification, as well as in the further development of chemotherapy regimens.
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UBE2C promotes rectal carcinoma via miR-381
.
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DNA hypermethylation as a predictor of extramural vascular invasion (EMVI) in rectal cancer
.
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Factors Associated with Sarcopenia in Patients with Colorectal Cancer.
Factors Associated with Sarcopenia in Patients with Colorectal Cancer.
Nutr Cancer. 2018 Jan 19;:1-8
Authors: Souza BU, Souza NCS, Martucci RB, Rodrigues VD, Pinho NB, Gonzalez MC, Avesani CM
Abstract
Introduction; Sarcopenia are frequently observed in cancer patients and was associated with poor prognosis. Objectives; to determine the association of nutritional status, body composition, and clinic parameters with sarcopenia in patients with colorectal cancer (CRC). Methods; We conducted a cross-sectional study of 197 patients with CRC. The sarcopenia elements, including lumbar skeletal muscle index (SMI), handgrip strength, and gait speed were measured. The SMI was assessed by computed tomography at third lumbar vertebra. Phase angle (PA), serum albumin (SAlb), muscle attenuation (MA), and the scored patient-generated subjective global assessment (PG-SGA) were also evaluated. Univariate and multivariate analysis of factors associated with sarcopenia were performed. Results; Sarcopenia was present in 29 of 195 patients (15%) and was significantly correlated with advance age, lower body mass index (BMI), SAlb, PA, MA, higher PG-SGA score, and malnutrition (PG-SGA B). In univariate analysis, age, BMI, SAlb, PA, MA, PG-SGA score, and malnutrition (PG-SGA B) were associated with sarcopenia. Multivariable analysis revealed that BMI, SAlb, PA, MA, and PG-SGA score were independent predictors of sarcopenia. Conclusion; BMI, SAlb, PA, MA, and PG-SGA score were independent predictors of sarcopenia in patients with CRC.
PMID: 29351494 [PubMed - as supplied by publisher]
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Factors Associated with Sarcopenia in Patients with Colorectal Cancer.
Factors Associated with Sarcopenia in Patients with Colorectal Cancer.
Nutr Cancer. 2018 Jan 19;:1-8
Authors: Souza BU, Souza NCS, Martucci RB, Rodrigues VD, Pinho NB, Gonzalez MC, Avesani CM
Abstract
Introduction; Sarcopenia are frequently observed in cancer patients and was associated with poor prognosis. Objectives; to determine the association of nutritional status, body composition, and clinic parameters with sarcopenia in patients with colorectal cancer (CRC). Methods; We conducted a cross-sectional study of 197 patients with CRC. The sarcopenia elements, including lumbar skeletal muscle index (SMI), handgrip strength, and gait speed were measured. The SMI was assessed by computed tomography at third lumbar vertebra. Phase angle (PA), serum albumin (SAlb), muscle attenuation (MA), and the scored patient-generated subjective global assessment (PG-SGA) were also evaluated. Univariate and multivariate analysis of factors associated with sarcopenia were performed. Results; Sarcopenia was present in 29 of 195 patients (15%) and was significantly correlated with advance age, lower body mass index (BMI), SAlb, PA, MA, higher PG-SGA score, and malnutrition (PG-SGA B). In univariate analysis, age, BMI, SAlb, PA, MA, PG-SGA score, and malnutrition (PG-SGA B) were associated with sarcopenia. Multivariable analysis revealed that BMI, SAlb, PA, MA, and PG-SGA score were independent predictors of sarcopenia. Conclusion; BMI, SAlb, PA, MA, and PG-SGA score were independent predictors of sarcopenia in patients with CRC.
PMID: 29351494 [PubMed - as supplied by publisher]
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Autophagy promotes metastasis and glycolysis by upregulating MCT1 expression and Wnt/β-catenin signaling pathway activation in hepatocellular carcinoma cells
Autophagy is a dynamic physiological process that can generate energy and nutrients for cell survival during stress. Autophagy can regulate the migration and invasive ability in cancer cells. However, the conn...
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Surveillance for cancer recurrence in long-term young breast cancer survivors randomly selected from a statewide cancer registry
Abstract
Purpose
This study examined clinical breast exam (CBE) and mammography surveillance in long-term young breast cancer survivors (YBCS) and identified barriers and facilitators to cancer surveillance practices.
Methods
Data collected with a self-administered survey from a statewide, randomly selected sample of YBCS diagnosed with invasive breast cancer or ductal carcinoma in situ younger than 45 years old, stratified by race (Black vs. White/Other). Multivariate logistic regression models identified predictors of annual CBEs and mammograms.
Results
Among 859 YBCS (n = 340 Black; n = 519 White/Other; mean age = 51.0 ± 5.9; diagnosed 11.0 ± 4.0 years ago), the majority (> 85%) reported an annual CBE and a mammogram. Black YBCS in the study were more likely to report lower rates of annual mammography and more barriers accessing care compared to White/Other YBCS. Having a routine source of care, confidence to use healthcare services, perceived expectations from family members and healthcare providers to engage in cancer surveillance, and motivation to comply with these expectations were significant predictors of having annual CBEs and annual mammograms. Cost-related lack of access to care was a significant barrier to annual mammograms.
Conclusions
Routine source of post-treatment care facilitated breast cancer surveillance above national average rates. Persistent disparities regarding access to mammography surveillance were identified for Black YBCS, primarily due to lack of access to routine source of care and high out-of-pocket costs.
Implications
Public health action targeting cancer surveillance in YBCS should ensure routine source of post-treatment care and address cost-related barriers. Clinical Trials Registration Number: NCT01612338.
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Prediction of progression in skull base meningiomas: additional benefits of apparent diffusion coefficient value
Abstract
A subset of benign (WHO grade I) skull base meningiomas show early progression/recurrence (P/R) in the first years after surgical resection. Besides, complete surgical resection may be difficult to achieve safely in skull base meningiomas due to complex neurovascular structures. The one main challenge in the treatment of skull base meningiomas is to determine factors that correlate with P/R. We retrospectively investigated the preoperative CT and MR imaging features for the prediction of P/R in skull base meningiomas, with emphasis on quantitative ADC values. Only patients had postoperative MRI follow-ups for more than 1 year (at least every 6 months) were included. From October 2006 to December 2015, total 73 patients diagnosed with benign (WHO grade I) skull base meningiomas were included (median follow-up time 41 months), and 17 (23.3%) patients had P/R (median time to P/R 28 months). Skull base meningiomas with spheno-orbital location, adjacent bone invasion, high DWI, and lower ADC value/ratio were significantly associated with P/R (P < 0.05). The cut-off points of ADC value and ADC ratio for prediction of P/R are 0.83 × 10− 3 mm2/s and 1.09 respectively, with excellent area under curve (AUC) values (0.86 and 0.91) (P < 0.05). In multivariate logistic regression, low ADC values (< 0.83 × 10− 3 mm2/s) and adjacent bone invasion are high-risk factors of P/R (P < 0.05), with odds ratios of 31.53 and 17.59 respectively. The preoperative CT and MRI features for prediction of P/R offered clinically vital information for the planning of treatment in skull base meningiomas.
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Prediction of progression in skull base meningiomas: additional benefits of apparent diffusion coefficient value
Abstract
A subset of benign (WHO grade I) skull base meningiomas show early progression/recurrence (P/R) in the first years after surgical resection. Besides, complete surgical resection may be difficult to achieve safely in skull base meningiomas due to complex neurovascular structures. The one main challenge in the treatment of skull base meningiomas is to determine factors that correlate with P/R. We retrospectively investigated the preoperative CT and MR imaging features for the prediction of P/R in skull base meningiomas, with emphasis on quantitative ADC values. Only patients had postoperative MRI follow-ups for more than 1 year (at least every 6 months) were included. From October 2006 to December 2015, total 73 patients diagnosed with benign (WHO grade I) skull base meningiomas were included (median follow-up time 41 months), and 17 (23.3%) patients had P/R (median time to P/R 28 months). Skull base meningiomas with spheno-orbital location, adjacent bone invasion, high DWI, and lower ADC value/ratio were significantly associated with P/R (P < 0.05). The cut-off points of ADC value and ADC ratio for prediction of P/R are 0.83 × 10− 3 mm2/s and 1.09 respectively, with excellent area under curve (AUC) values (0.86 and 0.91) (P < 0.05). In multivariate logistic regression, low ADC values (< 0.83 × 10− 3 mm2/s) and adjacent bone invasion are high-risk factors of P/R (P < 0.05), with odds ratios of 31.53 and 17.59 respectively. The preoperative CT and MRI features for prediction of P/R offered clinically vital information for the planning of treatment in skull base meningiomas.
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Understanding intratumor heterogeneity by combining genome analysis and mathematical modeling
Abstract
Cancer is composed of multiple cell populations with different genomes. Each of the populations is called a clone (or subclone) and this phenomenon is called intratumor heterogeneity (ITH). ITH is observed in various types of cancers and presumed to be a major cause leading to therapeutic resistance. If a tumor harbors a major clone sensitive to a specific anti-cancer treatment, the tumor shrinks within a given period after the treatment. However, in most cases, a minor clone resistant to the chemotherapy exists in the tumor and predominantly regrows in spite of the intensive therapy. It is supposed that ITH can be generated by clonal branching during cancer evolution.
This article is protected by copyright. All rights reserved.
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Limb Salvage Versus Amputation in Conventional Appendicular Osteosarcoma: a Systematic Review
Abstract
The overall survivorship in patients with appendicular osteosarcoma has increased in the past few decades. However, controversies and questions about performing an amputation or a limb salvage procedure still remain. Using three peer-reviewed library databases, a systematic review of the literature was performed to evaluate all studies that have evaluated the outcomes of appendicular osteosarcoma, either with limb salvage or amputation. The mean 5-year overall survivorship was 62% for salvage and 58% for amputation (p > 0.05). At mean 6-year follow-up, the local recurrence rates were 8.2% for salvage and 3.0% for amputation (p > 0.05). Additionally, at mean 6-year follow-up, the rate for metastasis was 33% for salvage and 38% for amputation (p > 0.05). The revision rates were higher with salvage (31 vs. 28%), and there were more complications in the salvage groups (52 vs. 34%; p > 0.05). Despite the heterogeneity of studies available for review, we observed similar survival rates between the two procedures. Although there was no significant statistical difference between rates of recurrence and metastasis, the local recurrence rate and risk of complications were higher for limb salvage as compared to amputation. Cosmetic satisfaction is often higher with limb salvage, whereas long-term expense is higher with amputation. Overall, current literature supports limb salvage procedures when wide surgical margins can be achieved while still retaining a functional limb.
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Cancers, Vol. 10, Pages 24: Contemporary Management of Localized Resectable Pancreatic Cancer
Cancers, Vol. 10, Pages 24: Contemporary Management of Localized Resectable Pancreatic Cancer
Cancers doi: 10.3390/cancers10010024
Authors: Anuhya Kommalapati Sri Tella Gaurav Goyal Wen Ma Amit Mahipal
Pancreatic cancer is the third most common cause of cancer deaths in the United States. Surgical resection with negative margins still constitutes the cornerstone of potentially curative therapy, but is possible only in 15–20% of patients at the time of initial diagnosis. Accumulating evidence suggests that the neoadjuvant approach may improve R0 resection rate in localized resectable and borderline resectable diseases, and potentially downstage locally advanced disease to achieve surgical resection, though the impact on survival is to be determined. Despite advancements in the last decade in developing effective combinational chemo-radio therapeutic options, preoperative treatment strategies, and better peri-operative care, pancreatic cancer continues to carry a dismal prognosis in the majority. Prodigious efforts are currently being made in optimizing the neoadjuvant therapy with a better toxicity profile, developing novel agents, imaging techniques, and identification of biomarkers for the disease. Advancement in our understanding of the tumor microenvironment and molecular pathology is urgently needed to facilitate the development of novel targeted and immunotherapies for this setting. In this review, we detail the current literature on contemporary management of resectable, borderline resectable and locally advanced pancreatic cancer with a focus on future directions in the field.
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Cancers, Vol. 10, Pages 26: Colorectal Cancers: An Update on Their Molecular Pathology
Cancers, Vol. 10, Pages 26: Colorectal Cancers: An Update on Their Molecular Pathology
Cancers doi: 10.3390/cancers10010026
Authors: Kentaro Inamura
Colorectal cancers (CRCs) are the third leading cause of cancer-related mortality worldwide. Rather than being a single, uniform disease type, accumulating evidence suggests that CRCs comprise a group of molecularly heterogeneous diseases that are characterized by a range of genomic and epigenomic alterations. This heterogeneity slows the development of molecular-targeted therapy as a form of precision medicine. Recent data regarding comprehensive molecular characterizations and molecular pathological examinations of CRCs have increased our understanding of the genomic and epigenomic landscapes of CRCs, which has enabled CRCs to be reclassified into biologically and clinically meaningful subtypes. The increased knowledge of the molecular pathological epidemiology of CRCs has permitted their evolution from a vaguely understood, heterogeneous group of diseases with variable clinical courses to characteristic molecular subtypes, a development that will allow the implementation of personalized therapies and better management of patients with CRC. This review provides a perspective regarding recent developments in our knowledge of the molecular and epidemiological landscapes of CRCs, including results of comprehensive molecular characterizations obtained from high-throughput analyses and the latest developments regarding their molecular pathologies, immunological biomarkers, and associated gut microbiome. Advances in our understanding of potential personalized therapies for molecularly specific subtypes are also reviewed.
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Understanding intratumor heterogeneity by combining genome analysis and mathematical modeling
Abstract
Cancer is composed of multiple cell populations with different genomes. Each of the populations is called a clone (or subclone) and this phenomenon is called intratumor heterogeneity (ITH). ITH is observed in various types of cancers and presumed to be a major cause leading to therapeutic resistance. If a tumor harbors a major clone sensitive to a specific anti-cancer treatment, the tumor shrinks within a given period after the treatment. However, in most cases, a minor clone resistant to the chemotherapy exists in the tumor and predominantly regrows in spite of the intensive therapy. It is supposed that ITH can be generated by clonal branching during cancer evolution.
This article is protected by copyright. All rights reserved.
http://ift.tt/2DxFh2i
Limb Salvage Versus Amputation in Conventional Appendicular Osteosarcoma: a Systematic Review
Abstract
The overall survivorship in patients with appendicular osteosarcoma has increased in the past few decades. However, controversies and questions about performing an amputation or a limb salvage procedure still remain. Using three peer-reviewed library databases, a systematic review of the literature was performed to evaluate all studies that have evaluated the outcomes of appendicular osteosarcoma, either with limb salvage or amputation. The mean 5-year overall survivorship was 62% for salvage and 58% for amputation (p > 0.05). At mean 6-year follow-up, the local recurrence rates were 8.2% for salvage and 3.0% for amputation (p > 0.05). Additionally, at mean 6-year follow-up, the rate for metastasis was 33% for salvage and 38% for amputation (p > 0.05). The revision rates were higher with salvage (31 vs. 28%), and there were more complications in the salvage groups (52 vs. 34%; p > 0.05). Despite the heterogeneity of studies available for review, we observed similar survival rates between the two procedures. Although there was no significant statistical difference between rates of recurrence and metastasis, the local recurrence rate and risk of complications were higher for limb salvage as compared to amputation. Cosmetic satisfaction is often higher with limb salvage, whereas long-term expense is higher with amputation. Overall, current literature supports limb salvage procedures when wide surgical margins can be achieved while still retaining a functional limb.
http://ift.tt/2rmNMbz
Cancers, Vol. 10, Pages 24: Contemporary Management of Localized Resectable Pancreatic Cancer
Cancers, Vol. 10, Pages 24: Contemporary Management of Localized Resectable Pancreatic Cancer
Cancers doi: 10.3390/cancers10010024
Authors: Anuhya Kommalapati Sri Tella Gaurav Goyal Wen Ma Amit Mahipal
Pancreatic cancer is the third most common cause of cancer deaths in the United States. Surgical resection with negative margins still constitutes the cornerstone of potentially curative therapy, but is possible only in 15–20% of patients at the time of initial diagnosis. Accumulating evidence suggests that the neoadjuvant approach may improve R0 resection rate in localized resectable and borderline resectable diseases, and potentially downstage locally advanced disease to achieve surgical resection, though the impact on survival is to be determined. Despite advancements in the last decade in developing effective combinational chemo-radio therapeutic options, preoperative treatment strategies, and better peri-operative care, pancreatic cancer continues to carry a dismal prognosis in the majority. Prodigious efforts are currently being made in optimizing the neoadjuvant therapy with a better toxicity profile, developing novel agents, imaging techniques, and identification of biomarkers for the disease. Advancement in our understanding of the tumor microenvironment and molecular pathology is urgently needed to facilitate the development of novel targeted and immunotherapies for this setting. In this review, we detail the current literature on contemporary management of resectable, borderline resectable and locally advanced pancreatic cancer with a focus on future directions in the field.
http://ift.tt/2Du8JpV
Cancers, Vol. 10, Pages 26: Colorectal Cancers: An Update on Their Molecular Pathology
Cancers, Vol. 10, Pages 26: Colorectal Cancers: An Update on Their Molecular Pathology
Cancers doi: 10.3390/cancers10010026
Authors: Kentaro Inamura
Colorectal cancers (CRCs) are the third leading cause of cancer-related mortality worldwide. Rather than being a single, uniform disease type, accumulating evidence suggests that CRCs comprise a group of molecularly heterogeneous diseases that are characterized by a range of genomic and epigenomic alterations. This heterogeneity slows the development of molecular-targeted therapy as a form of precision medicine. Recent data regarding comprehensive molecular characterizations and molecular pathological examinations of CRCs have increased our understanding of the genomic and epigenomic landscapes of CRCs, which has enabled CRCs to be reclassified into biologically and clinically meaningful subtypes. The increased knowledge of the molecular pathological epidemiology of CRCs has permitted their evolution from a vaguely understood, heterogeneous group of diseases with variable clinical courses to characteristic molecular subtypes, a development that will allow the implementation of personalized therapies and better management of patients with CRC. This review provides a perspective regarding recent developments in our knowledge of the molecular and epidemiological landscapes of CRCs, including results of comprehensive molecular characterizations obtained from high-throughput analyses and the latest developments regarding their molecular pathologies, immunological biomarkers, and associated gut microbiome. Advances in our understanding of potential personalized therapies for molecularly specific subtypes are also reviewed.
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Is invasion a necessary step for metastases in breast cancer?
Abstract
Purpose
To review the empirical evidence to support the conventional (sequential) model of breast cancer progression, which is based on the paradigm that cancer passes through several stages, including an in situ stage prior to an invasive stage, and thereafter (in some cases) disseminates to the lymph nodes and distant organs.
Methods
We review the cancer literature of the last 50 years which relates to the prevention of invasive breast cancer (through radiotherapy or surgery) and reductions in the mortality for breast cancer.
Results
For both invasive cancers and DCIS, the literature indicates that prevention of in-breast invasive recurrences does not prevent death from breast cancer. Moreover, the presence of residual cancer cells in the breast after breast-conserving surgery does not compromise the cure rate.
Conclusion
We propose an alternate (parallel) model of breast cancer wherein there is a small pool of cancer stem cells which have metastatic potential from their inception and which disseminate synchronously through several routes—to the breast stroma, to the lymph nodes and to distant organs. Cancer cells which disseminate to the breast give rise to cells which make up the bulk of the tumour mass but these are not the source of the distant metastases.
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