Nomograms to estimate long-term overall survival and tongue cancer-specific survival of patients with tongue squamous cell carcinoma

Abstract

The aim of this study was to construct nomograms to predict long-term overall survival (OS) and tongue cancer-specific survival (TCSS) of tongue squamous cell carcinoma (TSCC) patients based on clinical and tumor characteristics. Clinical, tumor, and treatment characteristics of 12,674 patients diagnosed with TSCC between 2004 and 2013 were collected from the Surveillance, Epidemiology, and End Results database. These patients were then divided into surgery and nonsurgery cohorts, and nomograms were developed for each of these groups. The step-down method and cumulative incidence function were used for model selection to determine the significant prognostic factors associated with OS and TCSS. These prognostic variables were incorporated into nomograms. An external cohort was used to validate the surgery nomograms. Seven variables were used to create the surgery nomograms for OS and TCSS, which had c-indexes of 0.709 and 0.728, respectively; for the external validation cohort, the c-indexes were 0.691 and 0.711, respectively. Nine variables were used to create the nonsurgery nomograms for OS and TCSS, which had c-indexes of 0.750 and 0.754, respectively. The calibration curves of the 5- and 8-year surgery and nonsurgery nomograms showed excellent agreement between the probabilities and observed values. By incorporating clinicopathological and host characteristics in patients, we are the first to establish nomograms that accurately predict prognosis for individual patients with TSCC. These nomograms ought to provide more personalized and reliable prognostic information, and improve clinical decision-making for TSCC patients.

Tongue squamous cell carcinoma (TSCC) is the most common type of oral carcinoma, with significantly worse prognosis compared to other head and neck squamous cell carcinomas (HNSCC). In this study, we have used a large population-based cohort to create a series of nomograms that can provide 5- and 8-year overall survival and tongue cause-specific survival for patients with TSCC for the first time. These accurate and easy-to-use nomograms ought to be helpful in improved individual management.

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Nomograms to estimate long-term overall survival and tongue cancer-specific survival of patients with tongue squamous cell carcinoma

Abstract

The aim of this study was to construct nomograms to predict long-term overall survival (OS) and tongue cancer-specific survival (TCSS) of tongue squamous cell carcinoma (TSCC) patients based on clinical and tumor characteristics. Clinical, tumor, and treatment characteristics of 12,674 patients diagnosed with TSCC between 2004 and 2013 were collected from the Surveillance, Epidemiology, and End Results database. These patients were then divided into surgery and nonsurgery cohorts, and nomograms were developed for each of these groups. The step-down method and cumulative incidence function were used for model selection to determine the significant prognostic factors associated with OS and TCSS. These prognostic variables were incorporated into nomograms. An external cohort was used to validate the surgery nomograms. Seven variables were used to create the surgery nomograms for OS and TCSS, which had c-indexes of 0.709 and 0.728, respectively; for the external validation cohort, the c-indexes were 0.691 and 0.711, respectively. Nine variables were used to create the nonsurgery nomograms for OS and TCSS, which had c-indexes of 0.750 and 0.754, respectively. The calibration curves of the 5- and 8-year surgery and nonsurgery nomograms showed excellent agreement between the probabilities and observed values. By incorporating clinicopathological and host characteristics in patients, we are the first to establish nomograms that accurately predict prognosis for individual patients with TSCC. These nomograms ought to provide more personalized and reliable prognostic information, and improve clinical decision-making for TSCC patients.

Tongue squamous cell carcinoma (TSCC) is the most common type of oral carcinoma, with significantly worse prognosis compared to other head and neck squamous cell carcinomas (HNSCC). In this study, we have used a large population-based cohort to create a series of nomograms that can provide 5- and 8-year overall survival and tongue cause-specific survival for patients with TSCC for the first time. These accurate and easy-to-use nomograms ought to be helpful in improved individual management.

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Therapeutic outcome of nasopharyngeal carcinoma with cranial nerve palsy: a single institution experience of 104 patients

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Impact of major life events on breast-cancer-specific mortality: A case fatality study on 8000 breast cancer patients

Publication date: June 2017
Source:Cancer Epidemiology, Volume 48
Author(s): Sanna Heikkinen, Joonas Miettinen, Eero Pukkala, Markku Koskenvuo, Nea Malila, Janne Pitkäniemi
BackgroundIt has been suggested that long-term activation of the body's stress–response system and subsequent overexposure to stress hormones may be associated with increased morbidity. However, evidence on the impact of major life events on mortality from breast cancer (BC) remains inconclusive. The main aim of this study is to investigate whether major negatively or positively experienced life events before or after diagnosis have an effect on BC-specific mortality in women who have survived with BC for at least 2 years.MethodsWe conducted a case fatality study with data on life events from a self-administered survey and data on BC from the Finnish Cancer Registry. Cox models were fitted to estimate BC mortality hazard ratios (MRs) between those who have undergone major life events and those who haven't.ResultsNone of the pre-diagnostic negative life events had any effect on BC-specific mortality. Regarding post-diagnostic events, the effect was greatest in women with moderate scores of events. As for event-specific scores, increased BC mortality was observed with spouse unemployment, relationship problems, and death of a close friend. By contrast, falling in love and positive developments in hobbies were shown to be associated with lower BC mortality (MRs 0.67, 95%CI: 0.49–0.92 and 0.74, 95%CI: 0.57–0.96, respectively). In an analysis restricted to recently diagnosed cases (2007), also death of a child and of a mother was associated with increased BC mortality.ConclusionsSome major life events regarding close personal relationships may play a role in BC-specific mortality, with certain negative life events increasing BC mortality and positive events decreasing it. The observed favorable associations between positive developments in romantic relationships and hobbies and BC mortality are likely to reflect the importance of social interaction and support.



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Impact of major life events on breast-cancer-specific mortality: A case fatality study on 8000 breast cancer patients

Publication date: June 2017
Source:Cancer Epidemiology, Volume 48
Author(s): Sanna Heikkinen, Joonas Miettinen, Eero Pukkala, Markku Koskenvuo, Nea Malila, Janne Pitkäniemi
BackgroundIt has been suggested that long-term activation of the body's stress–response system and subsequent overexposure to stress hormones may be associated with increased morbidity. However, evidence on the impact of major life events on mortality from breast cancer (BC) remains inconclusive. The main aim of this study is to investigate whether major negatively or positively experienced life events before or after diagnosis have an effect on BC-specific mortality in women who have survived with BC for at least 2 years.MethodsWe conducted a case fatality study with data on life events from a self-administered survey and data on BC from the Finnish Cancer Registry. Cox models were fitted to estimate BC mortality hazard ratios (MRs) between those who have undergone major life events and those who haven't.ResultsNone of the pre-diagnostic negative life events had any effect on BC-specific mortality. Regarding post-diagnostic events, the effect was greatest in women with moderate scores of events. As for event-specific scores, increased BC mortality was observed with spouse unemployment, relationship problems, and death of a close friend. By contrast, falling in love and positive developments in hobbies were shown to be associated with lower BC mortality (MRs 0.67, 95%CI: 0.49–0.92 and 0.74, 95%CI: 0.57–0.96, respectively). In an analysis restricted to recently diagnosed cases (2007), also death of a child and of a mother was associated with increased BC mortality.ConclusionsSome major life events regarding close personal relationships may play a role in BC-specific mortality, with certain negative life events increasing BC mortality and positive events decreasing it. The observed favorable associations between positive developments in romantic relationships and hobbies and BC mortality are likely to reflect the importance of social interaction and support.



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A Longitudinal Study of Smokeless Tobacco Use and Mortality in the United States

Abstract

Few studies in the United States have examined longitudinally the mortality risks associated with use of smokeless tobacco (SLT). The sample of this study was composed of participants from the National Longitudinal Mortality Study who completed a single Tobacco Use Supplement to the Current Population Survey between the years 1985 and 2011. Using survival methods, SLT use at the baseline survey was examined as a predictor of all-cause mortality and cause-specific mortalities in models that excluded individuals who had ever smoked cigarettes, cigars, or used pipes (final n=349,282). The participants had median and maximum follow-up times of 8.8 and 26.3 years, respectively. Regression analyses indicated that compared to the never tobacco users, the current SLT users did not have elevated mortality risks from all cancers combined, the digestive system cancers and cerebrovascular disease. However, current SLT users had a higher mortality risk for coronary heart disease (CHD) (HR(95% C.I.)=1.24 (1.05, 1.46)) relative to never tobacco users. In a separate model, the elevated risk for CHD mortality corresponded to the use of moist snuff (HR(95% C.I.) =1.30 (1.03, 1.63)). The associations with CHD mortality could be attributed to long-term nicotine exposure, other SLT constituents (e.g., metals), or the confounding effects of CHD risk factors not accounted for in this study. The study's findings could contribute to the ongoing dialogue on tobacco harm reduction and the U.S. FDA's evaluation of Modified Risk Tobacco Product applications submitted by American SLT manufacturers. This article is protected by copyright. All rights reserved.

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A Longitudinal Study of Smokeless Tobacco Use and Mortality in the United States

Abstract

Few studies in the United States have examined longitudinally the mortality risks associated with use of smokeless tobacco (SLT). The sample of this study was composed of participants from the National Longitudinal Mortality Study who completed a single Tobacco Use Supplement to the Current Population Survey between the years 1985 and 2011. Using survival methods, SLT use at the baseline survey was examined as a predictor of all-cause mortality and cause-specific mortalities in models that excluded individuals who had ever smoked cigarettes, cigars, or used pipes (final n=349,282). The participants had median and maximum follow-up times of 8.8 and 26.3 years, respectively. Regression analyses indicated that compared to the never tobacco users, the current SLT users did not have elevated mortality risks from all cancers combined, the digestive system cancers and cerebrovascular disease. However, current SLT users had a higher mortality risk for coronary heart disease (CHD) (HR(95% C.I.)=1.24 (1.05, 1.46)) relative to never tobacco users. In a separate model, the elevated risk for CHD mortality corresponded to the use of moist snuff (HR(95% C.I.) =1.30 (1.03, 1.63)). The associations with CHD mortality could be attributed to long-term nicotine exposure, other SLT constituents (e.g., metals), or the confounding effects of CHD risk factors not accounted for in this study. The study's findings could contribute to the ongoing dialogue on tobacco harm reduction and the U.S. FDA's evaluation of Modified Risk Tobacco Product applications submitted by American SLT manufacturers. This article is protected by copyright. All rights reserved.

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Critical points of T1 stage in primary melanoma.

No abstract available

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Successful treatment with imatinib after nilotinib and ipilimumab in a c-kit-mutated advanced melanoma patient: a case report.

Treatment of melanoma remains a challenge in advanced disease. Recently, the molecular differentiation in BRAF-mutated, NRAS-mutated and c-kit-mutated melanomas led to new treatment strategies. Different trials show that imatinib or nilotinib lead to meaningful responses in c-kit-mutated melanoma patients. There are little published data on sequential inhibition using these two drugs in melanoma. We describe the sequential use of imatinib after nilotinib in a c-kit-mutated melanoma patient, who progressed on interferon, Allovectin, dacarbazine, nilotinib and ipilimumab, and was finally treated with the c-kit inhibitor imatinib. From July 2011 to September 2011, the patient received ipilimumab (four doses with 3 mg/kg). Clinical assessment after immunotherapy showed disease progression. Therefore, a treatment change to imatinib 800 mg daily was made from February 2012 to May 2013. Under this treatment, the patient showed a partial response as per the RECIST criteria. The present lesions continued responding (computed tomography scans: May 2012-March 2013). Unfortunately, in October 2012, new brain metastases developed. Nevertheless, the use of c-kit inhibitors in c-kit-mutated melanoma patients seems to be a promising treatment option. Furthermore, a delayed response to ipilimumab after 6 months could also have led to or supported the partial response in this case. However, when two biologically similar compounds are administered in a melanoma patient and the tumour mass shows progressive disease upon administration of the first agent, an additional progression with no effect may be expected when the second one is used. This case shows, in contrast, that the use of imatinib after progression upon nilotinib can be beneficial. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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The aurora kinase inhibitor AMG 900 increases apoptosis and induces chemosensitivity to anticancer drugs in the NCI-H295 adrenocortical carcinoma cell line.

Adrenocortical tumor (ACT) is a malignancy with a low incidence rate and the current therapy for advanced disease has a limited impact on overall patient survival. A previous study from our group suggested that elevated expression of aurora-A and aurora-B is associated with poor outcome in childhood ACT. Similar results were also reported for adult ACTs. The present in-vitro study shows that AMG 900 inhibits aurora kinases in adrenocortical carcinoma cells. AMG 900 inhibited cell proliferation in NCI-H295 cells as well as in the ACT primary cultures and caused apoptosis in the cell line NCI-H295. Furthermore, it potentialized the mitotane, doxorubicin, and etoposide effects on apoptosis induction and acted synergistically with mitotane and doxorubicin in the inhibition of proliferation. In addition, we found that AMG 900 activated Notch signaling and rendered the cells sensitive to the combination of AMG 900 and Notch signaling inhibition. Altogether, these data show that aurora kinases inhibition using AMG 900 may be an adjuvant therapy to treat patients with invasive or recurrent adrenocortical carcinomas. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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The aurora kinase inhibitor AMG 900 increases apoptosis and induces chemosensitivity to anticancer drugs in the NCI-H295 adrenocortical carcinoma cell line.

Adrenocortical tumor (ACT) is a malignancy with a low incidence rate and the current therapy for advanced disease has a limited impact on overall patient survival. A previous study from our group suggested that elevated expression of aurora-A and aurora-B is associated with poor outcome in childhood ACT. Similar results were also reported for adult ACTs. The present in-vitro study shows that AMG 900 inhibits aurora kinases in adrenocortical carcinoma cells. AMG 900 inhibited cell proliferation in NCI-H295 cells as well as in the ACT primary cultures and caused apoptosis in the cell line NCI-H295. Furthermore, it potentialized the mitotane, doxorubicin, and etoposide effects on apoptosis induction and acted synergistically with mitotane and doxorubicin in the inhibition of proliferation. In addition, we found that AMG 900 activated Notch signaling and rendered the cells sensitive to the combination of AMG 900 and Notch signaling inhibition. Altogether, these data show that aurora kinases inhibition using AMG 900 may be an adjuvant therapy to treat patients with invasive or recurrent adrenocortical carcinomas. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Clinical experiences of Ultrasound-guided transversus thoracic muscle plane block for children

The transversus thoracic muscle plane (TTP) block has been reported to be able to block multiple anterior branches of intercostal nerves (Th2-6) in the internal mammary region [1]. Therefore, there were some publications for clinical setting [2,3,4]. However, there were no papers of TTP block for children. We reported two cases using the TTP block for children. Case 1 was a 7-year-old girl (120cm, 27kg) with no complications who underwent a funnel chest. To provide good perioperative pain management, we recommended her to receive an epidural anesthesia before a general anesthesia.

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A time for change; the need to modernise breast surgery training. Results of surveys of senior breast trainees and of current consultant practice

Publication date: May 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 5
Author(s): Rajiv Dave, Baek Kim, Fiona Langlands, Gina Weston-Petrides, John Benson, Anne Tansley, Julie Doughty




http://ift.tt/2ovmhb1

Teaching intimate examination in breast using Clinical Teaching Associates – Enhancing the learning environment

Publication date: May 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 5
Author(s): Joanne Moffatt, Anushka Chaudhry, Jessica Taylor, Kevin Jones




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Introduction – Precision Surgery

Publication date: May 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 5





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Local retrospective 5 year audit of breast cancer recurrence in patients post surgery (wide local excision/mastectomy) for Ductal Carcinoma In Situ (low, intermediate & high grade)

Publication date: May 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 5
Author(s): Veronica Rogers, Karen Ives-Smith, Carol-Ann Courtney




http://ift.tt/2pfZ3Z4

Tubular and mucinous breast cancer: Can sentinel node biopsy be safely omitted?

Publication date: May 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 5
Author(s): Elizabeth Morrow, Alison Lannigan, Laszlo Romics




http://ift.tt/2ovttDS

Development and validation of a predictive risk model for acute skin toxicity in patients undergoing breast radiotherapy

Publication date: May 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 5
Author(s): Tim Rattay, Kerstie Johnson, Gillian Barnett, Charlotte Coles, Jenny Chang-Claude, Petra Seibold, R. Paul Symonds, Frederik Wenz, Catharine West, Christopher Talbot




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Role of the Breast Clinical Nurse Specialist in bilateral risk reduction mastectomy decision–making

Publication date: May 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 5
Author(s): Charlotte Weston, Sarah Adomah, Vanda Ribeiro, Karen Thomas, Nichola Snuggs, Gerald Gui, Ana Agusti, Theresa Wiseman




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Editorial Board

Publication date: May 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 5





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Core biopsy is more sensitive than fine needle aspiration for preoperative axillary staging in invasive breast cancer

Publication date: May 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 5
Author(s): Elizabeth Morrow, Alison Lannigan, Julie Doughty, Laszlo Romics




http://ift.tt/2ovheHx

Prevalence and tumour characteristics of contralateral breast cancer over 5 years in a tertiary-referral cancer centre

Publication date: May 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 5
Author(s): X.T. Tan, L.A. Devane, C.K. Baban, J. Rothwell, D. Evoy, J. Geraghty, A. O'Doherty, C. Quinn, C. D'Arcy, E.W. McDermott, R.S. Prichard




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Clinical evidence supporting genomic tests in early breast cancer: Do all genomic tests provide the same information?

Publication date: May 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 5
Author(s): C. Markopoulos, C. van de Velde, D. Zarca, V. Ozmen, R. Masetti
Breast cancer (BC) has historically been treated as a single disease entity; however, in the last decade, insights into its molecular heterogeneity have underpinned the development/commercialisation of several genomic tools whose goal is to guide patient management in early BC. These include the Oncotype DX^® Breast Recurrence Score™ assay, MammaPrint^®, Prosigna^®, and EndoPredict^®. Although these assays are similar in that they are all multigene assays reflecting risk of recurrence, they differ substantially in the technological platform used to measure gene expression; the number and identity of genes assessed; the patient populations used for development and validation; and the level of evidence supporting clinical utility. They also differ in the amount of evidence demonstrating their impact on treatment decisions and cost effectiveness in different countries. This review discusses these 4 assays, highlighting the clinical evidence that supports each of them, while focussing on the Recurrence Score assay. This assay has the greatest body of evidence supporting its clinical utility and decision impact/effectiveness, and currently is the only one validated as a predictor of response to adjuvant chemotherapy in hormone-receptor positive early BC patients treated with endocrine therapy and to be included as such in international/national BC treatment guidelines. The review also discusses ongoing prospective trials investigating the 4 assays, recent outcome studies, as well as analyses comparing different assays on the same tumour blocks.



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A systematic review and meta-analysis of aberrant lymphatic drainage in recurrent breast cancer

Publication date: May 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 5
Author(s): Muneer Ahmed, Rose Baker, Michael Douek, Isabel Rubio




http://ift.tt/2ovyoVv

Self-Directed Aftercare: An audit which shows the pilot introduction of Patient Group Recovery Health Needs Assessment clinics being acceptable to our patients and meets the Department of Health, Social Services and Public Safety five standards

Publication date: May 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 5
Author(s): Eimer McGeown, Annie Treanor, Lucy Montgomery




http://ift.tt/2pfRtxu

Promoting breast awareness with female teenagers and the provision of breast health lifestyle advice

Publication date: May 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 5
Author(s): Lucy Montgomery




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Safety of autologous fat banking – A report on the Regenerys Pilot Study: A pilot study to determine the safety and efficacy of autologous tissue banking in breast reconstruction following cancer excision

Publication date: May 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 5
Author(s): Andrew Pieri, David Haddow, Elizabeth Baker, Venkat Ramakrishnan, Elaine Sassoon, Eva Weiler-Mithoff, Pud Bhaskar




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National Margins Audit – current practice questionnaire

Publication date: May 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 5
Author(s): Sarah Tang, National Margins Audit Collaborative




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Digital procedure specific consent forms (OpInform) compared to handwritten surgical consent forms in breast surgery

Publication date: May 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 5
Author(s): Edward St John, Ara Askari, Dickson Fenn, Mahdi Saleh, Georgina Keogh, Claudia Pisarek, Stephanie Rimmer, Peter Lion, Ara Darzi, Daniel Leff




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1. Outcome following 150 prepectoral implant based breast reconstruction using Braxon® (ADM): UK experience

Publication date: May 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 5
Author(s): Raghavan Vidya, Alison Hunter Smith, Fathi Salem, Neeraj Garg, Amar Dhespande, Pud Bhaskar, Tapan Sircar, Simon Cawthorn




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Audit of the routine introduction of Oncotype DX testing in a single breast unit

Publication date: May 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 5
Author(s): Nikki Green, Pippa Leighton, Clare Fowler




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Magseed – Safety and feasibility study of the use of magnetic marker seeds to localise breast cancers

Publication date: May 2017
Source:European Journal of Surgical Oncology (EJSO), Volume 43, Issue 5
Author(s): James Harvey, Yit Lim, John Murphy, Anthony Maxwell




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Other non-surgical treatments for liver cancer

Publication date: Available online 14 April 2017
Source:Reports of Practical Oncology & Radiotherapy
Author(s): Paul Revel-Mouroz, Philippe Otal, Marion Jaffro, Antoine Petermann, Olivier Meyrignac, Pierre Rabinel, Fatima-Zohra Mokrane
Interventional radiology plays a major role in the modern management of liver cancers, in primary hepatic malignancies or metastases and in palliative or curative situations. Radiological treatments are divided in two categories based on their approach: endovascular treatment and direct transcapsular access.Endovascular treatments include mainly three applications: transarterial chemoembolization (TACE), transarterial radioembolization (TARE) and portal vein embolization (PVE). TACE and TARE share an endovascular arterial approach, consisting of a selective catheterization of the hepatic artery or its branches. Subsequently, either a chemotherapy (TACE) or radioembolic (TARE) agent is injected in the target vessel to act on the tumor. PVE raises the volume of the future liver remnant in extended hepatectomy by embolizing a portal vein territory which results in hepatic regeneration.Direct transcapsular access treatments involve mainly three techniques: radiofrequency thermal ablation (RFA), microwave thermal ablation (MWA) and percutaneous ethanol injection (PEI). RFA and MWA procedures are almost identical, their clinical applications are similar. A probe is deployed directly into the tumor to generate heat and coagulation necrosis. PEI has known implications based on the chemical toxicity of intra-tumoral injection with highly concentrated alcohol by a thin needle.



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Accuracy of the online prognostication tools PREDICT and Adjuvant! for early-stage breast cancer patients younger than 50 years

Publication date: June 2017
Source:European Journal of Cancer, Volume 78
Author(s): Ellen G. Engelhardt, Alexandra J. van den Broek, Sabine C. Linn, Gordon C. Wishart, Emiel J. Th. Rutgers, Anthonie O. van de Velde, Vincent T.H.B.M. Smit, Adri C. Voogd, Sabine Siesling, Mariël Brinkhuis, Caroline Seynaeve, Pieter J. Westenend, Anne M. Stiggelbout, Rob A.E.M. Tollenaar, Flora E. van Leeuwen, Laura J. van 't Veer, Peter M. Ravdin, Paul D.P. Pharaoh, Marjanka K. Schmidt
ImportanceOnline prognostication tools such as PREDICT and Adjuvant! are increasingly used in clinical practice by oncologists to inform patients and guide treatment decisions about adjuvant systemic therapy. However, their validity for young breast cancer patients is debated.ObjectiveTo assess first, the prognostic accuracy of PREDICT's and Adjuvant! 10-year all-cause mortality, and second, its breast cancer–specific mortality estimates, in a large cohort of breast cancer patients diagnosed <50 years.DesignHospital-based cohort.SettingGeneral and cancer hospitals.ParticipantsA consecutive series of 2710 patients without a prior history of cancer, diagnosed between 1990 and 2000 with unilateral stage I–III breast cancer aged <50 years.Main outcome measuresCalibration and discriminatory accuracy, measured with C-statistics, of estimated 10-year all-cause and breast cancer–specific mortality.ResultsOverall, PREDICT's calibration for all-cause mortality was good (predicted versus observed) meandifference: −1.1% (95%CI: −3.2%–0.9%; P = 0.28). PREDICT tended to underestimate all-cause mortality in good prognosis subgroups (range meandifference: −2.9% to −4.8%), overestimated all-cause mortality in poor prognosis subgroups (range meandifference: 2.6%–9.4%) and underestimated survival in patients < 35 by −6.6%. Overall, PREDICT overestimated breast cancer–specific mortality by 3.2% (95%CI: 0.8%–5.6%; P = 0.007); and also overestimated it seemingly indiscriminately in numerous subgroups (range meandifference: 3.2%–14.1%). Calibration was poor in the cohort of patients with the lowest and those with the highest mortality probabilities. Discriminatory accuracy was moderate-to-good for all-cause mortality in PREDICT (0.71 [95%CI: 0.68 to 0.73]), and the results were similar for breast cancer–specific mortality. Adjuvant!'s calibration and discriminatory accuracy for both all-cause and breast cancer–specific mortality were in line with PREDICT's findings.ConclusionsAlthough imprecise at the extremes, PREDICT's estimates of 10-year all-cause mortality seem reasonably sound for breast cancer patients <50 years; Adjuvant! findings were similar. Prognostication tools should be used with caution due to the intrinsic variability of their estimates, and because the threshold to discuss adjuvant systemic treatment is low. Thus, seemingly insignificant mortality overestimations or underestimations of a few percentages can significantly impact treatment decision-making.



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Baseline carcinoembryonic antigen as a predictive factor of ramucirumab efficacy in RAISE, a second-line metastatic colorectal carcinoma phase III trial

Publication date: June 2017
Source:European Journal of Cancer, Volume 78
Author(s): Takayuki Yoshino, Radka Obermannová, György Bodoky, Rocio Garcia-Carbonero, Tudor Ciuleanu, David C. Portnoy, Tae Won Kim, Yanzhi Hsu, David Ferry, Federico Nasroulah, Josep Tabernero
BackgroundThe RAISE phase III clinical trial demonstrated that ramucirumab + (folinic acid plus 5-fluorouracil plus irinotecan) FOLFIRI significantly improved overall survival (OS) versus placebo + FOLFIRI for second-line metastatic colorectal carcinoma (mCRC) patients failing bevacizumab- and oxaliplatin-based chemotherapy (hazard ratio [HR] = 0.84, 95% CI = 0.73–0.98, P = 0.022). Post hoc analyses of RAISE patient data examined the association of carcinoembryonic antigen (CEA) subgroups with efficacy parameters.MethodsCEA subgroups (≤10 versus >10 ng/ml) were based on 2X upper limit of normal (ULN) (5 ng/ml). The Kaplan–Meier method estimated the median OS and the progression-free survival (PFS). Log-rank test compared the survival distributions within the subgroups. Hazard ratio (HR) (95% confidence interval [CI]) and treatment-by-subgroup interaction p-values were calculated by Cox proportional hazards model.ResultsRamucirumab treatment prolonged survival for the CEA ≤10 subgroup (HR = 0.68; 95% CI = 0.50–0.92; P = 0.013) and CEA >10 subgroup (HR = 0.90; 95% CI = 0.76–1.07; P = 0.233). However, the ramucirumab OS benefit over placebo was greater for the CEA ≤10 subgroup than for the CEA >10 subgroup (median OS: 3.6 versus 0.8 months greater, respectively). The interaction P-value between CEA level and treatment effect on OS was 0.088. This trend was observed across randomisation strata and to a lesser extent for PFS (P = 0.594).ConclusionsAlthough patients in both high- and low-CEA subgroups derive OS and PFS benefits from ramucirumab treatment, the low baseline CEA level may identify a subgroup of patients with mCRC who obtain greater benefit from ramucirumab.



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Online self-test identifies women at high familial breast cancer risk in population-based breast cancer screening without inducing anxiety or distress

Publication date: June 2017
Source:European Journal of Cancer, Volume 78
Author(s): A. van Erkelens, A.S. Sie, P. Manders, A. Visser, L.E. Duijm, R.M. Mann, M. ten Voorde, H. Kroeze, J.B. Prins, N. Hoogerbrugge
IntroductionIdentifying high familial breast cancer (FBC) risk improves detection of yet unknown BRCA1/2-mutation carriers, for whom BC risk is both highly likely and potentially preventable. We assessed whether a new online self-test could identify women at high FBC risk in population-based BC screening without inducing anxiety or distress.MethodsAfter their visit for screening mammography, women were invited by email to take an online self-test for identifying highly increased FBC risk-based on Dutch guidelines. Exclusion criteria were previously diagnosed as increased FBC risk or a personal history of BC. Anxiety (State-Trait Anxiety Inventory Dutch Version), distress (Hospital Anxiety Depression Scale) and BC risk perception were assessed using questionnaires, which were completed immediately before and after taking the online self-test and 2 weeks later.ResultsOf the 562 women invited by email, 406 (72%) completed the online self-test while 304 also completed questionnaires (response rate 54%). After exclusion criteria, 287 (51%) were included for data analysis. Median age was 56 years (range 50–74). A high or moderate FBC risk was identified in 12 (4%) and three (1%) women, respectively. After completion of the online self-test, anxiety and BC risk perception were decreased while distress scores remained unchanged. Levels were below clinical relevance. Most women (85%) would recommend the self-test; few (3%) would not.ConclusionThe online self-test identified previously unknown women at high FBC risk (4%), who may carry a BRCA1/2-mutation, without inducing anxiety or distress. We therefore recommend offering this self-test to women who attend population-based screening mammography for the first time.



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Emergency admission and survival from aggressive non-Hodgkin lymphoma: A report from the UK's population-based Haematological Malignancy Research Network

Publication date: June 2017
Source:European Journal of Cancer, Volume 78
Author(s): Eleanor Kane, Debra Howell, Alexandra Smith, Simon Crouch, Cathy Burton, Eve Roman, Russell Patmore
BackgroundNon-Hodgkin lymphoma (NHL) is often diagnosed after emergency presentation, a route associated with poor survival and an indicator of diagnostic delay. Accounting for around half of all NHLs, diffuse large B-cell lymphoma (DLBCL) is of particular interest since although it is potentially curable with standardised chemotherapy it can be challenging to identify at an early stage in the primary care setting.Patients and methodsSet within a socio-demographically representative United Kingdom population of around 4 million people, data are from an established patient cohort. This report includes all patients (≥18 years) diagnosed with DLBCL 2004–2011 (n = 1660). Emergency admissions were identified via linkage to Hospital Episode Statistics using standard methods, and survival was examined using proportional hazards regression.ResultsTwo out of every five patients were diagnosed following an emergency admission, and this was associated with advanced disease and poor survival (p < 0.001). Among the 80% of patients treated with curative chemotherapy, survival discrepancies emerged at the point of diagnosis; the adjusted hazard ratio (emergency versus non-emergency) at one month being 4.0 (95% confidence interval 1.9–8.2). No lasting impact was evident in patients who survived for 12 months or more.ConclusionEmergency presentation impacts negatively on DLBCL survival; patients presenting via this route have significantly poorer outcomes than patients with similar clinical characteristics who present via other routes.



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Volume-outcome relation in palliative systemic treatment of metastatic oesophagogastric cancer

Publication date: June 2017
Source:European Journal of Cancer, Volume 78
Author(s): N. Haj Mohammad, N. Bernards, M. van Putten, V.E.P.P. Lemmens, M.G.H. van Oijen, H.W.M. van Laarhoven
IntroductionPalliative systemic therapy has been shown to improve survival in metastatic oesophagogastric cancer. Administration of palliative systemic therapy in metastatic oesophagogastric cancer varies between hospitals. We aimed to explore the association between the annual hospital volume of oesophagogastric cancer patients and survival.MethodsPatients diagnosed in the Netherlands between 2005 and 2013 with metastatic oesophagogastric cancer were identified in the Netherlands Cancer Registry. Patients were attributed according to three definitions of high volume: (1) high-volume incidence centre, (2) high-volume treatment centre and (3) high-volume surgical centre. Independent predictors for administration of palliative chemotherapy were evaluated by means of multivariable logistic regression analysis, and multivariable Cox proportional hazard regression analysis was performed to assess the impact of high-volume centres on survival.ResultsOur data set comprised 4078 patients with metastatic oesophageal cancer, and 5425 patients with metastatic gastric cancer, with a median overall survival of 20 weeks (95% confidence interval [CI] 19–21 weeks) and 16 weeks (95% CI 15–17 weeks), respectively. Patients with oesophageal cancer treated in a high-volume surgical centre (adjusted hazard ratio [HR] 0.80, 95% CI 0.70–0.91) and a high-volume treatment centre (adjusted HR 0.88, 95% CI 0.78–0.99) exhibited a decreased risk of death. For gastric cancer, patients treated in a high-volume surgical centre (adjusted HR 0.83, 95% CI 0.74–0.92) had a superior outcome.ConclusionImproved survival in patients undergoing palliative systemic therapy for oesophagogastric cancer was associated with treatment in high-volume treatment and surgical centres. Further research should be implemented to explore which specific factors of high-volume centres are associated with improved outcomes.



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Baseline β-catenin, programmed death-ligand 1 expression and tumour-infiltrating lymphocytes predict response and poor prognosis in BRAF inhibitor-treated melanoma patients

Publication date: June 2017
Source:European Journal of Cancer, Volume 78
Author(s): Daniela Massi, Emanuela Romano, Eliana Rulli, Barbara Merelli, Romina Nassini, Francesco De Logu, Ivan Bieche, Gianna Baroni, Laura Cattaneo, Gongda Xue, Mario Mandalà
BackgroundThe activation of oncogenic Wnt/β-catenin pathway in melanoma contributes to a lack of T-cell infiltration. Whether baseline β-catenin expression in the context of tumour-infiltrating lymphocytes (TILs) and programmed death ligand-1 (PD-L1) overexpression correlates with prognosis of metastatic melanoma patients (MMPs) treated with mitogen-activated protein kinase, MAPK inhibitor (MAPKi) monotherapy, however, has not been fully clarified.Patients and methodsSixty-four pre-treatment formalin-fixed and paraffin embedded melanoma samples from MMP treated with a BRAF inhibitor (n = 39) or BRAF and MEK inhibitors (n = 25) were assessed for presence of β-catenin, PD-L1, cluster of differentiation (CD)8, CD103 and forkhead box protein P3 (FOXP3) expression by immunohistochemistry, and results were correlated with clinical outcome. Quantitative assessment of mRNA transcripts associated with Wnt/β-catenin pathway and immune response was performed in 51 patients.ResultsWe found an inverse correlation between tumoural β-catenin expression and the level of CD8, CD103 or forkhead box protein P3 (FOXP3) positivity in the tumour microenvironment (TME). By multivariate analysis, PD-L1 <5% (odds ratio, OR 0.12, 95% confidence interval, CI 0.03–0.53, p = 0.005) and the presence of CD8+ T cells (OR 18.27, 95%CI 2.54–131.52, p = 0.004) were significantly associated with a higher probability of response to MAPKi monotherapy. Responding patients showed a significantly increased expression of mRNA transcripts associated with adaptive immunity and antigen presentation. By multivariate analysis, progression-free survival (PFS) (hazards ratio (HR) = 0.25 95%CI 0.10–0.61, p = 0.002) and overall survival (OS) (HR = 0.24 95%CI 0.09–0.67, p = 0.006) were longer in patients with high density of CD8+ T cells and β-catenin <10% than those without CD8+ T cells infiltration and β-catenin ≥10%.ConclusionOur findings provide evidence that in the context of MAPKi monotherapy, immune subsets in the (TME) and gene signature predict prognosis in MMPs.



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Less-favourable prognosis for low-risk endometrial cancer patients with a discordant pre- versus post-operative risk stratification

Publication date: June 2017
Source:European Journal of Cancer, Volume 78
Author(s): F.A. Eggink, C.H. Mom, K. Bouwman, D. Boll, J.H. Becker, C.L. Creutzberg, G.C. Niemeijer, W.J. van Driel, A.K. Reyners, A.G. van der Zee, G.L. Bremer, N.P. Ezendam, R.F. Kruitwagen, J.M. Pijnenborg, H. Hollema, H.W. Nijman, M.A. van der Aa
BackgroundPre-operative risk stratification based on endometrial sampling determines the extent of surgery for endometrial cancer (EC). We investigated the concordance of pre- and post-operative risk stratifications and the impact of discordance on survival.MethodsPatients diagnosed with EC within the first 6 months of the years 2005–2014 were selected from the Netherlands Cancer Registry (N = 7875). Pre- and post-operative risk stratifications were determined based on grade and/or histological subtype for 3784 eligible patients.ResultsA discordant risk stratification was found in 10% of patients: 4% (N = 155) had high pre- and low post-operative risk and 6% (N = 215) had low pre- and high post-operative risk. Overall survival of patients with high pre- and low post-operative risk was less favourable compared to those with a concordant low risk (80% versus 89%, p = 0.002). This difference remained significant when correcting for age, stage, surgical staging and adjuvant therapy (hazard ratio 1.80, 95% confidence interval 1.28–2.53, p = 0.001). Survival of patients with low pre- and high post-operative risk did not differ from those with a concordant high risk (64% versus 62%, p = 0.295).ConclusionPatients with high pre- and low post-operative risk have a less favourable prognosis compared to patients with a concordant low risk. Pre-operative risk stratifications contain independent prognostic information and should be incorporated into clinical decision-making.



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Complications pulmonaires de la radiothérapie après cancer du sein : penser à la BOOP

Publication date: Available online 14 April 2017
Source:Cancer/Radiothérapie
Author(s): J. Ducray, S. Vignot, A. Lacout, I. Pougnet, P.-Y. Marcy, C. Chapellier, N. Foray, A. Creisson, J. Thariat




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Complications pulmonaires de la radiothérapie après cancer du sein : penser à la BOOP

Publication date: Available online 14 April 2017
Source:Cancer/Radiothérapie
Author(s): J. Ducray, S. Vignot, A. Lacout, I. Pougnet, P.-Y. Marcy, C. Chapellier, N. Foray, A. Creisson, J. Thariat




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Complications pulmonaires de la radiothérapie après cancer du sein : penser à la BOOP

Publication date: Available online 14 April 2017
Source:Cancer/Radiothérapie
Author(s): J. Ducray, S. Vignot, A. Lacout, I. Pougnet, P.-Y. Marcy, C. Chapellier, N. Foray, A. Creisson, J. Thariat




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Complications pulmonaires de la radiothérapie après cancer du sein : penser à la BOOP

Publication date: Available online 14 April 2017
Source:Cancer/Radiothérapie
Author(s): J. Ducray, S. Vignot, A. Lacout, I. Pougnet, P.-Y. Marcy, C. Chapellier, N. Foray, A. Creisson, J. Thariat




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Laparoscopy-specific ventral approach in laparoscopic hemihepatectomy

Background

The laparoscopic caudal approach is very different from the open ventral approach, specifically with respect to the surgical view, which is completely different and is the underlying reason for why laparoscopic hepatectomy is technically challenging. We have introduced a new laparoscopy-specific ventral approach in laparoscopic hemihepatectomy.

Methods

The liver was transected from the ventral side to the dorsal side, via a flexible laparoscope, as in open liver resection. The key characteristic of the ventral approach is the early opening of the cranial part, which guides the accurate transection and maintains an open cutting plane. The middle hepatic vein is exposed from the root side toward the periphery.

Results

From March to December 2016, this technique was performed on 12 patients. Of these patients, five underwent right hepatectomy, five underwent left hepatectomy, and two underwent extended left hepatectomy that included the middle hepatic vein. The median operative time was 250 min (range 210-350 min), and the median blood loss was 165 mL (range 100-260 mL). There was no postoperative morbidity or mortality. The median postoperative hospital stay was 8 days (range 5-14 days).

Conclusion

This ventral approach may be an effective and feasible technique for laparoscopic hemihepatectomy.

http://ift.tt/2oz3z3Q

Immune responses and long-term disease recurrence status after telomerase-based dendritic cell immunotherapy in patients with acute myeloid leukemia

BACKGROUND

Telomerase activity in leukemic blasts frequently is increased among patients with high-risk acute myeloid leukemia (AML). In the current study, the authors evaluated the feasibility, safety, immunogenicity, and therapeutic potential of human telomerase reverse transcriptase (hTERT)-expressing autologous dendritic cells (hTERT-DCs) in adult patients with AML.

METHODS

hTERT-DCs were produced from patient-specific leukapheresis, electroporated with an mRNA-encoding hTERT and a lysosomal-targeting sequence, and cryopreserved. A total of 22 patients with a median age of 58 years (range, 30-75 years) with intermediate-risk or high-risk AML in first or second complete remission (CR) were enrolled. hTERT-DCs were generated for 24 patients (73%). A median of 17 intradermal vaccinations (range, 6-32 intradermal vaccinations) containing 1×10⁷ cells were administered as 6 weekly injections followed by 6 biweekly injections. A total of 21 patients (16 in first CR, 3 in second CR, and 2 with early disease recurrence) received hTERT-DCs.

RESULTS

hTERT-DCs were well tolerated with no severe toxicities reported, with the exception of 1 patient who developed idiopathic thrombocytopenic purpura. Of the 19 patients receiving hTERT-DCs in CR, 11 patients (58%) developed hTERT-specific T-cell responses that primarily were targeted toward hTERT peptides with predicted low human leukocyte antigen (HLA)-binding affinities. With a median follow-up of 52 months, 58% of patients in CR (11 of 19 patients) were free of disease recurrence at the time of their last follow-up visit; 57% of the patients who were aged ≥60 years (4 of 7 patients) also were found to be free of disease recurrence at a median follow-up of 54 months.

CONCLUSIONS

The generation of hTERT-DCs is feasible and vaccination with hTERT-DCs appears to be safe and may be associated with favorable recurrence-free survival. Cancer 2017. © 2017 American Cancer Society.

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Immune responses and long-term disease recurrence status after telomerase-based dendritic cell immunotherapy in patients with acute myeloid leukemia

BACKGROUND

Telomerase activity in leukemic blasts frequently is increased among patients with high-risk acute myeloid leukemia (AML). In the current study, the authors evaluated the feasibility, safety, immunogenicity, and therapeutic potential of human telomerase reverse transcriptase (hTERT)-expressing autologous dendritic cells (hTERT-DCs) in adult patients with AML.

METHODS

hTERT-DCs were produced from patient-specific leukapheresis, electroporated with an mRNA-encoding hTERT and a lysosomal-targeting sequence, and cryopreserved. A total of 22 patients with a median age of 58 years (range, 30-75 years) with intermediate-risk or high-risk AML in first or second complete remission (CR) were enrolled. hTERT-DCs were generated for 24 patients (73%). A median of 17 intradermal vaccinations (range, 6-32 intradermal vaccinations) containing 1×10⁷ cells were administered as 6 weekly injections followed by 6 biweekly injections. A total of 21 patients (16 in first CR, 3 in second CR, and 2 with early disease recurrence) received hTERT-DCs.

RESULTS

hTERT-DCs were well tolerated with no severe toxicities reported, with the exception of 1 patient who developed idiopathic thrombocytopenic purpura. Of the 19 patients receiving hTERT-DCs in CR, 11 patients (58%) developed hTERT-specific T-cell responses that primarily were targeted toward hTERT peptides with predicted low human leukocyte antigen (HLA)-binding affinities. With a median follow-up of 52 months, 58% of patients in CR (11 of 19 patients) were free of disease recurrence at the time of their last follow-up visit; 57% of the patients who were aged ≥60 years (4 of 7 patients) also were found to be free of disease recurrence at a median follow-up of 54 months.

CONCLUSIONS

The generation of hTERT-DCs is feasible and vaccination with hTERT-DCs appears to be safe and may be associated with favorable recurrence-free survival. Cancer 2017. © 2017 American Cancer Society.

http://ift.tt/2ouUS99

Laparoscopy-specific ventral approach in laparoscopic hemihepatectomy

Background

The laparoscopic caudal approach is very different from the open ventral approach, specifically with respect to the surgical view, which is completely different and is the underlying reason for why laparoscopic hepatectomy is technically challenging. We have introduced a new laparoscopy-specific ventral approach in laparoscopic hemihepatectomy.

Methods

The liver was transected from the ventral side to the dorsal side, via a flexible laparoscope, as in open liver resection. The key characteristic of the ventral approach is the early opening of the cranial part, which guides the accurate transection and maintains an open cutting plane. The middle hepatic vein is exposed from the root side toward the periphery.

Results

From March to December 2016, this technique was performed on 12 patients. Of these patients, five underwent right hepatectomy, five underwent left hepatectomy, and two underwent extended left hepatectomy that included the middle hepatic vein. The median operative time was 250 min (range 210-350 min), and the median blood loss was 165 mL (range 100-260 mL). There was no postoperative morbidity or mortality. The median postoperative hospital stay was 8 days (range 5-14 days).

Conclusion

This ventral approach may be an effective and feasible technique for laparoscopic hemihepatectomy.

http://ift.tt/2oz3z3Q

Laparoscopy-specific ventral approach in laparoscopic hemihepatectomy

Background

The laparoscopic caudal approach is very different from the open ventral approach, specifically with respect to the surgical view, which is completely different and is the underlying reason for why laparoscopic hepatectomy is technically challenging. We have introduced a new laparoscopy-specific ventral approach in laparoscopic hemihepatectomy.

Methods

The liver was transected from the ventral side to the dorsal side, via a flexible laparoscope, as in open liver resection. The key characteristic of the ventral approach is the early opening of the cranial part, which guides the accurate transection and maintains an open cutting plane. The middle hepatic vein is exposed from the root side toward the periphery.

Results

From March to December 2016, this technique was performed on 12 patients. Of these patients, five underwent right hepatectomy, five underwent left hepatectomy, and two underwent extended left hepatectomy that included the middle hepatic vein. The median operative time was 250 min (range 210-350 min), and the median blood loss was 165 mL (range 100-260 mL). There was no postoperative morbidity or mortality. The median postoperative hospital stay was 8 days (range 5-14 days).

Conclusion

This ventral approach may be an effective and feasible technique for laparoscopic hemihepatectomy.

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Pharmacologic Properties of Novel Local Anesthetic Agents in Anesthesia Practice

Publication date: Available online 14 April 2017
Source:Anesthesiology Clinics
Author(s): Chih H. King, Sascha S. Beutler, Alan D. Kaye, Richard D. Urman

Teaser

Therapeutic duration of traditional local anesthetics when used in peripheral nerve blocks is normally limited. This article describes novel approaches to extend the duration of peripheral nerve blocks currently available or in development. Three newer approaches on extending the duration of peripheral nerve blocks include site-1 sodium channel blockers, novel local anesthetics delivery systems, and novel adjuvants of local anesthetics. Compared with plain amide-based and ester-based local anesthetics, alternative approaches show significant promise in decreasing postoperative pain, rescue opioid requirement, hospital length-of-stay, and overall health care cost, without compromising the established safety profile of traditional local anesthetics.


http://ift.tt/2ozb9v3

Ketorolac, Oxymorphone, Tapentadol, and Tramadol

Publication date: Available online 14 April 2017
Source:Anesthesiology Clinics
Author(s): Nalini Vadivelu, Daniel Chang, Erik M. Helander, Gregory J. Bordelon, Alice Kai, Alan D. Kaye, Dora Hsu, Daniel Bang, Inderjeet Julka

Teaser

Pain remains a tremendous burden on patients and for the health care system, with uncontrolled pain being the leading cause of disability in this country. There are a variety of medications that can be used in the treatment of pain, including ketorolac, oxymorphone, tapentadol, and tramadol. Depending on the clinical situation, these drugs can be used as monotherapy or in conjunction with other types of medications in a multimodal approach. A strong appreciation of pharmacologic properties of these agents and potential side effects is warranted for clinicians.


http://ift.tt/2ouP9jn

Pulmonary Vasodilators and Anesthesia Considerations

Publication date: Available online 14 April 2017
Source:Anesthesiology Clinics
Author(s): Jeremy B. Green, Brendon M. Hart, Elyse M. Cornett, Alan D. Kaye, Ali Salehi, Charles J. Fox

Teaser

Pulmonary hypertension (PH) is a complex disease process of the pulmonary vasculature system characterized by elevated pulmonary arterial pressures. Patients with PH are at increased risk for morbidity and mortality, including intraoperatively and postoperatively. Appreciation by the clinical anesthesiologist of the pathophysiology of PH is warranted. Careful and meticulous strategy using appropriate anesthetic medications, pulmonary vasodilator and inotropic agents, and careful fluid management all increase the likelihood of the best possible outcome in this challenging patient population.


http://ift.tt/2ozkHGr

Cardiovascular Pharmacology

Publication date: Available online 14 April 2017
Source:Anesthesiology Clinics
Author(s): Camellia Asgarian, Henry Liu, Alan D. Kaye

Teaser

Cardiovascular disease remains a leading cause of morbidity and mortality worldwide. The development of therapeutic agents for the treatment of cardiovascular diseases has always been a priority because of the huge potential market for these drugs. These medications should be part of the anesthesiologist's armamentarium because the typical surgical patient is older and has more comorbidities than in the past. This article reviews commonly used cardiovascular medications that are important in managing patients with unstable hemodynamics.


http://ift.tt/2ouXMdG

Total Parenteral and Enteral Nutrition in the ICU

Publication date: Available online 14 April 2017
Source:Anesthesiology Clinics
Author(s): Amir O. Elhassan, Lien B. Tran, Richard C. Clarke, Sumit Singh, Alan David Kaye

Teaser

Appropriate nutrition in the hospital setting, particularly in critically ill patients, has long been tied to improving clinical outcomes. During critical illness, inflammatory mediators and cytokines lead to the creation of a catabolic state to facilitate the use of endogenous energy sources to meet increased energy demands. This process results in increasing the likelihood of overfeeding. The literature has revealed exponential advances in understanding the molecular basis of nutritional support and evolution of clinical protocols aimed at treating artificial nutritional support as a therapeutic intervention, preventing loss of lean body mass and metabolic deterioration to improve clinical outcomes in the critically ill.


http://ift.tt/2oz8NwA

New Hypnotic Drug Development and Pharmacologic Considerations for Clinical Anesthesia

Publication date: Available online 14 April 2017
Source:Anesthesiology Clinics
Author(s): Mariah Kincaid Tanious, Sascha S. Beutler, Alan D. Kaye, Richard D. Urman

Teaser

Since the public demonstration of ether as a novel, viable anesthetic for surgery in 1846, the field of anesthesia has continually sought the ideal anesthetic—rapid onset, potent sedation-hypnosis with a high therapeutic ratio of toxic dose to minimally effective dose, predictable clearance to inactive metabolites, and minimal side effects. This article aims to review current progress of novel induction agent development and provide an update on the most promising drugs poised to enter clinical practice. In addition, the authors describe trends in novel agent development, implications for health care costs, and implications for perioperative care.


http://ift.tt/2ouYKa2

Pharmacologic Considerations of Anesthetic Agents in Pediatric Patients

Publication date: Available online 14 April 2017
Source:Anesthesiology Clinics
Author(s): Alan D. Kaye, Charles J. Fox, Ira W. Padnos, Kenny P. Ehrhardt, James H. Diaz, Elyse Cornett, Debbie Chandler, Sudipta Sen, Shilpadevi Patil

Teaser

Acute pain in the pediatric population has important differences in terms of biology, intrapopulation variation, and epidemiology. Discussion as to the pharmacologic considerations of anesthetic agents, such as induction agents, neuromuscular blockers, opioids, local anesthetics, and adjuvant agents, is presented in this article. Special considerations and concerns, such as risk for propofol infusion syndrome and adverse potential side effects of anesthesia agents, are discussed. Anesthesiologists managing pediatric patients need to have a firm understanding of physiologic and pharmacologic differences compared with the adult population. Future studies to improve the understanding of pharmacokinetics in the pediatric population are needed.


http://ift.tt/2oz0pNg

Qualitative analysis of the impact of Oral Potentially Malignant Disorders on daily life activities

by Jyothi Tadakamadla, Santhosh Kumar, Ratilal Lalloo, Newell W. Johnson

Objective

To evaluate the impact of Oral Potentially Malignant Disorders (OPMD) on daily life activities.

Materials and methods

Patients diagnosed with Oral Leukoplakia, Oral submucous fibrosis and Oral Lichen Planus attending the Oral Medicine clinic of Panineeya Institute of Dental Sciences & Research Centre, Hyderabad, India were invited to participate. Eighteen interviews and three focus groups were conducted in a non-clinical setting. Voice recordings were transcribed and translated from Telugu to English. Data coding was performed using the NVivo software.

Results

Sample size for this qualitative study comprised 32 patients. Four main themes emerged: (1) difficulties with diagnosis and knowledge about the condition, (2) physical impairment and functional limitations, (3) psychological and social wellbeing and (4) effects of treatment on daily life. In a majority of the patients, most of the interview time was spent discussing physical impairment and functional limitations. Patients also reported their mouth condition having a debilitating effect on their psychological well-being and social interactions.

Conclusions

'Physical impairment and functional limitations' was the most important theme for many of the patients. However, the impacts of OPMD also extended beyond physical impairment and functional limitations to aspects of daily living, notably psychological and social wellbeing.

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Qualitative analysis of the impact of Oral Potentially Malignant Disorders on daily life activities

by Jyothi Tadakamadla, Santhosh Kumar, Ratilal Lalloo, Newell W. Johnson

Objective

To evaluate the impact of Oral Potentially Malignant Disorders (OPMD) on daily life activities.

Materials and methods

Patients diagnosed with Oral Leukoplakia, Oral submucous fibrosis and Oral Lichen Planus attending the Oral Medicine clinic of Panineeya Institute of Dental Sciences & Research Centre, Hyderabad, India were invited to participate. Eighteen interviews and three focus groups were conducted in a non-clinical setting. Voice recordings were transcribed and translated from Telugu to English. Data coding was performed using the NVivo software.

Results

Sample size for this qualitative study comprised 32 patients. Four main themes emerged: (1) difficulties with diagnosis and knowledge about the condition, (2) physical impairment and functional limitations, (3) psychological and social wellbeing and (4) effects of treatment on daily life. In a majority of the patients, most of the interview time was spent discussing physical impairment and functional limitations. Patients also reported their mouth condition having a debilitating effect on their psychological well-being and social interactions.

Conclusions

'Physical impairment and functional limitations' was the most important theme for many of the patients. However, the impacts of OPMD also extended beyond physical impairment and functional limitations to aspects of daily living, notably psychological and social wellbeing.

http://ift.tt/2piZ6Ar

Liquid biopsy: a step forward towards precision medicine in urologic malignancies

Abstract

There is a growing trend towards exploring the use of a minimally invasive "liquid biopsy" to identify biomarkers in a number of cancers, including urologic malignancies. Multiple aspects can be assessed in circulating cell-free DNA, including cell-free DNA levels, integrity, methylation and mutations. Other prospective liquid biopsy markers include circulating tumor cells, circulating RNAs (miRNA, lncRNAs and mRNAs), cell-free proteins, peptides and exosomes have also emerged as non-invasive cancer biomarkers. These circulating molecules can be detected in various biological fluids, including blood, urine, saliva and seminal plasma. Liquid biopsies hold great promise for personalized medicine due to their ability to provide multiple non-invasive global snapshots of the primary and metastatic tumors. Molecular profiling of circulating molecules has been a stepping-stone to the successful introduction of several non-invasive multi-marker tests into the clinic. In this review, we provide an overview of the current state of cell-free DNA-based kidney, prostate and bladder cancer biomarker research and discuss the potential utility other circulating molecules. We will also discuss the challenges and limitations facing non-invasive cancer biomarker discovery and the benefits of this growing area of translational research.

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Liquid biopsy: a step forward towards precision medicine in urologic malignancies

Abstract

There is a growing trend towards exploring the use of a minimally invasive "liquid biopsy" to identify biomarkers in a number of cancers, including urologic malignancies. Multiple aspects can be assessed in circulating cell-free DNA, including cell-free DNA levels, integrity, methylation and mutations. Other prospective liquid biopsy markers include circulating tumor cells, circulating RNAs (miRNA, lncRNAs and mRNAs), cell-free proteins, peptides and exosomes have also emerged as non-invasive cancer biomarkers. These circulating molecules can be detected in various biological fluids, including blood, urine, saliva and seminal plasma. Liquid biopsies hold great promise for personalized medicine due to their ability to provide multiple non-invasive global snapshots of the primary and metastatic tumors. Molecular profiling of circulating molecules has been a stepping-stone to the successful introduction of several non-invasive multi-marker tests into the clinic. In this review, we provide an overview of the current state of cell-free DNA-based kidney, prostate and bladder cancer biomarker research and discuss the potential utility other circulating molecules. We will also discuss the challenges and limitations facing non-invasive cancer biomarker discovery and the benefits of this growing area of translational research.

http://ift.tt/2oz71v3

Some haematological parameters of albino mice experimentally inoculated with Trypanosoma brucei brucei after administration of Halofantrine hydrochloride, chloroquine and diaminazine aceturate

Abstract

Trypanosomosis has been a menace. When animals become infected with trypanosomosis, their physiology is altered leading to haematological aberrations. The comparative effects of Halofantrine chloride (Halfan), chloroquine and diaminazine aceturate (DA) were experimentally investigated in the treatment of Trypanosoma brucei brucei infected albino mice. This is to know whether Halfan and chloroquine can provide alternatives to diaminazine aceturate. White albino mice experimentally infected with T. brucei brucei which were separately treated 7 days post infection with Halfan at 100 mg/kg body weight as a single dose orally, chloroquine phosphate at 0.12 mg/kg body weight, administered intraperitoneally (IP) and DA given IP at 3.5 mg/kg body weight and the last group served as the untreated control. There was a slight depression of the packed cell volume (PCV) after infection of all the groups. However, following treatment, there was significant rise (P < 0.05) in the PCV values for animals in groups 1, 2, 3 but not for the control group, in which there was progressive reduction. Following infection with T. brucei brucei, this led to lymphocytosis in all the experimental groups but after treatment with Halfan, chloroquine and DA, there was gradual lymphocytopenia. There was neutropenia from day 0 to day 7 when they were subjected to different chemotherapeutic treatment; there was variable neutrophilia but never to pre-infection level till the termination of the experiment. Although, there was transient eosinophilia which subsided to normalcy just before treatment but stabilized after treatment except in group 3 (DA treated). There was significant decrease (P < 0.05) in monocyte count in Halfan treated group and untreated control throughout the experimental period; this changed by day 30 when the study was voluntarily terminated. In groups 2 and 3, there was fluctuation over time but, the overall trend was that of an increase of monocytes throughout the experimental period. There is a possibility that parenteral formulation of Halfan may, if explored, provide maximal blood levels that can be used therapeutically alone or in combination with diaminazine aceturate, instead of oral formulations used in this study.

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Nodular oncocytic hyperplasia: Can cytomorphology allow for the preoperative diagnosis of a nonneoplastic salivary disease?

BACKGROUND

Nodular oncocytic hyperplasia (oncocytosis) of the salivary glands is a benign process that does not inherently require surgical excision. However, cytologic findings in fine-needle aspiration (FNA) of oncocytosis cases have not been well characterized previously, limiting preoperative identification.

METHODS

All available cases of oncocytosis with corresponding FNA specimens were identified from the pathology archives of 3 academic institutions. Clinical, cytologic, and histologic findings were tabulated for all cases.

RESULTS

Twelve cases of oncocytosis were identified from 11 patients, including 11 parotid FNA specimens and 1 submandibular FNA specimen. On the original diagnoses, 6 specimens were classified as benign, 4 as atypical, and 2 as nondiagnostic. Oncocytosis was listed in the differential diagnosis in only 1 case. Among diagnostic aspirates, 8 demonstrated low cellularity and 2 demonstrated moderate cellularity. All 10 cases demonstrated oncocytic cells in small to medium groups, with single cells in just 1 case. Spindled and squamous morphology were each noted in 3 cases. Four cases demonstrated cystic change and 1 showed background mucin without goblet cells. No necrosis or mitoses were observed.

CONCLUSIONS

Although oncocytosis demonstrates some overlap with Warthin tumor and oncocytoma, it lacks the diagnostic findings specific to oncocytic salivary gland malignancies such as salivary duct carcinoma, acinic cell carcinoma, mammary analog secretory carcinoma, and mucoepidermoid carcinoma. Despite current limitations in the understanding of oncocytic salivary gland lesions, the presence of a paucicellular specimen comprised of small groups of oncocytic cells should raise the possibility of oncocytosis in the differential diagnosis and can favor it in elderly patients with multiple salivary nodules. Cancer (Cancer Cytopathol) 2017. © 2017 American Cancer Society.

http://ift.tt/2pf6oYN

Nodular oncocytic hyperplasia: Can cytomorphology allow for the preoperative diagnosis of a nonneoplastic salivary disease?

BACKGROUND

Nodular oncocytic hyperplasia (oncocytosis) of the salivary glands is a benign process that does not inherently require surgical excision. However, cytologic findings in fine-needle aspiration (FNA) of oncocytosis cases have not been well characterized previously, limiting preoperative identification.

METHODS

All available cases of oncocytosis with corresponding FNA specimens were identified from the pathology archives of 3 academic institutions. Clinical, cytologic, and histologic findings were tabulated for all cases.

RESULTS

Twelve cases of oncocytosis were identified from 11 patients, including 11 parotid FNA specimens and 1 submandibular FNA specimen. On the original diagnoses, 6 specimens were classified as benign, 4 as atypical, and 2 as nondiagnostic. Oncocytosis was listed in the differential diagnosis in only 1 case. Among diagnostic aspirates, 8 demonstrated low cellularity and 2 demonstrated moderate cellularity. All 10 cases demonstrated oncocytic cells in small to medium groups, with single cells in just 1 case. Spindled and squamous morphology were each noted in 3 cases. Four cases demonstrated cystic change and 1 showed background mucin without goblet cells. No necrosis or mitoses were observed.

CONCLUSIONS

Although oncocytosis demonstrates some overlap with Warthin tumor and oncocytoma, it lacks the diagnostic findings specific to oncocytic salivary gland malignancies such as salivary duct carcinoma, acinic cell carcinoma, mammary analog secretory carcinoma, and mucoepidermoid carcinoma. Despite current limitations in the understanding of oncocytic salivary gland lesions, the presence of a paucicellular specimen comprised of small groups of oncocytic cells should raise the possibility of oncocytosis in the differential diagnosis and can favor it in elderly patients with multiple salivary nodules. Cancer (Cancer Cytopathol) 2017. © 2017 American Cancer Society.

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Calreticulin Mutations in Bulgarian MPN Patients

Abstract

Somatic mutations in JAK2, MPL and CALR are recurrently identified in most of the cases with Philadelphia chromosome negative myeloproliferative neoplasms (MPNs). We applied four molecular genetic methods for identification of CALR exon 9 mutations, including high resolution melt (HRM) analysis, Sanger sequencing, semiconductor target genes sequencing and whole exome sequencing. A total of 78 patients with myeloid malignancies were included in the study. We identified 14 CALR exon 9 mutated cases out of 78 studied patients with myeloid malignancies. All mutated patients were diagnosed with MPN being either PMF (n = 7) or ET (n = 7). Nine cases had type 1 mutations and 5 cases had type 2 mutations. CALR exon 9, MPL exon 10 and JAK2 p. V617F were mutually exclusive. There were no statistically significant differences in the hematological parameters between the cases with CALR and JAK2 or MPL mutations. Notably, all four techniques were fully concordant in the detection of CALR mutations. This is one of the few reports on the CALR mutations frequency in South-eastern populations. Our study shows that the frequency and patterns of these mutations is identical to those in the patients' cohorts from Western countries. Besides we demonstrated the utility of four different methods for their detection.

http://ift.tt/2nN1baM

The Effect of miR-200c Inhibition on Chemosensitivity (5- FluoroUracil) in Colorectal Cancer

Abstract

5-Fluorouracil (5-FU) as a chemotherapeutic drug is used to treat colorectal cancer (CRC). However, 5-FU is associated with acquired CRC resistance, which decreases the therapeutic potential of 5-FU. Several studies indicated that miR-200c is also involved in chemotherapeutic drug resistance, but the exact mechanism of miR-200c mediated chemoresistance has not yet been fully understood. In this study, we examined the effect of inhibition of miR-200c on the sensitivity of HCT-116 cells to 5-FU. HCT-116 cells were transfected with LNA-anti- miR-200c for 48 h. mRNA expression of miR-200c was investigated by qRT-PCR. The protein expression of phosphatase and tensin homolog (PTEN) and E-cadherin were evaluated by western blotting. Annexin V/ PI staining and caspase 3 activity were used to detect apoptosis. LNA-anti-miR-200c inhibited the miR-200c expression in the transfected cells compared with that in the control group. LNA-anti-miR-200c suppressed the expression of PTEN and E-cadherin independent of the presence of the chemotherapeutic drug 5-FU. LNA-anti-miR-200c reduced the 5-FU-induced apoptosis and caspase 3 activity. miR-200c, as a novel prognostic marker in CRC, can be a potential therapeutic approach to overcome chemoresistance during 5-FU chemotherapy.

http://ift.tt/2phIt8q

Radiotherapie des Glioblastoms

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Kombination von Strahlentherapie mit Temozolomid bei über 65-jährigen Glioblastompatienten

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Cetuximab zur Radiochemotherapie von Analkarzinomen bei immunkompetenten Patienten ändert bisherigen Therapiestandard nicht

http://ift.tt/2pdwFE6

Calreticulin Mutations in Bulgarian MPN Patients

Abstract

Somatic mutations in JAK2, MPL and CALR are recurrently identified in most of the cases with Philadelphia chromosome negative myeloproliferative neoplasms (MPNs). We applied four molecular genetic methods for identification of CALR exon 9 mutations, including high resolution melt (HRM) analysis, Sanger sequencing, semiconductor target genes sequencing and whole exome sequencing. A total of 78 patients with myeloid malignancies were included in the study. We identified 14 CALR exon 9 mutated cases out of 78 studied patients with myeloid malignancies. All mutated patients were diagnosed with MPN being either PMF (n = 7) or ET (n = 7). Nine cases had type 1 mutations and 5 cases had type 2 mutations. CALR exon 9, MPL exon 10 and JAK2 p. V617F were mutually exclusive. There were no statistically significant differences in the hematological parameters between the cases with CALR and JAK2 or MPL mutations. Notably, all four techniques were fully concordant in the detection of CALR mutations. This is one of the few reports on the CALR mutations frequency in South-eastern populations. Our study shows that the frequency and patterns of these mutations is identical to those in the patients' cohorts from Western countries. Besides we demonstrated the utility of four different methods for their detection.

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The Effect of miR-200c Inhibition on Chemosensitivity (5- FluoroUracil) in Colorectal Cancer

Abstract

5-Fluorouracil (5-FU) as a chemotherapeutic drug is used to treat colorectal cancer (CRC). However, 5-FU is associated with acquired CRC resistance, which decreases the therapeutic potential of 5-FU. Several studies indicated that miR-200c is also involved in chemotherapeutic drug resistance, but the exact mechanism of miR-200c mediated chemoresistance has not yet been fully understood. In this study, we examined the effect of inhibition of miR-200c on the sensitivity of HCT-116 cells to 5-FU. HCT-116 cells were transfected with LNA-anti- miR-200c for 48 h. mRNA expression of miR-200c was investigated by qRT-PCR. The protein expression of phosphatase and tensin homolog (PTEN) and E-cadherin were evaluated by western blotting. Annexin V/ PI staining and caspase 3 activity were used to detect apoptosis. LNA-anti-miR-200c inhibited the miR-200c expression in the transfected cells compared with that in the control group. LNA-anti-miR-200c suppressed the expression of PTEN and E-cadherin independent of the presence of the chemotherapeutic drug 5-FU. LNA-anti-miR-200c reduced the 5-FU-induced apoptosis and caspase 3 activity. miR-200c, as a novel prognostic marker in CRC, can be a potential therapeutic approach to overcome chemoresistance during 5-FU chemotherapy.

from Cancer via ola Kala on Inoreader http://ift.tt/2phIt8q
via IFTTT

Calreticulin Mutations in Bulgarian MPN Patients

Abstract

Somatic mutations in JAK2, MPL and CALR are recurrently identified in most of the cases with Philadelphia chromosome negative myeloproliferative neoplasms (MPNs). We applied four molecular genetic methods for identification of CALR exon 9 mutations, including high resolution melt (HRM) analysis, Sanger sequencing, semiconductor target genes sequencing and whole exome sequencing. A total of 78 patients with myeloid malignancies were included in the study. We identified 14 CALR exon 9 mutated cases out of 78 studied patients with myeloid malignancies. All mutated patients were diagnosed with MPN being either PMF (n = 7) or ET (n = 7). Nine cases had type 1 mutations and 5 cases had type 2 mutations. CALR exon 9, MPL exon 10 and JAK2 p. V617F were mutually exclusive. There were no statistically significant differences in the hematological parameters between the cases with CALR and JAK2 or MPL mutations. Notably, all four techniques were fully concordant in the detection of CALR mutations. This is one of the few reports on the CALR mutations frequency in South-eastern populations. Our study shows that the frequency and patterns of these mutations is identical to those in the patients' cohorts from Western countries. Besides we demonstrated the utility of four different methods for their detection.

http://ift.tt/2nN1baM

The Effect of miR-200c Inhibition on Chemosensitivity (5- FluoroUracil) in Colorectal Cancer

Abstract

5-Fluorouracil (5-FU) as a chemotherapeutic drug is used to treat colorectal cancer (CRC). However, 5-FU is associated with acquired CRC resistance, which decreases the therapeutic potential of 5-FU. Several studies indicated that miR-200c is also involved in chemotherapeutic drug resistance, but the exact mechanism of miR-200c mediated chemoresistance has not yet been fully understood. In this study, we examined the effect of inhibition of miR-200c on the sensitivity of HCT-116 cells to 5-FU. HCT-116 cells were transfected with LNA-anti- miR-200c for 48 h. mRNA expression of miR-200c was investigated by qRT-PCR. The protein expression of phosphatase and tensin homolog (PTEN) and E-cadherin were evaluated by western blotting. Annexin V/ PI staining and caspase 3 activity were used to detect apoptosis. LNA-anti-miR-200c inhibited the miR-200c expression in the transfected cells compared with that in the control group. LNA-anti-miR-200c suppressed the expression of PTEN and E-cadherin independent of the presence of the chemotherapeutic drug 5-FU. LNA-anti-miR-200c reduced the 5-FU-induced apoptosis and caspase 3 activity. miR-200c, as a novel prognostic marker in CRC, can be a potential therapeutic approach to overcome chemoresistance during 5-FU chemotherapy.

http://ift.tt/2phIt8q

Advances of CD19-directed chimeric antigen receptor-modified T cells in refractory/relapsed acute lymphoblastic leukemia

Abstract

Refractory/relapsed B-cell acute lymphoblastic leukemia remains to be a significant cause of cancer-associated morbidity and mortality for children and adults. Developing novel and effective molecular-targeted approaches is thus a major priority. Chimeric antigen receptor-modified T cell (CAR-T) therapy, as one of the most promising targeted immunotherapies, has drawn extensive attention and resulted in multiple applications. According to published studies, CD19-directed CAR-T cells (CD19 CAR-T) can reach a complete remission rate of 94% in both children and adults with refractory/relapsed ALL, much higher than that of chemotherapy. However, the encouraging outcomes are often associated with complications such as cytokine release syndrome (CRS), serious neurotoxicity, and on-target off-tumor effect, which seriously impeded further clinical application of CAR-T cells. Moreover, CAR-T therapy is typically associated with high relapse rate. This article briefly reviews the manufacture technologies, the conditioning regimens, the cell infusion doses, as well as the prevention and treatment strategies of complications for CAR-T cell therapy.

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Advances of CD19-directed chimeric antigen receptor-modified T cells in refractory/relapsed acute lymphoblastic leukemia

Abstract

Refractory/relapsed B-cell acute lymphoblastic leukemia remains to be a significant cause of cancer-associated morbidity and mortality for children and adults. Developing novel and effective molecular-targeted approaches is thus a major priority. Chimeric antigen receptor-modified T cell (CAR-T) therapy, as one of the most promising targeted immunotherapies, has drawn extensive attention and resulted in multiple applications. According to published studies, CD19-directed CAR-T cells (CD19 CAR-T) can reach a complete remission rate of 94% in both children and adults with refractory/relapsed ALL, much higher than that of chemotherapy. However, the encouraging outcomes are often associated with complications such as cytokine release syndrome (CRS), serious neurotoxicity, and on-target off-tumor effect, which seriously impeded further clinical application of CAR-T cells. Moreover, CAR-T therapy is typically associated with high relapse rate. This article briefly reviews the manufacture technologies, the conditioning regimens, the cell infusion doses, as well as the prevention and treatment strategies of complications for CAR-T cell therapy.

http://ift.tt/2nMwl1U

Treatment of post-anesthesia dementia with perispinal etanercept injection and hyperbaric oxygen therapy: a case report

We report on the first case of successful treatment for post-anesthesia dementia with perispinal etanercept injection combined with hyperbaric oxygen therapy.

http://ift.tt/2pdW1EK

Acute symptomatic peri-lead edema 33 hours after deep brain stimulation surgery: a case report

Symptomatic peri-lead edema is a rare complication of deep brain stimulation that has been reported to develop 4 to 120 days postoperatively.

http://ift.tt/2pgCuRb

Moderate alcohol consumption is associated with lower chronic disease burden expressed in disability-adjusted life years: a prospective cohort study

Abstract

The relation of alcohol consumption with disease burden remains debated partly due to opposite associations with cardiovascular disease (CVD) and cancer. The relation of alcohol consumption with disease burden expressed in disability-adjusted life years (DALYs) summarizes opposing associations of alcohol consumption on chronic diseases. This study aimed to investigate the association of alcohol consumption with chronic disease burden expressed in DALYs based on individual-participant data. The study was a prospective study among 33,066 men and women from the EPIC-NL cohort. At baseline, alcohol consumption was assessed with a validated food-frequency questionnaire. Participants were followed for occurrence of and mortality from chronic diseases and DALYs were calculated. After 12.4 years follow-up, 6647 disease incidences and 1482 deaths were documented, resulting in 68,225 healthy years of life lost (6225 DALYs). Moderate drinkers (women 5–14.9 g/day, men 5–29.9 g/day) had a lower chronic disease burden (mean DALYs −0.27; 95% CI −0.43; −0.11) than light drinkers (0–4.9 g/day), driven by a lower disease burden due to CVD (−0.18: −0.29; −0.06) but not cancer (−0.05: −0.16; 0.06). The associations were most pronounced among older participants (≥50 years; −0.32; −0.53; −0.10) and not observed among younger women (−0.08; −0.43; 0.35), albeit non-significant (p_interaction > 0.14). Substantial drinking (women 15–29.9 g/day, men 30–59.9 g/day) compared to light drinking was not associated with chronic disease burden. Our results show that moderate compared to light alcohol consumption was associated with living approximately 3 months longer in good health. These results were mainly observed among older participants and not seen among younger women.

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Constitutional 3p26.3 terminal microdeletion in an adolescent with neuroblastoma.

Related Articles

Constitutional 3p26.3 terminal microdeletion in an adolescent with neuroblastoma.

Cancer Biol Ther. 2017 Apr 12;:0

Authors: Pezzolo A, Sementa AR, Lerone M, Morini M, Ognibene M, Defferrari R, Mazzocco K, Conte M, Gigliotti AR, Garaventa A, Pistoia V, Varesio L

Abstract
BACKGROUND: Neuroblastoma (NB) is a common and often lethal cancer of early childhood that accounts for 10% of pediatric cancer mortality. Incidence peaks in infancy and then rapidly declines, with less than 5% of cases diagnosed in children and adolescents ≥10 years. There is increasing evidence that NB has unique biology and an chronic disease course in older children and adolescents, but ultimately dismal survival.
METHODS: We describe a rare constitutional 3p26.3 terminal microdeletion which occurred in an adolescent with NB, with apparently normal phenotype without neurocognitive defects. We evaluated the association of expression of genes involved in the microdeletion with NB patient outcomes using R2 platform. We screened NB patient's tumor cells for CHL1 protein expression using immunofluorescence.
RESULTS: Constitutional and tumor DNA were tested by array-comparative genomic hybridization and single nucleotide-polymorphism-array analyses. Peripheral blood mononuclear cells from the patient showed a 2.54 Mb sub-microscopic constitutional terminal 3p deletion that extended to band p26.3. The microdeletion 3p disrupted the CNTN4 gene and the neighboring CNTN6 and CHL1 genes were hemizygously deleted, each of these genes encode neuronal cell adhesion molecules. Low expression of CNTN6 and CNTN4 genes did not stratify NB patients, whereas low CHL1 expression characterized 417 NB patients having worse overall survival. CHL1 protein expression on tumor cells from the patient was weaker than positive control.
CONCLUSION: This is the first report of a constitutional 3p26.3 deletion in a NB patient. Since larger deletions of 3p, indicative of the presence of one or more tumor suppressor genes in this region, occur frequently in neuroblastoma, our results pave the way to the identification of one putative NB suppressor genes mapping in 3p26.3.

PMID: 28402723 [PubMed - as supplied by publisher]

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Constitutional 3p26.3 terminal microdeletion in an adolescent with neuroblastoma.

Related Articles

Constitutional 3p26.3 terminal microdeletion in an adolescent with neuroblastoma.

Cancer Biol Ther. 2017 Apr 12;:0

Authors: Pezzolo A, Sementa AR, Lerone M, Morini M, Ognibene M, Defferrari R, Mazzocco K, Conte M, Gigliotti AR, Garaventa A, Pistoia V, Varesio L

Abstract
BACKGROUND: Neuroblastoma (NB) is a common and often lethal cancer of early childhood that accounts for 10% of pediatric cancer mortality. Incidence peaks in infancy and then rapidly declines, with less than 5% of cases diagnosed in children and adolescents ≥10 years. There is increasing evidence that NB has unique biology and an chronic disease course in older children and adolescents, but ultimately dismal survival.
METHODS: We describe a rare constitutional 3p26.3 terminal microdeletion which occurred in an adolescent with NB, with apparently normal phenotype without neurocognitive defects. We evaluated the association of expression of genes involved in the microdeletion with NB patient outcomes using R2 platform. We screened NB patient's tumor cells for CHL1 protein expression using immunofluorescence.
RESULTS: Constitutional and tumor DNA were tested by array-comparative genomic hybridization and single nucleotide-polymorphism-array analyses. Peripheral blood mononuclear cells from the patient showed a 2.54 Mb sub-microscopic constitutional terminal 3p deletion that extended to band p26.3. The microdeletion 3p disrupted the CNTN4 gene and the neighboring CNTN6 and CHL1 genes were hemizygously deleted, each of these genes encode neuronal cell adhesion molecules. Low expression of CNTN6 and CNTN4 genes did not stratify NB patients, whereas low CHL1 expression characterized 417 NB patients having worse overall survival. CHL1 protein expression on tumor cells from the patient was weaker than positive control.
CONCLUSION: This is the first report of a constitutional 3p26.3 deletion in a NB patient. Since larger deletions of 3p, indicative of the presence of one or more tumor suppressor genes in this region, occur frequently in neuroblastoma, our results pave the way to the identification of one putative NB suppressor genes mapping in 3p26.3.

PMID: 28402723 [PubMed - as supplied by publisher]

http://ift.tt/2oxIEy6

Down-regulated expression of OPCML predicts an unfavorable prognosis and promotes disease progression in human gastric cancer

Abstract

Background

OPCML belongs to the IgLON family of Ig domain–containing GPI-anchored cell adhesion molecules and was recently found to be involved in carcinogenesis, while its role in gastric cancer remains unclear.

Methods

We assessed expression and biological behavior of OPCML in gastric cancer.

Results

OPCML expression was markedly reduced in tumor tissues and cancer cell lines. Decreased OPCML expression had a significant association with unfavorable tumor stage (p = 0.007) and grading (p < 0.001). Furthermore, the results revealed that OPCML was an independent prognostic factor for overall survival in gastric cancer (p = 0.002). In addition, ectopic expression of OPCML in cancer cells significantly inhibited cell viability (p < 0.01) and colony formation (p < 0.001), arrest cell cycle in G0/G1 phase and induced apoptosis, and suppressed tumor formation in nude mice. The alterations of phosphorylation status of AKT and its substrate GSK3β, up-regulation of pro-apoptotic regulators including caspase-3, caspase-9 and PARP, and up-regulation of cell cycle regulator p27, were implicated in the biological activity of OPCML in cancer cells.

Conclusion

Down-regulated OPCML expression might serve as an independent predictor for unfavorable prognosis of patients, and the biological behavior supports its role as a tumor suppressor in gastric cancer.

http://ift.tt/2nLYGFz

Serum low-density lipoprotein and low-density lipoprotein expression level at diagnosis are favorable prognostic factors in patients with small-cell lung cancer (SCLC)

Abstract

Background

Patients with small-cell lung cancer (SCLC) patients demonstrate varied survival outcomes. Previous studies have reported that lipoproteins are associated with prognosis in various cancers; however, the role of low-density lipoprotein (LDL) and low-density lipoprotein- cholesterol (LDLR) in patients with SCLC has not been studied.

Methods

In this study, the impact of LDL and LDLR on the prognosis of SCLC patients was evaluated. A total of 601 patients with SCLC were retrospectively evaluated, in which 198 patients had adequate tissues for immunohistochemistry, and serum LDL and LDLR expression levels at baseline were tested. X-tile tool, and univariate and multivariate Cox analysis were used to assess the association between LDL, LDLR and overall survival (OS).

Results

Univariate analysis demonstrated that a lower LDL level was significantly associated with superior OS (P = 0.037). Similarly, LDLR also significantly predicted OS (P = 0.003). Multivariate Cox analyses confirmed that lower LDL and LDLR expression was independent prognostic factors associated with longer OS (P = 0.019 and P = 0.027, respectively).

Conclusions

This study showed that both LDL and LDLR are prognostic indexes for survival in patients with SCLC. Patients with high LDL or LDLR expression level may benefit from treatment that modulates lipoprotein combined with platinum-based chemotherapy.

http://ift.tt/2otwLHN

Overview of cancer incidence and mortality among people living with HIV/AIDS in British Columbia, Canada: Implications for HAART use and NADM development

Abstract

Background

The objective of this study is to evaluate the incidence of non-AIDS defining malignancies (NADMs) among people living with HIV/AIDS (PLWHA) in British Columbia, focusing on clinical correlates, highly active antiretroviral therapy (HAART) use, and survival, in order to elucidate mechanisms for NADM development.

Methods

A retrospective population based analysis was carried out for individuals with HIV/AIDS that began their treatment between 1996 and 2008.

Results

There were 145 (2.95%) NADMs and 123 (2.50%) AIDS defining malignancies (ADMs) identified in 4918 PLWHA in the study population. NADMs were represented by a range of cancer types including, most commonly, lung cancer, followed by anal, breast, head/neck, prostate, liver, rectal, and renal cancers. PLWHA had a SIR of 2.05 (CI:1.73, 2.41) for the development of NADMs compared to individuals without an HIV/AIDS diagnosis in the general population. Independent factors significantly associated with a NADM were: male gender, older age, lower CD4 cell counts, previous NADM, absence of HAART (non-HAART versus HAART) and treatment during the early-HAART era (before 2000 versus after 2000).

Conclusions

NADMs represent an important source of morbidity for PLWHA. Use of HAART with its associated improvement in immune-restoration, and tailored targeted cancer screening interventions, may be beneficial and improve outcomes in this unique patient population.

http://ift.tt/2otvpwx

Effects of omega-3 fatty acids on patients undergoing surgery for gastrointestinal malignancy: a systematic review and meta-analysis

Abstract

Background

Surgical resection remains the primary treatment for gastrointestinal (GI) malignancy including early-stage cancer. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been reported to have beneficial clinical and immune-modulating effects in the prognosis of GI cancer patients undergoing surgery.

Methods

We searched PubMed, Embase, EBSCO-Medline, Cochrane Central Register of Controlled Trials (CENTRAL), CNKI and Wanfang to identify primary research reporting the effects of n-3 PUFAs compared with isocaloric nutrition on GI cancer patients who underwent surgery up to the end of June 30, 2016. Two authors independently reviewed and selected eligible randomized controlled trials (RCTs).

Results

A total of 9 RCTs (623 participants) were included. The n-3 PUFAs regime resulted in lower levels of C-reactive protein (CRP) (P < 0.05), interleukin-6 (IL-6) (P < 0.01), and higher levels of albumin (ALB), CD3⁺ T cells, CD4⁺ T cells and CD4⁺/CD8⁺ ratio (P < 0.05) compared with the isocaloric nutrition regime. However, there was no significant difference in the level of tumor necrosis factor-α (TNF-α) between the n-3 PUFAs regime and the isocaloric nutrition regime (P = 0.17). And the level of CD8 ⁺ T cells decreased compared with the isocaloric nutrition regime (P < 0.0001).

Conclusions

Our meta-analysis revealed that n-3 PUFAs are effective in improving the nutritional status and immune function of GI cancer patients undergoing surgery as they effectively enhance immunity and attenuate the inflammatory response.

http://ift.tt/2nMjZa7