Prognosis of sentinel lymph node biopsy in patients with thick melanoma by a propensity score matching prospective study

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Pretreatment advanced lung cancer inflammation index (ALI) for predicting early progression in nivolumab-treated patients with advanced non–small cell lung cancer

Abstract

Programmed death-ligand 1 (PD-L1) expression status is inadequate for indicating nivolumab in patients with non–small cell lung cancer (NSCLC). Because the baseline advanced lung cancer inflammation index (ALI) is reportedly associated with patient outcomes, we investigated whether the pretreatment ALI is prognostic in NSCLC patients treated with nivolumab. We retrospectively reviewed the medical records of all patients treated with nivolumab for advanced NSCLC between December 2015 and May 2016 at three Japanese institutes. Multivariate logistic regression and Cox proportional hazards models were used to assess the impact of the pretreatment ALI (and other inflammation-related parameters) on progression-free survival (PFS) and early progression (i.e., within 8 weeks after starting nivolumab). A total of 201 patients were analyzed; their median age was 68 years (range, 27–87 years), 67% were men, and 24% had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or higher. An ECOG performance status ≥2, serum albumin <3.7 g/dL, neutrophil-to-lymphocyte ratio ≥4, and ALI <18 were significantly associated with poor PFS and early progression on univariate analysis. Multivariate analyses revealed that pretreatment ALI <18 was independently associated with inferior PFS (median, 1.4 vs. 3.7 months, P < 0.001) and a higher likelihood of early progression (odds ratio, 2.76; 95% confidence interval 1.44–5.34; P = 0.002). The pretreatment ALI was found to be a significant independent predictor of early progression in patients with advanced NSCLC receiving nivolumab, and may help identify patients likely to benefit from continued nivolumab treatment in routine clinical practice.

Pretreatment ALI was a significant independent predictor of early progression in advanced NSCLC patients receiving nivolumab. This may be useful for clinical decision making by identifying patients who may benefit from continued nivolumab treatment.

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Pretreatment advanced lung cancer inflammation index (ALI) for predicting early progression in nivolumab-treated patients with advanced non–small cell lung cancer

Abstract

Programmed death-ligand 1 (PD-L1) expression status is inadequate for indicating nivolumab in patients with non–small cell lung cancer (NSCLC). Because the baseline advanced lung cancer inflammation index (ALI) is reportedly associated with patient outcomes, we investigated whether the pretreatment ALI is prognostic in NSCLC patients treated with nivolumab. We retrospectively reviewed the medical records of all patients treated with nivolumab for advanced NSCLC between December 2015 and May 2016 at three Japanese institutes. Multivariate logistic regression and Cox proportional hazards models were used to assess the impact of the pretreatment ALI (and other inflammation-related parameters) on progression-free survival (PFS) and early progression (i.e., within 8 weeks after starting nivolumab). A total of 201 patients were analyzed; their median age was 68 years (range, 27–87 years), 67% were men, and 24% had an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or higher. An ECOG performance status ≥2, serum albumin <3.7 g/dL, neutrophil-to-lymphocyte ratio ≥4, and ALI <18 were significantly associated with poor PFS and early progression on univariate analysis. Multivariate analyses revealed that pretreatment ALI <18 was independently associated with inferior PFS (median, 1.4 vs. 3.7 months, P < 0.001) and a higher likelihood of early progression (odds ratio, 2.76; 95% confidence interval 1.44–5.34; P = 0.002). The pretreatment ALI was found to be a significant independent predictor of early progression in patients with advanced NSCLC receiving nivolumab, and may help identify patients likely to benefit from continued nivolumab treatment in routine clinical practice.

Pretreatment ALI was a significant independent predictor of early progression in advanced NSCLC patients receiving nivolumab. This may be useful for clinical decision making by identifying patients who may benefit from continued nivolumab treatment.

http://ift.tt/2jye4Ei

Sodium chloride pica causing recurrent nephrolithiasis in a patient with iron deficiency anemia: a case report

Iron deficiency anemia is a common finding in women of child-bearing age. Pica, or the ingestion of non-food or non-nutritive items, is a well-known manifestation of iron deficiency. A high sodium diet increas...

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Editorial Board

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Optimal blood pressure decreases acute kidney injury after gastrointestinal surgery in elderly hypertensive patients: A randomized study

To determine the appropriate mean arterial pressure (MAP) control level for elderly patients with hypertension during the perioperative period.

http://ift.tt/2zOIh8d

Anesthetic management of a patient with benign tracheal tumor identified at induction of general anesthesia

Benign tumors of the tracheobronchial tree are quite rare [1] and are sometimes misdiagnosed as asthma or chronic obstructive pulmonary disease (COPD) when the symptoms are not severe [1,2,3]. Delayed diagnosis is common and these tumors may not be identified for a long time if they are slow growing [1,2,3]. In such cases, routine examinations such as chest radiography will not reveal the tumor before elective surgery [1,3] and it is possible that induction of general anesthesia will be initiated before the anesthetist recognizes that there is a tumor in the tracheobronchial tree.

http://ift.tt/2zNaVH0

Intermittent bilateral anterior sub-costal quadratus lumborum block for effective analgesia in lower abdominal surgery

As one of new quadratus lumborum (QL) blocks, the anterior sub-costal QL block has been reported to be an effective analgesic in lower abdominal surgery [1]. However, there have been no reports on the efficacy of the anterior sub-costal QL block over the long postoperative period. In this article, we report two successful cases of intermittent anterior sub-costal QL block in lower abdominal surgery for pain management during the long postoperative period.

http://ift.tt/2hyvcpf

Combined spinal epidural in a parturient with tinea versicolor

Tinea versicolor is a benign condition with a prevalence of 2–8% in the United States [1]. The yeast, Malassezia globosa, a normal component of skin flora, can become pathogenic with exposure to heat and humidity and in immunosuppressive conditions such as pregnancy. Tinea versicolor responds to antifungal medications but recurrence is common. We present a case of a pregnant patient with a longstanding diagnosis of tinea versicolor in whom we performed a combined spinal technique for labor analgesia after exploring and discussing the theoretical risks.

http://ift.tt/2hAbARJ

Postpartum tubal ligation: A retrospective review of anesthetic management at a single institution and a practice survey of academic institutions

The primary aim was to evaluate institutional anesthetic techniques utilized for postpartum tubal ligation (PPTL). Secondarily, academic institutions were surveyed on their clinical practice for PPTL.

http://ift.tt/2zNaOLA

Surgeon assisted quadratus lumborum block – ‘Gaurav-Aditi’ technique case series

Quadratus lumborum block (QLB) is a new abdominal wall block which has been used successfully for the post operative pain management of patients undergoing abdominal surgeries [1,2]. Classically QLB can be given in four different approaches using ultrasound [3]. In many developing countries like India ultrasound is still not available at all centers. Many times in patients with central obesity it is difficult to perform this block using ultrasound [4]. So we present a new 'Gaurav-Aditi' technique of performing the QLB, wherein post-operative pain of six patients who were undergoing open radical nephrectomy was managed successfully.

http://ift.tt/2hzLE8K

Anesthetic management for retrieval of a large aspirated denture in a patient with Parkinson's disease

Airway foreign body aspiration is uncommon in adults. It is particularly likely in patients with impaired cough reflexes and reduced sensorium due to drugs, alcohol, or neurological dysfunction. Dental prosthetics are the most common foreign bodies aspirated in patients with Parkinson's disease [1]. If a large denture is aspirated, the airway can become totally obstructed. Below, we describe the challenging anesthetic management of a patient with Parkinson's disease who required removal of a large intratracheal denture via rigid bronchoscopy.

http://ift.tt/2zNaGf4

Reversal of trend in near infrared spectroscopy [NIRS] values in a patient with carotid artery stenosis

Near Infrared Spectroscopy (NIRS) monitors continuous non-invasive regional oxygen balance within the frontal cerebral cortex. Cerebral vasoneural coupling ensures that local brain metabolism increase is met normally with augmented regional blood flow [1]. Anaesthetics agents play a vital role and so rising doses of cortical suppressant anaesthetics may increase rSO2 as oxygen consumption is decreased [2].

http://ift.tt/2hBng6R

Strategies to prevent ischemic optic neuropathy following major spine surgery: A narrative review

Postoperative vision loss following a major spine operation is a rare but life-changing event. Most of reports have been linked to ischemic optic neuropathy, and patients undergoing surgery for scoliosis correction or posterior lumbar fusion seem to be at the highest risk. Despite that some key risk factors have been identified, much of the pathophysiology still remain unknown. In fact, whereas only a minority of patients at high risk will present this complication, others with similar risk factors undergoing different procedures may not develop it at all.

http://ift.tt/2zMGRLz

Medicaid insurance as primary payer predicts increased mortality after total hip replacement in the state inpatient databases of California, Florida and New York

To confirm the relationship between primary payer status as a predictor of increased perioperative risks and post-operative outcomes after total hip replacements.

http://ift.tt/2hyzDAt

Incidence of complications in the post-anesthesia care unit and associated healthcare utilization in patients undergoing non-cardiac surgery requiring neuromuscular blockade 2005–2013: A single center study

The use of neuromuscular blockade agents (NMBA), had been associated with significant residual post-operative paralysis and morbidity. There is a lack of clinical evidence on incidence of postoperative complications within the post-anesthesia care unit (PACU) in patients exposed to intraoperative NMBA's. This study aims to estimate the incidence of post-operative complications associated with use of NMBAs and assessing its association with healthcare resource utilization.

http://ift.tt/2zOIfND

Measuring satisfaction and anesthesia related outcomes in a surgical day care centre: A three-year single-centre observational study

To evaluate patient satisfaction and patient reported anaesthesia related outcome parameters after outpatient surgery.

http://ift.tt/2hyv8G1

Paraneuraxial Nerve Blocks: A well-defined novel terminology that is clinically essential for regional anesthesia

We read with great interest the articles "Clinical Experiences of the Continuous Thoracolumbar Interfascial Plane (TLIP) Block" by Ueshima et al. [1]. We would like to share our thoughts regarding this study as we have performed several continuous (TLIP) Blocks in the past 2months.

http://ift.tt/2zOR0aH

Emergency surgery in a newborn patient with severe congenital hypothyrodism

We aimed to discuss anaesthesia management in a newborn with severe hypothyroidism for whom we could not provide hypothyroidism treatment due to tracheoesophageal fistula and anal atresia.

http://ift.tt/2hBJVzS

Co-occurring Alterations Affect Outcomes in EGFR-Mutant Lung Cancer [Research Watch]

Sequencing cfDNA from 1,122 patients with EGFR-mutant lung cancer reveals co-occurring alterations.

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Inflammation-Induced IgA+ Cells Promote Hepatocellular Tumorigenesis [Research Watch]

Chronic inflammation may promote hepatocellular carcinoma by suppressing cytotoxic T-cell activity.

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The Active Conformation of Integrin {beta}7 May Be a Multiple Myeloma Target [Research Watch]

CAR T cells targeting active integrin β₇ have cytotoxic activity against multiple myeloma (MM) cells.

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High BCAT1 Expression Mimics IDH Mutations in Acute Myeloid Leukemia [Research Watch]

High BCAT1 expression is linked to shorter survival in patients with IDH– and TET2–wild-type AML.

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Postpartum infective endocarditis with Enterococcus faecalis in Japan: a case report

The clinical characteristics of infective endocarditis include the presence of predisposing cardiac disease, a history of illegal drug use, and high morbidity in the elderly. Only a few cases of the disease af...

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Influence of Enzalutamide on Cabazitaxel Pharmacokinetics; a Drug-Drug Interaction Study in Metastatic Castration Resistant Prostate Cancer (mCRPC) Patients

Purpose: In ongoing clinical research on metastatic castration-resistant prostate cancer (mCRPC) treatment, the potential enhanced efficacy of the combination of taxanes with AR-targeted agents, i.e. enzalutamide and abiraterone, is currently being explored. Since enzalutamide induces the CYP3A4 enzyme and taxanes are metabolized by this enzyme, a potential drug-drug interaction needs to be investigated. Design: Therefore, we performed a pharmacokinetic cross-over study in mCRPC patients who were scheduled for treatment with cabazitaxel Q3W (25 mg/m²). Patients were studied for three consecutive cabazitaxel cycles. Enzalutamide (160 mg QD) was administered concomitantly after the first cabazitaxel cycle, during 6 weeks. Primary endpoint was the difference in mean area under the curve (AUC) between the first (cabazitaxel monotherapy) and third cabazitaxel cycle, when enzalutamide was added. Results: A potential clinically relevant 22% (95%CI: 9-34%, p=0.005) reduction in cabazitaxel exposure was found with concomitant enzalutamide use. The geometric mean AUC_0-24h of cabazitaxel was 181 ng*h/mL (95%CI 150-219 ng*h/mL) in cycle 3 and 234 ng*h/mL (95%CI 209-261 ng*h/mL) in cycle 1 This combination did not result in excessive toxicity, while PSA response was promising. Conclusions: We found a significant decrease in cabazitaxel exposure when combined with enzalutamide. In an era of clinical trials on combination strategies for mCRPC, it is important to be aware of clinically relevant drug-drug interactions. Since recent study results support the use of a lower standard cabazitaxel dose of 20 mg/m2, the clinical relevance of this interaction may be substantial, since the addition of enzalutamide may result in sub-therapeutic cabazitaxel exposure.

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Interferon- 2; signaling in melanocytes and melanoma cells regulates expression of CTLA-4

CTLA-4 is a cell surface receptor on T cells that functions as an immune checkpoint molecule to enforce tolerance to cognate antigens. Anti-CTLA-4 immunotherapy is highly effective at reactivating T cell responses against melanoma, which is postulated to be due to targeting CTLA-4 on T cells. Here we report that CTLA-4 is also highly expressed by most human melanoma cell lines, as well as in normal human melanocytes. Interferon-gamma (IFNG) signaling activated the expression of the human CTLA-4 gene in a melanocyte and melanoma cell-specific manner. Mechanistically, IFNG activated CTLA-4 expression through JAK1/2-dependent phosphorylation of STAT1, which bound a specific gamma-activated sequence (GAS) site on the CTLA-4 promoter, thereby licensing CBP/p300-mediated histone acetylation and local chromatin opening. In melanoma cell lines, elevated baseline expression relied upon constitutive activation of the MAPK pathway. Notably, RNA-seq analyses of melanoma specimens obtained from patients who had received anti-CTLA-4 immunotherapy (ipilimumab) showed upregulation of an IFNG-response gene expression signature, including CTLA-4 itself, which correlated significantly with durable response. Taken together, our results raise the possibility that CTLA-4 targeting on melanoma cells may contribute to the clinical immunobiology of anti-CTLA-4 responses.

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Interferon- 2; signaling in melanocytes and melanoma cells regulates expression of CTLA-4

CTLA-4 is a cell surface receptor on T cells that functions as an immune checkpoint molecule to enforce tolerance to cognate antigens. Anti-CTLA-4 immunotherapy is highly effective at reactivating T cell responses against melanoma, which is postulated to be due to targeting CTLA-4 on T cells. Here we report that CTLA-4 is also highly expressed by most human melanoma cell lines, as well as in normal human melanocytes. Interferon-gamma (IFNG) signaling activated the expression of the human CTLA-4 gene in a melanocyte and melanoma cell-specific manner. Mechanistically, IFNG activated CTLA-4 expression through JAK1/2-dependent phosphorylation of STAT1, which bound a specific gamma-activated sequence (GAS) site on the CTLA-4 promoter, thereby licensing CBP/p300-mediated histone acetylation and local chromatin opening. In melanoma cell lines, elevated baseline expression relied upon constitutive activation of the MAPK pathway. Notably, RNA-seq analyses of melanoma specimens obtained from patients who had received anti-CTLA-4 immunotherapy (ipilimumab) showed upregulation of an IFNG-response gene expression signature, including CTLA-4 itself, which correlated significantly with durable response. Taken together, our results raise the possibility that CTLA-4 targeting on melanoma cells may contribute to the clinical immunobiology of anti-CTLA-4 responses.

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The sirtuin 1/2 inhibitor tenovin-1 induces a nonlinear apoptosis-inducing factor-dependent cell death in a p53 null Ewing’s sarcoma cell line

Summary

The sirtuin 1/2 inhibitor tenovin-1 activates p53 and may have potential in the management of cancer. Here, we investigated the responsiveness of Ewing's sarcoma cells to tenovin-1. We examined its effects in two Ewing's sarcoma cell lines with different p53 status, i.e. in p53 wild-type and p53 null cells. Effects were assessed by flow cytometric analyses of cell death, mitochondrial membrane depolarization and reactive oxygen species (ROS) generation, by caspase 3/7 activity measurement, by mRNA expression profiling and by immunoblotting. Tenovin-1 elicited caspase-mediated cell death in p53 wild-type cells, but caspase-independent cell death in p53 null cells. Remarkably, it induced a nonlinear concentration response in the latter: low concentrations of tenovin-1 were much more effective than were higher concentrations. Tenovin-1's effects in p53 null cells involved gene expression changes of Bcl-2 family members, mitochondrial membrane depolarization, nuclear translocation of apoptosis-inducing factor, ROS formation and DNA damage; all these effects followed a bell-shaped pattern. In conclusion, our results provide new insights into tenovin-1's mode of action by demonstrating that it can induce different pathways of cell death.

http://ift.tt/2zNx9Zy

The sirtuin 1/2 inhibitor tenovin-1 induces a nonlinear apoptosis-inducing factor-dependent cell death in a p53 null Ewing’s sarcoma cell line

Summary

The sirtuin 1/2 inhibitor tenovin-1 activates p53 and may have potential in the management of cancer. Here, we investigated the responsiveness of Ewing's sarcoma cells to tenovin-1. We examined its effects in two Ewing's sarcoma cell lines with different p53 status, i.e. in p53 wild-type and p53 null cells. Effects were assessed by flow cytometric analyses of cell death, mitochondrial membrane depolarization and reactive oxygen species (ROS) generation, by caspase 3/7 activity measurement, by mRNA expression profiling and by immunoblotting. Tenovin-1 elicited caspase-mediated cell death in p53 wild-type cells, but caspase-independent cell death in p53 null cells. Remarkably, it induced a nonlinear concentration response in the latter: low concentrations of tenovin-1 were much more effective than were higher concentrations. Tenovin-1's effects in p53 null cells involved gene expression changes of Bcl-2 family members, mitochondrial membrane depolarization, nuclear translocation of apoptosis-inducing factor, ROS formation and DNA damage; all these effects followed a bell-shaped pattern. In conclusion, our results provide new insights into tenovin-1's mode of action by demonstrating that it can induce different pathways of cell death.

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Mechanisms of propofol attenuation of ketamine-induced neonatal brain injury

OBJECTIVE: We studied the mechanisms of protective effects of propofol on ketamine-induced damage to neonatal cognitive function.

MATERIALS AND METHODS: We utilized a rat model of ketamine anaesthesia. Eighty neonatal rats (7 days after birth) were divided into four groups: normal saline group, ketamine group, and low- and high-dose propofol combined with ketamine groups. Six hours after anaesthesia, we obtained hippocampal tissue, and quantified apoptotic index and total protein concentration, and assessed global proteomics changes induced by two tested drugs. The latter changes were documented by two-dimensional electrophoresis and matrix-assisted laser desorption/ ionization time of flight mass spectrometry. To evaluate cognitive functions, water maze test was applied after animals grew for 21 days. We further repeated proteomics studies at 21 days post-anaesthesia.

RESULTS: Ketamine markedly up-regulated apoptotic index and decreased total protein concentration. Propofol dose-dependently reverted these adverse changes. Six hours post-anaesthesia, combined propofol and ketamine administration up-regulated the following proteins in the hippocampus: PD1A3, NDUFB10, HSPA8, ATP5JD, and PSMA1. Furthermore, the following proteins were down-regulated: PPIA, PKM2, GFAP, NSE, PPIA, PKM2, and GFAP. After 21 days, animals treated with ketamine showed marked disturbances in cognitive function as demonstrated by increased time of the water maze test, whereas propofol diminished these changes. In addition, expression of proteins largely normalized in propofol-treated animals, with only two up-regulated proteins (FUBP3 and PRDX5) and three down-regulated proteins (GAPDH, AKR1A1, and VCP).

CONCLUSIONS: Adverse effects of ketamine on cognitive function are reverted by propofol, also through beneficial effects on protein expression in the hippocampus.

L'articolo Mechanisms of propofol attenuation of ketamine-induced neonatal brain injury sembra essere il primo su European Review.

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Lumbar Spine Anatomy in Women Sustaining Unintentional Dural Puncture During Labor Epidural Placement: A Descriptive Study Using Magnetic Resonance Imaging and Ultrasound.

Background and Objectives: Unintentional dural puncture is one of the most frequent complications of the epidural technique. One previous study suggested that atypical sonoanatomy of the ligamentum flavum/dura mater unit may be a risk factor for this complication. In this study, we describe the anatomy of the lumbar spine, assessed by magnetic resonance imaging (MRI) and ultrasound, in women sustaining unintentional dural puncture during epidural catheter placement for labor analgesia. Methods: We approached women who sustained a recognized unintentional dural puncture. Following consent, technical aspects of the epidural catheter placement were documented. Postpartum MRI of the lumbar spine and bedside spinal ultrasound were performed. Ultrasound images of the ligamentum flavum/dura mater unit in the transverse view were classified as typical, atypical, or inconclusive. Magnetic resonance imaging images were reviewed by a neuroradiologist, who was blinded to the level of the puncture. Results: We included 10 women with unintentional dural punctures in the study. In 5 of the 10 women, these dural punctures occurred despite epidural catheter insertion by experienced practitioners. These women had a mean body mass index of 28.5 kg/m2 (range, 24-38 kg/m2). Two women suffered dural punctures twice. Ultrasound imaging in the paramedian view produced typical images in all patients. In the transverse view, 7 of 10 women showed atypical or inconclusive images, with atypical images seen at either L4/5 or L5/S1. Magnetic resonance imaging results revealed no anatomical abnormalities, with the exception of 1 woman who showed a ligamentum flavum gap away from the puncture site. Conclusions: Our results suggest that unintentional dural punctures occur in likely anatomically normal women. Furthermore, the transverse ultrasound views may fail to demonstrate typical ligamentum flavum/dura mater unit at the lower lumbar levels despite its confirmed presence by MRI. Copyright (C) 2017 by American Society of Regional Anesthesia and Pain Medicine.

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Intrapartum assessment of fetal well-being

1A012A043J02

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Treatment withdrawal and end-of-life care in the intensive care unit

1F052C063A07

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Prehabilitation

1I052A073J03

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Anaesthesia for head and neck cancer surgery

1C012A013A02

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Principles of resource allocation in critical care

1I022C073J02

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Associations Between Nucleus Size, and Immunohistochemical Galectin-3, Cytokeratine-19 and Hbme-1 Markers in Thyroid Papillary Carcinoma: A Morphometric Analyze

Abstract

This study aimed to evaluate the morphometric measurements in cases with papillary thyroid carcinoma, and determine a cut-off value to support diagnosis. Fifty cases with a diagnosis of papillary thyroid carcinoma (PTC) were included in the study with their Galectine-3, CK-19 and HBME-1 immunohistochemical staining results. Demographic and clinical data gathered from pathology reports, which included demographic information such as patients' sex, age, macroscopic tumor size, number of tumor focuses; prognostic parameters such as lenfovascular invasion, perineural invasion, thyroid capsule invasion; and results of immunohistochemical CK- 19, Galectin-3 and HBME-1 staining. Longest nuclear diameters of 150 tumor cells and 150 normal thyrocytes of each case were manually measured in an image analysis software, and mean longest nuclear diameters (MLND-TC and MLND-NC), and also tumor cell/normal cell longest nuclear diameter ratio (TC/NC-LNDR) were calculated. MLND-TC was higher than MLND-NC. The cases with higher MLND-TC had increased risk of capsule invasion in case of a negative staining with Galectine-3, HBME-1, or CK-19. When TC/NC-LNDR was high, number of tumor focus tended to be multiple and lymphovascular invasion risk was also increased. Subtypes of PTC were not differed regarding staining patterns. And finally, increased TC/NC-LNDR was associated with increased risk of having poor prognostic factors. The results of this study suggest that MLND-NC, MLND-TC, and TC/NCLNDR are valuable and easy-to-use measures, which can assist routine histology practice.

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You Will Never Walk Alone: A Simulation Experience for Caregiver’s Family and Friends

No abstract available

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Enhanced Recovery After Surgery: Current Controversies and Concerns

No abstract available

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Dr Ted Eger Obituary

No abstract available

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The Search for the Optimal Tidal Volume: Why Do We Use Body Weight?

No abstract available

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General Anesthesia Imposes Negative Effects on Heart Rate and Blood Pressure Regulation in Patients With a History of Head and Neck Radiation Therapy

BACKGROUND: Head and neck radiation therapy (HNRT) impairs baroreflex sensitivity, and it may potentiate the effects of anesthetics on heart rate (HR) and blood pressure (BP) regulation. Currently, the impacts of HNRT on HR and BP under anesthesia remain unclear. METHODS: In this study, 472 patients with primary oral cavity or oropharyngeal cancer at all stages were examined. Half of the patients underwent HNRT plus surgery. The other half underwent surgery only and was matched with the treatment patients according to age, sex, and body mass index at a 1:1 ratio. The HRs and BPs in the 2 groups during anesthetic induction, skin incision, and emergence were compared retrospectively. A multivariable model of repeated measures with unstructured covariance structure was used to examine the associations of HNRT with intraoperative HRs and BPs after adjusting for baseline HR and BP, time, use of β-blockers, history of chemotherapy, and American Society of Anesthesiologists physical status score. BPs and HRs were collected every 5 minutes. The baseline HR and BP measurements were not included in the outcome vector and were only used as adjustment for baselines. RESULTS: Compared with corresponding baseline values in controls, the baseline HR was significantly higher (P = .0012) and the baseline systolic BP was lower (P

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When Is “Never Enough” (Data) … Enough?

No abstract available

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Noninfectious Fever in the Near-Term Pregnant Rat Induces Fetal Brain Inflammation: A Model for the Consequences of Epidural-Associated Maternal Fever

BACKGROUND: Women laboring with epidural analgesia experience fever much more frequently than do women who chose other forms of analgesia, and maternal intrapartum fever is associated with numerous adverse consequences, including brain injury in the fetus. We developed a model of noninfectious inflammatory fever in the near-term pregnant rat to simulate the pathophysiology of epidural-associated fever and hypothesized that it would produce fetal brain inflammation. METHODS: Twenty-four pregnant Sprague-Dawley rats were studied at 20 days gestation (term: 22 days). Dams were treated by injection of rat recombinant interleukin (IL)-6 or vehicle at 90-minute intervals, and temperature was monitored every 30 minutes. Eight hours after the first treatment, dams were delivered of fetuses and then killed. Maternal IL-6 was measured at delivery. Fetal brains (n = 24) were processed and stained for ED-1/CD68, a marker for activated microglia, and cell counts in the lateral septal and hippocampal brain regions were measured. Fetal brains were also stained for cyclooxygenase-2 (COX-2), a downstream marker of neuroinflammation. Eight fetal brains were further analyzed for quantitative forebrain COX-2 by Western blotting compared to a β-actin standard. Maternal temperature and IL-6 levels were compared between treatments, as were cell counts, COX-2 staining, and COX-2 levels by Mann-Whitney U test, repeated-measures analysis of variance, or Fisher exact test, as appropriate. RESULTS: Injection of rat IL-6 at 90-minute intervals produced an elevation of maternal temperature compared to vehicle (P

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Subcellular Energetics and Metabolism: A Cross-Species Framework

No abstract available

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The Aortocaval Compression Conundrum

No abstract available

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Understanding the Significance of Aerosolized Vasodilator Use in Pulmonary Hypertension: What Is Numerically, Statistically, and Clinically Meaningful?

No abstract available

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Do No Harm, Except Unto Thyself

No abstract available

http://ift.tt/2irKuNv

Do You Do What I Do? Cardiac Anesthesia Surveys From Around the Globe

No abstract available

http://ift.tt/2ARapFg

Effect of an Intravenous Dexamethasone Added to Caudal Local Anesthetics to Improve Postoperative Pain: A Systematic Review and Meta-analysis With Trial Sequential Analysis

BACKGROUND: Caudal anesthesia has been used for postoperative pain control in pediatric surgical patients, but the duration of the analgesic effect is occasionally unsatisfactory. Intravenous steroids have been shown to be effective for postsurgical pain management after certain surgeries. The aim of this meta-analysis with trial sequential analysis (TSA) was to evaluate the analgesic effect of steroids in patients administered with caudal anesthesia. METHODS: This study was a systematic review and meta-analysis. A search of published literature was conducted in the MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials databases and in trial registration sites. Randomized controlled trials that compared intravenous steroids with a placebo in pediatric patients who had received caudal anesthesia for surgery were included in the study. The primary outcomes from the present meta-analysis were the analgesic duration and the number of patients who required rescue analgesics. The analgesic duration and incidence of rescue use were summarized using mean difference or risk ratio with a 97.5% confidence interval (CI), respectively. If the 97.5% CI of the mean difference or risk ratio included a value of 0 or 1, respectively, we considered the difference not to be significant. We used the random effects model to combine the results. Heterogeneity was quantified with the I2 statistic. The quality of the trials was evaluated using the Cochrane methodology. Moreover, a TSA with a risk of type 1 error of 2.5% and power of 90% was performed. We established the minimum clinically meaningful difference of analgesic duration as 3 hours. The target sample size for meta-analysis was also calculated in the TSA. We also assessed adverse events. RESULTS: Six trials with 424 patients were included; 211 patients received intravenous steroids. All trials compared dexamethasone of at least 0.5 mg/kg dose with a placebo. Dexamethasone prolonged the duration of caudal analgesia (mean difference, 244 minutes; 97.5% CI, 188–300). Heterogeneity was considerable with an I2 value of 94.8%. Quality of evidence was very low. The TSA suggested that only 17.0% of the target sample size had been reached, but the cumulative Z score crossed the trial sequential monitoring boundary to indicate a benefit. Rescue use was reported in 4 studies with 260 patients. Rescue use was not significantly reduced in the dexamethasone group (risk ratio, 0.53; 97.5% CI, 0.09–3.30; I2, 98.7%). No increase in adverse events was reported. CONCLUSIONS: Intravenous dexamethasone prolongs the analgesic duration of caudal anesthesia. Trials to investigate the effectiveness of a lower dose of the dexamethasone in prolonging analgesic effects would be of interest. Further trials with a low risk of bias are necessary.

http://ift.tt/2AQtKpO

Association of Surgery and Anesthesia With Mental Disorder Diagnoses: What Would Sir Austin Bradford Hill Say?

No abstract available

http://ift.tt/2irluFZ

Opioid Prescribing for the Treatment of Acute Pain in Children on Hospital Discharge

BACKGROUND: The epidemic of nonmedical use of prescription opioids has been fueled by the availability of legitimately prescribed unconsumed opioids. The aim of this study was to better understand the contribution of prescriptions written for pediatric patients to this problem by quantifying how much opioid is dispensed and consumed to manage pain after hospital discharge, and whether leftover opioid is appropriately disposed of. Our secondary aim was to explore the association of patient factors with opioid dispensing, consumption, and medication remaining on completion of therapy. METHODS: Using a scripted 10-minute interview, parents of 343 pediatric inpatients (98% postoperative) treated at a university children's hospital were questioned within 48 hours and 10 to 14 days after discharge to determine amount of opioid prescribed and consumed, duration of treatment, and disposition of unconsumed opioid. Multivariable linear regression was used to examine predictors of opioid prescribing, consumption, and doses remaining. RESULTS: Median number of opioid doses dispensed was 43 (interquartile range, 30–85 doses), and median duration of therapy was 4 days (interquartile range, 1–8 days). Children who underwent orthopedic or Nuss surgery consumed 25.42 (95% confidence interval, 19.16–31.68) more doses than those who underwent other types of surgery (P

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Being Mindful in Managing Pain: Integrative Medicine in Chronic Pain Management

No abstract available

http://ift.tt/2j2SjbS

Using Integrative Medicine in Pain Management: An Evaluation of Current Evidence

Complementary medicine therapies are frequently used to treat pain conditions such as headaches and neck, back, and joint pain. Chronic pain, described as pain lasting longer than 3–6 months, can be a debilitating condition that has a significant socioeconomic impact. Pharmacologic approaches are often used for alleviating chronic pain, but recently there has been a reluctance to prescribe opioids for chronic noncancer pain because of concerns about tolerance, dependence, and addiction. As a result, there has been increased interest in integrative medicine strategies to help manage pain and to reduce reliance on prescription opioids to manage pain. This article offers a brief critical review of integrative medical therapies used to treat chronic pain, including nutritional supplements, yoga, relaxation, tai chi, massage, spinal manipulation, and acupuncture. The goal of this article is to identify those treatments that show evidence of efficacy and to identify gaps in the literature where additional studies and controlled trials are needed. An electronic search of the databases of PubMed, The Cochrane Library, EMBASE, PsycINFO, and Science Citation Index Expanded was conducted. Overall, weak positive evidence was found for yoga, relaxation, tai chi, massage, and manipulation. Strong evidence for acupuncture as a complementary treatment for chronic pain that has been shown to decrease the usage of opioids was found. Few studies were found in which integrative medicine approaches were used to address opioid misuse and abuse among chronic pain patients. Additional controlled trials to address the use of integrative medicine approaches in pain management are needed.

http://ift.tt/2j2Sfc8

Massive Transfusion Protocols: When to Turn On, and Off, the Fire Hose

No abstract available

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Initiation and Termination of Massive Transfusion Protocols: Current Strategies and Future Prospects

The advent of massive transfusion protocols (MTP) has had a significant positive impact on hemorrhaging trauma patient morbidity and mortality. Nevertheless, societal MTP guidelines and individual MTPs at academic institutions continue to circulate opposing recommendations on topics critical to MTPs. This narrative review discusses up-to-date information on 2 such topics, the initiation and termination of an MTP. The discussion for each begins with a review of the recommendations and supporting literature presented by MTP guidelines from 3 prominent societies, the American Society of Anesthesiologists, the American College of Surgeons, and the task force for Advanced Bleeding Care in Trauma. This is followed by an in-depth analysis of the main components within those recommendations. Societal recommendations on MTP initiation in hemorrhaging trauma patients emphasize the use of retrospectively validated massive transfusion (MT) prediction score, specifically, the Assessment of Blood Consumption and Trauma-Associated Severe Hemorrhage scores. Validation studies have shown that both scoring systems perform similarly. Both scores reliably identify patients that will not require an MT, while simultaneously overpredicting MT requirements. However, each scoring system has its unique advantages and disadvantages, and this review discusses how specific aspects of each scoring system can affect widespread applicability and statistical performance. In addition, we discuss the often overlooked topic of initiating MT in nontrauma patients and the specific tools physicians have to guide the MT initiation decision in this unique setting. Despite the serious complications that can arise with transfusion of large volumes of blood products, there is considerably less research pertinent to the topic of MTP termination. Societal recommendations on MTP termination emphasize applying clinical reasoning to identify patients who have bleeding source control and are adequately resuscitated. This review, however, focuses primarily on the recommendations presented by the Advanced Bleeding Care in Trauma's MTP guidelines that call for prompt termination of the algorithm-guided model of resuscitation and rapidly transitioning into a resuscitation model guided by laboratory test results. We also discuss the evidence in support of laboratory result–guided resuscitation and how recent literature on viscoelastic hemostatic assays, although limited, highlights the potential to achieve additional benefits from this method of resuscitation.

http://ift.tt/2j3f27K

TSPO imaging using the novel PET ligand [ 18 F]GE-180: quantification approaches in patients with multiple sclerosis

Abstract

Background

PET ligands targeting the translocator protein (TSPO) represent promising tools to visualise neuroinflammation. Here, we analysed parameters obtained in dynamic and static PET images using the novel TSPO ligand [¹⁸F]GE-180 in patients with relapsing remitting multiple sclerosis (RRMS) and an approach for semi-quantitative assessment of this disease in clinical routine.

Seventeen dynamic [¹⁸F]GE-180 PET scans of RRMS patients were evaluated (90 min). A pseudo-reference region (PRR) was defined after identification of the least disease-affected brain area by voxel-based comparison with six healthy controls (HC) and upon exclusion of voxels suspected of being affected in static 60–90 min p.i. images. Standardised uptake value ratios (SUVR) obtained from static images normalised to PRR were correlated to the distribution volume ratios (DVR) derived from dynamic data with Logan reference tissue model.

Results

Group comparison with HC revealed white matter and thalamus as most affected regions. Fewest differences were found in grey matter, and normalisation to frontal cortex (FC) yielded the greatest reduction in variability of healthy grey and white matter. Hence, FC corrected for affected voxels was chosen as PRR, leading to time-activity curves of FC which were congruent to HC data (SUV_60–90 0.37, U test P = 0.42). SUVR showed a very strong correlation with DVR (Pearson ρ > 0.9). Focal MS lesions exhibited a high SUVR (range, 1.3–3.2).

Conclusions

This comparison with parameters from dynamic data suggests that SUVR normalised to corrected frontal cortex as PRR is suitable for the quantification of [¹⁸F]GE-180 uptake in lesions and different brain regions of RRMS patients. This efficient diagnostic protocol based on static [¹⁸F]GE-180 PET scans acquired 60–90 min p.i. allows the semi-quantitative assessment of neuroinflammation in RRMS patients in clinical routine.

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TSPO imaging using the novel PET ligand [ 18 F]GE-180: quantification approaches in patients with multiple sclerosis

Abstract

Background

PET ligands targeting the translocator protein (TSPO) represent promising tools to visualise neuroinflammation. Here, we analysed parameters obtained in dynamic and static PET images using the novel TSPO ligand [¹⁸F]GE-180 in patients with relapsing remitting multiple sclerosis (RRMS) and an approach for semi-quantitative assessment of this disease in clinical routine.

Seventeen dynamic [¹⁸F]GE-180 PET scans of RRMS patients were evaluated (90 min). A pseudo-reference region (PRR) was defined after identification of the least disease-affected brain area by voxel-based comparison with six healthy controls (HC) and upon exclusion of voxels suspected of being affected in static 60–90 min p.i. images. Standardised uptake value ratios (SUVR) obtained from static images normalised to PRR were correlated to the distribution volume ratios (DVR) derived from dynamic data with Logan reference tissue model.

Results

Group comparison with HC revealed white matter and thalamus as most affected regions. Fewest differences were found in grey matter, and normalisation to frontal cortex (FC) yielded the greatest reduction in variability of healthy grey and white matter. Hence, FC corrected for affected voxels was chosen as PRR, leading to time-activity curves of FC which were congruent to HC data (SUV_60–90 0.37, U test P = 0.42). SUVR showed a very strong correlation with DVR (Pearson ρ > 0.9). Focal MS lesions exhibited a high SUVR (range, 1.3–3.2).

Conclusions

This comparison with parameters from dynamic data suggests that SUVR normalised to corrected frontal cortex as PRR is suitable for the quantification of [¹⁸F]GE-180 uptake in lesions and different brain regions of RRMS patients. This efficient diagnostic protocol based on static [¹⁸F]GE-180 PET scans acquired 60–90 min p.i. allows the semi-quantitative assessment of neuroinflammation in RRMS patients in clinical routine.

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Understanding the molecular basis of acute myeloid leukemias: where are we now?

International Journal of Hematologic Oncology, Volume 6, Issue 2, Page 43-53, November 2017.


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Chronic lymphocytic leukemia: “The times they are a-changin”

International Journal of Hematologic Oncology, Volume 6, Issue 2, Page 27-29, November 2017.


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The influence of antiretroviral therapy on clinical aspects of HIV-related lymphoma

International Journal of Hematologic Oncology, Volume 6, Issue 2, Page 35-38, November 2017.


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Chronic lymphocytic leukemia: “The times they are a-changin”

International Journal of Hematologic Oncology, Volume 6, Issue 2, Page 27-29, November 2017.


http://ift.tt/2myZLAu

The influence of antiretroviral therapy on clinical aspects of HIV-related lymphoma

International Journal of Hematologic Oncology, Volume 6, Issue 2, Page 35-38, November 2017.


http://ift.tt/2zcq0CM

In Response

No abstract available

http://ift.tt/2yTcnEq

Risk of Cognitive Impairment by Sleep-Disordered Breathing

No abstract available

http://ift.tt/2AXLEI3

Comparison of Transcranial Doppler and Ultrasound-Tagged Near Infrared Spectroscopy for Measuring Relative Changes in Cerebral Blood Flow in Human Subjects

BACKGROUND: Currently, no reliable method exists for continuous, noninvasive measurements of absolute cerebral blood flow (CBF). We sought to determine how changes measured by ultrasound-tagged near-infrared spectroscopy (UT-NIRS) compare with changes in CBF as measured by transcranial Doppler (TCD) in healthy volunteers during profound hypocapnia and hypercapnia. METHODS: Ten healthy volunteers were monitored with a combination of TCD, UT-NIRS (c-FLOW, Ornim Medical), as well as heart rate, blood pressure, end-tidal PCO2 (PEtCO2), end-tidal O2, and inspired O2. Inspired CO2 and minute ventilation were controlled to achieve 5 stable plateau goals of EtCO2 at 15–20, 25–30, 35–40, 45–50, and 55–60 mm Hg, for a total of 7 measurements per subject. CBF was assessed at a steady state, with the TCD designated as the reference standard. The primary analysis was a linear mixed-effect model of TCD and UT-NIRS flow with PEtCO2, which accounts for repeated measures. Receiver operating characteristic curves were determined for detection of changes in CBF. RESULTS: Hyperventilation (nadir PEtCO2 17.1 ± 2.4) resulted in significantly decreased mean flow velocity of the middle cerebral artery from baseline (to 79% ± 22%), but not a consistent decrease in UT-NIRS cerebral flow velocity index (n = 10; 101% ± 6% of baseline). Hypercapnia (peak PEtCO2 59.3 ± 3.3) resulted in a significant increase from baseline in both mean flow velocity of the middle cerebral artery (153% ± 25%) and UT-NIRS (119% ± 11%). Comparing slopes versus PEtCO2 as a percent of baseline for the TCD (1.7% [1.5%–2%]) and UT-NIRS (0.4% [0.3%–0.5%]) shows that the UT-NIRS slope is significantly flatter, P

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Not All Calcium Formulations Are Alike

No abstract available

http://ift.tt/2AWC7kw

Unadjusted Bivariate Two-Group Comparisons: When Simpler is Better

Hypothesis testing involves posing both a null hypothesis and an alternative hypothesis. This basic statistical tutorial discusses the appropriate use, including their so-called assumptions, of the common unadjusted bivariate tests for hypothesis testing and thus comparing study sample data for a difference or association. The appropriate choice of a statistical test is predicated on the type of data being analyzed and compared. The unpaired or independent samples t test is used to test the null hypothesis that the 2 population means are equal, thereby accepting the alternative hypothesis that the 2 population means are not equal. The unpaired t test is intended for comparing dependent continuous (interval or ratio) data from 2 study groups. A common mistake is to apply several unpaired t tests when comparing data from 3 or more study groups. In this situation, an analysis of variance with post hoc (posttest) intragroup comparisons should instead be applied. Another common mistake is to apply a series of unpaired t tests when comparing sequentially collected data from 2 study groups. In this situation, a repeated-measures analysis of variance, with tests for group-by-time interaction, and post hoc comparisons, as appropriate, should instead be applied in analyzing data from sequential collection points. The paired t test is used to assess the difference in the means of 2 study groups when the sample observations have been obtained in pairs, often before and after an intervention in each study subject. The Pearson chi-square test is widely used to test the null hypothesis that 2 unpaired categorical variables, each with 2 or more nominal levels (values), are independent of each other. When the null hypothesis is rejected, 1 concludes that there is a probable association between the 2 unpaired categorical variables. When comparing 2 groups on an ordinal or nonnormally distributed continuous outcome variable, the 2-sample t test is usually not appropriate. The Wilcoxon-Mann-Whitney test is instead preferred. When making paired comparisons on data that are ordinal, or continuous but nonnormally distributed, the Wilcoxon signed-rank test can be used. In analyzing their data, researchers should consider the continued merits of these simple yet equally valid unadjusted bivariate statistical tests. However, the appropriate use of an unadjusted bivariate test still requires a solid understanding of its utility, assumptions (requirements), and limitations. This understanding will mitigate the risk of misleading findings, interpretations, and conclusions. Accepted for publication October 4, 2017. Funding: None. The authors declare no conflicts of interest. Address correspondence to Thomas R. Vetter, MD, MPH, Department of Surgery and Perioperative Care, Dell Medical School at the University of Texas at Austin, Health Discovery Bldg, Room 6.812, 1701 Trinity St, Austin, TX 78712. Address e-mail to thomas.vetter@austin.utexas.edu. © 2017 International Anesthesia Research Society

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Low- Versus High-Chloride Content Intravenous Solutions for Critically Ill and Perioperative Adult Patients: A Systematic Review and Meta-analysis

BACKGROUND: To assess whether use of low-chloride solutions in unselected critically ill or perioperative adult patients for maintenance or resuscitation reduces mortality and renal replacement therapy (RRT) use when compared to high-chloride fluids. METHODS: Systematic review and meta-analysis with random-effects inverse variance model. PubMed, Cochrane library, EMBASE, LILACS, and Web of Science were searched from inception to October 2016. Published and unpublished randomized controlled trials in any language that enrolled critically ill and/or perioperative adult patients and compared a low- to a highchloride solution for volume maintenance or resuscitation. The primary outcomes were mortality and RRT use. We conducted trial sequential analyses and assessed risk of bias of individual trials and the overall quality of evidence. Fifteen trials with 4067 patients, most at low risk of bias, were identified. Of those, only 11 and 10 trials had data on mortality and RRT use, respectively. A total of 3710 patients were included in the mortality analysis and 3724 in the RRT analysis. RESULTS: No statistically significant impact on mortality (odds ratio, 0.90; 95% confidence interval, 0.69–1.17; P = .44; I2 = 0%) or RRT use (odds ratio, 1.12; 95% confidence interval, 0.80–1.58; P = .52; I2 = 0%) was found. Overall quality of evidence was low for both primary outcomes. Trial sequential analyses highlighted that the sample size needed was much larger than that available for properly powered outcome assessment. CONCLUSIONS: The current evidence on low- versus high-chloride solutions for unselected critically ill or perioperative adult patients demonstrates no benefit, but suffers from considerable imprecision. We noted a limited exposure volume for study fluids and a relatively low risk of the populations in each study. Together with the relatively small pooled sample size, these data leave us underpowered to detect potentially important differences. Results from well-conducted, adequately powered randomized controlled trials examining sufficiently large fluid exposure are necessary. Accepted for publication October 6, 2017. Funding: This meta-analysis was supported by the Brazilian Ministry of Health. The authors declare no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's website (http://ift.tt/KegmMq). Reprints will not be available from the authors. Address correspondence to Leticia Kawano-Dourado, MD, Research Institute - Hospital do Coracao (HCor), Rua Abilio Soares 250, 12o andar, cep: 04005-000, São Paulo-SP, Brazil. Address e-mail to ldourado@hcor.com.br. © 2017 International Anesthesia Research Society

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In Response

No abstract available

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Increased Hyperalgesia and Proinflammatory Cytokines in the Spinal Cord and Dorsal Root Ganglion After Surgery and/or Fentanyl Administration in Rats

BACKGROUND: Perioperative fentanyl has been reported to induce hyperalgesia and increase postoperative pain. In this study, we tried to investigate behavioral hyperalgesia, the expression of proinflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the activation of microglia in the spinal cord and dorsal root ganglion (DRG) in a rat model of surgical plantar incision with or without perioperative fentanyl. METHODS: Four groups of rats (n = 32 for each group) were subcutaneously injected with fentanyl at 60 μg/kg or normal saline for 4 times with 15-minute intervals. Plantar incisions were made to rats in 2 groups after the second drug injection. Mechanical and thermal nociceptive thresholds were assessed by the tail pressure test and paw withdrawal test on the day before, at 1, 2, 3, 4 hours, and on the days 1–7 after drug injection. The lumbar spinal cord, bilateral DRG, and cerebrospinal fluid of 4 rats in each group were collected to measure IL-1β, IL-6, and TNF-α on the day before, at the fourth hour, and on the days 1, 3, 5, and 7 after drug injection. The lumbar spinal cord and bilateral DRG were removed to detect the ionized calcium-binding adapter molecule 1 on the day before and on the days 1 and 7 after drug injection. RESULTS: Rats injected with normal saline only demonstrated no significant mechanical or thermal hyperalgesia or any increases of IL-1β, IL-6, and TNF-α in the spinal cord or DRG. However, injection of fentanyl induced analgesia within as early as 4 hours and a significant delayed tail mechanical and bilateral plantar thermal hyperalgesia after injections lasting for 2 days, while surgical plantar incision induced a significant mechanical and thermal hyperalgesia lasting for 1–4 days. The combination of fentanyl and incision further aggravated the hyperalgesia and prolonged the duration of hyperalgesia. The fentanyl or surgical incision upregulated the expression of IL-1β, IL-6, and TNF-α in the spinal cord and bilateral DRG for more than 7 days and increase of ionized calcium-binding adapter molecule 1 in the spinal cord. The combination of fentanyl and incision resulted in higher increase of IL-1β, IL-6, and TNF-α in the spinal cord and bilateral DRG. CONCLUSIONS: The surgical plantar incision with or without perioperative fentanyl induced significant mechanical and thermal hyperalgesia, an increased expression of IL-1β, IL-6, TNF-α in the spinal cord and DRG, and activation of microglia in the spinal cord. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. Accepted for publication September 19, 2017. Funding: This study was supported by National Natural Science Foundation of China (Project No. 81571071) and Guangdong Provincial Natural Science Foundation of China (Project No. 2014A030313203). The authors declare no conflicts of interest. The authors Chang and Ye contributed equally to this study. Reprints will not be available from the authors. Address correspondence to Haihua Shu, MD, PhD, Department of Anesthesiology, Guangdong Second Provincial General Hospital, 466# Xingang Middle Rd, Guangzhou, Guangdong 510317, China. Address e-mail to shuhaihua@hotmail.com. © 2017 International Anesthesia Research Society

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Pharmacological considerations in the elderly

Purpose of review This review discusses the pharmacology of contemporary anesthetic medications in geriatric patients, neurophysiological changes with aging, current recommendations for dosing anesthetic drugs. It also addresses current practice patterns and ongoing studies, which are likely to affect future anesthetic drug management in the elderly. Recent findings Potency of anesthetic drugs is increased in the elderly. In addition to changes at the receptor level, neurophysiological changes in functional connectivity with aging contributes to increased sensitivity of anesthetic drugs. However, the extent of reduction is underappreciated by the practitioners and dose adjustment is not uniformly applied in practice. Large database studies demonstrate association of short-term intraoperative hypotension and CNS depression, to poor perioperative outcomes. These perturbations are probably of greater consequence in frail, elderly patients with reduced reserves. Summary Anesthetic dosing should be more closely age-adjusted to prevent anesthetic-induced hypotension and increased depth of anesthesia in the elderly. Pharmacologic studies are required in the elderly population (>80 years). Correspondence to Shamsuddin Akhtar, Associate Professor, Anesthesiology and Pharmacology, Department of Anesthesiology, Yale University School of Medicine, 333 Cedar Street, TMP # 3, PO Box 208051, New Haven, CT 06520-8051, USA. Tel: +1 203 785 2802; fax: +1 203 785 6664; e-mail: shamsuddin.akhtar@yale.edu Copyright © 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is frequently upregulated in prostate cancer, and its overexpression conveys tumor growth and angiogenesis by metabolizing asymmetric dimethylarginine (ADMA)

Abstract

Tissue microarray analysis confirmed higher dimethylarginine dimethylaminohydrolase-1 (DDAH1) expression in prostate cancer (PCa) compared to benign and normal prostate tissues. DDAH1 regulates nitric oxide (NO) production by degrading endogenous nitric oxide synthase (NOS) inhibitor, asymmetric dimethylarginine (ADMA). This study examined whether DDAH1 has any physiological role in PCa progression. Using overexpression of DDAH1 in PCa (PC3 and LNCaP) cell lines, we found that DDAH1 promotes cell proliferation, migration and invasion by lowering ADMA levels, as well as increasing NO production. VEGF, HIF-1α and iNOS were upregulated in DDAH1 expressing cells as result of elevated NO. DDAH1 increased secretion of pro-angiogenic signals bFGF and IL-8, into conditioned media. Treatment of DDAH1-positive PCa cells with NOS inhibitors (L-NAME and 1400 W) attenuated DDAH1 activity to promote cell growth. Xenografts derived from these cells grew significantly faster (> twofold) than those derived from control cells. Proliferation rate of cells stably expressing mutant DDAH1 was same as control cells unlike wild-type DDAH1-positive PCa cells. Xenograft tumors derived from mutant-positive cells did not differ from control tumors. VEGF, HIF-1α and iNOS expression did not differ in DDAH1 mutant-positive tumors compared to control tumors, but was upregulated in wild-type DDAH1 overexpressing tumors. Furthermore, CD31 immunostaining on xenograft tissues demonstrated that DDAH1 tumors had high endothelial content than mutant DDAH1 tumors. These data suggest that DDAH1 is an important mediator of PCa progression and NO/DDAH pathway needs to be considered in developing therapeutic strategies targeted at PCa.

http://ift.tt/2za6RBf

Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is frequently upregulated in prostate cancer, and its overexpression conveys tumor growth and angiogenesis by metabolizing asymmetric dimethylarginine (ADMA)

Abstract

Tissue microarray analysis confirmed higher dimethylarginine dimethylaminohydrolase-1 (DDAH1) expression in prostate cancer (PCa) compared to benign and normal prostate tissues. DDAH1 regulates nitric oxide (NO) production by degrading endogenous nitric oxide synthase (NOS) inhibitor, asymmetric dimethylarginine (ADMA). This study examined whether DDAH1 has any physiological role in PCa progression. Using overexpression of DDAH1 in PCa (PC3 and LNCaP) cell lines, we found that DDAH1 promotes cell proliferation, migration and invasion by lowering ADMA levels, as well as increasing NO production. VEGF, HIF-1α and iNOS were upregulated in DDAH1 expressing cells as result of elevated NO. DDAH1 increased secretion of pro-angiogenic signals bFGF and IL-8, into conditioned media. Treatment of DDAH1-positive PCa cells with NOS inhibitors (L-NAME and 1400 W) attenuated DDAH1 activity to promote cell growth. Xenografts derived from these cells grew significantly faster (> twofold) than those derived from control cells. Proliferation rate of cells stably expressing mutant DDAH1 was same as control cells unlike wild-type DDAH1-positive PCa cells. Xenograft tumors derived from mutant-positive cells did not differ from control tumors. VEGF, HIF-1α and iNOS expression did not differ in DDAH1 mutant-positive tumors compared to control tumors, but was upregulated in wild-type DDAH1 overexpressing tumors. Furthermore, CD31 immunostaining on xenograft tissues demonstrated that DDAH1 tumors had high endothelial content than mutant DDAH1 tumors. These data suggest that DDAH1 is an important mediator of PCa progression and NO/DDAH pathway needs to be considered in developing therapeutic strategies targeted at PCa.

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CK4, CK6, cyclin D1, p16(INK4a) and EGFR expression in glioblastoma with a primitive neuronal component

Abstract

Glioblastoma with primitive neuroectodermal tumor-like component (GBM-PNET) is a rare variant of glioblastoma, which was renamed as glioblastoma with a primitive neuronal component (GBM-PN) in new WHO classification of tumours of the central nervous system in 2016. There are few publications on the investigation of GBM-PN. In this study, PCR mRNA arrays on 6 cases of conventional GBM and 10 cases of GBM-PN showed high mRNA level of CDK4 in GBM-PN and low mRNA level of EGFR in GBM-PN. Immunohistochemical stains on tissue microarrays with 28 cases of conventional GBM and 13 cases of GBM-PN demonstrated that CDK4 was selectively expressed in the primitive neuronal component of all GBM-PN cases while EGFR was positive in conventional GBM and glial component of GBM-PN, but was negative in the primitive neuronal component of all GBM-PN cases. Immunohistochemical stains with antibodies against proteins that interact with CDK4 in cell cycle regulation, such as CDK6, cyclin D1 and p16(INK4a), were performed on these GBM-PN and GBM cases. CDK6 was patchily positive in rare cases of GBM-PN and cyclin D1 was negative in GBM-PN cases. p16(INK4a) is traditionally known as an inhibitor of CDK4 and CDK6. p16(INK4a) might not be the inhibitor of CDK4 in GBM-PN cases because seven GBM-PN cases were positive for both CDK4 and p16(INK4a). It indicates that CDK4 and p16(INK4a) might play a crucial role in GBM-PN pathogenesis. Since CDK4 and EGFR are highly expressed in the primitive neuronal component and in the glial component of GBM-PN respectively, the combination of CDK4/6 inhibitor and targeted therapy against EGFR might be potential effective therapeutic regimen for GBM-PN. CDK4 and EGFR immuohistochemical stain patterns make the diagnosis of GBM-PN much easier.

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High PDL1 mRNA expression predicts better survival of stage pT1 non-muscle-invasive bladder cancer (NMIBC) patients

Abstract

Introduction and objectives

Checkpoint inhibition has emerged as new therapeutic option in muscle-invasive bladder cancer. The objective of the present study was to evaluate the prognostic role of PD1 and PDL1 expression in non-muscle-invasive bladder cancer (NMIBC) and establish an objective measuring method using RNA quantification.

Materials and methods

We retrospectively analyzed clinical data and formalin-fixed paraffin-embedded tissues (FFPE) of patients with stage pT1 NMIBC who underwent transurethral resection of the bladder. mRNA expression of PD1, PDL1 and CD3 was measured by single step RT-qPCR and correlated to clinicopathological parameters, recurrence-free survival (RFS), progression-free survival (PFS) and carcinoma-specific survival (CSS).

Results

We have analyzed 334 patients with NMIBC at stage pT1 for mRNA analysis. Data from 296 patients (79% male, median age: 72 years) could be used. Spearman correlation revealed significant associations between mRNA expressions of PD1/PDL1 (ρ: 0.6024, p < 0.0001), CD3/PDL1 (ρ: 0.5728, p < 0.0001) and CD3/PD1 (ρ: 0.7005, p < 0.0001). Kaplan–Meier analysis revealed that high PDL1 mRNA expression (≥ 33.83) is a favorable prognostic factor with regard to better RFS (p = 0.0018), PFS (p = 0.021) and CSS (p = 0.012). Multivariate Cox-regression analysis proved PDL1 expression to be an independent prognosticator for RFS [HR 0.48 (0.31–0.72), p = 0.0005], PFS [HR 0.45 (0.24–0.80), p = 0.0059] and CSS [HR 0.31 (0.13–0.67), p = 0.0021].

Conclusion

High mRNA expression of PDL1 predicts improved RFS, PFS and CSS of pT1 NMIBC. Following prospective validation, this objective measurement of PD-L1 might help stratify patients with NMIBC for immunotherapy and identify patients who might benefit from early cystectomy.

http://ift.tt/2AW2ozv

High PDL1 mRNA expression predicts better survival of stage pT1 non-muscle-invasive bladder cancer (NMIBC) patients

Abstract

Introduction and objectives

Checkpoint inhibition has emerged as new therapeutic option in muscle-invasive bladder cancer. The objective of the present study was to evaluate the prognostic role of PD1 and PDL1 expression in non-muscle-invasive bladder cancer (NMIBC) and establish an objective measuring method using RNA quantification.

Materials and methods

We retrospectively analyzed clinical data and formalin-fixed paraffin-embedded tissues (FFPE) of patients with stage pT1 NMIBC who underwent transurethral resection of the bladder. mRNA expression of PD1, PDL1 and CD3 was measured by single step RT-qPCR and correlated to clinicopathological parameters, recurrence-free survival (RFS), progression-free survival (PFS) and carcinoma-specific survival (CSS).

Results

We have analyzed 334 patients with NMIBC at stage pT1 for mRNA analysis. Data from 296 patients (79% male, median age: 72 years) could be used. Spearman correlation revealed significant associations between mRNA expressions of PD1/PDL1 (ρ: 0.6024, p < 0.0001), CD3/PDL1 (ρ: 0.5728, p < 0.0001) and CD3/PD1 (ρ: 0.7005, p < 0.0001). Kaplan–Meier analysis revealed that high PDL1 mRNA expression (≥ 33.83) is a favorable prognostic factor with regard to better RFS (p = 0.0018), PFS (p = 0.021) and CSS (p = 0.012). Multivariate Cox-regression analysis proved PDL1 expression to be an independent prognosticator for RFS [HR 0.48 (0.31–0.72), p = 0.0005], PFS [HR 0.45 (0.24–0.80), p = 0.0059] and CSS [HR 0.31 (0.13–0.67), p = 0.0021].

Conclusion

High mRNA expression of PDL1 predicts improved RFS, PFS and CSS of pT1 NMIBC. Following prospective validation, this objective measurement of PD-L1 might help stratify patients with NMIBC for immunotherapy and identify patients who might benefit from early cystectomy.

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Sexual functioning among young adult cancer patients: A 2-year longitudinal study

BACKGROUND

Cancer-related sexual dysfunction has been reported among adolescents and young adults (AYAs); however, its prevalence over time has not been examined. This longitudinal study investigated sexual dysfunction in AYAs over the course of 2 years after the initial diagnosis.

METHODS

Young adult patients (18-39 years old) completed the Medical Outcomes Study Sexual Functioning Scale within the first 4 months of their diagnosis (n = 123) and again 6 (n = 107) and 24 months later (n = 95). An ordered multinomial response model analyzed changes in the probability of reporting sexual dysfunction over time and the independent effects of demographic, clinical, and psychosocial variables.

RESULTS

More than half of the participants reported sexual functioning to be problematic at each assessment. The probability of reporting sexual dysfunction increased over time (P < .01) and was greater for cancer patients who were female (P < .001), older (P < .01), married or in a committed relationship (P < .001), treated with chemotherapy (P < .05), and reporting comorbid psychological distress (P < .001) and lower social support (P < .05). For women, being in a relationship increased the likelihood of reporting sexual problems over time; for men, the likelihood of reporting sexual problems increased regardless of their relationship status.

CONCLUSIONS

A substantial proportion of young adults report ongoing problems with sexual functioning in the first 2 years after their cancer diagnosis. These findings justify the need to evaluate and monitor sexual functioning throughout a continuum of care. Cancer 2017. © 2017 American Cancer Society.

http://ift.tt/2zNNM7l

Pathfinders in oncology from the beginning of the 19th century to the inauguration of the first cancer hospital in the United States

The fields of medicine and oncology made substantial progress between 1800 and 1885. The first half of this period was dominated by the spectacular progress in physiology, cytology, histology, histopathology, and diagnostic microscopy. In the second half of the period, advancements in surgical techniques, anesthesia, asepsis, and laboratory medicine, including bacteriology, chemistry, and biochemistry, led to the development of medical specialties, including surgical pathology and surgical oncology. Although wars, revolutions, and socioeconomic upheavals interrupted the daily life of the populace, distinguished artists, scientists, and physicians continued, against all odds, to advance their field of interest. Among the many eminent individuals, there were 7 renowned physicians (4 pathologists and 3 surgeons) who revolutionized medical and oncology thinking in ways that are still felt today. They were polyglots with formidable erudition, beloved teachers, and mentors, and are remembered eponymically for their contributions to oncology to this day. As a passing note, the 3 surgeons also were skillful microscopists. Cancer 2017. © 2017 American Cancer Society.

http://ift.tt/2zNNFZt

A prospective, observational cohort study comparing cancer clinical trial availability and enrollment between early adolescents/young adults and children

BACKGROUND

Poor enrollment of adolescents and young adults (AYAs) (ages 15-39 years) onto cancer clinical trials (CCTs) may contribute to inferior survival gains compared with children. In this study, the authors assessed whether differences in CCT availability would explain lower CCT enrollment for early AYAs (eAYAs) (ages 15-21 years).

METHODS

This prospective, observational cohort study was conducted at a single academic children's hospital. For consecutive patients who were newly diagnosed with cancer over a 13-month period, it was determined whether an appropriate CCT existed nationally or was available locally and whether enrollment on that CCT occurred. The proportions of eAYAs versus children in each category were compared using the chi-square test. The impact of age and other factors on enrollment status was assessed using logistic regression analysis.

RESULTS

Among 216 patients, 58 were eAYAs, and 158 were children. There was no difference in the proportion of eAYAs versus children who had an existing CCT (28 of 58 eAYAs [48.3%] vs 85 of 158 children [53.8%]; P = .47) or an available CCT (23 of 58 eAYAs [39.7%] vs 75 of 158 children [47.5%]; P = .31). However, significantly fewer eAYAs were enrolled when a CCT was available (7 of 23 eAYAs [30.4%] vs 50 of 75 children [67.7%]; P = .002). In multivariable analysis, eAYAs were significantly less likely than children to be enrolled in an available CCT (adjusted odds ratio, 0.22; 95% confidence interval, 0.08-0.62).

CONCLUSIONS

Equal proportions of children and eAYAs had CCTs available, but significantly fewer eAYAs were enrolled. These findings suggest that, for eAYAs, factors other than CCT availability are important enrollment barriers and should be addressed. Cancer 2017. © 2017 American Cancer Society.

http://ift.tt/2hCpJxz

Hospital quality, patient risk, and Medicare expenditures for cancer surgery

BACKGROUND

Surgical resection is a cornerstone of curative-intent therapy for patients with solid organ malignancies. With increasing attention paid to the costs of surgical care, there is a new focus on variations in the costs of cancer surgery. This study evaluated the potential interactive effect of hospital quality and patient risk on expenditures for cancer resections.

METHODS

With 100% Medicare claim data for 2010-2013, patients aged 65 to 99 years who had undergone cancer resection were identified. Medicare payments were calculated for the surgical episode from the index admission through 30 days after discharge. Risk- and reliability-adjusted hospital rates of serious complications and mortality within 30 days of the index operation were assessed to categorize high- and low-quality hospitals.

RESULTS

There was no difference in patient characteristics between the highest and lowest quality hospitals. There were substantial increases in expenditures for procedures performed at the lowest quality hospitals for each procedure. Increased expenditures at the lowest quality hospitals were found for all patients, but they were highest for the highest risk patients. At low-quality hospitals, low-risk patients undergoing pancreatectomy had payments of $29,080, whereas high-risk patients had average payments of $62,687; this was a difference of $33,607 per patient episode.

CONCLUSIONS

Total episode expenditures for cancer resections were lower when care was delivered at low-complication, high-quality hospitals. Expenditure differences were particularly large for high-risk patients, and this suggests that the selective referral of high-risk patients to high-quality centers may be an effective strategy for optimizing value in cancer surgery. Cancer 2017. © 2017 American Cancer Society.

http://ift.tt/2zNwpnd

Impact of chronic hepatitis C virus infection on the survival of patients with oropharyngeal cancer

BACKGROUND

Although an association between hepatitis C virus (HCV) infection and oropharyngeal cancers (OPCs) has been reported, to the authors' knowledge the clinical significance of this epidemiological finding remains unknown. Therefore, the authors analyzed the oncologic outcomes of HCV-infected patients with OPCs.

METHODS

In this retrospective cohort study, all patients with OPCs who were seen at The University of Texas MD Anderson Cancer Center between January 2004 and December 2015 were reviewed. HCV infection was defined as detectable HCV RNA in the serum. Five-year overall survival and progression-free survival rates were compared between patients infected with HCV and those not infected.

RESULTS

A total of 161 patients were examined. The majority of the patients were white (141 patients; 88%) and male (132 patients; 82%) and had TNM stage III or IV disease (147 patients; 91%). The OPC involved the tonsils (83 patients; 52%), base of the tongue (67patients; 42%), or the soft palate (11 patients; 7%). The median follow-up after an OPC diagnosis was 3 years (range, 1-13 years). HCV-infected patients (25 patients) and HCV-uninfected patients (136 patients) were comparable with regard to smoking and alcohol status. In multivariate analysis, HCV was associated with increased cancer-specific mortality (hazard ratio, 2.15; 95% confidence interval, 1.08-6.85 [P = .02]) and risk of OPC progression (hazard ratio, 5.42; 95% confidence interval, 2.64-11.14 [P = .0008]) independent of age and cirrhosis status. Antivirals were administered after the diagnosis of OPC in 8 of the 25 HCV-infected patients (32%). HCV-infected patients who received antivirals were found to have better 5-year overall survival (70% vs 12%; P = .005) and progression-free survival (72% vs 19%; P = .005) compared with patients who did not.

CONCLUSIONS

The early detection of HCV is important in patients with OPC because this infection may affect their oncologic outcomes. Cancer 2017. © 2017 American Cancer Society.

http://ift.tt/2hz4Lj6

High PDL1 mRNA expression predicts better survival of stage pT1 non-muscle-invasive bladder cancer (NMIBC) patients

Abstract

Introduction and objectives

Checkpoint inhibition has emerged as new therapeutic option in muscle-invasive bladder cancer. The objective of the present study was to evaluate the prognostic role of PD1 and PDL1 expression in non-muscle-invasive bladder cancer (NMIBC) and establish an objective measuring method using RNA quantification.

Materials and methods

We retrospectively analyzed clinical data and formalin-fixed paraffin-embedded tissues (FFPE) of patients with stage pT1 NMIBC who underwent transurethral resection of the bladder. mRNA expression of PD1, PDL1 and CD3 was measured by single step RT-qPCR and correlated to clinicopathological parameters, recurrence-free survival (RFS), progression-free survival (PFS) and carcinoma-specific survival (CSS).

Results

We have analyzed 334 patients with NMIBC at stage pT1 for mRNA analysis. Data from 296 patients (79% male, median age: 72 years) could be used. Spearman correlation revealed significant associations between mRNA expressions of PD1/PDL1 (ρ: 0.6024, p < 0.0001), CD3/PDL1 (ρ: 0.5728, p < 0.0001) and CD3/PD1 (ρ: 0.7005, p < 0.0001). Kaplan–Meier analysis revealed that high PDL1 mRNA expression (≥ 33.83) is a favorable prognostic factor with regard to better RFS (p = 0.0018), PFS (p = 0.021) and CSS (p = 0.012). Multivariate Cox-regression analysis proved PDL1 expression to be an independent prognosticator for RFS [HR 0.48 (0.31–0.72), p = 0.0005], PFS [HR 0.45 (0.24–0.80), p = 0.0059] and CSS [HR 0.31 (0.13–0.67), p = 0.0021].

Conclusion

High mRNA expression of PDL1 predicts improved RFS, PFS and CSS of pT1 NMIBC. Following prospective validation, this objective measurement of PD-L1 might help stratify patients with NMIBC for immunotherapy and identify patients who might benefit from early cystectomy.

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Transcriptional alterations in hereditary and sporadic nonfunctioning pancreatic neuroendocrine tumors according to genotype

BACKGROUND

Nonfunctioning pancreatic neuroendocrine tumors (NFPanNETs) may be sporadic or inherited because of germline mutations associated with von Hippel-Lindau disease (VHL) or multiple endocrine neoplasia type 1 (MEN1). The clinical behavior of NFPanNETs is difficult to predict, even in tumors of the same stage and grade. The authors analyzed genotype-specific patterns of transcriptional messenger RNA (mRNA) levels of NFPanNETs to understand the molecular features that determine PanNET phenotype.

METHODS

Thirty-two samples were included for genome-wide mRNA gene expression analysis (9 VHL-associated, 10 MEN1-associated, and 9 sporadic NFPanNETs and 4 purified normal islet cell [NIC] samples). Validation of genes was performed by real-time polymerase chain reaction analysis and immunohistochemistry. Gene expression profiles were analyzed by tumor genotype, and pathway analysis was curated.

RESULTS

Consensus clustering of mRNA expression revealed separate clustering of NICs, VHL-associated NFPanNETs, and MEN1-associated NFPanNETs; whereas some sporadic tumors clustered with MEN1. Four of 5 MEN1-like sporadic PanNET subtypes had loss of heterozygosity at the MEN1 gene locus. Pathway analysis demonstrated subtype-specific pathway activation, comprising angiogenesis and immune response in VHL; neuronal development in MEN1; protein ubiquitination in the new MEN1/sporadic subtype; and cytokinesis and cilium/microtubule development in sporadic NFPanNETs. Among many genes, platelet-derived growth factor receptor β (PDGFRB), lymphoid enhancer-binding factor-1 (Lef-1), cyclin-dependent kinase 4 (CDK4), and CDK6 were upregulated in VHL or MEN1 NFPanNETs, providing potential subtype-specific treatment targets.

CONCLUSIONS

Distinct mRNA expression patterns were identified in sporadic-associated, VHL-associated, and MEN1-associated NFPanNETs. The current results uncover new pathways involved in NFPanNETs that are subtype-specific and provide potential new diagnostic or therapeutic targets based on tumor subtype. Cancer 2017. © 2017 American Cancer Society.

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Pathfinders in oncology from the beginning of the 19th century to the inauguration of the first cancer hospital in the United States

The fields of medicine and oncology made substantial progress between 1800 and 1885. The first half of this period was dominated by the spectacular progress in physiology, cytology, histology, histopathology, and diagnostic microscopy. In the second half of the period, advancements in surgical techniques, anesthesia, asepsis, and laboratory medicine, including bacteriology, chemistry, and biochemistry, led to the development of medical specialties, including surgical pathology and surgical oncology. Although wars, revolutions, and socioeconomic upheavals interrupted the daily life of the populace, distinguished artists, scientists, and physicians continued, against all odds, to advance their field of interest. Among the many eminent individuals, there were 7 renowned physicians (4 pathologists and 3 surgeons) who revolutionized medical and oncology thinking in ways that are still felt today. They were polyglots with formidable erudition, beloved teachers, and mentors, and are remembered eponymically for their contributions to oncology to this day. As a passing note, the 3 surgeons also were skillful microscopists. Cancer 2017. © 2017 American Cancer Society.

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

A prospective, observational cohort study comparing cancer clinical trial availability and enrollment between early adolescents/young adults and children

BACKGROUND

Poor enrollment of adolescents and young adults (AYAs) (ages 15-39 years) onto cancer clinical trials (CCTs) may contribute to inferior survival gains compared with children. In this study, the authors assessed whether differences in CCT availability would explain lower CCT enrollment for early AYAs (eAYAs) (ages 15-21 years).

METHODS

This prospective, observational cohort study was conducted at a single academic children's hospital. For consecutive patients who were newly diagnosed with cancer over a 13-month period, it was determined whether an appropriate CCT existed nationally or was available locally and whether enrollment on that CCT occurred. The proportions of eAYAs versus children in each category were compared using the chi-square test. The impact of age and other factors on enrollment status was assessed using logistic regression analysis.

RESULTS

Among 216 patients, 58 were eAYAs, and 158 were children. There was no difference in the proportion of eAYAs versus children who had an existing CCT (28 of 58 eAYAs [48.3%] vs 85 of 158 children [53.8%]; P = .47) or an available CCT (23 of 58 eAYAs [39.7%] vs 75 of 158 children [47.5%]; P = .31). However, significantly fewer eAYAs were enrolled when a CCT was available (7 of 23 eAYAs [30.4%] vs 50 of 75 children [67.7%]; P = .002). In multivariable analysis, eAYAs were significantly less likely than children to be enrolled in an available CCT (adjusted odds ratio, 0.22; 95% confidence interval, 0.08-0.62).

CONCLUSIONS

Equal proportions of children and eAYAs had CCTs available, but significantly fewer eAYAs were enrolled. These findings suggest that, for eAYAs, factors other than CCT availability are important enrollment barriers and should be addressed. Cancer 2017. © 2017 American Cancer Society.

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Hospital quality, patient risk, and Medicare expenditures for cancer surgery

BACKGROUND

Surgical resection is a cornerstone of curative-intent therapy for patients with solid organ malignancies. With increasing attention paid to the costs of surgical care, there is a new focus on variations in the costs of cancer surgery. This study evaluated the potential interactive effect of hospital quality and patient risk on expenditures for cancer resections.

METHODS

With 100% Medicare claim data for 2010-2013, patients aged 65 to 99 years who had undergone cancer resection were identified. Medicare payments were calculated for the surgical episode from the index admission through 30 days after discharge. Risk- and reliability-adjusted hospital rates of serious complications and mortality within 30 days of the index operation were assessed to categorize high- and low-quality hospitals.

RESULTS

There was no difference in patient characteristics between the highest and lowest quality hospitals. There were substantial increases in expenditures for procedures performed at the lowest quality hospitals for each procedure. Increased expenditures at the lowest quality hospitals were found for all patients, but they were highest for the highest risk patients. At low-quality hospitals, low-risk patients undergoing pancreatectomy had payments of $29,080, whereas high-risk patients had average payments of $62,687; this was a difference of $33,607 per patient episode.

CONCLUSIONS

Total episode expenditures for cancer resections were lower when care was delivered at low-complication, high-quality hospitals. Expenditure differences were particularly large for high-risk patients, and this suggests that the selective referral of high-risk patients to high-quality centers may be an effective strategy for optimizing value in cancer surgery. Cancer 2017. © 2017 American Cancer Society.

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High PDL1 mRNA expression predicts better survival of stage pT1 non-muscle-invasive bladder cancer (NMIBC) patients

Abstract

Introduction and objectives

Checkpoint inhibition has emerged as new therapeutic option in muscle-invasive bladder cancer. The objective of the present study was to evaluate the prognostic role of PD1 and PDL1 expression in non-muscle-invasive bladder cancer (NMIBC) and establish an objective measuring method using RNA quantification.

Materials and methods

We retrospectively analyzed clinical data and formalin-fixed paraffin-embedded tissues (FFPE) of patients with stage pT1 NMIBC who underwent transurethral resection of the bladder. mRNA expression of PD1, PDL1 and CD3 was measured by single step RT-qPCR and correlated to clinicopathological parameters, recurrence-free survival (RFS), progression-free survival (PFS) and carcinoma-specific survival (CSS).

Results

We have analyzed 334 patients with NMIBC at stage pT1 for mRNA analysis. Data from 296 patients (79% male, median age: 72 years) could be used. Spearman correlation revealed significant associations between mRNA expressions of PD1/PDL1 (ρ: 0.6024, p < 0.0001), CD3/PDL1 (ρ: 0.5728, p < 0.0001) and CD3/PD1 (ρ: 0.7005, p < 0.0001). Kaplan–Meier analysis revealed that high PDL1 mRNA expression (≥ 33.83) is a favorable prognostic factor with regard to better RFS (p = 0.0018), PFS (p = 0.021) and CSS (p = 0.012). Multivariate Cox-regression analysis proved PDL1 expression to be an independent prognosticator for RFS [HR 0.48 (0.31–0.72), p = 0.0005], PFS [HR 0.45 (0.24–0.80), p = 0.0059] and CSS [HR 0.31 (0.13–0.67), p = 0.0021].

Conclusion

High mRNA expression of PDL1 predicts improved RFS, PFS and CSS of pT1 NMIBC. Following prospective validation, this objective measurement of PD-L1 might help stratify patients with NMIBC for immunotherapy and identify patients who might benefit from early cystectomy.

http://ift.tt/2AW2ozv

CK4, CK6, cyclin D1, p16(INK4a) and EGFR expression in glioblastoma with a primitive neuronal component

Abstract

Glioblastoma with primitive neuroectodermal tumor-like component (GBM-PNET) is a rare variant of glioblastoma, which was renamed as glioblastoma with a primitive neuronal component (GBM-PN) in new WHO classification of tumours of the central nervous system in 2016. There are few publications on the investigation of GBM-PN. In this study, PCR mRNA arrays on 6 cases of conventional GBM and 10 cases of GBM-PN showed high mRNA level of CDK4 in GBM-PN and low mRNA level of EGFR in GBM-PN. Immunohistochemical stains on tissue microarrays with 28 cases of conventional GBM and 13 cases of GBM-PN demonstrated that CDK4 was selectively expressed in the primitive neuronal component of all GBM-PN cases while EGFR was positive in conventional GBM and glial component of GBM-PN, but was negative in the primitive neuronal component of all GBM-PN cases. Immunohistochemical stains with antibodies against proteins that interact with CDK4 in cell cycle regulation, such as CDK6, cyclin D1 and p16(INK4a), were performed on these GBM-PN and GBM cases. CDK6 was patchily positive in rare cases of GBM-PN and cyclin D1 was negative in GBM-PN cases. p16(INK4a) is traditionally known as an inhibitor of CDK4 and CDK6. p16(INK4a) might not be the inhibitor of CDK4 in GBM-PN cases because seven GBM-PN cases were positive for both CDK4 and p16(INK4a). It indicates that CDK4 and p16(INK4a) might play a crucial role in GBM-PN pathogenesis. Since CDK4 and EGFR are highly expressed in the primitive neuronal component and in the glial component of GBM-PN respectively, the combination of CDK4/6 inhibitor and targeted therapy against EGFR might be potential effective therapeutic regimen for GBM-PN. CDK4 and EGFR immuohistochemical stain patterns make the diagnosis of GBM-PN much easier.

http://ift.tt/2A79TGK

High PDL1 mRNA expression predicts better survival of stage pT1 non-muscle-invasive bladder cancer (NMIBC) patients

Abstract

Introduction and objectives

Checkpoint inhibition has emerged as new therapeutic option in muscle-invasive bladder cancer. The objective of the present study was to evaluate the prognostic role of PD1 and PDL1 expression in non-muscle-invasive bladder cancer (NMIBC) and establish an objective measuring method using RNA quantification.

Materials and methods

We retrospectively analyzed clinical data and formalin-fixed paraffin-embedded tissues (FFPE) of patients with stage pT1 NMIBC who underwent transurethral resection of the bladder. mRNA expression of PD1, PDL1 and CD3 was measured by single step RT-qPCR and correlated to clinicopathological parameters, recurrence-free survival (RFS), progression-free survival (PFS) and carcinoma-specific survival (CSS).

Results

We have analyzed 334 patients with NMIBC at stage pT1 for mRNA analysis. Data from 296 patients (79% male, median age: 72 years) could be used. Spearman correlation revealed significant associations between mRNA expressions of PD1/PDL1 (ρ: 0.6024, p < 0.0001), CD3/PDL1 (ρ: 0.5728, p < 0.0001) and CD3/PD1 (ρ: 0.7005, p < 0.0001). Kaplan–Meier analysis revealed that high PDL1 mRNA expression (≥ 33.83) is a favorable prognostic factor with regard to better RFS (p = 0.0018), PFS (p = 0.021) and CSS (p = 0.012). Multivariate Cox-regression analysis proved PDL1 expression to be an independent prognosticator for RFS [HR 0.48 (0.31–0.72), p = 0.0005], PFS [HR 0.45 (0.24–0.80), p = 0.0059] and CSS [HR 0.31 (0.13–0.67), p = 0.0021].

Conclusion

High mRNA expression of PDL1 predicts improved RFS, PFS and CSS of pT1 NMIBC. Following prospective validation, this objective measurement of PD-L1 might help stratify patients with NMIBC for immunotherapy and identify patients who might benefit from early cystectomy.

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CK4, CK6, cyclin D1, p16(INK4a) and EGFR expression in glioblastoma with a primitive neuronal component

Abstract

Glioblastoma with primitive neuroectodermal tumor-like component (GBM-PNET) is a rare variant of glioblastoma, which was renamed as glioblastoma with a primitive neuronal component (GBM-PN) in new WHO classification of tumours of the central nervous system in 2016. There are few publications on the investigation of GBM-PN. In this study, PCR mRNA arrays on 6 cases of conventional GBM and 10 cases of GBM-PN showed high mRNA level of CDK4 in GBM-PN and low mRNA level of EGFR in GBM-PN. Immunohistochemical stains on tissue microarrays with 28 cases of conventional GBM and 13 cases of GBM-PN demonstrated that CDK4 was selectively expressed in the primitive neuronal component of all GBM-PN cases while EGFR was positive in conventional GBM and glial component of GBM-PN, but was negative in the primitive neuronal component of all GBM-PN cases. Immunohistochemical stains with antibodies against proteins that interact with CDK4 in cell cycle regulation, such as CDK6, cyclin D1 and p16(INK4a), were performed on these GBM-PN and GBM cases. CDK6 was patchily positive in rare cases of GBM-PN and cyclin D1 was negative in GBM-PN cases. p16(INK4a) is traditionally known as an inhibitor of CDK4 and CDK6. p16(INK4a) might not be the inhibitor of CDK4 in GBM-PN cases because seven GBM-PN cases were positive for both CDK4 and p16(INK4a). It indicates that CDK4 and p16(INK4a) might play a crucial role in GBM-PN pathogenesis. Since CDK4 and EGFR are highly expressed in the primitive neuronal component and in the glial component of GBM-PN respectively, the combination of CDK4/6 inhibitor and targeted therapy against EGFR might be potential effective therapeutic regimen for GBM-PN. CDK4 and EGFR immuohistochemical stain patterns make the diagnosis of GBM-PN much easier.

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High PDL1 mRNA expression predicts better survival of stage pT1 non-muscle-invasive bladder cancer (NMIBC) patients

Abstract

Introduction and objectives

Checkpoint inhibition has emerged as new therapeutic option in muscle-invasive bladder cancer. The objective of the present study was to evaluate the prognostic role of PD1 and PDL1 expression in non-muscle-invasive bladder cancer (NMIBC) and establish an objective measuring method using RNA quantification.

Materials and methods

We retrospectively analyzed clinical data and formalin-fixed paraffin-embedded tissues (FFPE) of patients with stage pT1 NMIBC who underwent transurethral resection of the bladder. mRNA expression of PD1, PDL1 and CD3 was measured by single step RT-qPCR and correlated to clinicopathological parameters, recurrence-free survival (RFS), progression-free survival (PFS) and carcinoma-specific survival (CSS).

Results

We have analyzed 334 patients with NMIBC at stage pT1 for mRNA analysis. Data from 296 patients (79% male, median age: 72 years) could be used. Spearman correlation revealed significant associations between mRNA expressions of PD1/PDL1 (ρ: 0.6024, p < 0.0001), CD3/PDL1 (ρ: 0.5728, p < 0.0001) and CD3/PD1 (ρ: 0.7005, p < 0.0001). Kaplan–Meier analysis revealed that high PDL1 mRNA expression (≥ 33.83) is a favorable prognostic factor with regard to better RFS (p = 0.0018), PFS (p = 0.021) and CSS (p = 0.012). Multivariate Cox-regression analysis proved PDL1 expression to be an independent prognosticator for RFS [HR 0.48 (0.31–0.72), p = 0.0005], PFS [HR 0.45 (0.24–0.80), p = 0.0059] and CSS [HR 0.31 (0.13–0.67), p = 0.0021].

Conclusion

High mRNA expression of PDL1 predicts improved RFS, PFS and CSS of pT1 NMIBC. Following prospective validation, this objective measurement of PD-L1 might help stratify patients with NMIBC for immunotherapy and identify patients who might benefit from early cystectomy.

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Cytoreductive surgery and Hyperthermic intra-operative peritoneal chemotherapy with Cisplatin for gastric peritoneal Carcinomatosis Monocentric phase-2 nonrandomized prospective clinical trial

Abstract

Background

Cytoreductive surgery (CRS) plus hyperthermic intra-operative peritoneal chemotherapy (HIPC) for gastric peritoneal carcinomatosis (PC) is controversial, and selection criteria for this treatment modality are lacking.

Methods

Thirty-two patients (F/M ratio 12/20; median (range) age 58 (32-75) years) underwent CRS + HIPC with cisplatin for PC from gastric adenocarcinoma in 2010-2014. This monocentric phase-2 nonrandomized prospective study with a power of 90% aimed to improve the 1-year overall survival (OS) rate with 40% (historical reference of 52% to 72%). Median PCI score was 8 (range 1-20), number of regions involved was 6 (range 1-11). The impact of 16 prognostic factors on survival was evaluated using univariable and multivariable Cox regression models. Follow-up was complete in all patients, and closed 2 years after patient inclusion.

Results

All patients had complete cytoreduction (CCR-0) and histopathological R0 resection. PCI </= 12 without PC on any small bowel region with 4 or more non-small bowel regions resulted in a median OS time of 24.7 months (15.6–29.4), and 1, 2, 5-year OS rates of 90%, 55%, 5.6%, respectively. Independent predictors of OS were PC on the small bowel combined with PC on 4 or more non-small bowel regions (p = 0.0004), number of regions involved (p = 0.0029), and overall PCI score (p = 0.0104).

Conclusions

CRS + HIPC with cisplatin to treat gastric PC, providing complete cytoreduction and R0 resection, should be restricted to patients with PCI of 12 or less. Patients having PC on any small bowel region with 4 or more non-small bowel regions should be refused for CRS + HIPC.

Trial registration number

Registration number: NCT01116791. Registration date: May 5, 2010.

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