Hypofractionated stereotactic radiotherapy to the resection bed for intracranial metastases

Publication date: Available online 19 August 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Audrey Keller, Mélanie Doré, Hélène Cebula, François Thillays, François Proust, Ioana Darié, Stéphane-André Martin, Gregory Delpon, François Lefebvre, Georges Noël, Delphine Antoni
PurposeWe retrospectively report the outcomes of a large multicenter cohort of patients treated with surgery and hypofractionated stereotactic radiotherapy (HFSRT) to the resection cavities of brain metastases (BMs).Methods and materialsBetween March 2008 and February 2015, 181 patients with no prior whole-brain radiation therapy (WBRT) were treated by HFSRT to the surgical bed of BM at the dose of 33 Gy (3×11 Gy). The primary end-point was local control (LC). Secondary endpoints were distant brain control (DBC), overall survival (OS), risk of radionecrosis (RN) and leptomeningeal disease (LMD).ResultsOf the 189 resected lesions, 44% were metastatic from a non-small cell lung cancer (NSCLC) primary tumor, and 76% of patients had a single BM at the time of treatment. With a median follow up of 15 months, the 6-and 12-month LC rates were 93% and 88%, respectively. On multivariate analysis, PTV (p=0.005), GPA score (p=0.021) and meningeal contact of BM (p=0.032), were predictive of local failure. The 6-and 12-month DBC rates were 70% and 61%. Twenty-six patients (14%) developed signs of LMD at a median time of 3.8 months. The preoperative tumor volume was predictive of LMD (p=0.029). The median OS was 17months. The 6-,12-and 24-month OS rates were 79%, 62% and 39%, respectively. RPA Class 3 (p=0.02), piecemeal resection (p=0.017) and an increasing number of BMs (p<0.01) were independent unfavorable prognostic factors for OS. Fifty-four patients (30%) were subsequently treated with salvage WBRT at a median time of 6.5 months, and 41% were re-irradiated with SRT. RN occurred in 19% of cases at a median time of 15 months and was associated with the infratentorial location of the BM (p=0.0025).ConclusionThis study demonstrated the safety and efficacy of a 3×11 Gy HFSRT regimen for the irradiation of BMs resection cavities. It was an alternative to adjuvant WBRT.

Teaser

We retrospectively report the outcomes of a large multicenter cohort of patients treated with surgery and hypofractionated stereotactic radiotherapy (HFSRT) to the resection cavities of brain metastases (BMs). We analyzed the local control, distant brain control, overall survival, risk of radionecrosis and leptomeningeal disease. This study demonstrated the safety and efficacy of a 3×11Gy HFSRT regimen for the irradiation of BMs resection cavities. It was an alternative to adjuvant whole-brain radiotherapy (WBRT).


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Impact of surgery, adjuvant therapy and other prognostic factors for choroid plexus carcinoma; a systematic review and individual patient data analysis

Publication date: Available online 18 August 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Supriya Mallick, Rony Benson, Wineeta Melgandi, G.K. Rath
ObjectiveThe optimal management of patients with choroid plexus carcinoma (CPC) is unclear. We conducted a systematic review and meta-analysis of individual patient information to find the impact of surgery, adjuvant therapy and other prognostic factors in this disease.MethodologyA comprehensive search of the PubMed and Google scholar was performed with the following MesH terms: "choroid plexus tumor; choroid plexus carcinoma; choroid plexus carcinoma AND treatment; and choroid plexus carcinoma AND survival" to find all possible publications on CPC. We performed individual patient data analysis, to assess the strength of potential association between different variables and the outcome in patients with CPC.ResultsData from 284 patients was retrieved from 89 publications. The median age of the patients was 2 years with 26% patients diagnosed in the 1st year of their life. 52.8% of patients underwent a gross total resection [GTR] or near total resection. Median follow-up for the entire cohort was 10.8 months. Median progression free survival [PFS] was 13 months [95% CI 8.14-17.8]. PFS was better for patients older than 5 years and GTR. Median overall survival [OS] was 29 months (95% CI 16.3- 41.7). OS was better for patients older than 5 years, GTR, adjuvant treatment and parenchymal site of the tumor.ConclusionCPC is an aggressive tumor, with a median PFS of 13 months and a median OS of 29 months. All patients should undergo a maximal safe resection as GTR is associated with improved survival. Adjuvant radiation and chemotherapy were also associated with improved outcomes.

Teaser

Optimal management of patients with choroid plexus carcinoma (CPC) is not clear. We conducted a systematic review and meta-analysis of individual patient observations to find the impact of surgery, adjuvant therapy and other prognostic factors for CPC. Median overall survival for the entire cohort was 29 months. The overall survival was better for patients older than 5 years, patients undergoing GTR, adjuvant treatment, and parenchymal tumor. A gross total resection and adjuvant treatment need to be advocated for all patients as it improves survival outcome.


http://ift.tt/2uR9vKk

Priapism due to essential thrombocythaemia: a rare causation

Priapism is rarely caused by essential thrombocytosis, a disorder characterised by increased number of megakaryocytes. We report a case of a 21-year-old man who presented with priapism and on investigation was found to have essential thrombocytosis as the cause.

http://ift.tt/2ie6myd

Renal cell carcinoma presenting as a cutaneous horn and nodules on the gingiva and scalp

A 63-year-old man presented with a pulsatile cutaneous horn on the nose and multiple angiomatous nodules on the gingiva and scalp, which appeared over 2 months. He had severe hypercalcaemia, lytic lesions in multiple bones and acute kidney injury. Excision biopsy from the gingival nodule showed a clear cell neoplasm. The bone marrow showed atypical cells with similar morphology. Imaging showed a 7 cmx7.5 cm mass at the upper pole of the left kidney with metastases to the bones, liver and lung. Immunohistochemistry was consistent with metastatic renal cell carcinoma. Renal cell carcinoma presenting as a cutaneous horn is extremely rare and to the best of our knowledge only one other case was found in the literature. There was visible regression in the size of the cutaneous horn and nodules following initiation of pazopanib therapy. However, he succumbed to his illness a month later.

http://ift.tt/2fTZEN4

Bilateral optic disc coloboma

Description

A 5-month-old male child was brought with the history of right-sided corneal opacity noticed for the past 2 months. The baby was immunised until now with an uneventful antenatal and peripartum history. Ocular examination showed normal sized cornea having a paracentral nebular opacity along the inferior and nasal aspect without any discharge or significant exposure keratopathy. The baby was able to fix at the light with each eye separately, the anterior chamber in both the eyes was of normal depth having a clear lens and retinal examination showed a well-defined posteriorly excavated area along the inferior portion of the optic disc in both the eyes. Sleeping intraocular pressures were 10 and 12 mm Hg in right eye and left eye, respectively. Posterior segment B-scan ultrasound showed a well-defined symmetric excavation along the inferior aspect of the optic disc in both the eyes with an axial length of 20 mm...

http://ift.tt/2ie6iyt

Idiopathic spontaneous lesser sac haematoma: a perplexing case of abdominal apoplexy

A 37-year-old woman presented with a 3-hour history of back pain, nausea and vomiting and an episode of syncope. A fluid collection in the lesser sac was detected on ultrasound and CT scan. Emergency laparoscopy and subsequent laparotomy were performed and a large blood clot was evacuated from the lesser sac. No identifiable source or predisposition to bleeding was found. She made a full recovery postoperatively. There are few reported cases of spontaneous intraperitoneal haemorrhage. In a third of cases, there is no identifiable source of bleeding. Unfortunately, patients present late with non-specific symptoms and a prompt diagnosis is difficult to make. The case reiterates the importance of awareness of lesser sac haematoma formation; an unusual clinical entity with a high morbidity and mortality rate. A high index of suspicion, radiological adjuncts and appropriate surgical intervention, especially in unstable patients, is essential for a good outcome.

http://ift.tt/2fU4D02

Successful treatment of direct carotid-cavernous fistula in a patient with Ehlers-Danlos syndrome type IV without arterial puncture: the transvenous triple-overlay embolization (TAILOREd) technique

We report successful transvenous treatment of direct carotid–cavernous fistula in a patient with Ehlers–Danlos syndrome type IV using a novel triple-overlay embolization (TAILOREd) technique without the need for arterial puncture, which is known to be highly risky in this patient group. The TAILOREd technique allowed for successful treatment using preoperative MR angiography as a three-dimensional overlay roadmap combined with cone beam CT and live fluoroscopy, precluding the need for an arterial puncture.

http://ift.tt/2iemobp

Duration of Adjuvant Trastuzumab in HER2 Positive Breast Cancer: Overall and Disease Free Survival Results from Meta-Analyses of Randomized Controlled Trials

Publication date: Available online 19 August 2017
Source:Cancer Treatment Reviews
Author(s): Bishal Gyawali, Saroj Niraula
BackgroundOne year of trastuzumab, chosen empirically, improves survival of women with early-stage, HER2-positive breast cancer but also adds substantially to cost, toxicity, and inconvenience. Longer treatment does not improve outcomes, but potentiates toxicities.MethodsMedline, Embase, and major conference proceedings were searched systematically in June, 2017 to identify Randomized Controlled Trials (RCTs) comparing one year versus shorter durations of trastuzumab in adjuvant treatment of breast cancer. Reported Hazard-Ratios (HR) for Overall Survival (OS) and Disease-Free Survival (DFS), and Odds-Ratios for cardiac events, with respective 95% Confidence Intervals (CI) from each study was weighted using generic inverse-variance, and pooled in a meta-analysis. Inter-study heterogeneity and sub-group difference (based on hormone-receptors and node-positivity) were assessed using I², and chi² statistics, respectively.ResultsFour studies (n=7,614) satisfied inclusion criteria. Individual RCTs had diverse pre-specified upper-limits of 95% CI for declaring non-inferiority (range: <1.15 to <1.53). Pooled results demonstrated significant improvements in OS (HR 1.28, p=0.04), and DFS (HR 1.24, p=0.005) with 1 year of trastuzumab compared to shorter durations. Absence of multiplicity argument allowed for declaring superiority of 1 year of trastuzumab based on our results despite non-inferiority designs of individual trials. No influence on overall effect by duration of trastuzumab in experimental arm (9 weeks versus 6 months) was noted. No statistical interaction by hormone-receptor status and node-positivity on overall results was noticed [p(sub-group difference) 0.73, and 0.52, respectively]. Odds-Ratio for cardiac events was 2.65(p<0.001) favoring shorter duration.ConclusionOne year of trastuzumab prolongs overall, and disease-free survivals in women with early-stage HER2 positive breast cancer compared to shorter durations and this should remain as the standard of care. Cardiotoxicity increased significantly with the 1-year treatment.



http://ift.tt/2fUwmxL

Physiologic Considerations in Trauma Patients Undergoing Resuscitative Endovascular Balloon Occlusion of the Aorta

Resuscitative endovascular balloon occlusion of the aorta is a new procedure for adjunctive management of critically injured patients with noncompressible torso or pelvic hemorrhage who are in refractory hemorrhagic shock, ie, bleeding to death. The anesthesiologist plays a critical role in management of these patients, from initial evaluation in the trauma bay to definitive care in the operating room and the critical care unit. A comprehensive understanding of the effects of resuscitative endovascular balloon occlusion of the aorta is essential to making it an effective component of hemostatic resuscitation.

http://ift.tt/2v0eAvK

Resuscitative Endovascular Balloon Occlusion of the Aorta: Principles, Initial Clinical Experience, and Considerations for the Anesthesiologist

Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an endovascular technique that allows for temporary occlusion of the aorta in patients with severe, life-threatening, trauma-induced noncompressible hemorrhage arising below the diaphragm. REBOA utilizes a transfemoral balloon catheter inserted in a retrograde fashion into the aorta to provide inflow control and support blood pressure until definitive hemostasis can be achieved. Initial retrospective and registry clinical data in the trauma surgical literature demonstrate improvement in systolic blood pressure with balloon inflation and improved survival compared to open aortic cross-clamping via resuscitative thoracotomy. However, there are no significant reports of anesthetic implications and perioperative management in this challenging cohort. In this narrative, we review the principles, technique, and logistics of REBOA deployment, as well as initial clinical outcome data from our level-1 American College of Surgeons–verified trauma center. For anesthesiologists who may not yet be familiar with REBOA, we make several suggestions and recommendations for intraoperative management based on extrapolation from these initial surgical-based reports, opinions from a team with increasing experience, and translated experience from emergency aortic vascular surgical procedures. Further prospective data will be necessary to conclusively guide anesthetic management, especially as potential complications and implications for global organ function, including cerebral and renal, are recognized and described.

http://ift.tt/2uZJgNF

Optoacoustic detection of early therapy-induced tumor cell death using a targeted imaging agent

Purpose: The development of new treatments and their deployment in the clinic may be assisted by imaging methods that allow an early assessment of treatment response in individual patients. The C2A domain of Synaptotagmin-I (C2Am), which binds to the phosphatidylserine (PS) exposed by apoptotic and necrotic cells, has been developed as an imaging probe for detecting cell death. Multispectral optoacoustic tomography (MSOT) is a real-time and clinically applicable imaging modality that was used here with a near infrared (NIR) fluorophore-labeled C2Am to image tumor cell death in mice treated with a TNF-related apoptosis-inducing ligand receptor 2 (TRAILR2) agonist and with 5-fluorouracil (5-FU).<br /><br />Experimental Design: C2Am was labeled with a near infrared (NIR) fluorophore and injected intravenously into mice bearing human colorectal TRAIL-sensitive Colo205 and TRAIL-resistant HT-29 xenografts that had been treated with a potent agonist of TRAILR2 and in Colo205 tumors treated with 5-FU.<br /><br />Results: Three dimensional MSOT images of probe distribution showed development of tumor contrast within 3 h of probe administration and a signal-to-background ratio in regions containing dead cells of >10 after 24 h. A site-directed mutant of C2Am that is inactive in PS binding showed negligible binding. Tumor retention of the active probe was strongly correlated (R²=0.97, P value<0.01) with a marker of apoptotic cell death measured in histological sections obtained post mortem.<br /><br />Conclusions: The rapid development of relatively high levels of contrast suggests that NIR fluorophore-labeled C2Am could be a useful optoacoustic imaging probe for detecting early therapy-induced tumor cell death in the clinic.

http://ift.tt/2vM1c17

p53 non-genotoxic activation and mTORC1 inhibition lead to effective combination for neuroblastoma therapy.

Purpose: mTORC1 inhibitors are promising agents for neuroblastoma therapy, however they have shown limited clinical activity as monotherapy, thus rational drug combinations need to be explored to improve efficacy. Importantly, neuroblastoma maintains both an active p53 and an aberrant mTOR signaling. <br /><br />Experimental Design: Using an orthotopic xenograft model and modulating p53 levels, we investigated the anti-tumor effects of the mTORC1 inhibitor temsirolimus in neuroblastoma expressing normal, decreased, or mutant p53, both as single agent and in combination with first and second generation MDM2 inhibitors to reactivate p53. <p>Results: Non-genotoxic p53 activation suppresses mTOR activity. Moreover, p53 reactivation via RG7388, a second generation MDM2 inhibitor, strongly enhances the in vivo anti-tumor activity of temsirolimus. Single agent temsirolimus does not elicit apoptosis, and tumors rapidly re-grow after treatment suspension. In contrast, our combination therapy triggers a potent apoptotic response in wild-type p53 xenografts and efficiently blocks tumor re-growth after treatment completion. We also found that this combination uniquely led to p53-dependent suppression of survivin whose ectopic expression is sufficient to rescue the apoptosis induced by our combination.</p> <br />Conclusions: Our study supports a novel highly effective strategy that combines RG7388 and temsirolimus in wild-type p53 neuroblastoma, which warrants testing in early-phase clinical trials.

http://ift.tt/2wZnHhO

Synergy of WEE1 and mTOR inhibition in mutant KRAS-driven lung cancers

Purpose: KRAS-activating mutations are the most common oncogenic driver in non-small cell lung cancer (NSCLC), but efforts to directly target mutant KRAS have proved a formidable challenge. Therefore, multi-targeted therapy may offer a plausible strategy to effectively treat KRAS-driven NSCLCs. Here, we evaluate the efficacy and mechanistic rationale for combining mTOR and WEE1 inhibition as a potential therapy for lung cancers harboring KRAS mutations. <p>Experimental Design: We investigated the synergistic effect of combining mTOR and WEE1 inhibitors on cell viability, apoptosis, and DNA damage repair response using a panel of human KRAS-mutant and wild type NSCLC cell lines and patient-derived xenograft cell lines. Murine autochthonous and human transplant models were used to test the therapeutic efficacy and pharmacodynamic effects of dual treatment.</p> <p>Results: We demonstrate that combined inhibition of mTOR and WEE1 induced potent synergistic cytotoxic effects selectively in KRAS-mutant NSCLC cell lines, delayed human tumor xenograft growth and caused tumor regression in a murine lung adenocarcinoma model. Mechanistically, we show that inhibition of mTOR potentiates WEE1 inhibition by abrogating compensatory activation of DNA repair, exacerbating DNA damage in KRAS-mutant NSCLC, and that this effect is due in part to reduction in cyclin D1. </p> <p>Conclusions: These findings demonstrate that compromised DNA repair underlies the observed potent synergy of WEE1 and mTOR inhibition and support clinical evaluation of this dual therapy for patients with KRAS-mutant lung cancers.

http://ift.tt/2wZgi1R

Defective cyclin B1 induction in trastuzumab-emtansine (T-DM1) acquired resistance in HER2-positive breast cancer

Purpose: Trastuzumab-emtansine (T-DM1) is a standard treatment in advanced HER2 positive breast cancer. However, resistance inevitably occurs. We aimed to identify mechanisms of acquired T-DM1 resistance. <p>Experimental Design: HER2-positive breast cancer cells (HCC1954, HCC1419, SKBR3 and BT474) were treated in a pulse-fashion with T-DM1 to induce a resistant phenotype. Cellular and molecular effects of T-DM1 in parental versus resistant cells were compared. CDK1 kinase activity and cyclin B1 expression were assayed under various conditions. Genetic modifications to up or down regulate cyclin B1 were conducted. Effects of T-DM1 on cyclin B1 levels, proliferation and apoptosis were assayed in human HER2 positive breast cancer explants.</p> <p>Results: We obtained three cell lines with different levels of acquired T-DM1 resistance (HCC1954/TDR, HCC1419/TDR and SKBR3/TDR cells). HER2 remained amplified in the resistant cells. Binding to HER2 and intracellular uptake of T-DM1 were maintained in resistant cells. T-DM1 induced cyclin B1 accumulation in sensitive but not resistant cells. Cyclin B1 knock-down by siRNA in parental cells induced T-DM1 resistance, while increased levels of cyclin B1 by silencing cdc20, partially sensitized resistant cells. In a series of 18 HER2-positive breast cancer fresh explants, T-DM1 effects on proliferation and apoptosis paralleled cyclin B1 accumulation.</p> <p>Conclusion: Defective cyclin B1 induction by T-DM1 mediates acquired resistance in HER2 positive breast cancer cells. These results support the testing of cyclin B1 induction upon         T-DM1 treatment as a pharmacodynamic predictor in HER2 positive breast cancer.

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Dasatinib reversibly disrupts endothelial vascular integrity by increasing non-muscle myosin II contractility in a ROCK-dependent manner

Purpose: Dasatinib is a short-acting dual ABL/SRC family tyrosine kinase inhibitor (TKI), which is frequently used to treat chronic myeloid leukemia. Although very effective, dasatinib often displays severe adverse effects, including pleural effusions and increased risk of bleeding primarily in the gastrointestinal tract. The actual causes of these side effects are currently undetermined. We hypothesize that endothelial cells (ECs) that line the inner walls of blood vessels and control the traffic to the underlying tissues, might be involved. <p>Experimental design: The effects of TKIs on ECs were studied by various assays, such as real-time cell impedance measurements, live-cell microscopy, wound healing, western blot and an in vivo model.</p> <p>Results: Dasatinib uniquely causes a profound, dose-dependent disorganization of the EC monolayers. Dasatinib promoted the disassembly of cell-cell contacts, altered cell-matrix contacts and further altered the wound healing. A key observation is that this effect is fully reversible after drug washout. In line with these in vitro observations, intraperitoneal administration of dasatinib to mice caused significant vascular leakage in the intestine. The underlying molecular mechanism of dasatinib-induced reorganization of the actin involves ROCK activation, which increases the amount of the phosphorylation of myosin light chain and consequently activates the non-muscle myosin II.</p> <p>Conclusions: Our data are consistent with a scenario in which dasatinib triggers a transient increase in vascular leakage that probably contributes to adverse effects such as bleeding diathesis and pleural effusions.

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Selected alkylating agents can overcome drug tolerance of G0-like tumor cells and eradicate BRCA1-deficient mammary tumors in mice.

Purpose: We aimed to characterize and target drug-tolerant BRCA1-deficient tumor cells that cause residual disease and subsequent tumor relapse.<br /><br />Experimental Design: We studied responses to various mono- and bifunctional alkylating agents in a genetically engineered mouse model for BRCA1/p53-mutant breast cancer. Due to the large intragenic deletion of the Brca1 gene, no restoration of BRCA1 function is possible, and therefore no BRCA1-dependent acquired resistance occurs. To characterize the cell cycle stage from which Brca1^-/-;p53^-/- mammary tumors arise after cisplatin treatment, we introduced the fluorescent ubiquitination-based cell cycle indicator (FUCCI) construct into the tumor cells.<br /><br />Results: Despite repeated sensitivity to the maximum tolerated dose (MTD) of platinum drugs, the Brca1-mutated mammary tumors are not eradicated, not even by a frequent dosing schedule. We show that relapse comes from single nucleated cells delaying entry into S phase. Such slowly cycling cells, which are present within the drug-naïve tumors, are enriched in tumor remnants. Using the FUCCI construct we identified non-fluorescent G₀-like cells as the population most tolerant to platinum drugs. Intriguingly, these cells are more sensitive to the DNA crosslinking agent nimustine resulting in an increased number of multinucleated cells that lack clonogenicity. This is consistent with our in vivo finding that the nimustine MTD, among several alkylating agents, is most effective in eradicating Brca1-mutated mouse mammary tumors.<br /><br />Conclusions: Our data show that targeting G₀-like cells is crucial for the eradication of BRCA1/p53-deficient tumor cells. This can be achieved with selected alkylating agents such as nimustine.

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The feasibility analysis of omission of elective irradiation to level IB lymph nodes in low-risk nasopharyngeal carcinoma based on the 2013 updated consensus guideline for neck nodal levels

Level IB metastasis is rare in nasopharyngeal carcinoma (NPC). The purpose of this study is to investigate the high-risk factors for level IB metastasis and evaluate the feasibility of omission of elective irr...

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Hypo-fractionated SBRT for localized prostate cancer: a German bi-center single treatment group feasibility trial

For prostate cancer treatment, treatment options with minimal side effects are desired. External beam radiation therapy (EBRT) is non-invasive, standard of care and delivered in either conventional fractionati...

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Colorectal cancer patient’s self-efficacy for managing illness-related problems in the first 2 years after diagnosis, results from the ColoREctal Well-being (CREW) study

Abstract

Purpose

There is a growing emphasis on self-management of cancer aftercare. Little is known about patient's self-efficacy (confidence) to manage illness-related problems and how this changes over time. This paper describes the patterns of self-efficacy for managing illness-related problems amongst colorectal cancer patients in the 2 years following diagnosis.

Methods

In this prospective cohort study, questionnaires were administered at baseline (pre-surgery), 3, 9, 15 and 24 months to 872 colorectal cancer patients. Self-efficacy (confidence to manage illness-related problems), anxiety, social support, affect, socio-demographics, physical symptoms and clinical and treatment characteristics were assessed. Group-based trajectory analysis identified trajectories of self-efficacy up to 24 months and predictors.

Results

Four trajectories of self-efficacy were identified: group 1 (very confident) 16.0% (95% confidence interval (CI) 10.7–21.3%), group 2 (confident) 45.6% (95% CI 40.3–51.0%), group 3 (moderately confident) 29.5% (95% CI 25.1–33.8%) and group 4 (low confidence) 8.9% (95% CI 6.4–11.4%). Greater deprivation, domestic status, more co-morbidities, worse fatigue and pain, lower positivity and greater negativity were significantly associated with lower self-efficacy. There was an increase in mean scores for self-efficacy over time for the whole sample, but this did not reach the cut-off for minimally important differences. At 2 years, the lowest level of confidence to manage was for symptoms or health problems.

Conclusion

Around 40% of patients had suboptimal levels of confidence to manage illness-related problems with little change from the time of diagnosis across the four groups.

Implications for cancer survivors

Screening for self-efficacy at diagnosis would enable targeted, early intervention which could in turn enhance health-related quality of life.

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In Response

No abstract available

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The Need for a Global Perspective on Task-Sharing in Anesthesia

No abstract available

http://ift.tt/2wii15m

Lysosomal Storage Diseases: Past, Present, and Future

No abstract available

http://ift.tt/2wiiTqC

The WFSA Global Anesthesia Workforce Survey

BACKGROUND: Safe anesthesia and surgical care are not available when needed for 5 billion of the world's 7 billion people. There are major deficiencies in the specialist surgical workforce in many parts of the world, and specific data on the anesthesia workforce are lacking. METHODS: The World Federation of Societies of Anaesthesiologists conducted a workforce survey during 2015 and 2016. The aim of the survey was to collect detailed information on physician anesthesia provider (PAP) and non-physician anesthesia provider (NPAP) numbers, distribution, and training. Data were categorized according to World Health Organization regional groups and World Bank income groups. RESULTS: We obtained information for 153 of 197 countries, representing 97.5% of the world's population. There were marked differences in the density of PAPs between World Health Organization regions and between World Bank income groups, ranging from 0 to over 20 PAP per 100,000 population. Seventy-seven countries reported a PAP density of

http://ift.tt/2wilCAp

Perioperative Hypotension in Infants: Insights From the GAS Study

No abstract available

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Quality and Safety in Anesthesia and Perioperative Care

No abstract available

http://ift.tt/2wi1qOZ

No Surprise—For Long-term Opioid Avoidance, Do We Reap What We Sow?

No abstract available

http://ift.tt/2xcnMOs

Resuscitation Training for Schoolchildren Worldwide: Kids Save Lives: Erratum

No abstract available

http://ift.tt/2wi8PxC

The Anesthesiologist’s Dream: “Wireless” Vital Sign Monitoring?

No abstract available

http://ift.tt/2xcgYA5

Lack of Association Between the Use of Nerve Blockade and the Risk of Persistent Opioid Use Among Patients Undergoing Shoulder Arthroplasty: Evidence From the Marketscan Database

BACKGROUND: Persistent opioid use following surgery has received increasing attention from policymakers, researchers, and clinicians. Perioperative nerve blockade has been hypothesized to decrease the risk of persistent opioid use. We examined whether nerve blockade was associated with a decreased risk of persistent opioid use among patients undergoing shoulder arthroplasty, a procedure with high rates of persistent postoperative pain. METHODS: Using health care claims data, we constructed a sample of 6695 patients undergoing shoulder arthroplasty between 2002 and 2012 and used billing data to identify the utilization of nerve blockade. We then used a multivariable logistic regression to estimate the association between nerve blockade and 2 measures of opioid use: having filled at least 1 prescription for an opioid between postoperative days (PODs) 0 and 90, and between POD 91 and 365. This regression adjusted for a variety of potential confounders, such as preoperative opioid use and medical history. RESULTS: There was no association between nerve blockade and our 2 measures of persistent opioid use: adjusted odds ratio, 1.12 (97.5% confidence interval, 0.939–1.34; P = .15) for opioid use between POD 0 and 90, and adjusted odds ratio, 0.997 (97.5% confidence interval, 0.875–1.14; P = .95) for opioid use between POD 91 and 365. CONCLUSIONS: Although the use of perioperative nerve blockade may offer short-term benefits, in this study, it was not associated with a reduction in the risk of persistent opioid use for patients undergoing shoulder arthroplasty.

http://ift.tt/2xc0xnp

Studies on Postoperative Analgesic Efficacy: Focusing the Statistical Methods and Broadening Outcome Measures and Measurement Tools

No abstract available

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Fixing Medical Prices

No abstract available

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Resuscitative Endovascular Balloon Occlusion of the Aorta: A New Weapon to Combat Exsanguinating Hemorrhage

No abstract available

http://ift.tt/2xc6wZC

Do Not Fear the Difficult IV

No abstract available

http://ift.tt/2xcwRXk

Do Institution-Level Blood Utilization and Blood Management Initiatives Meaningfully Impact Transfusion Practices in Cardiac Surgery?

No abstract available

http://ift.tt/2xczDMk

Antibiotics and the Anesthesiologist: Is There a “Consensus?”

No abstract available

http://ift.tt/2whVZ2z

Human Resources in Anesthesia: The Road to 2030

No abstract available

http://ift.tt/2xc2BMv

A Graphical Guide to the REBOA: Five Life-Saving Steps

No abstract available

http://ift.tt/2xcajWN

Surveying the Literature: Synopsis of Recent Key Publications

No abstract available

http://ift.tt/2wi1kqB

Lack of Association Between the Use of Nerve Blockade and the Risk of Postoperative Chronic Opioid Use Among Patients Undergoing Total Knee Arthroplasty: Evidence From the Marketscan Database

BACKGROUND: Total knee arthroplasty (TKA) is associated with high rates of prolonged opioid use after surgery (10%–34%). By decreasing opioid use in the immediate postoperative period, perioperative nerve blockade has been hypothesized to decrease the risk of persistent opioid use. METHODS: Using health care utilization data, we constructed a sample of 120,080 patients undergoing TKA between 2002 and 2012 and used billing data to identify the utilization of peripheral or neuraxial blockade. We then used a multivariable logistic regression to estimate the association between nerve blockade and the risk of chronic opioid use, defined as having filled ≥10 prescriptions or ≥120 days' supply for an opioid in the first postsurgical year. Our analyses were adjusted for an extensive set of potential confounding variables, including medical comorbidities, previous opioid use, and previous use of other medications. RESULTS: We did not find an association between nerve blockade and the risk of postsurgical chronic opioid use across any of these 3 groups: adjusted relative risk (ARR) 0.984 for patients opioid-naïve in the year before surgery (98.3% confidence interval [CI], 0.870–1.12, P = .794), ARR 1.02 for intermittent opioid users (98.3% CI, 0.948–1.09, P = .617), and ARR 0.986 (98.3% CI, 0.963–1.01, P = .257) for chronic opioid users. Similar results held for alternative measures of postsurgical opioid use. CONCLUSIONS: Although the use of perioperative nerve blockade for TKA may improve short-term outcomes, the analyzed types of blocks do not appear to decrease the risk of persistent opioid use in the longer term.

http://ift.tt/2xc0pnV

Morus nigra and its major phenolic, syringic acid, have antidepressant-like and neuroprotective effects in mice

Abstract

Depression is a disorder with a high incidence that has been increasing worldwide although the pathophysiology remains unclear. Moreover, some studies revealed a higher concentration of glutamate and oxidative stress in the patients' brain, which causes cell death by excitotoxicity. Morus nigra L. is known as black mulberry and its leaves are popularly used to treat affections related to menopause, obesity and high cholesterol. M. nigra leaves are a rich fount of phenolics which well-known by the antioxidant property. Herein, we examined the phenolic profile and the antidepressant-like effect of the Morus nigra aqueous extract (MN) and its major phenolic constituent, syringic acid (SA). Furthermore, the involvement of antioxidant and neuroprotective activities were further evaluated. Our results show that acute and subchronic MN or SA administration exerted antidepressant-like property in the behavioral testes in mice. The results suggest that the antidepressant-like effect of MN, at least in part, could be due to the SA influence. Moreover, the observed effect involves the nitro-oxidative system modulation in both the serum and brain of mice. Furthermore, MN or SA was able to contain the glutamate-induced cell death in the hippocampal and cortical slices implicating the neuroprotection activity in the antidepressant-like effect.

http://ift.tt/2v9H8SO

Brainstem dose is associated with patient-reported acute fatigue in head and neck cancer radiation therapy

Radiation (RT) dose to the central nervous system (CNS) has been implicated as a contributor to treatment-related fatigue in head and neck cancer (HNC) patients undergoing radiation therapy (RT). This study evaluates the association of RT dose to CNS structures with patient-reported (PRO) fatigue scores in a population of HNC patients.

http://ift.tt/2vL7GgI

Patient-reported urinary incontinence after radiotherapy for prostate cancer: Quantifying the dose–effect

Urinary incontinence following radiotherapy (RT) for prostate cancer (PCa) has a relevant impact on patient's quality of life. The aim of the study was to assess the unknown dose–effect relationship for late patient-reported urinary incontinence (LPRUI).

http://ift.tt/2wYPjmW

Constitutional mosaicism of a de novo TP53 mutation in a patient with bilateral choroid plexus carcinoma

Publication date: October 2017
Source:Cancer Genetics, Volumes 216–217
Author(s): Joanna Trubicka, Iwona Filipek, Iwanowski Piotr, Małgorzata Rydzanicz, Wiesława Grajkowska, Dorota Piekutowska-Abramczuk, Krystyna Chrzanowska, Agnieszka Karkucińska-Więckowska, Katarzyna Iwanicka-Pronicka, Maciej Pronicki, Maria Łastowska, Rafał Płoski, Bożenna Dembowska-Bagińska
Choroid plexus tumors (CPT) constitute 2%–5% of all pediatric brain tumors and include high grade choroid plexus carcinoma (CPC). About 40% of CPC patients harbor germline TP53 mutations, associated with diminished survival rates. However, the number of TP53 carriers might be underestimated due to suboptimal ability of Sanger sequencing to identify mosaicism. We describe an 18-month-old boy with ultra-rare, bilateral disseminated CPC and negative family history of cancer. Next generation sequencing (NGS) revealed constitutional mosaicism of de novo TP53 mutation, which was barely detectable by Sanger sequencing. This is the first description of a de novo TP53 mutation mosaicism in a patient with CPC. Up to now four cases of de novo TP53 mutations in CPC patients have been described but none of them were mosaic. Since TP53 mutation mosaicism may have an impact on management of patients and predisposition to other cancers, a reliable method of identification is important. Our results highlight the utility of high-throughput technologies in detection of potentially important genetic markers.



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A phase 1/1B trial of ADI-PEG 20 plus nab-paclitaxel and gemcitabine in patients with advanced pancreatic adenocarcinoma

BACKGROUND

ADI-PEG 20 is a pegylated form of the arginine-depleting enzyme arginine deiminase. Normal cells synthesize arginine with the enzyme argininosuccinate synthetase (ASS1); ADI-PEG 20 selectively targets malignant cells, which lack ASS1.

METHODS

A single-arm, nonrandomized, open-label, phase 1/1B, standard 3 + 3 dose escalation with an expansion cohort of 9 patients at the recommended phase 2 dose (RP2D) was conducted. Patients who had metastatic pancreatic cancer, up to 1 line of prior treatment (the dose-escalation cohort) or no prior treatment (the expansion cohort), and an Eastern Cooperative Oncology Group performance status of 0 to 1 were included. Patients received both gemcitabine (1000 mg/m²) and nab-paclitaxel (125 mg/m²) for 3 of 4 weeks and intramuscular ADI-PEG 20 at 18 mg/m² weekly (cohort 1) or at 36 mg/m² weekly (cohort 2 and the expansion cohort).The primary endpoint was to determine the maximum tolerated dose and RP2D of ADI-PEG 20 in combination with nab-paclitaxel and gemcitabine.

RESULTS

Eighteen patients were enrolled. No dose-limiting toxicities (DLTs) were observed in cohort 1; cohort 2 was expanded to 6 patients because of 1 DLT occurrence (a grade 3 elevation in bilirubin, aspartate aminotransferase, and alanine aminotransferase). The most frequent adverse events (AEs) of any grade were neutropenia, thrombocytopenia, leukopenia, anemia, peripheral neuropathy, and fatigue; all 18 patients experienced grade 3/4 AEs. The most frequent grade 3/4 toxicities, regardless of the relation with any drugs, included neutropenia (12 patients or 67%), leukopenia (10 patients or 56%), anemia (8 patients or 44%), and lymphopenia (6 patients or 33%). The RP2D for ADI-PEG 20 was 36 mg/m² weekly in combination with standard-dose gemcitabine and nab-paclitaxel. The overall response rate among patients treated at the RP2D in the first-line setting was 45.5% (5 of 11).The median progression-free survival time for these patients treated at the RP2D was 6.1 months (95% confidence interval, 5.3-11.2 months), and the median overall survival time was 11.3 months (95% confidence interval, 6.7 months to not reached).

CONCLUSIONS

ADI-PEG 20 was well tolerated in combination with gemcitabine and nab-paclitaxel. Activity was observed in previously treated and untreated patients with advanced pancreatic cancer and in patients with ASS1-deficient and -proficient tumors. Cancer 2017. © 2017 American Cancer Society.

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Results of a prospective phase 2 study of pazopanib in patients with advanced intermediate-grade or high-grade liposarcoma

BACKGROUND

This phase 2, single-arm, multicenter study was designed to determine the treatment activity and safety of single-agent pazopanib in patients with unresectable or metastatic liposarcoma.

METHODS

Eligible patients had high-grade or intermediate-grade liposarcoma with measurable tumors that were unresectable or metastatic, documented disease progression, and had received any number of prior treatments, excluding previous treatment with a vascular endothelial growth factor inhibitor or a tyrosine kinase inhibitor. Patients received oral pazopanib 800 mg once daily for 28-day cycles. Tumor response was evaluated by local radiology assessments every 3 cycles. The primary endpoint was the progression-free rate (PFR) at 12 weeks (PFR12).

RESULTS

Forty-one patients were enrolled. The PFR12 was 68.3% (95% confidence interval [CI], 51.9%-81.9%), which was significantly greater than the null hypothesis value of 40% (P = .0002). At 24 weeks, 39% of patients (95% CI, 24.2%-55.5%) remained progression free, and 44% experienced tumor control (partial response or stable disease). The median progression-free survival was 4.4 months (95% CI, 3.2-6.5 months), and the median overall survival was 12.6 months (95% CI, 8.5-16.2 months). The most common adverse events overall were nausea (39%), hypertension (36.6%), diarrhea (34.1%), and fatigue (29.3%), which were typically less than grade 3. There were 5 deaths on study (12.2%), 3 of which were from possible complications of therapy.

CONCLUSIONS

The current study provides evidence of potential activity of pazopanib in the liposarcoma subset of patients with soft tissue sarcoma that was specifically excluded from the phase 3 PALETTE trial of other soft tissue sarcoma types. Cancer 2017. © 2017 American Cancer Society.

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Cytotechnology education from a Mayo perspective

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Semi-quantitative metabolic values on FDG PET/CT including extracardiac sites of disease as a predictor of treatment course in patients with cardiac sarcoidosis

Abstract

Background

Cardiac sarcoidosis is associated with major adverse cardiac events including cardiac arrest, for which anti-inflammatory treatment is indicated. Oral corticosteroid is the mainstay among treatment options; however, adverse effects are a major concern with long-term use. It would be beneficial for providers to predict treatment response and prognosis for proper management strategy of sarcoidosis, though it remains challenging. Fluorine (F)-18 fluorodeoxyglucose (FDG)-positron emission tomography(PET)/computed tomography(CT) has an advantage over anatomical imaging in providing semi-quantitative functional parameters such as standard uptake value (SUV), metabolic volume, and total lesion glycolysis (TLG), which are well-established biomarkers in oncology. However, the relationship between these parameters and treatment response has not been fully investigated in cardiac sarcoidosis. Also, the prognostic value of extracardiac active inflammation noted on FDG-PET/CT in the setting of cardiac sarcoidosis is unclear. The aim of this retrospective study was to investigate the prognostic value of semi-quantitative values of both cardiac and extracardiac disease sites derived from FDG-PET/CT in predicting treatment course in cardiac sarcoidosis.

Methods

Sixteen consecutive patients with suspected cardiac sarcoidosis, who demonstrated abnormal myocardial activity on cardiac-inflammation FDG-PET/CT encompassing the entire chest/upper abdomen and subsequently underwent corticosteroid therapy for diagnosis of active cardiac sarcoidosis, were included. Semi-quantitative values of hypermetabolic lesions were derived from all visualized organ system and were compared to daily corticosteroid dose at 6 months.

Results

 Of the 16 patients, 81.3% (13/16) of the patients showed extracardiac involvement. The lesion with the greatest SUV was identified in the heart in 11 patients (68.7%), in the liver in 1 patient (6.3%), and in lymph nodes in 4 patients (25%). The maximum SUV across all visualized organ systems including the heart were 8.8 ± 3.1 for the patients with corticosteroid dose ≤ 10 mg and 12.5 ± 3.3 for those with > 10 mg (P = 0.04). Metabolic volume and TLG across all visualized organ systems or any values in the heart alone showed no significant statistical difference between the two groups.

Conclusions

Maximum SUV across all involved organ-systems of the chest and upper abdomen, not that of the heart alone, could be a predictor of treatment course of steroid therapy at 6 months in patients with active cardiac sarcoidosis.

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Revisiting the Logan plot to account for non-negligible blood volume in brain tissue

Abstract

Background

Reference tissue-based quantification of brain PET data does not typically include correction for signal originating from blood vessels, which is known to result in biased outcome measures. The bias extent depends on the amount of radioactivity in the blood vessels. In this study, we seek to revisit the well-established Logan plot and derive alternative formulations that provide estimation of distribution volume ratios (DVRs) that are corrected for the signal originating from the vasculature.

Results

New expressions for the Logan plot based on arterial input function and reference tissue were derived, which included explicit terms for whole blood radioactivity. The new methods were evaluated using PET data acquired using [¹¹C]raclopride and [¹⁸F]MNI-659. The two-tissue compartment model (2TCM), with which signal originating from blood can be explicitly modeled, was used as a gold standard.

DVR values obtained for [¹¹C]raclopride using the either blood-based or reference tissue-based Logan plot were systematically underestimated compared to 2TCM, and for [¹⁸F]MNI-659, a proportionality bias was observed, i.e., the bias varied across regions. The biases disappeared when optimal blood-signal correction was used for respective tracer, although for the case of [¹⁸F]MNI-659 a small but systematic overestimation of DVR was still observed.

Conclusions

The new method appears to remove the bias introduced due to absence of correction for blood volume in regular graphical analysis and can be considered in clinical studies. Further studies are however required to derive a generic mapping between plasma and whole-blood radioactivity levels.

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Expression Profiling of the MAP Kinase Phosphatase Family Reveals a Role for DUSP1 in the Glioblastoma Stem Cell Niche

Abstract

The dual specificity phosphatases (DUSPs) constitute a family of stress-induced enzymes that provide feedback inhibition on mitogen-activated protein kinases (MAPKs) critical in key aspects of oncogenic signaling. While described in other tumor types, the landscape of DUSP mRNA expression in glioblastoma (GB) remains largely unexplored. Interrogation of the REpository for Molecular BRAin Neoplasia DaTa (REMBRANDT) revealed induction (DUSP4, DUSP6), repression (DUSP2, DUSP7–9), or mixed (DUSP1, DUSP5, DUSP10, DUSP15) DUSP transcription of select DUSPs in bulk tumor specimens. To resolve features specific to the tumor microenvironment, we searched the Ivy Glioblastoma Atlas Project (Ivy GAP) repository, which highlight DUSP1, DUSP5, and DUSP6 as the predominant family members induced within pseudopalisading and perinecrotic regions. The inducibility of DUSP1 in response to hypoxia, dexamethasone, or the chemotherapeutic agent camptothecin was confirmed in GB cell lines and tumor-derived stem cells (TSCs). Moreover, we show that loss of DUSP1 expression is a characteristic of TSCs and correlates with expression of tumor stem cell markers in situ (ABCG2, PROM1, L1CAM, NANOG, SOX2). This work reveals a dynamic pattern of DUSP expression within the tumor microenvironment that reflects the cumulative effects of factors including regional ischemia, chemotherapeutic exposure among others. Moreover, our observation regarding DUSP1 dysregulation within the stem cell niche argue for its importance in the survival and proliferation of this therapeutically resistant population.

http://ift.tt/2vPYeqW

Influence of optimizing protocol choice on the integral dose value in prostate radiotherapy planning by dynamic techniques – Pilot study

Publication date: September–October 2017
Source:Reports of Practical Oncology & Radiotherapy, Volume 22, Issue 5
Author(s): Anna Zaleska, Krzysztof Bogaczyk, Tomasz Piotrowski
AimThe purpose of this study was to compare the values of integral dose, calculated for treatment plans of dynamic radiotherapy techniques prepared with two different optimization protocols.BackgroundDelivering radiation by IMRT, VMAT and also HT techniques has an influence on the low dose deposition of large areas of the patient body. Delivery of low dose can induce injury of healthy cells. In this situation, a good solution would be to reduce the area, which receives a low dose, but with appropriate dose level for the target volume.Materials and methodsTo calculate integral dose values of plans structures, we used 90 external beam radiotherapy plans prepared for three techniques (intensity modulated radiotherapy, volumetric modulated arc therapy and helical tomotherapy). One technique includes three different geometry combinations. 45 plans were prepared with classic optimization protocol and 45 with rings optimization protocol which should reduce the low doses in the normal tissue.ResultsDifferences in values of the integral dose depend on the geometry and technique of irradiation, as well as optimization protocol used in preparing treatment plans. The application of the rings optimization caused the value of normal tissue integral dose (NTID) to decrease.ConclusionIt is possible to limit the area of low dose irradiation and reduce NTID in dynamic techniques with the same clinical constraints for OAR and PTV volumes by using an optimization protocol other than the classic one.



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Relevance of Bone Marrow Transplantation Nursing Training Program at King Faisal Specialist Hospital and Research Centre for National and Regional Nurses

Publication date: Available online 18 August 2017
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Reguia Belkhedim




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First person: Rüdiger Hehlmann

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Second primary cancers deadlier for younger patients

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Issue Information – TOC

http://ift.tt/2wo2wIo

Nivolumab improves survival for patients with advanced lung cancer

http://ift.tt/2uXyabX

Physical ExeRcise Following Esophageal Cancer Treatment (PERFECT) study: design of a randomized controlled trial

Abstract

Background

Following esophagectomy, esophageal cancer patients experience a clinically relevant deterioration of health-related quality of life, both on the short- and long-term. With the currently growing number of esophageal cancer survivors, the burden of disease- and treatment-related complaints and symptoms becomes more relevant. This emphasizes the need for interventions aimed at improving quality of life. Beneficial effects of post-operative physical exercise have been reported in several cancer types, but so far comparable evidence in esophageal cancer patients is lacking. The aim of this study is to investigate effects of physical exercise on health-related quality of life in esophageal cancer patients following surgery.

Methods

The Physical ExeRcise Following Esophageal Cancer Treatment (PERFECT) study is a multicenter randomized controlled trial including 150 esophageal cancer patients after surgery with curative intent. Patients are randomly allocated to an exercise group or usual care group. The exercise group participates in a 12-week combined aerobic and resistance exercise program, supervised by a physiotherapist near the patient's home-address. In addition, participants in the exercise group are requested to be physically active for at least 30 min per day, every day of the week. Participants allocated to the usual care group are asked to maintain their habitual physical activity pattern. The primary outcome is health-related quality of life (EORTC-QLQ-C30). Secondary outcomes include esophageal cancer specific quality of life, fatigue, anxiety and depression, sleep quality, work-related factors, cardiorespiratory fitness (VO_2peak), muscle strength, physical activity, malnutrition risk, anthropometry, blood markers, recurrence of disease and survival. All questionnaire outcomes, diaries and accelerometers are assessed at baseline, post-intervention (12 weeks post-baseline) and 24 weeks post-baseline. Physical fitness, anthropometry and blood markers are assessed at baseline and post-intervention. In addition, adherence and safety are monitored throughout the exercise program.

Discussion

This randomized controlled trial investigates effects of physical exercise versus usual care in esophageal cancer patients after surgery. As the design of the exercise program closely resembles daily practice, this study can contribute both to evidence on effects of exercise in esophageal cancer patients, and to potential implementation strategies.

Trial registration

Trial registration:Netherlands Trial Registry NTR5045

Date of trial registration: January 19th, 2015

Date and version study protocol: February 2017, version 1

http://ift.tt/2vPvdeI

Down-regulation of the tumour suppressor κ-opioid receptor predicts poor prognosis in hepatocellular carcinoma patients

Abstract

Background

Opioid receptors have become increasingly implicated in cancer progression and long-term patient outcomes. However, the expression and significance of the κ-opioid receptor (KOR) in hepatocellular carcinoma (HCC) remain unclear.

Methods

In this study, KOR mRNA expression was analysed by real-time quantitative PCR in 64 pairs of HCC tumour tissues and adjacent non-tumour tissues, and KOR protein expression was analysed by immunohistochemistry in 174 HCC patients. We investigated the correlation between KOR expression and clinicopathological parameters to illustrate the potential prognostic significance of KOR expression in HCC.

Results

KOR mRNA expression was significantly down-regulated in 79.69% (51 of 64) of the HCC tumour samples, and KOR expression in tumour tissue was significantly lower than that in adjacent non-tumour tissues (P < 0.001). ROC curve analysis showed that KOR mRNA expression yielded AUC of 0.745, for the detection of HCC patients. Low KOR mRNA expression in HCC was correlated with aggressive clinicopathological parameters, such as tumour size (P = 0.015), differentiation grade (P = 0.011), and TNM stage (P = 0.021). Moreover, down-regulation of KOR protein expression in HCC tissues was detected in 174 HCC patients. Similarly, negative KOR protein expression was significantly correlated with aggressive clinicopathological features, such as tumour size (P = 0.002), vascular invasion (P = 0.003), differentiation grade (P = 0.026), and TNM stage (P = 0.030). Furthermore, Kaplan-Meier survival analysis demonstrated that down-regulation of KOR in HCC indicated poor prognosis. KOR deficiency (KOR^T < N) was correlated to a shorter survival rate and an increased recurrence (both P < 0.001). In univariate and multivariate survival analyses, KOR was identified as a promising independent risk factor for both overall survival (OS, both P < 0.001) and recurrence-free survival (RFS, both P < 0.001).

Conclusions

Down-regulation of KOR in HCC tumour tissues has a strong association with poor prognosis and KOR might be a potential tumour suppressor.

http://ift.tt/2vPLrVk

Hypo-fractionated SBRT for localized prostate cancer: a German bi-center single treatment group feasibility trial

Abstract

Background

For prostate cancer treatment, treatment options with minimal side effects are desired. External beam radiation therapy (EBRT) is non-invasive, standard of care and delivered in either conventional fractionation over 8 weeks or with moderate hypo-fractionation over about 5 weeks. Recent advances in radiotherapy technology have made extreme hypo-fractionated stereotactic body radiation therapy (SBRT) of prostate cancer feasible, which has not yet been introduced as a standard treatment method in Germany. Initial results from other countries are promising, but long-term results are not yet available. The aim of this study is to investigate feasibility and effectiveness of SBRT for prostate cancer in Germany.

Methods/design

This German bi-center single group trial (HYPOSTAT) is designed to evaluate feasibility and effectiveness, as measured by toxicity and PSA-response, respectively, of an extreme hypo-fractionated SBRT regimen with five fractions of 7 Gy in treatment of localized low and intermediate risk prostate cancer. The target volume includes the prostate with or without the base of seminal vesicles depending on risk stratification and uncertainty margins that are kept at 3–5 mm. SBRT treatment is delivered with the robotic CyberKnife system, which was recently introduced in Germany. Acute and late toxicity after one year will be evaluated according to Common Terminology Criteria for Adverse Events (CTCAE v. 4.0), Radiation Therapy Oncology Group (RTOG) and International Prostate Symptom Score (IPSS) Scores. The quality of life will be assessed before and after treatment with the EORTC QLQ C30 questionnaire. Hypothesizing that the proportion of patients with grade 2 side effects or higher is less or equal than 2.8%, thus markedly lower than the standard EBRT percentage (17.5%), the recruitment target is 85 patients.

Discussion

The HYPOSTAT trial aims at demonstrating short term feasibility of extreme hypo-fractioned SBRT for the treatment of prostate cancer and might be used as the pilot study for a multi-center multi-platform or for randomized-controlled trials comparing conventional radiotherapy with SBRT for localized prostate cancer in the future. The study concept of patient enrollment, follow up and evaluation by multiple public university clinics and actual patient treatment in dedicated private radiosurgery practices with high-tech radiation equipment is unique for clinical trials.

Study status

The study is ongoing and currently recruiting patients.

Trial registration

Registration number: NCT02635256 (clinicaltrials.gov). Registered 8 December 2015.

http://ift.tt/2xb0Yyl

Retraction Note to: Relationship between inflammatory cytokines and risk of depression, and effect of depression on the prognosis of high grade glioma patients

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The feasibility analysis of omission of elective irradiation to level IB lymph nodes in low-risk nasopharyngeal carcinoma based on the 2013 updated consensus guideline for neck nodal levels

Abstract

Background

Level IB metastasis is rare in nasopharyngeal carcinoma (NPC). The purpose of this study is to investigate the high-risk factors for level IB metastasis and evaluate the feasibility of omission of elective irradiation to level IB in the low-risk subgroups in NPC.

Methods

This retrospective study identified 532 patients with NPC treated by definitive radiation in our institution from 2009 to 2010. Level IB nodes were electively irradiated based on the physician's decision. Diagnostic head and neck MRIs were reviewed. The involvements of nodal levels were evaluated according to 2013 updated guidelines of RTOG. The correlations of level IB metastasis and other factors were studied using Chi-square test and logistic regression model. Log-rank tests were used to compare survival rates. Cox proportional-hazards models were used to evaluate the effect of various factors. Patient-reported xerostomia was recoded in every follow-up and the extents of delayed xerostomia at 1 year post-radiation were compared between those with/without elective level IB irradiation.

Results

N stage, bilateral nodal metastasis, level II involvement, level IIA involvement, level IIA with multiple levels involvement, maximal axial diameter (MAD) of level IIA nodes > 20 mm, MAD of neck lymph nodes > 30 mm, necrosis of level IIA nodes, extracapsular spread of level IIA correlated with level IB metastasis by univariate analysis. In multivariate analysis (MVA), bilateral nodal involvement, MAD of level IIA nodes > 20 mm or extracapsular spread of level IIA nodes, were independent predictive factors for level IB metastasis. Patients without either these factors were denoted low-risk group and the rest high-risk group. Of the low-risk group, there was no significant difference of regional control and overall survival (OS) between those with or without elective irradiation. The percentage of level IB recurrence of those without elective irradiation was 0.46%. Elective level IB irradiation was not significant upon MVA both for regional control and OS. Of the high-risk group, elective level IB irradiation was marginal significant for regional control, but not for OS upon MVA. No regional recurrence located at level IB. Overall, omission of elective irradiation to level IB reduced the mean doses of submandibular glands, but did not improve patient-reported xerostomia.

Conclusion

For patients without high-risk factors of level IB metastasis, omission of elective level IB irradiation did not impair regional control and OS in NPC.

http://ift.tt/2fQEpeW

Metastatic colorectal cancer responsive to regorafenib for 2 years: a case report

Regorafenib is an oral multikinase inhibitor that has been demonstrated as clinically effective in patients with metastatic colorectal cancer in phase III studies. Although disease control was achieved in 40% ...

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Nuances of Morphology in Myelodysplastic Diseases in the Age of Molecular Diagnostics

Abstract

Morphologic dysplasia is an important factor in diagnosis of myelodysplastic syndrome (MDS). However, the role of dysplasia is changing as new molecular genetic and genomic technologies take a more prominent place in diagnosis. This review discusses the role of morphology in the diagnosis of MDS and its interactions with cytogenetic and molecular testing. Recent changes in diagnostic criteria have attempted to standardize approaches to morphologic diagnosis of MDS, recognizing significant inter-observer variability in assessment of dysplasia. Definitive correlates between cytogenetic/molecular and morphologic findings have been described in only a small set of cases. However, these genetic and morphologic tools do play a complementary role in the diagnosis of both MDS and other myeloid neoplasms. Diagnosis of MDS requires a multi-factorial approach, utilizing both traditional morphologic as well as newer molecular genetic techniques. Understanding these tools, and the interplay between them, is crucial in the modern diagnosis of myeloid neoplasms.

http://ift.tt/2wVZybI

Patient-Reported Outcomes in Myelodysplastic Syndromes and MDS/MPN Overlap Syndromes: Stepping Onto the Stage with Changing Times

Abstract

Quality of life (QOL) and symptom burden are important measures captured by patient-reported outcomes (PROs). Myelodysplastic and myelodysplastic/myeloproliferative (MDS/MPN) neoplasm overlap syndromes are notable for significant morbidity and mortality, including a wide spectrum of physical and psychosocial effects. Thus, the development and application of PROs can provide meaningful information to facilitate communication and assist in follow up care. Disease-specific measures can more accurately reflect the full breadth of functional restrictions and symptoms. While traditional endpoints include remission, relapse, and survival rates, adoption of PROs in myeloid neoplasm clinical trials can facilitate drug approval. Integration of PROs in myeloid neoplasms is an important measure to capture QOL and symptoms, which can improve disease management.

http://ift.tt/2vJlXuv

Immune Dysfunction in Non-Hodgkin Lymphoma: Avenues for New Immunotherapy-Based Strategies

Abstract

Purpose of this Review

The present review focuses on key aspects of non-Hodgkin lymphoma (NHL) evasion of immune surveillance and how these can be leveraged to devise effective immunotherapy strategies.

Recent Findings

In recent years, significant progress has been made in the field of cancer immunotherapy. In particular, the remarkable clinical results of anti-programmed death (PD)-1/PD-ligand (L)1 antibodies are revolutionizing the treatment approach to multiple solid and hematologic tumors. In patients with B or T cell NHL, immune checkpoint inhibition has produced mixed results, in part owing to the high complexity of the tumor immune microenvironment. Rationally designed combinations of PD-1/PD-L1 blockers with other antibody- or cell-based immunotherapies, or small molecules are being tested in clinical trials.

Summary

A clearer understanding of the relationship between host immune dysfunction and cancer development and growth, often referred to as cancer "immuno-editing," has enabled the discovery and successful clinical application of several immunotherapeutic agents, such as the immune checkpoint inhibitors (ICI).

http://ift.tt/2wVT38Z

Erratum to: Signal intensity at unenhanced T1-weighted magnetic resonance in the globus pallidus and dentate nucleus after serial administrations of a macrocyclic gadolinium-based contrast agent in children

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In-hospital clinical outcomes after upper gastrointestinal surgery: Data from an international observational study

Publication date: Available online 18 August 2017
Source:European Journal of Surgical Oncology (EJSO)
Author(s): Tamas Szakmany, James Ditai, Mikhail Kirov, Denis Protsenko, Babatunde Osinaike, Aurelien Venara, Nicolas Demartines, Martin Hubner, Rupert M. Pearse, John R. Prowle
AimsPrevious research suggests that patients undergoing upper gastrointestinal surgery are at high risk of poor postoperative outcomes. The aim of our study was to describe patient outcomes after elective upper gastrointestinal surgery at a global level.MethodsProspective analysis of data collected during an international seven-day cohort study of 474 hospitals in 27 countries. Patients undergoing elective upper gastrointestinal surgery were recruited. Outcome measures were in-hospital complications and mortality at 30-days. Results are presented as n(%) and odds ratios with 95% confidence intervals.Results2139 patients were included, of whom 498 (23.2%) developed one or more postoperative complications, with 30 deaths (1.4%). Patients with complications had longer median hospital stay 11 (6-18) days vs. 5 (2-10) days. Infectious complications were most frequent, affecting 368 (17.2%) patients. 328 (15.3%) patients were admitted to critical care postoperatively, of whom 161 (49.1%) developed a complication with 14 deaths (4.3%). In a multivariable logistic regression model we identified age (OR 1.02 [1.01-1.03]), American Society of Anesthesiologists physical status III (OR 2.12 [1.44-3.16]) and IV (OR 3.23 [1.72-6.09]), surgery for cancer (OR 1.63 [1.27-2.11]), open procedure (OR 1.40 [1.10-1.78]), intermediate surgery (OR 1.75 [1.12-2.81]) and major surgery (OR 2.65 [1.72-4.23]) as independent risk factors for postoperative complications. Patients undergoing major surgery for upper gastrointestinal cancer experienced twice the rate of complications compared to those undergoing other procedures (224/578 patients [38.8%] versus 274/1561 patients [17.6%]).ConclusionsComplications and death are common after upper gastrointestinal surgery. Patients undergoing major surgery for cancer are at greatest risk.



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The prognostic impact of combined pulmonary fibrosis and emphysema in patients with clinical stage IA non-small cell lung cancer

Abstract

Purpose

We evaluated the long-term outcomes of clinical stage IA non-small cell lung cancer (NSCLC) patients with combined pulmonary fibrosis and emphysema (CPFE) who underwent lobectomy.

Methods

We reviewed the chest computed tomography (CT) findings and divided the patients into normal, fibrosis, emphysema and CPFE groups. We evaluated the relationships among the CT findings, the clinicopathological findings and postoperative survival.

Results

The patients were classified into the following groups based on the preoperative chest CT findings: normal lung, n = 187; emphysema, n = 62; fibrosis, n = 8; and CPFE, n = 17. The patients with CPFE were significantly older, more likely to be men and smokers, had a higher KL-6 level and lower FEV 1.0% value and had a higher rate of squamous cell carcinoma. The 5-year overall survival (OS) and disease-free survival rates were as follows: normal group, 82.5 and 76.8%; emphysema group, 80.0 and 74.9%; fibrosis group, 46.9 and 50%; and CPFE group, 36.9 and 27.9%, respectively (p < 0.01). A univariate and multivariate analysis determined that the pathological stage and CT findings were associated with OS.

Conclusions

CPFE is a significantly unfavorable prognostic factor after lobectomy, even in early-stage NSCLC patients with a preserved lung function.

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Targeted next-generation sequencing for analyzing the genetic alterations in atypical adenomatous hyperplasia and adenocarcinoma in situ

Abstract

Purpose

Atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS) have been defined as preinvasive pulmonary adenocarcinoma lesions according to the 2015 World Health Organization lung adenocarcinoma classification. We aimed to search for the most common gene mutations in patients with AAH and AIS and investigate the distinctions between the two groups at the molecular level.

Methods

We performed targeted next-generation sequencing on 18 cases with AAH and 28 cases with AIS to screen for mutations with the Ion Torrent Oncomine Solid Tumor DNA panel. ALK and ROS1 fusions were detected by real-time PCR.

Results

Forty-six mutations were identified in 29 cases (76.1%), including 9 (50%) of 18 cases with AAH and 20 (71.4%) of 28 cases with AIS, in the following genes: EGFR, BRAF, KRAS, ERBB2, TP53, and FGFR3. The mutations in EGFR, BRAF, KRAS, ERBB2, and TP53 genes were more common in AIS lesions than in AAH lesions, whereas the FGFR3 gene was more frequently mutated in AAH compared to AIS. ALK and ROS1 fusions were not detected in any of the lesions.

Conclusions

Based on the molecular evidence, the proposal that AAH and AIS are preinvasive lesions of pulmonary adenocarcinomas is of great significance, and it is necessary to distinguish AAH from AIS. Our study provided insights into the genetic alterations in the early stage of lung adenocarcinoma, which could be beneficial for the pathologic diagnosis and early detection of these lesions.

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Serum calcitonin reference values for calcium stimulation tests by electrochemiluminescence immunoassay in Japanese men with non-medullary thyroid carcinoma

Abstract

Purpose

Calcitonin is the most sensitive tumor marker of medullary thyroid carcinoma (MTC) and a calcium stimulation test is used to improve this sensitivity. In Japan, the electrochemiluminescence immunoassay (ECLIA) is currently the only test performed to measure serum calcitonin. There is a gender difference in the reference value of serum calcitonin; however, a reference upper limit for use with ECLIA has been reported only for women, but not for men.

Methods

We conducted the calcium stimulation test using ECLIA in 21 men with non-medullary thyroid carcinoma (non-MTC), before and after total thyroidectomy.

Results

Preoperatively, the basal calcitonin values were within normal limits in all patients. They increased to a mean value of 37.6 pg/mL after calcium stimulation, and we calculated that the reference upper limit was 83.7 pg/mL. The stimulation test results after total thyroidectomy showed undetectable basal and stimulated calcitonin values in every patient (<0.5 pg/mL).

Conclusions

To our knowledge, this is the first study to calculate reference values for this stimulation test using an ECLIA in men with non-MTC. We propose that men can be regarded as biochemically cured or as having normal serum calcitonin values when the stimulated calcitonin values obtained by ECLIA are <83.7 pg/mL before and <0.5 pg/mL after total thyroidectomy.

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Depth of response predicts the clinical outcome of advanced HER2-positive gastric cancer to trastuzumab-based first-line chemotherapy

Abstract

Purpose

Accumulating evidence suggests that response-related parameters such as depth of response (DpR) might be associated with survival in colorectal cancer, which has not been shown in gastric cancer. This study aimed to evaluate whether DpR was associated with clinical outcomes in HER2-positive AGC patients treated with trastuzumab-based chemotherapy.

Methods

Fifty-seven HER2-positive AGC patients who were treated with trastuzumab in combination with fluoropyrimidines plus cisplatin therapy as first-line treatment were retrospectively enrolled. DpR was defined as the percent maximal tumor shrinkage of target lesions observed at the lowest point compared with baseline. The cutoff DpR level to discriminate better survival was based on receiver-operating characteristic curve analysis. Association of DpR with progression-free survival (PFS) and overall survival (OS) was assessed using the multivariable Cox proportional hazards model.

Results

Median DpR level was 56.8% (range −37.9 to 100%). In multivariate models adjusted for relevant variables, DpR, as a dichotomized variable with a cutoff level of 50% and a continuous variable, was significantly associated with PFS (hazard ratio [HR] 0.39 and 0.97; 95% confidence interval [CI] 0.22–0.68 and 0.96–0.98) and OS (HR 0.38 and 0.98; 95% CI 0.21–0.70 and 0.97–0.99). Clinically meaningful differences in PFS (median, 9.8 vs. 4.1 months; p < 0.001) and OS (median, 24.7 vs. 12.8 months; p < 0.001) were observed between the high DpR (≥50%) and the low DpR groups (<50%).

Conclusions

Higher DpR predicted favorable outcomes following trastuzumab-based chemotherapy in HER2-positive AGC patients.

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Functional IGF1R variant predicts breast cancer risk in women with preeclampsia in California Teachers Study

Abstract

Purpose

Hypertension in pregnancy has been associated with decreased future risk of breast cancer in many but not all studies. In the Marin Women's Study, pregnancy-induced hypertension was shown to interact with the T allele of a functional IGF1R gene variant, rs2016347, to result in lower breast density, as well as decreased breast cancer risk. Our objective was to explore these findings in a larger sample of women from the California Teachers Study (CTS).

Methods

The CTS cohort consists of over 130,000 female educators. DNA was available from a nested case–control study, which included 2,030 non-Hispanic white women who developed breast cancer and 1,552 controls. The current study included all participants from the case–control group with a self-reported history of preeclampsia (80 cases/57 controls).

Results

Comparing TT to GG genotypes revealed adjusted odds ratios of 0.38 (CI 0.13, 1.14) for all invasive breast cancers, 0.26 (CI 0.07, 0.89) for hormone receptor-positive (HR+) breast cancers, 0.15 (CI 0.04, 0.56) for those with age at first birth (AFB) < 30, and 0.10 (CI 0.02, 0.49) for those with AFB < 30 and HR+ breast cancers. Trend analysis yielded p values of 0.09, 0.03, 0.005, and 0.004 respectively, suggesting a biological effect for each T allele.

Conclusion

Study findings indicate that the T allele of IGF1R variant rs2016347 is associated with a significant reduction in breast cancer risk in women with a history of preeclampsia, most marked for HR+ breast cancer and in women with AFB < 30.

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mTOR co-targeting strategies for head and neck cancer therapy

Abstract

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. There is an urgent need to develop effective therapeutic approaches to prevent and treat HNSCC. Recent deep sequencing of the HNSCC genomic landscape revealed a multiplicity and diversity of genetic alterations in this malignancy. Although a large variety of specific molecules were found altered in each individual tumor, they all participate in only a handful of driver signaling pathways. Among them, the PI3K/mTOR pathway is the most frequently activated, which plays a central role in cancer initiation and progression. In turn, targeting of mTOR may represent a precision therapeutic approach for HNSCC. Indeed, mTOR inhibition exerts potent anti-tumor activity in HNSCC experimental systems, and mTOR targeting clinical trials show encouraging results. However, advanced HNSCC patients may exhibit unpredictable drug resistance, and the analysis of its molecular basis suggests that co-targeting strategies may provide a more effective option. In addition, although counterintuitive, emerging evidence suggests that mTOR inhibition may enhance the anti-tumor immune response. These new findings raise the possibility that the combination of mTOR inhibitors and immune oncology agents may provide novel precision therapeutic options for HNSCC.

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Myocardial regenerative therapy using a scaffold-free skeletal-muscle-derived cell sheet in patients with dilated cardiomyopathy even under a left ventricular assist device: a safety and feasibility study

Abstract

Background and purpose

Despite promising experimental results, clinically, intramyocardial myoblast injection failed to reverse remodeling and it induced arrhythmogenicity. In contrast, scaffold-free skeletal muscle-derived cell (SC) sheets attenuated cardiac dysfunction and arrhythmogenicity via paracrine effects. We report the first clinical trial of SC sheet implantation (SCSI) conducted in four patients with dilated cardiomyopathy (DCM) supported by a left ventricular assist device (LVAD).

Methods

SC sheets were made from muscle fibers and multi-layered SC sheets were applied to the left ventricular (LV) anterolateral surface via left thoracotomy.

Results

There were no major cardiac adverse events. Ventricular arrhythmia decreased in all except one patient, in whom global LV function did not improve. The LV volume decreased and LV ejection fraction improved in all except the same patient. Systolic wall thickening, reflecting regional wall motion, improved in the sheet-implanted areas, and vessels in the LV apex increased in all patients, suggesting angiogenesis. The LVAD was successfully removed in two patients.

Conclusions

SCSI induced reverse remodeling and angiogenesis, and improved LV function, allowing LVAD removal in two patients, although functional recovery failed to improve in the one non-responder, even with angiogenesis. SCSI is a promising regenerative therapy for DCM patients responsive to this strategy, even with LVAD assistance.

http://ift.tt/2uNugGO

Mind-Body Therapies in Cancer: What Is the Latest Evidence?

Abstract

Purpose of Review

Many people living with cancer use complementary therapies, and some of the most popular are mind-body therapies (MBTs), including relaxation and imagery, hypnosis, yoga, meditation, tai chi and qigong, and art therapies. The efficacy of these modalities was reviewed by assessing recent findings in the context of cancer care.

Recent Findings

These therapies show efficacy in treating common cancer-related side effects, including nausea and vomiting, pain, fatigue, anxiety, depressive symptoms and improving overall quality of life. Some also have effects on biomarkers such as immune function and stress hormones. Overall studies lack large sample sizes and active comparison groups. Common issues around clearly defining treatments including standardizing treatment components, dose, intensity, duration and training of providers make generalization across studies difficult.

Summary

MBTs in cancer care show great promise and evidence of efficacy for treating many common symptoms. Future studies should investigate more diverse cancer populations using standardized treatment protocols and directly compare various MBTs to one another.

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Methodological Considerations for Disentangling a Risk Factor's Influence on Disease Incidence versus Post-Diagnosis Survival: The Example of Obesity and Breast and Colorectal Cancer Mortality in the Women's Health Initiative

ABSTRACT

Often, studies modeling an exposure's influence on time to disease-specific death from study enrollment are incorrectly interpreted as if based on time to death from disease diagnosis. We studied 151,996 post-menopausal women without breast or colorectal cancer in the Women's Health Initiative with weight and height measured at enrollment (1993-1998). Using Cox regression models, we contrast hazard ratios (HR) from two time-scales and corresponding study subpopulations: time to cancer death after enrollment among all women and time to cancer death after diagnosis among only cancer survivors. Median follow-up from enrollment to diagnosis/censoring was 13-years for both breast (7633 cases) and colorectal cancer (2290 cases). Follow-up from diagnosis to death/censoring was 7-years for breast and 5-years for colorectal cancer. In analyses of time from enrollment to death, body mass index (BMI)≥35-kg/m² versus 18.5-<25-kg/m² was associated with higher rates of cancer mortality: HR=1.99; 95%CI: 1.54, 2.56 for breast cancer (p-trend <0.001) and HR=1.40; 95%CI: 1.04, 1.88 for colorectal cancer (p-trend=0.05). However, in analyses of time from diagnosis to cancer death, trends indicated no significant association (for BMI≥35-kg/m², HR=1.25; 95%CI: 0.94, 1.67 for breast [p-trend=0.33] and HR=1.18; 95%CI: 0.84, 1.86 for colorectal cancer [p-trend=0.39]). We conclude that a risk factor that increases disease incidence will increase disease-specific mortality. Yet, its influence on post-diagnosis survival can vary, and requires consideration of additional design and analysis issues such as selection bias. Quantitative tools allow joint modeling to compare an exposure's influence on time from enrollment to disease incidence and time from diagnosis to death. This article is protected by copyright. All rights reserved.

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Blood and tissue-based tumor genomics: a battle royale or match made in heaven?

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Inguinal canal spermatic cord leiomyoma presenting as an incarcerated inguinal hernia

Leiomyoma is a benign neoplasm originating from smooth muscle cells and is most commonly seen in the uterus, followed by the small bowel and oesophagus. We report a rare case of a 41-year-old male patient with a spermatic cord leiomyoma that presented as an inguinal canal mass mimicking an irreducible inguinal hernia without scrotal involvement. This report highlights the rare presentation and workup of an inguinal mass, importance of intraoperative decision making based on operative findings and the significance of postoperative pathology findings.

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Hypersegmented neutrophils and oval macrocytes in the setting of B12 deficiency and pancytopaenia

Vitamin B₁₂ deficiency is a recognised pathology in several populations, with a particular prevalence in an older adult population. We present two cases whereby vitamin B₁₂ deficiency is the causative factor in marked pancytopaenia. Oval macrocytosis and hypersegmented neutrophils were noted on both peripheral blood samples, which are a characteristic finding in macrocytic anaemia due to B₁₂ deficiency. Distinct underlying pathologies were identified in both cases; food-cobalamin malabsorption and pernicious anaemia. Parenteral vitamin B₁₂ supplementation resulted in a marked reticulocytosis and rapid improvement of haematological indices in both cases. We present this series to serve as a reminder that B₁₂ deficiency can present as life-threatening pancytopaenia.It has has multiple underlying pathologies,defined risk populations and has characteristic blood film findings which can guide investigations, diagnosis and treatment.

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Mega-giant coronary aneurysm: antithrombotic therapy is an option

A 69-year-old man with a history of hypercholesterolaemia presented to the emergency department with atypical chest pain. Physical examination was normal and ECG showed no evidence of ischaemic changes. Laboratory studies were notable for a D-dimer level of 1842 ng/mL (reference value <500 ng/mL) and the troponin I level was normal.

Chest X-ray was normal. Chest CT angiography ruled out a pulmonary embolism but showed a giant and extensive aneurysm of the right coronary artery (RCA) up to 45 mm in diameter with a partly thrombosed lumen and evidence of right ventricle compression on four-chamber view (figures 1 and 2). The volume of the aorta and the RCA appeared similar (figure 3). Doppler echocardiography did not demonstrate right or left heart haemodynamic abnormalities.

Figure 1

Coronary CT angiography in four-chamber view, evidence of external diameter with arrow and coronary lumen with head arrow.

...

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Prognostic implication of the primary tumor location in early-stage breast cancer: focus on lower inner zone

Abstract

Background

The aim of this study was to investigate the prognostic significance of tumor location of lower inner zone (LIZ) on the survival of patients with early-stage breast cancer.

Methods

We retrospectively identified 961 breast cancer patients from Jan 2000 to Apr 2016 from hospital database. We evaluated overall survival (OS) and disease-free survival (DFS) in patients with tumors in and outside LIZ. Subgroup analyses were performed according to clinicopathological characteristics and treatment strategies.

Results

A total of 838 cases were finally included. Patients with tumor location of LIZ showed significantly lower survival rates than tumors in other sites in terms of DFS (p = 0.028) but not OS (p = 0.106). When stratified into subgroups, tumors in LIZ retained a significant worse prognosis in DFS in patients with HER-2-negative, high ki-67 expression breast cancers, those who received neoadjuvant chemotherapy, axillary nodal negative patients, and patients with lymphovascular invasion. Univariate and multivariate analyses suggested that tumor location of LIZ was an independent prognostic factor for DFS (p = 0.022).

Conclusions

Our results suggested that tumor location of LIZ was an independent adverse prognostic factor for DFS in patients with early-stage breast cancer. Multicenter studies with larger sample size are needed to confirm the conclusion and anatomical experiments are desired to elaborate the mechanism.

http://ift.tt/2vIOVun