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10/31/23

Cancer chemotherapies have improved prognosis in cancer patients, resulting in a large and rapidly increasing number of cancer survivors.

Abstract

Cancer chemotherapies have improved prognosis in cancer patients, resulting in a large and rapidly increasing number of cancer survivors. "Onco-cardiology" or "cardio-oncology" is a new discipline for addressing the unanticipated cardiac side effects of newly developed cancer drugs. Lapatinib, a tyrosine kinase inhibitor suppressing the epidermal growth factor receptor and ErbB2, has been used in advanced or metastatic breast cancer treatment. Reportedly, lapatinib has induced cardiovascular adverse events including QT-interval prolongation and heart failure. However, they have not been predicted by preclinical studies. Hence, a new method to assess the tyrosine kinase inhibitor-induced adverse effects needs to be established. Here, we intravenously administered lapatinib to halothane-anaesthetised dogs, evaluating cardiohemodynamic, electrophysiological, and echocardiographic profiles for pharmacological safety assessments. We intravenously administered lapatinib to chronic atrioventricular block beagle dogs to assess its proarrhythmic potential. The therapeutic concentration of lapatinib significantly increased total peripheral vascular resistance, QT, QTc, monophasic action potential (MAP)90(sinus), MAP90(CL400), effective refractory period, and plasma concentration of cardiac troponin I (cTnI), suggesting that lapatinib prolonged the ventricular repolarization without inducing lethal ventricular arrhythmia. Careful monitoring of plasma cTnI concentration and an electrocardiogram could be supportive biomarkers, predicting the onset of lapatinib-induced cardiovascular adverse events.

PMID: 31959820 [PubMed - in process]

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Management of cardiac disease in cancer patients throughout oncological treatment: ESMO consensus recommendations.

Ann Oncol. 2020 Feb;31(2):171-190

Authors: Curigliano G, Lenihan D, Fradley M, Ganatra S, Barac A, Blaes A, Herrmann J, Porter C, Lyon AR, Lancellotti P, Patel A, DeCara J, Mitchell J, Harrison E, Moslehi J, Witteles R, Calabro MG, Orecchia R, de Azambuja E, Zamorano JL, Krone R, Iakobishvili Z, Carver J, Armenian S, Ky B, Cardinale D, Cipolla CM, Dent S, Jordan K, ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org

Background Patients with cancer and severe aortic stenosis are often ineligible for surgical aortic valve replacement (SAVR). Patients with

Abstract

Background Patients with cancer and severe aortic stenosis are often ineligible for surgical aortic valve replacement (SAVR). Patients with cancer may likely benefit from emerging transcatheter aortic valve replacement (TAVR), given its minimally invasive nature. Methods and Results The US-based National Inpatient Sample was queried between 2012 and 2015 using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), codes to identify all hospitalized adults (aged ≥50 years), who had a primary diagnosis of aortic stenosis. We examined the effect modification of cancer on the relative use rate, outcomes, and dispositions associated with propensity-matched cohort TAVR versus SAVR. Overall, 47 295 TAVRs (22.6% comorbid cancer) and 113 405 SAVRs (15.2% comorbid cancer) were performed among admissions with aortic stenosis between 2012 and 2015. In the year 2015, patients with cancer saw relatively higher rates of TAVR use compared with SAVR (relative use rateTAVR versus relative use rateSAVR, 67.8% versus 57.2%; P<0.0001).<0.001)

PMID: 31960751 [PubMed - in process]

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The Role of Angiotensin-Converting Enzyme Inhibitors and β-Blockers in Primary Prevention of Cardiac Dysfunction in Breast Cancer Patients.

J Am Heart Assoc. 2020 Jan 21;9(2):e015327

Authors: Brown SA, Okwuosa TM, Barac A, Volgman AS

PMID: 31960742 [PubMed - in process]

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Multimodality Cardiac Imaging in the Era of Emerging Cancer Therapies.

J Am Heart Assoc. 2020 Jan 21;9(2):e013755

Authors: Biersmith MA, Tong MS, Guha A, Simonetti OP, Addison D

PMID: 31960741 [PubMed - in process]

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Reverse Cardio-Oncology: Cancer Development in Patients With Cardiovascular Disease.

J Am Heart Assoc. 2020 Jan 21;9(2):e013754

Authors: Aboumsallem JP, Moslehi J, de Boer RA

PMID: 31960736 [PubMed - in process]

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Precise safety pharmacology studies of lapatinib for onco-cardiology assessed using in vivo canine models.

Sci Rep. 2020 Jan 20;10(1):738

Authors: Ando K, Wada T, Cao X

The Agency for Healthcare Research and Quality, in partnership with the American College of Surgeons and the Johns Hopkins

Abstract

The Agency for Healthcare Research and Quality, in partnership with the American College of Surgeons and the Johns Hopkins Medicine Armstrong Institute for Patient Safety and Quality, has developed the Safety Program for Improving Surgical Care and Recovery (ISCR), which is a national effort to disseminate best practices in perioperative care to more than 750 hospitals across multiple procedures in the next 5 years. The program will integrate evidence-based processes central to enhanced recovery and prevention of surgical site infection, venous thromboembolic events, catheter-associated urinary tract infections with socioadaptive interventions to improve surgical outcomes, patient experience, and perioperative safety culture. The objectives of this review are to evaluate the evidence supporting anesthesiology components of colorectal (CR) pathways and to develop an evidence-based CR protocol for implementation. Anesthesiology protocol components were identified through review of existing CR enhanced recovery pathways from several professional associations/societies and expert feedback. These guidelines/recommendations were supplemented by evidence made further literature searches. Anesthesiology protocol components were identified spanning the immediate preoperative, intraoperative, and postoperative phases of care. Components included carbohydrate loading, reduced fasting, multimodal preanesthesia medication, antibiotic prophylaxis, blood transfusion, intraoperative fluid management/goal-directed fluid therapy, normothermia, a standardized intraoperative anesthesia pathway, and standard postoperative multimodal analgesic regimens.

PMID: 29649026 [PubMed - indexed for MEDLINE]

13:29

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Immune Checkpoint Inhibitor Myocarditis: Pathophysiological Characteristics, Diagnosis, and Treatment.

J Am Heart Assoc. 2020 Jan 21;9(2):e013757

Authors: Palaskas N, Lopez-Mattei J, Durand JB, Iliescu C, Deswal A

PMID: 31960755 [PubMed - in process]

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Contemporary Trends and Outcomes of Percutaneous and Surgical Aortic Valve Replacement in Patients With Cancer.

J Am Heart Assoc. 2020 Jan 21;9(2):e014248

Authors: Guha A, Dey AK, Arora S, Cavender MA, Vavalle JP, Sabik JF, Jimenez E, Jneid H, Addison D

Venous thromboembolism (VTE) is a common complication of cancer. Its treatment is challenging because of the high risk for both VTE

Abstract

Venous thromboembolism (VTE) is a common complication of cancer. Its treatment is challenging because of the high risk for both VTE recurrence and bleeding. Evidence is particularly scarce for patients with hematological malignancies. This review aims to summarize new developments in anticoagulation for the prevention and treatment of VTE in patients with active cancer, largely derived from the formal introduction of direct anticoagulants (DOACs) in this population. We then offer our recommendations for the thromboprophylaxis and treatment of VTE in patients with hematological disorders (mature lymphoid disorders, plasma cell disorders, myeloproliferative neoplasms, myelodysplastic syndrome and acute leukemia/stem cell transplant). We conclude by emphasizing the lack of high-quality evidence in a majority of these settings, caution about the use of DOACs in clinical situations where evidence is lacking and, finally, note the importance of involving patients in the decision-making process.

PMID: 31960713 [PubMed - as supplied by publisher]

12:03

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Evidence Review Conducted for the Agency for Healthcare Research and Quality Safety Program for Improving Surgical Care and Recovery: Focus on Anesthesiology for Colorectal Surgery.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--tools.ovid.com-images-wklogo.jpg Related Articles

Evidence Review Conducted for the Agency for Healthcare Research and Quality Safety Program for Improving Surgical Care and Recovery: Focus on Anesthesiology for Colorectal Surgery.

Anesth Analg. 2019 05;128(5):879-889

Authors: Ban KA, Gibbons MM, Ko CY, Wick EC, Cannesson M, Scott MJ, Grant MC, Wu CL

BACKGROUND: Thrombosis is the formation of a blood clot, or thrombus, inside of a blood vessel. Pediatric patients with cancer are

Abstract

BACKGROUND: Thrombosis is the formation of a blood clot, or thrombus, inside of a blood vessel. Pediatric patients with cancer are at a higher risk of developing a thrombus because of their underlying disease, as well as their treatment and supportive care. Thrombosis can lead to significant morbidity, such as pulmonary embolism, in pediatric patients with cancer.

OBJECTIVES: The purpose of this study is to identify risk factors for developing a thrombus among pediatric patients with cancer, along with treatment and prevention protocols. This study also examines the clinical nurse's role in preventing thrombosis and caring for pediatric patients who present with thrombosis.

METHODS: The thrombosis literature was reviewed to identify risk factors, treatment regimens, and strategies for prevention.

FINDINGS: Thrombosis in pediatric patients with cancer requires management of potential complications so that cancer treatment may continue.

PMID: 31961846 [PubMed - in process]

12:03

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Recent developments and persisting challenges in the prevention and treatment of venous thromboembolism in patients with hematological malignancies.

Leuk Lymphoma. 2020 Jan 21;:1-15

Authors: Sorigue M, Cañamero E, Siguenza P, Nomdedeu M, López-Núñez JJ

BACKGROUND: Idiopathic hypertrophic pachymeningitis is a rare inflammatory condition with diffuse thickening of the dura mater,

Abstract

BACKGROUND: Idiopathic hypertrophic pachymeningitis is a rare inflammatory condition with diffuse thickening of the dura mater, which may cause a compressive effect or vascular compromise.

CASE DESCRIPTION: A 40-year-old Chinese man presented with persistent headache for 6 months and a sudden epileptic seizure 2 days ago. Magnetic resonance imaging demonstrated a large (71 × 34 × 27 mm) extra-axial mass at the right frontal convexity with severe edema mimicking meningioma. The lesion and peripheral dura mater showed contrast enhancement. Additionally, the skull near the lesion was eroded. Meningioma was diagnosed, and the patient underwent surgery. During the operation, we found the lesion texture was very tough, and the superior sagittal sinus was occluded. Histopathologic findings revealed a large number of infiltrated lymphocytes with fibrosis and microabscess formation; intracranial idiopathic hypertrophic pachymeningitis was diagnosed. Follow-up magnetic resonance imaging performed 3 months after surgery demonstrated the enhancement was notably alleviated.

CONCLUSIONS: Idiopathic hypertrophic pachymeningitis should be part of the differential diagnosis of some cases of meningioma.

PMID: 30965168 [PubMed - indexed for MEDLINE]

22 January 2020

12:03

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Thrombosis: Risk Factors Among Pediatric Patients With Cancer.

Clin J Oncol Nurs. 2020 Feb 01;24(1):58-64

Authors: Newman GM

Introduction: Venous thromboembolism (VTE) is a major cause of morbidity and mortality worldwide. Prior to this decade, treatment options

Abstract

Introduction: Venous thromboembolism (VTE) is a major cause of morbidity and mortality worldwide. Prior to this decade, treatment options were limited to warfarin or parenteral agents. The emergence of the direct oral anticoagulants (DOACs) offers patients a more convenient and accessible alternative. Apixaban (Eliquis®) is an oral, direct factor Xa inhibitor that is approved for the acute treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) as well as for the reduction in the risk of recurrent DVT and PE following initial therapy. Like other DOACs, apixaban has predictable pharmacological properties including fixed dosing, few drug interactions and no requirement for routine anticoagulation monitoring.Areas Covered: This article reviews results from preclinical and healthy volunteer studies that illustrate the noteworthy properties of apixaban such as a proportional dose-response relationship, low daily fluctuation in plasma concentrations, and safety over a 10-fold dosing range. Additionally, the large phase III trials evaluating the safety and efficacy of apixaban compared to low molecular weight heparin (LMWH) overlapped with and followed by vitamin K antagonist (VKA) warfarin for the treatment and secondary prevention of VTE will be discussed. The key studies that have led to apixaban's current licensing and use will be highlighted including the trials in the acute treatment of VTE where apixaban demonstrated noninferior efficacy and a reduced risk of bleeding in comparison to VKA, and in extended prophylaxis trials where apixaban reduced the risk of VTE/VTE-related deaths, with no increased risk of relevant bleedings in comparison to placebo. This review also will provide an overview of special populations where future areas of research is needed.Expert Commentary: Apixaban offers several advantages over historical therapy for the treatment and secondary prevention of VTE and is currently considered and widely used in many countries, along with other DOACs, as first line therapy for this indication. Importantly, there are many populations in which the use of apixaban has not been extensively studied. Large clinical trials had a low representation of patients > 75 years old, with cancer, low or high body weight, or poor renal function. Likewise, there is a dearth of data on pediatric patients and patients with a history of heparin-induced thrombocytopenia or identified forms of thrombophilia. Additional comparator studies on anticoagulation reversal involving andexanet alfa are also necessary to further assess its ability to sustain hemostasis and its potential for prothrombotic risk.

PMID: 31958251 [PubMed - as supplied by publisher]

15:18

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Idiopathic Hypertrophic Pachymeningitis Mimicking Meningioma with Occlusion of Superior Sagittal Sinus: Case Report and Review of Literature.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles

Idiopathic Hypertrophic Pachymeningitis Mimicking Meningioma with Occlusion of Superior Sagittal Sinus: Case Report and Review of Literature.

World Neurosurg. 2019 Jul;127:534-537

Authors: Yao A, Jia L, Wang B, Zhang J, Zhang J, Xu B

Patients with cancer are at an increased risk of symptomatic venous thromboembolism (VTE). In addition, an increasing number

Abstract

Patients with cancer are at an increased risk of symptomatic venous thromboembolism (VTE). In addition, an increasing number of patients with incidental thromboembolic events have been recorded in clinical practice. Therapeutic anticoagulation is crucial to prevent thrombus progression and reduce risk of recurrence; however, this comes at the price of an increased bleeding risk, which necessitates a personalised approach to choose the most appropriate type of therapy. Over the last decade, low-molecular-weight heparin has been the preferred anticoagulant agent for patients with cancer-associated thrombosis due to better efficacy and similar safety profile compared with vitamin K antagonists. While direct oral anticoagulants (DOAC) have emerged as new option for treatment of VTE in a general population, only limited data have been available specifically for patients with cancer until recently. Randomised, controlled trials have now been published, establishing DOAC as an alternative for the treatment of cancer-associated thrombosis. However, the improvement in the therapeutic armamentarium is accompanied by a number of special considerations. For instance, risk of bleeding is elevated in patients with cancer-associated VTE receiving DOAC, especially in certain tumour types (eg, gastrointestinal), and no guidance exists regarding their use in patients with severe thrombocytopaenia. Furthermore, DOAC are prone to certain drug-drug interactions and their effect might be altered due to nausea and vomiting in patients receiving chemotherapy. Here, we provide guidance on how to treat cancer-associated VTE and how new evidence from randomised controlled trials can be implemented in clinical practice. There are still clinical scenarios where robust evidence is lacking and treatment recommendations are based on extrapolations from other populations or expert opinion only. Therefore, additional research in special subpopulations is needed to optimise management of patients in challenging clinical scenarios.

PMID: 31958288 [PubMed - in process]

15:18

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A comprehensive evaluation of apixaban in the treatment of venous thromboembolism.

Expert Rev Hematol. 2020 Jan 20;:

Authors: Koehl JL, Hayes BD, Al-Samkari H, Rosovsky R

Several cardiovascular effects have been attributed to carfilzomib in the recent literature. These side effects must be recognized promptly

Abstract

Several cardiovascular effects have been attributed to carfilzomib in the recent literature. These side effects must be recognized promptly by treating physicians and pharmacists. Special attention is required in patients with pre-existing cardiac conditions, liver function abnormalities and/or advanced age. This is the first report of a severe left atrial enlargement due to carfilzomib use in the setting of multiple myeloma. This condition improved dramatically seven months after cessation of carfilzomib. The authors discuss further various cardiac and vascular abnormalities linked with carfilzomib in the medical literature. Prompt withdrawal of this agent is essential in these cases as it may prevent dismal outcomes.

PMID: 30636528 [PubMed - indexed for MEDLINE]

15:18

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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ASCO updated recommendations for preventing and treating VTE in adults with cancer.

Ann Intern Med. 2020 Jan 21;172(2):JC2

Authors: Stockler MR

PMID: 31958816 [PubMed - in process]

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How I treat cancer-associated thrombosis.

ESMO Open. 2020 Jan;5(1):

Authors: Moik F, Pabinger I, Ay C

PURPOSE: Anticancer drugs may cause cardiovascular toxicities, including QT interval prolongation. Niraparib, a potent and selective once-daily oral poly (ADP-ribose)

Abstract

PURPOSE: Anticancer drugs may cause cardiovascular toxicities, including QT interval prolongation. Niraparib, a potent and selective once-daily oral poly (ADP-ribose) polymerase inhibitor, is approved as a maintenance therapy in platinum-sensitive recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer (EOC). Here, we present the effects of niraparib on cardiac repolarization, and the correlation between changes in baseline QT interval corrected by Fridericia's formula (ΔQTcF) and niraparib plasma concentrations.

METHODS: Patients with EOC from the NOVA study (subset of n = 15), the food effect NOVA substudy (n = 17), and a QTc substudy (n = 26) underwent intensive electrocardiographic (ECG) monitoring that included triplicate ECG testing on Day 1 at baseline (predose) and at 1, 1.5, 2, 3, 4, 6, and 8 h postdose concurrent with time-matched blood sampling for determination of niraparib plasma concentrations. All patients received once-daily 300-mg niraparib until disease progression or toxicity.

RESULTS: Across the 3 substudies, the upper limit of the two-sided 90% confidence interval (CI) of ΔQTcF was ≤ 10 ms at every postdose timepoint, with a maximum upper limit of 4.3 ms, which indicates no clinically meaningful effect on QTc prolongation. No statistically significant relationship between ΔQTcF and niraparib plasma concentration was observed (estimated slope: 0.0049; 95% CI: - 0.0020, 0.0117; P = 0.164). There were no clinically relevant changes in other ECG parameters that could be attributable to niraparib.

CONCLUSION: Niraparib administration at the recommended daily dose of 300 mg for EOC is not associated with clinically relevant alteration of ECGs, including QTc prolongation.

PMID: 30680521 [PubMed - indexed for MEDLINE]

12:22

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Severe left atrial enlargement due to carfilzomib use in multiple myeloma.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--journals.sagepub.com-pb-assets-sage-pubmed-sage.png Related Articles

Severe left atrial enlargement due to carfilzomib use in multiple myeloma.

J Oncol Pharm Pract. 2019 Dec;25(8):2045-2048

Authors: Dasanu CA, Plaxe SC, Popescu IM, Gupta V, Sontz E, Codreanu I

Doxorubicin (DOX), a wide-spectrum chemotherapeutic agent, is recognized to have cardiotoxic side effects when it is applied in hematological

Abstract

Doxorubicin (DOX), a wide-spectrum chemotherapeutic agent, is recognized to have cardiotoxic side effects when it is applied in hematological diseases and solid tumor management. However, the mechanisms behind the DOX-induced anomaly of vascular homeostasis remain mostly elusive. qRT-PCR and immumohistochemical staining indicated cardiac increase of miR-526b-3p, and decrease of CD31 and CD34 in DOX-treated mice. The regulatory function of miR-526b-3p on cardiac function and cardiac microvessel density was detected via the transfection of miR-526b-3p mimics or inhibitor into Human Umbilical Vein Endothelial Cells (HUVECs) and the administration of rAAV in mice. HUVECs proliferation, apoptosis, tube formation, and migration were inspected by EdU, flow cytometry, tube formation and transwell assays. MiR-526b-3p was anti-proliferative but apoptosis-initiating in HUVECs, and aggravated cardiac abnormalities caused by DOX. Mechanically, the relationship between miR-526b-3p and VEGFA was disclosed by qRT-PCR. VEGFA and STAT3 interaction was confirmed by ChIP and luciferase reporter assay. MiR-526b-3p targeted STAT3 to reduce VEGFA transcription. We designed rescue assays and presented that the negative effects of miR-526b-3p on cardiac dysfunction and HUVECs were rescued by VEGFA reintroduction in DOX-affected mice. Overall, miR-526b-3p accelerated doxorubicin-induced cardiotoxicity through modulating STAT3/VEGFA, highlighting that targeting miR-526b-3p as a potential method to protect against DOX-induced cardiac dysfunction.

PMID: 31958751 [PubMed - as supplied by publisher]

12:22

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Effect of niraparib on cardiac repolarization in patients with platinum-sensitive, recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer.

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Effect of niraparib on cardiac repolarization in patients with platinum-sensitive, recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancer.

Cancer Chemother Pharmacol. 2019 04;83(4):717-726

Authors: Moore K, Chan JK, Secord AA, Patel MR, Callahan T, Guo W, Zhang ZY

Doxorubicin is a widely used cancer therapeutic, but its effectiveness is limited by cardiotoxic side effects. Evidence suggests cardiotoxicity is

Abstract

Doxorubicin is a widely used cancer therapeutic, but its effectiveness is limited by cardiotoxic side effects. Evidence suggests cardiotoxicity is due not to doxorubicin, but rather its metabolite, doxorubicinol. Identification of the enzymes responsible for doxorubicinol formation is important in developing strategies to prevent cardiotoxicity. In this study, the contributions of three murine candidate enzymes to doxorubicinol formation were evaluated: carbonyl reductase 1 (Cbr1), carbonyl reductase 3 (Cbr3), and thioredoxin reductase 1 (Tr1). Analyses with purified proteins revealed that all three enzymes catalyzed doxorubicin-dependent NADPH oxidation, but only Cbr1 and Cbr3 catalyzed doxorubicinol formation. Doxorubicin-dependent NADPH oxidation by Tr1 was likely due to redox cycling. Subcellular fractionation results showed that doxorubicin-dependent redox cycling activity was primarily microsomal, whereas doxorubicinol-forming activity was exclusively cytosolic, as were all three enzymes. An immunoclearing approach was used to assess the contributions of the three enzymes to doxorubicinol formation in the complex milieu of the cytosol. Immunoclearing Cbr1 eliminated 25% of the total doxorubicinol-forming activity in cytosol, but immunoclearing Cbr3 had no effect, even in Tr1 null livers that overexpressed Cbr3. The immunoclearing results constituted strong evidence that Cbr1 contributed to doxorubicinol formation in mouse liver, but that enzymes other than Cbr1 also played a role, a conclusion supported by ammonium sulfate fractionation results, which showed that doxorubicinol-forming activity was found in fractions that contained little Cbr1. In conclusion, the results show that Cbr1 accounts for 25% of the doxorubicinol-forming activity in mouse liver cytosol but that the majority of the doxorubicinol-forming activity remains unidentified. SIGNIFICANCE STATEMENT: Earlier genetic and drug inhibition results suggested Cbr1 plays a dominant role in converting chemotherapeutic doxorubicin to cardiotoxic doxorubicinol, but a new immunoclearing approach described herein shows that Cbr1 accounts for only 25% of the doxorubicinol-forming activity in mouse liver cytosol, that two other candidate enzymes Cbr3 and Tr1 play no role, and that the majority of the activity remains unidentified. The results suggest that targeting Cbr1 is necessary but not sufficient to eliminate doxorubicinol-associated cardiotoxicity; identification and targeting of the additional doxorubicinol-forming activity is an important next challenge.

PMID: 31955137 [PubMed - as supplied by publisher]

21 January 2020

12:22

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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MiR-526b-3p mediates doxorubicin-induced cardiotoxicity by targeting STAT3 to inactivate VEGFA.

Biomed Pharmacother. 2020 Jan 17;123:109751

Authors: Zhang L, Liu L, Li X

Low molecular weight heparins (LMWHs) and direct oral anticoagulants (DOACs) are among the recommended treatment options

Abstract

Low molecular weight heparins (LMWHs) and direct oral anticoagulants (DOACs) are among the recommended treatment options for cancer-associated thrombosis (CAT) in the 2019 National Comprehensive Care Network guidelines. Little is known about the current utilization of DOACs in CAT patients, particularly on the inpatient to outpatient therapy transition. This study assessed real-world treatment patterns of CAT in hospital/ED in adult cancer patients (≥ 18 years) diagnosed with CAT during a hospital visit in IQVIA's Hospital Charge Data Master database between July 1, 2015 and April 30, 2018, and followed their outpatient medical and pharmacy claims to evaluate the initial inpatient/ED and outpatient anticoagulants received within 3 months post-discharge. Results showed that LMWH and unfractionated heparin (UFH) were the most common initial inpatient/ED CAT treatments (35.2% and 27.4%, respectively), followed by DOACs (9.6%); 20.8% of patients received no anticoagulants. Most DOAC patients remained on DOACs from inpatient/ED to outpatient settings (71.4%), while 24.1%, 43.5%, and 0.1% of patients treated with LMWH, warfarin, or UFH respectively, remained on the same therapy after discharge. In addition, DOACs were the most common initial post-discharge outpatient therapy. Outpatient treatment persistence and adherence appeared higher in patients using DOACs or warfarin versus LMWH or UFH. This study shows that DOACs are used as an inpatient/ED treatment option for CAT, and are associated with less post-discharge treatment switching and higher persistence and adherence. Further research generating real-world evidence on the role of DOACs to help inform the complex CAT clinical treatment decisions is warranted.

PMID: 31955338 [PubMed - as supplied by publisher]

15:55

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Carbonyl reductase 1 plays a significant role in converting doxorubicin to cardiotoxic doxorubicinol in mouse liver, but the majority of the doxorubicinol-forming activity remains unidentified.

Drug Metab Dispos. 2020 Jan 18;:

Authors: Breysse DH, Boone RM, Long CM, Merrill ME, Schaupp CM, White CC, Kavanagh TJ, Schmidt EE, Merrill GF

BACKGROUND: As breast reconstructive microsurgeons increase their available flap techniques with experience, the need for stacked

Abstract

BACKGROUND: As breast reconstructive microsurgeons increase their available flap techniques with experience, the need for stacked and multiple flaps may generate an improved aesthetic outcome. The authors present their institutional experience of using single versus stacked free flap breast reconstruction.

METHODS: ONE THOUSAND SEVENTY: flaps were performed on 509 patients from 2010 to 2018 by two senior surgeons at a single university hospital. Three hundred eighty-eight flaps were either stacked profunda artery perforator (PAP) flaps, four-flap flaps [bilateral PAP plus bilateral deep inferior epigastric perforator (DIEP) flap], or double-pedicle DIEP/superficial inferior epigastric perforator flaps. Six hundred eighty-two flaps were either unilateral or bilateral DIEP or PAP flap (one flap per breast). Demographics, patient comorbidities, and flap complications were compared between the two groups.

RESULTS: Of the 509 patients, 359 underwent single DIEP or PAP flap (one flap per breast) and 150 patients underwent stacked free flaps. The stacked flap group had statistically lower body mass index, higher rates of radiation therapy, longer procedure time, smaller flaps, higher deep venous thrombosis rates, and higher take-back rates compared with the single flap group. There were no statistical differences in the rates of flap loss (2.2 percent in stacked flaps versus 1.1 percent in single flaps), wound complication, hematoma, or pulmonary embolism.

CONCLUSIONS: Autologous breast reconstruction is the gold standard for natural and durable breast reconstruction, often giving superior aesthetic outcomes and higher patient satisfaction. However, the true success of autologous breast reconstruction is limited to the amount of tissue available to provide total breast reconstruction. This study shows that stacked flap breast reconstruction is safe and has similar complication rates as single-flap breast reconstruction.

CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID: 31461004 [PubMed - indexed for MEDLINE]

14:50

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Sex differences in the trajectory of glomerular filtration rate in pediatric and murine sickle cell anemia.

Blood Adv. 2020 Jan 28;4(2):263-265

Authors: Kasztan M, Aban I, Hande SP, Pollock DM, Lebensburger JD

PMID: 31951651 [PubMed - in process]

20 January 2020

14:20

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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pubmed: caandvteortroorpul

Inpatient and outpatient treatment patterns of cancer-associated thrombosis in the United States.

J Thromb Thrombolysis. 2020 Jan 18;:

Authors: Guo JD, Hlavacek P, Poretta T, Wygant G, Lane D, Gorritz M, Wang X, Chen CC, Wade RL, Pan X, Rajpura J, Stwalley B, Rosenblatt L

BACKGROUND: BPI-9016M is a novel small-molecule inhibitor that simultaneously targets both c-Met and AXL tyrosine kinases

Abstract

BACKGROUND: BPI-9016M is a novel small-molecule inhibitor that simultaneously targets both c-Met and AXL tyrosine kinases. This phase I study aimed to determine the maximum tolerated dose (MTD), safety, pharmacokinetics, and antitumor activity of BPI-9016M in Chinese patients with advanced non-small cell lung cancer (NSCLC).

METHODS: Over the dose range of 100 mg to 800 mg, eligible patients were administered with a single dose of 9016M tablet and received 7 days of pharmacokinetics evaluation, followed by continuous dose administration (QD dosing, 28 days). Standard "3 + 3" dose escalations were performed.

RESULTS: Twenty NSCLC patients were treated. All patients experienced at least one adverse event (AE), of which treatment-related adverse events (TRAEs) were reported in 17 (85.0%) patients. The most common TRAEs were alanine transaminase (ALT) elevation (60%), bilirubin increased (40%), dysgeusia (40%), constipation (30%), hypertension (25%), and palmar-plantar erythrodysesthesia syndrome (15%). The TRAEs of grade 3 or higher during treatment were hypertension (15%), pulmonary embolism (5%), and laryngeal pain (5%). No dose-limiting toxicity (DLT) was observed, and the MTD was not reached. The median time to Cmax ranged from 2.0 to 3.5 h, and the plasma concentration of BPI-9016M declined rapidly after Tmax fitting a single-compartment model. The mean AUC0-72 h of M1 and M2-2, main metabolites of BPI-9016M, were 4.8-6.6 folds and 4.1-9.8 folds higher than that of BPI-9016M, respectively. Exposure to BPI-9016M, M1, and M2-2 reached moderate saturation at 600 mg. Among 19 evaluable patients, 1 had a partial response and 10 patients had stable disease.

CONCLUSION: BPI-9016M showed favorable safety and pharmacokinetic profiles, and no DLT was observed at doses up to 800 mg once daily. The promising antitumor activity in Chinese NSCLC patients supports further development of this tyrosine kinase inhibitor.

TRIAL REGISTRATION: Clinical Trial ID: NCT02478866, registered May 21, 2015.

PMID: 31948451 [PubMed - in process]

13:25

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Comparative Analysis of Single versus Stacked Free Flap Breast Reconstruction: A Single-Center Experience.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--tools.ovid.com-images-wklogo.jpg Related Articles

Comparative Analysis of Single versus Stacked Free Flap Breast Reconstruction: A Single-Center Experience.

Plast Reconstr Surg. 2019 09;144(3):369e-377e

Authors: Haddock NT, Cho MJ, Teotia SS

BACKGROUND: Testosterone Replacement Therapy (TRT) is indicated for symptomatic male hypogonadism. However, the safety

Abstract

BACKGROUND: Testosterone Replacement Therapy (TRT) is indicated for symptomatic male hypogonadism. However, the safety and efficacy profiles across different ethnicities for long term TRT remain unclear.

OBJECTIVE: To measure the impact of ethnicity on various biochemical parameters following Testosterone Undecanoate (TU) replacement.

METHOD: A retrospective analysis of 50 male patients treated with TU from 2006 to 2017 in a large secondary care centre was performed. Changes in total testosterone, PSA, haematocrit, haemoglobin, total cholesterol, low density lipoprotein (LDL) over eight years of treatment were analysed. Wilcoxon rank sum test was used to assess differences in these parameters between Caucasians and South Asians.

RESULTS: 31 Caucasians (age: median (IQR) 55.0 years (49.0-68.0); total duration of follow up 6.1 years (2.9-9.3) and 19 South Asians (age: median (IQR) 52.0 years (38.0-69.0); duration of follow up 6.5 years (1.3-8.4) were treated with TU during the study period. There was no significant difference in total testosterone levels between the two ethnicities. We noted a higher free and bioavailable testosterone in South Asians compared to Caucasians, albeit within their reference range. PSA was higher in Caucasians compared to South Asians at two and eight years of TU therapy. After one year of TRT, haematocrit was higher in South Asians compared to Caucasians at one year, whereas LDL and total cholesterol were significantly higher in Caucasians than South Asians.

CONCLUSIONS: Caucasians have a tendency towards increased PSA, total cholesterol and LDL compared to South Asians with TU replacement therapy. There is a higher increment of haematocrit in South Asians following one year of TU replacement therapy. All biochemical changes following TRT were within the respective reference ranges suggesting no apparent risk of prostate cancer and venous thromboembolism.

PMID: 31943322 [PubMed - as supplied by publisher]

18 January 2020

13:25

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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First-in-human phase I study of BPI-9016M, a dual MET/Axl inhibitor, in patients with non-small cell lung cancer.

J Hematol Oncol. 2020 Jan 16;13(1):6

Authors: Hu X, Zheng X, Yang S, Wang L, Hao X, Cui X, Ding L, Mao L, Hu P, Shi Y

Colon perforation is most common in patients with colorectal cancer and diverticulitis. It is one of the causes of the so-called "acute abdomen"

Abstract

Colon perforation is most common in patients with colorectal cancer and diverticulitis. It is one of the causes of the so-called "acute abdomen". Herein do we present a case in which dyspnea was the main symptom of colon perforation.

A CASE REPORT: A 62-year-old woman was urgently admitted to the hospital due to dyspnea and nonspecific chest pain. On examination quite vesicular sound with crepitations and massive legs edema were noticed. Performed tests included: an ECG showing no features of fresh myocardial infarction, myocardial enzymes not specific to acute coronary syndromes, a chest X-ray revealing peribronchial thickening in the lower lobes, bilateral supradiaphragmatic signs of atelectasis, fibrosis and small areas of consolidation, blood levels of D-dimer heightened to 577 μg/l, CRP to 41 mg/l. Differential diagnosis consisted of a chest angio-CT, which ruled out pulmonary embolism, but confirmed the presence of pneumomediastinum. Further diagnostic process included an abdominal CT. A 70 millimeter parasigmoidal abscess was revealed with signs of gastrointestinal perforation. The patient underwent an emergency operation. After opening the peritoneum perforation of the sigmoid colon and an abscess in the sigmoid mesocolon lower to the perforation area were confirmed.

CONCLUSIONS: Perforation of the gastrointestinal tract may lead to pneumomediastinum and appearance of dyspnea.

PMID: 31945024 [PubMed - in process]

17:01

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Long term testosterone undecanoate replacement therapy: impact of ethnicity.

Clin Endocrinol (Oxf). 2020 Jan 13;:

Authors: Kempegowda P, Quinn LM, Chandan JS, Shepherd L, Kauser S, Rahim A, Bates A

BACKGROUND: Haemostatic activation and hypercoagulability are frequently observed in patients with metastatic colorectal

Abstract

BACKGROUND: Haemostatic activation and hypercoagulability are frequently observed in patients with metastatic colorectal cancer (mCRC), increase risk of venous thromboembolism (VTE) and have been implicated in tumour proliferation and progression. To date, the association of haemostatic biomarkers with oncologic outcomes including overall survival (OS), progression free survival (PFS) and disease control rate (DCR) is incompletely understood.

METHODS: Within the framework of the Vienna Cancer and Thrombosis Study, a prospective observational cohort study, we conducted an exploratory analysis to investigate the association of six known biomarkers of haemostasis with oncologic outcomes in 99 patients with mCRC prior to chemotherapy initiation.

RESULTS: Patients with high levels of factor VIII activity (FVIII), D-dimer, prothrombin fragment 1 + 2 (F1 + 2) and fibrinogen (defined as levels >75th percentile) had significantly shorter median OS than patients with lower levels. Elevation of four biomarkers was associated with mortality in multivariable analysis, adjusting for age, sex, number of metastatic sites and VTE (hazard ratio [95% CI] for death per doubling of levels: FVIII: 2.06 [1.28-3.30]; sP-selectin: 1.55 [1.07-2.24]; D-dimer: 1.40 [1.18-1.65]; F1 + 2: 1.64 [1.10-2.46]). Patients with elevated levels had numerically shorter median PFS across all markers and disease control rate (DCR) was significantly smaller in those with high levels of FVIII and F1 + 2 (adjusted odds ratio [95% CI] for DCR per doubling of levels: 0.23 [0.09-0.62] and 0.36 [0.16-0.82]) compared to patients with lower levels.

CONCLUSION: Specific elevated haemostatic biomarkers are associated with higher mortality and partially with worse response to chemotherapy in patients with mCRC.

PMID: 31945589 [PubMed - as supplied by publisher]

17:01

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Pneumomediastinum as a complication of colon perforation - a case report.

Pol Merkur Lekarski. 2019 Dec 27;47(282):226-228

Authors: Pachowska K, Perlik M, Kałuża B, Sobiecka A, Walecki J, Franek E

Using the 'Korona' cava filter in a total of 1345 oncological patients revealed regularity of a change in the shape of the inferior

Abstract

Using the 'Korona' cava filter in a total of 1345 oncological patients revealed regularity of a change in the shape of the inferior vena cava at the level of implantation. This made it feasible to determine one of the causes of long-term complications following implantation of other models of cava filters. The absence of clinically significant complications in the remote period after using this model of cava filter made it possible to implant it for a longer period, which is of special importance in oncological patients.

PMID: 31855211 [PubMed - in process]

14:19

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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14:19

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pubmed: ctoall&ca or conall

Double Jeopardy: Cancer and Heart Failure.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles

Double Jeopardy: Cancer and Heart Failure.

J Card Fail. 2019 07;25(7):522-523

Authors: Nohria A

PMID: 31063826 [PubMed - in process]

17:01

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Haemostatic biomarkers for prognosis and prediction of therapy response in patients with metastatic colorectal cancer.

Thromb Res. 2020 Jan 07;187:9-17

Authors: Moik F, Posch F, Grilz E, Scheithauer W, Pabinger I, Prager G, Ay C

The ACS established an online risk calculator to help surgeons make patient-specific estimates of postoperative morbidity and

Abstract

The ACS established an online risk calculator to help surgeons make patient-specific estimates of postoperative morbidity and mortality. Our objective was to assess the accuracy of the ACS-NSQIP calculator for estimating risk after curative intent resection for primary GI neuroendocrine tumors (GI-NETs). Adult patients with GI-NET who underwent complete resection from 2000 to 2017 were identified using a multi-institutional database, including data from eight academic medical centers. The ability of the NSQIP calculator to accurately predict a particular outcome was assessed using receiver operating characteristic curves and the area under the curve (AUC). Seven hundred three patients were identified who met inclusion criteria. The most commonly performed procedures were resection of the small intestine with anastomosis (N = 193, 26%) and partial colectomy with anastomosis (N = 136, 18%). The majority of patients were younger than 65 years (N = 482, 37%) and ASA Class III (N = 337, 48%). The most common comorbidities were diabetes (N = 128, 18%) and hypertension (N = 395, 56%). Complications among these patients based on ACS NSQIP definitions included any complication (N = 132, 19%), serious complication (N = 118, 17%), pneumonia (N = 7, 1.0%), cardiac complication (N = 1, 0.01%), SSI (N = 80, 11.4%), UTI (N = 17, 2.4%), venous thromboembolism (N = 18, 2.5%), renal failure (N = 16, 2.3%), return to the operating room (N = 27, 3.8%), discharge to nursing/rehabilitation (N = 22, 3.1%), and 30-day mortality (N = 9, 1.3%). The calculator provided reasonable estimates of risk for pneumonia (AUC = 0.721), cardiac complication (AUC = 0.773), UTI (AUC = 0.716), and discharge to nursing/rehabilitation (AUC = 0.779) and performed poorly (AUC < 0.7) for all other complications Fig. 1). The ACS-NSQIP risk calculator estimates a similar proportion of risk to actual events in patients with GI-NET but has low specificity for identifying the correct patients for many types of complications. The risk calculator may require modification for some patient populations.

PMID: 31908214 [PubMed - in process]

12:48

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[Use of 'Korona' cava filter in oncological patients].

Angiol Sosud Khir. 2019;25(4):139-145

Authors: Cherkasov VA, Dolgushin BI, Andreev IG, Somonova OV

Doxorubicin (DOX) is an anthracycline widely used in cancer therapy and in particular in breast cancer treatment. The treatment with DOX

Abstract

Doxorubicin (DOX) is an anthracycline widely used in cancer therapy and in particular in breast cancer treatment. The treatment with DOX appears successful, but it is limited by a severe cardiotoxicity. This work evaluated the in vitro and in vivo anticancer effect of a new formulation of β-cyclodextrin nanosponges containing DOX (BNS-DOX). The BNS-DOX effectiveness was evaluated in human and mouse breast cancer cell lines in vitro in terms of effect on cell growth, cell cycle distribution, and apoptosis induction; and in vivo in BALB-neuT mice developing spontaneous breast cancer in terms of biodistribution, cancer growth inhibition, and heart toxicity. BNS-DOX significantly inhibited cancer cell proliferation, through the induction of apoptosis, with higher efficiency than free DOX. The breast cancer growth in BALB-neuT mice was inhibited by 60% by a BNS-DOX dose five times lower than the DOX therapeutic dose, with substantial reduction of tumor neoangiogenesis and lymphangiogenesis. Biodistribution after BNS-DOX treatment revealed a high accumulation of DOX in the tumor site and a low accumulation in the hearts of mice. Results indicated that use of BNS may be an efficient strategy to deliver DOX in the treatment of breast cancer, since it improves the anti-cancer effectiveness and reduces cardiotoxicity.

PMID: 31936526 [PubMed]

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17 January 2020

12:48

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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pubmed: caandvteortroorpul

Evaluating the ACS-NSQIP Risk Calculator in Primary GI Neuroendocrine Tumor: Results from the United States Neuroendocrine Tumor Study Group.

Am Surg. 2019 Dec 01;85(12):1334-1340

Authors: Armstrong EA, Beal EW, Lopez-Aguiar AG, Poultsides G, Cannon JG, Rocha F, Crown A, Barrett J, Ronnkleiv-Kelly S, Fields RC, Krasnick BA, Idrees K, Smith PM, Nathan H, Beems MV, Maithel SK, Schmidt CR, Pawlik TM, Dillhoff M

Marine organisms are sources of several natural compounds with potential clinical use. However, only a few marine-based pharmaceuticals hav

Abstract

Marine organisms are sources of several natural compounds with potential clinical use. However, only a few marine-based pharmaceuticals have been approved for use due to limited knowledge on their biological activities. Here, we identified the functional role of fucoidan extracted from Fucus vesiculosus on ovarian cancer. Fucoidan increased the death of ES-2 and OV-90 cells, through a reduction in proliferation, cell cycle arrest, releases of cytochrome c, reactive oxygen species (ROS) generation, and endoplasmic reticulum (ER) stress. Additionally, fucoidan increased the concentration of cytosolic and mitochondrial calcium in both cells. The decrease of cell proliferation was controlled by the inactivation of PI3K and MAPK signaling cascades in ES-2 and OV-90 cells. In a toxicity assay with normal zebrafish larvae, fucoidan did not induce toxicity, cardiotoxicity, development, kinesis, and apoptosis at different concentrations. However, it disrupted tumor formation and vascular development in a zebrafish xenograft model and angiogenesis transgenic (Tg, fli1-eGFP) model, respectively. Collectively, the results indicate that fucoidan may be a novel pharmaceutical for the management of human ovarian cancer.

PMID: 31936539 [PubMed - in process]

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13:41

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Improvement in the Anti-Tumor Efficacy of Doxorubicin Nanosponges in In Vitro and in Mice Bearing Breast Tumor Models.

Cancers (Basel). 2020 Jan 09;12(1):

Authors: Argenziano M, Gigliotti CL, Clemente N, Boggio E, Ferrara B, Trotta F, Pizzimenti S, Barrera G, Boldorini R, Bessone F, Dianzani U, Cavalli R, Dianzani C

Copy number variants (CNVs) are suggested to have a widespread impact on the human genome and phenotypes. To understand the role of CNV

Abstract

Copy number variants (CNVs) are suggested to have a widespread impact on the human genome and phenotypes. To understand the role of CNVs across human diseases, we examine the CNV genomic landscape of 100,028 unrelated individuals of European ancestry, using SNP and CGH array datasets. We observe an average CNV burden of ~650 kb, identifying a total of 11,314 deletion, 5625 duplication, and 2746 homozygous deletion CNV regions (CNVRs). In all, 13.7% are unreported, 58.6% overlap with at least one gene, and 32.8% interrupt coding exons. These CNVRs are significantly more likely to overlap OMIM genes (2.94-fold), GWAS loci (1.52-fold), and non-coding RNAs (1.44-fold), compared with random distribution (P < 1 × 10-3).

PMID: 31937769 [PubMed - in process]

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13:41

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Fucoidan Derived from Fucus vesiculosus Inhibits the Development of Human Ovarian Cancer via the Disturbance of Calcium Homeostasis, Endoplasmic Reticulum Stress, and Angiogenesis.

Mar Drugs. 2020 Jan 09;18(1):

Authors: Bae H, Lee JY, Yang C, Song G, Lim W

Context: Tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) play an indispensable role in the treatment of non

Abstract

Context: Tyrosine kinase inhibitors (TKIs) targeting epidermal growth factor receptor (EGFR) play an indispensable role in the treatment of non-small cell lung cancer (NSCLC), leading to a survival major breakthrough, but there remains no uniform standard for predicting the efficacy of TKI therapy.

Aims: We retrospectively reviewed the use of EGFR-TKIs for advanced NSCLC between January 2009 and December 2017 in a hospital, which 169 patients who treated with first-line TKIs were enrolled.

Subjects and Methods: Multiple clinical factors, including histology, age, and sex, were analyzed. We calculated the tumor shrinkage rate (TSR) by measuring the longest diameters of the main mass by computed tomography (CT) before TKI therapy and the first CT after TKI therapy. We evaluated overall survival (OS) and progression-free survival (PFS) after first-line TKI therapy, and we assessed factors predicting survival using the Kaplan-Meier method.

Results: Eligible patients were sorted into higher (n = 83) and lower (n = 86) TSR groups according to the mean TSR of 0.49%. The 83 patients with a higher TSR had longer PFS and OS than those in the 86 patients with a lower TSR (14.83 vs. 8.40 months, P < 0.001, and 31.03 vs. 20.10 months, P < 0.001, respectively). Multivariate analyses revealed that TSR was an independent predictor of PFS and OS (PFS hazard ratio [HR]: 0.506, P < 0.001, and OS HR: 0.291, P < 0.001).

Conclusions: These cumulative data support that TSR may be an early predictor of the treatment efficacy in NSCLC with EGFR mutations treated with first-line TKIs.

PMID: 31939440 [PubMed - in process]

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13:41

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Rare copy number variants in over 100,000 European ancestry subjects reveal multiple disease associations.

Nat Commun. 2020 Jan 14;11(1):255

Authors: Li YR, Glessner JT, Coe BP, Li J, Mohebnasab M, Chang X, Connolly J, Kao C, Wei Z, Bradfield J, Kim C, Hou C, Khan M, Mentch F, Qiu H, Bakay M, Cardinale C, Lemma M, Abrams D, Bridglall-Jhingoor A, Behr M, Harrison S, Otieno G, Thomas A, Wang F, Chiavacci R, Wu L, Hadley D, Goldmuntz E, Elia J, Maris J, Grundmeier R, Devoto M, Keating B, March M, Pellagrino R, Grant SFA, Sleiman PMA, Li M, Eichler EE, Hakonarson H

Importance: Trastuzumab improves outcomes in patients with ERBB2-positive (formerly HER2) breast cancer but is associated with treatment-

Abstract

Importance: Trastuzumab improves outcomes in patients with ERBB2-positive (formerly HER2) breast cancer but is associated with treatment-induced cardiotoxicity, most commonly manifest by an asymptomatic decline in left ventricular ejection fraction (LVEF). Little is known to date regarding the long-term effects of treatment-induced cardiotoxicity on cardiopulmonary function in patients who survive trastuzumab-treated breast cancer.

Objective: To determine whether treatment-induced cardiotoxicity recovers or is associated with long-term cardiopulmonary dysfunction in survivors of ERBB2-positive breast cancer.

Design, Setting, and Participants: This cross-sectional case-control study enrolled patients with nonmetastatic ERBB2-positive breast cancer after completion of trastuzumab-based therapy (median, 7.0 [interquartile range (IQR), 6.2-8.7] years after therapy) who met 1 of 2 criteria: (1) cardiotoxicity (TOX group) developed during trastuzumab treatment (ie, asymptomatic decrease of LVEF≥10% from baseline to <55%<55,

Main Outcomes and Measures: Speckle-tracking echocardiography and maximal cardiopulmonary exercise testing were performed to measure indices of left ventricular function (including LVEF and global longitudinal strain [GLS]) and peak oxygen consumption (peak VO2).

Results: A total of 57 participants (median age, 60.8 [IQR, 52.7-65.7] years) were included in the analysis. Overall, 38 of 42 patients with breast cancer (90%) were treated with anthracyclines before trastuzumab. Resting mean (SD) LVEF was significantly lower in the TOX group (56.9% [5.2%]) compared with the NOTOX (62.4% [4.0%]) and HC (65.3% [2.9%]) groups; similar results were found for GLS (TOX group, -17.8% [2.2%]; NOTOX group, -19.8% [2.2%]; HC group, -21.3% [1.8%]) (P < .001).< .001).

Conclusions and Relevance: Treatment-induced cardiotoxicity appears to be associated with long-term marked impairment of cardiopulmonary function and may contribute to increased risk of late-occurring cardiovascular disease in survivors of ERBB2-positive breast cancer.

PMID: 31939997 [PubMed - as supplied by publisher]

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13:41

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Tumor shrinkage rate as a potential marker for the prediction of long-term outcome in advanced non-small cell lung cancer treated with first-line tyrosine kinase inhibitors.

J Cancer Res Ther. 2019;15(7):1574-1580

Authors: Yu S, Wang X, Wang X, Wu X, Xu R, Wang X, Zhang X, Zhang C, Chen K, Cheng D, Wenfeng L

BACKGROUND: Primary cytoreduction followed by platinum-based chemotherapy is the primary treatment for advanced ovarian

Abstract

BACKGROUND: Primary cytoreduction followed by platinum-based chemotherapy is the primary treatment for advanced ovarian cancer. However, neoadjuvant chemotherapy followed by interval debulking is an alternative option, particularly in those who may be poor surgical candidates.

OBJECTIVE: The objective of this study was to determine factors associated with short-term, significant perioperative morbidity and mortality for women undergoing surgery for ovarian cancer and to create a nomogram to predict the risk of adverse perioperative outcomes.

STUDY DESIGN: We used the National Surgical Quality Improvement Program database to identify women with ovarian, fallopian tube, or primary peritoneal cancer who underwent surgery from 2011 to 2015. Demographic factors, clinical characteristics, comorbidity, functional status, and the extent of surgery were used to predict the risk of severe perioperative complications or death using multivariable models. Multiple imputation methods were employed for missing data. A nomogram was developed based on the final model. The discrimination ability of the model was assessed with a calibration plot and discrimination concordance index.

RESULTS: We identified a total of 7029 patients. Overall, 5.8% of patients experienced a Clavien-Dindo IV complication, 9.8% of patients were readmitted, 3.0% of patients required a reoperation, and 0.9% of patients died within 30 days. Among the baseline variables assessed, increasing age, emergent surgery, ascites, bleeding disorder, low albumin, higher American Society of Anesthesiology classification score, and a higher extended procedure score were associated with serious perioperative morbidity or mortality. Of these factors, performance of ≥3 cytoreductive procedures (adjusted odds ratio 4.53, 95% confidence interval 3.01-6.82), American Society of Anesthesiology classification score ≥ class 4 (adjusted odds ratio 2.89, 95% confidence interval 1.17-7.14), bleeding disorder (adjusted odds ratio 2.73, 95% confidence interval 1.82-4.10), and age ≥80 years (adjusted odds ratio 2.46, 95% confidence interval 1.66-3.63) were most strongly associated with risk of an event. The final nomogram included the above variables and had an internal discrimination concordance index of 0.71, with accurate predictions in an internal validation set, indicating a 71% correct identification of patients across all possible pairs.

CONCLUSION: Women undergoing surgery for ovarian cancer are at significant risk for the occurrence of adverse perioperative outcomes. Using readily identifiable characteristics, this nomogram can predict adverse outcomes.

PMID: 30771346 [PubMed - indexed for MEDLINE]

13:41

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Long-term Cardiopulmonary Consequences of Treatment-Induced Cardiotoxicity in Survivors of ERBB2-Positive Breast Cancer.

JAMA Cardiol. 2020 Jan 15;:

Authors: Yu AF, Flynn JR, Moskowitz CS, Scott JM, Oeffinger KC, Dang CT, Liu JE, Jones LW, Steingart RM

OBJECTIVE: To examine the use of in-hospital pharmacologic thromboprophylaxis (PTP) in patients undergoing radical cystectomy

Abstract

OBJECTIVE: To examine the use of in-hospital pharmacologic thromboprophylaxis (PTP) in patients undergoing radical cystectomy between 2004 and 2014 and to assess the risk of venous thromboembolism (VTE) across the study period.

MATERIAL AND METHODS: We identified 8322 patients without contraindications to PTP undergoing radical cystectomy in the US using the Premier Healthcare Database. Nonparametric Wilcoxon type test for trend was employed to examine the trend of PTP utilization across the study period. Ensuing, we employed multivariable logistic regression and generalized linear regression models to examine the odds of receiving PTP and the risk of being diagnosed with VTE, respectively.

RESULTS: Based on VTE risk-stratification, the majority of patients (87.8%) qualified as "high-risk." Across the study period the use of PTP increased (Odds ratio 1.02, 95% confidence interval (CI) 1.00-1.03, P = .044), but remained underutilized as the maximum percentage of patients receiving in-hospital PTP did not exceed 58.6%. The risk of VTE did not vary across the study period (risk ratio 0.97, 95%CI 0.92-1.02, P = .178).

CONCLUSION: Utilization of PTP increased throughout the study period, while the risk of VTE did not change. Future studies are necessary to improve implementation of guideline-driven care, as PTP remained underutilized throughout the study period.

PMID: 31586570 [PubMed - indexed for MEDLINE]

12:16

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Development and validation of a risk-calculator for adverse perioperative outcomes for women with ovarian cancer.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles

Development and validation of a risk-calculator for adverse perioperative outcomes for women with ovarian cancer.

Am J Obstet Gynecol. 2019 06;220(6):571.e1-571.e8

Authors: Cham S, Chen L, St Clair CM, Hou JY, Tergas AI, Melamed A, Ananth CV, Neugut AI, Hershman DL, Wright JD

Klippel-Trenaunay syndrome or KTS is a complex vascular syndrome associated with overgrowth occurring as a result o

Abstract

Klippel-Trenaunay syndrome or KTS is a complex vascular syndrome associated with overgrowth occurring as a result of somatic mutations in the PIK3CA gene. Patients are diagnosed on the basis of physical findings, sometimes with supportive imaging, of commonly a segmental anomaly with a cutaneous port-wine stain, lymphatic and venous malformations and overgrowth. The severity of the component vascular malformations and the degree of overgrowth varies from patient to patient which demands care given by a multi-professional team with regular follow-up in a specialist clinic. Some patients may present with acute life-threatening problems, often as a result of veno-thromboembolic events (VTEs) especially following surgical and invasive radiological procedures. Awareness of such problems is vital and prophylactic measures to reduce such risks are paramount. The interventional radiologist is vital to the care team as he/she can undertake procedures including endovascular closure of significant venous anomalies which predispose to such VTEs. Although these procedures can be lengthy and complex, they can now provide a minimally invasive means to reduce the risk from life-threatening and sometimes fatal VTEs. The results however from such interventions will require long-term studies which to date are unavailable.

PMID: 31864529 [PubMed - indexed for MEDLINE]

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Trends in Adherence to Thromboprophylaxis Guideline in Patients Undergoing Radical Cystectomy.

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Trends in Adherence to Thromboprophylaxis Guideline in Patients Undergoing Radical Cystectomy.

Urology. 2020 Jan;135:44-49

Authors: Tully KH, Krimphove MJ, Reese SW, Kibel AS, Noldus J, Krasnow RE, Trinh QD, Sonpavde GP, Chang SL, Mossanen M

Aim of the Study: The role of direct-acting oral anticoagulants in the treatment of venous thromboembolism (VTE)

Abstract

Aim of the Study: The role of direct-acting oral anticoagulants in the treatment of venous thromboembolism (VTE) in cancer patients compared with the current standard of low-molecular-weight heparin (LMWH) treatment remains unclear. This meta-analysis aimed to evaluate the efficacy and safety of direct factor Xa inhibitors compared with those of LMWH in the treatment of cancer-associated VTE.

Materials and Methods: We systematically searched PubMed, EMBASE, Cochrane library, and Web of Science for potential randomized controlled clinical trials and retrospective cohort studies. Data on recurrent VTE (efficacy) and major and minor bleeding events (safety) were extracted, and the odds risks (OR) were analyzed using a random-effect model.

Results: A total of nine studies involving 4208 cancer patients with VTE were included in these analyses. Pooled analysis showed that direct factor Xa inhibitors were significantly superior to LMWH in reducing the risk of recurrent VTE (OR = 0.67; 95% confidence interval [CI]: 0.54-0.82). There was no significant difference in the rate of major bleeding between the direct factor Xa inhibitor and LMWH treatments (OR = 1.25; 95% CI: 0.94-1.65). However, the rate of minor bleeding events was higher when a direct factor Xa inhibitor was used instead of LMWH (OR = 1.80; 95% CI: 1.05-3.07).

Conclusions: Direct factor Xa inhibitors are superior to LMWH in efficacy in the treatment of VTE in cancer patients, and the safety between the two regimens is comparable except for a slightly higher rate of minor bleeding when the former is used.

PMID: 31939435 [PubMed - in process]

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Klippel-Trenaunay Syndrome.

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Klippel-Trenaunay Syndrome.

Tech Vasc Interv Radiol. 2019 Dec;22(4):100634

Authors: John PR

It is uncertain if different immunomodulatory drugs (IMID) pose distinct thrombotic risk in patients with newly diagnosed

Abstract

It is uncertain if different immunomodulatory drugs (IMID) pose distinct thrombotic risk in patients with newly diagnosed multiple myeloma (MM). Among 2397 MM patients from the SEER-Medicare database from 2007 to 2013, 78% received lenalidomide, and 22% received thalidomide. After inverse probability weighting to balance confounders, the 12-month incidences of venous thromboembolism (VTE 10%) and arterial thromboembolism (ATE 5%) were similarly high in both groups. Lenalidomide versus thalidomide had a subdistribution hazard ratio of 1.11 (0.59-2.02) for VTE and a subdistribution hazard ratio of 0.96 (0.45-1.98) for ATE. Overall survival was not significantly different with a hazard ratio of 0.88 (0.60-1.18) for lenalidomide versus thalidomide. Concurrent anticoagulant prophylaxis was infrequently prescribed in < 20% of both groups. Our study demonstrates that despite improvement in myeloma-directed therapy and supportive care, thrombosis remains an important consideration for all IMID-treated MM patients. Appropriate risk stratification and vigilant thromboprophylaxis remain essential to prevent this complication.

PMID: 31773215 [PubMed - indexed for MEDLINE]

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Breast cancer and recurrent thrombosis - Results from prospective single center study.

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Breast cancer and recurrent thrombosis - Results from prospective single center study.

Breast J. 2019 07;25(4):783-785

Authors: Kovac M, Kovac Z, Tomasevic Z, Tomic B, Gvozdenov M, Radojkovic D

PMID: 31079419 [PubMed - indexed for MEDLINE]

16 January 2020

12:16

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Comparison between direct factor Xa inhibitors and low-molecular-weight heparin for efficacy and safety in the treatment of cancer-associated venous thromboembolism: A meta-analysis.

J Cancer Res Ther. 2019;15(7):1541-1546

Authors: Yang M, Li J, Sun R, Wang Y, Xu H, Yang B, Wu X, Yu L

Background: Fluoropyrimidines are mainstay chemotherapeutics in the treatment of gastrointestinal cancers and are also used to treat breast

Abstract

Background: Fluoropyrimidines are mainstay chemotherapeutics in the treatment of gastrointestinal cancers and are also used to treat breast cancer and head and neck cancers. However, 5-flourouracil (5-FU) and capecitabine may induce cardiotoxicity that mostly presents as acute coronary syndromes. We compared the incidence of cardiotoxicity induced by 5-FU and capecitabine in patients with colorectal cancer and sought to identify risk markers for cardiotoxicity.Methods: We reviewed all consecutive patients with colorectal cancer who received 5-FU or capecitabine at one institution in the neoadjuvant (2007-2016), adjuvant (2000-2016) or metastatic setting (2007-2016).Results: Totally, 995 patients received 5-FU and 1241 received capecitabine. The incidence of cardiotoxicity induced by 5-FU was 5.2% [95% confidence interval (CI): 3.8-6.6%] and 4.1% (95% CI: 3.0-5.2%) induced by capecitabine (p = .21). The most common events were angina without ischemia (5-FU: 1.6%, capecitabine: 1.3%, p = .53), angina with ischemia on ECG (5-FU: 0.9%, capecitabine: 0.8%, p = .53), unspecified chest pain (5-FU: 0.9%, capecitabine: 0.6%, p = .34), ST-elevation myocardial infarction (5-FU: 0.5%; capecitabine: 0.4%, p = .76) and non-ST-elevation myocardial infarction (5-FU: 0.7%, capecitabine: 0.5%, p = .50). Cardiac arrest or sudden death occurred in 0.5 and 0.4%, respectively (p = 1). No risk markers for cardiotoxicity induced by 5-FU were identified. In the capecitabine group, ischemic heart disease was a risk marker (odds ratio: 2.9, 95% CI: 1.2-7.0, p = .016).Conclusions: Five percent of patients treated with 5-FU developed cardiotoxicity and 4% treated with capecitabine. Ischemic heart disease was a risk marker for cardiotoxicity induced by capecitabine.

PMID: 31931649 [PubMed - as supplied by publisher]

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Early functional and structural changes of the left atrium in a patient with trastuzumab: related cardiotoxicity.

Minerva Cardioangiol. 2019 Aug;67(4):359-360

Authors: Cerrito LF, Bergamini C, Dolci G, Fiorio E, Ribichini FL

Abstract

PMID: 31347821 [PubMed - indexed for MEDLINE]

15:43

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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The incidence of thromboembolism for lenalidomide versus thalidomide in older patients with newly diagnosed multiple myeloma.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif Related Articles

The incidence of thromboembolism for lenalidomide versus thalidomide in older patients with newly diagnosed multiple myeloma.

Ann Hematol. 2020 Jan;99(1):121-126

Authors: Li A, Wu Q, Warnick G, Li S, Libby EN, Garcia DA, Lyman GH

INTRODUCTION: Although the human epidermal growth factor receptor 2 (HER2) blocker trastuzumab is generally

Abstract

INTRODUCTION: Although the human epidermal growth factor receptor 2 (HER2) blocker trastuzumab is generally well tolerated, cardiotoxicity can be an important therapeutic limitation.

OBJECTIVE: In this prespecified analysis, we compared the cardiac safety of the trastuzumab biosimilar ABP 980 (KANJINTI™) and the trastuzumab reference product (RP; Herceptin®) in the phase III LILAC study (ClinicalTrials.gov identifier NCT01901146).

METHODS: In the neoadjuvant phase of LILAC, after run-in chemotherapy, 725 patients were randomized 1:1 to ABP 980 (n = 364) or trastuzumab RP (n = 361) plus paclitaxel (every 3 weeks [Q3W] or every week [QW]) for four cycles. After surgery, patients continued treatment Q3W for up to 1 year; ABP 980-treated patients continued ABP 980 (ABP 980/ABP 980; n = 364), and trastuzumab RP-treated patients either continued on the RP (trastuzumab RP/trastuzumab RP; n = 190) or switched to ABP 980 (trastuzumab RP/ABP 980; n = 171). Cardiac safety was monitored by computerized 12-lead electrocardiogram, and left ventricular ejection fraction (LVEF) was assessed by two-dimensional (2D) echocardiogram. LVEF decline was defined as LVEF value decrease from study baseline by ≥ 10 percentage points and to

RESULTS: Over the entire study, 22 (3.1%) patients had protocol-defined LVEF decline; no meaningful between-group differences were observed (ABP 980/ABP 980: 2.8%; trastuzumab RP/trastuzumab RP: 3.3%; trastuzumab RP/ABP 980: 3.5%). The incidence of cardiac adverse events was low and comparable in the treatment groups. One grade 3 cardiac failure event reported in the trastuzumab RP/ABP 980 arm, and another in the trastuzumab RP/trastuzumab RP arm, were coincident with LVEF decline. One patient discontinued the investigational product during the adjuvant phase because of cardiac failure.

CONCLUSION: These prespecified analyses confirm the tolerability of ABP 980 and demonstrate clinical similarity of ABP 980 and trastuzumab RP with respect to cardiac safety. No new cardiac safety signals were observed whether patients were receiving ABP 980 or switched from the RP to ABP 980.

PMID: 31927716 [PubMed - as supplied by publisher]

15 January 2020

12:42

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Incidence and risk markers of 5-fluorouracil and capecitabine cardiotoxicity in patients with colorectal cancer.

Acta Oncol. 2020 Jan 14;:1-9

Authors: Dyhl-Polk A, Vaage-Nilsen M, Schou M, Vistisen KK, Lund CM, Kümler T, Appel JM, Nielsen DL

Bladder cancer (BCa) is a common solid tumor marked by high rates of recurrence, especially in non-muscle invasive disease

Abstract

Bladder cancer (BCa) is a common solid tumor marked by high rates of recurrence, especially in non-muscle invasive disease. Prostaglandin E2 (PGE2) is a ubiquitously present lipid mediator responsible for numerous physiological actions. Inhibition of cyclooxygenase (COX) enzymes by the non-steroidal anti-inflammatory (NSAID) class of drugs results in reduced PGE2 levels. NSAID usage has been associated with reductions in cancers such as BCa. Clinical trials using NSAIDs to prevent recurrence have had mixed results, but largely converge on issues with cardiotoxicity. The purpose of this review is to understand the basic science behind how and why inhibitors of PGE2 may be effective against BCa, and to explore alternate therapeutic modalities for addressing the role of PGE2 without the associated cardiotoxicity. We will address the role of PGE2 in a diverse array of cancer-related functions including stemness, immunosuppression, proliferation, cellular signaling and more.

PMID: 31931078 [PubMed - as supplied by publisher]

16:03

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Cardio-Immuno-Oncology.

Circulation. 2020 Jan 14;141(2):87-89

Authors: Zaha VG, Meijers WC, Moslehi J

PMID: 31928434 [PubMed - in process]

16:03

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Cardiac Safety of the Trastuzumab Biosimilar ABP 980 in Women with HER2-Positive Early Breast Cancer in the Randomized, Double-Blind, Active-Controlled LILAC Study.

Drug Saf. 2020 Jan 11;:

Authors: Kolberg HC, Colleoni M, Demetriou GS, Santi P, Tesch H, Fujiwara Y, Tomasevic Z, Hanes V

OBJECTIVE: The goal of this study was to determine the incidence of postoperative tachycardia and its predictive value of

Abstract

OBJECTIVE: The goal of this study was to determine the incidence of postoperative tachycardia and its predictive value of complications in patients following microvascular free flap surgery in the head and neck.

STUDY DESIGN: Retrospective chart review.

SETTING: Single tertiary care academic medical center.

SUBJECTS AND METHODS: All patients who underwent a microvascular free flap of the head and neck by surgeons in the department of otolaryngology from 2013 to 2017 were included in this study.

RESULTS: Of the 344 who patients met inclusion criteria, 40.4% had a maximum heart rate (HR) of the hospitalization over 110 beats per minute (bpm). Patients with a maximum HR greater than 110 bpm were 19 times more likely to experience a composite vascular complication (myocardial infarction, myocardial necrosis, or pulmonary embolism) than patients with a maximum HR <110

CONCLUSION: Postoperative tachycardia is significantly associated with adverse outcomes and should not be dismissed as a normal variant. Identifying patients at an increased risk of having an underlying complication can help guide interpretation, workup, and management of postoperative patients in the head and neck population.

PMID: 30717618 [PubMed - indexed for MEDLINE]

16:03

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Prostaglandin E2 as a Therapeutic Target in Bladder Cancer: From Basic Science to Clinical Trials.

Prostaglandins Other Lipid Mediat. 2020 Jan 10;:106409

Authors: Woolbright BL, Pilbeam CC, Taylor JA

BACKGROUND: Bladder cancer is a disease of the older adult, and management of comorbid conditions requiring anticoagulation (AC)

Abstract

BACKGROUND: Bladder cancer is a disease of the older adult, and management of comorbid conditions requiring anticoagulation (AC) or antiplatelet agents (APA) around the time of radical cystectomy (RC) is a frequent clinical challenge. It is estimated that 10% of adult surgical patients are on chronic anticoagulation medications, and considerations surrounding the perioperative disruption, resumption, and modification or substitution of AC and APA in patients undergoing radical cystectomy are critical for the practicing urologist.

METHODS: In our report, we performed a comprehensive literature review using PubMed to evaluate all available studies from 1950 to present. Additionally, we reviewed current multidisciplinary guideline papers from the American College of Surgeons, American College of Cardiology, and CHEST Society regarding perioperative management of anticoagulation and antiplatelet agents.

RESULTS: Our keyword search yielded 35 articles from 1950 to 2019. We identified 16 studies pertaining specifically to evaluation and perioperative management of anticoagulation in patient undergoing RC. Many of the recommendations in this realm are informed by trial data outside the RC population in the general surgical population or general adult population. Current guidelines from the American College of Surgeons, American College of Cardiology/American Heart Association, and CHEST Society inform our recommendations heavily and are summarized in Table 1.

CONCLUSIONS: Radical cystectomy remains both a mainstay of therapy for patients with muscle-invasive bladder cancer and a morbid procedure. Competing risks of perioperative hemorrhage and thromboembolic events make management of anticoagulation and antiplatelet agents an important and modifiable risk factor. Our review of the current literature highlights the knowledge gap that exists in management of these agents in the radical cystectomy patient. A multi-disciplinary approach to management of this clinical challenge remains a mainstay of treatment.

PMID: 31928866 [PubMed - as supplied by publisher]

14:28

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Follow-up to comment on "Direct Oral Anticoagulants in Patients with Venous Thromboembolism and Thrombophilia: Systematic Review and Meta-Analysis".

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--media.wiley.com-assets-7388-69-wiley-full-text.png Related Articles

Follow-up to comment on "Direct Oral Anticoagulants in Patients with Venous Thromboembolism and Thrombophilia: Systematic Review and Meta-Analysis".

J Thromb Haemost. 2019 06;17(6):1007-1009

Authors: Elsebaie MAT, Van Es N, Langston A, Büller HR, Gaddh M

PMID: 31009157 [PubMed - indexed for MEDLINE]

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Postoperative Tachycardia in Head and Neck Microvascular Free Flap Patients.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--journals.sagepub.com-pb-assets-sage-pubmed-sage.png Related Articles

Postoperative Tachycardia in Head and Neck Microvascular Free Flap Patients.

Otolaryngol Head Neck Surg. 2019 06;160(6):1019-1022

Authors: Ziegler A, Schneider A, Pittman A, Thorpe E

INTRODUCTION: The role of testosterone (T) replacement therapy (TRT) in men is still conflicting. In particular, safety concerns and cardiovascular (CV)

Abstract

INTRODUCTION: The role of testosterone (T) replacement therapy (TRT) in men is still conflicting. In particular, safety concerns and cardiovascular (CV) risk related to TRT have not been completely clarified yet. Similarly, the clear beneficial effects of TRT are far to be established.

AIM: To systematically and critically analyze the available literature providing evidence of the benefit-risk ratio derived from TRT in aging men.

METHODS: A comprehensive PubMed literature search was performed to collect all trials, either randomized controlled trials (RCTs) or observational studies, evaluating the effects of TRT on different outcomes.

MAIN OUTCOME MEASURE: Whenever possible, data derived from RCTs were compared with those resulting from observational studies. In addition, a discussion of the available meta-analyses has been also provided.

RESULTS: Data derived from RCT and observational studies clearly documented that TRT can improve erectile function and libido as well as other sexual activities in men with hypogonadism (total T < 12 nm).

CLINICAL IMPLICATIONS: Before prescribing TRT, hypogonadism (total T < 12 nm)

STRENGTH & LIMITATIONS: When correctly diagnosed and administered, TRT is safe, and it can improve several aspects of sexual function. However, its role in complicated vasculogenic erectile dysfunction is limited. Conversely, TRT is not recommended for weight reduction and metabolic improvement. Further well-powered studies are advisable to better clarify TRT for long-term CV risk and prostate safety in complicated patients as well as in those curatively treated for prostate cancer.

CONCLUSION: TRT results in sexual function improvement when men with hypogonadism (total T < 12 nm)

PMID: 31928918 [PubMed - as supplied by publisher]

14:28

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Management of anticoagulation and antiplatelet agents in the radical cystectomy patient.

Urol Oncol. 2020 Jan 09;:

Authors: Smelser WW, Jones CP

Venous thromboembolism is a frequent complication occurring in patients suffering from neoplastic diseases. Since neutrophil

Abstract

Venous thromboembolism is a frequent complication occurring in patients suffering from neoplastic diseases. Since neutrophil extracellular traps (NETs) play an important role both in the development of the tumor growth process and in inducing complications such as thrombosis, indubitably the investigation of the effect of antitumor drugs on the formation of neutrophil extracellular traps and on the ability of such drugs to prevent NETs contribution on carcinogenesis is of great interest. In the present work we studied the effect of 5-fluorouracil (5FU) and its shielded -by amphiphilic poly-N-vinylpyrrolidone (Amph-PVP) nanoparticles-nanoscaled polymeric form on the activation of human neutrophils under ex vivo conditions. Free 5FU at concentrations varying from 0.01 to 10 mg/ml was found to cause a significant (two to three times) and rapid (after 20 min) increase in the total amount of NETs in the blood. Importantly, when 5FU-loaded Amph-PVP nanoparticles were studied under the same conditions, the appearance of NETs in the blood was completely blocked providing strong evidence of their potential as delivery system for 5FU in antitumor therapy.

PMID: 31924010 [PubMed - in process]

14 January 2020

14:28

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Testosterone Therapy: What We Have Learned From Trials.

J Sex Med. 2020 Jan 09;:

Authors: Corona G, Torres LO, Maggi M

BACKGROUND & AIMS: Inhibitors of Janus kinases (JAKs) are being developed for treatment of inflammatory bowel diseases

Abstract

BACKGROUND & AIMS: Inhibitors of Janus kinases (JAKs) are being developed for treatment of inflammatory bowel diseases and other immune-mediated diseases. Tofacitinib is effective in treatment of ulcerative colitis, but there are safety concerns. We performed a systematic review and meta-analysis to investigate the safety profile of tofacitinib, upadacitinib, filgotinib, and baricitinib in patients with rheumatoid arthritis, inflammatory bowel diseases, psoriasis, or ankylosing spondylitis.

METHODS: We searched the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from January 1, 1990 through July 1, 2019. We performed a manual review of conference databases from 2012 through 2018. The primary outcome was incidence rates of adverse events (AEs) and serious AEs. We also estimated incidence rates of serious infections, herpes zoster infection, non-melanoma skin cancer, other malignancies, major cardiovascular events, venous thromboembolism, and mortality. We performed a meta-analysis, which included controlled studies, to assess the relative risk of these events.

RESULTS: We identified 973 studies; of these 82 were included in the final analysis, comprising 66159 patients with immune-mediated diseases who were exposed to a JAK inhibitor. Two-thirds of the included studies were randomized controlled trials. The incidence rate of AEs was 42.65 per 100 person-years and of and serious AEs was 9.88 per 100 person-years. Incidence rates of serious infections, herpes zoster infection, malignancy, and major cardiovascular events were 2.81 per 100 person-years, 2.67 per 100 person-years, 0.89 per 100 person-years, and 0.48 per 100 person-years, respectively. Mortality was not increased in patients treated with JAK inhibitors compared to patients given placebo or active comparator (relative risk 0.72; 95% CI, 0.40-1.28). The meta-analysis showed a significant increase in risk of herpes zoster infection among patients who received JAK inhibitors (relative risk 1.57; 95% CI, 1.04-2.37).

CONCLUSIONS: In a systematic review and meta-analysis, we found an increased risk of herpes zoster infection among patients with immune-mediated diseases treated with JAK inhibitors. All other AEs were not increased among patients treated with JAK inhibitors.

PMID: 31926171 [PubMed - as supplied by publisher]

15:27

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Fluorouracil neutrophil extracellular traps formation inhibited by polymer nanoparticle shielding.

Mater Sci Eng C Mater Biol Appl. 2020 Mar;108:110382

Authors: Basyreva LY, Voinova EV, Gusev AA, Mikhalchik EV, Kuskov AN, Goryachaya AV, Gusev SA, Shtilman MI, Velonia K, Tsatsakis AM

5-Fluorouracil is a key element to the treatment of colon cancer. But it is also one of the most cardiotoxic chemotherapies

Abstract

5-Fluorouracil is a key element to the treatment of colon cancer. But it is also one of the most cardiotoxic chemotherapies, and the management of those that experience cardiotoxicity can be challenging. We present three cases of 5-FU cardiac toxicity that manifested as myocardial infarction, cardiogenic shock, and ventricular fibrillation. Additionally, we discuss the current literature regarding 5-fluorouracil cardiotoxicity mechanisms as well as management.

PMID: 31925673 [PubMed - as supplied by publisher]

15:27

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Safety of Janus Kinase Inhibitors in Patients with Inflammatory Bowel Diseases or Other Immune-mediated Diseases: a Systematic Review and Meta-Analysis.

Gastroenterology. 2020 Jan 08;:

Authors: Olivera P, Lasa J, Bonovas S, Danese S, Peyrin-Biroulet L

INTRODUCTION: Venous thromboembolism (VTE) is a serious life-threatening complication in patients with gastric cancer.

Abstract

INTRODUCTION: Venous thromboembolism (VTE) is a serious life-threatening complication in patients with gastric cancer. Abnormal coagulation function and tumour-related treatment may contribute to the occurrence of VTE. Many guidelines considered that surgical treatment would put patients with cancer at high risk of VTE, so positive prevention is needed. However, there are no studies that have systematically reviewed the postoperative risk and distribution of VTE in patients with gastric cancer. We thus conduct this systematic review to determine the risk of VTE in patients with gastric cancer undergoing surgery and provide some evidence for clinical decision-making.

METHODS AND ANALYSIS: Studies reporting the incidence of VTE after gastric cancer surgery will be included. Primary studies of randomised controlled trials, cohort studies, population-based surveys and cross-sectional studies are eligible for this review and only studies published in Chinese and English will be included. We will search the Medline, Embase, Web of Science, CBM, CNKI and Wanfang data from their inception to November 2019. Two reviewers will independently select studies and extract data. The quality of each included study will be assessed with tools corresponding to their study design. Meta-analysis will be used to pool the incidence data from included studies. Heterogeneity of the estimates across studies will be assessed, if necessary, a subgroup analysis will be performed to explore the source of heterogeneity. The Grades of Recommendation, Assessment, Development and Evaluation method is applied to assess the level of evidence obtained from this systematic review.

ETHICS AND DISSEMINATION: This proposed systematic review and meta-analysis is based on published data, and thus ethical approval is not required. The results of this review will be sought for publication.

PROSPERO REGISTRATION NUMBER: CRD42019144562.

PMID: 31919125 [PubMed - in process]

12 January 2020

13:02

Cancer & Heart (Cardio-Oncology, Cardiotoxicity, TEV)

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Various Manifestations of 5-Fluorouracil Cardiotoxicity: A Multicenter Case Series and Review of Literature.

Cardiovasc Toxicol. 2020 Jan 10;:

Authors: Allison JD, Tanavin T, Yang Y, Birnbaum G, Khalid U

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