Occurrence In Cancer Patients Research Articles

Cardiac Autonomic and Endothelial Function in Acute Lymphoblastic Leukaemia Patients Immediately After Chemotherapy and at the Three-Month Follow-up.

Acute lymphoblastic leukemia (ALL) is a malignant uncontrolled overproduction of immature lymphoid cells in blood and bone marrow. The primary treatment of ALL is chemotherapy. Chemotherapy can have myriad systemic side effects, notably cardiovascular derangement. Autonomic derangement occurrence in cancer patients signifies cardiovascular risk in them and is a determinant of cardiovascular morbidity and mortality. Elevated soluble vascular cell adhesion molecule-1 (sVCAM-1) and soluble intercellular adhesion molecule-1 (sICAM-1) levels implicated in the regulation of inflammation indicate endothelial dysfunction. High levels of high-sensitivity C-reactive protein (hsCRP) can be indicative of low-grade inflammation. Hence, in this study the cardiac autonomic function and endothelial and inflammatory biomarker levels in adult patients with ALLwere assessed immediately and three months after chemotherapy. In this longitudinal study, 30 ALL patients (23 males, seven females) aged between 18 to 50 years, who had completed chemotherapy regimens, and 30 age and gender-matched healthy participants (controls) were recruited. Cardiac autonomic function tests (short-term heart rate variability (HRV), 30:15 ratio, synaptic excitation and inhibition (E/I) ratio, diastolic blood pressure (DBP) response to isometric hand grip), endothelial markers (sVCAM-1 and sICAM-1), and inflammatory marker (hsCRP) were assessed immediately and at three months after chemotherapy. Magnitudes of time domain and frequency domain indices, conventional autonomic function test indices, and biomarkers were deranged in ALL patients immediately after chemotherapy. After three months, cardiac autonomic function parameters were found to improve in the form of increased root mean square of successive differences between normal heartbeats (RMSSD), standard deviation of the interbeat intervals of normal sinus beats (SDNN), total power, high-frequency (HF)nu, and decreased low-frequency(LF)nu & LF-HF ratio. Endothelial (sVCAM-1) and inflammatory markers (hsCRP) were lower in the patient group as compared to the controls immediately after chemotherapy. Three months after chemotherapy, the levels of endothelial and inflammatory markers did not show much change. In this study, we found ALL patients showed higher sympathetic drive, decreased parasympathetic modulation, and sympathovagal imbalance immediately after chemotherapy as compared to the controls, indicating cardiovascular risk. After three months, improvement in cardiovascular autonomic function was observed. ALL itself is a state of inflammation with elevated endothelial and inflammatory markers; thus, the decreased endothelial and inflammatory markers could be attributed to the immediate effect of chemotherapy.

Targeting T regulatory (Treg) cells in immunotherapy-resistant cancers.

Primary or secondary (i.e., acquired) resistance is a common occurrence in cancer patients and is often associated with high numbers of T regulatory (Treg) cells (CD4+CD25+FOXP3+). The approval of ipilimumab and the development of similar pharmacological agents targeting cell surface proteins on Treg cells demonstrates that such intervention may overcome resistance in cancer patients. Hence, the clinical development and subsequent approval of Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) targeting agents can serve as a prototype for similar agents. Such new agents aspire to be highly specific and have a reduced toxicity profile while increasing effector T cell function or effector T/T regulatory (Teff/Treg) ratio. While clinical development with large molecules has shown the greatest advancement, small molecule inhibitors that target immunomodulation are increasingly entering early clinical investigation. These new small molecule inhibitors often target specific intracellular signaling pathways [e.g., phosphoinositide-3-kinase delta (PI3K-δ)] that play an important role in regulating the function of Treg cells. This review will summarize the lessons currently applied to develop novel clinical agents that target Treg cells.

Establishment and validation of a predictive nomogram for central venous catheter-related thrombosis in cancer patients: a retrospective nested case-control study.

Catheter-related thrombosis (CRT) is a common complication for patients who receive central venous catheter (CVC) placement. This study investigated the risk factors for CRT and developed a nomogram for CRT prediction among cancer patients. This nested case-control study was conducted in the Third Affiliated Hospital of Kunming Medical University between January 2019 and February 2021. Univariable and multivariable logistic regression analyses were used to identify the risk factors for CRT. A nomogram was developed to predict CRT. Receiver operating curves (ROC), calibration curves, and decision curves were used to evaluate the performance of the nomogram in the training and validation sets. A total of 4,691 cancer patients were included in this study. Among them, 355 (7.57%) had CRT, and 70% of CRTs occurred in the first week of insertion. Among the 3,284 patients in the training set, the multivariable analysis showed that nine characteristics were independently associated with CRT, and a nomogram was constructed based on the multivariable analysis. The ROC analysis indicated good discrimination in the training set (area under the curve [AUC] = 0.832, 95% CI: 0.802-0.862) and the testing set (AUC = 0.827, 95% CI: 0.783-0.871) for the CRT nomogram. The calibration curves showed good calibration abilities, and the decision curves indicated the clinical usefulness of the prediction nomograms. The validated nomogram accurately predicts CRT occurrence in cancer patients. This model may assist clinicians in developing treatment plans for each patient.

Artificial Intelligence-Based Hazard Detection in Robotic-Assisted Single-Incision Oncologic Surgery.

Single-incision surgery is a complex procedure in which any additional information automatically collected from the operating field can be of significance. While the use of robotic devices has greatly improved surgical outcomes, there are still many unresolved issues. One of the major surgical complications, with higher occurrence in cancer patients, is intraoperative hemorrhages, which if detected early, can be more efficiently controlled. This paper proposes a hazard detection system which incorporates the advantages of both Artificial Intelligence (AI) and Augmented Reality (AR) agents, capable of identifying, in real-time, intraoperative bleedings, which are subsequently displayed on a Hololens 2 device. The authors explored the different techniques for real-time processing and determined, based on a critical analysis, that YOLOv5 is one of the most promising solutions. An innovative, real-time, bleeding detection system, developed using the YOLOv5 algorithm and the Hololens 2 device, was evaluated on different surgical procedures and tested in multiple configurations to obtain the optimal prediction time and accuracy. The detection system was able to identify the bleeding occurrence in multiple surgical procedures with a high rate of accuracy. Once detected, the area of interest was marked with a bounding box and displayed on the Hololens 2 device. During the tests, the system was able to differentiate between bleeding occurrence and intraoperative irrigation; thus, reducing the risk of false-negative and false-positive results. The current level of AI and AR technologies enables the development of real-time hazard detection systems as efficient assistance tools for surgeons, especially in high-risk interventions.

Venous thromboembolism risk in cancer patients receiving first-line immune checkpoint inhibitor versus chemotherapy.

It remains unclear if immune checkpoint inhibitor (ICI) therapy is associated with higher rate of venous thromboembolism (VTE) compared with cytotoxic chemotherapy (chemo) in patients with comparable cancer type, staging, and comorbidities. Using the national Veterans Affairs healthcare system database from 2016 to 2021, we performed a propensity score (PS)-weighted retrospective cohort study to compare the incidence of VTE in patients with selected stage III/IV cancer receiving first-line ICI versus chemo. The PS model utilized overlap weights to balance age, sex, race, treatment year, VTE history, paralysis/immobilization, prolonged hospitalization, cancer type, staging, time between diagnosis and treatment, and National Cancer Institute comorbidity index. Weighted Cox regressions with robust standard error were used to assess the hazard ratio (HR) and 95% confidence interval (CI). We found that among comparable advanced cancers, first-line ICI (n = 1823) and first-line chemo (n = 6345) had similar rates of VTE (8.49% for ICI and 8.36% for chemo at 6 months). The weighted HR was 1.06 (95% CI 0.88-1.26) for ICI versus chemo. In a subgroup analysis restricted to lung cancers, first-line ICI/chemo (n = 828), ICI monotherapy (n = 428), and chemo monotherapy (n = 4371) had similar rates of VTE (9.60% for ICI/chemo, 10.04% for ICI, and 8.91% for chemo at 6 months). The weighted HR was 1.05 (95% CI 0.77-1.42) for ICI versus chemo, and 1.08 (95% CI 0.83-1.42) for ICI/chemo versus chemo. In conclusion, ICI as a systemic therapy has a similarly elevated risk as cytotoxic chemo for VTE occurrence in cancer patients. This finding can inform future prospective studies exploring thromboprophylaxis strategies.

Venous Thromboembolism in Cancer Patients Undergoing Chemotherapy: A Systematic Review and Meta-Analysis.

Objective: Venous thromboembolism (VTE) is a life-threatening complication that may exacerbate cancer prognosis. Whilst some studies indicate an increased risk of VTE in cancer patients undergoing chemotherapy, the prevalence estimates on the pooled prevalence of VTE in cancer patients undergoing chemotherapy are not known. This study aims to calculate the pooled prevalence of VTE in chemotherapy-treated cancer patients. Methods: Studies on VTE occurrence in cancer patients undergoing chemotherapy were retrieved after database search. The terms used included "cancer", "chemotherapy", and "venous thromboembolism". A random-effects meta-analysis was conducted to obtain a pooled estimate of VTE prevalence in cancer patients undergoing chemotherapy. Results: A total of 102 eligible studies involving 30,671 patients (1773 with VTE, 28,898 without) were included in the meta-analysis. The pooled estimate of VTE prevalence was found to be 6%, ranging from 6% to 7% (ES 6%; 95% CI 6-7%; z = 18.53; p < 0.001). Conclusions: The estimated pooled prevalence rate of VTEs was 6% in cancer patients undergoing CRT, which was higher than the overall crude prevalence rate (5.78%). Comprehensive cancer care should consider stratified VTE risk assessment based on cancer phenotype, given that certain phenotypes of cancer such as bladder, gastric and ovarian posing particularly high risks of VTE.

SPIN-01 RADIATION THERAPY ALONE VERSUS RADIATION THERAPY PLUS RADIOFREQUENCY ABLATION/VERTEBRAL AUGMENTATION FOR SPINE METASTASIS: TRIAL IN PROGRESS

BACKGROUNDSpine metastases are a common occurrence in cancer patients and result in pain, neurologic deficits, decline in performance status, disability, inferior quality of life (QOL), and reduction in ability to receive cancer-directed therapies. Conventional external beam radiation therapy (EBRT) is associated with modest rates of pain relief, high rates of disease recurrence, low response rates for those with radioresistant histologies, and limited improvement in neurologic deficits. The addition of radiofrequency ablation/percutaneous vertebral augmentation (RFA/PVA) to index sites together with EBRT may improve pain response rates and corresponding quality of life. METHODS/DESIGNThis is a single-center, prospective, randomized, controlled trial in patients with spine metastases from T5-L5, stratified according to tumor type (radioresistant vs. radiosensitive) in which patients in each stratum are randomized in a 2:1 ratio to either RFA/PVA and EBRT or EBRT alone. All patients are treated with EBRT to a dose of 20-30 Gy in 5-10 fractions. The target parameters are measured and recorded at the baseline clinic visit, and daily at home with collection of weekly measurements at 1, 2, and 3 weeks after treatment, and at 3, 6, 12, and 24 months following treatment with imaging and QOL assessments. DISCUSSIONThe primary objective of this randomized trial is to determine whether RFA/PVA in addition to EBRT improves pain control compared to palliative EBRT alone for patients with spine metastases, defined as complete or partial pain relief (measured using the Numerical Rating Pain Scale [NRPS]) at 3 months. Secondary objectives include determining whether combined modality treatment improves the rapidity of pain response, duration of pain response, patient reported pain impact, health utility, and overall QOL. The results from this study will be used to allow for comparisons to alternative treatment approaches. This trial was activated 5/2020 and is open to accrual.

Primary cilia regulate gastric cancer-induced bone loss via cilia/Wnt/β-catenin signaling pathway.

Cancer-associated bone disease is a frequent occurrence in cancer patients and is associated with pain, bone fragility, loss, and fractures. However, whether primary or non-bone metastatic gastric cancer induces bone loss remains unclear. Here, we collected clinical evidence of bone loss by analyzing serum and X-rays of 25 non-bone metastatic gastric cancer patients. In addition, C57BL mice were injected with the human gastric cancer cell line HGC27 and its effect on bone mass was analyzed by Micro-CT, immunoblotting, and immunohistochemistry. Furthermore, the degree of the proliferation and osteogenic differentiation of mesenchymal stem cells (MSCs) co-cultured with HGC-27 or SGC-7901 cells was analyzed by colony-formation assay, alizarin red staining, immunofluorescence, qPCR, immunoblotting, and alkaline phosphatase activity assay. These indicated that gastric cancer could damage bone tissue before the occurrence of bone metastases. We also found that cilia formation of MSCs was increased in the presence of HGC27 cells, which was associated with abnormal activation of the Wnt/β-catenin pathway. Expression of DKK1 inhibited the Wnt/β-catenin signaling pathway and partially rescued osteogenic differentiation of MSCs. In summary, our results suggest that gastric cancer cells might cause bone damage prior to the occurrence of bone metastasis via cilia-dependent activation of the Wnt/β-catenin signaling pathway.

Mesenchymal Stem Cell-Derived Exosomes: Biological Function and Their Therapeutic Potential in Radiation Damage.

Radiation-induced damage is a common occurrence in cancer patients who undergo radiotherapy. In this setting, radiation-induced damage can be refractory because the regeneration responses of injured tissues or organs are not well stimulated. Mesenchymal stem cells have become ideal candidates for managing radiation-induced damage. Moreover, accumulating evidence suggests that exosomes derived from mesenchymal stem cells have a similar effect on repairing tissue damage mainly because these exosomes carry various bioactive substances, such as miRNAs, proteins and lipids, which can affect immunomodulation, angiogenesis, and cell survival and proliferation. Although the mechanisms by which mesenchymal stem cell-derived exosomes repair radiation damage have not been fully elucidated, we intend to translate their biological features into a radiation damage model and aim to provide new insight into the management of radiation damage.

Stem Cell-Derived Exosomes Ameliorate Doxorubicin-Induced Muscle Toxicity through Counteracting Pyroptosis.

Doxorubicin (Dox)-induced muscle toxicity (DIMT) is a common occurrence in cancer patients; however, the cause of its development and progression is not established. We tested whether inflammation-triggered cell death, “pyroptosis” plays a role in DIMT. We also examined the potential role of exosomes derived from embryonic stem cells (ES-Exos) in attenuating DIMT. C57BL/6J mice (10 ± 2 wks age) underwent the following treatments: Control (saline), Dox, Dox+ES-Exos, and Dox+MEF-Exos (mouse-embryonic fibroblast-derived exosomes, negative control). Our results demonstrated that Dox significantly reduced muscle function in mice, which was associated with a significant increase in NLRP3 inflammasome and initiation marker TLR4 as compared with controls. Pyroptosis activator, ASC, was significantly increased compared to controls with an upregulation of specific markers (caspase-1, IL-1β, and IL-18). Treatment with ES-Exos but not MEF-Exos showed a significant reduction in inflammasome and pyroptosis along with improved muscle function. Additionally, we detected a significant increase in pro-inflammatory cytokines (TNF-α and IL-6) and inflammatory M1 macrophages in Dox-treated animals. Treatment with ES-Exos decreased M1 macrophages and upregulated anti-inflammatory M2 macrophages. Furthermore, ES-Exos showed a significant reduction in muscular atrophy and fibrosis. In conclusion, these results suggest that DIMT is mediated through inflammation and pyroptosis, which is attenuated following treatment with ES-Exos.

Radiation therapy alone versus radiation therapy plus radiofrequency ablation/vertebral augmentation for spine metastasis: study protocol for a randomized controlled trial

BackgroundSpine metastasis is a common occurrence in cancer patients and results in pain, neurologic deficits, decline in performance status, disability, inferior quality of life (QOL), and reduction in ability to receive cancer-directed therapies. Conventional external beam radiation therapy (EBRT) is associated with modest rates of pain relief, high rates of disease recurrence, low response rates for those with radioresistant histologies, and limited improvement in neurologic deficits. The addition of radiofrequency ablation/percutaneous vertebral augmentation (RFA/PVA) to index sites together with EBRT may improve pain response rates and corresponding quality of life.Methods/designThis is a single-center, prospective, randomized, controlled trial in patients with spine metastasis from T5-L5, stratified according to tumor type (radioresistant vs. radiosensitive) in which patients in each stratum will be randomized in a 2:1 ratio to either RFA/PVA and EBRT or EBRT alone. All patients will be treated with EBRT to a dose of 20–30 Gy in 5–10 fractions. The target parameters will be measured and recorded at the baseline clinic visit, and daily at home with collection of weekly measurements at 1, 2, and 3 weeks after treatment, and at 3, 6, 12, and 24 months following treatment with imaging and QOL assessments.DiscussionThe primary objective of this randomized trial is to determine whether RFA/PVA in addition to EBRT improves pain control compared to palliative EBRT alone for patients with spine metastasis, defined as complete or partial pain relief (measured using the Numerical Rating Pain Scale [NRPS]) at 3 months. Secondary objectives include determining whether combined modality treatment improves the rapidity of pain response, duration of pain response, patient reported pain impact, health utility, and overall QOL.Trial registrationClinicalTrials.gov NCT04375891. Registered on 5 May 2020.

Death anxiety in patients with cancer: A systematic review and meta-analysis.

The present study was designed to estimate the rate of death anxiety and the factors influencing its occurrence in cancer patients using a systematic review and meta-analysis approach. Five academic databases, including Scopus, PubMed, Science Direct, Embase, and ProQuest, were searched systematically from inception until the end of January 2020. Observational studies that reported mean score of death anxiety in cancer patients, regardless of language restriction, were eligible to be included. The Newcastle-Ottawa Scale was used to assess the methodological quality of included studies. A meta-analysis was performed using a random effect model with the DerSimonian and Laird weighted method. Publication bias was assessed using the funnel plot and Begg's and Egger's tests. The estimated pooled mean for death anxiety among cancer patients was 6.84 (CI95%=[5.98, 7.69]). Publication bias and small study effects were not detected. Subgroup analysis and a meta-regression showed that the estimated pooled mean was higher in Asian studies (M=7.57) compared to European (M=6.47) and North American studies (M=5.57); in breast cancer patients (M=9.68) compared to studies examining different types of cancers; in female only participants (M=7.37) compared to studies with both genders (M=6.60); and in married participants compared to non-married participants. The findings suggest that death anxiety in patients with cancer is moderate and is influenced by socio-demographic factors such as region, type of cancer, sex, and marital status.

The circadian clock protects against acute radiation-induced dermatitis

Radiation-induced dermatitis is a common occurrence in cancer patients undergoing radiation therapy (RT) and is caused when ionizing radiation (IR) induces DNA strand breaks in skin cells. The wide use of RT in cancer treatments makes it important to minimize RT-induced toxicities including radiodermatitis. This study sought to determine if the circadian clock plays a protective role in minimizing radiodermatitis. We treated mice in control (Day Shift), environmentally-disrupted (Rotating Shift) and genetically-disrupted (Per 1/2−/−) circadian conditions with 6 Gy of IR to the whole body. There was a significantly increased number of radiodermatitis spots on mice with circadian clock disruption compared to control mice. Additionally, circadian clock disrupted mice exhibited reduced protein levels of Bmal1, a phenomenon that sensitized circadian synchronized keratinocytes to IR-induced DNA damage. Furthermore, the skin phenotype results corresponded with significantly reduced body weights and increased genomic DNA damage in blood cells of mice with clock disruption compared to control mice. These findings suggest that the circadian clock plays a protective role in IR-induced DNA damage and skin toxicity, possibly through BMAL1-dependent mechanisms, and potentially impacts RT-associated radiodermatitis in cancer patients.

Direct Oral Anticoagulants in Cancer Patients. Time for a Change in Paradigm

Thrombosis is a more common occurrence in cancer patients compared to the general population and is one of the main causes of death in these patients. Low molecular weight heparin (LMWH) has been the recognized standard treatment for more than a decade, both in cancer-related thrombosis and in its prevention. Direct oral anticoagulants (DOACs) are a new option for anticoagulation therapy. Recently published results of large randomized clinical trials have confirmed that DOAC may be a reasonable alternative to LMWH in cancer patients. The following review summarizes the current evidence on the safety and efficacy of DOAC in the treatment and prevention of cancer-related thrombosis. It also draws attention to the limitations of this group of drugs, knowledge of which will facilitate the selection of optimal therapy.

Spinal metastasis: diagnosis, management and follow-up.

Spine metastatic disease is an increasingly common occurrence in cancer patients due to improved patient survival. Close proximity of the bony spinal column to the spinal cord limits many conventional treatments for metastatic disease. In the past decade, we have witnessed dramatic advancements in therapies, with improvements in surgical techniques and recent adoption of spine stereotactic radiotherapy techniques leading to improved patient outcomes. Multidisciplinary approaches to patient evaluation, treatment and follow-up are essential. Imaging plays an ever increasing role in disease detection, pre-treatment planning and assessment of patient outcomes. It is important for the radiologist to be familiar with imaging algorithms, best practices for surgery and/or radiotherapy and imaging findings in the post-treatment period that may indicate disease recurrence. In this review, we present a multidisciplinary discussion of spine metastases, with specific focus on pre-treatment imaging, planning, current treatment approaches, and post-treatment assessment.

Abstract 2129: Breast tumor microenvironment & metastasis is controlled by activity of a2 isoform of V-ATPase in mammary epithelium

Abstract Extracellular matrix (ECM) critically impacts tumor progression and is influenced by both cancer and host tissue cells. While our understanding of cancer cell ECM remodeling is widespread, the importance of host tissue ECM, which provides an initial congenial environment for primary tumor formation, is only partly understood. Previously, we have shown that epithelial cell associated vacuolar (V)-ATPase ‘a2' isoform (a2V) regulates stiffness of mammary gland ECM. Here, we investigated how a2V mediated alterations in ECM of breast tissues affects the tumor microenvironment and metastasis of breast cancer. We also established the correlation of a2V expression in the normal breast tissue with metastatic occurrence in cancer patients. In this study, using the MMTV-Cre-Lox system, we deleted the a2V gene in epithelial cells of mouse mammary glands. Tumors were transplanted in mammary fat pads of a2V conditional knockout mice (a2VcKO) using E0771/Py230 mouse mammary cancer cells. These tumors were evaluated for the histopathology, ECM stiffness, immune cell populations, cytokines, angiogenic factors and metastasis. We show that in a2VcKO, breast tumors exhibit less tumor rigidity, increased inflammation and a more necrotic tumor microenvironment. These mice showed an increased metastasis of tumors compared to control evident by cytokeratin (Ck)14 staining of cancer cells in lung tissues (3.3 fold increase, P=0.004). Immuno-phenotyping of breast tumor microenvironment revealed increased infiltration of CD45 cells with higher number of anti-tumor M1 macrophages (2.1 fold increase, P=0.007) and elevated expression of inflammatory cytokines TNF-α and iNOS in a2VcKO mice compared to control (P=0.01). The tumors in a2VcKO mice were much more highly vascularized and angiogenic compared to control (P=0.01) evident by increased number of Meca32+SMA+ cells. Clinically, in cancer patients, low a2V expression levels in normal breast tissue correlated directly with lymph-node metastasis. Thus, this study has identified a2V expression in epithelial cells as a key modulator of tumor microenvironment and its expression levels can significantly modulate breast tumor dissemination. Citation Format: Gajendra K. Katara, Arpita Kulshrestha, Manoranjan Sahoo, Kenneth Beaman. Breast tumor microenvironment & metastasis is controlled by activity of a2 isoform of V-ATPase in mammary epithelium [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2129.

Protective effect of early low-dose hydrocortisone on ventilator-associated pneumonia in the cancer patients: a propensity score analysis

BackgroundVentilator-associated pneumonia (VAP) is a care-related event that could be promoted by immune suppression caused by critical diseases, malignancies and cancer treatments. Low dose of hydrocortisone was proposed for modulation of immune response in the critically ill population.MethodsIn this monocentric observational study, all cancer patients mechanically ventilated for more than 48 h were included. Effect of low-dose hydrocortisone administered during the first 48 h of mechanical ventilation was evaluated applying inverse probability weighting analysis after propensity score assessment. VAP impact on 1-year mortality, ICU length of stay and mechanical ventilation duration was secondarily determined.ResultsWithin this cohort, 190 cancer patients were followed. VAP was confirmed in 22.1% of cases in the early hydrocortisone group and confirmed in 42.6% of cases in the no or late hydrocortisone group. Early hydrocortisone exhibited a protective effect on the risk of VAP (OR 0.23; 95% CI 0.12–0.44; P < 0.0001). VAP was associated with 1-year mortality (HR 1.60; 95% CI 1.10–2.34; P = 0.017) and increased ICU length of stay (mean extra length of stay: 4.2 days; 95% CI 0.6–7.8).ConclusionsImmune modulation with low-dose hydrocortisone administered in the first days of mechanical ventilation could protect from VAP occurrence in cancer patients.

Gender Differences in Cancer-associated Venous Thromboembolism.

Venous thromboembolism (VTE) is a commonly diagnosed multifactorial condition with significant morbidity and mortality, occurring in up to 20% of cancer patients. Indeed, patients with cancer are in a higher pro-thrombotic state due to alterations in their haemostatic- coagulative system, stasis and blood flow slowdown, endothelial dysfunction, vascular inflammation and platelet activation. Moreover, several cancer-dependent factors can sum up to trigger a first episode of VTE or to cause its recurrence in the course of anticoagulant treatment. Such a pro-thrombotic condition is further worsened by additional favoring risks such as immobilization, infection, surgery, or insertion of a central venous catheter, and anti-cancer therapy. Furthermore, in the secondary prevention setting, the anticoagulant therapy is accompanied by a high incidence of bleeding complications. Given the above, understanding and identifying the factors associated with the incidence and clinical outcome of VTE in cancer patients might be of great value in the prevention and management of VTEattributable complications, including death. Differences associated to gender on cancerrelated VTEs are not yet fully defined; many of the studies that addressed the question have been biased by erroneous/non homogeneous inclusion criteria. In the present review, we analyzed the potential differences in VTEs occurrence in cancer patients, by reporting the most significant findings in the recent literature. The identification of a differential clinical approach according to patient sex, might prompt the design of personalized treatment options tailored and optimized according to algorithms for oncological VTE prevention.

P2.04-040 Pleural Effusion Characteristics and Relationship with Outcomes in Cancer Patients: Topic: Esophageal Cancer and Other Malignancies

Pleural effusion is a common occurrence in cancer patients, with an estimated annual incidence of 150,000 in the United States. It generally represents advanced malignant disease with median survival of 3-12 months. It can lead to debilitating symptoms such as dyspnea and pain, adversely affecting the quality of life. We performed a retrospective analysis of a dataset of 62 cancer patients with pleural effusion after first thoracentesis procedure. The recorded data included: age, gender, type of cancer, number of thoracentesis, pleural fluid volume characteristics and volume. We studied 62 patients, with ages between 20-77 years, median 57 years; 64% were females and 36% were males. The number of patients deceased by the end of follow up was 43 (69.4%), alive at the end of follow up was 8 (12.9%), lost to follow up 11 (17.7%). Median overall survival was 3 months. The cancer type was divided into breast, 32.3%, non-small cell lung, 25.8% and 41.9% other cancers. Thirty-three (53.2%) patients had malignant pleural effusion with a median of 3 months of survival. Twenty-nine (46.8%) patients had non-malignant effusion with a similar median survival of 3 months. We analyzed the correlation of the radiologically estimated effusion volume, thoracentesis volume and presence of blood and malignant cells with outcomes (overall survival, OS). There is a negative correlation between the radiologically estimated effusion volume and OS (Pearson rank correlation of -0.43). This negative correlation is maintained in subgroup analysis (breast -0.56; lung -0.33). The thoracentesis volume was also negatively correlated with OS (Pearson rank correlation of -0.45), finding also maintained in subgroup analysis (breast -0.39, lung -0.66). We found no statistically significant difference in OS between malignant effusions (average OS 6.1 months, median 3 months) and non-malignant effusions (average OS 4.9 months, median 3 months). There was no statistically significant difference in survival between bloody effusions (average survival 3.5 months, median survival 1.25 months) and non-bloody effusions (average survival 6.2 months, median 3.5 months). We found an inverse correlation between the radiologically estimated pleural fluid volumes and OS as well as between thoracentesis volume and OS among cancer patients. This correlation is maintained in subset analysis of the two most common types of cancer in our sample, breast and NSCLC. Survival was not influenced by the presence of malignant cells or blood in the pleural fluid. A prospective study to better characterize the prognostic value of first thoracentesis may be warranted.

Relationship of pleural fluid analysis with outcomes in cancer patients.

e23214Background: Pleural effusion is common occurrence in cancer patients, with an estimated annual incidence of 150 000 in the United States. It generally represents advanced malignant disease, c...