Platelet count correlates with stage and predicts survival in melanoma

Cancer is a chronic inflammatory state which is often associated with increased platelet counts. Cancer cells induce thrombopoiesis and activate platelets, which in turn facilitate cancer invasion and metastasis. In this study, we investigate the correlation between platelet counts with each of stage and overall survival in melanoma. This is a retrospective cohort study of 642 melanoma patients diagnosed or treated at a tertiary medical center between 2000 and 2016. Multivariable analysis adjusted for age, sex, stage, and treatment modality. Using multivariable analysis, patients with thrombocytosis around time of diagnosis were more likely to present with distant metastasis (Prevalence Ratio 3.5, 95% CI 2.35–5.22). In patients with metastatic disease and in all stages combined, thrombocytosis predicted decreased 5-year overall survival in univariate and multivariable analysis, and this was most pronounced during the first year after diagnosis. Finally, we show that mice with thrombocytopenia due to the lack of heat shock protein gp96 in their megakaryocytes are protected from melanoma dissemination to the lungs. These findings are concordant with preclinical studies showing a role for platelets in cancer metastasis and suppression of antitumor immunity, further supporting targeting platelets as an adjuvant to immunotherapy in melanoma

Preoperative platelet counts and postoperative outcomes in cancer surgery: a multicenter, retrospective cohort study

Platelets play roles in malignancy, wound healing, and immunity. Nevertheless, their significance in postoperative outcomes is not established. This is a retrospective cohort study of 100,795 patients undergoing cancer surgery in 2010 and 2014 in >500 hospitals. Patients were stratified into five groups based on preoperative platelet counts. Multivariable logistic regression was used to determine the risk of 30-day mortality, morbidities, readmission, and prolonged hospitalization using the mid-normal group as a reference. We adjusted for demographic variables, comorbidities, and operation complexity. In the 2014 cohort, multivariable analysis showed that mortality was higher in patients with thrombocytopenia (OR 1.49, 95% CI [1.23–1.81]), high-normal platelets (OR 1.29, [1.06–1.55]), and thrombocytosis (OR 1.78, [1.45–2.19]). Composite postoperative morbidity followed a similar trend with thrombocytopenia (OR 1.34, [1.25–1.43]), high-normal counts (OR 1.41, [1.33–1.49]), and thrombocytosis (OR 2.20, [2.05–2.36]). Concordantly, the risks of prolonged hospitalization and 30-day readmission followed the same pattern. These results were validated in a large colon cancer cohort from the 2010 database. In conclusion, platelet count is a prognostic indicator in cancer surgeries. This could be related to the role of platelets in wound healing and immunity on one hand, and propagating malignancy on the other

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Intramuscular myxoma of the paraspinal muscles: A case report and systematic review of the literature

Intramuscular myxoma (IM) is a rare mesenchymal tumor of the head and neck region. The current study reports a case of a 45-year-old man who presented with a painless neck mass. Imaging showed involvement of the levator scapulae and scalene muscles. Core needle biopsy was consistent with intramuscular myxoma. Surgical excision was performed and follow-up for 30 months showed no recurrence. The present study includes a systematic review of head and neck IMs, with a summary of the clinical and demographic parameters of all reported cases in the head and neck region. Surgery was curative in 28 of the 29 published cases, as well as in the current case (96.7%), with the lone recurrent tumor cured following re-resection. Females constituted 57% of the cases and the mean age was 49.7±20.4 years. Although uncommon, IM should be considered in the differential diagnosis of deep neck masses, and surgical excision is the treatment of choice with a low risk of recurrence

Risky substance exposure during pregnancy: a pilot study from Lebanese mothers

Samar Rachidi,1 Sanaa Awada,1 Amal Al-Hajje,1 Wafaa Bawab,1 Salam Zein,1 Nadine Saleh,1,2 Pascale Salameh1,21Laboratory of Epidemiological and Clinical Research, Lebanese University, Beirut, Lebanon; 2Faculty of Public Health Labanese University, Beirut, LebanonBackground: The harmful effects of medication and licit substance use during pregnancy may potentially constitute a major public health concern. Our study aims to assess risky exposure of Lebanese pregnant women to drugs, tobacco, caffeine, and alcohol, and to determine their effect on postnatal outcomes.Methods: Women at term were addressed after delivery in five university hospitals of Beirut and Mount Lebanon between February and June 2012. A standardized questionnaire was administered to them. Moreover, medical files of both mothers and their respective newborns were checked to confirm information given by mothers, and to assess the health outcome of the babies.Results: Among the interviewed 350 women, active and passive smoking of tobacco (cigarette or water pipe), and consumption of category C, D, and X drugs were common during pregnancy in Lebanon; they were shown to negatively affect the neonatal outcome in multivariate analyses: they significantly decreased Apgar scores and increased the risk of underweight and medical complications of babies (P < 0.05).Conclusion: Our study demonstrated that Lebanese women were exposed during pregnancy to multiple medications and licit substances that affected the neonates&#39; health. Our findings have implications for clinical obstetric practice and prevention programs in Lebanon. Efforts should be made to decrease exposure to harmful substances during pregnancy.Keywords: pregnancy, smoking, cigarette, water pipe, caffeine, alcohol, drugs, Apgar scor

Molecular Profiling of Multiple Human Cancers Defines an Inflammatory Cancer-Associated Molecular Pattern and Uncovers KPNA2 as a Uniform Poor Prognostic Cancer Marker

<div><p>Background</p><p>Immune evasion is one of the recognized hallmarks of cancer. Inflammatory responses to cancer can also contribute directly to oncogenesis. Since the immune system is hardwired to protect the host, there is a possibility that cancers, regardless of their histological origins, endow themselves with a common and shared inflammatory cancer-associated molecular pattern (iCAMP) to promote oncoinflammation. However, the definition of iCAMP has not been conceptually and experimentally investigated.</p> <p>Methods and Findings</p><p>Genome-wide cDNA expression data was analyzed for 221 normal and 324 cancer specimens from 7 cancer types: breast, prostate, lung, colon, gastric, oral and pancreatic. A total of 96 inflammatory genes with consistent dysregulation were identified, including 44 up-regulated and 52 down-regulated genes. Protein expression was confirmed by immunohistochemistry for some of these genes. The iCAMP contains proteins whose roles in cancer have been implicated and others which are yet to be appreciated. The clinical significance of many iCAMP genes was confirmed in multiple independent cohorts of colon and ovarian cancer patients. In both cases, better prognosis correlated strongly with high <i>CXCL13</i> and low level of <i>GREM1, LOX, TNFAIP6, CD36</i>, and <i>EDNRA</i>. An “Inflammatory Gene Integrated Score” was further developed from the combination of 18 iCAMP genes in ovarian cancer, which predicted overall survival. Noticeably, as a selective nuclear import protein whose immuno-regulatory function just begins to emerge, karyopherin alpha 2 (KPNA2) is uniformly up-regulated across cancer types. For the first time, the cancer-specific up-regulation of KPNA2 and its clinical significance were verified by tissue microarray analysis in colon and head-neck cancers.</p> <p>Conclusion</p><p>This work defines an inflammatory signature shared by seven epithelial cancer types and KPNA2 as a consistently up-regulated protein in cancer. Identification of iCAMP may not only serve as a novel biomarker for prognostication and individualized treatment of cancer, but also have significant biological implications.</p> </div