Thrombocytosis accompanying solid tumors and predicting the prognosis of malignant tumors has been the subject of intensive research lately. Reports so far have evaluated the role of preoperative platelet count. In our present study we looked at the effect of tumor removal on platelet count and the predictive power of postoperative thrombocytosis on the survival of patients with colorectal cancer (CRC). We retrospectively evaluated the clinical and histopathological data of 336 patients operated due to CRC between 2001 and 2011. Thrombocytosis was defined as a platelet count exceeding 400 × 10(3)/μL. Preoperative platelet count was compared with the value measured 1 month postoperatively. The platelet count significantly decreased after the removal of the primary tumor (paired Wilcoxon test p < 0.001). In univariate analysis preoperative thrombocytosis was a significant marker of overall survival (OS) with HR 2.2, p < 0.001 while the postoperative thrombocytosis was nearly significant with HR = 1.59, p = 0.087. In multivariate setting, when corrected for location, stage, tumor size and controlling for gender and age (> 65 years vs. ≤ 65 years), both pre- and postoperative thrombocytosis were significant independent prognostic markers with HR 1.80, p = 0.20 and HR = 1.98, p = 0.018, respectively. Although the pathomechanism of thrombocytosis related to solid tumors is not known the decrease of platelet count after the removal of the primary tumor raises the possibility that the tumor may play an active role in the development of thrombocytosis. Furthermore, the observation of postoperative thrombocytosis with significant worse outcome underlines the predictive power of elevated platelet count.

Thrombosis and Haemostasis publishes original basic research and clinical studies in vascular biology and medicine, serving as an international platform for dissemination and debate of scientific information at the cutting edge.

There is an increasing number of studies showing that thrombocytosis—accompanying a variety of solid tumors including colorectal cancer (CRC)—is associated with shorter survival and earlier development of metastases. The mechanisms of cancer-associated thrombocytosis are not completely understood yet. The aim of our study was to evaluate the role of IL-6 in tumor development and thrombocytosis in mice with inflammation-induced CRC, using a CRISPR/cas9 IL-6 knockout (KO) strain. Adult male FB/Ant mice (n = 39) were divided into four groups: (1) IL-6 KO controls (n = 5); (2) IL-6 KO CRC model group (n = 18); (3) Wild-type (WT) controls (n = 6); and (4) WT CRC model group (n = 10). CRC model animals in (2) and (4) received azoxymethane (AOM)/dextran sodium sulfate (DSS) treatment to induce inflammation-related CRC. Plasma and liver tissues were obtained to determine platelet counts, IL-6 and thrombopoietin-1 (TPO) levels. In 1 WT and 2 IL-6 KO mice in vivo confocal endomicroscopy and 18F-fluorodeoxyglucose (FDG) PET/MRI examinations were performed to evaluate the inflammatory burden and neoplastic transformation. At the end of the study, tumorous foci could be observed macroscopically in both CRC model groups. Platelet counts were significantly elevated in the WT CRC group compared to the IL-6 KO CRC group. TPO levels moved parallelly with platelet counts. In vivo fluorescent microscopy showed signs of disordered and multi-nuclear crypt morphology with increased mucus production in a WT animal, while regular mucosal structure was prominent in the IL-6 KO animals. The WT animal presented more intense and larger colonic FDG uptake than IL-6 KO animals. Our study confirmed thrombocytosis accompanying inflammation-related CRC and the crucial role of IL-6 in this process. Significantly higher platelet counts were found in the WT CRC group compared to both the control group and the IL-6 KO group. Concomitantly, the tumor burden of WT mice was also greater than that of IL-6 KO mice. Our findings are in line with earlier paraneoplastic IL-6 effect suggestions.

Background: The neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) may be useful for drawing conclusions about the survival of head and neck squamous cell carcinoma (HNSCC) patients. Methods: Clinical data of 156 patients managed for HNSCC at two head and neck surgery centres were analyzed retrospectively. We studied the relationships between survival and PLR as well as NLR. Results: With regards to 5-year survival, the difference between the two groups with PLR values lower or higher than the threshold was statistically significant (p = 0.004), and we found the same for disease-free survival (p = 0.05), and tumour-specific mortality (p = 0.009). Concerning NLR, the difference in tumour-specific survival was statistically significant (p = 0.006). According to the multivariate analysis, NLR values higher than the threshold indicated an enhanced risk for overall as well as for tumour-specific mortality. Conclusion: In HNSCC patients, a high NLR may be considered as an independent risk factor for 5-year overall survival.

The ATP-Binding Cassette (ABC)-transporter MultiDrug Resistance Protein 1 (MDR1) and Multidrug Resistance Related Protein 1 (MRP1) are expressed on the surface of enterocytes, which has led to the belief that these high capacity transporters are responsible for modulating chemosensitvity of colorectal cancer. Several immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR) studies have provided controversial results in regards to the expression levels of these two ABC-transporters in colorectal cancer. Our study was designed to determine the yet uninvestigated functional activity of MDR1 and MRP1 transporters in normal human enterocytes compared to colorectal cancer cells from surgical biopsies. 100 colorectal cancer and 28 adjacent healthy mucosa samples were obtained by intraoperative surgical sampling. Activity of MDR1 and MRP1 of viable epithelial and cancer cells were determined separately with the modified calcein-assay for multidrug resistance activity and sufficient data of 73 cancer and 11 healthy mucosa was analyzed statistically. Significantly decreased mean MDR1 activity was found in primary colorectal cancer samples compared to normal mucosa, while mean MRP1 activity showed no significant change. Functional activity was not affected by gender, age, stage or grade and localization of the tumor. We found lower MDR activity in cancer cells versus adjacent, apparently, healthy control tissue, thus, contrary to general belief, MDR activity seems not to play a major role in primary drug resistance, but might rather explain preferential/selective activity of Irinotecan and/or Oxaliplatin. Still, this picture might be more complex since chemotherapy by itself might alter MDR activity, and furthermore, today limited data is available about MDR activity of cancer stem cells in colorectal cancers. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1675739129145824