Ratios derived from an array of standard haematological indices predict the oncological outcome in colon cancer.

AIM: The interaction between inflammation and cancer is well established. Surrogate markers of systemic inflammation, such as the neutrophil/lymphocyte ratio (NLR), may be associated with the long-term oncological outcome. The present study aimed to characterize the relationship between several ratios derived from haematological indices using a classification and regression tree analysis. METHOD: Haematological white-cell ratios were established for all patients undergoing colonic cancer resection with curative intent (n = 436) in a regional cancer centre. The optimal ratios associated with overall survival (OS) were established in a training set (n = 386) using a classification and regression tree (CRT) technique. The association between ratios and OS was assessed in a separate test set (n = 50). Within the test set, two groups were generated based on each ratio (one group above and one group below the cut-off value identified in the training set). The association between ratios and OS was assessed using a stepwise Cox proportional-hazards regression model. RESULTS: The following ratios, identified by the CRT, were associated with adverse OS in the test set: an NLR of ≥ 3.4 [hazard ratio (HR) = 3.4, P < 0.001]; and a white-cell-count/lymphocyte ratio (WLR) of ≥ 5.28 (HR = 4.1, P = 0.03). CONCLUSION: This is the first study to apply recursive partitioning in determining the relationship between haematological ratios and OS in colon cancer. Haematological ratios were predictive of oncological outcome. What does this paper add to the literature? This study suggests an association between systemic inflammation and oncological outcome.

An appraisal of lymph node ratio in colon and rectal cancer: not one size fits all.

BACKGROUND: Lymph node ratio (LNR) is increasingly accepted as a useful prognostic indicator in colorectal cancer. However, variations in methodology, statistical stringency and cohort composition has led to inconsistency in respect of the optimally prognostic LNR. OBJECTIVE: The aim was to apply a robust regression-based analysis to generate and appraise LNRs optimally prognostic for colon and rectal cancer, both separately and in combination. METHODS: LNR was established for all patients undergoing either a colonic (n = 379) or rectal (n = 160) cancer resection with curative intent. The optimal LNR associated with disease-free and overall survival were established using a classification and regression tree technique. This process was repeated separately for patients who underwent either colonic or rectal resection and for the combined cohort. Survival associated with differing LNR was estimated using the Kaplan-Meier method and compared using a log-rank test. Relationships between LNR, disease-free survival (DFS) and overall survival (OS) were further characterised using Cox regression analysis. All statistical analyses were conducted in the R programming environment, with statistical significance was taken at a level of p < 0.05. RESULTS: Optimal LNRs differed between each cohort, when either overall or disease-free survival was considered. LNRs generated from combined cohorts also differed from those generated by individual cohorts. In relation to DFS, LNR values were obtained and included 0.18 for the colon cancer cohort and 0.19 for the rectal and combined colorectal cancer cohorts. In relation to OS, multiple LNR values were obtained for colon and combined cohorts; however, an optimal LNR was not evident in the rectal cancer cohort. Survival patterns according to LNR closely resembled those associated with standard nodal staging. CONCLUSION: Application of a data-driven approach based on recursive partitioning generates differing lymph node ratios for colon, rectal and combined colorectal cohorts. In each cohort, LNR was similarly prognostic to standard nodal staging in respect to overall and disease-free survival. Overall survival was associated with a multiplicity of LNR values, whilst disease-free survival was associated with a single LNR only. The paper demonstrates the merits of utilising a data-driven approach to determining lymph node ratios from specific patient cohorts. Utilising such an approach enabled the generation of those LNRs that were most associated with particular survival trends in relation to overall and disease-free survival. These differed markedly for colon cancer, rectal cancer and combined cohorts. In general, the survival patterns associated with LNRs generated were similar to those observed with standard nodal staging.

Prostaglandin D2 regulates human colonic ion transport via the DP1 receptor.

AIMS: Prostaglandin D2 is released by mast cells and is important in allergies. Its role in gastrointestinal function is not clearly defined. This study aimed to determine the effect of exogenous PGD2 on ion transport in ex vivo normal human colonic mucosa. MATERIALS AND METHODS: Mucosal sheets were mounted in Ussing chambers and voltage clamped to zero electric potential. Ion transport was quantified as changes in short-circuit current. In separate experiments epithelial monolayers or colonic crypts, isolated by calcium chelation, were treated with PGD2 and cAMP levels determined by ELISA or calcium levels were determined by fluorimetry. KEY FINDINGS: PGD2 caused a sustained, concentration-dependent rise in short-circuit current by increasing chloride secretion (EC50=376nM). This effect of PGD2 is mediated by the DP1 receptor, as the selective DP1 receptor antagonist BW A686C inhibited PGD2-induced but not PGE2-induced rise in short-circuit current. PGD2 also increased intracellular cAMP in isolated colonic crypts with no measurable influence on cytosolic calcium. PGD2 induces chloride secretion in isolated human colonic mucosa in a concentration-dependent manner with concomitant elevation of cytoplasmic cAMP in epithelial cells. SIGNIFICANCE: The involvement of DP2 receptor subtypes has not previously been considered in regulation of ion transport in human intestine. Since inflammatory stimuli may induce production of eicosanoids, selective regulation of these pathways may be pivotal in determining therapeutic strategies and in understanding disease.

A MultiCenter Pilot Randomized Controlled Trial of Remote Ischemic Preconditioning in Major Vascular Surgery.

A pilot randomized controlled trial that evaluated the effect of remote ischemic preconditioning (RIPC) on clinical outcomes following major vascular surgery was performed. Eligible patients were those scheduled to undergo open abdominal aortic aneurysm repair, endovascular aortic aneurysm repair, carotid endarterectomy, and lower limb revascularization procedures. Patients were randomized to RIPC or to control groups. The primary outcome was a composite clinical end point comprising any of cardiovascular death, myocardial infarction, new-onset arrhythmia, cardiac arrest, congestive cardiac failure, cerebrovascular accident, renal failure requiring renal replacement therapy, mesenteric ischemia, and urgent cardiac revascularization. Secondary outcomes were components of the primary outcome and myocardial injury as assessed by serum troponin values. The primary outcome occurred in 19 (19.2%) of 99 controls and 14 (14.1%) of 99 RIPC group patients (P = .446). There were no significant differences in secondary outcomes. Our trial generated data that will guide future trials. Further trials are urgently needed.

Laryngeal cancer in Egypt: quality of life measurement with different treatment modalities.

BACKGROUND: Quality of life (QOL) reflects the need to assess the patient's overall sense of well-being. A nonrandomized, prospective longitudinal study was conducted to evaluate QOL in Egyptian patients treated for laryngeal cancer. METHODS: In all, 60 newly diagnosed patients with laryngeal cancer were divided into 3 groups: surgical resection, radiotherapy, and combined therapy. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaires (EORTC-QLQ) were administered to the patients at 4 points: prior to treatment, during active treatment, and at 3 and 6 months after completion of treatment. RESULTS: All pretreatment scales were worse in the combined therapy group. The functional scales reached their lowest levels in all groups during active treatment. Radiotherapy group scales showed persistent slow recovery. There was striking prevalence of the financial difficulties score in all groups. CONCLUSION: QOL measurement provides information to guide clinical decision making in patients treated for laryngeal carcinoma.