Elevated serum levels of proinflammatory cytokines potentially correlate with depression and anxiety in colorectal cancer patients in different stages of the antitumor therapy.

Depression and anxiety, the most important psychological disorders in cancer patients, have now been considered as psychoneuroimmunological disorders, in which peripheral immune activation, through the release of proinflammatory cytokines, is implicated in the variety of behavioral, neuroendocrine and neurochemical alterations associated with these disorders. Along with the tumor itself, cancer treatment can also contribute to exacerbate the production of proinflammatory cytokines. This study aimed to investigate whether proinflammatory cytokine levels are related to depression and anxiety in CRC patients in different stages of the antitumor therapy We evaluated 60 patients in three stages of antitumor therapy (Pre-chemotherapy, Under-chemotherapy and Post-chemotherapy, n=20 in each group) and 20 healthy volunteers by the Hospital Anxiety and Depression Scale (HADS). Serum levels of cytokines were measured by CBA. Depression and/or anxiety were found at clinically relevant levels in CRC patients during all antitumor therapy. Patients in pre-chemotherapy group exhibited the highest concentrations of pro-inflammatory cytokines and the lowest levels of IL-10. In latter stages of treatment, cytokines reached levels similar to the control group. Correlation analysis between HADS score and cytokine serum levels revealed positive associations of anxiety and/or depression with IL-1ß, IL-6, IL-8, and TNF-α, and a negative correlation with IL-10, suggesting that cytokines are involved in the pathophysiology of these psychological disorders in CRC patients. A better understanding of the molecular mechanisms involved in these psychological disorders will allow the design of new therapeutic strategies to assist in alleviating such symptoms in cancer patients.

Assessment of the integration between oncology and palliative care in advanced stage cancer patients.

PURPOSE: Chemotherapy is indicated for patients with metastatic malignancy in order to improve quality of life and in some cases to increase survival. However, the greatest difficulty regarding the choice of treatment is to evaluate the clinical benefit and intrinsic toxicity of each procedure. The best strategy is the integration between oncology and palliative care, which is still mostly insufficient. The main objective of this study was to assess time to palliative care referral for cancer patients with advanced local or metastatic disease and to investigate the impact of covariates on this relationship. METHODS: A retrospective, cross-sectional, observational pilot study was conducted on 286 patients divided into two groups, one consisting of metastatic patients and the other of non-metastatic patients at diagnosis. Karnofsky Performance Scale (KPS), setting, and survival time were evaluated. RESULTS: One hundred eighteen patients (41.25%) were metastatic and 168 (58.74%) had locally advanced malignant disease. The median time of metastatic patient referral to the group of palliative care (GPC) was 5.3 months, with 39.8% referred earlier and 60.2% referred late (≥3 months). 60.2% of metastatic patients were referred to the GPC with a KPS <70% and 56% of non-metastatic patients were referred earlier and 44% after 3 months. There was improved survival only in metastatic patients referred to the GPC with a KPS ≥70% (p = 0.02). CONCLUSIONS: Many oncology patients were referred late to the GPC. A higher KPS was a risk factor for late referral because only severe patients were referred earlier. Metastatic patients referred with a KPS ≥70% had a longer survival.

A mechanistic breast cancer survival modelling through the axillary lymph node chain.

In this paper, we proposed a mechanistic breast cancer survival model based on the axillary lymph node chain structure, considering lymph nodes as a potential dissemination arrangement. We assume a naive breast cancer treatment protocol consisting of exposing patients first to a chemotherapy treatment on r intervals at k-cycles separated by equal time intervals, and then they proceed to surgery. Our model, different from former ones, accommodates a quantity of contaminated lymph nodes, which is observed during surgery. We assume a generalised negative binomial survival distribution for the unknown number of contaminated lymph nodes after surgery, which, during an unknown period, may potentially propagate the disease. Estimation is based on a maximum likelihood approach. A simulation study assesses the coverage probability of asymptotic confidence intervals when small or moderate samples are considered. A Brazilian breast cancer data illustrate the applicability of our modelling.

Pleiotrophin expression in astrocytic and oligodendroglial tumors and it's correlation with histological diagnosis, microvascular density, cellular proliferation and overall survival.

BACKGROUND: Pleiotrophin (PTN) is a secreted cytokine with several properties related with tumor development, including differentiation, angiogenesis, invasion, apoptosis and metastasis. There is evidence that PTN has also a relevant role in primary brain neoplasms and its inactivation could be important to treatment response. Astrocytic and oligodendroglial tumors are the most frequent primary brain neoplasms. Astrocytic tumors are classified as pilocytic astrocytoma (PA), diffuse astrocytoma (DA), anaplastic astrocytoma (AA) and glioblastoma (GBM). Oligodendroglial tumors are classified as oligodendroglioma (O) and anaplastic oligodendroglioma (AO). The aim of the present study was to compare PTN expression, in astrocytomas and oligodendrogliomas and its association with the histological diagnosis, microvascular density, proliferate potential and clinical outcome. METHODS: Seventy-eight central nervous system tumors were analyzed. The histological diagnosis in accordance with WHO classification was: 13PA, 18DA, 8AA, 15GBM, 16O and 8AO. Immunohistochemistry was realized with these specific antibodies: pleiotrophin, CD31 to microvascular density and Ki-67 to cell proliferation. RESULTS: PTN expression was significantly higher in GBM and AA when compared to PA and higher in GBM compared to DA. PTN expression did not differ between O and AO. Proliferate index and microvascular density were evaluated only in high grade tumors (AA, GBM and AO) divided in three groups according to PTN expression (low, intermediate and high). These results showed no statistical difference between PTN expression and index of cellular proliferation and neither to PTN expression and microvascular density. Overall survival (OS) analysis (months) showed similar results in high grade gliomas with different levels of PTN expression. CONCLUSIONS: Our results suggest that PTN expression is associated with histopathological grade of astrocytomas. Proliferation rate, microvascular density and overall survival do not seem to be associated with PTN expression.

Clinical, radiographic, and manometric evolution of esophageal involvement by Chagas' disease.

The complete manifestation of esophageal Chagas' disease includes nonperistaltic contractions in the esophageal body, absent lower esophageal sphincter (LES) relaxation, and dilatation of the organ. However, some patients have a minor degree of esophageal denervation and esophageal motility that does not imply a diagnosis of achalasia. Our objective was to evaluate the evolution of esophageal involvement by Chagas' disease in 28 patients with dysphagia for solids and liquids and a positive serologic test for the disease, 14 with complete LES relaxation, 4 with partial (incomplete) LES relaxation, and 10 with absent LES relaxation; only 2 of them had mild dilatation. The patients (21 women), aged 43-74 years (median 60 years), were evaluated by clinical, radiographic, and manometric methods that were repeated 3-14 years (median 7 years) later. Dysphagia improved in 13 (46.4%) patients, was worse in 5 (17.9%), and did not change in 10 (35.7%). The radiographic examination did not change in 24 (85.7%) and was worse in 3 (10.7%). Esophageal manometry revealed a change from peristaltic to simultaneous contractions in 2 patients (7.1%), LES relaxation changed from complete to partial in 5 (17.9%), and from partial to absent in 2 (7.1%). There was no further clinical, radiographic, or manometric impairment in 15 (53.6%) patients. The symptom duration was longer and the age when they were evaluated was older in patients with no progression of the disease. We conclude that a conspicuous part of this group of patients with esophageal Chagas' disease and dysphagia had no progression of esophageal disease after 3-14 years. This possibility should be considered when making therapeutic decisions.