Potential role of chemerin in recruitment of plasmacytoid dendritic cells to diseased skin.

Interferon alpha-producing plasmacytoid dendritic cells (pDC) are crucial contributors to pro-inflammatory or tolerogenic immune responses and are important in autoimmune diseases such as psoriasis. pDC accumulate in the lesional skin of psoriasis patients, but are rarely found in the affected skin of patients with atopic dermatitis (AD). While homeostatic chemokine CXCL12 and inducible pro-inflammatory CXCR3 chemokine ligands may regulate pDC influx to psoriatic skin, the mechanism responsible for selective pDC recruitment in psoriasis vs. AD remains unknown. Circulating pDC from normal donors express a limited number of chemoattractant receptors, including CXCR3 and CMKLR1 (chemokine-like receptor 1). In this work, we demonstrate that circulating pDC from normal donors as well as psoriasis and AD patients express similar levels of CXCR3 and responded similarly in functional migration assays to CXCL10. We next found that blood pDC from normal, AD, and psoriasis patients express functional CMKLR1. In contrast to normal skin, however, lesional skin from psoriasis patients contains the active form of the CMKLR1 ligand chemerin. Furthermore, in affected skin from psoriatic patients the level of active chemerin was generally higher than in AD skin. Taken together, these results indicate that local generation of active chemerin may contribute to pDC recruitment to psoriatic skin.

Differences in prognosis of Siewert II and III oesophagogastric junction cancers are determined by the baseline tumour staging but not its anatomical location.

BACKGROUND: The anatomical Siewert classification for adenocarcinoma of the oesophagogastric junction (OGJ) was dictated by the potential differences in tumour epidemiology and pathology. However, there are some uncertainties whether the distinction of true carcinoma of the cardia (type II) and subcardial gastric cancer (type III) is of clinical value. METHODS: Using a multicentre data set, we studied 243 patients with OGJ adenocarcinomas who underwent gastric resections between 1998 and 2008. Postoperative complications and long-term survival were compared to evaluate the potential differences in clinically relevant outcomes. RESULTS: A group of 109 patients with Siewert type II and 134 with Siewert type III OGJ adenocarcinoma was identified. Both groups showed similar baseline characteristics, including clinical symptoms and duration of diagnostic delay. However, the prevalence of node-negative cancers and superficial (T1-T2) lesions was significantly higher among type II tumours, i.e. 42% vs 21% (P = 0.003) and 43% vs 20% (P = 0.045), respectively. Morbidity and mortality rates were 25% and 3.7%, respectively, but types and incidence of postoperative complications were not affected by the anatomical location of the tumour. The overall median survival was significantly longer for Siewert type II tumours (42 vs 16 months; P < 0.001). However, only patients' age >70 years, depth of tumour infiltration, lymph node metastases, distant metastases, and radical resection were identified as independent prognostic factors using the Cox proportional hazards model. CONCLUSION: The topographic-anatomic sub-classification of OGJ adenocarcinomas does not correspond to relevant differences in clinical parameters of safety and efficacy of surgical treatment.

New insights into IL-12-mediated tumor suppression.

During the past two decades, interleukin-12 (IL-12) has emerged as one of the most potent cytokines in mediating antitumor activity in a variety of preclinical models. Through pleiotropic effects on different immune cells that form the tumor microenvironment, IL-12 establishes a link between innate and adaptive immunity that involves different immune effector cells and cytokines depending on the type of tumor or the affected tissue. The robust antitumor response exerted by IL-12, however, has not yet been successfully translated into the clinics. The majority of clinical trials involving treatment with IL-12 failed to show sustained antitumor responses and were associated to toxic side effects. Here we discuss the therapeutic effects of IL-12 from preclinical to clinical studies, and will highlight promising strategies to take advantage of the antitumor activity of IL-12 while limiting adverse effects.

Dietary inflammatory index as a potential determinant of a length of hospitalization among surgical patients treated for colorectal cancer.

BACKGROUND/OBJECTIVES: Inflammation is a central process responsible for health outcomes among surgical patients. Immunonutrition has been investigated as a promising modifying factor; however, inflammatory properties of habitual diet have not yet been investigated. The purpose of this study was to describe inflammatory properties of diet measured by the dietary inflammatory index (DII) among surgical patients treated for colorectal cancer and to link inflammatory properties of habitual diet with a duration of hospitalization. SUBJECTS/METHODS: A follow-up study among colorectal cancer patients treated surgically was performed in Krakow, Poland. In total, 689 patients were recruited for the study. Habitual diet was assessed using a standardized semiquantitative food frequency questionnaire. Overall, 23 dietary items (including macro-and micronutrients) were used to calculate individuals' DII. Gender, age, marital status, body mass index, smoking status, lifetime physical activity, taking vitamin supplements, number of chronic diseases, cancer site, Duke's staging and surgery type were considered as potential covariates. RESULTS: Participants were aged 58 years, with the average hospitalization time of 11 days. Higher DII (meaning diet with higher anti-inflammatory properties) was negatively associated with the duration of hospitalization (univariable linear regression: b=-0.59; P=0.005). Multivariable logistic regression has shown the decrease of the risk of longer stays (>7 days) among patients with the DII >-4.25, but only among younger (⩽60 years) patients, irrespective of Duke's staging. CONCLUSIONS: The DII might be used as a potential predictor of longer hospitalization among colorectal cancer patients treated surgically. The study provides evidence for the role of dietary-related low-grade inflammation among surgical patients.

Non-curative gastrectomy for metastatic gastric cancer: rationale and long-term outcome in multicenter settings.

BACKGROUND: Metastatic gastric cancer remains a significant problem as the majority of Western patients are diagnosed with disseminated disease and no routine therapeutic regimen is accepted in such cases. METHODS: A cohort of 3141 patients with gastric cancer operated between 1990 and 2005 was evaluated using a multicenter data set held by the Polish Gastric Cancer Study Group to determine potential risks and benefits of non-curative gastrectomy for metastatic disease. Additionally, parameters of Quality of Life (QoL) were evaluated prospectively in 140 patients undergoing gastrectomy using the QLQ-C30 questionnaire. RESULTS: Gastrectomy was carried out in 2258 patients. Distant organ metastases were diagnosed in 951 patients, 415 of which underwent non-curative gastrectomy. The overall mortality rates were significantly higher in patients undergoing non-resectional surgery (10%) than either curative (3%, P < 0.001) or non-curative (4%, P = 0.002) gastrectomy. The overall median survival in patients with metastatic disease was significantly higher for non-curative gastrectomy (10.6 months, 95% confidence interval (CI) 9.3-11.9) than for non-resective operations (4.4 months, 95% CI 4.0 to 4.8, P < 0.001). The hazard ratio of death in patients subject to non-resectional surgery compared to those treated by gastrectomy was 2.923 (95% CI 2.473 to 3.454, P < 0.001). A gradual impairment in QoL parameters was found over 12 months after non-curative resections but changes did not reach statistical significance and individual parameters were similar to gastrectomy without distant metastases. CONCLUSION: Non-curative gastrectomy for metastatic gastric cancer is associated with significantly better survival compared to non-resective surgery and does not impair quality of life.

Serum albumin: its relationship to marrow and renal toxicity from platinum-based combination chemotherapy.

One hundred and three patients treated with CAP chemotherapy were evaluated to determine the relationship between low prechemotherapy serum albumin (less than 3 g/dl) and low WBC nadir (less than 2000 cells/mm3). Additionally, the relationship of serum albumin to renal toxicity (delta serum creatinine) was examined. Low prechemotherapy serum albumin appears to be a marker for advanced disease, but does not appear to predict marrow or renal toxicity.