Differential expansion of circulating human MDSC subsets in patients with cancer, infection and inflammation

Background Myeloid-derived suppressor cells (MDSC) are a functional myeloid cell subset that includes myeloid cells with immune suppressive properties. The presence of MDSC has been reported in the peripheral blood of patients with several malignant and non-malignant diseases. So far, direct comparison of MDSC across different diseases and Centers is hindered by technical pitfalls and a lack of standardized methodology. To overcome this issue, we formed a network through the COST Action Mye-EUNITER (www.mye-euniter.eu) with the goal to standardize and facilitate the comparative analysis of human circulating MDSC in cancer, inflammation and infection. In this manuscript, we present the results of the multicenter study Mye-EUNITER MDSC Monitoring Initiative, that involved 13 laboratories and compared circulating MDSC subsets across multiple diseases, using a common protocol for the isolation, identification and characterization of these cells. Methods We developed, tested, executed and optimized a standard operating procedure for the isolation and immunophenotyping of MDSC using blood from healthy donors. We applied this procedure to the blood of almost 400 patients and controls with different solid tumors and non-malignant diseases. The latter included viral infections such as HIV and hepatitis B virus, but also psoriasis and cardiovascular disorders. Results We observed that the frequency of MDSC in healthy donors varied substantially between centers and was influenced by technical aspects such as the anticoagulant and separation method used. Expansion of polymorphonuclear (PMN)-MDSC exceeded the expansion of monocytic MDSC (M-MDSC) in five out of six solid tumors. PMN-MDSC expansion was more pronounced in cancer compared with infection and inflammation. Programmed death-ligand 1 was primarily expressed in M-MDSC and e-MDSC and was not upregulated as a consequence of disease. LOX-1 expression was confined to PMN-MDSC. Conclusions This study provides improved technical protocols and workflows for the multi-center analysis of circulating human MDSC subsets. Application of these workflows revealed a predominant expansion of PMN-MDSC in solid tumors that exceeds expansion in chronic infection and inflammation

Multiple Giant Splenic Artery Aneurysms Causing Sinistral (Left-Sided) Portal Hypertension

Background. Splenic artery aneurysm is the most common type of visceral aneurysms. They are usually asymptomatic and have a potential for rupture and therefore life-threatening hemorrhage. It is rare for them to cause sinistral portal hypertension. Case Report. A 23-year-old female patient presented to our clinic with gastric varices, splenomegaly, pancytopenia, and normal liver functions. She was thus diagnosed with left-sided portal hypertension. Radiologic evaluation showed splenomegaly, splenic vein obstruction, and multiple aneurysms along the splenic artery ranging from 2.5 cm to 7 cm. Splenic artery aneurysm was thought to be the cause of portal hypertension and hypersplenism. We decided splenectomy is the best course of treatment. Pancytopenia could not be corrected preoperatively despite the transfusion treatment. Surgical exploration revealed multiple aneurysms deeply embedded in pancreas. Thrombocyte and erythrocyte transfusion was performed after splenic artery ligation to correct pancytopenia before further intervention. Splenic artery, spleen, and distal pancreas were resected en bloc. Patient's blood parameters became normal within first postoperative day. Patient had an uneventful postoperative course and was discharged without incident. Conclusion. Splenic artery aneurysms are rare but potentially life-threatening incidents. Therefore, it is important to know the unusual presentations and prepare accordingly.PubMe

Nonfunctional Pancreatic Neuroendocrine Tumors: Advances In Diagnosis, Management, And Controversies

In this article, we aimed to review the literature on the clinics and management of nonfunctional pancreatic neuroendocrine tumors (NPNET). Pancreatic neuroendocrine tumors (PNET) are rare tumors with a <1/100,000 incidence and constitute approximately 2 to 10% of all pancreatic tumors. Nonfunctional PNETs are difficult to detect at early stages since they have no symptoms. Except those detected accidentally during different diagnoses, the majority of PNETs are detected in the advanced stages, with symptoms related to tumor size or liver metastasis. We reviewed the studies published in the English medical literature through PubMed and summarized the clinical features and current approaches to the treatment and follow-up of the NPNET. The common imaging techniques used for the detection of tumor localization, size, locoregional, and metastatic involvement are contrasted computed tomography, magnetic resonance imaging, endoscopic ultrasonography, and somatostatin receptor scintigraphy. Surgical resection is the only curative treatment. However, in advanced locoregional disease and liver metastasis, interventive ablative therapies such as palliative reductive surgery, selective hepatic arterial embolization, radiofrequency ablation; and systemic therapies, such as peptide receptor radionuclide therapy, chemotherapy, somatostatin analogous therapy, interferon, VEGF inhibitor, and mTOR inhibitor may be used as symptom relieving or may improve progression-free survival and total survival. Current knowledge on NPNET shows that the treatment should be personalized considering the prognostic features and life expectancy of the patient.Wo

Intraductal Papillary Mucinous Neoplasm of the Pancreas: Current Perspectives

In this article, we aimed to review the literature on the clinics and management of intraductal papillary mucinous neoplasm (IPMN). Intraductal papillary mucinous neoplasm of the pancreas is a mucin-producing cystic mass originating from the pancreatic ductal system. Approximately 25% of the pancreatic neoplasms resected surgically and 50% of pancreatic cysts detected incidentally are IPMNs. They can be benign or malignant in character, while malignant transformation of benign forms can be encountered. It is important to determine IPMNs in the early stages, implementation of appropriate treatment approaches, and follow-up to provide better prognosis. We reviewed the studies published in the English medical literature through PubMed and summarized the clinical features and current approaches to the treatment and follow-up of the IPMN. Due to the recent advances and widespread implementation of radiological imaging techniques, the incidental detection rate of IPMNs has increased significantly. The effective treatment of the disease is possible via the detailed diagnosis of the disease, determination of the prognostic factors, and a multidisciplinary approach. Recent literature also emphasized the molecular profile determination approaches for assessment of prognosis of patients with IPMN. Current knowledge on IPMN, a clinically important epidemiologic problem, shows that the treatment should be personalized considering the prognostic features and life expectancy of the patient.Wo

What Changed In Necrotizing Fasciitis In Twenty-Five Years?

Necrotizing fasciitis (NF) is a deadly soft tissue infection characterized by necrosis of subcutaneous tissues. In this study, our aim was to identify variables affecting patient outcome and mortality in necrotizing fasciitis and their temporal changes. We reviewed records of 45 patients treated at our institution between 1979 and 2004. Data about gender, age, etiology, site of involvement, bacteriology, type of surgery, supportive treatment, accompanying diseases, mortality were collected. Factors contributing to mortality were sepsis, renal failure, liver failure, multi organ failure, disseminated intravascular coagulopathy and long term intubation. Mortalities accumulated in first 23 patients. There was not difference in microbiology, demographics, etiology, site of involvement, debridement technics between first patients and recent patients of the institution. Mortality in necrotizing fasciitis is mostly because of sepsis and associated disorders. Adequate control of the microbiological agent and preventing further contamination of the wound is cardinal part of treatment in NF.Wo

Exhaled breath condensate MMP-9 level and its relationship with asthma severity and interleukin-4/10 levels in children

WOS: 000303441900004PubMed ID: 22541398Background: Matrix metalloproteases (MMPs) are key mediators in airway remodeling, and MMP-9 is the main type investigated to discover its implication for the pathogenesis and severity of asthma. Objective: To evaluate MMP-9 and its natural tissue inhibitors of metalloproteinases (TIMP-1) levels of exhaled breath condensate (EBC) in children with asthma. We also analyzed any potential relationship between these enzymes and EBC interleukin (IL)-4/10 levels as well as asthma severity. Methods: Three study groups were formed: group 1, children with persistent asthma (n = 20); group 2, children with intermittent asthma (n = 10), and group 3, healthy controls (n = 12). Pulmonary functions were measured as forced expiratory volume in 1 second (FEV1), peak expiratory flow (PEF), and forced expiratory flow from 25% to 75% of vital capacity values by spirometry, and MMP-9, TIMP-1 and IL-4/10 levels in EBC were analyzed by enzyme-linked immunosorbent assay (ELISA). Results: The MMP-9 levels of EBC were found to be 57.7 +/- 17.5, 35.4 +/- 11.7, and 30.6 +/- 3.7 ng/mL in children belonging to group 1, group 2 and group 3, respectively. Children belonging to group 1 and group 2 showed significantly higher MMP-9 levels of EBC in comparison with the controls (P < .001 and P < .047, respectively). No statistically significant difference was found between groups regarding TIMP-1 levels of EBC. EBC MMP-9 levels were inversely correlated with both FEV1 and PEF values (r = -0.472, P = .011, and r = -0.571, P = .002, respectively) in children with asthma. Positive correlations were also seen between MMP-9 levels and IL-4/10 levels of EBC (r = 0.419, P = .027 and r = 0.405, P = .032, respectively) in children with asthma. Conclusion: We showed that MMP-9 levels of EBC are elevated in children with asthma and correlated with lung functions and other inflammatory markers such as IL-4/IL10 in EBC. (C) 2012 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved