Plasma Lipid Profile and Systemic Inflammation in Patients With Cancer Cachexia.

Cancer cachexia affects about 80% of advanced cancer patients, it is linked to poor prognosis and to date, there is no efficient treatment or cure. The syndrome leads to progressive involuntary loss of muscle and fat mass induced by systemic inflammatory processes. The role of the white adipose tissue (WAT) in the onset and manifestation of cancer cachexia gained importance during the last decade. WAT wasting is not only characterized by increased lipolysis and release of free fatty acids (FFA), but in addition, owing to its high capacity to produce a variety of inflammatory factors. The aim of this study was to characterize plasma lipid profile of cachectic patients and to correlate the FA composition with circulating inflammatory markers; finally, we sought to establish whether the fatty acids released by adipocytes trigger and/or contribute to local and systemic inflammation in cachexia. The study selected 65 patients further divided into 3 groups: control (N); weight stable cancer (WSC); and cachectic cancer (CC). The plasma FA profile was significantly different among the groups and was positively correlated with pro-inflammatory cytokines expression in the CC patients. Therefore, we propose that saturated to unsaturated FFA ratio may serve as a means of detecting cachexia.

Association between ANGPTL-4 and the proinflammatory process in cancer cachexia patients.

BACKGROUND: Contradictory results are reported for the role of angiopoietin-like 4 (ANGPTL-4) in the development of cancer-cachexia and inflammation, given its importance in angiogenesis and inflammatory signaling. Our aim was to analyze the levels of ANGPTL-4 in colorectal cancer patients with a stable weight and those with cachexia in order to establish a relationship between ANGPTL-4 and the inflammatory process. RESULTS: Plasma and tumor levels of ANGPTL-4 were higher in CC in comparison to other groups. A positive association was verified between plasmatic ANGPTL-4 and NFκB levels in tumor from CC. In WSC, we identified an association between the plasmatic ANGPTL-4, IL-15, and IL-10 in tumor and IL-15 in MES. Increased levels of NFκB and TNF-R1 in MES were detected in CC in comparison to WSC. Specifically in CC-group, a positive correlation was found between ANGPTL-4 levels and those of IL-1ß, TNF-α, and NFκB in tumor, along with an association between ANGPTL-4 levels with IL-1ß and MCP-1 levels in tumor; and ANGPTL-4 and IL-1ß levels in MES. METHODS: We studied 102 patients, who were divided into three groups: control patients (C, n=37), cancer patients with a stable weight (WSC, n=23), and cancer-cachexia patients (CC, n=42). Samples of plasma, tumor, mesenteric (MES) and subcutaneous adipose tissue were removed for the determination of ANGPTL-4 levels and other proinflammatory factors. CONCLUSIONS: ANGPTL-4 levels were higher in plasma and tumor of CC-group, and positively associated with pro-inflammatory and pro-tumorigenic factors. Our results suggest an opposite effect of ANGPTL-4 depending on the concentration and presence of cachexia.

Adipose tissue fibrosis in human cancer cachexia: the role of TGFß pathway.

BACKGROUND: Cancer cachexia is a multifactorial syndrome that dramatically decreases survival. Loss of white adipose tissue (WAT) is one of the key characteristics of cachexia. WAT wasting is paralleled by microarchitectural remodeling in cachectic cancer patients. Fibrosis results from uncontrolled ECM synthesis, a process in which, transforming growth factor-beta (TGFß) plays a pivotal role. So far, the mechanisms involved in adipose tissue (AT) re-arrangement, and the role of TGFß in inducing AT remodeling in weight-losing cancer patients are poorly understood. This study examined the modulation of ECM components mediated by TGFß pathway in fibrotic AT obtained from cachectic gastrointestinal cancer patients. METHODS: After signing the informed consent form, patients were enrolled into the following groups: cancer cachexia (CC, n = 21), weight-stable cancer (WSC, n = 17), and control (n = 21). The total amount of collagen and elastic fibers in the subcutaneous AT was assessed by histological analysis and by immunohistochemistry. TGFß isoforms expression was analyzed by Multiplex assay and by immunohistochemistry. Alpha-smooth muscle actin (αSMA), fibroblast-specific protein (FSP1), Smad3 and 4 were quantified by qPCR and/or by immunohistochemistry. Interleukin (IL) 2, IL5, IL8, IL13 and IL17 content, cytokines known to be associated with fibrosis, was measured by Multiplex assay. RESULTS: There was an accumulation of collagen and elastic fibers in the AT of CC, as compared with WSC and controls. Collagens type I, III, VI, and fibronectin expression was enhanced in the tissue of CC, compared with both WSC and control. The pronounced expression of αSMA in the surrounding of adipocytes, and the increased mRNA content for FSP1 (20-fold) indicate the presence of activated myofibroblasts; particularly in CC. TGFß1 and TGFß3 levels were up-regulated by cachexia in AT, as well in the isolated adipocytes. Smad3 and Smad4 labeling was found to be more evident in the fibrotic areas of CC adipose tissue. CONCLUSIONS: Cancer cachexia promotes the development of AT fibrosis, in association with altered TGFß signaling, compromising AT organization and function.

NF-κBp65 and Expression of Its Pro-Inflammatory Target Genes Are Upregulated in the Subcutaneous Adipose Tissue of Cachectic Cancer Patients.

Cancer cachexia, of which the most notable symptom is severe and rapid weight loss, is present in the majority of patients with advanced cancer. Inflammatory mediators play an important role in the development of cachexia, envisaged as a chronic inflammatory syndrome. The white adipose tissue (WAT) is one of the first compartments affected in cancer cachexia and suffers a high rate of lipolysis. It secretes several cytokines capable of directly regulating intermediate metabolism. A common pathway in the regulation of the expression of pro-inflammatory cytokines in WAT is the activation of the nuclear transcription factor kappa-B (NF-κB). We have examined the gene expression of the subunits NF-κBp65 and NF-κBp50, as well as NF-κBp65 and NF-κBp50 binding, the gene expression of pro-inflammatory mediators under NF-κB control (IL-1ß, IL-6, INF-γ, TNF-α, MCP-1), and its inhibitory protein, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκB-α). The observational study involved 35 patients (control group, n = 12 and cancer group, n = 23, further divided into cachectic and non-cachectic). NF-κBp65 and its target genes expression (TNF-α, IL-1ß, MCP-1 and IκB-α) were significantly higher in cachectic cancer patients. Moreover, NF-κBp65 gene expression correlated positively with the expression of its target genes. The results strongly suggest that the NF-κB pathway plays a role in the promotion of WAT inflammation during cachexia.

Subserous lymphangioma of the sigmoid colon: an uncommon cause of acute abdomen in pediatric patients.

Lymphangioma is a rare, benign lesion derived from a malformation of the lymphatic system, which is more frequently found in the head, neck, and axilla. However, it may be present anywhere in the body, and the diagnosis involves adults as children with some distinct clinical features among them. In pediatric patients, abdominal cystic lymphangioma occurs mostly in the mesentery presenting abdominal pain, intestinal obstruction, or, more rarely, hemorrhage. The authors report the case of a child with a short-course history of fever, abdominal pain, and constipation. The physical examination disclosed the presence of an abdominal mass and signs of peritoneal irritation. Imaging was consistent with a cystic lesion compressing the sigmoid colon and laterally displacing the remaining loops. Exploratory laparotomy was undertaken, and a sigmoidectomy, followed by Hartman's colostomy, was performed. Histological examination revealed the nature of the lesion as a cystic lymphangioma. The authors highlight the clinical features of this entity and call attention to this disease in the differential diagnosis of acute abdomen or abdominal pain, mainly in pediatric patients.

Unilateral giant renal angiomyolipoma and pulmonary lymphangioleiomyomatosis.

Angiomyolipomas (AMLs) are mesenchymal neoplasms, named so because of the complex tissue composition represented by variable proportions of mature adipose tissue, smooth muscle cells, and dysmorphic blood vessels. Although AMLs may rise in different sites of the body, they are mostly observed in the kidney and liver. In the case of renal AMLs, they are described in two types: isolated AMLs and AMLs associated with tuberous sclerosis (TS). While most cases of AMLs are found incidentally during imaging examinations and are asymptomatic, others may reach huge proportions causing symptoms. Pulmonary lymphangioleiomyomatosis (LAM) is a rare benign disease characterized by cystic changes in the pulmonary parenchyma and smooth muscle proliferation, leading to a mixed picture of interstitial and obstructive disease. AML and LAM constitute major features of tuberous sclerosis complex (TSC), a multisystem autosomal dominant tumor-suppressor gene complex diagnosis. The authors report the case of a young female patient who presented a huge abdominal tumor, which at computed tomography (CT) show a fat predominance. The tumor displaced the right kidney and remaining abdominal viscera to the left. Chest CT also disclosed pulmonary lesions compatible with lymphangioleiomyomatosis. Because of sudden abdominal pain accompanied by a fall in the hemoglobin level, the patient underwent an urgent laparotomy. The excised tumor was shown to be a giant renal AML with signs of bleeding in its interior. The authors call attention to the diagnosis of AML and the huge proportions that the tumor can reach, as well as for ruling out the TSC diagnosis, once it may impose genetic counseling implications..

Fibrosarcoma: a challenging diagnosis.

Fibrosarcoma represent a rare group of soft tissue malignancies derived from fibrous connective tissue and immature proliferating fibroblasts or undifferentiated anaplastic spindle cells. It affects patients in the fourth and fifth decade of life. Fibrosarcomas can be classified in subtypes such as low-grade fibromyxoid sarcoma (LGFMS) and sclerosing epithelioid fibrosarcoma (SEF), and others. Histological features that overlap between types of fibrosarcomas is well known and reported in the literature. We report the case of a 53-year-old patient who presented a tumor in the axillary fossa, which was initially diagnosed as a solitary fibrous tumor. Due to recurrence of the lesion, as well as the presence of distant metastases, the histological revision considered the diagnosis of breast metaplastic carcinoma, since the tumor expressed the p63 antigen and estrogen and progesterone receptors. Unexpected resistance to chemotherapy motivated the diagnosis re-evaluation, which was due to MUC4 expression and morphological characteristics concluded by a hybrid LGFMS-SEF tumor. The authors call attention to the difficult diagnosis in cases of soft tissue tumors. A broad panel of immunohistochemical research is required as the clinical course is essential to the final diagnosis.

Nodular lymphocyte predominance Hodgkin lymphoma of the parotid gland: a case report.

The parotid is the most frequent site of primary salivary gland tumors. Lymphomas represent 0.2 to 0.8% of all malignant parotid tumors. Primary Hodgkin lymphoma of the parotid gland is rare with few cases reported in literature. The nodular lymphocyte predominance Hodgkin lymphoma (HL) is considered a particular clinical and histopathological subtype of HL. It has never been reported in the parotid gland since its incorporation in the 2001 World Health Organization Classification. The authors describe a case of a 32-year-old male who sought medical attention because of a one-year history of right cheek enlargement. A parotid nodule was submitted to a fine needle aspiration biopsy which disclosed a suspected lymphoproliferative disorder. A surgical dissection of the parotid gland was performed and an enlarged intraparotid lymph node measuring 4cm in its longest axis was excised, preserving the parotid gland integrity as well as the facial nerve. The pathological examination disclosed the diagnosis of nodular lymphocyte predominance Hodgkin lymphoma in this lymph node within the parotid gland. The treatment was completed with local radiotherapy and the 5-year follow up was uneventful.