Role of surgical setting and patients-related factors in predicting the occurrence of postoperative pulmonary complications after abdominal surgery.

OBJECTIVE: The aim of this retrospective study was to evaluate the role of surgical setting (urgent vs. elective) and approach (open vs. laparoscopic) in affecting postoperative pulmonary complications (PPCs) prevalence in patients undergoing abdominal surgery. PATIENTS AND METHODS: After local Ethical Committee approval, 409 patients who had undergone abdominal surgery between January and December 2014 were included in the final analysis. PPCs were defined as the development of one of the following new findings: respiratory failure, pulmonary infection, aspiration pneumonia, pleural effusion, pneumothorax, atelectasis on chest X-ray, bronchospasm or un-planned urgent re-intubation. RESULTS: PPCs prevalence was greater in urgent (33%) vs. elective setting (7%) (χ2 with Yates correction: 44; p=0.0001) and in open (6%) vs. laparoscopic approach (1.9%) (χ2 with Yates correction: 12; p=0.0006). PPCs occurrence was positively correlated with in-hospital mortality (Biserial Correlation r=0.37; p=0.0001). Logistic regression showed that urgent setting (p=0.000), Ariscat (Assess Respiratory Risk in Surgical Patients in Catalonia) score (p=0.004), and age (p=0.01) were predictors of PPCs. A cut-off of 23 for Ariscat score was also identified as determining factor for PPCs occurrence with 94% sensitivity and 29% specificity. CONCLUSIONS: Patients undergoing abdominal surgery in an urgent setting were exposed to a higher risk of PPCs compared to patients scheduled for elective procedures. Ariscat score fitted with PPCs prevalence and older patients were exposed to a higher risk of PPCs. Prospective studies are needed to confirm these results.

Furin expression in squamous cell carcinomas of the oral cavity and other sites evaluated by tissue microarray technology.

Furin is a proprotein convertase that activates many cancer development-related substrates such as growth factors, growth factor-receptors, adhesion molecules, and matrix degrading enzymes. Furin expression was studied in sections from tissue microarrays (TMA) and conventional paraffin blocks in a collection of squamous cell carcinomas (SCC) from three different sites. A total of 118 SCCs from the oral cavity, lung and esophagus as well as 34 precursor lesions (intraepithelial neoplasia) from the oral and bronchial mucosae were studied by immunohistochemistry. Furin expression was notably higher in most precursor lesions than in normal epithelia. Tumors from either the TMAs or the conventional blocks showed significant differences when compared to the mostly negative normal epithelia. High levels of furin expression were observed in approximately 50% SCCs of three different sites as well as in precursor lesions of the oral and bronchial mucosae. In addition another 30% showed low furin expression that was localized in all tumor cells including those in a basaloid position. Normal epithelia sometimes showed low level expression but the normal basal cells were always negative. These results show that furin is up-regulated in SCCs from three different organs and validates its use as a tumor marker in both invasive and pre-invasive neoplasia.

Furin expression in squamous cell carcinomas of the oral cavity and other sites evaluated by tissue microarray technology

Furin is a proprotein convertase that activates many cancer development-related substrates such as growth factors, growth factor-receptors, adhesion molecules, and matrix degrading enzymes. Furin expression was studied in sections from tissue microarrays (TMA) and conventional paraffin blocks in a collection of squamous cell carcinomas (SCC) from three different sites. A total of 118 SCCs from the oral cavity, lung and esophagus as well as 34 precursor lesions (intraepithelial neoplasia) from the oral and bronchial mucosae were studied by immunohistochemistry. Furin expression was notably higher in most precursor lesions than in normal epithelia. Tumors from either the TMAs or the conventional blocks showed significant differences when compared to the mostly negative normal epithelia. High levels of furin expression were observed in approximately 50

SCCs of three different sites as well as in precursor lesions of the oral and bronchial mucosae. In addition another 30

showed low furin expression that was localized in all tumor cells including those in a basaloid position. Normal epithelia sometimes showed low level expression but the normal basal cells were always negative. These results show that furin is up-regulated in SCCs from three different organs and validates its use as a tumor marker in both invasive and pre-invasive neoplasia.

Furin expression in squamous cell carcinomas of the oral cavity and other sites evaluated by tissue microarray technology.

Furin is a proprotein convertase that activates many cancer development-related substrates such as growth factors, growth factor-receptors, adhesion molecules, and matrix degrading enzymes. Furin expression was studied in sections from tissue microarrays (TMA) and conventional paraffin blocks in a collection of squamous cell carcinomas (SCC) from three different sites. A total of 118 SCCs from the oral cavity, lung and esophagus as well as 34 precursor lesions (intraepithelial neoplasia) from the oral and bronchial mucosae were studied by immunohistochemistry. Furin expression was notably higher in most precursor lesions than in normal epithelia. Tumors from either the TMAs or the conventional blocks showed significant differences when compared to the mostly negative normal epithelia. High levels of furin expression were observed in approximately 50

SCCs of three different sites as well as in precursor lesions of the oral and bronchial mucosae. In addition another 30

showed low furin expression that was localized in all tumor cells including those in a basaloid position. Normal epithelia sometimes showed low level expression but the normal basal cells were always negative. These results show that furin is up-regulated in SCCs from three different organs and validates its use as a tumor marker in both invasive and pre-invasive neoplasia.

Elevated furin expression in aggressive human head and neck tumors and tumor cell lines.

Pro-protein convertases (PCs) are proteases that recognize and cleave precursor proteins. Furin, a well-studied PC, is ubiquitously expressed, and it has been implicated in many physiological and pathological processes. Some substrates for furin, such as membrane type 1 (MT1) matrix metalloproteinase (MMP), an MMP that activates gelatinase, a collagen-degrading enzyme, are associated with the advanced malignant phenotype. This report examines the expression of furin in carcinoma cell lines of different invasive ability. The levels of furin mRNA and protein correlated with the aggressiveness of tumor cell lines derived from head and neck and lung cancers. Furin expression also was investigated in primary head and neck squamous cell carcinomas (HNSCCs). Furin mRNA was not detected in nonmetastasizing carcinomas. In contrast, furin mRNA was expressed in metastasizing HNSCCs. Immunohistochemistry and Western blot analysis confirmed these results at the protein level. Furin activity was investigated indirectly by evaluating the expression of the pro-form and the processed form of MT1-MMP. Metastasizing HNSCCs showed increased expression of MT1-MMP. Furthermore, pro-MT1-MMP expression was noted in most of the nonmetastasizing HNSCCs analyzed by Western blot, and it was absent in the metastasizing HNSCCs. This finding suggests a lower level of furin-mediated MT1-MMP activation in the less aggressive cancers. These observations indicate that furin plays a role in tumor progression. Its overexpression in more aggressive or metastasizing cancers resulted in increased MMP processing.

Furin inhibition results in absent or decreased invasiveness and tumorigenicity of human cancer cells.

Pro-protein convertases such as furin are expressed in many human tumor lines and primary tumors. Furin processes stromelysin-3, membrane type 1 matrix metalloproteinase (MMPs) involved in tumor cell invasiveness, as well as growth factors such as transforming growth factor beta1. Evaluation of furin expression in head and neck squamous cell carcinoma (HNSCC) cells exhibiting different invasive ability showed that furin overexpression correlated with their respective invasiveness. The use of a selective furin inhibitor, alpha 1-PDX (PDX) was studied in three furin-expressing invasive HNSCC cell lines. The effects of PDX transfection were evaluated in vivo and in vitro to determine changes in the malignant phenotype. Transfection of HNSCC cell lines with PDX resulted in significant decrease or absence of tumorigenicity after s.c. inoculation into severe combined immunodeficient mice. Likewise, in vitro invasiveness was reduced approximately 50%. The in vivo invasion assay using tracheal xenotransplants showed even more drastic reductions of the invasive ability of PDX-transfected cells (up to an 80% decrease). PDX-transfected cells did not invade or penetrated less into the tracheal wall tissues than their vector alone-transfected counterparts. In addition, the former cells showed a remarkable decrease in MMP-2 processing and activity. After PDX transfection the cells were less efficient in processing the tumor progression-associated furin substrates transforming growth factor beta1 and pro-membrane type 1-MMP. These findings indicate that furin inhibition is a feasible approach to attenuate and even abolish certain critical attributes of the advanced malignant phenotype. Thus, furin should be considered as a promising target for cancer therapy.