Receptor-Binding Cancer Antigen Expression in Thyroid Neoplasms: A Retrospective Study.

Background: Receptor-binding cancer antigen (RCAS1) is a membrane protein, regarded as a tumor-associated antigen. Cancer cells evade immune response with RCAS1 up-regulation, inducing apoptosis to tumor infiltrating lymphocytes. Thyroid cancer incidence is rising and its accurate diagnosis in early stage is targeted. The aim of this study is to access RCAS1 expression in benign and malignant thyroid pathology. Methods: This is a retrospective study of 110 patients, who had thyroidectomy in a single tertiary referral centre between January 2008 until December 2014. Immunohistochemistry study for RCAS1 expression was carried out and correlation with clinical and histopathological data is attempted. Results: RCAS1 immunostaining was found positive in 81 out of 110 cases. Notably it was deemed positive in all malignant thyroid tissue samples (p 0.001). In thyroid malignancy, tumor size, thyroid capsule invasion and positive lymph nodes status were positively correlated with moderate and strong expression of RCAS1. For papillary thyroid carcinoma, the vast majority (35/37 cases, 94.6%) were also classified as having moderate or strong RCAS1 expression. Conclusions: RCAS1 expression can aid in differential diagnosis between benign and malignant thyroid pathology, while its strong expression correlates with worse oncological features.

Low expression of miR-20b-5p indicates favorable prognosis in laryngeal squamous cell carcinoma, especially in patients with non-infiltrated regional lymph nodes.

PURPOSE: Tumor recurrence and distant metastasis are very common in laryngeal squamous cell carcinoma (LSCC). In this study, we examined the potential prognostic value of microRNA-20b-5p (miR-20b-5p), a component of the tumor-related miR-106a/363 cluster. MATERIALS AND METHODS: Total RNA was purified from 105 tissue specimens resected from patients having undergone surgical treatment for primary LSCC. After in vitro polyadenylation and reverse transcription, a sensitive real-time quantitative polymerase chain reaction (qPCR) methodology was applied for the relative quantification of miR-20b-5p levels. Then, we proceeded with biostatistical analysis, seeking to assess the prognostic value of miR-20b-5p expression in LSCC. RESULTS: miR-20b-5p positivity constitutes a predictor of inferior DFS and OS in LSCC (P < 0.001 and P = 0.002, respectively). The significant prognostic value of miR-20b-5p expression status seems to be independent of tumor size, histological grade, and TNM stage, as revealed by the multivariate bootstrap Cox regression analysis. Kaplan-Meier survival analysis showed also that miR-20b-5p expression status can stratify LSCC patients with non-infiltrated regional lymph nodes (N0) into two subgroups with distinct prognosis (P = 0.004 and P = 0.004, respectively). CONCLUSIONS: The miR-20b-5p expression status is a promising molecular tissue biomarker in LSCC, with an independent prognostic value, and thus merits further validation in larger cohorts of patients.

Early Diagnosis and Surgical Treatment for Necrotizing Fasciitis: A Multicenter Study.

BACKGROUND: Necrotizing fasciitis (NF) is a group of relatively rare infections, usually caused by two or more pathogens. It affects the skin and subcutaneous tissues of lower and upper limbs, perineal area (Fournier's gangrene), and the abdominal wall. Early diagnosis and aggressive surgical management are of high significance for the management of this potentially lethal disease. METHODS: We conducted a retrospective study in patients who presented, during the last decade, at four University Surgical Departments in the area of Athens, Greece, with an admission diagnosis of NF. Demographic, clinical, and laboratory data were gathered, and the preoperative and surgical treatment, as well as the postoperative treatment was analyzed for these patients. RESULTS: A total of 62 patients were included in the study. The mean age of patients was 63.7 (47 male patients). Advanced age (over 65 years) (P < 0.01) and female sex (P = 0.04) correlated significantly with mortality. Perineum was the mostly infected site (46.8%), followed by the lower limbs (35.5%), the upper limbs, and the axillary region (8.1%). Diabetes mellitus was the most common coexisting disease (40.3%), followed by hypertension (25.8%) and obesity (17.7%). The most common symptom was local pain and tenderness (90.3%). Septic shock occurred in eight patients (12.9%) and strongly correlated with mortality (P < 0.01). Laboratory data were used to calculate the LRINEC score of every patient retrospectively; 26 patients (41.9%) had LRINEC score under 6, 20 patients (32.3%) had LRINEC score 6-8, and 16 patients (25.8%) had LRINEC score >9. Surgical debridement was performed in all patients (mean number of repeated debridement 4.8), and in 16 cases (25.8%) the infected limb was amputated. The mean length of hospital stay was 19.7 days, and the overall mortality rate of our series was 17.7%. CONCLUSION: Diagnosis of NF requires high suspect among clinicians, as its clinical image is non-specific. Laboratory tests can depict the severity of the disease; therefore, they must be carefully evaluated. Urgent surgical debridement is the mainstay of treatment in all patients; the need of repetitive surgical debridement is undisputed.

Changes in T-lymphocytes' viability after laparoscopic versus open cholecystectomy.

Laparoscopic surgery results in decreased immune and metabolic stress response compared to open surgery. Our aim was to evaluate the suspension of host immune defense in terms of apoptosis, necrosis, and survival of peripheral T-lymphocytes in patients undergoing laparoscopic versus open cholecystectomy. Apoptosis, necrosis and viability of peripheral T-lymphocytes were measured preoperatively and postoperatively by means of flow cytometry in 27 patients undergoing laparoscopic cholecystectomy and 25 undergoing open cholecystectomy. White cell count, CRP, and serum glucose levels were also measured. Viable peripheral T-lymphocytes were significantly decreased in open cholecystectomy (P = 0.02), while their late apoptotic as well as the overall necrotic rate were significantly increased (P = 0.01 and P < 0.01, respectively). Open cholecystectomy was also associated with lower levels of surviving circulating T-lymphocytes (P = 0.01) and higher percentage of necrotic T lymphocytes (P = 0.03) 24 hours postoperatively compared to laparoscopic cholecystectomy. Serum CRP was increased 24 hours after open cholecystectomy (P = 0.04). All differences failed to sustain more than 48 hours postoperatively. Increased viability and decreased necrosis of circulating T-lymphocytes were observed in laparoscopic cholecystectomy. Necrosis (and not apoptosis) seems to be the predominant pathway of T-lymphocyte death in open cholecystectomy, in a process reaching its peak at 24 hours and further attenuating 48 hours postoperatively.

Mycophenolate mofetil and sirolimus in hepatocyte transplantation in an experimental model of toxic acute liver failure.

INTRODUCTION: Hepatocyte transplantation is proposed as a solution for liver failure. The allotransplantation of hepatocytes has been studied extensively, however, graft rejection remains a major problem. The aim of the present study was to evaluate the immunosuppressive activity of mycophenolate mofetil (MMF), sirolimus, and their combination in an experimental model of hepatocyte allotransplantation in rats with acute liver failure. MATERIALS AND METHODS: Five male Wistar rats were used as hepatocyte donors and 60 male Lewis rats as recipients. The recipients were divided into five groups of 12 animals each. Group 1: no treatment. Group 2: cyclosporine. Group 3: sirolimus. Group 4: MMF. Group 5: MMF and sirolimus. All surviving animals were preserved for 15 days. For the induction of acute liver failure the recipients were injected with N-dimethyl-nitrosamine 24 hr before transplantation. The isolated hepatocytes were transplanted intrasplenically. RESULTS: Analysis of the results showed a statistically significant prolongation of animal survival for groups 3, 4, and 5. More animals in group 5 survived than those in groups 3 and 4, although the difference was not statistically significant. Transplant hepatocyte survival was significantly better in groups 3, 4, and 5. Hepatocytes transplanted in the spleen of animals of group 5 showed better survival compared with those of groups 3 and 4. CONCLUSION: Use of MMF and sirolimus, as monotherapy or in combination, is both effective and safe as immunosuppressive treatment in hepatocyte transplantation, as was proven in this experimental protocol.

Economic evaluation of intravenous iron treatments in the management of anemia patients in Greece.

PURPOSE: To conduct an economic evaluation comparing Ferinject(®) (ferric carboxymaltose [FCM]) with Venofer(®) (iron sucrose [IS]) and CosmoFer(®) (low-molecular-weight iron dextran [LMWID]) in the management of iron deficiency anemia in Greece. PATIENTS AND METHODS: A cost-minimization analysis was conducted since there are no clear data indicating that one of these regimens is superior to the others in terms of efficacy. Main data inputs were based on bibliography and validated by clinicians. The economic evaluation was conducted for inpatients (ie, surgical patients or patients hospitalized due to a disease related to chronic or acute blood loss) and outpatients (eg, nondialysis chronic kidney disease patients), separately. Analysis was carried out from a National Health Service (NHS) perspective and also from a patient perspective. Total cost treatment reflects the cost of drugs, the cost of all resources expended in patient management such as the cost of disposables for each infusion, the monitoring costs during infusion (salaries of personnel), other hospital expenses, the cost for management of adverse events, the productivity loss, and the traveling cost for patients. RESULTS: In the case of outpatients, the mean total cost per patient in the FCM arm was €198.6, in the IS arm €627.7, and in the LMWID arm, €510.5. For inpatients the mean total cost was estimated at €189.2 for FCM while it was €419.9 and €228.8 for IS and LMWID, respectively. Budget impact analysis for a typical Greek hospital with 100 patients revealed that the total cost of FCM (inpatients analysis) was 113% and 15.4% lower against their comparators. In an outpatient situation, the total cost of FCM was 201.1% and 151.8% lower compared with IS and LMWID, respectively. CONCLUSION: Ferric carboxymaltose may represent a cost-saving option compared with the most likely alternative existing therapies used for the management of anemia in the National Health Service of Greece.

Apoptotic and proliferative status in HPV (+) and HPV (-) inverted papilloma patients. Correlation with local recurrence and clinicopathological variables.

Inverted papilloma (IP) is a rare sinonasal benign lesion characterized by aggressive biological behavior. Our aim was to evaluate the expression of various proliferation and apoptotic markers and the presence of HPV genotypes in paraffin sections gathered from surgically treated IP patients. Immunohistochemistry for PCNA, bax, cytochrome c and caspase-8 and flow cytometry for the detection of apoptosis, necrosis and ki67 expression were performed. The identification of various HPV subtypes was achieved by nested PCR amplification. Nasal polyps (NP) and specimens from normal nasal epithelium (NE) were used as controls. PCNA was more frequently expressed in IP compared to NE (p=0.04) and caspase-8 and bax staining were less frequently observed in IP compared to NP (p=0.004 and p=0.01 respectively) and NE (p=0.003 and p=0.01, respectively). IP and NP presented significantly higher Ki67 flow cytometry values compared to NE (p<0.001 and p=0.02 respectively). Cytochrome c was more frequently expressed in IP specimens with more prominent inflammation (p=0.02). A low HPV DNA detection rate was observed. Neither HPV status nor any of the apoptotic or proliferative markers studied was associated with the patients' clinicopathological characteristics. Increased Ki67 appeared to correlate with disease recurrence (p=0.01). Increased PCNA and Ki67 and decreased bax and caspase-8 expression indicate that cell proliferation is increased while apoptosis is inhibited in IP, explaining its biological behavior.