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International audience; Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case-control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (p

BACKGROUND We studied factors influencing early and late results in patients operated on for aortic valve replacement and coronary artery bypass graft. METHODS 175 patients were retrospectively analysed over a 10-year period ending in December 2002. There were 135 males and 40 females with a mean age of 62.7 +/- 8.9 years; 109 were in NYHA class III/IV; 45 required an urgent operation, and 103 mechanical valves and 72 biological valves were implanted. RESULTS There were 11 operative deaths (6.3 %). Statistical analysis (logistic regression) showed that previous myocardial infarction, poor NYHA class, and low LVEF had a significant effect on early death. There were 52 late deaths at a mean follow-up of 82.7 +/- 38.8 months. Using a Cox survival analysis for any causes, age, urgent operation, low LVEF, and creatinine had a strong impact on unfavourable late outcome. CONCLUSIONS A combination of a patient-related factor (age), cardiac-related condition (low LVEF), co-morbid condition (renal dysfunction), and operative cause (urgent operation) is the most important predictor of late clinical outcome for this combined surgical procedure.

Background In this study, we compared our experience about early and midterm follow-up outcomes for right anterolateral minithoracotomy (RAMT) vs full sternotomy (FS) in surgical aortic valve replacement (AVR) among adolescents with bicuspid aortic valve (BAV). Methods Patients were retrospectively enrolled from January 2008 to December 2017. Inclusion criteria were patients with BAV who had to undergo to AVR. They were divided in two groups: RAMT and FS. The choice of RAMT was based on individual surgeon's preferences or when expressly requested by patient that was informed of nonconventional approach. Results We enrolled 61 patients, 23 in RAMT group and 38 in FS group. The mean age was 15.6 ± 1.7 years for RAMT group and 16.1 ± 1.5 years for FS group (P = .23). The RAMT group had a higher prevalence of female gender (P = .04). The patients in the RAMT group had longer cardiopulmonary bypass (115.2 ± 18.5 vs 102.2 ± 16.5 min; P = .006) and cross-clamp time (78.6 ± 18.1 vs 74.3 ± 15.2 min; P = .01). No patients required intraoperative conversion to FS. No differences were found in ventilation times, postoperative intensive care unit (ICU), and hospital length of stay for both groups. Follow-up echocardiograms were available for all patients at median of 5.2 years (range 0.5-9.6 years, median 5.4 years for RAMT and 5.1 for FS) and no patient required reoperation for aortic prosthesis malfunction. Conclusions Our study shows that RAMT is safe and effective as FS. Although the RAMT operation takes slightly more operation time, it is not associated with major adverse effects.

Background: Cholangiocarcinomas (CC) as well as gallbladder cancers are relatively rare and intractable diseases. Clinical, pathological, and epidemiological studies on these tumors have been under investigation. The current status and/or topics on biliary tract cancers have been reported in the East West Association of Liver Tumor (EWALT), held in Milano, Italy in 2015. Summary: All the authors, herein, specifcally reported the current status and leading-edge findings on biliary tract cancers as the following sequence: epidemiology of CC, surgical therapy for intrahepatic CC, surgical therapy for perihilar CC, surgical therapy for gallblad der cancer, chemotherapy for biliary tract cancers, and new histological features in CC. Key Message: The present review article will update the knowledge on biliary tract cancers, en hancing the quality of daily clinical practice. However, many features about these cancers remain unknown; further studies are required to establish disease-specific optimal treatment strategies.

Background Prostate-specific membrane antigen (PSMA) is overexpressed on the endothelial cells of tumor neo-vessels of several solid malignancies, including differentiated thyroid cancer (DTC). We aimed to test the potential role of PSMA as a biomarker for DTC aggressiveness and outcome prediction. We retrospectively screened all patients who underwent thyroidectomy between 1 January 2010 and 31 December 2017 in our institution. Applying the inclusion (histological diagnosis of thyroid cancer and tissue availability) and exclusion criteria (no clinical or follow-up data or diagnosis of medullary thyroid cancer), a cohort of 59 patients was selected. The monoclonal mouse anti-human PSMA antibody was used to stain tissue sections. A 3-point scale was used to score PSMA positivity: 0–5% expression was considered as negative (score 0), 6–50% as moderately positive (score 1), and 51–100% as highly positive (score 2). A cumulative score (0–10%, 11–79%, and 80–100%) was also explored. Univariate and multivariate logistic regression analyses were performed to predict the presence of distant metastases, chosen as endpoint of aggressiveness. The area under the curve (AUC) was calculated. Cox models were built to predict patient outcome in terms of recurrence, iodine refractoriness, and status at last follow-up, which were calculated using the Kaplan-Meier failure function. Results At immunostaining, 12, 25, and 22 patients had scores of 0, 1, and 2, respectively. According to the cumulative score, PSMA expression was ≤ 10% in 17 cases, 11–79% in 31 cases, and ≥ 80% in 11 cases. At multivariate analysis, age, sex, histotype, vascular invasion, T and N parameters, and PSMA positivity were significant predictors of distant metastases. The AUC was 0.92. Recurrence or progression occurred in 19/59 patients. Twelve patients developed radioiodine (RAI) refractoriness, after a median time of 17 months (range 2–32). One patient died of DTC; 46 of the 58 patients alive at last follow-up were disease free. Median DFS was 23 months (range 3–82). The final multivariate model to predict RAI refractoriness included as covariates the stage, high PSMA expression (≥ 80%), and the interaction between moderate PSMA expression (11–79%) and stage. Conclusions PSMA, a marker of neovasculature formation expressed by DTC, contributes in the prediction of tumor aggressiveness and patient outcome.

Background A hallmark of pancreatic ductal adenocarcinoma is the desmoplastic reaction, but its impact on the tumor behavior remains controversial. Our aim was to introduce a computer -aided method to precisely quantify the amount of pancreatic collagenic extra-cellular matrix, its spatial distribution pattern, and the degradation process. Methods A series of normal, inflammatory and neoplastic pancreatic ductal adenocarcinoma formalin-fixed and paraffin-embedded Sirius red stained sections were automatically digitized and analyzed using a computer-aided method. Results We found a progressive increase of pancreatic collagenic extra-cellular matrix from normal to the inflammatory and pancreatic ductal adenocarcinoma. The two-dimensional fractal dimension showed a significant difference in the collagenic extra-cellular matrix spatial complexity between normal versus inflammatory and pancreatic ductal adenocarcinoma. A significant difference when comparing the number of cycles necessary to degrade the pancreatic collagenic extra-cellular matrix in normal versus inflammatory and pancreatic ductal adenocarcinoma was also found. The difference between inflammatory and pancreatic ductal adenocarcinoma was also significant. Furthermore, the mean velocity of collagenic extra-cellular matrix degradation was found to be faster in inflammatory and pancreatic ductal adenocarcinoma than in normal. Conclusion These findings demonstrate that inflammatory and pancreatic ductal adenocarcinomas are characterized by an increased amount of pancreatic collagenic extra-cellular matrix and by changes in their spatial complexity and degradation. Our study defines new features about the pancreatic collagenic extra-cellular matrix, and represents a basis for further investigations into the clinical behavior of pancreatic ductal adenocarcinoma and the development of therapeutic strategies.

We describe the rare case of a 61-year-old man admitted to our emergency department with visceral-organ and lower-limb malperfusion because of an unknown retroperitoneal high-grade undifferentiated pleomorphic sarcoma and a severe paraneoplastic obstruction of the descending thoracic aorta, treated with thoracic endovascular aortic repair. The postoperative period was uneventful, and the patient was discharged within 4 days. At 6-month follow-up, computed tomography showed complete patency of the descending thoracic aorta. This single case experience shows that thoracic endovascular aortic repair can be a less invasive and effective off-label alternative to exclude infiltrated or obstructed descending thoracic aorta, thus avoiding conventional surgery.

Although thoracic endovascular aortic repair (TEVAR) is the standard of care in acute complicated type B dissections, its role in chronic type B dissections remains controversial. This controversy stems from anatomical differences between acute and chronic dissections, such as a thicker intimal clap and improved results in descending aortic replacement. However, despite these important differences, there has been accumulating evidence on the safety and efficacy of TEVAR in chronic type B aortic dissections, especially when considering the alternative of open surgical repair, which is associated with significantly higher morbidity and in many hands also higher mortality. Herein, we discuss the evidence in the literature highlighting TEVAR's safety and efficacy in this setting.

Background The transatrial repair of the ventricular septal defect (VSD) requires an adequate exposure of its rim. We retrospectively evaluated the effect of using the tricuspid valve incision (TVI) technique, with detachment or radial incision, on the postoperative outcome of children undergoing surgical VSD repair. Methods From January 2008 to September 2017, we retrospectively enrolled 141 patients, divided into two groups: 97 patients (68.8%) underwent TVI and 44 patients (31.2%) did not undergo TVI. All patients received an echocardiogram upon discharge from the hospital and after 1 month, 3 months, 6 months, and 1 year from the treatment. Results No perioperative or late deaths occurred. TVI was associated with a slightly longer cardiopulmonary bypass and cross-clamp time, but there were no differences in the surgical outcome between the two groups. Moreover, no differences occurred concerning residual VSD, atrioventricular block, or tricuspid regurgitation at discharge. Echocardiograms at follow-up were available for 134 patients (95%) with a median of 5.3 years (range, 0.5 to 9.3 years), and the degree of tricuspid regurgitation did not differ between groups. No patient required reoperation for tricuspid regurgitation or residual interventricular shunt. Finally, no difference was found when the two TVI subgroups were compared. Conclusions TVI should be used whenever intraoperative exposure of VSD is compromised to avoid a residual shunt and atrioventricular block. Here we show that this procedure does not significantly compromise tricuspid function, although a large, multicenter, randomized controlled trial is advised to validate this hypothesis.

Purpose No effective salvage treatments are available for patients with advanced/recurrent thymoma (T) or thymic carcinoma (TC) who have progressed after platinum-based chemotherapy. This study evaluated the activity of everolimus in patients with advanced/recurrent T or TC previously treated with cisplatin-containing chemotherapy. Patients and Methods This was a single-arm, single-stage, open-label, multicenter, phase II trial. Patients received oral everolimus 10 mg/d until disease progression, unacceptable toxicity, or patient refusal. A Fleming phase II trial was designed. The null hypothesis of a true disease control rate (DCR) of 40% was tested against a one-sided alternative of a true DCR of 60% (α = β = 0.10): If disease control were achieved in ≥ 21 of the first 41 evaluable patients, everolimus could be recommended for further evaluation. Progression-free survival, overall survival, and safety were also evaluated. Results From 2011 to 2013, 51 patients were enrolled (T, n = 32; TC, n = 19). Complete remission was observed in one patient with TC, partial response in five patients (T, n = 3; TC, n = 2), and stable disease in 38 patients (T, n = 27; TC, n= 11), with a DCR of 88% (T,: 93.8%; TC, 77.8%). With a median follow up of 25.7 months, median progression-free survival was 10.1 months (T,: 16.6 months; TC, 5.6 months), and median overall survival was 25.7 months (T, not reached; TC, 14.7 months). Fourteen patients had a serious drug-related adverse event; of these patients, nine permanently discontinued treatment. Three patients died of pneumonitis while in the study. Immunohistochemical positivity for p4E-BP1 or insulin-like growth factor-1 receptor was statistically significantly related to a shorter survival. Conclusion Everolimus may induce durable disease control in a high percentage of patients with T or TC, albeit with a potential high risk of fatal pneumonitis.

Background: Here we evaluate the usefulness of transfemoral uncovered stent implantation to avoid secondary conventional surgery for residual type A aortic dissection (TAAD) of the aortic arch after ascending aorta replacement. Methods: From June 2009 to April 2015, 11 patients were treated with transfemoral implantation of uncovered stents in the aortic arch after surgical replacement of ascending aorta performed on average 4.7±2.3 years earlier. An enlarged dissected aortic arch or a dangerous median growth of more than 5 mm/yr or impending rupture presenting as chest pain were indications for treatment. The dissected aortic tracts diameter must not exceed 45 mm. Five patients (45.5%) were treated with Djumbodies Dissection System, 6 patients (54.5%) with Jotec E-XL aortic stent. Results: There were no perioperative deaths or permanent neurologic complications. Primary procedural success was obtained in all patients and the residual TAAD in aortic arch was obliterated, with disappearance of the false lumen. Median intensive care unit (ICU) stay was 24 hours; post-operative hospital stay was 5.2±1.4 days. One death, not aortic related, occurred during follow-up period (mean 5.2±1.9 years). Descending thoracic aorta diameter significantly increased in 3 patients (27.3%): one patient (9.0%) needed a secondary conventional surgery, the other 2 (18.2%) of a distal extension with PETTICOAT approach. Conclusions: Endovascular approach with uncovered metal bare stent is surely an evolving strategy to perform a purely endovascular treatment, indicated only for treatment of an aortic arch with a diameter of less than 40 or 45 mm, to avoid progressive thoracic aortic dilatation and/or rupture.

Coronary artery anomalies (CAA) are common in many congenital heart disease (1,2) and to know the origin and the course of coronary artery is essential for patients when underwent cardiac catheterization or surgery.

Objectives: A history of percutaneous coronary intervention increases the risk of death and complications of coronary artery bypass grafting. This retrospective multicenter study evaluated the impact of continuative use of statin on postoperative outcomes when subsequent elective coronary artery bypass grafting is required after percutaneous coronary intervention. Methods: Among 14,575 patients who underwent isolated first-time coronary artery bypass grafting between January 2000 and December 2010, 2501 who had previous percutaneous coronary intervention with stenting and fulfilled inclusion criteria were enrolled. Continuative statin therapy was used in 1528 patients and not used in 973 patients. Logistic multiple regression and propensity score analyses were used to assess the risk-adjusted impact of statin therapy on in-hospital mortality and major adverse cardiac events. The Cox proportional hazards model was constructed to assess the effect of continuative statin therapy on 24-month outcome. Results: At multivariate analysis, age more than 70 years, 3-vessel or 2-vessel plus left main coronary disease, multivessel percutaneous coronary intervention, ejection fraction 0.40 or less, diabetes mellitus, and logistic European System for Cardiac Operative Risk Evaluation 5 or greater were independent predictors of hospital mortality and major adverse cardiac events. After propensity score matching, conditional logistic regression analysis demonstrated that continuative statin therapy before coronary artery bypass grafting reduced the risk for hospital and 2-year mortality (odds ratio [OR], 0.27; 95% confidence interval [CI], 0.12-0. 57; P ¼ .004 and OR, 0.6; 95% CI, 0.36-0.96; P ¼ .04, respectively) and major adverse cardiac events (OR, 0.31; 95% CI, 0.18-0.78; P ¼ .003 and OR, 0.5; 95% CI, 0.34-0.76; P ¼ .006, respectively). Conclusions: Long-term statin treatment after percutaneous coronary intervention improves early and midterm outcome when surgical revascularization will be required. (J Thorac Cardiovasc Surg 2014;148(5):1876-8)

Objective: An increasing number of patients presenting for urgent coronary surgery have been exposed to clopidogrel, which constitutes a risk of bleeding and related events. Based on the wide variability in clopidogrel response and platelet function recovery after cessation, we evaluated the role of point-of-care platelet function testing to define the optimal time for off-pump coronary artery bypass graft (CABG) surgery in a case-control study. Methods: Three equally matched groups (300 patients in total) undergoing isolated off-pump CABG for acute coronary syndrome were compared. Group A were treated with clopidogrel and prospectively underwent a strategy guided by platelet function testing. Outcomes were compared with 2 propensity score matched groups: group B underwent CABG after the currently recommended 5 days without clopidogrel; group C were never exposed to clopidogrel. Results: Patients in group A had reduced postoperative bleeding compared with those in group B (523 ± 202 mL vs 851 ± 605 mL; P < .001) and a lower number of units packed red blood cells (PRBCs) transfused during the postoperative hospital stay (1.2 ± 1.6 units vs 1.9 ± 1.8 units; P = .004). Postoperative bleeding and the number of units of PRBCs transfused were similar in group A and group C. There was no difference in blood-derived products and platelet consumption, mortality, or the need for reoperation among the groups. Patients in group A waited 3.6 ± 1.7 days for surgery. The strategy used for group A saved 280 days of hospital stay in total. Conclusions: The strategy guided by platelet function testing for off-pump CABG offers improved guidance for optimal timing of CABG in patients treated with clopidogrel. This strategy significantly reduces postoperative bleeding and blood consumption, and has a shorter waiting time for surgery than current clinical practice. © 2014 The American Association for Thoracic Surgery.

Background significance of incidental thyroid 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) uptake on positron emission tomography/computed tomography (PET/CT) scans remains controversial. We aimed to evaluate the ability of [18F]FDG-PET/CT texture analysis to predict final diagnosis in thyroid incidentaloma. Methods We retrospectively evaluated medical records of all patients who performed a [18F]FDG-PET/CT from January 2012 to October 2016. Those patients who presented a thyroid incidentaloma described in the medical records and performed a fine needle aspiration in our institution were considered for the analysis. Cytological and/or histological results were used as reference standard to define the final diagnosis. In case of negative cytology, the nodule was considered benign. In case of non-diagnostic or inconclusive results ultrasound, follow-up and further cytology/histology were used as final diagnosis. For suspected or positive cytological result, histology was used as reference standard. PET images were segmented using a General Electric AW workstation running PET VCAR software (GE Healthcare, Waukesha, WI, USA) settled with a threshold of 40% SUVmax. LifeX software (http://www.lifexsoft.org) was used to perform texture analysis. Statistical analysis was performed with R package (https://www.r-project.org). Results We identified 55 patients with incidental thyroid [18F]FDG uptake. Five patients were excluded from the analysis because a final diagnosis was not available. Thirty-two out of 50 patients had benign nodules while in 18/50 cases a malignancy (primary thyroid cancer = 15, metastases = 3) was diagnosed. Conventional PET parameters and histogram-based features were calculated for all 50 patients, while other matrices-based features were available for 28/50 patients. SUVmax and skewness resulted significantly different in benign and malignant nodules (p = 0.01 and = 0.02, respectively). Using ROC analysis, seven features were identified as potential predictors. Among all the textural features tested, skewness showed the best area under the curve (= 0.66). SUV-based parameters resulted in the highest specificity while MTV, TLG, skewness and kurtosis, as well as correlationGLCM resulted better in sensitivity. Conclusions [18F]FDG-PET/CT texture analysis seems to be a promising approach to stratify the patients with thyroid incidentaloma identified on PET scans, with respect to the risk of the diagnosis of a malignant thyroid nodule and thus, could refine the selection of the patients to be referred for cytology. Electronic supplementary material The online version of this article (10.1186/s41824-017-0009-8) contains supplementary material, which is available to authorized users.

IMPORTANCE: Localization of small lung nodules are challenging because of the difficulty of nodule recognition during video-assisted thoracoscopic surgery. Using 3-dimensional (3-D) printing technology, a navigational template was recently created to assist percutaneous lung nodule localization; however, the efficacy and safety of this template have not yet been evaluated. OBJECTIVE: To assess the noninferiority of the efficacy and safety of a 3-D–printed navigational template guide for localizing small peripheral lung nodules. DESIGN, SETTING, AND PARTICIPANTS: This noninferiority randomized clinical trial conducted between October 2016 and October 2017 at Shanghai Pulmonary Hospital, Shanghai, China, compared the safety and precision of lung nodule localization using a template-guided approach vs the conventional computed tomography (CT)-guided approach. In total, 213 surgical candidates with small peripheral lung nodules (

Background: Patients having undergone femoropopliteal bypass surgery remain at significant risk of graft failure. Although antithrombotic therapy is of paramount importance in these patients, the effect of oral anticoagulation therapy (OAT) on outcomes remains unresolved. We performed a randomized, prospective study to assess the impact of OAT plus clopidogrel vs dual antiplatelet therapy on peripheral vascular and systemic cardiovascular outcomes in patients who had undergone femoropopliteal bypass surgery. Methods: Three hundred forty-one patients who had undergone femoropopliteal surgery were enrolled and randomized: 173 patients received clopidogrel 75 mg/d plus OAT with warfarin (C + OAT), and 168 patients received dual antiplatelet therapy with clopidogrel 75 mg/d plus aspirin 100 mg/d (C + acetylsalicylic acid [ASA]). Study end points were graft patency and the occurrence of severe peripheral arterial ischemia, and the incidence of bleeding episodes. Results: Follow-up ranged from 4 to 9 years. The graft patency rate and the freedom from severe peripheral arterial ischemia was significantly higher in C + OAT group than in C + ASA group (P =.026 and.044, respectively, Cox-Mantel test). The linearized incidence of minor bleeding complications was significantly higher in C + OAT group than in C + ASA group (2.85% patient-years vs 1.37% patient-years; P =.03). The incidence of major adverse cardiovascular events, including mortality, was found to be similar (P =.34) for both study groups. Conclusions: In patients who have undergone femoropopliteal vascular surgery, combination therapy with clopidogrel plus warfarin is more effective than dual antiplatelet therapy in increasing graft patency and in reducing severe peripheral ischemia. These improvements are obtained at the expenses of an increase in the rate of minor anticoagulation-related complications. © 2012 Society for Vascular Surgery.

This multicenter study investigated the impact of previous percutaneous coronary interventions (PCI) on postoperative outcome and 5-year survival of subsequent coronary artery bypass grafting.Among 7,855 patients who underwent isolated first-time coronary artery bypass grafting between January 2000 and December 2005, 6,834 (87%) had no previous PCI and 1,021 (13%) had previous PCI with stenting. Logistic multiple regression and propensity score analyses were used to assess the risk-adjusted impact of prior PCI on in-hospital mortality and major adverse cardiac events. The Cox regression model was used to assess the effect of prior PCI on 3-year and 5-year survival.After risk-adjusted multivariate analysis, age over 70 years, female sex, 3-vessel or 2-vessel plus left main coronary disease, multivessel PCI, ejection fraction 0.40 or less, diabetes mellitus, previous myocardial infarction, and chronic obstructive pulmonary disease were identified as independent predictors of both hospital mortality and major adverse cardiac events. After propensity score matching, conditional logistic regression analysis identified history of previous PCI as significantly associated with an increased risk for hospital mortality (odds ratio, 2.8; 95% confidence interval 1.4 to 4.8; p=0.003) and major adverse cardiac events (odds ratio 2.1; 95% confidence interval 1.2 to 3.6; p0.001). Survival at 3 and 5 years was lower in patients with previous PCI compared with the no-PCI patients (97.4%±0.01% vs 96.5%±0.02% and 94.2%±0.03% vs 92.1%±0.05%; log-rank test: p=0.03).Our results provided further evidence that history of PCI before coronary artery bypass grafting increases risk of both operative death and perioperative complications, and decreases survival at 5 years follow-up.

Background Prophylactic intraaortic balloon pump (IABP) support showed better outcomes in critical patients undergoing coronary revascularization compared with intraoperative or postoperative insertion. We conducted a prospective, randomized study to determine the optimal timing for preoperative IABP insertion in high-risk patients undergoing off-pump coronary artery revascularization. Methods The study enrolled 230 consecutive high-risk patients (having a logistic European System for Cardiac Operative Risk Evaluation score of ≥10) undergoing off-pump coronary artery revascularization. They were randomized for preoperative IABP starting at 2 hours (2T, n=115) or 12 hours (12T, n=115). Clinical, biochemical, and hemodynamic results, and the need for inotropic drug support, were markers of outcome and compared between groups. Results Hospital mortality in group 12T was reduced by 60%, but the difference between groups was not statistically significant (hazard ratio, 0.4; 95% confidence interval, 0.1 to 1.5; p = 0.1). Twelve hours of preoperative IABP therapy reduced postoperative low output syndrome (hazard ratio, 0.4; 95% confidence interval, 0.1 to 0.9; p = 0.03) and biomarker leakage upper normal limit (hazard ratio, 0.3; 95% confidence interval, 0.1 to 0.7; p = 0.001). Postoperative left ventricular function was similar between the groups. Group 2T patients required higher inotropic support for a longer average duration and prolonged postoperative intensive care unit and hospital length of stay. Conclusions Twelve hours preoperative IABP therapy improved treatment efficacy. Postoperative morbidity was reduced, but hospital mortality rate was not affected. The IABP-related complication rate was low and not related to the length of treatment.

The American Association for the Study of Liver Diseases guidelines recommend the use of all available markers for improving the accuracy of the diagnosis of small hepatocellular carcinoma (HCC). To determine whether clathrin heavy chain (CHC), a novel HCC marker, is effective in combination with glypican 3 (GPC3), heat shock protein 70, and glutamine synthetase, we compared the performances of a three-marker panel (without CHC) and a four-marker panel (with CHC) in a series of small HCCs (≤2 cm) and nonsmall HCCs by core biopsy with a 20- to 21-gauge needle. The series included 39 nonsmall HCCs and 47 small HCCs (86 in all); the latter showed a well-differentiated histology [small grade 1 (G1)] in 30 cases (63.8%). The panel specificity was analyzed with the adjacent/extranodular cirrhotic liver (n = 30) and low-grade (n = 15) and high-grade dysplastic nodules (n = 16) as a control group. Absolute specificity (100%) for HCC was obtained only when at least two of the markers were positive (which two markers were positive did not matter). The addition of CHC to the panel increased the diagnostic accuracy for small HCCs (from 76.9% to 84.3%), and there was an important gain in sensitivity (from 46.8% to 63.8%). The four-marker panel had lower rates of accuracy (67.4%) and sensitivity (50%) for small G1 HCCs versus nonsmall G1 HCCs (93.9% and 88.2%, respectively). In seven cases (including six small G1 HCCs), there was no staining with any of the markers. Cirrhotic control livers were stained for CHC in four cases (13.3%) and for GPC3 in one case (3.3%). Conclusion: The addition of CHC to the panel supports the diagnosis of small HCCs in challenging nodules on thin core biopsy samples. Small G1 HCCs include a group of earlier tumors characterized by a more silent phenotype and the progressive acquisition of the markers under study. The search for additional markers for early HCC diagnosis is warranted. © 2011 American Association for the Study of Liver Diseases

Background. We investigated whether the use of left ventricular-assisted (LVA) technique in beating heart myocardial revascularization would exert less impact on patients adhesion molecules and oxygenation index as compared with conventional cardiopulmonary bypass (CPB). Methods. Sixty-six consecutive patients undergoing myocardial revascularization were randomly assigned either to LVA (group A, 34 patients) or CPB (group B, 32 patients). Adhesion molecules and oxygenation indexes were measured at baseline and at various time points postoperatively. Results. Pre-operative clinical and demographic data did not differ between the 2 groups. The 2 groups were also similar with respect to mortality, number of grafts performed, duration of extracorporeal circulation, and need for inotropes. However, postoperatively patients treated with LVA had a reduced levels of adhesion molecules compared with patients treated with CPB, as indicated by a significant difference in endothelial leukocyte adhesion molecule-1 (P = .002), intercellullar adhesion molecule- 1 (P = .0001), and vascular cell adhesion molecule-1 (P = .004). The oxygenation index at 1 (P = .04) and 3 hours (P = .03) postoperatively was better in the LVA group than in the CPB group. Conclusion. Patients undergoing beating heart myocardial revascularization with LVA show reduced levels of adhesion molecules and better oxygenation index than patients treated with CPB. (Surgery 2010;147:434-40.)

Background & Aims Sorafenib is the standard of care in advanced hepatocellular carcinoma (HCC), however no criteria have been established to select patients likely to benefit from this therapy. In this study, we evaluated the predictive role of microRNAs (miRNAs) in this setting of patients. Methods We profiled 522 miRNA in a series of 26 HCC patients treated with sorafenib (training set) and validated the results in an independent series of 58 patients (validation set). Formalin-fixed paraffin-embedded tumour and cirrhotic liver biopsies were used for RNA extraction and miRNAs profiling with TaqMan Arrays technology. Statistical analyses were used to correlate miRNA levels with clinical outcome, including time to progression (TTP), progression free (PFS), and overall survival. Cell viability and cell motility of HuH-7 or HepG2 HCC cells were tested in vitro after transfection with specific miRNA precursor, inhibitor or controls and sorafenib treatment. Results Six miRNAs were significantly associated with clinical variables in the training set and only miR-425-3p could be further validated. Higher levels of miR-425-3p were associated with longer TTP and PFS (P = 0.0008; HR = 0.4; 95% CI = 0.2–0.7 and P = 0.007; HR = 0.5; 95% CI = 0.3–0.9 respectively). Multivariate analysis confirmed the predictive significance of miR-425-3p. Furthermore, an association between increased miR-425-3p, cell death and reduced cell motility was defined in vitro in HCC cell lines treated with sorafenib. Conclusions Assessment of miR-425-3p levels in liver biopsies could help in stratifying patients with advanced HCC for sorafenib treatment. These promising results need to be confirmed in a large prospective study.

Background . This retrospective cohort study investigated the functional and haemodynamic mid-term results over 3-years follow up of the left internal mammary artery (LIMA) conduit in composite Y-graft configuration with radial artery (RA) in a population of patients who underwent off-pump coronary artery bypass grafting (CABG). Methods . 148 patients who underwent off-pump CABG with composite Y-graft, were evaluated over 3-year follow up. Two-day dipyridamole induced maximal hyperaemia/rest 99mTc-sestamibi was scheduled preoperatively and 36 months after surgery for functional evaluation. Morphological evaluation was performed by 64 slice multidetector computed tomography (CT) 36 months after surgery. Results . Clinical adverse events were rare within 3 years follow up. Minimal to severe scintigraphic evidence of stress induced ischaemia occurred in 24 patients. Left ventricular (LV) hypertrophy (HR 3.1; 95% CI, 1.5–9.3; p = 0.01) and poor coronary run off (HR 4.1; 95% CI, 2.1–10.8; p = 0.005) were significant multivariate predictors of reversible stress induced ischaemia. 64 slice multidetector CT showed that the main stem of Y composite grafts was patent in all patients, while distal LIMA or RA was stenosed or occluded in 9 patients. Conclusion . Composite Y-graft was adequate to meet the flow requirements of target coronary artery either at rest or during maximal hyperaemia. The use of Y-graft should be carefully evaluated in patients with LV hypertrophy and/or poor coronary run-off.

The Ki-67 labeling index has been found to bear prognostic significance in gastrointestinal neuroendocrine tumors (NETs), and it was recently incorporated in NET histological grading. Nevertheless, a reliable preoperative determination of NET grading could be useful in clinical practice. The aim of this study is to compare the results of Ki-67 labeling index, as measured on cytological samples and on surgical specimens of patients with pancreatic NETs (P-NETs). We also investigated whether concordance might be improved, using a 5 % (instead of 2 %) cutoff value for defining G2 tumors. We retrospectively identified 48 consecutive patients with 53 P-NETs, from our five institutions, and we measured Ki-67 labeling index on their cytological samples and surgical specimens. The traditional 2 % and the alternative 5 % cutoff values were used to classify G2 tumors. The concordance rate between cytological and histological grading was 46/53 (86.8 %; weighted κ statistic 0.77; 95 % confidence interval (95 % CI) 0.60-0.94). No cases of cytological G1-G2 NETs were upgraded to G3 neuroendocrine carcinoma (NEC) at histological grading. Cytology was found to be highly specific in the diagnosis of both G2 (94.1 %; 95 % CI 80.3-99.3) and G3 tumors (100.0 %; 95 % CI 92.8-100), but the sensitivity was poor for G2 NETs (66.7 %; 95 % CI 38.4-88.2) and high for the prediction of G3 NECs (100 %; 95 % CI 39.8-100.0). When the 5 % cutoff value was adopted, concordance rate was 49/53 (92.4 %; weighted κ 0.82; 95 % CI 0.64-1.00). In conclusion, Ki-67 cytological expression can distinguish well-differentiated (both G1 and G2) from poorly differentiated P-NETs, and it may be useful for their preoperative classification. © 2014 Springer-Verlag.

BACKGROUND:: The relation between visceral fat accumulation and development of cardiovascular and metabolic disorders has been demonstrated. The aim of this study was to determine the relationship between a new ultrasound visceral fat thickness (VFT) measurement and clinical and anthropometric data in a consecutive series of obese patients. METHODS:: Fifty-five consecutive male obese patients underwent ultrasound evaluation and metabolic and anthropometric parameters determination at baseline and after 3 weeks of a very low-calorie diet (VLCD) therapy. The new ultrasound measurement, the thickness of the fat between the aorta and the superior mesenteric artery (AMFT), was determined along with the maximum thickness of preperitoneal fat and the global VFT. RESULTS:: AMFT showed a better correlation than VFT and preperitoneal fat with all anthropometric and metabolic parameters, both at baseline and after VLCD regimen. At baseline, patients in the middle and high AMFT and VFT tertiles had a significantly higher prevalence of metabolic diseases with respect to AMFT and VFT low tertile patients, whereas after VLCD period, AMFT only showed significant difference within tertiles. The odds ratios for the various metabolic diseases were higher in the middle and high AMFT tertiles than those in the middle and high VFT tertiles, remaining significant after adjustment for age, body mass index and VLCD regimen only in the middle and high AMFT tertiles. CONCLUSIONS:: The ultrasonographic AMFT evaluation is strongly correlated to the presence of metabolic syndrome and could be a valuable tool to predict metabolic diseases and associated cardiovascular risks in men. © 2013 Lippincott Williams and Wilkins.

We herein report the case of a high-risk patient with complicated acute type B aortic dissection (B-AD) involving the arch up to both common iliac arteries. The patient was treated by a simultaneous hybrid approach accomplished with local anesthesia.

Introduction We report the endovascular treatment of aortic arch injury due to direct puncture during pacemaker implantation. Report After pacemaker implantation a 74-year-old woman showed a progressive decrease in haematocrit with elevation of cardiac troponin-I. Coronary angiography revealed the malposition of the catheters introduced through the aortic wall. The atrial lead was placed in the left circumflex coronary artery. Computed tomography scan confirmed distal aortic arch perforation. A Medtronic-Valiant stent–graft was implanted in the distal aortic arch while the two catheters were removed. A new VVI pacemaker was implanted and, 3 days later, the patient underwent percutaneous coronary intervention (PCI) on the dissected left circumflex artery. Four days later the patient was discharged. One-year computed tomography scan showed successful repair of the injured aorta. Discussion Endovascular stent grafting has emerged as a less invasive therapeutic alternative to treat traumatic or iatrogenic injuries of the distal aortic arch.

OBJECTIVES: Left ventricular (LV) diastolic dysfunction after aortic valve replacement (AVR) carries a substantial risk of development of heart failure and reduced survival. In addition to echocardiography, B-type natriuretic peptide (BNP) provides a powerful incremental assessment of diastolic function. This study evaluates BNP as a marker of LV diastolic dysfunction in a cohort of patients with preserved LV ejection fraction who underwent AVR for pure aortic stenosis and the relationship between BNP values and the grade of LV diastolic dysfunction. METHODS: A total of 113 patients were included in the study. Echocardiographic evaluation was performed preoperatively, 5 days postoperatively and at 12-month follow-up, to assess LV dimensional and functional parameters. Diastolic function was labelled as normal, mild, moderate or severe dysfunction. Concomitantly, BNP levels were evaluated. RESULTS: Mild to severe diastolic dysfunction occurred preoperatively in all patients. At 12-month follow-up, 65 (62.5%) patients had mild and 25 (24.1%) moderate to severe diastolic dysfunction. BNP values, categorized for quartile distribution, correlated with diastolic dysfunction grade (P< 0.001 for each comparison). At receiver operating characteristic analysis, the BNP level of 120 pg/ml was 91% sensitive and 85% specific for diastolic disease, while 300 pg/ml was 80% sensitive and 91% specific for moderate or severe diastolic dysfunction. Twelve months after AVR, BNP values were strongly correlated with the significant echocardiographic parameters suggestive of diastolic dysfunction (P ≤ 0.006 in all cases). CONCLUSIONS: The BNP level following AVR is related to diastolic disease severity and may complement echocardiographic evaluation when symptoms are unclear and LV function is difficult to interpret.

Objectives. The development of intimal hyperplasia and graft failure is an important problem in cardiac surgery. A fundamental process in intimal hyperplasia is the degradation of extracellular matrix by metalloproteases which induces the vascular smooth-muscle cells migration and sets the scene for graft atherosclerosis. This study investigated whether doxycycline, a metalloproteases inhibitor, can prevent the intimal hyperplasia occurrence in cultured human internal mammary artery, thus extending graft patency. Methods. Segments of internal mammary artery from 20 consecutive patients were prepared and cultured for 2 weeks in serum-supplemented medium (control) or in medium supplemented with 10−5 M and 10−6 M doxycycline concentrations. Tissues were fixed, sectioned, and stained, and neointimal thickness was measured by computer-aided image analysis. Further sections were cultured and prepared for gel enzymography to measure the matrix metalloproteinase-2 and -9 levels. Results. At the end of the culture period, neointimal thickness was significantly (P = 0.001) dose-dependently reduced in samples treated with doxycycline when compared with controls. Gelatin enzymography demonstrated a reduction in values for both latent and active forms of metalloproteases. Conclusions. Doxycycline, in a model of internal mammary artery intimal hyperplasia, has a specific role in inhibiting metalloproteases activity and may prevent graft stenosis.

To determine the individual variability in the response to aspirin and/or clopidogrel and its impact on graft patency after off-pump coronary artery bypass grafting.A single-centre prospective randomised controlled study designed according to the Consolidated Standards of Reporting Trials statement. Randomisation was obtained by a computer-generated algorithm.University medical school in Italy.300 patients who underwent off-pump coronary artery bypass grafting were randomised to receive aspirin (n=150) or aspirin plus clopidogrel (n=150).Aspirin 100 mg or aspirin 100 mg plus clopidogrel 75 mg daily was initiated when postoperative chest tube drainage was ≤ 50 ml/h for 2 h and patients were followed up for 12 months.Qualitative and quantitative assessment of platelet function, angiographic evaluation of coronary revascularisation by 64-slice CT and clinical outcome.In the aspirin group, 49 patients (32.6%) were aspirin resistant and, in the aspirin-clopidogrel group, 19 patients (12.6%) were aspirin and clopidogrel resistant. The platelet response to aspirin was similar in all aspirin responders despite the study arm (Aspirin Reaction Units 313.2 ± 44.8 vs 323.6 ± 53.6; p=0.07). The platelet response to clopidogrel was enhanced by aspirin in patients responsive to both aspirin and clopidogrel (synergistic effect) compared with responders to clopidogrel only (P2Y12 Reaction Units 139.9 ± 15.5 vs 179.4 ± 18.5; p0.001). Combined therapy was associated with a reduced vein graft occlusion rate (7.4% vs 13.1%; p=0.04). Antiplatelet resistance was a predictor of graft occlusion (RR 3.6, 95% CI 2.5 to 6.9; p0.001). Synergistic aspirin and clopidogrel activity was a strong predictor of vein graft patency (RR 5.1, 95% CI 1.4 to 16.3; p0.01).Combined clopidogrel and aspirin overcome single drug resistances, are safe for bleeding and improve venous graft patency.

ObjectiveAsymmetric septal hypertrophy frequently coexists with severe aortic stenosis and can be unmasked after successful aortic valve replacement (AVR), jeopardizing the clinical and echocardiographic results. The aim of our study was to investigate, at 5 years postoperatively, the effectiveness of myectomy associated with AVR on left ventricular (LV) mass regression and LV diastolic function.MethodsFrom 1997 and 2004, 86 patients with a diagnosis of severe aortic stenosis and asymmetric septal hypertrophy consecutively underwent AVR (group A) or AVR and concomitant myectomy (group B). To assess the improvement in LV mass and LV diastolic function, we studied the 52 survivors (23 in group A and 29 in group B) who had the same prosthesis type (beleaflet mechanical), the same size (21 mm), and the same follow-up length.ResultsIn group A, the LV mass index regressed from 119.2 ± 22.0 to 113.8 ± 21.8, and in group B, it regressed from 121.6 ± 20.8 to 112.7 ± 20.0 (P

Aims: Acute aortic syndromes (AAS) still represent life-threatening conditions. The aim of this study was to describe our experience in the management of patients (pts) with AAS and to evaluate the safety and feasibility of endovascular treatment (EVT) in high surgical risk patients. Methods and results: One hundred and four patients underwent EVT. We selected 56 pts with AAS: 17 complicated type B aortic dissections, five traumatic aortic ruptures at the isthmus, 11 thoracic aneurysms and 23 pts with large AAA with impending rupture. All these pts were at high surgical risk because of their comorbidities and/or their emergency situation. They were clinically followed during hospitalisation and they underwent a 2 mm-interval CT-scan two weeks, six and 12 months after discharge and every year after. Death. paraplegia, open surgical conversion did not occur. Two pts underwent a successful secondary EVT for type I endoleak. One patient with thoracic aortic aneurysm died of septic shock from pneumonia 78 days after discharge and two pts with AAA suffering from a severe three-vessel coronary disease experienced sudden death at one year follow-up. Conclusions: EVT seems to be a safe and effective therapeutic option with good short- and midterm results in patients with AAS at high surgical risk. Thus, it can be considered as a less-invasive alternative in patients considered otherwise unsuitable for conventional surgery, even though a careful, continued follow-up is still necessary to confirm the long-term safety and effectiveness of EVT in AAS.

Hepatocellular nodules in cirrhosis include regenerative (large regenerative, LRN) and dysplastic (low and high grade, LGDN and HGDN) nodules, early and grade 1 HCC (eHCC-G1), and overt HCC. The differential diagnosis may be particularly difficult when lesions such as HGDN and eHCC-G1 are involved. We investigated the diagnostic yield of a panel of 3 putative markers of hepatocellular malignancy such as HSP70, glypican 3 (GPC3), and glutamine synthetase (GS). We selected 52 surgically removed nonmalignant nodules (15 LRNs, 15 LGDNs, 22 HGDNs) and 53 HCCs (10 early, 22 grade 1, and 21 grade 2-3) and immunostained them for HSP70, GPC3, and GS. The sensitivity and specificity of the individual markers for the detection of eHCC-G1 were 59% and 86% for GS, 69% and 91% for GPC3, and 78% and 95% for HSP70. We identified 2 main phenotypes: (1) all negative, seen in 100% LRN and LGDN, 73% HGDN and 3% eHCC-G1; (2) all positive, a feature detected in less than half the eHCC-G1. Using a 3-marker panel, when at least 2 of them, regardless which, were positive, the sensitivity and specificity for the detection of eHCC-G1 were respectively 72% and 100%; the most sensitive combination was HSP70+/GPC3+ (59%) when a 2-marker panel was used. Conclusion: The adopted panel of 3 markers is very helpful in distinguishing eHCC-G1 from dysplastic nodules arising in cirrhosis. (HEPATOLOGY 2007;45:725–734.)

Objective: To describe our experience of endovascular repair of paraanastomotic aortic aneurysm. Methods and results: From March 2001 to December 2004 we identified 6 patients with a paraanastomotic aortic aneurysms following previous open repair of abdominal aortic aneurysm. All patients were treated with endovascular surgery under epidural anaesthesia. There were no major complications, surgical conversions or deaths. Four patients received a bifurcated aortic stent-graft, and two an aorto-uniliac stent-graft followed by a femoro-femoral bypass. At follow-up (mean 26.1 ± 10.2 months) there were no deaths, endoleaks or graft migrations observed. Conclusion: Endovascular surgery, avoiding general anesthesia and re-laparotomy, is the ideal technique for treatment of this complication resulting from failed primary conventional AAA repair. © 2006 Elsevier Ltd. All rights reserved.

treme condition of vanishing of the muscular support of the hemidiaphragm forced us to perform an alternative technique with optimal functional results. The aim of this technique was as follows: (1) tailoring a plastic correction with a prosthetic mesh with a greater pressure-proof guarantee compared with that seen in the traditional surgical techniques; (2) creating an area of thickness corresponding to a new durable central tendon able to resist the constant abdominal pressure exerted by the viscera; and (3) avoiding a direct contact between the prosthesis and the lung parenchyma. Optimal functional results and complete anatomic integration led us to believe that this technique could be worthy of consideration in the treatment of major diaphragmatic eventration. References

Encouraging results obtained with endovascular treatment of subclavian artery aneurysms (SAAs)(1) led us to use this technique as an alternative to conventional operation in a young female patient with an intrathoracic SAA on the right side complicated by a left-sided cervical aortic arch and agenesis of the left common carotid and vertebral arteries.

Background. Conventional surgery for thoracic aortic emergencies, such as contained or free rupture of thoracic aortic aneurysms, acute type B dissections, and traumatic rupture of the thoracic aorta, is frequently associated with a high rate of mortality and morbidity. To obviate this risk, endovascular surgery is considered to be a valid alternative procedure. Methods. From March 2001 to July 2002, 15 of 22 patients with acute thoracic aortic syndromes were submitted to endovascular surgery: 3 patients (20%) for traumatic rupture, 4 patients (26.7%) for contained or free rupture of thoracic aortic aneurysm, and 8 patients (53.3%) for acute type B dissection evolving to rupture. Computed tomographic scan was diagnostic in all patients. The stent grafts were introduced through the femoral artery. Results. In the endovascular group there were no perioperative deaths or open conversions. The intraoperative angiography and computed tomographic scan performed on discharge showed no significant endoleaks and successful sealing of the aortic dissection. Average intensive care unit and hospital stay was 1.7 +/- 0.8 and 5.9 +/- 3.0 days. Follow-up ranged between 4 and 23 months and included clinical examinations and serial computed tomographic scan at 3, 6, and 12 months, and every 6 months thereafter. One 84-year-old patient with thoracic aortic aneurysm died of pneumonia 78 days after endovascular surgery. Only one type 1 endoleak was noted in the first patient with traumatic rupture, 3 months after the procedure. Conclusions. Endovascular surgery is a safe technique, showing encouraging early and midterm results and allowing for prompt treatment of associated lesions in complex multitrauma patients. (C) 2004 by The Society of Thoracic Surgeons.

TEVAR OFFERS THE ADVANTAGE OF A LESS INVASIVE TREATMENT, REDUCING THE RISK OF PARAPLEGIA,VISCERL ISCHAEMIA AND PULMONARY COMPLICATION. THE HYBRID APRROACH DON'T PRECLUDE THE POSSIBILITY OF A SECONDARY TEVAR OR OF A CONVETIONAL SURGERY OF AORTIC PATHOLOGIES

ObjectiveThe role of matrix metalloproteinases and their tissue endogenous inhibitors has been documented in abdominal aortic aneurysms, but few articles have investigated their role after thoracic aortic aneurysm treatment. Our report investigates matrix metalloproteinases and tissue endogenous inhibitor-1 plasmatic changes in patients who have undergone endovascular aneurysm repair for descending thoracic aortic aneurysms and assesses their clinical significance.MethodsThirty-two patients with thoracic aortic aneurysms who underwent endovascular aneurysm repair were compared with 25 healthy volunteers. Plasma matrix metalloproteinase-3/matrix metalloproteinase-9 and tissue endogenous inhibitor-1 values were determined by an enzyme-linked immunosorbent assay method at a predetermined time interval.ResultsThe preoperative levels of matrix metalloproteinases in the endovascular aneurysm repair group were 3-fold and 2-fold higher than those in the control group (P < .001 and .02, respectively). Matrix metalloproteinase values normalized after endovascular aneurysm repair, whereas patients experiencing endoleaks had higher matrix metalloproteinase values and matrix metalloproteinase-9/tissue endogenous inhibitor-1 ratio compared with the control group (P = .003, < .001, and = .02, respectively, at 1-month follow-up). These values normalized with the resolution of the endoleak.ConclusionsPlasma matrix metalloproteinase values are increased in patients with thoracic aortic aneurysms, along with reduced tissue endogenous inhibitor-1 expression. Successful endovascular aneurysm repair results in values normalization, whereas high levels persist in patients with endoleaks. The enzyme-linked immunosorbent assay test is a simple and reliable technique that is useful to assess the efficacy of endovascular aneurysm repair and to detect endoleaks.