Endoscopic Contrast-Enhanced Ultrasound and Fine-Needle Aspiration or Biopsy for the Diagnosis of Pancreatic Solid Lesions: A Systematic Review and Meta-Analysis.

INTRODUCTION: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) are currently recommended for the pathologic diagnosis of pancreatic solid lesions (PSLs). The application of contrast-enhanced endoscopic ultrasound (ECEUS) could aid the endoscopist during an FNA and/or FNB procedure. CEUS is indeed able to better differentiate the pathologic tissue from the surrounding healthy pancreatic parenchyma and to detect necrotic areas and vessels. OBJECTIVES: Our objective was to evaluate if ECEUS could reduce the number of needle passes and side effects and increase the diagnostic efficacy of FNA and/or FNB. METHODS: A comprehensive literature search of clinical studies was performed to explore if ECEUS-FNA or FNB could increase diagnostic accuracy and reduce the number of needle passes and adverse effects compared to standard EUS-FNA or FNB. In accordance with the study protocol, a qualitative and quantitative analysis of the evidence was planned. RESULTS: The proportion of established diagnoses of ECEUS was 90.9% compared to 88.3% of EUS, with no statistically significant difference (p = 0.14). The diagnosis was made through a single step in 70.9% of ECEUS patients and in 65.3% of EUS patients, without statistical significance (p = 0.24). The incidence of adverse reactions was substantially comparable across both groups (p = 0.89). CONCLUSION: ECEUS-FNA and FNB do not appear superior to standard EUS-FNA and FNB for the diagnosis of pancreatic lesions.

Shear-wave elastography to predict hepatocellular carcinoma after hepatitis C virus eradication: A systematic review and meta-analysis.

BACKGROUND: Direct-acting antiviral agents (DAAs) are highly effective treatment for chronic hepatitis C (CHC) with a significant rate of sustained virologic response (SVR). The achievement of SVR is crucial to prevent additional liver damage and slow down fibrosis progression. The assessment of fibrosis degree can be performed with transient elastography, magnetic resonance elastography or shear-wave elastography (SWE). Liver elastography could function as a predictor for hepatocellular carcinoma (HCC) in CHC patients treated with DAAs. AIM: To explore the predictive value of SWE for HCC development after complete clearance of hepatitis C virus (HCV). METHODS: A comprehensive literature search of clinical studies was performed to identify the ability of SWE to predict HCC occurrence after HCV clearance. In accordance with the study protocol, a qualitative and quantitative analysis of the evidence was planned. RESULTS: At baseline and after 12 wk of follow-up, a trend was shown towards greater liver stiffness (LS) in those who go on to develop HCC compared to those who do not [baseline LS standardized mean difference (SMD): 1.15, 95% confidence interval (95%CI): 020-2.50; LS SMD after 12 wk: 0.83, 95%CI: 0.33-1.98]. The absence of a statistically significant difference between the mean LS in those who developed HCC or not may be related to the inability to correct for confounding factors and the absence of raw source data. There was a statistically significant LS SMD at 24 wk of follow-up between patients who developed HCC vs not (0.64; 95%CI: 0.04-1.24). CONCLUSION: SWE could be a promising tool for prediction of HCC occurrence in patients treated with DAAs. Further studies with larger cohorts and standardized timing of elastographic evaluation are needed to confirm these data.

Low-Dose Rivaroxaban to Prevent Recurrences of Venous Thromboembolism in Cancer: A Real-Life Experience with a Focus on Female Patients.

BACKGROUND: The way in which to prevent recurrent venous thromboembolism (VTE) is an unmet clinical need in cancer patients. International guidelines only provide conditional recommendations and do not specify which anticoagulant and dose should be used. In the last 2 years, we have been using low-dose rivaroxaban to prevent VTE recurrences in cancer patients. The results of this real-life experience are presented in this study. METHODS: All patients had cancer and had previously completed a cycle of at least six months of full-dose anticoagulation for the treatment of a VTE index event, before receiving a prescription of low-dose rivaroxaban (10 mg once daily) for secondary prevention of VTE. Effectiveness and safety of this therapeutic regimen were evaluated in terms of VTE recurrences, major bleedings (MB), and clinically relevant non-major bleedings (CRNMB). RESULTS: The analysis included 106 cancer patients. Their median age was 60 years (IQR 50-69). Metastatic cancer was present in 87 patients (82.1%). Six patients (5.7%) had brain metastases. Over a median follow-up time of 333 days (IQR 156-484), the incidence of VTE recurrences was 3.8% (95%CI 1.0-9.4), with a recurrence rate of 4.0 per 100 person-years (95%CI 1.1-10.2). We observed no MB (0.0%) and three CRNMB (2.8%) (95%CI 0.6-8.1). CONCLUSIONS: Low-dose rivaroxaban is potentially effective and safe in cancer patients that require prevention of recurrent VTE. Large-scale studies are needed to confirm these findings.

Evidence for Detrimental Cross Interactions between Reactive Oxygen and Nitrogen Species in Leber's Hereditary Optic Neuropathy Cells.

Here we have collected evidence suggesting that chronic changes in the NO homeostasis and the rise of reactive oxygen species bioavailability can contribute to cell dysfunction in Leber's hereditary optic neuropathy (LHON) patients. We report that peripheral blood mononuclear cells (PBMCs), derived from a female LHON patient with bilateral reduced vision and carrying the pathogenic mutation 11778/ND4, display increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), as revealed by flow cytometry, fluorometric measurements of nitrite/nitrate, and 3-nitrotyrosine immunodetection. Moreover, viability assays with the tetrazolium dye MTT showed that lymphoblasts from the same patient are more sensitive to prolonged NO exposure, leading to cell death. Taken together these findings suggest that oxidative and nitrosative stress cooperatively play an important role in driving LHON pathology when excess NO remains available over time in the cell environment.

The inflammatory circuitry of miR-149 as a pathological mechanism in osteoarthritis.

Osteoarthritis (OA) is a multifactorial degenerative pathology, whose progression is exacerbated by pro-inflammatory cytokines signaling. Among the changes triggered in chondrocytes during inflammation, modified expression of tiny epigenetic regulators as microRNAs was shown having deleterious implications for articular cartilage. Aim of the present study was to identify differentially expressed microRNAs in human OA cartilage and to determine their relevance to pathological progression. An OA model based on inflammatory stimulation of a chondrocytic human cell line was used to analyze microRNAs deregulation, and results revealed miR-149 severely down-regulated by IL1ß and TNFα. Real-time PCR analysis of miR-149 was exerted also in human primary chondrocytes isolated from cartilage of OA donors and postmortem from subjects with no known history of OA, confirming down-regulation in osteoarthritis. Moving on a functional study, miR-149 regulatory effect on tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL1ß) and interleukin 6 (IL6) 3'UTRs was evaluated by luciferase assays, and chondrocytes production of TNFα upon miR-149 transfection was measured by enzyme-linked immuno sorbent assay. We found that miR-149 is down-regulated in OA chondrocytes, and this decrease seems to be correlated to increased expression of pro-inflammatory cytokines such as TNFα, IL1ß and IL6. OA is a multifactorial disease and we think that our results give new insights for understanding the complex mechanisms of osteoarthritic pathogenesis.

Extracardiac findings detected by cardiac magnetic resonance imaging.

OBJECTIVE: To determine the prevalence and importance of extracardiac findings (ECF) in patients undergoing clinical CMR and to test the hypothesis that the original CMR reading focusing on the heart may underestimate extracardiac abnormalities. METHODS: 401 consecutive patients (mean age 53 years) underwent CMR at 1.5 T. Main indications were ischaemic heart disease (n = 183) and cardiomyopathy (n = 164). All CMR sequences, including scout images, were reviewed with specific attention to ECF in a second reading by the same radiologist who performed the first clinical reading. Potentially significant findings were defined as abnormalities requiring additional clinical or radiological follow-up. RESULTS: 250 incidental ECF were detected, of which 84 (34%) had potentially significant ECF including bronchial carcinoma (n = 1), lung consolidation (n = 7) and abdominal abnormalities. In 166 CMR studies (41%) non-significant ECF were detected. The number of ECF identified at second versus first reading was higher for significant (84 vs. 47) and non-significant (166 vs. 36) findings (P < 0.00001). CONCLUSIONS: About one fifth of patients undergoing CMR were found to have potentially significant ECF requiring additional work-up. The second dedicated reading detected significantly more ECF compared with the first clinical reading emphasising the importance of active search for extracardiac abnormalities when evaluating CMR studies. KEY POINTS: • Many patients undergoing cardiac MR have significant extracardiac findings (ECF) • These impact on management and require additional work-up. • Wide review of scout and cine sequences will detect most ECFs. • Education of radiologists is important to identify ECFs on CMR studies.

Adverse effects of fibrin sealants in thoracic surgery: the safety of a new fibrin sealant: multicentre, randomized, controlled, clinical trial.

OBJECTIVES: The safety of fibrin sealants (FS) has been questioned in the light of recent reports of adverse effects. We evaluated the safety of a new FS in a randomized controlled trial (RCT). METHODS: Multicentre, open-label Phase II/III RCT to evaluate the safety of the new FS. The trial was approved by the Ethic Committee of each three participating Centre. FS includes two components (component 1: fibrinogen; component 2: thrombin), each of them subjected to two viral inactivation procedures. Out of 200 screened patients, 185 eligible patients (49 females, 136 males), aged between 18 and 75 years, undergoing major thoracic surgery were randomized to receive FS (#91 patients) as an adjuvant for air leak control or no treatment (#94 patients, control group). Safety variables were: percentage of subjects with adverse events associated with the therapy; formation of antibodies against bovine aprotinin; vital signs (blood pressure, body temperature, heart and respiratory rate); laboratory parameters. RESULTS: Overall operative mortality was 3.2% (6/185), 1.1% in the FS group and 5.3% in the control group, respectively. Twenty patients (22%) had adverse events in the FS group and 22 (23.4%) in the control group. Atrial fibrillation (five patients in the FS group and four in the control group) and hyperpyrexia (five and seven patients, respectively, in the two groups) were the most common adverse events. No patient reported thromboembolic events (pulmonary embolism or deep vein thrombosis) during the in hospital stay or within 1 month from discharge. None of the adverse events was considered as treatment related. The formation of bovine aprotinin antibodies was reported in a total of 34 patients (37.4%) in the FS group and was not related to any adverse effect. CONCLUSIONS: The present RCT did not show any increased risk of adverse events, and of surgical complications, related to the use of the new FS.

Safety and effectiveness of a new fibrin pleural air leak sealant: a multicenter, controlled, prospective, parallel-group, randomized clinical trial.

BACKGROUND: This study evaluated the sealing capacity and safety of a new fibrin sealant (FS) to reduce alveolar air leaks (AALs) after pulmonary resections in a randomized controlled clinical trial conducted in 3 Italian centers. METHODS: The study randomized (1:1) 185 patients with an intraoperative AAL graded 1 to 3 according to the Macchiarini scale: 91 received FS and 94 had standard lung closure. The primary outcomes were the length of postoperative AAL duration and the mean time to chest drain removal. Other end points included the percentage of patients without AAL, the development of serum antibodies against bovine aprotinin, and any adverse event related to FS. Chest drains were removed when fluid output was 100 mL/day or less, with no air leak. RESULTS: The study groups were comparable with respect to demographic variables and surgical procedures. The FS group showed a statistically significant reduction in duration of postoperative AALs (9.52 vs 35.8 hours; p < 0.005) and in the percentage of patients with AALs at wound closure (81.11% vs 100%; p < 0.001); the difference in time to chest drain removal was not significant. Pleural empyema developed in 1 patient with FS treatment vs in 4 with standard treatment, and antibodies against bovine aprotinin were found in 34 of 91 FS-treated patients. CONCLUSIONS: The present study showed that the new FS is safe and effective in preventing AALs after lung resections and in shortening the duration of postoperative AALs.

Post-operative radiotherapy in N2 non-small cell lung cancer: a retrospective analysis of 175 patients.

BACKGROUND AND PURPOSE: Post-operative radiotherapy (PORT) in radically resected non-small cell lung cancer (NSCLC) has the aim to reduce loco regional recurrence and to improve overall survival. PORT has been evaluated in several trials but indication to post-operative treatment in N2 patients is still debated. MATERIAL AND METHODS: We retrospectively analyzed 175 patients treated at University of Florence between 1988 and 2004 with completely resected NSCLC stages IIIA-IIIB, N2 disease. Surgery consisted in a lobectomy in 58.9% and in a bi-lobectomy or in a pneumonectomy in 41.1% of patients. One hundred and nineteen patients underwent PORT and 56 patients did not receive PORT (no-PORT). RESULTS: At a median follow-up of 27.6 months (range 4-233 months), we found a significant reduction in local recurrence (LR) in PORT group (log-rank test p=0.015; HR: 0.45; 95%CI: 0.24-0.87). No statistical difference were found in terms of overall survival (OS) (log-rank test p=0.92). Concerning other prognostic factors, male sex emerged as statistically significant (HR:4.33;1.04-18.02) on local progression free survival (LPFS) at univariate analysis. Acute and long-term toxicity was mild. CONCLUSION: Our retrospective analysis showed that PORT may improve local disease control in N2 NSCLC patients with an acceptable treatment-related toxicity.

Malignant primary chest-wall tumours: techniques of reconstruction and survival.

OBJECTIVES: We analysed our experience in primary malignant chest-wall tumours (PMCWTs) with an emphasis on a new reconstruction technique and on survival. METHODS: From 1998 to 2008, 41 patients (23 (56%) male, mean age 48 years) with PMCWT were operated in our unit: chondrosarcoma n=25; osteosarcoma n=8; Ewing's sarcoma n=2; other n=6. We performed nine sternectomies and 32 lateral chest-wall resections (median number of ribs resected=3.5). Resections were extended to the lung (n=2), diaphragm (n=3), vertebral body (n=3), scapula (n=1) and upper limb (n=1). Stability was obtained by a prosthetic material, rigid and non-rigid and a muscular flap. As non-rigid material, we mostly used a polytetrafluoroethylene patch (n=24). In the past 2 years, two patients (one total sternectomy and one wide anterior chest-wall resection) were reconstructed with a rigid system composed of mouldable titanium connecting bars and rib clips (Strasbourg Thoracic Osteosyntheses System--STRATOS, MedXpert GMbH, Heitersheim, Germany). A muscular flap was added in 12 patients (29.3%). RESULTS: There was no perioperative mortality or significant morbidity and all patients were extubated within first 24h. At a mean follow-up of 60.5 months (range 4-130 months), the overall 5- and 10-year survival was 61% and 47%, respectively. In the chondrosarcoma group, 5- and 10-year survival was 80%. CONCLUSIONS: Wide resection with tumour-free margins is necessary in PMCWT to minimise local recurrence and to contribute to long-term survival. The STRATOS system, developed for chest-wall replacement, allows a firm reconstruction, simple to handle and to fix, avoiding instability or paradoxical movement also in wide chest-wall resections.

Pulmonary resection for inflammatory complications due to benign oesophageal disease.

Benign oesophageal disease is sometimes causes an irreversible damage to the pulmonary parenchyma. The earliest symptoms often occur when the respiratory tract is involved. Primary oesophageal disease can only be detected by taking an accurate and precise medical history of the patient, so that oesophageal contrast radiography can provide the correct diagnosis. In this article we present two cases in which it was necessary to carry out a diverticulectomy with pulmonary resection, left lower lobectomy and left pneumonectomy. Reports from the literature agree that diverticular disease of the oesophagus, if misdiagnosed, can have serious consequences for the pulmonary parenchyma, even if this is rare. In both cases we present the contrast radiographic study of the oesophagus together with a double endoscopic examination of the airways and upper digestive tract which played a crucial role in the diagnosis. We can therefore conclude that respiratory symptoms in an otherwise healthy patient may constitute the basis for the diagnosis of a benign oesophageal lesion.