A pharmacoeconomic analysis from Italian guidelines for the management of prolactinomas.

Background: Prolactinoma, the most common pituitary adenoma, is usually treated with dopamine agonist (DA) therapy like cabergoline. Surgery is second-line therapy, and radiotherapy is used if surgical treatment fails or in relapsing macroprolactinoma. Objective: This study aimed to provide economic evidence for the management of prolactinoma in Italy, using a cost-of-illness and cost-utility analysis that considered various treatment options, including cabergoline, bromocriptine, temozolomide, radiation therapy, and surgical strategies. Methods: The researchers conducted a systematic literature review for each research question on scientific databases and surveyed a panel of experts for each therapeutic procedure's specific drivers that contributed to its total cost. Results: The average cost of the first year of treatment was €2,558.91 and €3,287.40 for subjects with microprolactinoma and macroprolactinoma, respectively. Follow-up costs from the second to the fifth year after initial treatment were €798.13 and €1,084.59 per year in both groups. Cabergoline had an adequate cost-utility profile, with an incremental cost-effectiveness ratio (ICER) of €3,201.15 compared to bromocriptine, based on a willingness-to-pay of €40,000 per quality-adjusted life year (QALY) in the reference economy. Endoscopic surgery was more cost-effective than cabergoline, with an ICER of €44,846.64. Considering a willingness-to-pay of €40,000/QALY, the baseline findings show cabergoline to have high cost utility and endoscopic surgery just a tad above that. Conclusions: Due to the favorable cost-utility profile and safety of surgical treatment, pituitary surgery should be considered more frequently as the initial therapeutic approach. This management choice could lead to better outcomes and an appropriate allocation of healthcare resources.

Pathologic comparison of conventional video-assisted thoracic surgical (VATS) biopsy versus non-intubated/"awake" biopsy in fibrosing interstitial lung diseases.

Surgical lung biopsy remains the standard procedure for the subset of patients with fibrosing interstitial lung disease (F-ILD) who require a lung biopsy to secure a confident diagnosis. Little is known about the pathologic features of samples obtained via non-intubated/"awake" surgical lung biopsy and the diagnostic accuracy of awake biopsy in patients with F-ILD. Two expert thoracic pathologists blinded to the type of lung biopsy compared the clinical-pathologic features of 120 conventional VATS biopsies with those of 21 consecutive non-intubated/"awake" VATS biopsies. No statistically significant differences between the two procedures were observed with regard to identification of histopathological features. Biopsy length, average of sampled lobes and mean number of slides were similar with the two procedures, while the width of the biopsies was significantly deeper with conventional VATS (31.5 mm versus 25.6 mm; p = 0.01). By contrast, the mean age of patients (69.5 versus 64.5 years; p = 0.02) and the level of diagnostic confidence (100% versus 75%; p = 0.007) were significantly higher among patients undergoing the "awake" procedure. Diagnostic yield was 100% in both groups, with a similar distribution of ILD diagnoses. Non-intubated/"awake" biopsy has the potential to become the standard surgical procedure in patients with F-ILD requiring a histological confirmation of their diagnosis. However, larger prospective studies are needed to validate the safety and diagnostic yield of "awake" compared to conventional VATS.

Competence in flexible bronchoscopy and basic biopsy technique.

Diagnostic bronchoscopy and tissue sampling techniques using forceps (endobronchial biopsy [EBB] and transbronchial biopsies [TBB]) or needle aspiration (transbronchial needle aspiration-TBNA), all performed with a flexible bronchoscope, are the basic elements of any interventional procedure. The flexible fibrobronchoscopy allows the visualization of the airways and is used both for diagnostic and therapeutic purposes. The working channel of both fibrobronchoscopes with optical fibers and videobronchoscopes, even if of relatively small diameter, allows the insertion of various diagnostic and therapeutic accessories. Fiber optic systems have been widely replaced by video cameras using a miniaturized charge-coupled device camera positioned at the end of the scope that provides electronic transmission of images to a monitor. The indications for both diagnostic and therapeutic fibrobronchoscopy derive from a correct evaluation of symptoms and objective signs of the patient and from the correct interpretation of imaging methods. Although bronchoscopy techniques keep evolving at a rapid pace, basic procedures such as bronchoalveolar lavage, transbronchial lung biopsy, and transbronchial needle aspiration still play a key role in pulmonary disease diagnostics, and therefore, these methods must still be part of the training of interventional pulmonologists. Trainees will acquire a thorough knowledge of thoracic anatomy and become skilled in the interpretation of thoracic imaging, after which they will be given a theoretical and practical training course on virtual reality simulators, on animal or cadaver models, the effectiveness of which has been fully demonstrated by scientific studies. Specific DOPS tests have been developed for a qualitative evaluation of procedures on simulators, on animal models and on the patient.

DIPNECH: Association Between Histopathology and Clinical Presentation.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare disorder which can be an incidental finding in imaging tests performed during the investigation of another condition, or is the final diagnosis in patients evaluated for chronic obstructive complaints. To explore the possible association between specific histopathology features and the mode of clinical presentation, we retrieved the clinical, functional, radiological, and pathological data of all 13 patients diagnosed with DIPNECH at our Institution over a 14-year period (2000-2014). As compared to patients with incidental disease (6/13, 46 %), patients with symptomatic disease were younger [mean (SD): 57.7 vs. 68.7 years, p = 0.046], were more likely to have mosaic attenuation (100 vs. 0 %, p = 0.001) and small multiple nodules (100 vs. 17 %, p = 0.005) at CT, and showed a significantly higher number of foci of linear neuroendocrine proliferation [median (IQR): 28 (13-37) vs. 6 (5-13), p = 0.018] and of tumorlets [median (IQR): 10 (8-20) vs. 1 (1-1), p = 0.002] at histology. Incidental disease was found in association with pulmonary adenocarcinoma in five out of six patients (83.3 %). The results of our study provide preliminary evidence that symptomatic patients with DIPNECH represent a specific subset characterized by younger age and a higher burden of foci of neuroendocrine proliferation.

Randomized Trial of Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration With and Without Rapid On-site Evaluation for Lung Cancer Genotyping.

BACKGROUND: Experts and scientific society guidelines recommend that rapid on-site evaluation (ROSE) be used with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to optimize lung cancer genotyping, but no comparative trial has been carried out to confirm and quantify its usefulness. METHODS: To assess the influence of ROSE on the yield of EBUS-TBNA for a multigene molecular analysis of lung cancer samples, consecutive patients with suspected or known advanced lung cancer were randomized to undergo EBUS-TBNA without ROSE (EBUS arm) or with ROSE (ROSE arm). The primary end point was the rate of the successful accomplishment of the institution's clinical protocol for molecular profiling of nonsquamous non-small cell lung cancer (EGFR and KRAS testing, followed by ALK testing for tumors with EGFR and KRAS wild-type status). RESULTS: Complete genotyping was achieved in 108 of 126 patients (85.7%) (90.8% in the ROSE arm vs 80.3% in the EBUS arm, P = .09). The patients in the ROSE arm were less likely to have samples that could be used only for pathologic diagnosis because of minimal tumor burden (0 vs 6, P = .05), and were more likely to have the bronchoscopy terminated after a single biopsy site (58.9% vs 44.1%, P = .01). CONCLUSIONS: ROSE prevents the need for a repeat invasive diagnostic procedure aimed at molecular profiling in at least one out of 10 patients with advanced lung cancer and significantly reduces the risk of retrieving samples that can be used only for pathologic subtyping because of minimal tumor burden. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01799382; URL: www.clinicaltrials.gov.

Point of care perioperative coagulation management in liver transplantation and complete portal vein thrombosis.

Liver transplantation (LT) is a serious hemostatic challenge in patients with portal vein thrombosis (PVT). Advances in monitoring systems have improved surgery in this setting. We report the successful application of a point-of-care (POC) rotational viscoelastic thromboelastometry-guided (TEM) testing system (ROTEM) which allowed management of coagulation during LT in a 64-year-old cirrhotic patient with a model for end-stage liver disease (MELD) score of 16. Perioperatively, the patient showed complete PVT, hepatomegaly, splenomegaly, recanalization of the umbilical vein, and portosystemic shunt. Macroscopic liver and spleen adherences with collateral circulation were evident. Coagulation factors and fibrinolysis were assessed preoperatively and at graft reperfusion to evaluate the need of hemostatic therapy. Based on ROTEM findings, the patient received 16 g of human fibrinogen concentrate, half preoperatively (with prothrombin complex concentrate 2000 IU, tranexamic acid 1 g, and platelets 2 IU), and two doses of 4 g before and after graft reperfusion; we achieved normalization of all monitored parameters. No ischemia-reperfusion syndrome was present. Postoperatively portal vein flux at Color-Doppler ultrasonography was normal. After a 3-day ICU stay, the patient was moved to the Department of Surgery and discharged on day 14. The postoperative course was uneventful and did not require any further haemostatic therapy.

Idiopathic pulmonary fibrosis and polymorphisms of the folate pathway genes.

OBJECTIVES: This study aims to determine the possible association between folate pathway gene polymorphisms and idiopathic pulmonary fibrosis. This represents the first study carried out on folate pathway gene polymorphisms as possible risk factors in this kind of pathology. The premise is that several polymorphisms mapping on genes responsible for folate uptake are associated with the risk of numerous diseases occurring between pregnancy and old age, and that too little is currently known about idiopathic pulmonary fibrosis. DESIGN AND METHODS: We genotyped 9 single nucleotide polymorphisms and 1 polymorphic insertion in 7 essential genes belonging to the folate pathway in 32 Italian idiopathic pulmonary fibrosis patients and 81 control subjects. This was done by PCR and restriction analysis. RESULTS: Allelic and genotypic association tests indicated that for all the analysed polymorphisms there were no significant differences between patients and controls. Nevertheless, the haplotype association analysis revealed a significant association between idiopathic pulmonary fibrosis and transcobalamin II gene polymorphisms: specifically the haplotype 776G (rs1801198)-c.1026-394G (rs7286680)-444C (rs10418) (OR=2.84; 95% C.I. 1.36-5.93, P value=0.004). CONCLUSIONS: This small-scale preliminary study would suggest the importance of further research focusing on the role of folate in the onset of idiopathic pulmonary fibrosis.

A role for epidermal growth factor receptor in idiopathic pulmonary fibrosis onset.

In idiopathic pulmonary fibrosis (IPF) patients the presence of missense polymorphisms (SNP) in members of the epidermal growth factor receptor (EGFR) family or their genetic association could influence the binding affinity of natural ligands, modifying the expression and the behavior of the correlated genes. EGFR family members are particularly involved in the epithelial injury and fibrotic process in IPF. Genetic variations in HER family of receptors may alter the possible therapeutic efficacy of EGFR inhibitors. This study aimed to analyze the relationships between IPF and specific EGF receptor family functional polymorphisms. We tested the presence of common EGFR, HER2 and HER3 non-synonymous SNPs in the peripheral blood of 20 Italian IPF patients and their association with the disease. Our data indicated that the HER2 variant allele frequency was significantly lower in patients than in controls, with an odds ratio of 0.31 (95% CI 0.080, 0.98). Our finding suggests that HER2 variant could be a protective factor against IPF onset.