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Objectives: Our goal was to assess the postoperative 90-day hospital costs of patients with prolonged air leak (PAL) including costs incurred after discharge from the initial index hospitalization., Methods: We performed a retrospective analysis of 982 patients undergoing lobectomy (898) or segmentectomy (78) (April 2014-August 2018). A total of 167 operations were open, 780 were video-assisted thoracoscopic surgery and 28 were robotic. A PAL was defined as an air leak >5 days. The 90-day postoperative costs included all fixed and variable costs incurred during the 90 days following surgery. The postoperative costs of patients with and without PAL were compared. The independent association of PAL with postoperative 90-day costs was tested after adjustment for patient-related factors and other complications by a multivariable regression analysis., Results: PAL occurred in 261 patients (27%). Their postoperative stay was 4 days longer than that of those without PAL (9.6 vs 5.7; P < 0.0001). Compared to patients without PAL, those with PAL had 27% higher index postoperative costs [7354€, standard deviation (SD) 7646 vs 5759€, SD 7183, P < 0.0001] and 40% higher 90-day postoperative costs (18 340€, SD 23 312 vs 13 102€, SD 10 264; P < 0.0001). The relative postoperative costs (the difference between 90-day and index postoperative costs) were 50% higher in PAL patients compared to non-PAL patients (P < 0.0001) and accounted for 60% of the total 90-day costs. Multivariable regression analysis showed that PAL remained an independent factor associated with 90-day costs (P < 0.0001) along with the occurrence of other cardiopulmonary complications (P < 0.0001), male gender (P = 0.018), low carbon monoxide lung diffusion capacity (P = 0.043) and thoracotomy approach (P = 0.022)., Conclusions: PAL is associated not only with increased index hospitalization costs but also with increased costs after discharge. Evaluation of the cost-effectiveness of measures to prevent air leaks should also include post-discharge costs., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: The study aimed to assess the total cost (TC) and relative cost (RC) of 90-day postoperative care at the hospital after anatomic lung resection., Methods: Six hundred and forty lung resections (April 2014-September 2016) were performed at a single centre (547 lobectomies, 55 pneumonectomies and 38 segmentectomies). TC was calculated up to 90 days from the date of surgery and included the postoperative cost of the index hospitalization and the costs of hospital or emergency department readmissions, clinic appointments, medications and radiology post-discharge up to 90 days from the operation. RC was calculated as the difference between the TC and the postoperative cost of the index hospitalization. Bivariate comparisons were performed by using the Mann-Whitney test. Multivariable regression analysis was used to identify the factors associated with TC., Results: Median TC was €12 389.5 [interquartile range (IQR) 8455-23 043] for pneumonectomy, €9192.1 (IQR 6897-17 274) for open lobectomy, €7932.5 (IQR 5806-12 697) for video-assisted thoracoscopic surgery (VATS) lobectomy and €6609.9 (IQR 5215-13 907) for VATS segmentectomy. Median RCs were €4461.4 (IQR 1240-11 828) for pneumonectomy, €3326.8 (IQR 1626-8271) for open lobectomy, €2729.3 (IQR 1348-6312) for VATS lobectomy and €2771.5 (IQR 1229-9705) for segmentectomy. RC accounted for 36% of the TC for pneumonectomy, 36% for open lobectomy, 34% for VATS lobectomy and 42% for segmentectomy. Generalized linear models showed that age (P = 0.024), carbon monoxide lung diffusion capacity (P = 0.030) and body mass index (P = 0.015) were inversely associated with TC, whereas male gender (P = 0.054) was associated with increased cost., Conclusions: Cost-saving measures should be implemented to target not just the in-hospital but also the post-discharge period, particularly in patients with risk factors associated with increased cost., (© The Author(s) 2018. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Objectives: To detect factors associated with costs of anatomic lung resection without major complications., Methods: Two hundred and fifty consecutive patients submitted to anatomic lung resection (185 by VATS) in 1 fiscal year (1 April 2014–31 March 2015) were included. Thoracic Morbidity and Mortality (TMM) system was used to grade the severity of complications. Two hundred and ten patients who did not develop major complications (TMM < 3) were analysed. Postoperative costs were retrieved from the Financial Department through a Patient Level Information and Costing System. Multivariable regression and bootstrap analyses were used to test the association of several baseline patient characteristics with costs and obtain an aggregate scoring system to estimate postoperative costs., Results: Among the 210 patients, 117 (56%) did not develop any complication and 93 (44%) had minor complications. Their average postoperative cost was 4040€, significantly lower than the one observed in patients with major complications (13 156€, P < 0.0001). Multivariable regression revealed that open thoracotomy (P = 0.01), carbon monoxide lung diffusion capacity (DLCO) < 60% (P = 0.001) and coronary artery disease (CAD) (P = 0.009) were associated with postoperative costs. Open thoracotomy would increase the cost by 648€, DLCO < 60% by 935€ and CAD by 1043€. If all three factors were present, they would cause an increase of postoperative costs from 3592€ to 6219€., Conclusion: We were able to identify clinical factors associated with postoperative costs in patients without major complications. Recognizing groups of increased cost may lead to specific process analyses aimed at optimising their pathways of care and ultimately saving money. Moreover, these findings may help administrators to tailor future individualized lung resection reimbursement tariffs based on patient characteristics., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Everolimus, an oral mTOR (mammalian target of rapamycin) inhibitor, is currently approved for the treatment of progressive pancreatic neuroendocrine tumors (NETs). Although promising, only scattered data, often from nondedicated studies, are available for extrapancreatic NETs., Patients and Methods: A systematic review of the published data was performed concerning the use of everolimus in extrapancreatic NET, with the aim of summarizing the current knowledge on its efficacy and tolerability. Moreover, the usefulness of everolimus was evaluated according to the different sites of the primary., Results: The present study included 22 different publications, including 874 patients and 456 extrapancreatic NETs treated with everolimus. Nine different primary sites of extrapancreatic NETs were found. The median progression-free survival ranged from 12.0 to 29.9 months. The median time to progression was not reached in a phase II prospective study, and the interval to progression ranged from 12 to 36 months in 5 clinical cases. Objective responses were observed in 7 prospective studies, 2 retrospective studies, and 2 case reports. Stabilization of the disease was obtained in a high rate of patients, ranging from 67.4% to 100%. The toxicity of everolimus in extrapancreatic NETs is consistent with the known safety profile of the drug. Most adverse events were either grade 1 or 2 and easy manageable with a dose reduction or temporary interruption and only rarely requiring discontinuation., Conclusion: Treatment with everolimus in patients with extrapancreatic NETs appears to be a promising strategy that is safe and well tolerated. The use of this emerging opportunity needs to be validated with clinical trials specifically designed on this topic., Implications for Practice: The present study reviewed all the available published data concerning the use of everolimus in 456 extrapancreatic neuroendocrine tumors (NETs) and summarized the current knowledge on the efficacy and safety of this drug, not yet approved except for pancreatic NETs. The progression-free survival rates and some objective responses seem promising and support the extension of the use of this drug. The site-by-site analysis seems to suggest that some subtypes of NETs, such as colorectal, could be more sensitive to everolimus than other primary NETs. No severe adverse events were usually reported and discontinuation was rarely required; thus, everolimus should be considered a valid therapeutic option for extrapancreatic NETs., (©AlphaMed Press.)

The expression of intercellular adhesion molecule-1 (ICAM-1) in tumoral tissues may promote their interaction with the immune system and cytotoxic effect on tumoral cells. This observation led to the investigation of ICAM-1 expression and modulation in different tumoral cell systems in vitro. Recently, retinoic acid-responsive elements have been found in the 5'-regulatory region of the human ICAM-1 gene. In the present study, we investigated, by flow cytometry, the effect of retinoic acid on the surface expression of ICAM-1 in human thyroid carcinoma cell lines. Two papillary (NPA and TPC-1), one follicular (WRO), one anaplastic (ARO) and one immortalized fetal (TAD-2) cell line have been studied. All of them produced constitutively ICAM-1; its surface expression and specific messenger ribonucleic acid (mRNA) levels were increased significantly by retinoic acid in all except the WRO cell line. ICAM-1 hyperexpression by retinoic acid was time dependent, reversible, and dependent on mRNA and protein synthesis. Furthermore, cytokines, such as interferon-gamma and tumor necrosis factor-alpha, both individually and, to a greater extent, in combination with retinoic acid, increased ICAM-1 surface expression and its mRNA levels. In conclusion, retinoic acid is able to induce ICAM-1 up-regulation via mRNA accumulation in human thyroid carcinoma cell lines.

To assess the expression of the very late antigens family of the integrin superfamily in normal and diseased thyroid glands, tissue specimens were digested to a single cell suspension and analyzed by flow cytometry with antibodies against the common beta 1 chain and the six alpha chains known to be associated to beta 1. In multinodular goiters, two cell populations were recognized. The thyroglobulin containing follicular cell population, represented the majority of cells; a minor population was composed of leukocytes. In normal glands, more than 97% of follicular cells expressed the beta 1 chain, associated with high levels of alpha 3 and very low levels of alpha 1, alpha 5, and alpha 6. The remaining cells (< 3%) expressed the beta 1 chain with a 10-fold higher intensity, associated with relatively high levels of alpha 1, alpha 5, and alpha 6, in addition to alpha 3. This small subset was much more represented in multinodular goiters, where it ranged from 10-60% of the total follicular cell population. Immunofluorescence on tissue sections showed that very late antigens were mostly located on the basal cell membrane and that in multinodular goiters cells expressing the alpha 1, alpha 5, and alpha 6 chains occurred in clusters.