Malignant pleural mesothelioma (MPM) is an aggressive asbestos-related cancer arising from the mesothelial cells lining the pleural cavity. MPM is characterized by a silent clinical progression and a ...highly resistance to conventional chemo/radio-therapies. MPM patients die in a few months/years from diagnosis. Notch signaling is a well-conserved cell communication system, which regulates many biological processes. In humans, the dysregulation of Notch pathway potentially contributes to cancer onset/progression, including MPM. Metformin is the first-line drug used to treat type 2 diabetes mellitus. Metformin is proven to be an effective antitumor drug in preclinical models of different types of cancer. To date, clinical efficacy is being studied in many clinical trials. In this study, the anti-proliferative effect of metformin on MPM cells and the putative involvement of Notch1 as a mediator of metformin activities, were investigated. MPM cells showed high levels of Notch1 activation compared to normal pleural mesothelial cells. Furthermore, metformin treatment hampered MPM cell proliferation and enhanced the apoptotic process, accompanied by decreased Notch1 activation.
Bronchial carcinoids (BCs) are rare neuroendocrine tumors that are still orphans of medical treatment. Human BC primary cultures may display resistance to everolimus, an inhibitor of the mammalian ...target of rapamycin (mTOR), in terms of cell viability reduction. Our aim was to assess whether the novel dual phosphatidylinositol 3-kinase (PI3K)/mTOR inhibitor NVP-BEZ235 is effective in everolimus-resistant human BC tissues and cell lines. In addition, we searched for possible markers of the efficacy of mTOR inhibitors that may help in identifying the patients who may benefit from treatment with mTOR inhibitors, sparing them from ineffective therapy. We found that NVP-BEZ235 is twice as potent as everolimus in reducing cell viability and activating apoptosis in human BC tissues that display sensitivity to mTOR inhibitors, but is not effective in everolimus-resistant BC tissues and cell lines that bypass cyclin D1 downregulation and escape G0/G1 blockade. Rebound AKT activation was not observed in response to treatment with either mTOR inhibitor in the ‘resistant’ BC cells. In addition to total mTOR levels, putative markers of the sensitivity of BCs to mTOR inhibitors are represented by AKT, p70S6K (RPS6KB2), and ERK1/2 (MAPK3/1) protein levels. Finally, we validated these markers in an independent BC group. These data indicate that the dual PI3K/mTOR inhibitor NVP-BEZ235 is more potent than everolimus in reducing the proliferation of human BC cells. ‘Resistant’ cells display lower levels of mTOR, p70S6K, AKT, and ERK1/2, indicating that these proteins may be useful as predictive markers of resistance to mTOR and PI3K/mTOR inhibitors in human BCs.
COVID-19 pandemic has impacted professional, economic and social activities. In the surgical field, it has brought changes to operating activities, the organization of workforces, the protection ...measures for patients and personnel against possible intraoperative transmissions as well as training young surgeons. This study intends to assess the extent of this impact in our institution.
The patients operated on in nine Operating Units (OUs) in the period February 1 - March 31, 2020, with follow-ups on April 30, 2020, were evaluated both retrospectively and prospectively. Organizational, clinical and impact parameters on staff were evaluated.
Of the 833 consecutive admitted patients, 742 were operated on, 705 of whom were recruited for the study. Compared to the same period in 2019 there was a decrease in the number of operations (742 compared to 1187), similar use of intensive care unit (ICU), a diagnostic activity only for symptomatic patients, heterogeneity in organizational behaviors, an impact on staff who highlighted concerns about getting sick or passing the infection on to others (87.64%) or their family members (75.14%).
The present study made it possible to detect the need to make significant changes in the clinical, organizational and teaching fields, for which some operational proposals are suggested.
The purpose of this study was to evaluate the perception of the quality of care, considering both patient experience and health care professionals' perceptions as well as patient outcome measures of ...an integrated lung cancer pathway.
A cross-sectional study was conducted in 2016 at Ferrara University Hospital, Italy. OPportunity for Treatment In ONcology (OPTION) questionnaires were administered to 77 patients, and the Care Process Self-Evaluation Tool (CPSET) questionnaires were given to 38 health care professionals. The effectiveness of the pathway was evaluated by analysing the tool's positive impact on lung cancer surgery volume and 30-day mortality.
Seventy-seven patients were enrolled, and 38 health care professionals assessed the CPSET questionnaire. The highest scores were related to "respect" (100%), "satisfaction" (98.7%), and "trust" (97.4%) on the OPTION and to "patient-focused vision" (97.2%) and "patient engagement" (94.4%) on the CPSET. The lowest scores were related to "information" (26%) and "cooperation with general practitioner" (17.6%) on the OPTION and "cooperation between the hospital and primary care" (23.5%) for the CPSET. The outcomes analysis shows an increase in the volume of activity and a decrease in 30-day mortality after pathway implementation.
The lung cancer pathway is a patient-centred intervention that enables care to be shaped for patient needs in order to improve the quality and efficiency of service and clinical outcome.
Trypsin and mast cell tryptase cleave proteinase-activated receptor 2 (PAR2) to induce alterations in contraction of airway smooth muscle that have been implicated in asthma in experimental animals. ...Although tryptase inhibitors are under development for treatment of asthma, little is known about the localization and function of PAR2 in human airways. We detected PAR2 expression in primary cultures of human airway smooth muscle cells using reverse transcriptase/polymerase chain reaction (RT-PCR) and immunofluorescence. The PAR2 agonists trypsin, tryptase, and an activating peptide (SLIGKV-NH2) stimulated calcium mobilization in these cells. PAR2 agonists strongly desensitized responses to a second challenge of trypsin and SLIGKV-NH2, but not to thrombin, indicating that they activate a receptor distinct from the thrombin receptors. Immunoreactive PAR2 was detected in smooth muscle, epithelium, glands, and endothelium of human bronchi. Trypsin, SLIGKV-NH2, and tryptase stimulated contraction of isolated human bronchi. Contraction was increased by removal of the epithelium and diminished by indomethacin. Thus, PAR2 is expressed by human bronchial smooth muscle where its activation mobilizes intracellular Ca2+ and induces contraction. These results are consistent with the hypothesis that PAR2 agonists, including tryptase, induce bronchoconstriction of human airway by stimulating smooth muscle contraction. PAR2 antagonists may be useful drugs to prevent bronchoconstriction.
Cutaneous melanoma is one of the most studied neoplastic lesions in biology and clinical oncology. It has been well documented that this type of neoplasm presents a high metastatic rate, and is able ...to involve nearly every tissue. Non-cutaneous melanoma represents an unusual pattern of melanoma, and the small intestine is an uncommon anatomic localization. Herein we report an extremely rare clinical case of a young woman affected by a bleeding jejunal melanoma, whose early clinical presentation was an intestinal invagination.
Broncho-pulmonary neuroendocrine neoplasms (BP-NENs) are neoplasms orphan of an efficient therapy. Available medical treatments derived from clinical trials are not specific for the management of ...this malignancy. Sunitinib is a multi-receptor tyrosine-kinases (RTKs) inhibitor that has already shown its efficacy in NENs, but there are no available data about its action in BP-NENs. Therefore, our aim was to understand the effects of RTKs inhibition promoted by sunitinib in order to evaluate new putative targets useful in malignancy treatment. Since our results underlined a role for EGFR and IGF1R in modulating sunitinib antiproliferative action, we investigated the effects of erlotinib, an EGFR inhibitor, and linsitinib, an IGF1R inhibitor, in order to understand their function in regulating cells behaviour. Cell viability and caspase activation were evaluated on two immortalised human BP-NEN cell lines and primary cultures. Our results showed that after treatment with sunitinib and/or IGF1, EGF and VEGF, the antiproliferative effect of sunitinib was counteracted by EGF and IGF1 but not by VEGF. Therefore, we evaluated with AlphaScreen technology the phosphorylated EGFR and IGF1R levels in primary cultures treated with sunitinib and/or EGF and IGF1. Results showed a decrease of p-IGF1R after treatment with sunitinib and an increase after co-treatment with IGF1. Then, we assessed cell viability and caspase activation on BP-NEN cell lines after treatment with linsitinib and/or erlotinib. Results demonstrate that these two agents have a stronger antiproliferative effect compared to sunitinib. In conclusion, our results suggest that IGF1R and EGF1R could represent putative molecular targets in BP-NENs treatment.
Thoracoscopic thymectomy is increasingly performed for the treatment of early stage thymoma. It is characterized by shorter postoperative hospital stay, decreased intraoperative blood loss, and fewer ...complications compared with transsternal thymectomy. Unilateral video-assisted thoracic surgery (VATS) thymectomy can be easily performed from either side of the thorax, because thymus is located in the middle of mediastinum. However, the side that provides better outcomes remains controversial. The purpose of this study was to compare the efficacy of right and left approaches in performing unilateral thoracoscopic thymectomy for thymoma.
Consecutive patients affected by thymoma who underwent VATS thymectomy on either side between February 2001 and March 2020 were enrolled in the study. Clinicopathologic, surgical, and oncological outcomes were retrospectively analyzed and compared among the two surgical approaches.
Unilateral VATS approaches were performed on 29 patients: 12 (41%) on the left side and 17 (59%) on the right side. The mean age was 63.1 ± 11.3 years and the female/male ratio was 1.73:1. The mean operative time and the hospital stay for the left-side VATS and right-side VATS groups were, respectively, 168 ± 49.5 versus 171 ± 47.9 minutes (
= 0.9) and 3 ± 1.03 days versus 3.65 ± 1.93 days (
= 0.7). Postoperative complications occurred in one patient (3%) for left-side VATS group and one patient (3%) for right-side VATS. The 5-year disease-free survival was comparable between two groups (
= 0.74).
Unilateral VATS thymectomy in patients with thymoma can be safely and effectively performed by experienced surgeons in either side of the thorax with equivalent oncological outcomes.
The management of patients affected by lung cancer requires the expertise of specialists from different disciplines. Although the advantages of multidisciplinary team discussions seem obvious, there ...are limited studies evaluating the influence of this approach on postoperative outcomes in non-small-cell lung cancer (NSCLC). The aim of this study is to examine the impact of a multidisciplinary approach on survival of patients undergoing surgery for NSCLC.
A retrospective analysis was performed on consecutive patients who underwent surgery for NSCLC between January 2008 and December 2015. Data were compared between patients treated before the implementation of a multidisciplinary tumour board (MTB), between 2008 and 2012, and those who received treatment after the implementation of the MTB, between 2012 and 2015. Patients were matched one to one according to the discussion of the MTB and on the basis of a propensity score built using several patient characteristics. A propensity score-matched analysis was performed to compare patient outcomes.
A total of 246 patients were treated prior to the initiation of the MTB and 231 patients after the initiation of the MTB. Based on the propensity score, 2 well-matched groups of 170 patients were identified. Patients who were discussed at the MTB were noted to have better outcomes when compared with those who were not discussed at the MTB on different terms including complete staging evaluation, early tumour, node and metastasis (TNM) stages and 1-year survival rate.
Implementation of a multidisciplinary thoracic malignancy conference increased the 1-year survival rate of patients who underwent a surgical resection for NSCLC.
This study aims to describe the relationship between the new tumor nodes metastasis (TNM) staging and World Health Organization (WHO) classification and to identify how these two variables relate to ...each other and whether they possess a prognostic value in predicting survival and recurrence of disease.
Medical records of 54 patients who underwent surgery for thymic epithelial tumors between 1996 and 2015 were reviewed.The histologic type of neoplasm was classified according to the criteria of WHO and staging was evaluated using the new TNM classification system.
A significant correlation between the TNM stages and the histological classification was found (
< 0.001). Complete resection is related to both TNM stage and histological grading (
< 0.001). Evaluation of the 5- and 10-year survival curves shows how these are significantly correlated only at the stage (
= 0.03 and = 0.04, respectively). The risk of death at 5 and 10 years for stages III to IV is six and three times higher than in stages I to II, respectively. Regarding the disease-free survival, there is significant correlation with both staging and histology (
= 0.001 and = 0.02, respectively).
There is a significant correlation between the new TNM staging and the histological grade WHO. The ability to implement a complete resection, the overall and disease-free survival is closely related to the thymoma stage. Furthermore, both histotype and stage correlate with disease-free survival. In fact, the least aggressive stages, both WHO and TNM, have a free time out of disease superior to advanced stages.
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