Publications by authors named "Alessandro Borri"

67 Publications

A quasi-equilibrium reduced model of pancreatic insulin secretion.

J Math Biol 2021 Mar 1;82(4):25. Epub 2021 Mar 1.

CNR-IASI Biomathematics Laboratory (BioMatLab), Rome, Italy.

Much attention has been devoted in the last few decades to mathematical models of insulin secretion, in order to better understand the regulation of glycemia and its derangements. The glucose-insulin homeostatic mechanism is so complex and gives rise to such diverse behavior following perturbations that different models had been published, which reproduced the results of single experiments. More recently, a unifying model of pancreatic insulin secretion was proposed, which is able to account, with a single value of the (meta)parameters, for the wide array of clinically observed behavior. This model explicitly represented the pulsatile nature of the many pancreatic hormone-secreting firing units: the price to pay for its flexibility and performance is the very high dimensionality (hundreds of thousand equations) of the corresponding dynamical system. Clearly, it would be desirable to reduce this model to a much simpler form while retaining its power to reproduce heterogeneous phenomena. The present work reviews the qualitative behavior of this pancreas pulsatile model and offers some insight into its reduction in equilibrium and quasi-equilibrium conditions, also considering single-shot (non-repeated) glucose jumps from an approximately resting condition (such as would occur in standard Intra-Venous bolus dosing of glucose during diabetes diagnostic maneuvers). The resulting quasi-steady-state model can be further endowed with additional lower-order dynamics to also approximate transient behavior. Although a more accurate reduction of the original pulsatile model is left to further investigation, numerical results confirm the biomedical applicability of the formulation already obtained.
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http://dx.doi.org/10.1007/s00285-021-01575-5DOI Listing
March 2021

Optimal design of lock-down and reopening policies for early-stage epidemics through SIR-D models.

Annu Rev Control 2020 Dec 23. Epub 2020 Dec 23.

Istituto di Analisi dei Sistemi ed Informatica "A. Ruberti", Consiglio Nazionale delle Ricerche (IASI-CNR), 00185 Roma, Italy.

The diffusion of COVID-19 represents a real threat for the health and economic system of a country. Therefore the governments have to adopt fast containment measures in order to stop its spread and to prevent the related devastating consequences. In this paper, a technique is proposed to optimally design the lock-down and reopening policies so as to minimize an aggregate cost function accounting for the number of individuals that decease due to the spread of COVID-19. A constraint on the maximal number of concomitant infected patients is also taken into account in order to prevent the collapse of the health system. The optimal procedure is built on the basis of a simple SIR model that describes the outbreak of a generic disease, without attempting to accurately reproduce all the COVID-19 epidemic features. This modeling choice is motivated by the fact that the containing measurements are actuated during the very first period of the outbreak, when the characteristics of the new emergent disease are not known but timely containment actions are required. In fact, as a consequence of dealing with poor preliminary data, the simplest modeling choice is able to reduce unidentifiability problems. Further, the relative simplicity of this model allows to compute explicitly its solutions and to derive closed-form expressions for the maximum number of infected and for the steady-state value of deceased individuals. These expressions can be then used to design static optimization problems so to determine the (open-loop) optimal lock-down and reopening policies for early-stage epidemics accounting for both the health and economic costs.
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http://dx.doi.org/10.1016/j.arcontrol.2020.12.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758039PMC
December 2020

A revised Sorensen model: Simulating glycemic and insulinemic response to oral and intra-venous glucose load.

PLoS One 2020 14;15(8):e0237215. Epub 2020 Aug 14.

Institute of System Analysis and Informatics (IASI) "A. Ruberti", National Research Council (CNR), Rome, Italy.

In 1978, Thomas J. Sorensen defended a thesis in chemical engineering at the University of California, Berkeley, where he proposed an extensive model of glucose-insulin control, model which was thereafter widely employed for virtual patient simulation. The original model, and even more so its subsequent implementations by other Authors, presented however a few imprecisions in reporting the correct model equations and parameter values. The goal of the present work is to revise the original Sorensen's model, to clearly summarize its defining equations, to supplement it with a missing gastrio-intestinal glucose absorption and to make an implementation of the revised model available on-line to the scientific community.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237215PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428140PMC
October 2020

Laparoscopic vaginal lateral suspension: technical aspects and initial experience.

Minerva Chir 2020 Aug 6. Epub 2020 Aug 6.

Division of Gastrointestinal Surgery, Careggi University Hospital, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.

Background: Pelvic Organ Prolapse etiology is a combination of anatomical, physiological, genetic, lifestyle, and reproductive factors determine pelvic floor dysfunction. POP is very common across all ages women worldwide and has become an increasing socioeconomic problem with public health consequences, with symptoms that could lead to a significant decrease in quality of life.

Methods: This study retrospectively analyzes a small case series of our initial experience of laparoscopic vaginal suspension with mesh focusing on the technical aspects of the technique. Although sacrocolpopexy and sacrohysteropexy are the most performed surgical techniques, they are associated with serious complications. Laparoscopic vaginal suspension appears reproducible and safe to learn.

Results: Between November 2017 and January 2020, fifteen patients underwent laparoscopic vaginal suspension for pelvic organ prolapse repair. Despite the small number, for a minimally invasive skilled surgeon, we notice a significative reduction of the learning curve to become proficient in this procedure.

Conclusions: The diagnosis and management of pelvic organ prolapse are further complicated by what is considered "successful" treatment. Laparoscopic vaginal suspension is a feasible surgical procedure for one-stage treatment of pelvic organ prolapse.
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http://dx.doi.org/10.23736/S0026-4733.20.08414-XDOI Listing
August 2020

Mixture distributions in a stochastic gene expression model with delayed feedback: a WKB approximation approach.

J Math Biol 2020 07 24;81(1):343-367. Epub 2020 Jun 24.

University of Delaware, Newark, DE, USA.

Noise in gene expression can be substantively affected by the presence of production delay. Here we consider a mathematical model with bursty production of protein, a one-step production delay (the passage of which activates the protein), and feedback in the frequency of bursts. We specifically focus on examining the steady-state behaviour of the model in the slow-activation (i.e. large-delay) regime. Using a formal asymptotic approach, we derive an autonomous ordinary differential equation for the inactive protein that applies in the slow-activation regime. If the differential equation is monostable, the steady-state distribution of the inactive (active) protein is approximated by a single Gaussian (Poisson) mode located at the globally stable fixed point of the differential equation. If the differential equation is bistable (due to cooperative positive feedback), the steady-state distribution of the inactive (active) protein is approximated by a mixture of Gaussian (Poisson) modes located at the stable fixed points; the weights of the modes are determined from a WKB approximation to the stationary distribution. The asymptotic results are compared to numerical solutions of the chemical master equation.
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http://dx.doi.org/10.1007/s00285-020-01512-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363733PMC
July 2020

Erratum to: Ten Years' Experience in Robotic-Assisted Thoracic Surgery for Early Stage Lung Cancer.

Thorac Cardiovasc Surg 2019 Oct 4. Epub 2019 Oct 4.

Department of Thoracic Surgery, IEO, European Institute of Oncology IRCCS, Milan, Italy.

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http://dx.doi.org/10.1055/s-0039-1698411DOI Listing
October 2019

Pleural catheters after thoracoscopic treatment of malignant pleural effusion: a randomized comparative study on quality of life.

J Thorac Dis 2018 May;10(5):2999-3004

Department of Thoracic Surgery, European Institute of Oncology, Milan, Italy.

Background: Malignant pleural effusion (MPE) complicates many neoplasms and its incidence is expected to rise in parallel with the aging population and longer survival of cancer patients. Although a clear consensus exists on indwelling catheters in patients with poor performance status, no study has hitherto compared different devices in patients requiring temporary or definitive drainage following talc poudrage.

Methods: This is a prospective, two-arm, pilot study on patients with MPE undergoing talc poudrage, comparing two different catheters (PleurX versus Pleurocath) positioned because of the inefficacy of the procedure or the high risk of short-term failure. End points of the study were quality of life (QoL), median dyspnea and chest pain assessment by EORTC questionnaires and a 100 mm visual analog scale, total in-hospital length of stay and frequency of serious adverse events.

Results: No difference was observed between the two groups in in mean dyspnea and mean chest pain in any questions of the EORTC QLQ-C30 and QLQ-LC13 questionnaires. Duration of the procedure was significantly longer in the PleurX group versus the Pleurocath group (72±33 versus 44±13 minutes; P=0.03). No difference was observed between the two groups in total length of hospital stay (P=1.00) or complication rate (P=1.00).

Conclusions: For the cohort of patients still needing indwelling pleural catheters (PC) after thoracoscopic talc poudrage, PleurX is suggested when drain removal is unlikely due to short life expectancy or the high chance of pleurodesis failure. Conversely, Pleurocath should be recommended in all other patients as it is faster to place and easier to remove.

Keywords: Malignant pleural effusion (MPE); talc poudrage; indwelling pleural catheter (indwelling PC).
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http://dx.doi.org/10.21037/jtd.2018.05.49DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006061PMC
May 2018

Robotic-assisted thymectomy for early-stage thymoma: a propensity-score matched analysis.

J Robot Surg 2018 Dec 28;12(4):719-724. Epub 2018 Apr 28.

Division of Thoracic Surgery, European Institute of Oncology, University of Milan, Via G. Ripamonti, 435, 20141, Milan, Italy.

The aim of this study was to analyse the feasibility and safety of robotic-assisted thymectomy (RoT) in patients with clinically early stage thymoma, investigating clinical and early oncological results. Between 1998 and 2017, we retrospectively reviewed 76 (42.2%) patients who underwent radical thymectomy for clinically early stage thymoma (Masaoka-Koga I and II), identifying all patients who underwent RoT (n = 28) or open thymectomy (OT) with eligibility criteria for robotic surgery (n = 48). Using a propensity-score matched for tumor size (3.9 ± 1.8 cm) and stage (35% stage I, 42% stage IIA, 23% stage IIB), we paired 24 patients who had RoT with 24 patients undergoing OT. RoT was left-sided in 19 (79.2%) patients. None of the patients required conversion to open surgery. OT was via sternotomy in 21 (87.5%) patients and thoracotomy in 3 (12.5%). Mean operating time was shorter in the RoT group (117 ± 40 min) than in the OT (141 ± 46 min) (p = 0.06), even if not statistically significant. Length of stay was significantly shorter in the RoT group (mean 4.0 ± 1.9 days) than in the OT (mean 5.9 ± 1.7 days) (p = 0.0009). No significant difference between the two groups regarding post-operative complications. Five patients died in the OT group after a median follow-up of 6.1 years (only one for recurrence). After a median follow-up of 1.3 years, all patients in the RoT group were alive without disease. RoT is feasible and safe for early stage thymoma with clear advantage compared to OT in term of short term outcomes. A longer follow-up is needed to better evaluate the oncological results.
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http://dx.doi.org/10.1007/s11701-018-0816-3DOI Listing
December 2018

Ten Years' Experience in Robotic-Assisted Thoracic Surgery for Early Stage Lung Cancer.

Thorac Cardiovasc Surg 2019 Oct 1;67(7):564-572. Epub 2018 Apr 1.

Department of Thoracic Surgery, IEO, European Institute of Oncology IRCCS, Milan, Italy.

Background:  This study analyzed the short- and long-term outcomes of robotic-assisted thoracic surgery (RATS) for early stage non-small cell lung cancer (NSCLC).

Methods:  From November 2006 to December 2016, we performed 363 RATS procedures. This study retrospectively reviewed 339 patients who underwent RATS for clinical stages I ( = 318) or II ( = 21) NSCLC.

Results:  Twenty-nine patients underwent segmentectomy, 307 lobectomy, and 3 pneumonectomy. Conversion occurred in 22 patients (6.5%): 15 (4.4%) due to technical issues, 4 (1.2%) for oncological reasons, and 3 (0.9%) for bleeding. The median number of N1 and N2 stations resected was 2 and 3, respectively, and the median number of N1 and N2 lymph nodes resected was 9 and 6, respectively. Median operative time was 192 minutes for lobectomy, 172 minutes for segmentectomy, and 275 minutes for pneumonectomy. Median length of hospital stay was 5 days (2-191). The most common postoperative complication was prolonged air leak (12.1%). Major complications occurred in eight patients (2.4%). The 30-day and 90-day operative mortality was 0% and 0.3%, respectively. Two and 5-year cancer-specific survival rate was 96.1% and 91.5%, respectively. Five-year survival rate was 96.2% for patients who underwent segmentectomy, and 89.1% for lobectomy. All three patients who underwent pneumonectomy were alive at 5 years with no disease.

Conclusions:  Besides the well-known short-term outcomes showing very low morbidity and mortality rates, mediastinal lymph node dissection during RATS adequately assesses lymph node stations detecting occult lymph node metastasis and leading to excellent oncologic results. However, these results await longer follow-up studies.
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http://dx.doi.org/10.1055/s-0038-1639575DOI Listing
October 2019

Emergency drain for post pneumonectomy bronchopleural fistula: a drain placement technique based on the siphon principle.

J Thorac Dis 2018 Jan;10(1):468-471

Division of Thoracic Surgery, European Institute of Oncology, Milan, Italy.

Post pneumonectomy bronchopleural fistula (BPF) is a life-threatening complication requiring pleural cavity drainage to avoid acute mediastinal shift and contralateral aspiration pneumonia. Chest drain insertion in this situation may be technically difficult because of drastic anatomical changes such as mediastinal dislocation, diaphragm elevation and, sometimes, massive subcutaneous emphysema. In addition, the most important part of the pleural cavity to be drained is the costophrenic recess that is scarcely drained by a standard chest tube with its tip aiming high and upwards. We propose a safe, simple and effective technique based on the siphon principle to drain the lowest part of the pleural cavity.
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http://dx.doi.org/10.21037/jtd.2017.11.145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863130PMC
January 2018

New stapling devices in robotic surgery.

J Vis Surg 2017 10;3:45. Epub 2017 Apr 10.

Division of Thoracic Surgery, European Institute of Oncology, Milan, Italy.

Minimally invasive thoracic surgery is rapidly diffusing worldwide. Robotic anatomic pulmonary resection is gaining popularity and acceptance in the thoracic community for the reported feasibility, safety, and good outcomes. The last available robotic system, da Vinci Xi System, added new technical improvements on robotic device allowing best performances in robotic lung resection. We report our initial experience in the use of EndoWrist Stapler during robotic anatomic surgery for lung cancer.
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http://dx.doi.org/10.21037/jovs.2017.02.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5637468PMC
April 2017

Diagnostic biomarkers for lung cancer prevention.

J Breath Res 2018 02 6;12(2):027111. Epub 2018 Feb 6.

Division of Thoracic Surgery, European Institute of Oncology, Milan, Italy.

Lung cancer is the leading cause of death for neoplasm. Lung cancer mortality is frequently associated with late diagnosis, therefore an early diagnosis is a key factor to significantly improve overall survival in high risk populations of asymptomatic patients. Conventional cancer screenings (low-dose computed tomography or chest x-ray) today offer early detection but are invasive and expensive. Previously these studies evaluated the solid and topographic cancer structure and morphology. Today the concept of tumor has been remodelled, being defined as a disease that has its own genetic, biological and metabolic identity; it is on this new awareness that we should base new screening methods. Recent research has shown great reliability of new tests such as exhaled breath analysis, serum biomarkers and urine analysis in early diagnosis of lung cancer. Analysis of new biomarkers associated with the high specificity of these new screening methods, which are non-invasive, safe, inexpensive and simple to perform, could allow a non-invasive approach to determine a big change in the early diagnosis of cancer and its survival rate. Furthermore, these new techniques put the patient at the core of a non-invasive diagnostic process and ensure a better quality of life during medical diagnosis. In this article, we want to analyze the possible benefits of these new and promising methods, suggesting a possible combination between them to ensure, as soon as possible, an early and effective diagnosis of lung cancer with a special focus on the patient, in a new era of personalized medicine.
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http://dx.doi.org/10.1088/1752-7163/aa9386DOI Listing
February 2018

Single-Incision Versus Three-Port Laparoscopic Appendectomy: Short- and Long-Term Outcomes.

J Laparoendosc Adv Surg Tech A 2017 Aug 12;27(8):804-811. Epub 2017 Apr 12.

2 Department of Emergency and Accident, Azienda Ospedaliera Universitaria Careggi (AOUC) , Florence, Italy .

Aim: To compare the outcome of patients who had undergone single-incision laparoscopic appendectomy (SILA) with others who had undergone three-port laparoscopic appendectomy (3-PORT).

Materials And Methods: Data from all adults with uncomplicated appendicitis treated by laparoscopic appendectomy between June 2012 and December 2015 were prospectively collected. Patients with chronic pain, appendix malignancy, at least two previous laparotomies, and those undergoing concomitant surgery for different condition were excluded from analysis. Postoperative pain was assessed by a visual analog scale (VAS). Patients were reviewed postoperatively at 7 days and 1 month in the outpatient clinic. Late complications were assessed with a telephonic interview.

Results: A total of 91 patients were included (46 SILA; 45 3-PORT). There were 16 males and 30 females in the SILA group (mean age = 26.76 ± 10.58 years) and 18 males and 27 females in the 3-PORT group (mean age = 26.84 ± 10.79 years). The mean operative time for SILA was 48.54 ± 12.80 min, for the 3-PORT group the mean operative time was 46.33 ± 15.54 min (P = 0.46). No case required conversion. Mean postoperative hospital length of stay was 1.87 ± 0.69 days for SILA and 2.38 ± 1.11 days for 3-PORT (P = 0.01). VAS value of 3.91 ± 1.96 and mean ketorolac usage of 0.38 ± 0.65 in 3-PORT group and SILA patients reported 3.70 ± 1.58 and 0.39 ± 0.58, respectively (P = 0.91). Our mean follow-up in SILA group was 25.75 ± 10.82 months, for 3-PORT group the mean follow-up was 26.9 ± 11.8 months. Eleven patients missed long-term follow-up. No incisional hernia was found. There is a statistically significant difference in cosmetic evaluation in favor of SILA (P < 0.005).

Conclusions: There was no difference in operative time, early complications, postoperative pain, analgesia requirement between SILA and 3-PORT laparoscopic appendectomy, but after SILA procedure discharge was quicker and long-term cosmetic satisfaction was superior.
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http://dx.doi.org/10.1089/lap.2016.0406DOI Listing
August 2017

Efficacy and safety of Innoseal for air leak after pulmonary resection: a case-control study.

J Surg Res 2016 11 1;206(1):22-26. Epub 2016 Jul 1.

Department of Thoracic Surgery, European Institute of Oncology, Milan, Italy; Department of Oncology and Hematology-Oncology-DIPO, University of Milan, Milan, Italy.

Background: Prolonged air leak is one of the most common complications after lung surgery and the cause of prolonged hospital stay frequently associated with major postoperative morbidity and thus responsible for even higher hospital costs. This case-control study was designed to test the sealing efficacy and safety of Enable-Innoseal TP4 in patients undergoing pulmonary resection for lung cancer.

Methods: This was a case-control trial enrolling patients with primary or single site metastatic lung cancer scheduled for elective anatomic or nonanatomic pulmonary resection presenting intraoperative grade 1 or 2 air leak at water submersion test; the study group population was then matched 1:1 according to surgical procedure, male/female ratio, preoperative FEV1, and age.

Results: In the study population, 21 patients (70.0%) presented intraoperative grade 1 air leak and 9 patients grade 2 (30.0%) air leak; after comparison with the control group, we observed a significant shorter time for chest drain removal in the study population (P = 0.0050), whereas no difference was registered in terms of number of days needing for discharge (P = 0.0762).

Conclusions: Enable-Innoseal TP4 was effective in treating limited intraoperative air leaks after pulmonary resection and preventing prolonged postoperative air leaks in patients receiving either anatomic or nonanatomic lung resections. Further randomized double-arm studies are required to confirm the efficacy of Enable-Innoseal TP4 demonstrated by this pilot study.
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http://dx.doi.org/10.1016/j.jss.2016.06.066DOI Listing
November 2016

Impact of negative feedback in metabolic noise propagation.

IET Syst Biol 2016 Oct;10(5):179-186

Department of Electrical and Computer Engineering, Biomedical Engineering, Mathematical Sciences, Center for Bioinformatics and Computational Biology, University of Delaware, Newark, DE 19716, USA.

Synthetic biology combines different branches of biology and engineering aimed at designing synthetic biological circuits able to replicate emergent properties useful for the biotechnology industry, human health and environment. The role of negative feedback in noise propagation for a basic enzymatic reaction scheme is investigated. Two feedback control schemes on enzyme expression are considered: one from the final product of the pathway activity, the other from the enzyme accumulation. Both schemes are designed to provide the same steady-state average values of the involved players, in order to evaluate the feedback performances according to the same working mode. Computations are carried out numerically and analytically, the latter allowing to infer information on which model parameter setting leads to a more efficient noise attenuation, according to the chosen scheme. In addition to highlighting the role of the feedback in providing a substantial noise reduction, our investigation concludes that the effect of feedback is enhanced by increasing the promoter sensitivity for both schemes. A further interesting biological insight is that an increase in the promoter sensitivity provides more benefits to the feedback from the product with respect to the feedback from the enzyme, in terms of enlarging the parameter design space.
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http://dx.doi.org/10.1049/iet-syb.2016.0003DOI Listing
October 2016

Simulation of Trauma Incidents : Modelling the Evolution of Patients and Resources.

J Med Syst 2016 Nov 21;40(11):234. Epub 2016 Sep 21.

CNR-IASI Biomathematics Laboratory (BioMatLab), Largo A. Gemelli 8, 00168, Rome, Italy.

Mathematical modeling and simulation with medical applications has gained much interest in the last few years, mainly due to the widespread availability of low-cost technology and computational power. This paper presents an integrated platform for the in-silico simulation of trauma incidents, based on a suite of interacting mathematical models. The models cover the generation of a scenario for an incident, a model of physiological evolution of the affected individuals, including the possible effect of the treatment, and a model of evolution in time of the required medical resources. The problem of optimal resource allocation is also investigated. Model parameters have been identified according to the expertise of medical doctors and by reviewing some related literature. The models have been implemented and exposed as web services, while some software clients have been built for the purpose of testing. Due to its extendability, our integrated platform highlights the potential of model-based simulation in different health-related fields, such as emergency medicine and personal health systems. Modifications of the models are already being used in the context of two funded projects, aiming at evaluating the response of health systems to major incidents with and without model-based decision support.
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http://dx.doi.org/10.1007/s10916-016-0599-xDOI Listing
November 2016

Glasgow Prognostic Score Class 2 Predicts Prolonged Intensive Care Unit Stay in Patients Undergoing Pneumonectomy.

Ann Thorac Surg 2016 Dec 20;102(6):1898-1904. Epub 2016 Aug 20.

Department of Thoracic Surgery, European Institute of Oncology, Milan, Italy; Department of Oncology and Hematology-Oncology-DIPO, University of Milan, Milan, Italy.

Background: The Glasgow prognostic score (GPS) is an inflammation-based score based on albuminemia and C-reactive protein concentration proved to be associated with cancer-specific survival in several neoplasms. The present study explored the immediate postoperative value of the GPS for patients undergoing pneumonectomy for lung cancer.

Methods: The value of the GPS preoperatively was studied in 250 patients undergoing pneumonectomy for non-small cell lung cancer (NSCLC). We analyzed overall postoperative complications, pulmonary and cardiac complications, 30-day postoperative death, reoperation for early complications, intensive care unit (ICU) length of stay and total length of hospital stay.

Results: Patients with a GPS of 0 and 1 had a mean ICU length of stay of 0.8 days, whereas patients with a GPS of 2 had a mean ICU stay of 5.0 days (p = 0.004). The postoperative mortality rate in patients with a GPS of 2 was much higher than in patients with a GPS of 1 and 2, although it was not statistically significant (p = 0.083).

Conclusions: A preoperative GPS of 2 effectively predicts a prolonged ICU stay in patients who undergo pneumonectomy for cancer. The score may be proposed as an easy-to-determine, economical, and fast preoperative tool to plan and optimize ICU admissions after elective pneumonectomy.
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http://dx.doi.org/10.1016/j.athoracsur.2016.05.111DOI Listing
December 2016

Volatile signature for the early diagnosis of lung cancer.

J Breath Res 2016 Feb 9;10(1):016007. Epub 2016 Feb 9.

Division of Thoracic Surgery, European Institute of Oncology, Milan, Italy.

Exhaled breath contains hundreds of volatile organic compounds (VOCs). Several independent researchers point out that the breath of lung cancer patients shows a characteristic VOC-profile which can be considered as lung cancer signature and, thus, used for diagnosis. In this regard, the analysis of exhaled breath with gas sensor arrays is a potential non-invasive, relatively low-cost and easy technique for the early detection of lung cancer. This clinical study evaluated the gas sensor array response for the identification of the exhaled breath of lung cancer patients. This study involved 146 individuals: 70 with lung cancer confirmed by computerized tomography (CT) or positron emission tomography-(PET) imaging techniques and histology (biopsy) or with clinical suspect of lung cancer and 76 healthy controls. Their exhaled breath was measured with a gas sensor array composed of a matrix of eight quartz microbalances (QMBs), each functionalized with a different metalloporphyrin. The instrument produces, for each analyzed sample, a vector of signals encoding the breath (breathprint). Breathprints were analyzed with multivariate analysis in order to correlate the sensor signals to the disease. Breathprints of the lung cancer patients were differentiated from those of the healthy controls with a sensitivity of 81% and specificity of 91%. Similar values were obtained in patients with and without metabolic comorbidities, such as diabetes, obesity and dyslipidemia (sensitivity 85%, specificity 88% and sensitivity 76%, specificity 94%, respectively). The device showed a large sensitivity to lung cancer at stage I with respect to stage II/III/IV (92% and 58% respectively). The sensitivity for stage I did not change for patients with or without metabolic comorbidities (90%, 94%, respectively). Results show that this electronic nose can discriminate the exhaled breath of the lung cancer patients from those of the healthy controls. Moreover, the largest sensitivity is observed for the subgroup of patients with a lung cancer at stage I.
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http://dx.doi.org/10.1088/1752-7155/10/1/016007DOI Listing
February 2016

A glycemia-structured population model.

J Math Biol 2016 07 6;73(1):39-62. Epub 2015 Oct 6.

BioMatLab, IASI-CNR, Rome, Italy.

Structured models are population models in which the individuals are characterized with respect to the value of some variable of interest, called the structure variable. In the present paper, we propose a glycemia-structured population model, based on a linear partial differential equation with variable coefficients. The model is characterized by three rate functions: a new-adult population glycemic profile, a glycemia-dependent mortality rate and a glycemia-dependent average worsening rate. First, we formally analyze some properties of the solution, the transient behavior and the equilibrium distribution. Then, we identify the key parameters and functions of the model from real-life data and we hypothesize some plausible modifications of the rate functions to obtain a more beneficial steady-state behavior. The interest of the model is that, while it summarizes the evolution of diabetes in the population in a completely different way with respect to previously published Monte Carlo aggregations of individual-based models, it does appear to offer a good approximation of observed reality and of the features expected in the clinical setting. The model can offer insights in pharmaceutical research and be used to assess possible public health intervention strategies.
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http://dx.doi.org/10.1007/s00285-015-0935-7DOI Listing
July 2016

Surgical Techniques and Long-Term Results of Pulmonary Artery Reconstruction in Patients With Lung Cancer.

Ann Thorac Surg 2015 Oct 21;100(4):1196-202; discussion 1202. Epub 2015 Jul 21.

Division of Thoracic Surgery, European Institute of Oncology, Milan; University of Milan School of Medicine, Milan, Italy.

Background: Pulmonary artery (PA) reconstruction for lung cancer is technically feasible with low morbidity and mortality. We assessed our experience with partial or circumferential resection of the PA during lung resection.

Methods: Between 1998 and 2013, we performed PA angioplasty in 150 patients with lung cancer. Partial PA resection was performed in 146 patients. PA reconstruction was performed by running suture in 113 patients and by using a pericardial patch in 33. A circumferential PA resection was performed in 4 patients, and reconstruction was made with polytetrafluoroethylene and by a custom-made bovine pericardial conduit. Bronchial sleeve resection was associated in 56 patients. Stage I disease was present in 32 patients, stage II in 43, stage IIIA in 51, and stage IIIB in 17. Seventy-five patients received induction chemotherapy, and 7 patients had a complete response.

Results: Thirty-day mortality was 3.3% (n = 5); two of these patients died of a massive hemoptysis. Pulmonary complications occurred in 33 patients, cardiac in 28, and air leaks in 17. Overall 5-year and 10-year survival was 50% and 39%, respectively. Survival at 5 and 10 years for stages I and II vs stage III was, respectively, 66% vs 32% and 56% vs 20% (p < 0.0001). Five-year survival was 61% for N0 and N1 nodal involvement vs 28% for N2, and the respective 10-year survival was 45% vs 28% (p = 0.001). Induction chemotherapy did not influence survival. Multivariate analysis yielded advanced stage, N2 status, and squamous cell carcinoma as negative prognostic factors.

Conclusions: PA reconstruction is safe, with excellent long-term survival. Our results support this technique as an effective option to pneumonectomy for patients with lung cancer.
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http://dx.doi.org/10.1016/j.athoracsur.2015.04.124DOI Listing
October 2015

Current Perspectives in Mesenchymal Stromal Cell Therapies for Airway Tissue Defects.

Stem Cells Int 2015 8;2015:746392. Epub 2015 Jun 8.

Department of Thoracic Surgery, European Institute of Oncology, 20143 Milan, Italy ; University of Milan School of Medicine, 20122 Milan, Italy.

Lung cancer is the leading cause of cancer death and respiratory diseases are the third cause of death in industrialized countries; for this reason the airways and cardiopulmonary system have been the focus of extensive investigation, in particular of the new emerging branch of regenerative medicine. Mesenchymal stromal cells (MSCs) are a population of undifferentiated multipotent adult cells that naturally reside within the human body, which can differentiate into osteogenic, chondrogenic, and adipogenic lineages when cultured in specific inducing media. MSCs have the ability to migrate and engraft at sites of inflammation and injury in response to cytokines, chemokines, and growth factors at a wound site and they can exert local reparative effects through transdifferentiation and differentiation into specific cell types or via the paracrine secretion of soluble factors with anti-inflammatory and wound-healing activities. Experimental and clinical evidence exists regarding MSCs efficacy in airway defects restoration; although clinical MSCs use, in the daily practice, is not yet completely reached for airway diseases, we can argue that MSCs do not represent any more merely an experimental approach to airway tissue defects restoration but they can be considered as a "salvage" therapeutic tool in very selected patients and diseases.
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http://dx.doi.org/10.1155/2015/746392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4475757PMC
July 2015

Operative rigid bronchoscopy: indications, basic techniques and results.

Multimed Man Cardiothorac Surg 2014 May 27;2014. Epub 2014 May 27.

Department of Thoracic Surgery, European Institute of Oncology, Milan, Italy University of Milan School of Medicine, Milan, Italy.

Palliative airway treatments are essential to improve quality and length of life in lung cancer patients with central airway obstruction. Rigid bronchoscopy has proved to be an excellent tool to provide airway access and control in this cohort of patients. The main indication for rigid bronchoscopy in adult bronchology remains central airway obstruction due to neoplastic or non-neoplastic disease. We routinely use negative pressure ventilation (NPV) under general anaesthesia to prevent intraoperative apnoea and respiratory acidosis. This procedure allows opioid sparing, a shorter recovery time and avoids manually assisted ventilation, thereby reducing the amount of oxygen needed, while maintaining optimal surgical conditions. The major indication for NPV rigid bronchoscopy at our institution has been airway obstruction by neoplastic tracheobronchial tissue, mainly treated by laser-assisted mechanical dissection. When strictly necessary, we use silicone stents for neoplastic or cicatricial strictures, reserving metal stents to cover tracheo-oesophageal fistulae. NPV rigid bronchoscopy is an excellent tool for the endoscopic treatment of locally advanced tumours of the lung, especially when patients have exhausted the conventional therapeutic resources. Laser-assisted mechanical resection and stent placement are the most effective procedures for preserving quality of life in patients with advanced stage cancer.
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http://dx.doi.org/10.1093/mmcts/mmu006DOI Listing
May 2014

Lung metastases from colorectal cancer: analysis of prognostic factors in a single institution study.

Ann Thorac Surg 2014 Oct 5;98(4):1238-45. Epub 2014 Aug 5.

Division of Thoracic Surgery, European Institute of Oncology, Milan, Italy.

Background: The aim of our study was to evaluate retrospectively in a large single institution setting all cases of lung resections for colorectal metastases from 1998 to 2008 and to assess clinicopathologic factors influencing outcome.

Methods: In all, 199 patients, 125 men and 74 women, with lung metastases of colorectal cancer, 120 colon and 79 rectum, underwent resection with curative intent; mean interval between primary surgery and lung metastasis was 35 months. Carcinoembryonic antigen preoperative value was abnormal in 52 patients; K-RAS wild-type was detected in 60 of 97 examined cases; 75 patients received preoperative or postoperative chemotherapy or both. A solitary lesion was described in 95 patients (47.7%), two or three metastases in 72 (36.2%), and more than three metastases in 26 (13.1%). Nodal status was reported in 130 patients (73%). One hundred twenty patients (60.3%) underwent wedge resection, 27 (13.6%) underwent segmentectomy, and 52 (26.1%) had lobectomy. An R0 resection was achieved in 178 cases (89.4%).

Results: Median overall survival was 4.2 years (95% confidence interval: 3.1 to 5.1) with a 5-year overall survival of 43% (95% confidence interval: 36% to 50%). An R1 resection (log rank p = 0.0001), thoracic nodal involvement (log rank p = 0.0002), and preoperative abnormal carcinoembryonic antigen value (log rank p < 0.001) were significantly associated with poor outcome in univariate analysis. In multivariate analysis, the same variables plus the number of lesions (single versus multiple, p = 0.04) were shown to affect outcome.

Conclusions: An R0 resection, preoperative carcinoembryonic antigen, nodal involvement, and number of lesions represent strong prognostic factors in patient with lung metastases of colorectal cancer. The role of systemic treatments and biomolecular tests deserve future prospective investigations.
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http://dx.doi.org/10.1016/j.athoracsur.2014.05.048DOI Listing
October 2014

Outcome and prognostic factors of resected non-small-cell lung cancer invading the diaphragm.

Interact Cardiovasc Thorac Surg 2014 Oct 26;19(4):632-6; discussion 636. Epub 2014 Jun 26.

Division of Thoracic Surgery, European Institute of Oncology, Milan, Italy University of Milan School of Medicine, Milan, Italy.

Objectives: Diaphragmatic infiltration by non-small-cell lung cancer (NSCLC) is a rare occurrence and surgical results are unclear. We assessed our experience with en bloc resection of lung cancer invading the diaphragm, analysing prognostic factors and long-term outcomes.

Methods: We analysed a prospective database of patients with NSCLC infiltrating the diaphragm who underwent en bloc resection. Univariate analysis was performed to identify prognostic factors. Survival was calculated by the Kaplan-Meier method.

Results: Nineteen patients (14 men, mean age 64 ± 11 years) were identified. Surgery included nine pneumonectomies, eight lobectomies and two segmentectomies. A partial diaphragmatic infiltration was observed in 10 patients (53%) and full-depth invasion in 9 (47%). Diaphragmatic reconstruction was done primarily in 13 patients (68%), and by prosthetic material in 6 (32%). Pathological nodal status included nine N0, four N1 and six N2. The median hospital stay was 7 days (range, 4-36 days). The postoperative mortality rate was 5% (1/19). Two patients (10%) had major complications (acute respiratory distress syndrome and bleeding) and 10 minor complications, arrhythmia in 7 (37%) and pneumonia in 3 (16%). The 5-year survival was 30 ± 11%. The median survival and disease-free survival were 15 ± 9 months (range, 1-164 months) and 9 ± 7 months (range, 1-83 months), respectively. Factors adversely affecting survival were diaphragmatic infiltration (50% superficial vs 0% full-depth infiltration; log-rank test, P = 0.04) and nodal involvement (43% N0 vs 20% N1-2; log-rank test, P = 0.03).

Conclusions: Resection of NSCLC invading the diaphragm is technically feasible and could be a valid therapeutic option with acceptable morbidity and mortality and long-term survival in highly selected patients.
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http://dx.doi.org/10.1093/icvts/ivu183DOI Listing
October 2014

Chest wall resection and reconstruction for locally recurrent breast cancer: From technical aspects to biological assessment.

Surgeon 2016 Feb 6;14(1):26-32. Epub 2014 Apr 6.

Department of Thoracic Surgery, European Institute of Oncology, Italy; University of Milan School of Medicine, Italy.

Introduction: Breast cancer is the leading cause of cancer death among women in the industrialized countries. The incidence of local recurrences after mastectomy and breast-conserving therapy varies between 5% and 40% depending on risk factors and primary therapy.

Methods: From April 1999 to April 2011, 40 patients underwent chest wall resection and reconstruction for locally recurrent breast carcinoma with chest wall invasion. The main goal of surgery was local disease control to palliate clinical symptoms.

Results: Local radical resection was achieved in 26 patients (65%). One, 2 and 5 year overall survival rates were 94.4%, 82.0% and 68.5%; 1, 2 and 5 year disease-free survival rates were 94.4%, 73.6% and 45.5% respectively. Univariate analysis indicated age (p = 0.002) and synchronous distant metastases (p = 0.020) as factors having a negative impact on overall survival; multivariate analysis disclosed age (p = 0.052) and synchronous metastases (p = 0.059) as factors with a slight negative impact on overall survival. Older age was associated with improved overall survival. Univariate analysis indicated synchronous distant metastases (p = 0.029) and the need of post resectional additional treatments (p = 0.022) as factors adversely conditioning disease-free survival or time to progression; multivariate analysis disclosed the need of post resectional additional treatments (p = 0.036) as the only factor adversely conditioning disease-free survival or time to progression.

Conclusions: Chest wall resection and reconstruction for locally recurrent breast cancer is a feasible and safe procedure providing adequate local disease control and an excellent palliation of very disabling symptoms in a selected group of patients.
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http://dx.doi.org/10.1016/j.surge.2014.03.001DOI Listing
February 2016

Giant solitary fibrous tumor of the pleura requiring left pneumonectomy.

Thorac Cancer 2014 01 2;5(1):108-10. Epub 2014 Jan 2.

Division of Thoracic Surgery, European Institute of Oncology Milan, Italy; University of Milan School of Medicine Milan, Italy.

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http://dx.doi.org/10.1111/1759-7714.12052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4704290PMC
January 2014

Endobronchial tumor embolism.

J Bronchology Interv Pulmonol 2013 Oct;20(4):366-8

*Division of Thoracic Surgery European Institute of Oncology †Division of Bronchopneumology San Carlo Borromeo Hospital ‡University of Milan School of Medicine Milan, Italy.

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http://dx.doi.org/10.1097/LBR.0000000000000017DOI Listing
October 2013

Survival after extended resection for mediastinal advanced lung cancer: lessons learned on 167 consecutive cases.

Ann Thorac Surg 2013 May 6;95(5):1717-25. Epub 2013 Apr 6.

Division of Thoracic Surgery, European Institute of Oncology, Milan, Italy.

Background: Extended resections (ER) for lung cancer may improve survival in selected patients. However, analysis on large series is still lacking. We reviewed our experience to identify prognostic factors useful for patient selection.

Methods: Between 1998 and 2010, 167 patients with involvement of one or more mediastinal organs underwent operations with the intent to perform ER. At thoracotomy, 42 patients (25%) were considered unresectable (explorative thoracotomy [ET]), and 125 (75%) underwent ER. The types of ER were superior vena cava in 43 patients (34.4%), carina in 33 (26.4%), combined with superior vena cava in 18 (14.4%), with the left atrium in 35 (28%), and with the aorta in 14 (11.2%). We excluded Pancoast tumors and vertebral resections. The minimum follow-up was 6 months. Kaplan-Meier method and log-rank test were used for statistical analysis of survival.

Results: There were 136 men (81.4%), with mean age of 63 years (range, 36 to 81 years). Of the 167 patients, induction chemotherapy was administered in 119 (71.3%), including 34 ET patients (81%) and 85 ER patients (68%). Complete resection was achieved in 106 patients (84.8%). The overall 5-year survival was 23% (27% in ER and 13% in ET, p = 0.41). Overall 30-day mortality was 4.8% and morbidity was 34.1%. Factors affecting survival were complete resection (p < 0.01), pStage 0-I-II disease (p < 0.0007), and age younger than 60 years (p < 0.01).

Conclusions: ER for lung cancer invading mediastinal organs could improve long-term survival (46% at 5-years in pN0). The best surgical candidates are young patients without lymph nodes involvement who undergo radical resection. Multimodality treatment is suggested in case of mediastinal lymph node involvement.
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http://dx.doi.org/10.1016/j.athoracsur.2013.01.088DOI Listing
May 2013

Bronchovascular reconstruction for lung cancer: does induction chemotherapy influence the outcomes?

Ann Thorac Surg 2012 Sep 7;94(3):907-13; discussion 913. Epub 2012 Jul 7.

Division of Thoracic Surgery, European Institute of Oncology, Milan, Italy.

Background: Bronchoangioplastic interventions (BAIs) for lung cancer are challenging procedures associated with a high risk of postoperative morbidity and mortality. The role of induction chemotherapy (IC) in these patients is debated.

Methods: We reviewed clinical records of patients who underwent a BAI between 1998 and 2009 using a prospective clinical and operative database.

Results: Among 47 patients (39 men; mean age, 66 years) who underwent BAI, 26 (55.3%) received IC for N2 disease or for locally advanced lung cancer. We performed 35 pulmonary artery (PA) sleeve resections (31 partial and 4 circumferential), 10 PA reconstructions with a pericardial patch (8 autologous, and 2 heterologous), and 2 PA reconstructions using heterologous conduit. The 30-day mortality rate was 4.2% (n=2). Morbidity occurred in 19 (40.4%) patients; 5 patients (10.6%) had major complications (3 [6.4%] patients with fatal bronchovascular fistulas and 1 patient each with cardiac dislocation and acute respiratory distress syndrome) (2.2%). Fourteen patients (29.8%) had minor complications: 6 (12.7%) cardiac, 7 (14.9%) pulmonary, and 1 (2.2%) stroke. IC did not influence the complication rate. Overall 5-year survival and disease-free survival was 39.2% and 36.9%, respectively. Early pathologic stage and the absence of nodal involvement significantly influenced survival (p=0.005 and p=0.002, respectively). Patients receiving IC had a better prognosis (62.7% versus 10.7%; p=0.0003). At multivariate analysis, IC influenced long-term survival (p=0.003 [95% CI, 2.92-8.56]).

Conclusions: BAIs are feasible and effective surgical procedures with acceptable morbidity and mortality. IC does not influence morbidity and allows good long-term outcomes.
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http://dx.doi.org/10.1016/j.athoracsur.2012.05.050DOI Listing
September 2012

Robotic anatomic segmentectomy of the lung: technical aspects and initial results.

Ann Thorac Surg 2012 Sep 28;94(3):929-34. Epub 2012 Jun 28.

Division of Thoracic Surgery, European Institute of Oncology, Milan, Italy.

Background: Robotic lobectomy with radical lymph node dissection is a new frontier of minimally invasive thoracic surgery. Series of sublobar anatomic resection for primary initial lung cancers or for metastasis using video-assisted thoracic surgery have been reported but no cases have been so far reported using the robot-assisted approach. We present the technique and surgical outcome of our initial experience.

Methods: Clinical data of patients undergoing robotic lung anatomic segmentectomy were retrospectively reviewed. All cases were done using the DaVinci System. A 3- or 4-incision strategy with a 3-cm utility incision in the anterior fourth or fifth intercostal space was performed. Individual ligation and division of the hilar structures was performed using Hem-o-Lok (Teleflex Medical, Research Triangle Park, NC) or endoscopic staplers. The parenchyma was transected with endovascular staplers introduced by the bedside assistant mainly through the utility incision. Systematic mediastinal lymph node dissection or sampling was performed.

Results: From 2008 to 2010, 17 patients underwent a robot-assisted lung anatomic segmentectomy in two centers. There were 10 women and 7 men with a mean age of 68.2 years (range, 32 to 82). Mean duration of surgery was 189 minutes. There were no major intraoperative complications. Conversion to open procedure was never required. Postoperative morbidity rate was 17.6% with pneumonia in 1 case and prolonged air leaks in 2 patients. Median postoperative stay was 5 days (range, 2 to 14), and postoperative mortality was 0%. Final pathology was non-small cell lung cancer in 8 patient, typical carcinoids in 2, and lung metastases in 7.

Conclusions: Robotic anatomic lung segmentectomy is feasible and safe procedure. Robotic system, by improving ergonomic, surgeon view and precise movements, may make minimally invasive segmentectomy easier to adopt and perform.
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http://dx.doi.org/10.1016/j.athoracsur.2012.04.086DOI Listing
September 2012