Cost-effectiveness analysis of baricitinib versus dupilumab for moderate to severe atopic dermatitis: an Italian healthcare system perspective.

AIMS: To assess, within the Italian healthcare system, the cost-effectiveness of baricitinib versus dupilumab, both in combination with topical corticosteroids (TCS), in adults with moderate to severe atopic dermatitis (AD) who are eligible for but have failed, have contraindications to, or cannot tolerate ciclosporin. MATERIALS AND METHODS: Using the perspective of the Italian healthcare payer, direct medical costs associated with each intervention were estimated over a lifetime horizon. A Markov cohort model utilized the proportions of patients with ≥75% improvement Eczema Area and Severity Index obtained from clinical trials. Health outcomes were evaluated in quality-adjusted life years (QALYs) to assess the cost effectiveness of baricitinib against a willingness-to-pay threshold of €35,000 per QALY gained. RESULTS: In the base case, with secondary censoring applied, patients treated with dupilumab or baricitinib, in combination with TCS, accumulated total costs of €135,780 or €129,586, and total QALYs of 18.172 or 18.133, respectively. The incremental cost-effectiveness ratio of dupilumab versus baricitinib was estimated at €160,905/QALY. LIMITATIONS: Core assumptions were needed to extrapolate available short-term clinical trial data to lifelong data, adding uncertainty. Benefits of baricitinib seen in clinical trials and not assessed in dupilumab clinical trials were not included. Discontinuation rates for each treatment were derived from different sources potentially introducing bias. Results may not be generalizable to other populations. CONCLUSIONS: This cost-effectiveness analysis shows that, from the Italian healthcare payer perspective, in the treatment of patients with moderate to severe AD who have experienced failure on, are intolerant to, or have contraindication to ciclosporin, dupilumab cannot be considered cost-effective when compared with baricitinib. Given its oral administration, favorable risk/benefit profile and lower acquisition cost compared with dupilumab, baricitinib may offer a valuable, cost-effective treatment option-after failure on conventional systemic agents-for patients with moderate to severe AD in Italy.

Baricitinib is the first oral systemic treatment for patients with moderate to severe atopic dermatitis (AD). The drug was effective for treating patients with AD in clinical trials, producing improvements in skin inflammation, itch, sleep disturbances due to itch and skin pain, as well as the quality of life of patients. However, it is important to ensure that healthcare funds are well spent. We therefore compared the cost-effectiveness of baricitinib, with another new systemic treatment for AD, dupilumab, (both in combination with topical corticosteroids) in patients with moderate to severe AD who are eligible for but have failed or are unable to take ciclosporin, in Italy. We found that using dupilumab to treat these patients with AD cost more than using baricitinib, although dupilumab was more effective. Combining these considerations showed that the cost of obtaining the additional benefit from dupilumab over baricitinib was not cost-effective for the Italian healthcare system. Baricitinib may be a better treatment option because it is given orally, has a favorable balance between the risks and benefits of treatment, and costs less than dupilumab.

Analysis of Drug Utilization in Patients with Psoriasis: A Real-World Retrospective Study Among the Italian Population.

Purpose: An Italian real-world retrospective study was conducted in patients with psoriasis (PSO) to evaluate their characteristics, treatment patterns, and biological/targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) drug utilization. Patients and Methods: The retrospective analysis was carried out on real-world data collected from administrative databases of selected Italian health-departments; the dataset covered approximately 22% of the Italian population. PSO patients (identified by PSO hospitalization, and/or active exemption code and/or a topical anti-psoriatic medication prescription) were included. In prevalent patients identified during 2017-2018-2019-2020, baseline characteristics and treatment patterns were investigated. Moreover, b/tsDMARD drug utilization (focusing on persistence, monthly dosage, and mean duration between prescriptions) was evaluated in bionaïve patients included during 2015 and 2018. Results: PSO was diagnosed in 241,552 (in 2017), 269,856 (in 2018), 293,905 (in 2019) and 301,639 (in 2020) patients. At the index date, almost 50% of patients had not received systemic medications, and 2% had received biological treatment. Among the b/tsDMARD-treated patients, a decrease in the use of tumour necrosis factor (TNF) inhibitors (60.0-36.4%, from 2017 to 2020) and an increase in the use of interleukin (IL) inhibitors (36.3-50.6%, from 2017 to 2020) were observed. In 2018, the persistence rates of TNF inhibitors and IL inhibitors in bionaïve patients ranged from 60.8-79.7% and 83.3-87.9%, respectively. Conclusion: This real-world study of PSO drug utilization in Italy showed that a significant number of patients were not treated with systemic medications and only 2% of patients were treated with biologics. An increase in the use of IL inhibitors and a decrease in the prescription of TNF inhibitors over years were found. Patients treated with biologics were highly persistent with treatment. These data provide insight into routine clinical practice for PSO patients in Italy, suggesting that the optimization of treatment for PSO still represents an unmet medical need.

Thromboembolism in COVID-19: the unsolved problem.

INTRODUCTION: The recent Sars-CoV-2 pandemic (COVID-19) has led to growing research to explain the poor clinical prognosis in some patients. While early observational studies highlighted the role of the virus in lung failure, in a second moment thrombosis emerged as a possible explanation of the worse clinical course in some patients. Despite initial difficulties in management of such patients, the constant increase of literature in the field is to date clarifying some questions from clinicians. However, several other questions need answer. EVIDENCE ACQUISITION: We performed systematic research using Embase and PubMed, inserting the keywords and mesh terms relative to the new coronavirus and to VTE: "COVID-19," "SARS," "MERS," "coronavirus," "2019 n-CoV," venous thromboembolism," "pulmonary embolism," "deep vein thrombosis," "thromboembolism," "thrombosis." Boolean operators "AND," "OR," "NOT" were used where appropriate. We found 133 articles of interest but only 20 were selected, providing the most representative information. EVIDENCE SYNTHESIS: A novel disease (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2) infection was responsible for thousands of hospitalizations for severe acute respiratory syndrome, with several cases of thrombotic complications due to excessive inflammation, platelet activation, endothelial dysfunction, and stasis. COVID-19 and hospitalizations for COVID-19 may carry several potential risk factors for thrombosis. Severe coagulation abnormalities may occur in almost all the severe and critical ill COVID-19 cases. CONCLUSIONS: Despite a strong pathophysiological rationale, the evidence in literature is not enough to recommend an aggressive antithrombotic therapy in COVID-19. However, it is our opinion that an early use, even at home at the beginning of the disease, could improve the clinical course.

Analysis of the Pharmacoutilization of Biological Drugs in Psoriatic Arthritis Patients: A Real-World Retrospective Study Among an Italian Population.

INTRODUCTION: Real-world pharmacoutilization analysis of biological drugs in psoriatic arthritis (PsA) patients with the aim to evaluate biologic treatment patterns and pharmacoutilization among patients with PsA in Italy. METHODS: A retrospective study was conducted using administrative databases of Italian Entities. PsA patients were included and diagnosed by hospitalization and/or an active exemption code. Two analyses were performed: a cross-sectional for treatment patterns in patients enrolled among 2017-2020, and a longitudinal study during 2015 to investigate the pharmacoutilization, in terms of persistence and monthly maintenance dosage of biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs). Patients with or without b/tsDMARDs prescriptions before inclusion were defined as bioexperienced or naïve, respectively. An analysis on ixekizumab-treated patients (IXE patients) from the 2017-to study ending was performed. RESULTS: PsA was diagnosed in 24,786 (2017), 27,221 (2018), 28,889 (2019), and 29,292 (2020) patients. Across 2017-2020, 31.1-40.5% of PsA patients were untreated with systemic medications, and 16.4-18.8% were under biological therapies. Among b/tsDMARD-treated patients, decreasing use of TNF-inhibitors (77.6-57.1%) and increasing IL-inhibitors (19.6-33.2%) was found across 2017-2020, respectively. Persistence to TNF-inhibitors and IL inhibitors as first-line ranged, respectively, 74.9-83.0% and 73.0-84.6%; specifically, 73.1-76.9% and 73.0-83.8% among bio-naïve, 83.3-90.0%, and 87.0% among bio-experienced. Among IXE-patients (N = 178), 55.6% were bio-naïve, while 21.9% previously used secukinumab, 12.9% adalimumab, 10.1% etanercept. During a 1-year follow-up, 6.8% of IXE patients switched therapy. CONCLUSIONS: This real-world study of PsA pharmacoutilization in Italy showed that more than one-third of patients were systemically untreated, and almost 20% were receiving biological medications. Among biological users, increasing use of IL-inhibitors and a decrease in TNF-inhibitors prescriptions over the years were found. A rather-high extent of persistency in treatment was observed. A focused analysis on IXE patients revealed over half of them to be bio-naïve, while around one-fourth were bio-experienced to IL inhibitors.

Novel active fixation lead guided by electrical delay can improve response to cardiac resynchronization therapy in heart failure.

AIMS: Cardiac resynchronization therapy (CRT) for heart failure (HF) recently has shown optimal results by targeting electrically delayed sites in coronary sinus (CS) branches. However this purpose often cannot be reached because of unstable left ventricular (LV) lead position. In current study were assessed the long-term effects of the novel active fixation LV lead in CS, guided by electrical delay (QLV), in patients with HF due to coronary artery disease. METHODS: One hundred eighty-five consecutive patients underwent CRT with intraoperative evaluation of QLV in the target position of the LV lead. When the novel active fixation LV lead was available, 98 consecutive patients received it, composing the Fix group. They were compared with 87 patients with a conventional passive fixation lead (No Fix group). The final LV lead position was assessed by fluoroscopy. Clinical response to CRT was assessed within a period of about 3 years: patients experiencing HF rehospitalization and death due to HF were defined as non-responders. RESULTS: There were no significant differences between groups in the final position of LV lead in left anterior oblique view (Pearson χ2  = 0.12; P = 0.73). In right anterior oblique view, a basal position was reached more in the Fix group (38%) than in the No Fix group (6.5%) (Pearson χ2  = 23.095; P < 0.001). QLV was significantly greater in the Fix group (122.6 ± 33.2 ms; SE = 3.6) than in the No Fix group (97.5 ± 37.8 ms; SE = 4.9) (t = 4.17; P < 0.001). Rehospitalizations for HF were 37 in the No Fix group and 14 in the Fix group. Deaths due to HF were 49 in the No Fix group and 18 in the Fix group. Survival analysis, assessed by Cox regression, showed that the Fix group had a better outcome both for HF rehospitalizations [hazard ratio (HR) = 0.48; 95% confidence interval (CI) = 0.25-0.9; P = 0.023] and death due to HF (HR = 0.55; 95% CI = 0.31-0.97; P = 0.04) in comparison with the No Fix group. Adjustment for baseline characteristics by multivariate analysis showed that an active fixation lead in CS, as a covariate, was still significant both for HF rehospitalizations (HR 0.46; 95% CI = 0.24-0.88; P = 0.019) and for death due to HF (HR 0.5; 95% CI = 0.28-0.9; P = 0.021). CONCLUSIONS: The novel active fixation LV lead allowed to target sites with greater QLV. Often maximum QLV was documented in basal segments, were stability of conventional passive fixation leads is not enough. Patients receiving it experienced less HF rehospitalizations and less death due to HF. Active fixation lead in CS guided by QLV can improve long-term prognosis in patients with HF due to coronary artery disease undergoing to CRT.

Therapy Of Cardiac Arrhythmias In Children: An Emerging Role Of Electroanatomical Mapping Systems.

INTRODUCTION: Cardiac arrhythmias are challenging diseases in childhood. Most of them in pediatric subjects (90.2%) are atrioventricular reentrant tachycardias and atrioventricular nodal reentrant tachycardias. The standard 12-lead ECG is a highly accurate diagnostic tool but an invasive electrophysiological study is often required. The main concern about this kind of procedures is their invasive nature and the need of radiations, so antiarrhythmic agents are currently the first line therapy. However, they often show side effects and can be insufficient for the rate control. MATERIALS AND METHODS: We performed a systematic research on Embase and PubMed. We found 563 articles and selected the most representative 50. DISCUSSION: Management of cardiac arrhythmias could be very difficult in several scenarios, especially in children with body weight <15 kg and age <4 years. In general, pediatric subjects show a cumulative risk of malignancy greater than adults, having greater life expectancy. On this basis the guiding principle during radiation delivery in electrophysiological procedures is "as low as reasonably achievable" (acronym: ALARA). The development of 3-dimensional (3D) electroanatomical mapping systems allowed significant reduction of exposure. The most recently reported experiences demonstrate safety and feasibility of fluoroless ablation in the most common arrhythmias in children, even in challenging conditions. CONCLUSION: The first reasonable approach in cardiac arrhythmias involving younger patients seems to be pharmacological. However antiarrhythmic drugs pose problems both in terms of side effects and often have poor efficacy. Expertise in electrophysiological techniques is constantly increasing and the development of new technologies allow us to encourage the use of electroanatomical mapping systems in order to reduce the radiation exposure in children undergoing to catheter ablation, especially for accessory pathways.

Multicenter institutional experience of surgically resected thymic epithelial tumors (TETs): an observational report on behalf of F.O.N.I.C.A.P. (Forza Operativa Nazionale Interdisciplinare Contro il Cancro del Polmone).

BACKGROUND: This multicenter analysis evaluated patient outcome and clinical pathologic features of thymic epithelial tumors after complete surgical resection and adjuvant treatment. METHODS: Histologic classification and clinical staging were performed according to WHO classification and Masaoka staging system, respectively. RESULTS: We analyzed 62 patients, 20 (32%) of whom had myasthenia at diagnosis. Clinical and pathologic staging was as follows: 31 (50%) and 30 (48%) patients had stage I disease, 19 (30%) and 22 (35%) stage II, 5 (8%) and 3 (6%) stage III, 2 (4%) and 2 (3%) stage IVa, and 5 (8%) and 5 (8%) stage IVb, respectively. Histologic examination revealed 11 (19%) type A tumors, 19 (30%) type AB tumors, 7 (12%) type B1 tumors, 11 (17%) type B2 tumors, 11 (17%) type B3 tumors, and 3 (5%) type C tumors. Adjuvant therapies comprised chemotherapy in 3 (5%) patients and radiotherapy in 16 (26%) patients. Median follow-up was 71 months (range 1-145). DFS and OS at 48, 60, and 72 months were 89 and 89%, 86 and 97%, and 95% and 92%, respectively. Myasthenia at the onset of disease (P=0.18 for DFS; P=0.97) and tumor size>5 cm (P=0.94 for DFS; P=0.56) were not prognostic factors. CONCLUSIONS: TETs are rare and indolent tumors. Complete surgical resection followed by adjuvant therapies, such as chemotherapy and/or radiotherapy, in patients at risk of recurrence show very good DFS and OS results, even in cases with radically resected pleural-pulmonary metastases.

[Cardiac troponin-I elevations after thoracic surgery. Incidence and correlations with baseline clinical characteristics, C-reactive protein and perioperative parameters]. / Elevaciones de la troponina I cardiaca tras la cirugía torácica. Incidencia y correlaciones con las características clínicas basales, la proteína C reactiva y los parámetros perioperatorios.

INTRODUCTION AND OBJECTIVES: The exact incidence of cardiac troponin-I elevation after thoracic surgery and its correlation with other clinical parameters have not been fully described. The aims of this study were to determine the frequency of postoperative cardiac troponin-I elevation following lung or pleural surgery for suspected cancer, and to investigate correlations with baseline clinical characteristics, the C-reactive protein level, and perioperative parameters. METHODS: Fifty consecutive patients were enrolled in the study. In each patient, the following parameters were measured: clinical characteristics and C-reactive protein level at baseline, cardiac troponin-I level on postoperative days 1, 3 and 5, and blood pressure, heart rate and ECG parameters every day from the day of the operation until postoperative day 5. RESULTS: The cardiac troponin-I level was elevated postoperatively in 20% of patients. There were significant associations with either a history of coronary artery disease or the presence of more than two coronary risk factors (80% vs. 32.5%; P=.011), a history of chronic antiplatelet therapy (50% vs. 17.5%; P=.046), pneumonectomy compared with less invasive procedures (40% vs. 10%; P=.041), pericardiotomy (30% vs. 2.5%; P=.022), and transient ST-segment alterations on perioperative ECGs (60% vs. 20%; P=.02). No significant correlation was found between cardiac troponin-I elevation and the baseline C-reactive protein level. CONCLUSIONS: Cardiac troponin-I elevation occurs frequently after thoracic surgery and it is associated with clinical markers of coronary artery disease, extensive surgical procedures, and ischemic changes observed on perioperative ECGs.

Elevaciones de la troponina I cardiaca tras la cirugía torácica. Incidencia y correlaciones con las características clínicas basales, la proteína C reactiva y los parámetros perioperatorios / Cardiac troponin-I elevations after thoracic surgery. Incidence and correlations with baseline clinical characteristics, C-reactive protein and perioperative parameters

Introducción y objetivos. La incidencia real de las elevaciones de la troponina I cardiaca tras la cirugía torácica y su correlación con otros parámetros clínicos no está plenamente definida. El objetivo de este estudio fue evaluar la frecuencia de las elevaciones postoperatorias de la troponina I cardiaca después de cirugía pulmonar o pleural por sospecha de cáncer e investigar las correlaciones con los perfiles clínicos basales, con la proteína C reactiva y los parámetros perioperatorios. Métodos. Se registró a 50 pacientes consecutivos y se midieron los siguientes parámetros en cada paciente: variables clínicas basales y concentración de la proteína C reactiva, concentración de troponina I cardiaca en los días 1, 3 y 5 del postoperatorio, electrocardiograma, presión arterial, y frecuencia cardiaca diarias desde el día de la operación hasta el día 5 del postoperatorio. Resultados. Se produjeron elevaciones postoperatorias de la troponina I cardiaca en el 20% de los pacientes y éstas estaban significativamente asociadas con los antecedentes de coronariopatía o más de 2 factores de riesgo coronario (el 80 frente al 32,5%; p = 0,011), los antecedentes de tratamiento antiagregante plaquetario crónico (el 50 frente al 17,5%; p = 0,046), la neumonectomía comparada con los procedimientos menos invasivos (el 40 frente al 10%; p = 0,041), la pericardiotomía (el 30 frente al 2,5%; p = 0,022) y las modificaciones transitorias del segmento ST en el electrocardiograma perioperatorio (el 60 frente al 20%; p = 0,02). No se observó correlación significativa entre las elevaciones de la troponina I cardiaca y la proteína C reactiva basal. Conclusiones. Las elevaciones de la troponina I cardiaca después de la cirugía torácica son frecuentes y están asociadas con marcadores clínicos de coronariopatía, procedimientos quirúrgicos extensos y cambios isquémicos en el electrocardiograma perioperatorio (AU)

Introduction and objectives. The exact incidence of cardiac troponin-I elevation after thoracic surgery and its correlation with other clinical parameters have not been fully described. The aims of this study were to determine the frequency of postoperative cardiac troponin-I elevation following lung or pleural surgery for suspected cancer, and to investigate correlations with baseline clinical characteristics, the C-reactive protein level, and perioperative parameters. Methods. Fifty consecutive patients were enrolled in the study. In each patient, the following parameters were measured: clinical characteristics and C-reactive protein level at baseline, cardiac troponin-I level on postoperative days 1, 3 and 5, and blood pressure, heart rate and ECG parameters every day from the day of the operation until postoperative day 5. Results. The cardiac troponin-I level was elevated postoperatively in 20% of patients. There were significant associations with either a history of coronary artery disease or the presence of more than two coronary risk factors (80% vs. 32.5%; P=.011), a history of chronic antiplatelet therapy (50% vs. 17.5%; P=.046), pneumonectomy compared with less invasive procedures (40% vs. 10%; P=.041), pericardiotomy (30% vs. 2.5%; P=.022), and transient ST-segment alterations on perioperative ECGs (60% vs. 20%; P=.02). No significant correlation was found between cardiac troponin-I elevation and the baseline C-reactive protein level. Conclusions. Cardiac troponin-I elevation occurs frequently after thoracic surgery and it is associated with clinical markers of coronary artery disease, extensive surgical procedures, and ischemic changes observed on perioperative ECGs (AU)

Patients with known or suspected lung cancer: evaluation of clinical management changes due to 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) study.

AIM: To determine prospectively from the referring physician's point of view the impact of F-fluorodeoxyglucose positron emission tomography (F-FDG PET) results on the management decisions in patients with known or suspected lung cancer. METHODS: Seventy-five consecutive patients (58 men, 17 women; age range, 33-82 years; mean age, 64 years) with a diagnosis of a pulmonary lesion, obtained by means of morphological imaging studies and/or cytological sampling, were included in the study. The patient population consisted of three groups: (A) patients (n=18) with a solitary lung nodule; (B) patients (n=37) with untreated lung cancer; and (C) patients (n=20) with treated lung cancer. All were referred for whole-body F-FDG PET within 15 days (mean, 11 days) of lung lesion detection. To determine whether and how PET findings could modify the treatment strategy, a questionnaire was sent to the referring physician before and after the PET results. With regard to the treatment strategy, four major options were recognized: (1) further diagnostic investigations; (2) medical therapy; (3) surgical treatment; (4) wait-and-see. For data analysis, intermodality changes, defined as changes between treatment strategies related to PET findings, were considered. RESULTS: Before the PET study, the planned management for the overall patient population was as follows: further diagnostic investigations in 44 cases (58%), medical therapy in 17 (23%), surgical treatment in nine (12%) and wait-and-see in five (7%). After the PET study, further diagnostic tools were indicated in 27 cases (36%), medical therapy in 17 (23%), surgical treatment in 28 (37%) and wait-and-see in three (4%). Relative to the initially planned strategy, changes in patient management after PET imaging occurred in 34 (45%) cases. Overall, the most relevant variation after PET concerned the surgical treatment strategy. The highest percentage (67%) of changes in management after PET was found in patients with a solitary pulmonary nodule; the percentages of changes of the three patient groups were significantly different (chi-squared test; P=0.021). CONCLUSIONS: In patients with known or suspected lung cancer, F-FDG PET results determined significant variations in major clinical management decisions.

Personal experience in surgical management of pulmonary pleomorphic carcinoma.

BACKGROUND: Pleomorphic carcinoma is a rare epithelial malignant tumor. Pulmonary pleomorphic carcinoma was introduced by the 1999 World Health Organization classification as a new peculiar type of lung carcinoma showing concurrent malignant epithelial and sarcomatoid spindle cell elements. Few reports describe its clinical behavior. My colleagues and I report a series of patients surgically treated for pulmonary pleomorphic carcinoma to describe our experience with this malignant neoplasm. METHODS: Twenty cases of pleomorphic pulmonary carcinoma were collected and studied clinicopathologically. All patients underwent surgical resection. The cases were as follows: 6 stage I, 12 stage II, and 2 stage IIIA. Histologic diagnosis was established by using light microscopic examination and immunohistochemistry. Survival rates were calculated with the Kaplan-Meier method. RESULTS: We postoperatively diagnosed 20 cases of pleomorphic carcinoma: 14 cases were exclusively spindle and giant-cell carcinomas, 2 cases were spindle and giant-cell carcinoma combined with adenocarcinoma, 2 were combined with squamous cell carcinoma, and 2 were combined with large cell carcinoma. At last follow-up, 4 patients were still alive; they were postoperative T1 N0 and T2 N0. The remaining 16 patients died from early distant metastases. The median duration of disease-free survival was 5 months. The median duration of overall survival was 8 months. CONCLUSIONS: The prognosis of patients with pleomorphic carcinoma was poor, despite surgery and adjuvant chemotherapy, because of early relapse of disease. Nodal involvement was a determinant prognostic variable, because advanced stages were related to worse prognosis. In case of preoperatively proven pulmonary pleomorphic carcinoma, surgery should be recommended to N0 patients.

Assessment of outcomes in typical and atypical carcinoids according to latest WHO classification.

BACKGROUND: Pulmonary carcinoid tumors represent a group of malignant neoplasms comprised of neuroendocrine cells. In 1999, the World Health Organization (W.H.O.) proposed the definitive classification of neuroendocrine tumors based on the criteria from Travis and associates. The W.H.O. described two different groups of carcinoid tumors: typical carcinoids (TC) and atypical carcinoids (AC). Few reports have reviewed their data according to the current classification, and therefore, prognosis and standard therapy for TC and AC are still uncertain. METHODS: From 1980 to 2001, 98 pulmonary resections have been performed for primary bronchial carcinoid tumors in our Thoracic Department of the University of Milan. We reviewed original histology using the current W.H.O. criteria and identified 88 patients with TC and 10 with AC. We reviewed the outcomes in each group. RESULTS: The 5 year-overall survival rate was 91.9% for TC and 71% for AC. The 10-year overall survival rate was 89.7% for TC and 60% for AC. The 5-year TNM-related survival rates in the TC group were: IA-B, 100%; IIA-B, 75%; and IIIA, 50%. At 10 years, they were: IA-B, 100%; IIA-B, 75%; and IIIA, 0%. The 5-year survival rates in the AC group were: IA-B, 100%; IIA-B, 100%; and IIIA, 0%. At 10 years, they were: IA-B, 100%; IIA-B, 66%; and IIIA, 0%. CONCLUSIONS: Prognosis is favorable for both subtypes in the early stage. Advanced stages are related to better prognosis in TC. Recurrences rate is worse in the AC subtype. Our data suggest avoiding limited resections when feasible in AC. Parenchyma-sparing resections should be encouraged in TC.

Surgical experience of 15 solitary benign fibrous tumor of the pleura.

OBJECTIVE: The localized benign fibrous tumor of the pleura represents 8% of all benign pathologies of the chest and 10% of neoplasms of the pleura. The authors review the literature, and report on 15 cases of localized benign fibrous tumors of the pleura surgically treated over a period of 15 years to further knowledge of this pathology, its therapy and prognosis. METHODS: With respect to the well-known diffuse malignant mesothelioma, different etiopathogenesis, prognosis, and therapeutic approaches characterize the localized benign fibrous tumor of the pleura. In our experience, 15 patients underwent thoracotomy with excision of a pathological endothoracic mass, then histologically proved to be a localized benign tumor of the pleura. The whole group underwent pre-operative evaluation and, when clinic suggested, stadiation and post-operative frequent follow-up. RESULTS: The whole group of 15 patients underwent surgical approach well tolerated the surgical treatment with perfect recovery of post-operative respiratory function. There was no relapse of disease in any patients. At the moment all patients are still alive except one dead of heart failure. CONCLUSION: The differential diagnosis of benign fibrous tumor of the pleura and lung and pleural malignancy depends upon immunohistochemistry of the surgical specimen so that prognosis could be formulated only after surgery. We consider surgery as the treatment of choice in this pathology.

Effect of DNA repair gene polymorphisms on BPDE-DNA adducts in human lymphocytes.

To determine whether variations in DNA repair genes are related to host DNA damage, we investigated the association between polymorphism in the XPD gene (codon 199, 312, 751) and the XRCC1 gene (codon 194, 399) and the presence of benzo(a)pyrene diolepoxide adducts to lymphocyte DNA (BPDE-DNA) in a group of male patients with incident lung cancer, all current smokers. BPDE-DNA adducts were analyzed by high-resolution gas chromatography-negative ion chemical ionization-mass spectrometry. XPD and XRCC1 genotypes were identified by PCR-RFLP. XRCC1 and XPD genotypes did not affect the levels and proportion of detectable BPDE-DNA adducts. The patients were also genotyped for the GSTM1 polymorphism, given its role in the detoxification of BPDE. Individuals with the GSTM1 deletion had significantly higher levels of BPDE-DNA adducts when they were XPD-Asp312Asp+Lys751Lys than carriers of at least one variant allele. No such association was found with the XRCC1 genotypes. Because of the small study population (n = 60), further statistical analysis of possible gene-gene and gene-environment would not be informative. This is the first study analysing the specific BPDE-DNA adduct in vivo with regard to polymorphic repair genes (XPD, XRCC1) and xenobiotic metabolizing gene (GSTM1). Our results raise the possibility that the XPD-Asp312Asp+Lys751Lys genotype may increase BPDE-DNA damage; this effect might be evident in individuals who are especially likely to have accumulated damage, probably because of lower detoxification capacity and high environmental exposure.

Personal experience in lung cancer sleeve lobectomy and sleeve pneumonectomy.

BACKGROUND: Sleeve lobectomy (SL) and tracheal sleeve pneumonectomy (TSP) represent valuable alternative techniques to standard resections in the treatment of benign and malignant conditions of the airway and allow preservation of lung parenchyma. METHODS: Eighty-three sleeve lobectomies and 27 tracheal sleeve pneumonectomies have been performed for nonsmall cell lung cancer in the thoracic department of the University of Milan from 1979 to 1999. There were 46 upper right lobectomies, 11 upper and middle lobectomies, 18 upper left lobectomies, 8 lower left lobectomies, and 27 right pneumonectomies. RESULTS: Mortality rate was 3.6% in SL and 7.4% in TSP. Complications were 10.8% of all SLs and 15% of all TSPs. The overall 5-year survival rate was 43% for SL and 20% for TSP; the 10-year survival rate was 34% and 14%, respectively. There was a highly significant difference in survival between patients with N0 and N1-N2 disease. CONCLUSIONS: Sleeve lobectomy is an appropriate surgical procedure and an alternative to pneumonectomy in patients with limited respiratory reserve whenever the situation permits. Trachael sleeve pneumonectomy is associated with more complications and poor survival.