Paraskevas Lyberis

Clinical significance of tumor-infiltrating lymphocytes in lung neoplasms.

BACKGROUND Tumor-infiltrating lymphocytes (TIL) are considered important in anticancer immunosurveillance, although their role has not been clearly established yet. We examined prevalence, correlations, and prognostic significance of TIL among our patient population of resected lung neoplasms. METHODS From 1993 to 2006, the presence of TIL was retrospectively evaluated in 1,290 patients operated on for primary lung neoplasms. Tumor-infiltrating lymphocytes were defined as those intraepithelial lymphocytes located within the cancer cell nests. RESULTS Tumor-infiltrating lymphocytes were detected in 294 patients (23%). A significant difference was found between prevalence in non-small cell lung carcinomas versus neuroendocrine tumors (290 of 1,208, 24% versus 4 of 82, 5%; p = 0.0001). Prevalence was similar in adenocarcinomas, squamous-cell carcinomas, and large-cell anaplastic carcinomas. Logistic regression analysis indicates that TIL correlate with grading (odds ratio, 1.27; 95% confidence interval, 1.04 to 1.55; p = 0.02), tumor dimension (odds ratio, 0.86; 95% confidence interval, 0.79 to 0.94; p = 0.0008), and vascular invasion (odds ratio, 1.62; 95% confidence interval, 1.21 to 2.16; p = 0.0009). A not significantly better survival in the presence of TIL was observed overall (p = 0.20), becoming significant in squamous-cell carcinomas (p = 0.03). In patients with stage I disease, TIL is associated with a significant survival advantage in squamous-cell carcinomas (p = 0.03). The survival advantage increases with the duration of follow-up and is more evident after 4 to 6 years. CONCLUSIONS Tumor-infiltrating lymphocytes are observed in about one fourth of resected lung neoplasms: they are rare in neuroendocrine tumors. Tumor-infiltrating lymphocytes are more frequent in poorly differentiated tumors and in tumors with microscopic vascular invasion. The presence of TIL correlates with an improved survival in squamous cell carcinomas, particularly at early stage. The survival advantage increases with the duration of follow-up.

The significance of intrapulmonary metastasis in non-small cell lung cancer: upstaging or downstaging? A re-appraisal for the next TNM staging system §

OBJECTIVE The management of patients with non-small cell lung cancer (NSCLC) with intrapulmonary metastases (PM) is controversial. In TNM classification, PM are designed as T4 when in the same lobe of the primary tumour (PM1) and M1 when in a different lobe(s) (PM2). Some authors have questioned the negative prognostic impact of PM. The present study assessed prevalence, correlation with clinico-pathologic variables and impact on survival of PM, along with a review of the literature. METHODS From January 1993 to December 2006, 2013 NSCLC patients underwent surgical resection at our institution. Of these, 74 presented with PM (39 PM1, 35 PM2). Patients with bronchioloalveolar carcinoma (BAC), carcinoid tumours, contralateral disease and preoperative chemo/radiotherapy were excluded from the analysis. A logistic regression analysis was undertaken to evaluate a relationship between the presence of PM and different clinico-pathologic variables. Survival analysis was undertaken to investigate the prognostic significance of PM. RESULTS PM represent 3.6% of our patient population of operated NSCLC. Metastases were multiple in 36 cases and single in 38. Thirty-six patients had node-negative disease. Among all the variables for the logistic regression analysis only vascular invasion (OR: 0. 45; 95% CI 0.24-0.85, p=0.01) and N status (OR: 0. 6; 95% CI 0.43-0.82, p=0.001) were significantly correlated with the presence of PM. Median survival rates of PM1, PM2, other T4 and other M1 patients were 25, 23, 15 and 14 months, respectively. A survival advantage was observed in patients with PM as compared to other T4/M1 patients, although the difference was not significant either overall (p=0.21) or in the N0 disease group (p=0.12). CONCLUSIONS The presence of PM in NSCLC patients is a rare occurrence. Risk factors for the development of PM are a microscopic vascular invasion and a high nodal status. A survival advantage over other T4/M1 patients is evident from our experience, although not significant. The results of the literature which have been accumulating in the most recent years including ours bend to the conclusion that there is sufficient validated information to consider a downstaging in the presence of intrapulmonary metastases from NSCLC for the seventh edition of the TNM classification.

Outcome and Prognostic Factors in Bronchial Carcinoids: A Single-Center Experience

Introduction: The aim of this study is to assess factors influencing survival in patients with bronchial carcinoids (BCs). Methods: A retrospective review of our surgical database of patients operated for primary lung cancer with a final histologic diagnosis of BC in the period from January 1, 1995 to December 31, 2010 was carried out. Results: There were 126 patients (74 women): 83 had a typical carcinoid and 43 an atypical one (AC). All patients received a radical resection; systematic lymphadenectomy was accomplished in 120. Lymph nodal metastases were observed in 26 cases (12 N2) and were more frequent in ACs (p = 0.009). Twelve patients received adjuvant therapy (chemo/radio/biological). Distant metastases (DM) and local tumor recurrence occurred in 28 (22%) and 8 (6.3%) cases, respectively: DM were more frequent in ACs (p = 0.0001) and in N2 patients (p = 0.0001). Smoke, atypical histology, lymph nodal metastases, and high cellular proliferative index demonstrated to be statistically negative prognostic factors. Conclusion: Even if characterized by an indolent behavior, BCs may spread to lymph node or distant or present with local recurrence. Amid all prognostic factors, the presence of DM demonstrated to be the strongest negative one.

Outcome of surgically resected thymic carcinoma: A multicenter experience

OBJECTIVE Thymic carcinoma (TC) is a rare and invasive mediastinal tumor, with poor prognosis. Most of the previous published papers are single-institution based, reporting small series of patient, sometimes including palliative resection. This study collected patients with TC treated in 5 high-volume Italian Thoracic Surgery Institutions. METHODS A multicenter retrospective study of patients operated for TC between 2000 and 2011 was conducted. Exclusion criteria were: Neuroendocrine thymic neoplasms, debulking/palliative resection and tumor biopsy. Cause specific survival (CSS) was the primary endpoint. RESULTS Four hundred and seventy-eight patients underwent surgery for thymic malignancies: 40 of them (8.4%) had TC. Eleven (27.5%) received induction chemotherapy because of their radiological invasiveness. A complete resection (R0) was achieved in 36 (90%; 9/11 submitted to induction chemotherapy). Adjuvant radio/chemotherapy was offered to 37 patients, according to the type of surgical resection and tumor invasiveness. Three, 5 and 10-year survival rates were 79%, 75% and 58%. Recurrences developed in 10 patients. R0 resection (p<0.0003) and absence of tumor recurrences (p=0.03) resulted significant prognostic factors at univariate analysis. Independent CSS predictor was the achievement of a complete resection (p<0.05). CONCLUSIONS TC is a rare and invasive mediastinal tumor. A multimodal approach is indicated especially in TC invasive forms. The achievement of a complete surgical resection is fundamental to improve survival.

Prognostic factors in neuroendocrine tumours of the lung: a single-centre experience

OBJECTIVES To assess the independent prognostic role of histological subtypes, tumour size and lymph nodal involvement upon survival in lung neuroendocrine tumours (NETs). METHODS A retrospective search of the database of the Department of Thoracic Surgery (Turin, Italy) identified 157 patients operated on for a newly diagnosed NET between January 1995 and December 2011. Multivariable Cox models were used to analyse predictors of overall survival and progression-free survival. RESULTS According to histology, 71 (45.2%) were typical carcinoids (TCs), 35 (22.3%) atypical carcinoids (ACs), 37 (23.6%) large-cell neuroendocrine carcinomas (LCNCs) and 14 (8.9%) small-cell lung carcinomas (SCLCs). After a median follow-up time of 6.5 years, 60 patients died and 73 had a recurrence or died. The overall 5-, 10- and 15-year survival rates were 64%, 53% and 46%, respectively. Older age, histology (ACs, LCNCs and SCLCs vs TCs) and lymph nodal involvement were confirmed to be independent negative prognostic factors in the multivariable models for overall survival and progression-free survival. CONCLUSIONS Tumour histology and lymph nodal involvement are definitively the predominant and relevant factors influencing survival. ACs showed an intermediate prognosis between TCs and poorly differentiated NETs.

Spontaneous pneumomediastinum: A rare complication of anorexia nervosa

FIGURE 1. A and B, Thoracic computed tomographic scans of the patient. Diffuse subcutaneous emphysema, from the neck to the thorax, and pneumomediastinum are evident. Spontaneous pneumomediastinum (PM) usually results from alveolar wall rupture and must be distinguished from posttraumatic PM resulting from traumatic events (chest trauma, endobronchial or esophageal procedures with wall laceration, mechanical ventilation, or other invasive procedures). Spontaneous PM is a rare entity in anorexia nervosa (AN): approximately 20 cases have been described in the literature. Vomiting (a common symptom in AN) is often the cause of PM in patients with AN. We describe the case of spontaneous PM in a young anorexic woman in whom vomiting was not the cause of the PM.

Radical resection of a giant, invasive and symptomatic malignant Solitary Fibrous Tumour (SFT) of the pleura.

Solitary Fibrous Tumours (SFTs) of the pleura are rare neoplasms, with unpredictable biological behaviour. Although usually benign, malignant SFTs are described, and they are often associated with large, necrotic and locally invasive tumours. Radical resection represents the treatment of choice in all cases; recurrences are uncommon, and redo-surgery should be considered. The case of a giant, invasive, radically resected malignant SFT, is described. The role of postoperative radiotherapy, to reduce the risk of recurrence, is also discussed.

Lung sealant and morbidity after pleural decortication: a prospective randomized, blinded study

ObjectivesProlonged postoperative air leaks (AL) are a major cause of morbidity. Aim of this work was evaluating use of a Lung Sealant System (Pleuraseal™, Covidien, Mansfield, MA, U.S.A.) in pleural decortications for empyema thoracis.MethodsFrom January 2008 to December 2008, 46 consecutive patients received pleural decortications for empyema thoracis. Post-procedural and malignancy-related empyemas were excluded. After hydro-pneumatic test and surgical correction of AL (until satisfaction), patients were assigned (23 per group) to Control or Sealant group. Control group underwent no additional interventions. In Sealant group, lung sealant was applied over AL areas. Following variables were measured daily: patients with AL; time to chest drainage (CD) removal; CD drainage volume at removal, postoperative length of hospital stay, postoperative C-reactive protein (CRP), and leukocyte counts. Personnel recording parameters were blinded to intervention. Two-tailed t-tests (normally distributed data) or Mann - Whitney U-test (not-normally distributed data) were used for evaluating significance of differences between group means or medians. Significance of any proportional differences in attributes were evaluated using Fishers Exact Test. Statistical analysis was carried out using R-software (version 2.8.1).ResultsGroups were similar regarding demographic and baseline characteristics. No patients were withdrawn from study; no adverse effects were recorded. There were no significative differences on CRP and leukocyte levels between two groups. Compared with the Control group, in Sealant group significantly fewer patients had AL (30 versus 78%, p = 0.012), and drains were inserted for a shorter time (medians, 3 versus 5 days, p = 0.05). Postoperative hospitalization time was shorter in Sealant group than in control group, but difference was not significant (0.7 days, p = 0.121).ConclusionsPleuraseal™ Lung Sealant System significantly reduces AL following pleural decortications for empyema and, despite of not-increased infectious indexes, is suitable for routinely use, even in procedures with contaminated pleura.

Efficacy and safety of human fibrinogen-thrombin patch (Tachosil(®)) in the management of diffuse bleeding after chest wall and spinal surgical resection for aggressive thoracic neoplasms.

Diffuse bleeding after chest wall and spine resection represents a major problem in General Thoracic Surgery. Several fibrin sealants (FS) have been developed over the years and their use has been gradually increasing over time, becoming an important aid to the surgeons, justifying their use across numerous fields of surgery due to its valid haemostatic properties. Among the several FS available, TachoSil(®) (Takeda Austria GmbH, Linz, Austria) stands out for its haemostatic and aerostatic properties, the latter being demonstrated even in high-risk patients after pulmonary resections for primary lung cancers. Several papers available in literature demonstrated TachoSil(®)s effectiveness in controlling intraoperative and postoperative bleeding in different surgical branches, including hepatic and pancreatic surgery, as well as cardiac and thoracic surgery. However, the use of TachoSil(®) to control diffuse bleeding following major resections for advanced lung cancers, with requirement of chest wall and vertebral body resection for oncological radicality, was never published so far. In this paper, we report three cases of pulmonary lobectomy associated to chest wall resection and haemivertebrectomy for primary malignant lung neoplasms and for a recurrence of malignant solitary fibrous tumour of the pleura in which we used TachoSil(©), which demonstrated its efficacy in controlling diffuse bleeding following resection.

Extended transcervical thymectomy with partial upper sternotomy: results in non-thymomatous patients with myasthenia gravis

OBJECTIVES Thymectomy is a recognized treatment for myasthenia gravis (MG), but the optimal surgical approach is yet to be determined. This study analysed the results in non-thymomatous MG patients treated at our institution using an extended transcervical access with partial upper sternotomy (TC-US), in order to describe cumulative incidence of remission and its predictors. METHODS In the period 1988-2012, 215 non-thymomatous MG patients underwent thymectomy using the TC-US approach. There were 61 males and 154 females (median age: 33 years). Primary end points were complete stable remission (CSR) and pharmacological remission (PR). Clinico-pathological predictors of CSR/PR were analysed including age, gender, preoperative MG symptom duration, preoperative immunosuppression therapy and disease severity. RESULTS The median follow-up period was 127 months. The median preoperative duration of MG symptoms was 9 months (interquartile range 4-13). The median operative time was 65 min (range: 45-135). There was no postoperative death. Morbidity rate was 7% (14 patients, no major complication). Ten patients died at the follow-up (3 of MG). MG symptoms improved in 85% (150/176) of the patients. CSR rate was 34%, PR rate was 4%. Cumulative incidence of CSR/PR was 27, 37 and 46% at 5, 10 and 15 years, respectively. Independent predictors of increased CSR/PR rate were age (P = 0.028) and MG symptom duration <6 months (P = 0.013). CONCLUSIONS Our data suggest that in patients with non-thymomatous MG, thymectomy by TC-US has a remission rate not inferior to those reported after trans-sternal or video-assisted thoracic surgery techniques. The short duration of MG symptoms before thymectomy is a predictor of remission. The technique strikes a reasonable balance between the extent of thymic resection, operative and anaesthesia time, patient acceptance, neurological outcome and costs.