Giovanni Leuzzi

Thymectomy in myasthenia gravis: proposal for a predictive score of postoperative myasthenic crisis

OBJECTIVES Thymectomy plays an important role in patients with myasthenia gravis (MG). This study aimed to explore predictors of postoperative myasthenic crisis (POMC) after thymectomy and to define a predictive score of respiratory failure. METHODS The clinical data of 177 patients with MG undergoing thymectomy from January 1995 to December 2011 were retrospectively reviewed. The following factors were analysed in relation to the occurrence of myasthenic crisis: gender, age, body mass index (BMI), anti-acetylcholine receptor-antibody level, bulbar symptoms, comorbidities, duration of symptoms, Osserman-stage, Myasthenia Gravis Foundation of America (MGFA) stage, history of myasthenic crisis, use of immoglobulins or plasmapheresis, kind of therapy, spirometric and blood gas parameters, histology, kind of surgery, non-myasthenic complications and duration of intubation. RESULTS Twenty-two patients experienced postoperative respiratory failure after thymectomy. Univariate analysis revealed a correlation with age >60 years (odds ratio (OR) = 1.79, 95% confidence interval (CI) = 1.04-6.78; P = 0.040); Osserman-stage (IIB- OR = 5.16, 95% CI = 1.10-24.18; P = 0.037, III-IV- OR = 8.75, 95% CI = 1.53-50.05; P = 0.015); bulbar symptoms (OR = 7.42, 95% CI = 1.67-32.84; P = 0.008); BMI >28 (OR = 3.99, 95% CI = 1.58-10.03; P = 0.003); preoperative plasmapheresis (OR = 2.97, 95% CI = 1.18-14.04; P = 0.021); duration of symptoms >2 years (OR = 4.00, 95% CI = 1.09-14.762; P = 0.036); extended surgery (OR = 2.52, 95% CI = 1.02-6.22; P = 0.045); lung (OR = 4.05, 95% CI = 1.44-11.42; P = 0.008), pericardial (OR = 3.78, 95% CI = 1.45-9.82; P = 0.006) or pleural resection (OR = 3.23, 95% CI = 1.30-8.03; P = 0.012); Vital Capacity % <80% (OR = 0.20, 95% CI = 0.05-0.82; P = 0.025) and PaCO2 >40 mmHg (OR = 3.76, 95% CI = 1.12-12.68; P = 0.032). Multivariate logistic regression analysis showed that Osserman-stage (IIB- OR = 5.69, 95% CI = 1.09-29.69; P = 0.039 (III-IV- OR = 11.33, 95% CI = 1.67-76.72; P = 0.013), BMI >28 (OR = 3.65, 95% CI = 1.10-12.15; P = 0.035), history of myasthenic crisis (OR = 24.10, 95% CI = 2.34-248.04; P = 0.007), duration of symptoms >2 years (OR = 5.94, 95% CI = 1.12-31.48; P = 0.036) and lung resection (OR = 8.48, 95% CI = 2.18-32.97; P = 0.002) independently predict POMC. Excluding history of preoperative myasthenic crisis (statistically associated with Osserman-stage), we built a scoring system according to the OR of Osserman-stage (I-IIA, IIB, III-IV), BMI (<28, ≥ 28), duration of symptoms (<1, 1-2, >2 years) and association with a pulmonary resection. This model helped in creating four classes with increasing risk of respiratory failure (Group I, 6%; Group II, 10%; Group III, 25%; Group IV, 50%). CONCLUSIONS Our model facilitates the stratification of patient risk and prediction of the occurrence of POMC. Moreover, it could help to guide the anaesthesiologists decision on the duration of intubation. Further studies based on larger series are needed to confirm these preliminary data.

Chest wall giant lipoma with a thirty-year history

Benign chest wall tumours are very uncommon and chest wall lipomas are rarely reported in literature. We report herein a case of a 68-year old man who developed a giant, symptomless mass of the chest wall. A chest computed tomography scan evidenced a solid neoplasm measuring 27 cm in its major axis. A radical excision was performed and the histology was consistent with lipoma. To our knowledge, this is the first case reporting a giant lipoma of the chest wall with a thirty-year history.

Chest wall tumors and prosthetic reconstruction: A comparative analysis on functional outcome

To address the question of how much chest‐wall (CW) resections and prosthetic reconstructions influence functional outcome.

Second primary non-small-cell lung cancer: implications of the new adenocarcinoma classification in the challenging decision of the best surgical strategy

Zuin et al. [1] have recently reported an interesting retrospective analysis on a relative large series of second primary non-small-cell lung cancers (NSCLCs), comparing the long-term outcomes between patients treated with a lobectomy and those where a sub-lobar resection was performed, which prompted a series of reflections by us, discussed here. The best therapeutic strategy for synchronous/metachronous primary NSCLCs remains an open subject of discussion in the scientific community, particularly regarding the surgical approach. By commenting on the paper by Zuin et al. [1], we wish to contribute to this debate. The International Association for the Study of Lung Cancer (IASLC) has issued a revised adenocarcinoma classification [2] jointly with the American Thoracic Society (ATS) and the European Respiratory Society (ERS). Briefly, the confusing term ‘bronchioloalveolar carcinoma’ has been discontinued and the entire category of pulmonary adenocarcinomas has been reclassified into three different subgroups: adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinomas (IA). As remarked in detail by Van Schil et al. [3], this new classification has profound implications for thoracic surgeons in the management of ‘early-stage’ adenocarcinomas; indeed the ‘early-stages’ AIS and MIA should have 100% or near 100% disease-specific survival after sub-lobar resection and mediastinal sampling, respectively, where the oncological need to perform a lobar resection and mediastinal lymph nodal systematic resection is reserved for IAs only. By extreme simplification we may infer that such relevant new evidence deserves focal attention when planning the best surgical strategy in second primary NSCLCs. First, we would like to encourage the authors to abandon the ‘old’ histopathological classification when matching data with the most updated TNM framework (7th). In particular, it would be extremely helpful to reclassify the vast amount of precious data according to the new classification to get significant clues (albeit with the limitations of a retrospective analysis exercise) for further prospective evaluations. Secondly and more generally, when an ‘early-stage’ adenocarcinoma is detected and rightfully classified as a synchronous or metachronous primary lung tumour, the decision-making process and the best strategy of treatment should mandatorily take into the account the new IASLC/ATS/ERS classification. Indeed, the same profound implications in the management of ‘early-stage’ adenocarcinomas (summarized above) may have a crucial value (or even more) in the management of ‘early-stage’ second adenocarcinomas too. Basically, the different surgical outcomes between lobar vs sub-lobar resections in a ‘second adenocarcinoma’ may be potentially influenced by the different prognostic pattern at the base of the new categories (AIS, MIA and IA). Thirdly and finally, as correctly remarked by the authors, ‘. . . the possibility that some cases of solitary pulmonary metastasis always exist within the group of patients with synchronous and early metachronous lung cancers could be included.’. In this context, although the IASLC/ATS/ERS classification recommended testing only patients with advanced adenocarcinomas for epidermal growth factor receptor (EGFR) mutations, we strongly advocate the assessment of EGFR mutations also in patients with synchronous/ metachronous primary adenocarcinomas, also, because the eventual differences in clonality may indeed be a helpful tool for the differential diagnosis of pulmonary metastases vs secondary lung neoplasms [4]. We would greatly appreciate the authors reflections and reactions to the points raised.

Baseline C-reactive protein level predicts survival of early-stage lung cancer: evidence from a systematic review and meta-analysis.

Purpose The prognostic impact of baseline C-reactive protein (CRP) in non-small-cell lung cancer (NSCLC) is debated. To evaluate this issue, we performed a systematic review and meta-analysis to explore the role of CRP value in predicting early-stage NSCLC survival. Methods Ten articles on early-stage NSCLC were eligible and included in our study. We performed a random-effects meta-analysis and assessed heterogeneity and publication bias. We pooled hazard ratio (HR) estimates and their 95% confidence intervals (CIs) on mortality for the comparison between the study-specific highest category of CRP level versus the lowest one. Results In overall analysis, elevated pretreatment CRP values were significantly associated with poor overall survival (HR 1.60, 95% CI 1.30-1.97, p<0.001, I2 = 71.9%). Similar results were observed across considered strata. However, higher mortality risk was reported in studies in which CRP was combined with other factors (HR 1.96, 95% CI 1.58-2.45) and in those using a cutoff value of 3 mg/L (HR 1.89, 95% CI 1.52-2.35). Conclusions Based on our analysis, baseline high CRP level is significantly associated with poor prognosis in early-stage NSCLC. Further prospective controlled studies are needed to confirm these data.

Multimodality therapy for locally advanced thymomas: A propensity score-matched cohort study from the European Society of Thoracic Surgeons Database.

OBJECTIVE This study investigated the prognostic impact of multimodality therapies in locally advanced thymomas. METHODS From January 1990 to January 2010, clinicopathological, surgical, and oncological features were retrospectively reviewed in a cohort of 370 Masaoka-Koga stage III thymomas (World Health Organization classification A to B3) collected from 37 institutions. A multivariate Cox proportional hazard model was created to identify independent predictors of overall, cancer-specific (CSS), and relapse-free survivals. Furthermore, a propensity score-matching analysis for exposure to adjuvant (AT) therapy was generated. RESULTS Induction therapy and AT were administered to 88 (24.9%) and 245 (69.4%) patients, respectively. Overall, 5- and 10-year overall survival, CSS, and relapse-free survivals were 82.8%, 88.4%, and 80.0%, and 68.9%, 83.3%, and 71.5%, respectively. At multivariable analysis performed in the matched cohort, AT was confirmed as the strongest predictive factor for overall survival (hazard ratio, 2.83; 95% confidence interval, 0.88-9.12; P = .08) and CSS (hazard ratio, 4.70; 95% confidence interval, 1.00-22.2; P = .05). Pathologic T classification (according to International Association for the Study of Lung Cancer and International Thymic Malignancy Interest Group TNM staging proposal) was an independent factor for relapse (hazard ratio, 8.69; 95% confidence interval, 1.08-70.04; P = .04). When CSS was adjusted for T classification, AT confirmed a significant survival advantage for pT3 tumors (P = .04). On the other hand, for thymomas larger than 5 cm, stratifying for tumor size and AT did not affect 5-year CSS (P = .17). CONCLUSIONS Our results indicate that AT is beneficial for locally advanced thymomas, mainly for specific pathologic features (pT3 or tumor size smaller than 5 cm). Further larger studies are needed to confirm these data.

Risk Stratification Model for Resected Squamous-Cell Lung Cancer Patients According to Clinical and Pathological Factors

Introduction: The aim of this analysis (AIRC-MFAG project no. 14282) was to define a risk classification for resected squamous-cell lung cancer based on the combination of clinicopathological predictors to provide a practical tool to evaluate patients’ prognosis. Methods: Clinicopathological data were retrospectively correlated to disease-free/cancer-specific/overall survival (DFS/CSS/OS) using a Cox model. Individual patient probability was estimated by logistic equation. A continuous score to identify risk classes was derived according to model ratios and dichotomized according to prognosis with receiver operating characteristic analysis. Results: Data from 573 patients from five institutions were gathered. Four hundred ninety-four patients were evaluable for clinical analysis (median age: 68 years; male/female: 403/91; T-descriptor according to TNM 7th edition 1–2/3–4: 330/164; nodes 0/>0: 339/155; stages I and II/III and IV: 357/137). At multivariate analysis, age, T-descriptor according to TNM 7th edition, nodes, and grading were independent predictors for DFS and OS; the same factors, except age and grading, predicted CSS. Multivariate model predict individual patient probability with high prognostic accuracy (0.67 for DFS). On the basis of receiver operating characteristic-derived cutoff, a two-class model significantly differentiated low-risk and high-risk patients for 3-year DFS (64.6% and 32.4%, p < 0.0001), CSS (84.4% and 44.5%, p < 0.0001), and OS (77.3% and 38.8%, p < 0.0001). A three-class model separated low-risk, intermediate-risk, and high-risk patients for 3-year DFS (64.6%, 39.8%, and 21.8%, p < 0.0001), CSS (84.4%, 55.4%, and 30.9%, p< 0.0001), and OS (77.3%, 47.9%, and 27.2%, p < 0.0001). Conclusions: A risk stratification model including often adopted clinicopathological parameters accurately separates resected squamous-cell lung cancer patients into different risk classes. The project is currently ongoing to integrate the clinicopathological model with investigational molecular predictors.

Transoesophageal endoscopic ultrasound-guided fine-needle aspiration of pleural effusion for the staging of non-small cell lung cancer

OBJECTIVES The efficacy of endoscopic ultrasound (EUS) for evaluating mediastinal adenopathy in lung cancer is nowadays proven. However, its accuracy for detection of malignant pleural effusion per se has not been yet investigated. Herein we report our experience with EUS for detecting pleural effusion during the staging procedure of non-small cell lung cancer (NSCLC) patients. METHODS Between January 2009 and December 2011, we performed endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) on 92 selected NSCLC patients to evaluate the T and N factors and to acquire bioptic material and when this was detected, to sample the pleural effusion. RESULTS In 10 patients (8 males and 2 females, mean age 66.9±9.2 years) a pleural effusion was detected and sampled. In 7 out of the 10 cases, the cytological examination of the fluid obtained by EUS-FNA tested positive for malignant cells, thereby upgrading the case to Stage IV, irrespective of T and N statuses. In 3 cases the cytology on the EUS-FNA material was proven to be negative for malignancy thereby allowing patients to be treated with curative intent without further delay. CONCLUSIONS EUS-FNA of the pleural fluid is a safe and simple procedure. Our data, albeit stemming from a limited study population, show that it can be efficient in selected NSCLC cases for obtaining useful material and information with significant impact on the staging and, therefore, on the planning of the optimum therapeutic strategy.

Pleurectomy-decortication in malignant pleural mesothelioma: are different surgical techniques associated with different outcomes? Results from a multicentre study†

OBJECTIVES The potential benefit of surgery for malignant pleural mesothelioma (MPM), especially concerning pleurectomy/decortication (P/D), is unclear from the literature. The aim of this study was to evaluate the outcome after multimodality treatment of MPM involving different types of P/D and to analyse the prognostic factors. METHODS We reviewed 314 patients affected by MPM who were operated on in 11 Italian centres from 1 January 2007 to 11 October 2014. RESULTS The characteristics of the population were male/female ratio: 3.7/1, and median age at operation was 67.8 years. The epithelioid histotype was observed in 79.9% of patients; neoadjuvant chemotherapy was given to 57% of patients and Stage III disease was found following a pathological analysis in 62.3% of cases. A total of 162 (51.6%) patients underwent extended P/D (EP/D); 115 (36.6%) patients had P/D and 37 (11.8%) received only a partial pleurectomy. Adjuvant radiotherapy was delivered in 39.2% of patients. Median overall survival time after surgery was 23.0 [95% confidence interval (CI): 19.6-29.1] months. On multivariable (Cox) analysis, pathological Stage III-IV [ P  = 0.004, hazard ratio (HR):1.34; 95% CI: 1.09-1.64], EP/D and P/D ( P  = 0.006, HR for EP/D: 0.46; 95% CI: 0.29-0.74; HR for P/D: 0.52; 95% CI: 0.31-0.87), left-sided disease ( P  = 0.01, HR: 1.52; 95% CI: 1.09-2.12) and pathological status T4 ( P  = 0.0003, HR: 1.38; 95% CI: 1.14-1.66) were found to be independent significant predictors of overall survival. CONCLUSIONS Whether the P/D is extended or not, it shows similarly good outcomes in terms of early results and survival rate. In contrast, a partial pleurectomy, which leaves gross tumour behind, has no impact on survival.

Second malignancy risk in patients with bronchopulmonary carcinoids: Epidemiological results from Italian Network of Cancer Registries

Purpose This epidemiological study aimed to determine the prevalence and characteristics of second tumors (STs) in patients with bronchopulmonary carcinoids (BCs). Methods Data on neuroendocrine carcinomas (NECs) from the AIRTUM registry (1975-2011) were used for the analysis. Among 32,325 NECs, we focused our analysis on 3,205 patients (9.9%) affected by BCs. The overall ST number and incidence were calculated. The number of STs was compared with the expected cancer number in the healthy Italian population, and the standardized incidence ratio (SIR) and 95% confidence intervals were calculated. Results The male/female ratio was 1.5:1 and the mean age 61.7 years (range: 7-94). A total of 640 STs were observed (overall incidence: 20%): 198 tumors were metachronous, 23 synchronous, and 419 occurred before the diagnosis of BC. The most common STs were bladder tumors (12.2%) followed by breast tumors (11.1%). We observed a large number of thyroid tumors (SIR = 3.88), with a remarkably higher frequency of thyroid tumors being synchronously detected with BC in female patients (SIR = 61.39). In male patients there was an increased frequency of urinary system tumors, in particular metachronous tumors of the kidney and renal pelvis (SIR = 3.34) and synchronous tumors of the urinary bladder (SIR = 11.48). Conclusions A high frequency of STs is predictable in patients with BCs, with synchronous thyroid tumors being observed in women and kidney and urinary bladder tumors in men. However, these data should be interpreted with caution, considering that the diagnosis of such tumors often occurs as an incidental finding during investigations for other malignancies.