Claudio Mossetti

Significance of the presence of microscopic vascular invasion after complete resection of Stage I-II pT1-T2N0 non-small cell lung cancer and its relation with T-Size categories: did the 2009 7th edition of the TNM staging system miss something?

Introduction: The aim of this study was to assess the significance of microscopic vascular invasion (MVI) in a population of resected patients with early-stage non-small cell lung cancer (NSCLC), along with an analysis of the effect of the combination of MVI and tumor size for the T-size categories T1a-T2b according to the 2009 7th edition of the tumor, node, metastasis (TNM) classification. Methods: From January 1993 to August 2008, 746 patients with pT1-T2N0 NSCLC received resection at our institution. MVI was ascertained using histopathological and immunohistochemical techniques. Results: MVI was observed in 257 patients (34%). Prevalence was higher in adenocarcinoma (ADK) than in squamous cell carcinoma (p = 0.002). A significant correlation was found between MVI and ADK (p = 0.03), increased tumor dimension (p = 0.05), and the presence of tumor-infiltrating lymphocytes (p = 0.02). The presence of MVI was associated with a reduced 5-year survival overall (p = 0.003) and in ADK (p = 0.0002). In a multivariate survival analysis, MVI was an indicator of poor survival overall (p = 0.003) and in ADK (p = 0.0005). In each T category (T1a-T2b) of the 2009 TNM staging system, survival of MVI+ patients was significantly lower than the corresponding MVI− patients; T1a and T1b MVI+ patients had a survival similar to MVI− T2 patients. Conclusions: The finding of MVI in pT1-T2N0 NSCLC is frequent. MVI correlates with adenocarcinoma histotype, increased tumor dimensions, and tumor-infiltrating lymphocytes. The presence of MVI is an independent negative prognostic factor. In our experience, MVI was a stronger prognostic indicator than T size in T1a-T2b categories according to the 2009 TNM staging system.

Thymoma: inter-relationships among World Health Organization histology, Masaoka staging and myasthenia gravis and their independent prognostic significance: a single-centre experience §

OBJECTIVE In thymomas, World Health Organization (WHO) histology, Masaoka stage and myasthenia gravis (MG) have long been considered important for patient management and outcome. Their role has been independently investigated in the past. Few studies, however, focussed on the correlations among these variables. The aim of the present study was to retrospectively evaluate, in our patient population of resected thymomas, the inter-relationships among MG, WHO histology and Masaoka stage, and to look at how and to what extent one variable is associated with the other two in terms of clinical presentation and survival. METHODS From January 1990 to October 2008, 255 patients received resection of thymoma. MG was present in 105 cases (41%). Histology by WHO was: 25 A (10%), 72 AB (28%), 65 B1 (25%), 69 B2 (27%) and 24 B (9%). Masaoka staging was stage I, 54 cases (21%), stage II, 86(34%), stage III 79 (31%), and stage IVA 36 (14%). Ordinal and logistic regression models were undertaken to analyse correlations among ordinal (WHO histology and Masaoka stage) and categorical (MG, A vs B WHO types) variables. Univariate and multivariate survival analysis were also performed using the same covariates. Overall survival (OS) and disease-free survival (DFS) were calculated. RESULTS MG was associated with early Masaoka stages (odds ratio (OR) 0.45, 95% confidence interval (CI) 0.33-0.62) and B-type thymomas (OR 1.59, 95% CI 1.23-2.05). B-type thymomas were associated with high Masaoka stage (OR 0.46, 95% CI 0.36-0.60). High Masaoka stage was associated with non-MG (OR 3.27; 95% CI 2.00-5.34). In univariate survival analysis, MG (p = 0.01) and Masaoka stage (p = 0.0001) were significant prognostic indicators using OS. Using DFS, WHO histology (A/AB vs B1/B2/B3 types) (p = 0.05) and Masaoka stage (p = 0.0001) had a prognostic significance. In multivariate analysis, only Masaoka stage was an independent prognostic covariate using OS (hazard ratio (HR) 2.57, 95% CI 1.46-4.52, p = 0.001) and DFS (HR 3.18, 95% CI 1.56-6.52, p = 0.001). CONCLUSIONS In thymomas, MG, WHO histology and Masaoka stage are inter-related. MG has an influence on histology and stage at presentation, while two clinical/histologic patterns are more likely: early Masaoka stage A/AB WHO type and high Masaoka stage/B WHO type. Among the three factors, only Masaoka stage had a prognostic significance on OS and DFS. Our results suggest that a consistent staging system for thymomas should take into account all three variables.

Recommended changes for T and N descriptors proposed by the International Association for the Study of Lung Cancer — Lung Cancer Staging Project: a validation study from a single-centre experience

OBJECTIVE The International Association for the Study of Lung Cancer (IASLC) recently recommended changes for T and N descriptors for the next TNM (Tumour, Node, Metastasis) edition. We re-classify our operated patients to evaluate the effectiveness of the IASLC suggestions. METHODS IASLC proposals include: (1) a subdivision of T1 into T1a (< or =2 cm) and T1b (2-3 cm); (2) a subdivision of T2 into T2a (3-5 cm) and T2b (5-7 cm); (3) a re-assignment of T2 >7 cm to T3; (4) a re-assignment of intrapulmonary metastasis in the primary lobe (PM1) and in ipsilateral different lobes (PM2) from T4 to T3 and from M1 to T4, respectively; and (5) a classification of N descriptor by the number of involved lymph node zones into: N0; single-zone N1 (N1a); multiple-zone N1/single-zone N2 (N1b/N2a) and multiple-zone N2 (N2b). From 1994 to 2007, 1805 patients were operated on for non-small-cell lung carcinoma (NSCLC); survival analysis was performed using Cox proportional hazard model to assess the prognostic significance of the T and N descriptors. RESULTS Stratification by T descriptor was: T1a (362 patients), T1b (286), T2a (536), T2b (154), T2 >7 cm (58), T3 (243), PM1 (50) and PM2 (36). Stratification by N descriptor was: N0 (1150 patients), N1a (289), N1b/N2a (200) and N2b (67). A significant survival difference was found between T1a and T1b (hazard ratio (HR) 1.45, 95% confidence interval (CI): 1.10-1.90, p=0.006) but not between T2a and T2b (HR: 1.11, 95% CI: 0.86-1.43, p=0.38). Tumours >7 cm and PM1 had a survival similar to other T3 tumours (HR: 1.05, 95% CI: 0.97-1.14, p=0.2 and HR: 0.99, 95% CI: 0.81-1.21, p=0.94). An excellent patient stratification was provided with the proposed four-category nodal grouping, with significant survival differences between N0 and N1a (HR: 1.81, 95% CI: 1.50-2.21, p=0.0000001), N1a and N1b/N2a (HR: 1.54, 95% CI: 1.21-2.00, p=0.02) and between N1b/N2a and N2b (HR: 1.61, 95% CI: 1.14-2.27, p=0.02). CONCLUSIONS Our experience confirms the IASLC recommendations to subdivide patients by tumour size at 2, 3 and 7 cm, to re-assign PM1 tumours to T3 and to group patients according to the number of involved lymph nodal zones are valid and provide excellent survival stratification.

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.

Pulmonary Metastasectomy for Melanoma

After primary tumor treatment, 30% of patients with malignant melanoma develop metastatic disease, usually associated with a poor prognosis. Effective chemotherapeutic regimens for metastatic melanoma are not currently available. Surgical treatment of pulmonary metastases remains controversial because of the dismal survival rates reported in several studies. However, for patients with good performance status, long disease-free interval, limited metastatic disease, and less aggressive tumor biology, it remains an option. The authors have analyzed their experience in 26 patients operated on between 2000 and 2008 alongside a review of the large series in the literature.

Surgery of colorectal cancer lung metastases: analysis of survival, recurrence and re-surgery

BACKGROUND Surgery is considered an effective therapeutic option for patients with lung metastasis (MTS) of colorectal cancer (CRC). The purpose of the study was to evaluate efficacy and feasibility of lung metastasectomy in CRC patients and to explore factors of prognostic relevance. METHODS This is a retrospective study of patients operated for lung MTS of CRC from 2004 to 2012 in a single Institution. Overall survival (OS) was the primary endpoint. Secondary endpoints were progression free survival (PFS) in resection status R0 and OS in in patients submitted to re-resections. In order to evaluate prognostic factors, a multivariable Cox proportional hazard model was performed. RESULTS One-hundred eighty-eight consecutive patients were included in the final analysis. The median follow-up (FU) was 45 months. The 5-year OS and PFS were 53% (95% CI: 44-60%) and 33% (95% CI: 25-42%), respectively. Two- and 5-year survival after re-resection were 79% (95% CI: 63-89%) and 49% (95% CI: 31-65%), respectively. Multivariate adjusted analysis showed that primary CRC pathological TNM stages (P=0.019), number of resected MTS ≥5 (P=0.009) and lymph nodal involvement (P<0.0001) are independent predictors of poor prognosis. CONCLUSIONS Patients operated and re-operated for lung MTS from CRC cancers showed encouraging survival rates. Our results indicated that primary CRC stage, number of MTS and lymph nodal involvement are strong predictive factors. Prognosis after surgery remained comforting up to four resected MTS. Adjuvant chemotherapy seems to have a benefit on survival in patients affected by multiple metastases. Finally, according to the high rate of unidentified lymph node involvement in pre-operative setting, lymph node sampling should be advisable for a correct staging.

KRAS exon 2 codon 13 mutation is associated with a better prognosis than codon 12 mutation following lung metastasectomy in colorectal cancer

Introduction The utilization of molecular markers as routinely used biomarkers is steadily increasing. We aimed to evaluate the potential different prognostic values of KRAS exon 2 codons 12 and 13 after lung metastasectomy in colorectal cancer (CRC). Results KRAS codon 12 mutations were observed in 116 patients (77%), whereas codon 13 mutations were observed in 34 patients (23%). KRAS codon 13 mutations were associated with both longer time to pulmonary recurrence (TTPR) (median TTPR: 78 months (95% CI: 50.61–82.56) vs 56 months (95% CI: 68.71–127.51), P = 0.008) and improved overall survival (OS) (median OS: 82 months vs 54 months (95% CI: 48.93–59.07), P = 0.009). Multivariate analysis confirmed that codon 13 mutations were associated with better outcomes (TTPR: HR: 0.40 (95% CI: 0.17–0.93), P = 0.033); OS: HR: 0.39 (95% CI: 0.14–1.07), P = 0.07). Otherwise, no significant difference in OS (P = 0.78) or TTPR (P = 0.72) based on the type of amino-acid substitutions was observed among KRAS codon 12 mutations. Materials and Methods We retrospectively reviewed data from 525 patients who underwent a lung metastasectomy for CRC in two departments of thoracic surgery from 1998 to 2015 and focused on 150 patients that had KRAS exon 2 codon 12/13 mutations. Conclusions KRAS exon 2 codon 13 mutations, compared to codon 12 mutations, seem to be associated with better outcomes following lung metastasectomy in CRC. Prospective multicenter studies are necessary to fully understand the prognostic value of KRAS mutations in the lung metastases of CRC.

Segmental tracheal resection for invasive differentiated thyroid carcinoma. Our experience in eight cases

PurposeIn differentiated thyroid carcinoma (DTC), complete resection of local disease provides the longest survival and the best palliation. In pursuit of this goal, segmental tracheal or laryngotracheal resection can be performed on patients with DTC invading the airway. The study summarizes the technical aspects of the intervention and analyzes its results in eight patients.MethodsThe results of eight tracheal or laryngotracheal resections for DTC invading the airway were analyzed. Three patients presented with local recurrent disease, whereas five underwent airway resection at the time of thyroidectomy or shortly after. All received a circumferential sleeve resection of the trachea (2–4 tracheal rings) that in three cases extended to the cricoid, followed by end-to-end anastomosis.ResultsPathologic evaluation identified seven papillary and one poorly differentiated carcinomas. No postoperative deaths occurred; one patient required surgical reexploration because of postoperative bleeding, and two air leaks resolved with conservative treatment. Functional results were excellent. During follow-up, one patient died of lung and bone metastases, while in two cases locally persistent/recurrent disease has been detected; two patients are currently free of disease, and in the last three cases only persistent thyroglobulin levels are indicative of residual disease.ConclusionsIn our experience, segmental airway resection is safe, provides excellent functional results, and can warrant adequate control of local disease.

Mediastinoscopy-assisted Treatment of an Aberrant Right Subclavian Artery

Aberrant right subclavian artery (ARSA) is a rare congenital anomaly characterized by the origin of the right subclavian artery from the aortic arch distally to the left subclavian artery. We describe the case of a young patient with symptomatic ARSA treated by mediastinoscopy-assisted ligation at its origin and subclavian-carotid transposition.