Pulmonary Hamartoma Associated With Lung Cancer (PHALC Study): Results of a Multicenter Study.

PURPOSE: Pulmonary hamartoma is the most common benign tumor of the lung. We analyzed a 20-year historical series of patients with pulmonary hamartoma undergoing surgical resection, aiming to evaluate the characteristics, the outcomes, and the association between hamartoma and lung cancer. METHODS: It was a retrospective multicenter study including the data of all consecutive patients with pulmonary hamartoma undergoing surgical resection. The end-points were to evaluate: (i) the characteristics of hamartoma, (ii) outcomes, and (iii) whether hamartoma was a predictive factor for lung cancer development RESULTS: Our study population included 540 patients. Upfront surgical or endoscopic resection was performed in 385 (71%) cases while in the remaining 155 (29%) cases, the lesions were resected 20 ± 3.5 months later due to increase in size. In most cases, lung sparing resection was carried out including enucleation (n = 259; 48%) and wedge resection (n = 230; 43%) while 5 (1%) patients underwent endoscopic resection. Only two patients (0, 2%) had major complications. One patient (0.23%) had recurrence after endoscopic resection, while no cases of malignant degeneration were seen (mean follow-up:103.3 ± 93 months). Seventy-six patients (14%) had associated lung cancer, synchronous in 9 (12%) and metachronous in 67 (88%). Only age > 70-year-old (p = 0.0059) and smokers > 20 cigarettes/day (p < 0.0001) were the significant risk factors for lung cancer. CONCLUSION: PH was a benign tumor, with no evidence of recurrence and/or of malignant degeneration after resection. The association between hamartoma and lung cancer was a spurious phenomenon due to common risk factors.

Apparent diffusion coefficient measurements in diffusion-weighted magnetic resonance imaging of the anterior mediastinum: inter-observer reproducibility of five different methods of region-of-interest positioning.

OBJECTIVES: To investigate inter-reader reproducibility of five different region-of-interest (ROI) protocols for apparent diffusion coefficient (ADC) measurements in the anterior mediastinum. METHODS: In eighty-one subjects, on ADC mapping, two readers measured the ADC using five methods of ROI positioning that encompassed the entire tissue (whole tissue volume [WTV], three slices observer-defined [TSOD], single-slice [SS]) or the more restricted areas (one small round ROI [OSR]), multiple small round ROI [MSR]). Inter-observer variability was assessed with interclass correlation coefficient (ICC), coefficient of variation (CoV), and Bland-Altman analysis. Nonparametric tests were performed to compare the ADC between ROI methods. The measurement time was recorded and compared between ROI methods. RESULTS: All methods showed excellent inter-reader agreement with best and worst reproducibility in WTV and OSR, respectively (ICC, 0.937/0.874; CoV, 7.3 %/16.8 %; limits of agreement, ±0.44/±0.77 × 10-3 mm2/s). ADC values of OSR and MSR were significantly lower compared to the other methods in both readers (p < 0.001). The SS and OSR methods required less measurement time (14 ± 2 s) compared to the others (p < 0.0001), while the WTV method required the longest measurement time (90 ± 56 and 77 ± 49 s for each reader) (p < 0.0001). CONCLUSIONS: All methods demonstrate excellent inter-observer reproducibility with the best agreement in WTV, although it requires the longest measurement time. KEY POINTS: • All ROI protocols show excellent inter-observer reproducibility. • WTV measurements provide the most reproducible ADC values. • ROI size and positioning influence ADC measurements in the anterior mediastinum. • ADC values of OSR and MSR are significantly lower than other methods. • OSR and WTV methods require the shortest and longest measurement time, respectively.

Minute ventilation to carbon dioxide output (V'E/V'CO2 slope) is the strongest death predictor before larger lung resections.

The minute ventilation to CO2 production ratio (V'E/V'CO2 slope) was recently identified as a mortality predictor after lung surgery, but the effect of the resection extent was not taken into account.  The aim of this study was to investigate the role of V'E/V'CO2 slope as preoperative mortality predictor depending on the type of surgery performed. Retrospective analysis was performed on 263 consecutive patients evaluated before surgery for lung cancer. Death within 30 days and serious respiratory complications were considered. Univariate and multivariate regression analyses were used to identify independent predictors of death. Lobectomy or bilobectomy were performed in 186 patients with 29/186 (15.6%) serious pulmonary complications and 6/186 (3.2%) deaths. Pneumonectomy was performed in 77 patients with 14/77 (18.2%) serious complications and 5/77 (6.5%) deaths.  Considering the whole group, the peak oxygen consumption (V'02peak, L/ min; z=-2.66, p<0.008, OR 0.007) and V'E/V'C02 slope (z=2.80, p<0.005, OR 1.14) were independent predictors of mortality whereas in pneumonectomies V'E/V'C02 slope (z=2.34, p<0.02, OR 1.22) was the only independent predictor of mortality. High V'E/V'CO2 slope, age and low V'02peak are predictors of death and severe complications after lung surgery. Before larger resections as pneumonectomies an increased V'E/V'CO2 slope represents the best mortality predictor.

Diffusion-weighted quantitative MRI to diagnose benign conditions from malignancies of the anterior mediastinum: Improvement of diagnostic accuracy by comparing perfusion-free to perfusion-sensitive measurements of the apparent diffusion coefficient.

PURPOSE: To compare perfusion-free to perfusion-sensitive measurements of the apparent diffusion coefficient (ADC) to diagnose benign conditions from malignancies of the anterior mediastinum. MATERIALS AND METHODS: Seventy-six subjects were divided into a "benign conditions" group (A, n = 44) and a "malignancies" group (B, n = 32), based on histological findings. diffusion-weighted magnetic resonance imaging (DW-MRI) was performed at b of 0/150/800 sec/mm(2) . The ADCs were obtained on an ADC map by including (perfusion-sensitive = ADCb0-800 ) and excluding (perfusion-free = ADCb150-800 ) the b = 0 sec/mm(2) . The Mann-Whitney U-test was used to detect differences in ADCb0-800 compared with ADCb150-800 values between all cases, benign conditions, and malignancies. The same test was used to evaluate differences in ADCs between the two groups for each type of measurement (ADCb0-800 and ADCb150-800 ), and receiver-operating characteristic (ROC) curves were obtained to evaluate discrimination abilities with comparison of areas-under-ROC-curves (AUROC). Optimal cutpoints for discrimination between groups were determined by the Youden-Index with computation of accuracy. RESULTS: The median ADCb0-800 was significantly greater compared with ADCb150-800 for all cases (P = 0.0014), benign conditions (P = 0.0412), and malignancies (P = 0.0001). The median percentage of increase was 5.30% for group-A and 22.39% for group-B (P < 0.0001). AUROC of ADC in discriminating between groups was significantly greater for ADCb150-800 (0.932) compared with ADCb0-800 (0.831) (P = 0.001). The optimal cutpoint for distinction between groups was 1.52 × 10(-3) mm(2) /sec (sensitivity = 93.7%, specificity = 88.6%, accuracy = 90.8%) for ADCb150-800 and 1.75 × 10(-3) mm(2) /sec (sensitivity = 75.0%, specificity = 79.5%, accuracy = 77.6%) for ADCb0-800 . CONCLUSION: The use of perfusion-free ADC measurements significantly improves diagnostic accuracy of DW-MRI in differentiating benign conditions from malignancies of the anterior mediastinum. J. Magn. Reson. Imaging 2016;44:758-769.

Sublobar resection versus lobectomy for stage I non-small cell lung cancer: an appropriate choice in elderly patients?

PURPOSES: The aim of this study was to evaluate whether sublobar resection could achieve recurrence and survival rates equivalent to lobectomy in high-risk elderly patients. METHODS: We conducted a retrospective multicenter study that including all consecutive patients (aged >75 years) who underwent operation for clinical stage I non-small cell lung cancer (NSCLC). The clinicopathological data, postoperative morbidity and mortality, recurrence rate and vital status were retrieved. The overall survival, cancer-specific survival and disease-free survival were also assessed. RESULTS: Two hundred and thirty-nine patients (median age 78 years) were enrolled. Lobectomies were performed in 149 (62.3 %) patients and sublobar resections in 90 (39 segmentectomies, 51 wedge resections). There were no differences in the recurrence rates following lobar versus sublobar resections (19 versus 23 %, respectively; p = 0.5) or the overall survival (p = 0.1), cancer-specific survival (p = 0.3) or disease-free survival (p = 0.1). After adjusting for 1:1 propensity score matching and a matched pair analysis, the results remained unchanged. A tumor size >2 cm and pN2 disease were independent negative prognostic factors in unmatched (p = 0.01 and p = 0.0003, respectively) and matched (p = 0.02 and p = 0.005, respectively) analyses. CONCLUSIONS: High-risk elderly patients may benefit from sublobar resection, which provides an equivalent long-term survival compared to lobectomy.

Pulmonary metastasectomy in colorectal cancer patients with previously resected liver metastasis: pooled analysis.

BACKGROUND: Data addressing the outcomes and patterns of recurrence after pulmonary metastasectomy (PM) in patients with colorectal cancer (CRC) and previously resected liver metastasis are limited. METHODS: We searched the PubMed database for studies assessing PM in CRC and gathered individual data for patients who had PM and a previous curative liver resection. The influence of potential factors on overall survival (OS) was analyzed through univariate and multivariate analysis. RESULTS: Between 1983 and 2009, 146 patients from five studies underwent PM and had previous liver resection. The median interval from resection of liver metastasis until detection of lung metastasis and the median follow-up from PM were 23 and 48 months, respectively. Five-year OS and recurrence-free survival rates calculated from the date of PM were 54.4 and 29.3 %, respectively. Factors predicting inferior OS in univariate analysis included thoracic lymph node (LN) involvement and size of largest lung nodule ≥2 cm. Adjuvant chemotherapy and whether lung metastasis was detected synchronous or metachronous to liver metastasis had no influence on survival. In multivariate analysis, thoracic LN involvement emerged as the only independent factor (hazard ratio 4.86, 95 % confidence interval 1.56-15.14, p = 0.006). CONCLUSIONS: PM offers a chance for long-term survival in selected patients with CRC and previously resected liver metastasis. Thoracic LN involvement predicted poor prognosis; therefore, significant efforts should be undertaken for adequate staging of the mediastinum before PM. In addition, adequate intraoperative LN sampling allows proper prognostic stratification and enrollment in novel adjuvant therapy trials.

Safety and diagnostic performance of image-guided lung biopsy in the targeted therapy era.

OBJECTIVE OF THE STUDY: To identify risk factors for the adverse events and determine the diagnostic yield of a large series of image-guided thoracic biopsies performed in a single institution. MATERIALS AND METHODS: We reviewed a consecutive series of 811 patients (546 males; average age: 68 years.) who underwent 824 image-guided biopsies of pulmonary lesions performed between 2009 and 2013. Indications for biopsy were always evaluated by a multidisciplinary board. All complications were registered. The diagnostic accuracy was calculated on the basis of histology after surgery, response to medical therapy, or outcome at imaging follow-up. Safety and accuracy was correlated with patient-related and lesion-related factors. RESULTS: 61 biopsies were performed under US-guidance, 750 under CT-guidance, and 13 under combined guidance. The average lesion size was 36.4 mm (6-150 mm). FNAB was exclusively performed in 247 patients, whereas 577 patients underwent also or only core biopsy (CB). 40 (4.8 %) major complications and 172 (20.8 %) minor complications occurred. US-guidance, absence of perilesional emphysema and minor depth of the target lesion from the skin resulted as favorable predictors against major complications. According to the gold standard criteria, we demonstrated 497 true positives, 72 true negatives, 18 false negatives, 0 false positives. Sensitivity, specificity and diagnostic accuracy were 96.5, 100 and 97 %. No predictors for accuracy were found, but the number of samples largely related to the pathologist on site. CONCLUSIONS: Image-guided lung biopsy is safe and highly accurate for diagnosing thoracic lesions. In the targeted therapy era, CB with larger needles can be safely applied when the need for larger amounts of tumor tissue is presumed.

Repeated resection of colorectal cancer pulmonary oligometastases: pooled analysis and prognostic assessment.

BACKGROUND: Repeated resection of colorectal cancer pulmonary metastasis is associated with long-term survival. Nevertheless, very limited data addressing the best candidates for repeated pulmonary resection is available. PATIENTS AND METHODS: We searched the PubMed database for retrospective studies evaluating lung metastasectomy for metastatic colorectal cancer (CRC). We included studies with available data about repeated pulmonary metastasectomy. Potential prognostic factors were analyzed for possible impact on survival following the second metastasectomy through univariate and multivariate analysis. RESULTS: Between 1983 and 2008, 944 lung metastasectomies were carried out on 759 patients. Of those, 148 patients had a second metastasectomy. The 5-year survival rate was 52 % for patients who had 1 metastasectomy and 57.9 % from the second metastasectomy for patients who had repeated resection. More than 2 metastatic pulmonary nodules and maximum diameter of largest pulmonary nodule ≥3 cm were the only independent factors associated with inferior survival following repeated pulmonary resection. CONCLUSIONS: In selected patients with metastatic CRC, repeated pulmonary metastasectomy offers an excellent chance for long-term survival and is associated with a quite low operative mortality. Patients with more than 2 metastatic nodules and a maximum diameter of the largest metastatic lung nodule of ≥3 cm have a significantly inferior survival.

Expression and pharmacological inhibition of thymidylate synthase and Src kinase in nonsmall cell lung cancer.

The combination of cytotoxic chemotherapy with signaling pathway inhibitors represents a potential strategy to improve the treatment of nonsmall cell lung cancer (NSCLC). Thymidylate synthase (TS) is an enzyme essential for DNA synthesis, and its overexpression has been associated with the reduced sensitivity to antifolate agents. Src is a tyrosine kinase that modulates the cytotoxicity of cancer cells after drug treatment, and in vitro data indicate that its inhibition could revert the resistance to TS-inhibiting drugs. Our study investigated the significance of TS and Src expression in NSCLC tissues, and the effects of their pharmacological inhibition in cell lines. In tumor and normal tissues from 94 resected NSCLC patients, TS and Src transcript levels were found positively correlated (R(S) = 0.66), associated with patients smoking history and overall survival. At multivariate analysis, TS gene expression was an independent prognostic factor (relative risk (RR) = 1.78, from 1.16 to 2.72; p < 0.01). Immunohistochemical detection in tumor specimens confirmed that Src kinase activation, evaluated by phospho-specific antibody, was associated to a higher TS expression. In cell lines, dasatinib, a Src-inhibiting agent, synergistically enhanced pemetrexed-cytotoxicity of A549 cells, as evaluated by MTT and apoptosis assays. The biological explanation for this interaction was based on the upregulation of TS messenger RNA and protein levels induced by pemetrexed, which was significantly prevented by dasatinib cotreatment. The data of our study suggest that TS and Src may belong to a common pathway that bears prognostic significance in NSCLC, and that Src represents a potential target to improve the efficacy of TS-inhibiting agents.

The role of lung metastasis resection in improving outcome of colorectal cancer patients: results from a large retrospective study.

BACKGROUND: The role of surgery for lung metastases (LM) secondary to colorectal cancer (CRC) remains controversial. The bulk of evidence is derived from single surgical series, hampering any definitive conclusions. The aim of this study was to compare the outcomes of CRC patients with LM submitted to surgery with those who were not. PATIENTS AND METHODS: Data from 409 patients with LM as the first evidence of advanced disease were extracted from a database of 1,411 patients. Patients were divided into three groups: G1, comprised of 155 patients with pulmonary and extrapulmonary metastases; G2, comprised of 104 patients with LM only and no surgery; G3, comprised of 50 patients with LM only and submitted to surgery. RESULTS: No difference in response rates emerged between G1 and G2. Median progression-free survival (PFS) times were: 10.3 months, 10.5 months, and 26.2 months for G1, G2, and G3, respectively. No difference in PFS times was observed between G1 and G2, whereas there was a statistically significant difference between G2 and G3. Median overall survival times were 24.2 months, 31.5 months, and 72.4 months, respectively. Survival times were longer in resected patients: 17 survived >5 years and three survived >10 years. In patients with LM only and no surgery, four survived for 5 years and none survived >10 years. CONCLUSIONS: Even though patients with resectable LM are more likely to be those with a better outcome, our study provides evidence suggesting an active role of surgery in improving survival outcomes in this patient subset.

Role of surgical resection in colorectal lung metastases: analysis of 137 patients.

PURPOSE: The aim of this study is to investigate clinicopathologic characteristics and to identify prognostic factors in patients undergoing pulmonary metastasectomy for colorectal carcinoma. METHODS: This study is a single-institution retrospective study of 137 consecutive patients who underwent 158 pulmonary resections for metastatic colorectal carcinoma between January 1989 and June 2008. RESULTS: Median disease-free interval between colorectal resection and pulmonary metastasectomy was 35.6 months (range, 0.6 to 154.3 months). No perioperative deaths occurred. Follow-up was 100% complete and mean follow-up was 41.6 ± 27.6 months. Median survival was 36.2 months (range, 4.6 to 126 months). Overall 5- and 10-year survival rates were 55.4% and 30.8%, respectively, after pulmonary metastasectomy. At univariate analysis of patient survival, number of lung metastases (p = 0.002), disease-free interval of more than 24 month (p = 0.013), and absence of residual tumor (p = 0.024) were significant prognostic factors. At multivariate analysis, presence of solitary lung metastasis and disease-free interval of more than 24 months remained significant prognostic factors. There was no significant difference in the 5-year survival for 121 patients undergoing single thoracotomy compared with 16 patients undergoing repeated resection(s) for recurrent colorectal lung metastasis (55.1% vs 59.5%; p = 0.79). Nor was the presence of hepatic metastasis associated with lower outcome (p = 0.77). CONCLUSIONS: Disease-free interval and number of metastases are the most significant prognostic factors for survival after pulmonary metastasectomy for colorectal carcinoma. Recurrent pulmonary disease can benefit from repeated resection. Prior hepatectomy for liver involvement does not influence survival.

Correlation between CT findings and thoracoscopic diagnosis in diffuse pleural disease.

OBJECTIVE: Computed Tomography (CT) is considered part of the routine diagnostic workup for pleural malignancy. The definitive diagnosis of pleural malignancy depends upon histological confirmation by pleural biopsy. The aim of this study is to assess the sensitivity and specificity of CT, in view of the latest imaging technologies, in detecting pleural malignancy compared to definitive histology achieved via thoracoscopy (VATS). MATERIALS AND METHODS: We included in this retrospective study 90 patients (36 F, 54 M) with suspected pleural malignancy  evaluated in our Institution with CT scan who received a definitive diagnosis after VATS biopsy. Unaware of histopathologic diagnoses CT scans were evaluated by a junior and two experts thoracic radiologist. Conclusions were reached by consensus. RESULTS: We evaluated all CT signs suggestive for malignant pleural diseases: pleural thickening > 10 mm (Se 0,41 , Sp 0,79); nodular thickening (Se 0,86, Sp 0,75); circumferential thickening (Se 0,79, Sp 0,69); irregular pleural thickening (Se 0,77, Sp 0,91); mediastinal involvement (Se 0,88, Sp 0,64); costal involvement (Se 0,89, Sp 0,60); diaphragmatic involvement (Se 0,88, Sp 0,53). Furthermore, the diagnostic performance of additional CT features was evaluated: concomitant costal, mediastinal and diaphragmatic pleura lesions (Se 0,84, Sp 0,69); nodular/irregular thickening with mediastinal pleural involvement (Se 0,83, Sp 0,90); nodular/irregular thickening with diaphragmatic pleural involvement (Se 0,81, Sp 0,90). CONCLUSIONS: CT confirms its central role in the pleura malignancy. The high sensibility, respect to previous studies, especially in the presence of nodular pleural thickening, may lead to reconsider at least partly the diagnostic pathway of diffuse pleural disease, avoiding the use of VATS in patients not eligible for surgery, in favor of US or CT guided core biopsy.

Prognostic factors of lung cancer in lymphoma survivors (the LuCiLyS study).

BACKGROUND: Second cancer is the leading cause of death in lymphoma survivors, with lung cancer representing the most common solid tumor. Limited information exists about the treatment and prognosis of second lung cancer following lymphoma. Herein, we evaluated the outcome and prognostic factors of Lung Cancer in Lymphoma Survivors (the LuCiLyS study) to improve the patient selection for lung cancer treatment. METHODS: This is a retrospective multicentre study including consecutive patients treated for lymphoma disease that subsequently developed non-small cell lung cancer (NSCLC). Data regarding lymphoma including age, symptoms, histology, disease stage, treatment received and lymphoma status at the time of lung cancer diagnosis, and data on lung carcinoma as age, smoking history, latency from lymphoma, symptoms, histology, disease stage, treatment received, and survival were evaluated to identify the significant prognostic factors for overall survival. RESULTS: Our study population included 164 patients, 145 of which underwent lung cancer resection. The median overall survival was 63 (range, 58-85) months, and the 5-year survival rate 54%. At univariable analysis no-active lymphoma (HR: 2.19; P=0.0152); early lymphoma stage (HR: 1.95; P=0.01); adenocarcinoma histology (HR: 0.59; P=0.0421); early lung cancer stage (HR: 3.18; P<0.0001); incidental diagnosis of lung cancer (HR: 1.71; P<0.0001); and lung cancer resection (HR: 2.79; P<0.0001) were favorable prognostic factors. At multivariable analysis, no-active lymphoma (HR: 2.68; P=0.004); early lung cancer stage (HR: 2.37; P<0.0001); incidental diagnosis of lung cancer (HR: 2.00; P<0.0001); and lung cancer resection (HR: 2.07; P<0.0001) remained favorable prognostic factors. Patients with non-active lymphoma (n=146) versus those with active lymphoma (n=18) at lung cancer diagnosis presented better median survival (64 vs. 37 months; HR: 2.4; P=0.02), but median lung cancer specific survival showed no significant difference (27 vs. 19 months; HR: 0.3; P=0.17). CONCLUSIONS: The presence and/or a history of lymphoma should not be a contraindication to resection of lung cancer. Inclusion of lymphoma survivors in a lung cancer-screening program may lead to early detection of lung cancer, and improve the survival.

A case of intermittent lumbar pain radiating to the right shoulder in a 76-year-old woman.

Malignant fibrous histiocytoma (MFH) is a pleomorphic sarcoma, occurring most frequently in the deep soft tissues of the extremities, and it is most frequently seen in elderly patients. A primary MFH of the diaphragm is very rare, and to the best of our knowledge, a multi-phased spiral CT appearance of this tumour has not been previously reported. In this report, we describe the clinical and multi-phase CT features of a primary MFH of the diaphragm.

Risk of recurrence in stage I adenocarcinoma of the lung: a multi-institutional study on synergism between type of surgery and type of nodal staging.

BACKGROUND: In last years, an increasing interest emerges on the role of sub-lobar resection and lobe-specific lymph nodal dissection in the treatment of early-stage lung cancer. The aim of our study was to define the impact on cumulative incidence of recurrence (CIR) of type of surgical resection and type of nodal staging in this subset of patients. Furthermore, we evaluated the possible synergism between the different kinds of procedure. METHODS: An analysis of 969 consecutive stage I pulmonary adenocarcinoma patients, operated in six Thoracic Surgery Institutions between 2001 and 2013, was conducted. Type of surgical resection included lobectomy and sub-lobar resection; while pneumonectomy and bilobectomy were excluded from the analysis. Nodal staging procedures were classified in nodal sampling (NS), lobe-specific lymph node dissection (LS-ND) and systematic lymph node dissection (SND). Multivariable-adjusted comparisons for CIR was performed using Fine and Grey model, taking into account of death by any cause as competing event. In order to evaluate synergism between the different procedures, the test of interaction between type of surgical resection and type of nodal staging was carried out and results presented in a stratified way. RESULTS: Eight-hundred forty-six (87%) patients were submitted to lobectomy, while 123 (13%) to sub-lobar resection. Four-hundred fifty-five (47%) patients received SND, 98 (10%) LS-ND and 416 (43%) NS. Two-hundred forty-seven (26%) patients developed a local/distant recurrence with a 5-year CIR of 24.2%. Multivariable-adjusted comparisons showed an independent negative effect of sub-lobar resection (HR =1.52; 95% CI: 1.07-2.17), LS-ND (HR =1.74; 95% CI: 1.16-2.6) and NS (HR =1.49; 95% CI: 1.12-1.98) on CIR. Test of interaction showed a homogeneity of results among subgroups. CONCLUSIONS: Patients affected by stage I pulmonary adenocarcinoma and submitted to lobectomy presented a significant lower recurrence rate than those submitted to sub-lobar resection. Moreover, SND presented an independent positive effect on recurrence development than other lymph node assessment strategy. Finally, lobectomy in combination with systematic lymph nodal resection showed the best results in term of CIR.

Potential Diagnostic and Prognostic Role of Microenvironment in Malignant Pleural Mesothelioma.

INTRODUCTION: A comprehensive analysis of the immune cell infiltrate collected from pleural fluid and from biopsy specimens of malignant pleural mesothelioma (MPM) may contribute to understanding the immune-evasion mechanisms related to tumor progression, aiding in differential diagnosis and potential prognostic stratification. Until now such approach has not routinely been verified. METHODS: We enrolled 275 patients with an initial clinical diagnosis of pleural effusion. Specimens of pleural fluids and pleural biopsy samples used for the pathologic diagnosis and the immune phenotype analyses were blindly investigated by multiparametric flow cytometry. The results were analyzed using the Kruskal-Wallis test. The Kaplan-Meier and log-rank tests were used to correlate immune phenotype data with patients' outcome. RESULTS: The cutoffs of intratumor T-regulatory (>1.1%) cells, M2-macrophages (>36%), granulocytic and monocytic myeloid-derived suppressor cells (MDSC; >5.1% and 4.2%, respectively), CD4 molecule-positive (CD4+) programmed death 1-positive (PD-1+) (>5.2%) and CD8+PD-1+ (6.4%) cells, CD4+ lymphocyte activating 3-positive (LAG-3+) (>2.8% ) and CD8+LAG-3+ (>2.8%) cells, CD4+ T cell immunoglobulin and mucin domain 3-positive (TIM-3+) (>2.5%), and CD8+TIM-3+ (>2.6%) cells discriminated MPM from pleuritis with 100% sensitivity and 89% specificity. The presence of intratumor MDSC contributed to the anergy of tumor-infiltrating lymphocytes. The immune phenotype of pleural fluid cells had no prognostic significance. By contrast, the intratumor T-regulatory and MDSC levels significantly correlated with progression-free and overall survival, the PD-1+/LAG-3+/TIM-3+ CD4+ tumor-infiltrating lymphocytes correlated with overall survival. CONCLUSIONS: A clear immune signature of pleural fluids and tissues of MPM patients may contribute to better predict patients' outcome.

Anatomical resections are superior to wedge resections for overall survival in patients with Stage 1 typical carcinoids.

OBJECTIVES: Typical carcinoids (TCs) are rare, slow-growing neoplasms, usually characterized by satisfactory surgical outcomes. Due to the rarity of TCs, international guidelines for the management of particular clinical presentations currently do not exist. In particular, non-anatomical resections (wedges) are sometimes advocated for Stage 1 TCs because of their indolent behaviour. The aim of this paper was to evaluate the most effective type of surgery for Stage 1 TCs, using the European Society of Thoracic Surgeons retrospective database of the Neuroendocrine Tumors of the Lung Working Group. METHODS: We analysed the effect of surgical procedure on the survival of patients with Stage 1 TCs. Overall survival (OS) was calculated from the date of intervention. The cumulative incidence of cause-specific death (tumour- and non-tumour-related) was also estimated. The impact of the surgical procedure (i.e. lobectomy vs segmentectomy vs wedge resection) on survival was investigated using the Cox model with shared frailty (for OS, accounting for the within-centre correlation) and the Fine and Gray model (for cause-specific mortality) using the approach based on the multinomial propensity score. Effects were estimated including in the model the logit-transformed propensity scores of segmentectomy and wedge resection as covariates. RESULTS: A total of 876 patients with Stage 1 TCs (569 women, 65%) were included in this study. The median age was 60 years (interquartile range 47-69). At the last follow-up, 66 patients had died: The 5-year OS rate was 94.3% [95% confidence interval (CI) 92.2-95.9]. The 5-year cumulative incidences of tumour- and non-tumour-related deaths were 2.4% (95% CI 1.4-3.9) and 3.9% (95% CI 2.5-5.6%), respectively. The analysis performed using the multinomial propensity score approach confirmed the significantly worse survival of patients treated with a wedge resection compared to those treated with a lobectomy (hazard ratio 2.01, 95% CI 1.09-3.69; P = 0.024). Similar effects of wedge resection are detectable for cause-specific deaths: tumour-related (hazard ratio 2.28, 95% CI 0.86-6.02; P = 0.096) and non-tumour-related (hazard ratio 1.74, 95% CI 0.89-3.40; P = 0.105). CONCLUSIONS: In a large cohort of patients, we were able to demonstrate the superiority of anatomical surgical resection in Stage 1 TCs in terms of OS. This result should therefore be considered for future clinical guidelines for the management of TCs.

Prognostic role of osteopontin expression in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) represents highly aggressive neoplasms with a mean survival of approximately 10 months. Osteopontin, a glycoprotein involved in cell-matrix interactions correlated with invasion and metastatic spread in several tumors, has recently been proposed as a serum marker of MPM in asbestos-exposed subjects. The aim of this study was to define the prognostic role of osteopontin in MPM. For the study, 32 long-term survivors (>24 months) and a random sample of 69 short-term survivors (

Malignant pleural mesothelioma: clinicopathologic and survival characteristics in a consecutive series of 394 patients.

OBJECTIVE: Treatment of malignant pleural mesothelioma (MPM) remains disappointing, although recent reports suggest that multimodality therapy including surgery may provide a significant survival benefit. The aims of this single institution study were: to investigate clinicopathologic characteristics and potential prognostic factors in MPM patients, and to ascertain whether surgery followed by adjuvant therapy had an independent prognostic role. METHODS: Retrospective review of a prospectively compiled computerized database of all patients with MPM evaluated between 1989 and 2003. Kaplan-Meier method, log-rank test, and Cox model were used in the statistical analysis. RESULTS: There were 394 patients: 270 men (68.5%), 124 women, median age 64 (range 28-93). Twenty-seven patients (6.8%) underwent surgical resection (extrapleural pneumonectomy 15, pleurectomy/decortication 12), followed by adjuvant therapy. As of March 2006, 381 patients (96.7%) had died (median survival, 11.7 months; range 0.03-117.9). Median follow-up of 13 surviving patients (3.3%) was 45.2 months (range 28.7-126.5). Overall survival at 2 years was 18.8%. Multimodality therapy including surgery yielded a median survival of 14.5 months and a 2-year survival rate of 29.6%. Using univariate analysis, age (p=0.009), chest pain (p=0.01), weight loss (p=0.001), performance status (p=0.0001), platelet count (p=0.008), histology (p=0.0001), macroscopic appearance of pleural surface (non-specific inflammation, tumor-like thickening, or nodules; p=0.0001), visceral pleura involvement (p=0.0001), degree of involvement of pleural cavity (less than or more than one third of the cavity; p=0.0001), and multimodality therapy (p<0.01) were found to be significant prognostic factors. At multivariate analysis, performance status, platelet count, histology, and degree of involvement of pleural cavity remained independently associated with survival, whereas multimodality therapy failed to enter the model. CONCLUSIONS: Significant predictors of survival include performance status, platelet count, histology, and degree of involvement of pleural cavity. Within the confines of this retrospective study and the small number of patients undergoing multimodality therapy, the role of surgery in the treatment of MPM remains unclear. Further investigation is warranted to determine the optimal treatment strategy in this disease.