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.

Lymph node isolated tumor cells and micrometastases in pathological stage I non-small cell lung cancer: prognostic significance.

OBJECTIVE: To determine the prevalence and prognostic significance of lymph node micrometastases and isolated tumor cells (ITC) in patients submitted for radical resection for pathological stage I non-small cell lung cancer (NSCLC). METHODS: From January 1998 through December 2005, 87 consecutive pT1-2, pN0 NSCLC patients were enrolled. Surgical specimens were submitted to pathological routine examinations to define histotype, grade, stage, vascular invasion, necrosis and tumor proliferative index. A total of 694 regional lymph nodes were examined by means of serial sections stained with hematoxylin and eosin and labelled by immunohistochemistry (antibody AE1/AE3, DAKO). Relationships between these parameters and patients' prognosis were investigated. RESULTS: By histological examination, there were 36 squamous-cell carcinoma, 38 adenocarcinoma and 13 large-cell carcinoma. Micrometastases and ITC were detected in 19 lymph nodes (2.7%) of 14 patients (16%). Significant correlation was observed between micrometastases or ITC and adenocarcinoma (p=0.03) and the absence of necrosis (p=0.05). No relationship was demonstrated between micrometastases or ITC and T-status, vascular invasion or proliferative index (p>0.05). Median follow-up was 3.2 (range 0.25-8.6) years. Two- and 5-year disease-free survival was similar for patients with and without micrometastases or ITC (79% and 64% vs 81% and 64%, respectively). Recurrence occurred in three patients with (two local, 66%) and in 21 patients without micrometastases or ITC (three local, 14%) (p=0.186). By multivariate analysis only T-status was demonstrated to be a significant prognostic factor. DISCUSSION: Micrometastases or ITC to regional lymph nodes are demonstrated to be not a rare aspect of pathological stage I resected lung cancer. In our series, the presence of lymph nodes micrometastases does not affect long-term disease-free survival.

Exploring Stage I non-small-cell lung cancer: development of a prognostic model predicting 5-year survival after surgical resection†.

OBJECTIVES: Despite impressive results in diagnosis and treatment of non-small-cell lung cancer (NSCLC), more than 30% of patients with Stage I NSCLC die within 5 years after surgical treatment. Identification of prognostic factors to select patients with a poor prognosis and development of tailored treatment strategies are then advisable. The aim of our study was to design a model able to define prognosis in patients with Stage I NSCLC, submitted to surgery with curative intent. METHODS: A retrospective analysis of two surgical registries was performed. Predictors of survival were investigated using the Cox model with shared frailty (accounting for the within-centre correlation). Candidate predictors were: age, gender, smoking habit, morbidity, previous malignancy, Eastern Cooperative Oncology Group performance status, clinical N stage, maximum standardized uptake value (SUV(max)), forced expiratory volume in 1 s, carbon monoxide lung diffusion capacity (DLCO), extent of surgical resection, systematic lymphadenectomy, vascular invasion, pathological T stage, histology and histological grading. The final model included predictors with P < 0.20, after a backward selection. Missing data in evaluated predictors were multiple-imputed and combined estimates were obtained from 10 imputed data sets. RESULTS: Analysis was performed on 848 consecutive patients. The median follow-up was 48 months. Two hundred and nine patients died (25%), with a 5-year overall survival (OS) rate of 74%. The final Cox model demonstrated that mortality was significantly associated with age, male sex, presence of cardiac comorbidities, DLCO (%), SUV(max), systematic nodal dissection, presence of microscopic vascular invasion, pTNM stage and histological grading. The final model showed a fair discrimination ability (C-statistic = 0.69): the calibration of the model indicated a good agreement between observed and predicted survival. CONCLUSIONS: We designed an effective prognostic model based on clinical, pathological and surgical covariates. Our preliminary results need to be refined and validated in a larger patient population, in order to provide an easy-to-use prognostic tool for Stage I NSCLC patients.

Chemical-shift and diffusion-weighted magnetic resonance imaging of thymus in myasthenia gravis: usefulness of quantitative assessment.

OBJECTIVES: The objective of this study was to prospectively investigate the usefulness of chemical-shift and diffusion-weighted (DW) magnetic resonance imaging (MRI) in patients with myasthenia gravis (MG) for distinguishing thymic lymphoid hyperplasia (TLH), normal thymus (NT), and thymoma (THY) by using the signal intensity index (SII) and the apparent diffusion coefficient (ADC). MATERIALS AND METHODS: We examined 87 subjects (44 males, 43 females; range, 15-71 years) with generalized MG and antibodies to the acetylcholine receptor seropositivity who underwent surgery. They were divided into a TLH/NT group (A, 64 patients; TLH, 49; NT, 15) and a THY group (B, 24 patients; nonadvanced THY, 15; advanced THY, 9) on the basis of histological findings. One patient with contemporary findings of TLH and nonadvanced THY at histology was listed in both groups (87 subjects, 88 findings). Chemical-shift MRI (CS-MRI) was performed with dual-echo acquisition, and the SII was measured for each subject. Diffusion-weighted MRI was performed at b values of 0, 150, 500, and 800 s/mm, and the ADC value was obtained on the ADC map after excluding the 0-s/mm b value diffusion weighting. All measures were performed independently by 2 radiologists, and interreader agreement was assessed by calculating the intraclass correlation coefficient. Differences on SII and ADC levels between the groups and subgroups were tested using the Student t test. Logistic regression models were estimated, and discrimination abilities were individuated according to the area under the receiver operating characteristic curve (AUROC). The optimal cut points for the differentiation of the groups and subgroups were obtained by using the Youden index. RESULTS: The interreader agreement was excellent (intraclass correlation coefficient: SII, 0.998; ADC, 0.944). For CS-MRI, the mean (SD) SII value was significantly different between the groups (A, 36.37% [12.60%]; B, -0.06% [3.85%]; P < 0.001). No overlap in indexes was found with sensitivity, specificity, and cut point of 100%, 100%, and 6.37%, respectively. Conversely, the mean SII value was not different between the subgroups of each group (A, P = 0.607; B, P = 0.252). For DW-MRI, the mean (SD) ADC values were significantly different between the groups (A, 1.92 [0.21] × 10·mm/s; B, 1.36 [0.33] × 10 mm/s; P < 0.001) and between the subgroups of group A (TLH, 1.86 [0.17] × 10 mm/s; NT, 2.10 [0.23] × 10 mm/s; P = 0.002), although overlapped values were found. The AUROC of ADC in discriminating TLH/NT from THY was 0.931 (95% confidence interval, 0.863-0.998), and the optimal cut point for this distinction was 1.625 × 10 mm/s (Youden index, J = 0.760) with sensitivity of 96.8% and specificity of 79.2%. For the subgroups of group A, the AUROC of ADC in discriminating NT from TLH was 0.794 (95% confidence interval, 0.666-0.923), and the optimal cut point for this distinction was 2.01 × 10 mm/s (Youden index, J = 0.458) with sensitivity of 66.7% and specificity of 79.2%. CONCLUSIONS: CS-MRI and DW-MRI are both useful tools for examining patients with MG. The SII is more accurate than the ADC to differentiate TLH and NT from THY (AUROC, 1.000 and 0.931, respectively). Furthermore, the ADC is a noninvasive parameter that could be used for distinguishing TLH from NT, which is useful in selecting patients for surgery because, for nonthymomatous MG, acceptable rates of complete stable remission after thymectomy are found in TLH but not in NT.

The prognostic significance of maximum standardized uptake value of primary tumor in surgically treated non-small-cell lung cancer patients: analysis of 413 cases.

BACKGROUND: Integrated PET/CT is widely used in the preoperative staging and prognostic assessment of non-small-cell lung cancer (NSCLC) patients. The aims of this study were to evaluate the prognostic significance of SUVmax of primary tumor in patients undergoing surgical treatment and, in order to minimize technical interferences, to verify whether SUVmax standardized by SUVmax liver or SUVmax blood pool provided additional prognostic information. PATIENTS AND METHODS: A retrospective study of 413 consecutive NSCLC patients undergoing potentially curative surgical resection after PET/CT obtained in the same PET center over a 6-year period. The SUVmax was calculated drawing region of interest around the primitive tumor, the liver, and the aortic arch in PET images. The same procedure was performed for 2 adjacent planes and the average of these measures was considered. RESULTS: Nine patients were considered 30-day postoperative deaths and were excluded from the analysis. At the end of the study, 312 (77.2%) of the 404 patients were alive (median follow-up, 26 months) and 92 had died (median survival, 17 months). At multivariate analysis tumor-node-metastasis stage, primary tumor grading and primary tumor SUVmax (T-SUVmax) were found to be independent prognostic factors, while T-SUVmax/SUVmax blood pool ratio, and T-SUVmax/SUVmax liver ratio were not. CONCLUSIONS: T-SUVmax is an independent predictor for survival in NSCLC patients undergoing surgery and might be helpful in guiding adjuvant treatment strategies. SUVmax of primary tumor normalized by SUV blood pool or SUV liver does not provide additional prognostic information.

Evaluation of integrated positron emission tomography and computed tomography accuracy in detecting lymph node metastasis in patients with adenocarcinoma vs squamous cell carcinoma.

OBJECTIVES: The aim of our study was to analyze the specificity and sensitivity of integrated positron emission tomography and computed tomography (PET/CT) in detecting nodal metastasis according to histology (adenocarcinoma vs squamous cell carcinoma), and to identify the factors related to false-negative findings. METHODS: A retrospective, single-institution review of 353 consecutive patients with suspected or pathologically proven, potentially resectable non-small-cell lung cancer (NSCLC) who had integrated PET/CT scanning at the same centre. Lymph node staging was pathologically confirmed on tissue specimens obtained at mediastinoscopy and/or thoracotomy. Statistical evaluation of PET/CT results was performed on a per-patient and per-nodal-station basis. RESULTS: A total of 2286 nodal stations (1643 mediastinal, 333 hilar and 310 intrapulmonary) were evaluated. Adenocarcinoma was the final diagnosis in 244 patients and squamous carcinoma in 109 patients. Nodes were positive for malignancy in 80 (32.8%) of 244 patients with adenocarcinoma (N1 = 31; N2 = 48 and N3 = 1) and in 32 (29.3%) of 109 with squamous carcinoma (N1 = 21 and N2 = 11). PET/CT in the adenocarcinoma group had a sensitivity, specificity and accuracy of 53.8, 91.5 and 79.1%, and in the squamous cell group, of 87.5, 81.8 and 83.5%, respectively in a per-patient analysis. In the analysis for N2 disease on a per-patient basis, the sensitivity, specificity and accuracy were 38.8, 97.4, and 85.7% for the adenocarcinoma group and 81.8, 91.8 and 90.8% in the squamous cell group. In the adenocarcinoma group, the mean diameter of false-negative lymph nodes was 7 mm (standard deviation [SD] ± 2.5 mm) compared with the diameter of true-positive lymph nodes of 12.5 (SD ± 4 mm; P < 0.00001). In the squamous cell group, the mean diameter of false-negative lymph nodes was 7.4 mm (SD ± 2.8 mm) compared with the diameter of true-positive lymph nodes of 14.7 (SD ± 6 mm; P < 0.005). In the adenocarcinoma group, false-negative lymph nodes were statistically correlated with the presence of vascular invasion and in the squamous cell group only with the maximum standardized uptake value (SUV(max)) < 5.4. CONCLUSIONS: The sensitivity of PET/CT in detecting nodal metastasis in patients with adenocarcinoma is too low to avoid any further invasive staging procedure. Ultrasound-guided needle biopsy or mediastinoscopy is still necessary in staging patients undergoing lung resection for adenocarcinoma.

A suitable system of reconstruction with titanium rib prosthesis after chest wall resection for Ewing sarcoma.

The recent improvements in chemotherapy and surgical resection in Ewing sarcoma (ES) increased the overall survival as well as the importance of chest wall reconstruction. These improvements are in order to avoid asymmetrical growth, functional and cosmetic compromise after surgery. Chest wall reconstruction still remains a big issue in young patients with ES. We present a case of ES of the left chest wall, arising from a rib, in a 14-year-old patient. He was admitted after neoadjuvant chemotherapy and radiotherapy. The patient underwent a chest wall resection of three ribs and a wedge lung resection of the upper lobe followed by chest wall reconstruction with Stratos™ rib titanium prostheses. This new device is suitable for reconstruction after major chest wall resection with good cosmetic and functional results. During the follow-up, there was no evidence of local and distant recurrence, the pain was under control and there were no functional alterations in the chest wall.

Suitable device for thoracoscopic talc poudrage in malignant pleural effusion.

Chemical pleurodesis is widely used in symptomatic patients with malignant pleural effusion to relieve symptoms, prevent fluid recurrence, and improve quality of life. Talc has been repeatedly found to be the most effective sclerosant agent, and thoracoscopic talc poudrage has been found to be the most effective pleurodesis technique. A homogeneous talc distribution on the visceral and parietal pleura helps to achieve complete pleural symphysis. We have recently adopted a new suitable sterile device that delivers talc under low and constant pressure, facilitating uniform coating of the whole pleural surface and avoiding inappropriate deposition of talc clumps.

Air leaks following pulmonary resection for malignancy: risk factors, qualitative and quantitative analysis.

Air leaks are a common complication of pulmonary resection. The aims of this study were to analyze risk factors for postoperative air leak and to evaluate the role of air leak measurement in identifying patients at increased risk for cardiorespiratory morbidity and prolonged air leak. From March to December 2009, 142 consecutive patients underwent pulmonary resection for malignancy and were prospectively followed up. Preoperative and intraoperative risk factors for air leak were evaluated. Air leaks were qualitatively and quantitatively labeled twice daily. There were 52 (36.6%) patients who had an air leak on day 1, and 32 (22.5%) who had an air leak on day 2. Air leak was ≥180 ml/min in 12 (37.5%) of these patients. Independent predictors of air leak on day 2 included type of pulmonary resection, presence of adhesions, and incomplete fissures. Cardiorespiratory morbidity was significantly higher (34.4%) in patients who experienced air leak on day 2 than in those who did not (10.9%) (P=0.002). Nine (75%) out of 12 patients with air leak ≥180 ml/min on day 2 had prolonged air leak (greater than five days) (P=0.0001).

Preoperative intrathoracic lymph node staging in patients with non-small-cell lung cancer: accuracy of integrated positron emission tomography and computed tomography.

OBJECTIVE: To evaluate the accuracy of integrated positron emission tomography with 18F-fluoro-2-deoxy-D-glucose (FDG) and computed tomography (PET/CT) in preoperative intrathoracic lymph node staging in patients with non-small-cell lung cancer (NSCLC) and to ascertain the role of invasive staging in verifying positron emission tomography (PET)/computed tomography (CT) results. METHODS: Retrospective, single institution study of consecutive patients with suspected or pathologically proven, potentially resectable NSCLC undergoing integrated PET/CT scanning in the same PET centre. Lymph node staging was pathologically confirmed on tissue specimens obtained at mediastinoscopy and/or thoracotomy. Statistical evaluation of PET/CT results was performed on a per-patient and per-nodal-station bases. RESULTS: A total of 1001 nodal stations (723 mediastinal, 148 hilar and 130 intrapulmonary) were evaluated in 159 patients. Nodes were positive for malignancy in 48 (30.2%) out of 159 patients (N1=17; N2=30; N3=1) and 71 (7.1%) out of 1001 nodal stations (N1=24; N2=46; N3=1). At univariate analysis, lymph node involvement was significantly associated (p<0.05) with the following primary tumour characteristics: increasing diameter, maximum standardised uptake value >9, central location and presence of vascular invasion. PET/CT staged the disease correctly in 128 out of 159 patients (80.5%), overstaging occurred in nine patients (5.7%) and understaging in 22 patients (13.8%). The overall sensitivity, specificity, positive and negative predictive values, and accuracy of PET/CT for detecting metastatic lymph nodes were 54.2%, 91.9%, 74.3%, 82.3% and 80.5% on a per-patient basis, and 57.7%, 98.5%, 74.5%, 96.8% and 95.6% on per-nodal-station basis. With regard to N2/N3 disease, PET/CT accuracy was 84.9% and 95.3% on a per-patient basis and on per-nodal-station basis, respectively. Referring to nodal size, PET/CT sensitivity to detect malignant involvement was 32.4% (12/37) in nodes <10mm, and 85.3% (29/34) in nodes > or = 10mm. CONCLUSION: Our data show that integrated PET/CT provides high specificity but low sensitivity and accuracy in intrathoracic nodal staging of NSCLC patients and underscore the continued need for surgical staging.