Prognostic factors of recurrence and disease-free survival in radically resected pulmonary carcinoids: a real-world analysis.

Background: Pulmonary carcinoids (PCs) are rare neuroendocrine lung tumors which may recur, thus worsening their otherwise favorable overall prognosis. Aiming to identify patients at risk for recurrence, we examined parameters affecting disease-free survival (DFS). Methods: A retrospective single-center analysis of 82 consecutive patients undergoing curative intent resection for primary PC tumors between 2010 and 2019 was carried out. Kaplan-Meier method was utilized for survival analysis. Independent prognostic factors were determined using multivariable Cox and logistic regression. Results: During the observation period 82 patients, 48 females (58.5%) and 34 males (41.5%) were operated, representing 84 cases of PCs, 56 typical (TCs) (66.7%) and 28 atypical (ACs) (33.3%) carcinoids. Five-year overall survival was 87.5% and 84.7%, 5-year DFS 97.5% and 74.9% (P=0.012) for TCs and ACs, respectively. Recurrences occurred in one patient (1.8%) with TCs and five patients (17.9%) with ACs (P=0.014). Using multivariable Cox regression, tumor size (cm) remained as an independent prognostic factor for reduced DFS (P=0.018). In logistic regression, nodal involvement (P=0.043) and tumor size (cm) (P=0.023) were independently associated with higher risk of recurrence. Age, sex, smoking, location, and Ki-67 index were not independently associated with recurrence or DFS. Conclusions: Recurrence in PCs after complete resection is relatively rare. However, DFS is reduced in ACs compared to TCs. Tumor size (cm) and nodal involvement appear as the most important prognostic factors associated with recurrence in PCs, independent of histologic type.

Resection of a giant mediastinal liposarcoma by median sternotomy with vascular reconstruction-a case report.

Background: Primary mediastinal liposarcoma is a rare malignancy of mesenchymal origin with local aggressive biological behavior which is often diagnosed as an incidental finding without any symptoms. Chemoresistance and low radiosensitivity of these tumors favors surgical resection as the only option for radical treatment. The potential need for extended resections of adjacent structures is not uncommon and could be challenging. Only a limited number of cases with successful vascular reconstruction for the treatment of mediastinal liposarcoma has been reported so far. Case Description: A 69-year-old female patient was admitted to our department with dry cough and a huge mediastinal mass for further investigation and treatment. Based on the results of preoperative examinations a mediastinal liposarcoma was suspected. The tumor was resected through median sternal incision with resection of the pericardium with subsequent mesh replacement and "en bloc" resection of the innominate vein with vascular graft reconstruction. The postoperative course was uneventful. Six months follow-up after surgery showed no signs of local recurrence or dissemination. Conclusions: Extended resection and vascular reconstruction for the surgical treatment of primary mediastinal liposarcoma is often necessary to ensure adequate radicality and to reduce the risk of local recurrence. Therefore, these patients should be treated in high-volume centers with sufficient experience.

Laser ablation-inductively coupled plasma-mass spectrometry analysis reveals differences in chemotherapeutic drug distribution in surgically resected pleural mesothelioma.

AIMS: Pleural mesothelioma (PM) is a highly aggressive thoracic tumour with poor prognosis. Although reduced tissue drug accumulation is one of the key features of platinum (Pt) resistance, little is known about Pt distribution in human PM. METHODS: We assessed Pt levels of blood samples and surgically resected specimens from 25 PM patients who had received neoadjuvant Pt-based chemotherapy (CHT). Pt levels and tissue distributions were measured by laser ablation-inductively coupled plasma-mass spectrometry and correlated with clinicopathological features. RESULTS: In surgically resected PM specimens, mean Pt levels of nontumourous (fibrotic) areas were significantly higher (vs tumourous regions, P = 0.0031). No major heterogeneity of Pt distribution was seen within the tumourous areas. Pt levels correlated neither with the microvessel area nor with apoptosis rate in the tumourous or nontumourous regions. A significant positive correlation was found between serum and both full tissue section and tumourous area mean Pt levels (r = 0.532, P = 0.006, 95% confidence interval [95% CI] 0.161-0.771 and r = 0.415, P = 0.039, 95% CI 0.011-0.702, respectively). Furthermore, a significant negative correlation was detected between serum Pt concentrations and elapsed time from the last cycle of CHT (r = -0.474, P = 0.017, 95% CI -0.738--0.084). Serum Pt levels correlated negatively with overall survival (OS) (P = 0.029). CONCLUSIONS: There are major differences in drug distribution between tumourous and nontumourous areas of PM specimens. Serum Pt levels significantly correlate with full section and tumourous area average Pt levels, elapsed time from the last CHT cycle, and OS. Further studies investigating clinicopathological factors that modulate tissue Pt concentration and distribution are warranted.

Lymph Node Log-Odds Ratio Accurately Defines Prognosis in Resectable Non-Small Cell Lung Cancer.

OBJECTIVES: The ratio of positive and resected lymph nodes (LN ratio) has been shown to be prognostic in non-small cell lung cancer (NSCLC). Contrary to the LN ratio, calculating the LN log-odds ratio (LN-LOR) additionally considers the total number of resected lymph nodes. We aim to evaluate LN-LOR between positive and resected lymph nodes as a prognostic factor in operable NSCLC. METHODS: Patients with NSCLC who underwent curative intent lobectomy treated at two high-volume centers were retrospectively studied. LN-LOR was dichotomized according to impact on OS and further combined with N descriptors and correlated with clinical variables and survival. RESULTS: 944 patients were included. Cut-off analysis revealed that an LN-LOR of -0.34 significantly discriminated patients according to OS (p < 0.001, chi-squared test 41.26). When combined with N1 and N2 descriptors, LN-LOR low risk (median OS not reached and 83 months) and LN-LOR high-risk patients (median OS 50 and 59 months) had similar survival irrespective of the anatomical location of the positive lymph nodes. Multivariable Cox regression analysis revealed that age (HR 1.02, 95% CI 1.001-1.032), sex (male, HR 1.65, 95% CI 1.25-2.19), histological subtype (HR 2.11, 95% CI 1.35-3.29), pathological stage (HR 1.23, 95% CI 1.01-1.45) and LN-LOR risk groups (low risk, HR 0.48, 95% CI 0.32-0.72) were independent prognostic factors for OS. CONCLUSIONS: This retrospective two-center analysis shows that LN-LOR is significantly associated with OS in resectable NSCLC and might better reflect the biological behavior of the disease, regardless of anatomical lymph node locations. This finding may additionally support the value of extensive LN dissection.

Prediction of Postoperative Complications: Ventilatory Efficiency and Rest End-tidal Carbon Dioxide.

BACKGROUND: Cardiopulmonary exercise testing parameters including ventilatory efficiency (VE/VCO2 slope) are used for risk assessment of lung resection candidates. However, many patients are unable or unwilling to undergo exercise. VE/VCO2 slope is closely related to the partial pressure of end-tidal carbon dioxide (PETCO2). We hypothesized PETCO2 at rest predicts postoperative pulmonary complications. METHODS: Consecutive lung resection candidates were included in this prospective multicenter study. Postoperative respiratory complications were assessed from the first 30 postoperative days or from the hospital stay. Student t test or Mann-Whitney U test was used for comparison. Multivariate stepwise logistic regression analysis was used to analyze association with the development of postoperative pulmonary complications. The De Long test was used to compare area under the curve (AUC). Data are summarized as median (interquartile range). RESULTS: Three hundred fifty-three patients were analyzed, of which 59 (17%) developed postoperative pulmonary complications. PETCO2 at rest was significantly lower (27 [24-30] vs 29 [26-32] mm Hg; P < .01) and VE/VCO2 slope during exercise significantly higher (35 [30-40] vs 29 [25-33]; P < .01) in patients who developed postoperative pulmonary complications. Both rest PETCO2 with odds ratio 0.90 (95% confidence interval [CI] 0.83-0.97); P = .01 and VE/VCO2 slope with odds ratio 1.10 (95% CI 1.05-1.16); P < .01 were independently associated with postoperative pulmonary complications by multivariate stepwise logistic regression analysis. There was no significant difference between AUC of both models (rest PETCO2: AUC = 0.79 (95% CI 0.74-0.85); VE/VCO2 slope: AUC = 0.81 (95% CI 0.75-0.86); P = .48). CONCLUSIONS: PETCO2 at rest has similar prognostic utility as VE/VCO2 slope, suggesting rest PETCO2 may be used for postoperative pulmonary complications prediction in lung resection candidates.

Poor ventilatory efficiency during exercise may predict prolonged air leak after pulmonary lobectomy.

Poor ventilatory efficiency, defined as the increase in minute ventilation relative to carbon dioxide production during exercise (VE/VCO2 slope), may be associated with dynamic hyperinflation and thereby promote the development of prolonged air leak (PAL) after lung resection. Consecutive lung lobectomy candidates (n = 96) were recruited for this prospective two-centre study. All subjects underwent pulmonary function tests and cardiopulmonary exercise testing prior to surgery. PAL was defined as the presence of air leaks from the chest tube on the 5th postoperative day and developed in 28 (29%) subjects. Subjects with PAL were not different in terms of age, sex, American Society of Anesthesiologists class, type of surgery (thoracotomy/video-assisted thoracoscopic surgery) and site of surgery (right/left lung; upper/lower lobes). Subjects with PAL had more frequent pleural adhesions (50% vs 21%; P = 0.006) and steeper VE/VCO2 slope (35 ± 7 vs 30 ± 5; P = 0.001). Stepwise logistic regression showed that only the presence of pleural adhesions [odds ratio (OR) 3.9, 95% confidence interval (CI) 1.4-10.9; P = 0.008] and VE/VCO2 slope (OR 1.1, 95% CI 1.0-1.2; P = 0.003) were independently associated with PAL (AUC 0.74, 95% CI 0.62-0.86). We conclude that a high VE/VCO2 slope during exercise may be helpful in identifying patients at greater risk for the development of PAL after lung lobectomy. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT03498352.

Ventilatory Efficiency Identifies Patients Prone to Hypoxemia During One-Lung Ventilation.

OBJECTIVES: One-lung ventilation (OLV) may be complicated by hypoxemia. Ventilatory efficiency, defined as the ratio of minute ventilation to carbon dioxide output (VE/VCO2), is increased with ventilation/perfusion mismatch and pulmonary artery hypertension, both of which may be associated with hypoxemia. Hence, the authors hypothesized increased VE/VCO2 will predict hypoxemia during OLV. DESIGN: Prospective observational study. SETTING: Single-center, university, tertiary care hospital. PARTICIPANTS: The study comprised 50 consecutive lung resection candidates. INTERVENTIONS: All patients underwent cardiopulmonary exercise testing before surgery. Patients who required inspired oxygen fraction (FiO2) ≥0.7 to maintain arterial oxygen (O2) saturation >90% after 30 minutes of OLV were considered to be hypoxemic. The Student t or Mann-Whitney U test were used for comparison of patients who became hypoxemic and those who did not. Multiple regression analysis adjusted for age, sex, and body mass index was used to evaluate which parameters were associated with the VE/VCO2 slope. Data are summarized as mean ± standard deviation. MEASUREMENTS AND MAIN RESULTS: Twenty-four patients (48%) developed hypoxemia. There was no significant difference in age, sex, and body mass index between hypoxemic and nonhypoxemic patients. However, patients with hypoxemia had a significantly higher VE/VCO2 slope (30 ± 5 v 27 ± 4; p = 0.04) with exercise and lower partial pressure of oxygen/FiO2 (129 ± 92 v 168 ± 88; p = 0.01), higher mean positive end-expiratory pressure (6.6 ± 1.5 v 5.6 ± 0.9 cmH2O; p = 0.02), and lower mean pulse oximetry O2 saturation/FiO2 index (127 ± 20 v 174 ± 17; p < 0.01) during OLV. Multiple regression showed VE/VCO2 to be independently associated with the mean pulse oximetry O2 saturation/FiO2 index (b = -0.28; F = 3.1; p = 0.05). CONCLUSIONS: An increased VE/VCO2 slope may predict hypoxemia development in patients who undergo OLV.

Soft tissue metastasis of mediastinal non-functioning paraganglioma with unusual TTF-1 expression: a potential diagnostic pitfall.

Metastatic extra-adrenal paragangliomas are very rare and can represent diagnostic challenges. We report a case of 69-year-old man with a tumor of the right shoulder. Histologic and immunohistochemical examinations confirmed the diagnosis of paraganglioma. Surprisingly, tumor cells were diffusely thyroid transcription factor 1 (TTF-1) positive. Succinate dehydrogenase complex subunit B (SDHB) deficiency has not been detected. Inherited syndromes associated with paragangliomas were ruled out. The primary tumor was identified in the mediastinum. This is the first report of TTF-1 expression in paraganglioma. To avoid misdiagnosis, careful clinical and pathological examination of any tumor with organoid growths pattern is necessary.