The assessment of Dickkopf-1 and Dickkopf-2 protein concentration in different subtypes of non-small cell lung cancer subtypes.

Introduction: Lung cancer is one of the most prevalent cancers worldwide. Dickkopf-1 (DKK-1) and -2 (DKK-2) are important proteins for the regulated Wnt signalling pathway. Alternations in the Wnt pathway are associated with tumour progression. The aim of the study was to analyse the concentration of DKK-1 and DKK-2 in tumour and matched non-tumour (NT) samples of 65 patients with non-small cell lung cancer (NSCLC), including 3 subtypes: adenocarcinoma (AC), squamous cell carcinoma (SCC), and large cell carcinoma (LCC). Material and methods: The protein concentration was measured by enzyme-linked immunosorbent assay (ELISA) in homogenates. Results: The difference between the level of DKK-1 in tumour and NT specimens was not significant for the whole NSCLC group and SCC and LCC subtype, while in AC samples they were significantly higher (p = 0.028). The highest concentration of DKK-1 was found in the advanced NSCLC samples, with the T4 parameter as well as stage III. Significantly decreased DKK-2 concentrations were detected in all NSCLC subtypes (p < 0.05). Moreover, the DKK-2 level was higher in non-smokers than in smokers. The results indicate that concentrations of DKKs were different in relation to subtypes as well as clinical and socio-demographic parameters. The concentration of DKKs could be associated with the progression of NSCLC. Conclusions: We suggest that DKK-1 could play an oncogenic role in AC, while DKK-2 could be a tumour suppressor in all NSCLC subtypes. Dickkopf-1 and DKK-2 proteins could have differential roles in the Wnt signalling pathway, which is important in many cellular processes, such as proliferation and apoptosis.

Comparison of Early Postoperative Diaphragm Muscle Function after Lobectomy via VATS and Open Thoracotomy: A Sonographic Study.

Although a growing body of evidence emphasizes the superiority of VATS over conventional thoracotomy, little is still known about early postoperative diaphragm muscle function after lobectomy via these two approaches. To fill the gap in existing literature, we conducted a comparative study between VATS and conventional thoracotomy in terms of postoperative diaphragm muscle function, assessing its contractility, strength, the magnitude of effort and potential risk of dysfunction such as atrophy and paralysis. A total of 59 patients (30 after VATS), who underwent anatomical pulmonary resection at our institution, were enrolled in this study. The control group consisted of 28 health subjects without medical conditions that could contribute to diaphragm dysfunction. Diaphragm muscle was assessed before and after surgery using ultrasonography. We found that both surgical approaches were associated with postoperative impairment of diaphragm muscle function-compared to baseline data. Postoperative reduction in diaphragm contraction was demonstrated in most of the 59 patients. In the case of the control group, the differences between measurements were not observed. We noted that lobectomy via thoracotomy was linked with a greater percentage of patients with diaphragm paralysis and/or atrophy than VATS. Similar findings were observed in referring to diaphragm magnitude effort, as well as diaphragm contraction strength, where minimally invasive surgery was associated with better diaphragm function parameters-in comparison to thoracotomy. Disturbance of diaphragm work was reported both at the operated and non-operated side. Upper-right and left lobectomy were connected with greater diaphragm function impairment than other segments. In conclusion, the VATS technique seems to be less invasive than conventional thoracotomy providing a better postoperative function of the main respiratory muscle.

Concentration of Secreted Frizzled-Related Proteins (SFRPs) in Non-Small Cell Lung Carcinoma Subtypes-A Preliminary Study.

Non-small cell lung carcinoma (NSCLC) is the most common lung cancer worldwide. Secreted frizzled-related proteins (SFRPs) are important tumour suppressors and antagonists of the Wnt signalling pathway, which is linked with cancer development. The aim of this study was to evaluate the concentrations of SFRP1, SFRP2, and SFRP5 proteins in tumour and non-tumour (NT) samples obtained from 65 patients with primary NSCLC. An enzyme-linked immunosorbent assay (ELISA) was used to measure the concentrations of SFRPs in the tissue homogenates. A significantly lower SFRP2 protein concentration was found in the total NSCLC tumour samples and the following NSCLC subtypes: squamous cell carcinoma (SCC) and adenocarcinoma (AC) (p > 0.05, p = 0.028 and p = 0.001, respectively). AC tumour samples had a higher SFRP1 level than NT samples (p = 0.022), while the highest SFRP1 concentration was found in NSCLC samples from patients with clinical stage T4 cancer. Increased concentrations of SFRP1 and SFRP5 were present in stage III NSCLC samples, while the tumour samples with high pleural invasion (PL2) had an increased level of SFRP2. The results from this study suggest that the tumour suppressor or oncogenic roles of SFRPs could be connected with the NSCLC subtype. The levels of SFRPs varied according to the clinicopathological parameters of NSCLC.

Incidence of Concomitant Neoplastic Diseases, Tumor Characteristics, and the Survival of Patients with Lung Adenocarcinoma or Squamous Cell Lung Carcinoma in Tobacco Smokers and Non-Smokers-10-Year Retrospective Single-Centre Cohort Study.

Changes in smoking trends and changes in lifestyle, together with worldwide data regarding the incidence of lung cancer in the group of patients with no previous history of smoking, leads to consideration of the differences in the course of the disease, the time of cancer diagnosis, the survival rate, and the occurrence of comorbidities in this group of patients. This study aimed to determine the occurrence of non-smokers among patients undergoing anatomical resection of the lung tissue due to lung carcinoma and to investigate the differences between the course of lung cancer, survival, and the comorbidities in the groups of patients with lung cancer depending on the history of tobacco smoking. The study included a cohort of 923 patients who underwent radical anatomical resection of the lung tissue with lung primary adenocarcinoma or squamous cell carcinoma. The Chi2 Pearson's test, the t-test, the Mann-Whitney U test, the Kaplan-Meier method, the Log-rank test with Mantel correction, and the Cox proportional hazard model were used for data analysis. We observed a significantly higher mean age of smoking patients compared to the mean age of non-smoking patients. The coexistence of former neoplastic diseases was significantly more frequent in the group of non-smokers compared to the group of smoking patients. We did not observe differences depending on smoking status in the tumor stage, grade, vascular and pleural involvement status in the diagnostic reports. We did not observe differences in the survival between smokers vs. non-smokers, however, we revealed better survival in the non-smoker women group compared to the non-smoker men group. In conclusion, 22.11% of the patients undergoing radical anatomical resection of the lung tissue due to lung cancers were non-smokers. More research on survival depending on genetic differences and postoperative treatment between smokers and non-smokers is necessary.

Systematic Review and Meta-Analysis of Efficiency and Safety of Double-Lumen Tube and Bronchial Blocker for One-Lung Ventilation.

One-lung ventilation is also used in some thoracic or cardiac surgery, vascular surgery and oesophageal procedures. We conducted a search of the literature for relevant studies in PubMed, Web of Science, Embase, Scopus and Cochrane Library. The final literature search was performed on 10 December 2022. Primary outcomes included the quality of lung collapse. Secondary outcome measures included: the success of the first intubation attempt, malposition rate, time for device placement, lung collapse and adverse events occurrence. Twenty-five studies with 1636 patients were included. Excellent lung collapse among DLT and BB groups was 72.4% vs. 73.4%, respectively (OR = 1.20; 95%CI: 0.84 to 1.72; p = 0.31). The malposition rate was 25.3% vs. 31.9%, respectively (OR = 0.66; 95%CI: 0.49 to 0.88; p = 0.004). The use of DLT compared to BB was associated with a higher risk of hypoxemia (13.5% vs. 6.0%, respectively; OR = 2.27; 95%CI: 1.14 to 4.49; p = 0.02), hoarseness (25.2% vs. 13.0%; OR = 2.30; 95%CI: 1.39 to 3.82; p = 0.001), sore throat (40.3% vs. 23.3%; OR = 2.30; 95%CI: 1.68 to 3.14; p < 0.001), and bronchus/carina injuries (23.2% vs. 8.4%; OR = 3.45; 95%CI: 1.43 to 8.31; p = 0.006). The studies conducted so far on comparing DLT and BB are ambiguous. In the DLT compared to the BB group, the malposition rate was statistically significantly lower, and time to tube placement and lung collapse was shorter. However, the use of DLT compared to BB can be associated with a higher risk of hypoxemia, hoarseness, sore throat and bronchus/carina injuries. Multicenter randomized trials on larger groups of patients are needed to draw definitive conclusions regarding the superiority of any of these devices.

Ninety-Day Mortality of Thoracoscopic vs Open Lobectomy: A Large Multicenter Cohort Study.

BACKGROUND: Studies have demonstrated a lower incidence of complications after video-assisted thoracoscopic surgery (VATS) lobectomy compared with thoracotomy, but the data on in-hospital and 90-day mortality are inconclusive. This study analyzed whether surgical approach, VATS or thoracotomy, was related to early mortality of lobectomy in lung cancer and determined the differences between in-hospital and 90-day mortality. METHODS: Data of all patients with non-small cell lung cancer who underwent lobectomy between January 1, 2007, and July 30, 2018, were retrieved from Polish National Lung Cancer Registry. Included were 31 433 patients who met all study criteria. After propensity score matching, 4946 patients in the VATS group were compared with 4946 patients in the thoracotomy group. RESULTS: Compared with thoracotomy, VATS lobectomy was related to lower in-hospital (1.5% vs 0.9%, P = .004) and 90-day mortality (3.4% vs 1.8%, P < .001). Mortality at 90 days was twice as high as in-hospital mortality in both the VATS (1.8% vs 0.9%, P < .001) and thoracotomy groups (3.4% vs 1.5%, P < .001). Postoperative complications were less common after VATS compared with thoracotomy (23.6% vs 31.8%, P < .001). CONCLUSIONS: VATS lobectomy is associated with lower in-hospital and 90-day mortality compared with thoracotomy and should be recommended for lung cancer treatment, if feasible. Patients should also be closely monitored after discharge from the hospital, because 90-day mortality is significant higher than in-hospital mortality.

Opioid-Free Anaesthesia Effectiveness in Thoracic Surgery-Objective Measurement with a Skin Conductance Algesimeter: A Randomized Controlled Trial.

BACKGROUND: Chest surgery is associated with significant pain, and potent opioid medications are the primary medications used for pain relief. Opioid-free anaesthesia (OFA) combined with regional anaesthesia is promoted as an alternative in patients with an opioid contraindication. METHODS: Objective: To assess the efficacy of OFA combined with a paravertebral block in pain treatment during video-assisted thoracic surgery. DESIGN: A randomized, open-label study. SETTING: A single university hospital between December 2015 and March 2018. PARTICIPANTS: Sixty-six patients scheduled for elective video-assisted thoracic surgery were randomized into two groups. Of these, 16 were subsequently excluded from the analysis. INTERVENTIONS: OFA combined with a paravertebral block with 0.5% bupivacaine in the OFA group; typical general anaesthesia with opioids in the control group. MAIN OUTCOME MEASURES: Intraoperative nociceptive intensity measured with a skin conductance algesimeter (SCA) and traditional intraoperative monitoring. RESULTS: Higher mean blood pressure was observed in the control group before induction and during intubation (p = 0.0189 and p = 0.0095). During chest opening and pleural drainage, higher SCA indications were obtained in the control group (p = 0.0036 and p = 0.0253), while in the OFA group, the SCA values were higher during intubation (p = 0.0325). SCA during surgery showed more stable values in the OFA group. Pearson analysis revealed a positive correlation between the SCA indications and mean blood pressure in both groups. CONCLUSIONS: OFA combined with a paravertebral block provides effective nociception control during video-assisted thoracic surgery and can be an alternative for general anaesthesia with opioids. OFA provides a stable nociception response during general anaesthesia, as measured by SCA.

Thoracic surgery may alter body static balance via diaphragm dysfunction.

Many diseases and conditions can alter an ability to maintain body balance. The aim of the present study was to investigate whether thoracic surgery may elicit diaphragm dysfunction thereby impairing postural stability. 40 patients qualified to video-assisted thoracoscopy (VATS) lobectomy or lobectomy via thoracotomy due to pulmonary carcinoma were examined two times: a day before lung resection and 3-5 days after surgical procedure. Diaphragm assessment was performed using ultrasonography, while postural sways were evaluated by Zebris FDM-S stabilometric platform. Thoracic surgery was associated with decrease of diaphragm thickness and movement, as well as, with deterioration of static body balance maintenance. Upper lobe resection was linked with greater diaphragm excursion restriction and worse body sway parameters than middle and lower lobe resection. VATS lobectomy was associated with better postoperative diaphragm function and better postural sway parameters than lobectomy via thoracotomy. Patients after lobectomy via thoracotomy had significantly more load on lower limb on the operated side than patients after VATS lobectomy. Impairment of diaphragm function is closely associated with equilibrium impairment after pulmonary resection. VATS lobectomy was less invasive than lobectomy via thoracotomy in terms of primary respiratory muscle function and body balance maintenance parameters.

Endosonography and endosonography guided needle aspiration for left adrenal gland assessment in lung cancer patients - 10 years' experience.

INTRODUCTION: Lung cancer patients (LCP) require invasive evaluation of left adrenal glands (LAG) if distant metastases (M1b/1c) are suspected in CT or PET-CT. Only few studies showed utility of endosonography and particularly EUS-b-FNA as minimally invasive endoscopic method of LAG analysis. MATERIAL AND METHODS: A retrospective study of consecutive LCP was conducted in two pulmonology centers between January 2010 and December 2019. Records of complete endosonographic staging with use of single ultrasound bronchoscope or two scopes were overviewed. The analysis included cases of enlarged LAG (body size or limbs > 10 mm) examined and sampled by EUS-b-FNA or EUS-FNA. RESULTS: 142 of 2596 LCP staged by complete endosonography (M: 88, F: 54 mean age 64.7) had enlarged LAG, which were biopsied by conventional EUS-FNA (52) and/or by EUS-b-FNA (90). Strong correlation with gland diameter (P < 0.001) was observed. The incidence of LAG metastases in analyzed group was 52.1% (74/142) and regarding histology: SCLC 76.9% (10/13), adenocarcinoma 66.7% (44/66), NSCLC 56.3% (9/16) and SCC 17.5% (7/40). A specificity and PPV for both methods were 100%. A sensitivity, accuracy and NPV for EUS-FNA were 91.7%, 96.2%, 93.3% and for EUS-b-FNA 88%, 93.3% and 87%, respectively and no significant differences for both methods were noted (P = 0.62, 0.44, 0.35). No severe complications afterall biopsies were observed. A six months clinical follow up included all negative LCP with enlarged LAG. CONCLUSIONS: After our study EUS-b-FNA seems to be a reasonable method of choice for LAG assesssment in LCP.

The bone microstructure from anterior cruciate ligament footprints is similar after ligament reconstruction and does not affect long-term outcomes.

PURPOSE: The purpose of this study was to assess the quality of the bone tissue microstructure from the footprints of the anterior cruciate ligament (ACL) and its impact on late follow-up outcomes in patients who undergo anterior cruciate ligament reconstruction (ACLR). METHODS: The records of 26 patients diagnosed with a completely torn ACL who underwent ACLR were collected. During the surgery performed using the Felmet method, bone blocks from the native ACL footprints were collected. The primary measurements of the bone microstructure were made using a microtomographic scanner. In late follow-up examinations, a GNRB arthrometer was used. RESULTS: There was no significant difference in the bone microstructure assessed using micro-CT histomorphometric data according to the blood test results, plain radiographs, age or anthropometric data. There was no difference in the bone volume/total volume ratio or trabecular thickness in the area of the native ACL footprints. Routine preoperative examinations were not relevant to the quality of the bone microstructure. The elapsed time from an ACL injury to surgery had no relevance to the results of arthrometry. CONCLUSION: The similarities in the microstructure of bone blocks from ACL footprints from the femur and tibia allow the variable use of these blocks to stabilize grafts in the Felmet method. The bone microstructure is not dependent on the time from injury to surgery. Histomorphometric values of the structure of the femoral and tibial ACL footprints have no impact on the long-term stability of the operated knee joint. TRIAL REGISTRATION: The approval of the Bioethics Committee of the Silesian Medical Chamber in Katowice, Poland (resolution 16/2014) was given for this research. LEVEL OF EVIDENCE: II.

Ultrasound predictors of left adrenal metastasis in patients with lung cancer: a comparison of computed tomography, positron emission tomography-computed tomography, and endoscopic ultrasound using ultrasound bronchoscope.

INTRODUCTION: Patients with resectable lung cancer require invasive evaluation of the enlarged left adrenal gland (LAG). Few studies showed the utility of endoscopic ultrasound using ultrasound bronchoscope (EUS­B) in LAG assessment. Moreover, little is known on the combination of computed tomography (CT), positron emission tomography-computed tomography (PET­CT), and EUS­B for predicting left adrenal metastasis. PATIENTS AND METHODS: In this retrospective cohort study performed from 2012 to 2019, patients with left adrenal enlargement were evaluated by CT, PET­CT, and EUS­B, followed by complete endoscopic mediastinal staging. The adrenal glands were sampled by EUS­B-guided fine­needle aspiration. Patients were followed for 6 months. RESULTS: During the staging of lung cancer in 2176 patients, 113 enlarged LAGs (5.19%) were biopsied. Malignancy was reported in 51 LAGs (45.13%). Endoscopic ultrasound upstaged 7 patients (6.2%) and downstaged 11 patients (9.37%) after false CT or PET­CT findings. There were no biopsy­related complications. Radiologic predictors of left adrenal metastases had the highest yield at the following cutoff points: Hounsfield units >23, standardized uptake value >4.2, and LAG size >25 mm. Hypoechogenic LAGs with loss of sea­gull shape on EUS­B were associated with a 28.67­fold higher likelihood of metastases. The sensitivity, specificity, accuracy, negative predictive value, and positive predictive value for all ultrasound predictors were 86.21%, 85.45%, 85.84%, 85.45%, and 86.21%, respectively. When combined with radiologic features, the respective values were 93.10%, 94.55%, 93.81%, 92.86%, and 94.74%. CONCLUSIONS: Hypoechogenicity and loss of sea­gull shape on EUS­B are the most reliable predictors of left adrenal metastasis. The combination of CT, PET­CT, and EUS­B improves the noninvasive diagnosis of left adrenal metastases in lung cancer patients.

Comparison of the diagnostic effectiveness between an expert and a student in the diagnosis of sarcoidosis by transbronchial biopsy of mediastinal lymph nodes under the control of endosonography.

INTRODUCTION: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) of mediastinal lymph nodes is currently considered to be the most effective minimally invasive diagnostic method in patients with suspected stage I and II sarcoidosis. However, diagnostic effectiveness depends on the experience and skills of the doctor which is dependent on the number of correctly performed procedures. The aim of the study is to compare the diagnostic effectiveness of the EBUS-TBNA test obtained by an expert in this field vs that of his student. MATERIAL AND METHODS: in patients with a clinical and radiological suspicion of sarcoidosis, EBUS-TBNA procedures were performed by an expert (over 1000 previously performed tests) and by his student who completed basic training (15 procedures performed). In the expert's opinion, the student was experienced enough to perform the EBUS-TBNA on his own. Previously, more than 100 conventional fibreoptic bronchoscopies had been performed by the student. During that time, he had been working in the department of pulmonary diseases and tuberculosis for two years. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+), negative likelihood ratio (LR-), and accuracy of the EBUS-TBNA test in diagnosing sarcoidosis were calculated. Statistical evaluation was made using ROC curves for the expert and for the student. RESULTS: The study included 215 patients between 22-68 years of age with suspected sarcoidosis who were diagnosed between 2013-2016. 124 EBUS-TBNA tests were performed by the expert, and 91 procedures were performed by the student. The presence of sarcoid granulomas was confirmed by a biopsy in 165 (76.7%) patients. In terms of the diagnosis of sarcoidosis, a higher sensitivity and accuracy of the EBUS test was found in the procedures done by the expert (76.7% and 95.3%, respectively) as compared to the results obtained by the student (66.1% and 93.1%, respectively). However, these differences were not statistically significant (p = 0.11). All tests were assessed in a hospital pathology unit, but not necessarily by one person, which may be a limitation of our research. In this study, only cytological smears were taken into consideration. CONCLUSIONS: In the diagnosis of sarcoidosis, the student, after appropriate training by an expert, achieved a comparable level of diagnostic effectiveness with EBUS-TBNA after performing 90 tests independently.

An assessment of the effectiveness of regional analgesia after VATS measured by an objective method for assessing testosterone, cortisol, α-amylase, sIgA, and ß-endorphin levels - a randomised controlled trial.

INTRODUCTION: Thoracic surgeries are associated with intense postoperative pain. General opioid analgesia is still the main anaesthetic method. Due to the large number of opioid-induced side effects, alternative methods of pain relief are sought. One of them is the use of balanced analgesia, which consists of regional analgesia, non-opioid painkillers, and small doses of opioids. MATERIAL AND METHODS: The objective of this study was to assess the effectiveness of preoperative thoracic paravertebral block (ThPVB) in the treatment of postoperative pain after video-assisted thoracic surgery (VATS) by measuring hormone levels in blood serum or saliva. It was a randomised, open-label study conducted in a single university hospital setting between May 2018 and September 2019. In total, 119 patients were scheduled for elective video-assisted thoracic surgery. Performed interventions included: preoperative thoracic paravertebral block with 0.5% bupivacaine, followed by postoperative oxycodone combined with nonopioid analgesics. Follow-up period comprised first 24 hours and one, two, and six months after surgery. Main outcomes were measured by pain intensity assessed using the Numerical Rating Scale (NRS) and the levels of the following hormones: testosterone, cortisol, α-amylase activity, sIgA, and ß-endorphin. RESULTS: A total of 119 patients were randomised into two groups and, of these, 49 were subsequently excluded from the analysis. The final analysis included 37 patients from the study group and 33 from the control group. There were no statistically significant differences in the analysed parameters the relative change T1-T0. There was a tendency towards statistical significance in the relative change T2-T0 in testosterone levels. At rest, no statistically significant differences were found between groups and time in the percentage of patients with NRS ≥ 1. During cough, the percentage of patients with NRS ≥ 1 was higher at T1 and T2 time points in the ThPVB group. Of the factors considered, only α-amylase levels statistically significantly increased the chance for higher NRS score after a month [OR = 1.013; 95% PU: 1.001-1.025; p < 0.01]. CONCLUSIONS: ThPVB is effective and safe for patients undergoing VATS. It can be an effective alternative for general anaesthesia using high doses of opioids.

Prospective Evaluation of the NETest as a Liquid Biopsy for Gastroenteropancreatic and Bronchopulmonary Neuroendocrine Tumors: An ENETS Center of Excellence Experience.

BACKGROUND: There is a substantial unmet clinical need for an accurate and effective blood biomarker for neuroendocrine neoplasms (NEN). We therefore evaluated, under real-world conditions in an ENETS Center of Excellence (CoE), the clinical utility of the NETest as a liquid biopsy and compared its utility with chromogranin A (CgA) measurement. METHODS: The cohorts were: gastroenteropancreatic NEN (GEP-NEN; n = 253), bronchopulmonary NEN (BPNEN; n = 64), thymic NEN (n = 1), colon cancer (n = 37), non-small-cell lung cancer (NSCLC; n = 63), benign lung disease (n = 59), and controls (n = 86). In the GEPNEN group, 164 (65%) had image-positive disease (IPD, n = 135) or were image-negative but resection-margin/biopsy-positive (n = 29), and were graded as G1 (n = 106), G2 (n = 49), G3 (n = 7), or no data (n = 2). The remainder (n = 71) had no evidence of disease (NED). In the BPNEN group, 43/64 (67%) had IPD. Histology revealed typical carcinoids (TC, n = 14), atypical carcinoids (AC, n = 14), small-cell lung cancer (SCLC, n = 11), and large-cell neuroendocrine carcinoma (LCNEC, n = 4). Disease status (stable or progressive) was evaluated according to RECIST v1.1. Blood sampling involved NETest (n = 563) and NETest/CgA analysis matched samples (n = 178). NETest was performed by PCR (on a scale of 0-100), with a score ≥20 reflecting a disease-positive status and >40 reflecting progressive disease. CgA positivity was determined by ELISA. Samples were deidentified and measurements blinded. The Kruskal-Wallis, Mann-Whitney U, and McNemar tests, and the area under the curve (AUC) of the receiver-operating characteristics (ROC) were used in the statistical analysis. RESULTS: In the GEPNEN group, NETest was significantly higher (34.4 ± 1.8, p < 0.0001) in disease-positive patients than in patients with NED (10.5 ± 1, p < 0.0001), colon cancer patients (18 ± 4, p < 0.0004), and controls (7 ± 0.5, p < 0.0001). Sensitivity for detecting disease compared to controls was 89% and specificity was 94%. NETest levels were increased in G2 vs. G1 (39 ± 3 vs. 32 ± 2, p = 0.02) and correlated with stage (localized: 26 ± 2 vs. regional/distant: 40 ± 3, p = 0.0002) and progression (55 ± 5 vs. 34 ± 2 in stable disease, p = 0.0005). In the BPNEN group, diagnostic sensitivity was 100% and levels were significantly higher in patients with bronchopulmonary carcinoids (BPC; 30 ± 1.3) who had IPD than in controls (7 ± 0.5, p < 0.0001), patients with NED (24.1 ± 1.3, p < 0.005), and NSCLC patients (17 ± 3, p = 0.0001). NETest levels were higher in patients with poorly differentiated BPNEN (LCNEC + SCLC; 59 ± 7) than in those with BPC (30 ± 1.3, p = 0.0005) or progressive disease (57.8 ± 7), compared to those with stable disease (29.4 ± 1, p < 0.0001). The AUC for differentiating disease from controls was 0.87 in the GEPNEN group and 0.99 in BPC patients (p < 0.0001). Matched CgA analysis was performed in 178 patients. In the GEPNEN group (n = 135), NETest was significantly more accurate for detecting disease (99%) than CgA positivity (53%; McNemar test χ2 = 87, p < 0.0001). In the BPNEN group (n = 43), NETest was significantly more accurate for disease detection (100%) than CgA positivity (26%; McNemar's test χ2 = 30, p < 0.0001). CONCLUSIONS: The NETest is an accurate diagnostic for GEPNEN and BPNEN. It exhibits tumor biology correlation with grading, staging, and progression. CgA as a biomarker is significantly less accurate than NETest. The NETest has substantial clinical utility that can facilitate patient management.

Usefulness of combined endobronchial and endoscopic ultrasound-guided needle aspiration in the diagnosis of sarcoidosis: a prospective multicenter trial.

INTRODUCTION: Needle biopsy of enlarged lymph nodes is an accepted method for the diagnostic workup of sarcoidosis, but the optimal endosonography­guided approach is yet to be determined. OBJECTIVES: The aim of our study was to assess the relative diagnostic yield of combined ultrasound­guided needle aspiration (CUS­b­NA), which includes endobronchial ultrasound­guided transbronchial needle aspiration (EBUS­TBNA) with endoscopic ultrasound fine­needle aspiration (EUS­b­FNA), as well as the role of the cell block (CB) technique and lymph node localization in the diagnostic workup of sarcoidosis. PATIENTS AND METHODS: This was a prospective multicenter study including consecutive patients with clinical suspicion of stage I or II sarcoidosis. CUS­b­NA with smears and CB technique were performed in the whole study group. If a biopsy result was not conclusive, an invasive diagnostic workup and a 6-month follow­up were scheduled. RESULTS: Out of 77 screened patients, 54 signed written consent and 50 were enrolled for the final analysis. The overall sensitivity of EBUS­TBNA, EUS­b­FNA, and CUS­b­NA was 76.6%, 70.2%, and 91.7%, respectively. There were no differences between EBUS­TBNA and EUS­b­FNA (P = 0.52) but CUS­b­NA had a higher diagnostic yield (P = 0.005 and P = 0.001, respectively). Adding the CB method to smear technique (P = 0.008) and biopsy of the subcarinal lymph nodes increased the diagnostic yield (P = 0.001).  Conclusions: The diagnostic yield of CUS­b­NA is higher than that of endosonographic techniques alone in the diagnostic workup of stage I and II sarcoidosis. The preparation of cytological material including CB and the choice of the subcarinal lymph node station for the biopsy increase the diagnostic efficacy.

Transbronchial lung cryobiopsy guided by radial mini-probe endobronchial ultrasound in interstitial lung diseases - a multicenter prospective study.

INTRODUCTION: Transbronchial lung cryobiopsy (TBLC) is commonly used in diagnosing interstitial lung diseases (ILDs). Ageneral anesthesia with endotracheal intubation, balloon blockers and fluoroscopy control is the most common modality. Simplifying the procedure without decreasing it's safety could result in wider use. Prospective, observational study was conducted in three Polish pulmonology centers to evaluate safety and diagnostic yield of TBLC under conscious sedation, without intubation and bronchial blockers and with radial-EBUS guidance instead of fluoroscopy. MATERIAL AND METHODS: In patients suspected of ILD, in accordance with high resolution computer tomography (HRCT) selected lung segments were examined with radial-EBUS mini probe without aguide sheath. If the lung infiltrations were visible this locations were preferred. If not, specimens were taken from two different segments of the same lobe. Two to five biopsies with freezing time 5-8 seconds were performed. Moreover ultrasound examination was used to avoid injury of lung vessels. RESULTS: From March 2017 to September 2019 - 114 patients (M: 59, F: 55) of mean (SD) age 54 (14) years were included to the study on the basis of medical history and HRCT. Histopathology was conclusive in 90 (79%) patients and included 16 different diagnoses (sarcoidosis, EAA, COP predominantly). 24 inconclusive biopsies of unclassifiable pulmonary fibrosis were followed up. Complications included five cases (4.4%) of pneumothorax requiring achest tube drainage and aminor and moderate bleeding in few cases. There was no need for use of balloon bronchial blockers. CONCLUSIONS: TBLC under conscious sedation guided by radial EBUS mini-probe is novel, reasonable and safe technique for histological diagnosis of ILDs.

Emphysema affects the number and characteristics of solitary pulmonary nodules identified by chest low-dose computed tomography. A study on screenees with high-risk lung cancer recruited in Upper Silesia.

INTRODUCTION: Chest low-dose computed tomography (LDCT) has recently been proved effective in lung cancer screening. OBJECTIVES: We aimed to assess the association between the occurrence of emphysema and solitary pulmonary nodules (SPNs) in first­round screening with LDCT. PATIENTS AND METHODS: A total of 601 asymptomatic volunteers with a smoking history underwent LDCT; 523 patients were assigned to one of the following groups: E, emphysema without nodules (n = 103); E + N, emphysema with coexisting nodules (n = 96); N, nodules without emphysema (n = 142); and NENN, no nodules and no emphysema (n = 182). The effect of emphysema and demographic factors on the profile of SPNs was assessed. RESULTS: Patients in the E + N group were older than those in the N group (median age, 65 vs 63 years; P = 0.001) and they smoked more (median pack­years, 37.8 vs 32; P = 0.01). Emphysema was detected in 199 of the 523 patients (38%), while nodules, in 238 (45.5%). The number of nodules in the E + N group was 390 (4.1 nodules per patient), and in the N group, 540 (3.8 nodules per patient). Multiple SPNs, of different size and morphology, constituted 93.3% of the nodules in the E + N group. Seven cases of cancer were detected among 238 patients with nodules, and their distribution was similar in the groups with and without emphysema (4.2 per 100 patients in the E + N group and 2.1 per 100 in the N group; P = 0.44). CONCLUSIONS: Emphysema was more frequently associated with multiple SPNs of different morphology among elderly patients with a higher number of smoking pack­years.

Elective lung resection increases spatial QRS-T angle and QTc interval.

BACKGROUND: Lung resection changes intra-thoracic anatomy, which may affect electrocardiographic results. While postoperative cardiac arrhythmias have been recognized after lung resection, no study has documented changes in vectorcardiographic variables in patients undergoing this surgery. The purpose of this study was to analyse changes in spatial QRS-T angle (spQRS-T) and corrected QT interval (QTc) after lung resection. METHODS: Adult patients undergoing elective lung resection under general anaesthesia were studied. The patients were allocated into four groups: those undergoing (1) left lobectomy (LL); (2) left pneumonectomy (LP); (3) right lobectomy (RL); and (4) right pneumonectomy (RP). The spQRS-T angle and QTc interval were measured one day before surgery (baseline) and 24, 48 and 72 h after surgery. RESULTS: Seventy-one adult patients (47 men and 24 women) aged 47-80 (65 ± 7) years were studied. In the study group as a whole, lung resection was associated with significant increases in spQRS-T (p < 0.001) and QTc (p < 0.05 at 24 and 48 h and p < 0.01 at 72 h). The greatest changes were noted in patients undergoing LP. Postoperative atrial fibrillation (AF) was noted in 6.4% of patients studied, in whom the widest spQRS-T angle and the most prolonged QTc intervals were also noted. CONCLUSIONS: Lung resection widens the spQRS-T angle and prolongs the QTc interval, especially in patients undergoing LP. While postoperative AF was a relatively rare complication after lung resection in this study, it was associated with the widest spQRS-T angles and most prolonged QTc intervals.

NETest Liquid Biopsy Is Diagnostic of Lung Neuroendocrine Tumors and Identifies Progressive Disease.

BACKGROUND: There are no effective biomarkers for the management of bronchopulmonary carcinoids (BPC). We examined the utility of a neuroendocrine multigene transcript "liquid biopsy" (NETest) in BPC for diagnosis and monitoring of the disease status. AIM: To independently validate the utility of the NETest in diagnosis and management of BPC in a multicenter, multinational, blinded study. MATERIAL AND METHODS: The study cohorts assessed were BPC (n = 99), healthy controls (n = 102), other lung neoplasia (n = 101) including adenocarcinomas (ACC) (n = 41), squamous cell carcinomas (SCC) (n = 37), small-cell lung cancer (SCLC) (n = 16), large-cell neuroendocrine carcinoma (LCNEC) (n = 7), and idiopathic pulmonary fibrosis (IPF) (n = 50). BPC were histologically classified as typical (TC) (n = 62) and atypical carcinoids (AC) (n = 37). BPC disease status determination was based on imaging and RECIST 1.1. NETest diagnostic metrics and disease status accuracy were evaluated. The upper limit of normal (NETest) was 20. Twenty matched tissue-blood pairs were also evaluated. Data are means ± SD. RESULTS: NETest levels were significantly increased in BPC (45 ± 25) versus controls (9 ± 8; p < 0.0001). The area under the ROC curve was 0.96 ± 0.01. Accuracy, sensitivity, and specificity were: 92, 84, and 100%. NETest was also elevated in SCLC (42 ± 32) and LCNEC (28 ± 7). NETest accurately distinguished progressive (61 ± 26) from stable disease (35.5 ± 18; p < 0.0001). In BPC, NETest levels were elevated in metastatic disease irrespective of histology (AC: p < 0.02; TC: p = 0.0006). In nonendocrine lung cancers, ACC (18 ± 21) and SCC (12 ± 11) and benign disease (IPF) (18 ± 25) levels were significantly lower compared to BPC level (p < 0.001). Significant correlations were evident between paired tumor and blood samples for BPC (R: 0.83, p < 0.0001) and SCLC (R: 0.68) but not for SCC and ACC (R: 0.25-0.31). CONCLUSIONS: Elevated -NETest levels are indicative of lung neuroendocrine neoplasia. NETest levels correlate with tumor tissue and imaging and accurately define clinical progression.