Comparison of peripheral blood saturation with brain oxygenation in patients undergoing thoracic surgery.

Introduction: Near-infrared spectroscopy (NIRS) is a non-invasive method of regional tissue oxygenation measurement. Intraoperative use of NIRS to monitor brain oxygenation (BO) during surgery might be beneficial to identify cerebral desaturations. Aim: To compare peripheral blood saturation (SpO2) with BO measurements and evaluate the utility of BO in thoracic surgery. Material and methods: We took BO and SpO2 measurements in a group of 100 patients undergoing standard thoracic surgery. Measurements were made every 15 minutes. The Mann-Whitney U test was used to compare study groups. Spearman's rank correlation coefficient was used to determine correlation between studied parameters. Results: We found a negative correlation between patients' age and BO at the beginning of surgery. Operations lasted between 30 and 200 minutes. We found a positive correlation between BO and SpO2 between 15 and 90 minutes of surgery. Subsequently, BO remained at a low level while SpO2 returned to baseline values. Higher minimum SpO2 values were noted in patients undergoing left-sided procedures. Conclusions: Cerebral oxygenation does not return to baseline values until the end of the surgery as opposed to the SpO2. Furthermore, both SpO2 and BO correlate negatively with the overall duration of thoracic surgery. In addition, after 90 minutes of surgery, SpO2 stopped reflecting brain oxygenation.

Defining a natural killer cell-enriched molecular rejection-like state in lung transplant transbronchial biopsies.

In lung transplantation, antibody-mediated rejection (AMR) diagnosed using the International Society for Heart and Lung Transplantation criteria is uncommon compared with other organs, and previous studies failed to find molecular AMR (ABMR) in lung biopsies. However, understanding of ABMR has changed with the recognition that ABMR in kidney transplants is often donor-specific antibody (DSA)-negative and associated with natural killer (NK) cell transcripts. We therefore searched for a similar molecular ABMR-like state in transbronchial biopsies using gene expression microarray results from the INTERLUNG study (#NCT02812290). After optimizing rejection-selective transcript sets in a training set (N = 488), the resulting algorithms separated an NK cell-enriched molecular rejection-like state (NKRL) from T cell-mediated rejection (TCMR)/Mixed in a test set (N = 488). Applying this approach to all 896 transbronchial biopsies distinguished 3 groups: no rejection, TCMR/Mixed, and NKRL. Like TCMR/Mixed, NKRL had increased expression of all-rejection transcripts, but NKRL had increased expression of NK cell transcripts, whereas TCMR/Mixed had increased effector T cell and activated macrophage transcripts. NKRL was usually DSA-negative and not recognized as AMR clinically. TCMR/Mixed was associated with chronic lung allograft dysfunction, reduced one-second forced expiratory volume at the time of biopsy, and short-term graft failure, but NKRL was not. Thus, some lung transplants manifest a molecular state similar to DSA-negative ABMR in kidney and heart transplants, but its clinical significance must be established.

Arterial sleeve lobectomy for lung cancer invading chest wall.

Lung cancer is a leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) is a predominant subtype and treatment may include immunotherapy, radiotherapy, chemotherapy, and surgery. Tumors of bigger size infiltrating large bronchi and vessels require more invasive resection such as pneumonectomy. To save lung parenchyma, sleeve lobectomy can be performed in certain patients.We report the case of a patient with NSCLC infiltrating the chest wall who underwent arterial sleeve lobectomy with rib resection. Furthermore, we discuss other surgical treatment strategies.A 58-year-old female patient was admitted to the hospital in 2020 with pain in her left posterolateral chest. Radiological imaging revealed a tumor (5.0×3.5×4.8 cm) in the top of the left lung, infiltrating pulmonary artery and ribs. Therefore, left upper sleeve lobectomy together with resection of rib blocks II to V was performed. The surgery was uncomplicated, but a few weeks postoperatively, the patient experienced repeated episodes of consciousness disturbances. Contrast CT revealed a cerebral malformation in the patient who died 3.5 months after surgery.Sleeve lobectomy can be safely performed in patients with lung tumors infiltrating larger bronchi and vessels who would not tolerate pneumonectomy.

Lung transplantation in patients with a history of anatomical native lung resection.

OBJECTIVES: History of anatomical lung resection complicates lung transplantation (LTx). Our aim was to identify indications, intraoperative approach and outcome in these challenging cases in a retrospective multicentre cohort analysis. METHODS: Members of the ESTS Lung Transplantation Working Group were invited to submit data on patients undergoing LTx after a previous anatomical native lung resection between January 2005 and July 2020. The primary end point was overall survival (Kaplan-Meier estimation). RESULTS: Out of 2690 patients at 7 European centres, 26 (1%) patients (14 males; median age 33 years) underwent LTx after a previous anatomical lung resection. The median time from previous lung resection to LTx was 12 years. The most common indications for lung resection were infections (n = 17), emphysema (n = 5), lung tumour (n = 2) and others (n = 2). Bronchiectasis (cystic fibrosis or non-cystic fibrosis related) was the main indication for LTx (n = 21), followed by COPD (n = 5). Two patients with a previous pneumonectomy underwent contralateral single LTx and 1 patient with a previous lobectomy had ipsilateral single LTx. The remaining 23 patients underwent bilateral LTx. Clamshell incision was performed in 12 (46%) patients. Moreover, LTx was possible without extracorporeal life support in 13 (50%) patients. 90-Day mortality was 8% (n = 2) and the median survival was 8.7 years. CONCLUSIONS: The history of anatomical lung resection is rare in LTx candidates. The majority of patients are young and diagnosed with bronchiectasis. Although the numbers were limited, survival after LTx in patients with previous anatomical lung resection, including pneumonectomy, is comparable to reported conventional LTx for bronchiectasis.

Right Heart Echocardiography Parameters and Other Predictors to Evaluate Mechanical Cardiac Support Necessity During Lung Transplantation.

BACKGROUND: Lung transplantation (LuTx) is a challenge when right heart function fails. Mechanical circulatory support (MCS) is then necessary. METHODS: We aimed to investigate whether preoperative transthoracic echocardiography (TTE) can predict MCS use and help to exclude the sickest patients. Between 2011 and 2018, 52 patients at our institution received LuTx and qualified for this study: 35 bilateral, 16 single, 1 lobar [1] and 1 retransplantation procedure. Of these, 22 were operated using MCS and 30 without MCS. The patients were aged between 18 and 65 years, and 23 were women. The indications were lung fibrosis for 18 patients, chronic obstructive lung disease for 16, cystic fibrosis for 15, primary pulmonary hypertension for 2 and bronchiectasis for 1. TTE was performed up to 30 days before treatment and 1 to 7 days after. RESULTS: Patients undergoing MCS versus patients not undergoing MCS: preoperative right ventricular systolic pressure 56.5 (30) vs 37.8 (11.5) mm Hg (P = .03); tricuspid regurgitation pressure gradient 48.7 (27) vs 30.2 (10.8) mm Hg (P = .015); tricuspid annular plane systolic excursion 17.8 (4.3) vs 19.9 (2.8) mm Hg (P = .04); pulmonary artery diameter 27.5 (5.2) vs 23.9 (4.1) mm (P = .004); age 41.9 (14.1) vs 54.3 (11.8) years (P = .001). Patients who were Dead versus patients who were alive pulmonary valve acceleration time of 82.8 (24.1) vs 104.9 (27.2) ms (hazard ratio [HR] = 0.959, 95% confidence interval [CI] = 0.923-0.996 per ms, P = .02) and pulmonary artery diameter of 28.9 (5.8) vs 24.4 (4.1) mm HR = 1.225, 95% CI = 1.028-1.460 per 1 mm, P = .016 were predictors of death. CONCLUSIONS: Preoperative TTE parameters: right ventricular systolic pressure, tricuspid regurgitation pressure gradient, tricuspid annular plane systolic excursion, and pulmonary artery diameter predicted MCS use during LuTx. Certain values of valve acceleration time and pulmonary artery diameter could help discern LuTx qualification.

Transcripts associated with chronic lung allograft dysfunction in transbronchial biopsies of lung transplants.

Transplanted lungs suffer worse outcomes than other organ transplants with many developing chronic lung allograft dysfunction (CLAD), diagnosed by physiologic changes. Histology of transbronchial biopsies (TBB) yields little insight, and the molecular basis of CLAD is not defined. We hypothesized that gene expression in TBBs would reveal the nature of CLAD and distinguish CLAD from changes due simply to time posttransplant. Whole-genome mRNA profiling was performed with microarrays in 498 prospectively collected TBBs from the INTERLUNG study, 90 diagnosed as CLAD. Time was associated with increased expression of inflammation genes, for example, CD1E and immunoglobulins. After correcting for time, CLAD manifested not as inflammation but as parenchymal response-to-wounding, with increased expression of genes such as HIF1A, SERPINE2, and IGF1 that are increased in many injury and disease states and cancers, associated with development, angiogenesis, and epithelial response-to-wounding in pathway analysis. Fibrillar collagen genes were increased in CLAD, indicating matrix changes, and normal transcripts were decreased-dedifferentiation. Gene-based classifiers predicted CLAD with AUC 0.70 (no time-correction) and 0.87 (time-corrected). CLAD related gene sets and classifiers were strongly prognostic for graft failure and correlated with CLAD stage. Thus, in TBBs, molecular changes indicate that CLAD primarily reflects severe parenchymal injury-induced changes and dedifferentiation.

Central, peripheral ECMO or CPB? Comparsion between circulatory support methods used during lung transplantation.

BACKGROUND: Chronic obstructive pulmonary disease, cystic fibrosis and usual interstitial pneumonia are three most common indications for lung transplantation (LuTx) in Poland. As a result of irreversible destruction of pulmonary parenchyma and extended respiratory insufficiency that appear afterwards, it is crucial to estimate the reserve of gas exchange in each lung before and during surgery. Altering conditions of gas exchange require adaptation in circulatory system as well. In some of the cases the use of extracorporeal life support appears to be necessary to undergo the transplantation successfully. Cardiopulmonary bypass (CPB) or extracorporeal membrane oxygenation (ECMO) used during operation allow to replace the function of heart and lung, but they are also related to complications in the form of acute kidney failure, bleeding, heart arrhythmias or thromboembolic complications. METHODS: We reviewed 77 LuTx from 2009 to 2020 performed at the Department of Thoracic Surgery and Transplantation. 40/77 (51%) patients required intraoperative extracorporeal assistance: 8 required CBP and 32 required ECMO. In the ECMO group 14/32 (44%) patients had peripheral cannulation and 18/32 (56%) had central one. We have calculated the survival rates and reviewed postoperative complications after lung transplantations. Cumulative Kaplan-Meier survival curves were calculated. Differences between the groups were evaluated by the Chi- square analysis for discontinuous variables and t-test for continuous variables. RESULTS: The use of intraoperative central extracorporeal membrane oxygenator was associated with increased survival rates comparing to patients without external support (30-days, 1-year, 3-years, 5-years rates: 78%, 66%, 66%, 66% vs 83%, 65%, 59%, 44% respectively). Furthermore, survival was enhanced comparing to peripheral ECMO or cardiopulmonary bypass as well (50%, 41%, 41%, 33%; 75%, 50%, 50%, 38% respectively). Acute kidney injury and thromboembolic complications occurred statistically more often in case of patients that underwent lung transplantation with support devices (p = 0.005, p = 0.02 respectively). Frequency of other complications was comparable among groups. CONCLUSIONS: The use of central extracorporeal membrane oxygenation should be favorized over peripheral cannulation or cardiopulmonary bypass. CPB should be no longer used during LuTx. Trial registration Not applicable.

Lung Cancer Occurrence-Correlation with Serum Chromium Levels and Genotypes.

Lung cancer is the leading cause of cancer-related death worldwide. Exposure to environmental and occupational carcinogens is an important cause of lung cancer. One of these substances is chromium, which is found ubiquitously across the planet. The International Agency for Research on Cancer has classified chromium(VI) as a human carcinogen. The aim of this study was to assess whether serum chromium levels, as well as DNA variants in selected genes involved in carcinogenesis, xenobiotic-metabolism, and oxidative stress could be helpful in the detection of lung cancer. We conducted a study using 218 lung cancer patients and 218 matched healthy controls. We measured serum chromium levels and genotyped ten genetic variants in ERCC2, XRCC1, MT1B, GSTP1, ABCB1, NQ01, CRTC3, GPX1, SOD2 and CAT. The odds ratios of being diagnosed with lung cancer were calculated using conditional logistic regression with respect to serum chromium level and genotypes. The odds ratio for the occurrence of lung cancer increased with increasing serum chromium levels. The difference between the quartiles with the lowest vs. highest chromium level was more than fourfold in the entire group (OR 4.52, CI 2.17-9.42, p < 0.01). This correlation was significantly increased by more than twice when specific genotypes were taken into consideration (ERCC-rs12181 TT, OR 12.34, CI 1.17-130.01, p = 0.04; CRTC3-rs12915189 non GG, OR 9.73, CI 1.58-60.10, p = 0.01; GSTP1-rs1695 non AA, OR 9.47, CI 2.06-43.49, p = < 0.01; CAT-rs1001179 non CC, OR 9.18, CI 1.64-51.24, p = 0.01). Total serum chromium levels > 0.1 µg/L were correlated with 73% (52/71) of lung cancers diagnosed with stage I disease. Our findings support the role of chromium and the influence of key proteins on lung cancer burden in the general population.

Blood cadmium levels as a marker for early lung cancer detection.

BACKGROUND: We assessed whether blood cadmium levels were associated with incident lung cancer and could be used in the context of a screening program for early-stage lung cancer. MATERIAL AND METHODS: We measured blood cadmium levels among 205 lung cancer patients and 205 matched controls. Cases and controls were matched for sex, age and smoking history (total pack-years, years since cessation for former smokers). RESULTS: The odds ratio for those in the highest quartile of cadmium level (versus lowest) was four-fold (OR = 4.41, 95 % CI:2.01-9.67, p < 0.01). The association was present in former smokers (OR = 16.8, 95 % CI:3.96-71.2, p < 0.01), but not in current smokers (OR = 1.23, 95 % CI: 0.34-4.38) or in never smokers (OR not defined). Among former smokers, the association was present in both early- and late-stage lung cancer. CONCLUSION: Blood cadmium levels may be a marker to help with the early detection of lung cancer among former smokers.

Rare indications for a lung transplant. A European Society of Thoracic Surgeons survey.

OBJECTIVES: The European Society of Thoracic Surgeons Lung Transplantation Working Group promoted a survey to evaluate overall survival in a large cohort of patients receiving lung transplants for rare pulmonary diseases. METHODS: We conducted a retrospective multicentre study. The primary end point was overall survival; secondary end points were survival of patients with the most common diagnoses in the context of rare pulmonary diseases and chronic lung allograft dysfunction (CLAD)-free survival. Finally, we analysed risk factors for overall survival and CLAD-free survival. RESULTS: Clinical records of 674 patients were extracted and collected from 13 lung transplant centres; diagnoses included 46 rare pulmonary diseases. Patients were followed for a median of 3.1 years. The median survival after a lung transplant was 8.5 years. The median CLAD-free survival was 8 years. The multivariable analysis for mortality identified CLAD as a strong negative predictor [hazard ratio (HR) 6.73)], whereas induction therapy was a protective factor (HR 0.68). The multivariable analysis for CLAD occurrence identified induction therapy as a protective factor (HR 0.51). When we stratified patients by CLAD occurrence in a Kaplan-Meier plot, the survival curves diverged significantly (log-rank test: P < 0.001). Patients with rare diseases who received transplants had chronic rejection rates similar to those of the general population who received transplants. CONCLUSIONS: We observed that overall survival and CLAD-free survival were excellent. We support the practice of allocating lungs to patients with rare pulmonary diseases because a lung transplant is both effective and ethically acceptable.

Molecular T-cell‒mediated rejection in transbronchial and mucosal lung transplant biopsies is associated with future risk of graft loss.

BACKGROUND: We previously developed molecular assessment systems for lung transplant transbronchial biopsies (TBBs) with high surfactant and bronchial mucosal biopsies, identifying T-cell‒mediated rejection (TCMR) on the basis of the expression of rejection-associated transcripts, but the relationship of rejection to graft loss is unknown. This study aimed to develop molecular assessments for TBBs and mucosal biopsies and to establish the impact of molecular TCMR on graft survival. METHODS: We used microarrays and machine learning to assign TCMR scores to an expanded cohort of 457 TBBs (367 high surfactant plus 90 low surfactant) and 314 mucosal biopsies. We tested the score agreement between TBB-TBB, mucosal-mucosal, and TBB-mucosal biopsy pairs in the same patient. We also assessed the association of molecular TCMR scores with graft loss (death or retransplantation) and compared it with the prognostic associations for histology and donor-specific antibodies. RESULTS: The molecular TCMR scores assigned in all the TBBs performed similarly to those in high-surfactant TBBs, indicating that variation in alveolation in TBBs does not prevent the detection of TCMR. Mucosal biopsy pieces showed less piece-to-piece variation than TBBs. TCMR scores in TBBs agreed with those in mucosal biopsies. In both TBBs and mucosal biopsies, molecular TCMR was associated with graft loss, whereas histologic rejection and donor-specific antibodies were not. CONCLUSIONS: Molecular TCMR can be detected in TBBs regardless of surfactant and in mucosal biopsies, which show less variability in the sampled tissue than TBBs. On the basis of these findings, molecular TCMR appears to be an important predictor of the risk of future graft failure. TRIAL REGISTRATION: ClinicalTrials.gov NCT02812290.

Influence of the selenium level on overall survival in lung cancer.

BACKGROUND: Although the results of studies in populations with low selenium status indicate an inverse correlation between body selenium levels and the risk of the lung cancer, the effect of this microelement on survival has not been studied. MATERIALS AND METHODS: We performed a prospective study of 302 patients diagnosed with lung cancer in Szczecin, Poland. Selenium concentration in serum was measured at the time of diagnosis and before treatment. All patients were followed for a maximum of 80 months or until death. Vital status was obtained from the Polish National Death Registry. RESULTS: Using Cox proportional hazard analysis, performed for all individuals with lung cancer, the hazard ratio (HR) for death from all causes was 1.25 (95% CI: 0.86-1.83, P = 0.99) for patients in the lowest tertile compared to those in the highest tertile of serum selenium levels. Among the patients with stage I disease this relationship was significant (HR-2.73; P = 0.01) for selenium level in tertile 1 (<57 µg/L) compared to tertile 3 (>69 µg/L, reference). The 80 months crude survival after diagnosis was 79.5% (95% CI: 68.5-92.4%) for individuals in the highest tertile and 58.1% (95% CI: 45.1-74.9%) for individuals in the lowest tertile with stage I lung cancer. CONCLUSION: These results suggest that in patients undergoing treatment for stage I lung cancer, serum selenium levels at the time of diagnosis (>69 µg/L) may be associated with improved overall survival.

Prognostic Factors in Early-stage NSCLC: Analysis of the Placebo Group in the MAGRIT Study.

BACKGROUND/AIM: The analysis of prognostic factors is important to identify determinants of disease-free survival (DFS) and overall survival (OS) in resected non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We examined baseline characteristics associated with DFS and OS among 757 patients with resected, histologically proven, MAGE-A3-positive Stage IB-IIIA NSCLC assigned to placebo in the MAGRIT study (NCT00480025). We explored characteristics of NSCLC that could predict DFS and OS using Cox regression models. RESULTS: The multivariate analysis showed that lower nodal stage, the presence of squamous cell carcinoma (SCC), a broader surgical resection in patients with SCC, and being female with non-SCC were significantly associated with longer DFS. Lower nodal stage and smaller tumor size were significantly associated with an improved OS. Compared to Other International, enrollment in East Asia was associated with an improved OS in patients with non-SCC. CONCLUSION: This is the first prognostic factor analysis in NSCLC performed on data from a large prospective study. These results confirm retrospective studies and add that histopathology subtype is a strong determinant of DFS in resected MAGE-A3-positive NSCLC.

Clinicopathological comparison and therapeutic approach to Castleman disease-a case-based review.

Castleman disease (CD) is a rare, B-cell lymphoproliferative disorder affecting lymph nodes and extranodal anatomical locations. Four types of clinical presentations can be distinguished after exclusion of mimics. The first division is into unicentric CD (UCD) and multicentric CD (MCD). MCD is classified further as HHV-8-negative (idiopathic), MCD associated with HHV-8 infection, and POEMS associated MCD. From the histological standpoint, UCD and MCD can be classified as hyaline-vascular (HV), plasma cell (PC), or mixed cellularity (MC) type, with a spectrum of histopathological manifestations. We present clinical and histopathological features and grading of 25 cases of CD classified according to CDCN histological criteria and according to this clinical algorithm, along with outcomes. Here we provide a fine-resolution description of the histological features of CD. We review and discuss the current diagnostic algorithm, grading system, and recently recommended treatment options. In the presented group of 25 patients with CD there were 14 women and 11 men in the age range 15-79 years. UCD was identified in 15 patients and it was most often located in mediastinum. MCD most frequently occurred as generalized lymphadenopathy. The most common type of CD was HV. All patients with UCD underwent complete surgical resection with a positive outcome. Patients with MCD had diagnostic partial surgical excision of the lesions, later followed by different types of treatment (corticosteroids, chemotherapy, radiotherapy, immunomodulatory agents) or 'watch and wait'. In four cases CD was associated with other malignancies (laryngeal cancer, small lymphocytic lymphoma, gallbladder cancer with hepatic metastases, primary squamous cell lung cancer). The accuracy of histopathological examination is essential and re-evaluation has to be performed in case of relapse or unexpected course of CD. Treatment tailored to fit the disease type and severity should follow the novel recommendations, including anti-IL-6 treatment in the case of MCD.

Evaluation of the metabolic response to open and minimally invasive resection of the oesophagus due to oesophageal cancer.

AIM: The aim of this study was to compare the metabolic response in the early postoperative period after radical resection of stage I and II oesophageal cancer applying a minimally invasive procedure and an open procedure involving classical laparotomy and thoracotomy. MATERIAL AND METHODS: Serum concentrations of interleukin 6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), and total serum protein (TP) and leukocyte count (WBC) in blood collected on the day of surgery prior to the procedure (day 0) and on days 1, 2 and 7 after the surgery were measured in two groups of patients undergoing oesophageal resection due to cancer: applying a minimally invasive procedure involving laparoscopy and videothoracoscopy (group A) and applying a classical procedure involving full opening of the chest and abdominal cavity (group B). The study involved a total of 24 patients divided into two groups of 12 patients each. RESULTS: Tumour necrosis factor-α concentration was lower in group A compared to group B on day 0, PCT concentration was lower in group A compared to group B on day 2 after surgery, and on the remaining days TNF-α and PCT concentrations were not statistically different between groups. CONCLUSIONS: Lower concentration of PCT on post-surgery day 2 in the group of patients undergoing minimally invasive oesophageal resection seems to be associated with a smaller perioperative injury. Lower TNF-α concentration in serum collected on day 0 in the group of patients undergoing minimally invasive resection is associated with a lower stage of oesophageal cancer in this group.