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Many lung transplants fail due to chronic lung allograft dysfunction (CLAD). We recently showed that transbronchial biopsies (TBBs) from CLAD patients manifest severe parenchymal injury and dedifferentiation, distinct from time-dependent changes. The present study explored time-selective and CLAD-selective transcripts in mucosal biopsies from the third bronchial bifurcation (3BMBs), compared to those in TBBs.We used genome-wide microarray measurements in 324 3BMBs to identify CLAD-selective changes as well as time-dependent changes and develop a CLAD classifier. CLAD-selective transcripts were identified with linear models for microarray data (limma) and were used to build an ensemble of 12 classifiers to predict CLAD. Hazard models and random forests were then used to predict the risk of graft loss using the CLAD classifier, transcript sets associated with rejection, injury, and time.T cell-mediated rejection and donor-specific antibody were increased in CLAD 3BMBs but most had no rejection. Like TBBs, 3BMBs showed a time-dependent increase in transcripts expressed in inflammatory cells that was not associated with CLAD or survival. Also like TBBs, the CLAD-selective transcripts in 3BMBs reflected severe parenchymal injury and dedifferentiation, not inflammation or rejection. While 3BMBs and TBBs did not overlap in their top 20 CLAD-selective transcripts, many CLAD-selective transcripts were significantly increased in both for example LOXL1, an enzyme controlling matrix remodeling. In Cox models for one-year survival, the 3BMB CLAD-selective transcripts and CLAD classifier predicted graft loss and correlated with CLAD stage. Many 3BMB CLAD-selective transcripts were also increased by injury in kidney transplants and correlated with decreased kidney survival, including LOXL1.Mucosal and transbronchial biopsies from CLAD patients reveal a diffuse molecular injury and dedifferentiation state that impacts prognosis and correlates with the physiologic disturbances. CLAD state in lung transplants shares features with failing kidney transplants, indicating elements shared by the injury responses of distressed organs.

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 e.g. 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.

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.

Introduction: In 2019, new Coronavirus (SARS-CoV-2) has spread around the globe. The virus can replicate in the cells of the lower respiratory tract, causing pneumonia, oedema and hypoxia. In some patients, the disease will progress to acute respiratory distress syndrome (ARDS) which is a life-threatening condition. Lung transplantation (LuTx) might be the only rescue therapy for severe respiratory failure. Additionally, little is known about the impact of SARS-CoV-2 on lung transplant recipients. The purpose of this systematic review is to present current knowledge about lung transplantation as a treatment method for ARDS associated with COVID-19 infection and to summarize information regarding the management of COVID infection in lung transplant recipients. Materials and methods: Literature search through different databases was conducted. Only case report and case series were included. Results: Out of 525 initial results, 16 studies were included in this systematic review. 7 articles presented patients with LuTx as a treatment option for ARDS and 9 presented management of lung recipients infected with COVID-19. A total of 37 patients were included in this systematic review. Discussion: The course of reviewed patients with SARS-CoV-2 infection was similar and lung transplantation should be considered as a treatment of last chance when extracorporeal life support cannot be withdrawn. Further research is still required to assess the impact of new coronavirus on graft function in lung transplant recipients. Currently, the treatment strategy involves immunosuppression modification and supplemental oxygen therapy. However, some patients do not present clinical symptoms.

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.

Introduction: An esophagorespiratory fistula is a pathological communication between the esophagus and respiratory tract. The most common type is a communication with the trachea, while the least common is with lung parenchyma. These fistulas are classified as congenital or acquired while etiology is benign or malignant. Aim: We present a case report of a patient who developed esophagopulmonary fistula several years after gunshot in the right side of the chest. Additionally, we discuss the treatment methods and compare the outcomes with other case studies and analyses from world literature. Case study: A 48-year-old male patient was admitted to the Department of Thoracic Surgery and Transplantation due to bleeding from the respiratory tract. Radiological images revealed a fistula between the esophagus and right lung parenchyma. Furthermore, bronchiectasis in the right lung was found. Tissues of the fistula, right middle and lower lobes were resected. The patient required renewed hospitalization due to pleural empyema. Furthermore, recurrence of the fistula was observed. Results and discussion: Treatment of esophagorespiratory fistula depends on the etiology and location of the pathological communication. Surgery provides the best possible outcomes in patients with a benign fistula. Proximal location requires cervicotomy, while distal location a thoracotomy. In addition, a distal fistula may damage lung parenchyma. Conclusions: A long-term distal fistula may require pulmonary resection, but early diagnosis would help to avoid more invasive procedures. As symptoms are non-specific and benign etiology is not frequent, thorough examination in search of malignancy is required.

Introduction: Single lung transplantation (SLuTx) is a challenging operation for patients with end-stage chronic pulmonary diseases. After surgery, native lung hyperinflation (NLH) and a mediastinal shift may develop, which changes the anatomical position of the lungs and heart and may lead to graft compression. Aim: We present a case report of a patient who developed NLH after SLuTx. We discuss the treatment methods and compare the outcomes with other case reports and analysis from world literature. Case study: A 56-year-old female patient was diagnosed with end-stage chronic obstructive pulmonary disease (FEV1 < 30%) and qualified for right SLuTx. After the procedure, spirometry revealed gradual loss in FEV1. Radiological images confirmed NLH and compression of the graft. Therefore, a native lung pneumonectomy was performed with positive outcomes. Results and discussion: NLH is a known complication of SLuTx. Typically, lung volume reduction surgery is performed to reduce the compression and a pneumonectomy is a rare treatment, even in centres with extensive experience with SLuTx. Conclusions: Despite SLuTx being a common approach in many pulmonary diseases, NLH should be always taken into consideration. Hyperinflation could cause a dangerous loss of respiratory efficiency and require invasive surgeries for lung transplant recipients.

Background Infection is the most common cause of mortality within the first year after lung transplantation (LTx). The management of perioperative antibiotic therapy is a major issue, but little is known about worldwide practices. Methods We sent by email a survey dealing with 5 daily clinical vignettes concerning perioperative antibiotic therapy to 180 LTx centers around the world. The invitation and a weekly reminder were sent to lung transplant specialists for a single consensus answer per center during a 3-month period. Results We received a total of 99 responses from 24 countries, mostly from Western Europe (n = 46) and the USA (n = 34). Systematic screening for bronchial recipient colonization before LTx was mostly performed with sputum samples (72%), regardless of the underlying lung disease. In recipients without colonization, antibiotics with activity against gram-negative bacteria resistant strains (piperacillin / tazobactam, cefepime, ceftazidime, carbapenems) were reported in 72% of the centers, and antibiotics with activity against methicillin-resistant Staphylococcus aureus (mainly vancomycin) were reported in 38% of the centers. For these recipients, the duration of antibiotics reported was 7 days (33%) or less (26%) or stopped when cultures of donor and recipients were reported negatives (12%). In recipients with previous colonization, antibiotics were adapted to the susceptibility of the most resistant strain and given for at least 14 days (67%). Conclusion Practices vary widely around the world, but resistant bacterial strains are mostly targeted even if no colonization occurs. The antibiotic duration reported was longer for colonized recipients.

Lung squamous cell carcinoma (LSCC) remains a leading cause of cancer death with few therapeutic options. We characterized the proteogenomic landscape of LSCC, providing a deeper exposition of LSCC biology with potential therapeutic implications. We identify NSD3 as an alternative driver in FGFR1-amplified tumors and low-p63 tumors overexpressing the therapeutic target survivin. SOX2 is considered undruggable, but our analyses provide rationale for exploring chromatin modifiers such as LSD1 and EZH2 to target SOX2-overexpressing tumors. Our data support complex regulation of metabolic pathways by crosstalk between post-translational modifications including ubiquitylation. Numerous immune-related proteogenomic observations suggest directions for further investigation. Proteogenomic dissection of CDKN2A mutations argue for more nuanced assessment of RB1 protein expression and phosphorylation before declaring CDK4/6 inhibition unsuccessful. Finally, triangulation between LSCC, LUAD, and HNSCC identified both unique and common therapeutic vulnerabilities. These observations and proteogenomics data resources may guide research into the biology and treatment of LSCC.

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 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.

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.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).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.Blood cadmium levels may be a marker to help with the early detection of lung cancer among former smokers.

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 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 = 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.

Chronic lung tissue disease leads to secondary pulmonary hypertension (PH). The conservative treatment has limited possibilities and lung transplantation (LuTx) remains the final treatment solution. This case report presents the natural course of diagnostics and treatment of the patient with idiopatic pulmonary fibrosis and secondary PH, who underwent LuTx.

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.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.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.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.Porównanie odpowiedzi metabolicznej organizmu we wczesnym okresie pooperacyjnym po radykalnej resekcji raka przełyku w stopniu zaawansowania I i II sposobem małoinwazyjnym i sposobem związanym z wykonaniem klasycznych dostępów do jamy brzusznej (laparotomii) i klatki piersiowej (torakotomii).Badano stężenia interleukiny 6 (IL-6), prokalcytoniny (PCT), białka C-reaktywnego (CRP), czynnika martwicy nowotworów α (TNF-α), białka całkowitego (TP) w surowicy oraz liczbę leukocytów (WBC) we krwi pobranej w dniu operacji przed zabiegiem (doba 0) oraz w 1., 2. i 7. dobie pooperacyjnej w dwóch grupach chorych poddanych resekcji przełyku z powodu raka: sposobem małoinwazyjnym z zastosowaniem laparoskopii oraz wideotorakoskopii (grupa A) i sposobem klasycznym – z wykonaniem laparotomii i torakotomii (grupa B). W badaniu wzięło udział łącznie 24 pacjentów podzielonych na dwie równe liczebnie grupy składające się każda z 12 pacjentów.Stężenie TNF-α było mniejsze w grupie A niż w grupie B w dobie 0, stężenie PCT – mniejsze w grupie A niż w grupie B w 2. dobie pooperacyjnej, w pozostałych dobach stężenia TNF-α i PCT w obu grupach nie różniły się statystycznie.Wydaje się, że mniejsze stężenie PCT w 2. dobie pooperacyjnej u pacjentów poddanych resekcji przełyku sposobem małoinwazyjnym wiąże się z mniejszym urazem okołooperacyjnym. Mniejsze stężenie TNF-α u pacjentów poddanych resekcji sposobem małoinwazyjnym w surowicy pobranej w dobie 0 jest związane z mniejszym stopniem zaawansowania raka przełyku w tej grupie.

Konrad Jarosz,1 Bartosz Kubisa,2 Agata Andrzejewska,3 Katarzyna Mrówczyńska,3 Zbigniew Hamerlak,4 Alicja Bartkowska-Śniatkowska5 1Department of Clinical Nursing, Pomeranian Medical University, 2Thoracic Surgery and Transplantation Department, Pomeranian Medical University, 3Anaesthesiology and Intensive Care Department, Pomeranian Medical University, 4Stomatology Department, Pomeranian Medical University, 5Anaesthesiology and Pediatric Intensive Care Department, Poznan University of Medical Sciences, Szczecin, Poland Abstract: Tracheostomy is a routinely done procedure in the setting of intensive care unit (ICU) in patients requiring prolonged mechanical ventilation. There are two ways of making a tracheostomy: an open surgical tracheostomy and percutaneous dilatational tracheostomy. Percutaneous dilatational tracheostomy is associated with fewer complications than open tracheostomy. In this study, we would like to compare both techniques of performing a tracheostomy in ICU patients and to present possible complications, methods of diagnosing and treating and minimizing their risk. Keywords: tracheostomy, percutaneous tracheostomy, percutaneous dilatational tracheostomy, bronchoscopy, surgical tracheostomy, tracheoesophageal fistula, tracheostomy complications

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.

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 ( 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.

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. ispartof: ANTICANCER RESEARCH vol:39 issue:3 pages:1403-1409 ispartof: location:Greece status: published

Purpose The molecular pathogenesis of chronic lung allograft dysfunction (CLAD) is poorly understood. We hypothesized that microarray analysis of TBBs and mucosal biopsies from the third bronchial bifurcation (3BMBs) would provide insight into biological pathways through gene ontology (GO) analysis. Methods We performed gene expression microarray analysis of 498 TBBs and 324 3BMBs from 10 international centers, comparing CLAD+ and CLAD- cases. CLAD was defined per 2019 ISHLT guidelines. Bayes-moderated t-tests were used to identify CLAD-associated genes. We performed GO biological process analysis with CLAD-associated genes with false discovery rate Results In TBBs CLAD-associated GO terms described lung development regulation, injury response, epithelial proliferation, epithelial-mesenchymal transition, and angiogenesis (Fig. 1A). In 3BMBs the GO terms included endocytosis and intracellular trafficking, cell-cell/cell-substrate adhesion, collagen/matrix metabolism, but unlike TBBs included immunity (Fig. 1B). Time correction did not affect transcript associations with CLAD in TBBs but diminished them in 3BMBs. Excluding biopsies with coexistent rejection or infection removed associations in TBBs but strengthened them in 3BMBs even after correcting for time post-transplant. Conclusion In our biopsy set the molecular CLAD phenotype resembles a parenchymal response to wounding that overlaps other pathologies. CLAD-associated molecular changes were independent of time in TBBs but not 3BMBs, suggesting that CLAD is primarily a time dependent airway process involving injury and either adaptive or innate immunity. Unlike TBBs, molecular changes in 3BMBs were identifiable despite coexistent rejection or infection, suggesting this biopsy format may better capture CLAD information.

Lung transplantation is a method useful in such non-malignant end-stage parenchymal and vascular diseases as: chronic obstructive pulmonary disease (COPD), idiopathic interstitial pulmonary fibrosis, cystic fibrosis, or primary pulmonary hypertension. The main aim of this procedure is to extend the patient's lifespan and quality of life. However, the availability of the operation is limited by organ access. In this paper we present the case of a 58-year-old female in the fourth stage of COPD, who was classified to have a single lung transplantation. Because of some technical problems it was decided to transplant a left donor lung in the right recipient lung locus. Positive cross match was demonstrated retrospectively, and we applied five courses of plasmapheresis. Human immunoglobulin and rituximab treatment were performed to decrease the impact of lymphocytotoxic antibodies. The patient survived 498 days after transplantation, 271 in the hospital.

To explore the biology of lung adenocarcinoma (LUAD) and identify new therapeutic opportunities, we performed comprehensive proteogenomic characterization of 110 tumors and 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, and acetylproteomics. Multi-omics clustering revealed four subgroups defined by key driver mutations, country, and gender. Proteomic and phosphoproteomic data illuminated biology downstream of copy number aberrations, somatic mutations, and fusions and identified therapeutic vulnerabilities associated with driver events involving KRAS, EGFR, and ALK. Immune subtyping revealed a complex landscape, reinforced the association of STK11 with immune-cold behavior, and underscored a potential immunosuppressive role of neutrophil degranulation. Smoking-associated LUADs showed correlation with other environmental exposure signatures and a field effect in NATs. Matched NATs allowed identification of differentially expressed proteins with potential diagnostic and therapeutic utility. This proteogenomics dataset represents a unique public resource for researchers and clinicians seeking to better understand and treat lung adenocarcinomas.

Primary pulmonary lymphoma accounts only 0,5% of all primary lung neoplasms. Mucosa-associated lymphoid tissue (MALT) lymphoma is a low grade B-cell extranodal lymphoma. It is a quite infrequent entity, however it constitutes from 72% to 90% of all pulmonary lung lymphomas. Long-term stimulation of bronchus-associated lymphoid tissue by antigens, smoking, inflammatory disorders or autoimmune diseases are thought to be leading to the development of MALT lymphoma. We present the case of primary pulmonary mucosa-associated lymphoid tissue lymphoma. A 76-year-old man with a history of heavy smoking (22.5 pack years) was admitted to the hospital for a further diagnostics of an abnormal finding in the right lung visualized on the chest X-ray. The diagnostic process, including imagining studies did not reveal the etiology of a lesion in the right lung. The patient was qualified for surgical diagnostics. The histological finding confirmed extranodal marginal low-grade B-cell lymphoma of mucosa -associated lymphoid tissue.

Acute respiratory failure resistant to conventional pulmonary therapy often requires intensive medical care. In rare cases, ventilator therapy proves insufficient, and only the option of employing veno-venous extracorporeal membrane oxygenation (ECMO V-V) remains. The present article describes the case of a 23-year-old patient who experienced severe acute respiratory distress syndrome with associated multiple organ failure. The patient was admitted to the pulmonary ward of the Alfred Sokolowski Regional Pulmonary Hospital in Szczecin-Zdunowo with suspected pneumonia of unknown etiology. After the initial 5 days of diagnostics at the pulmonary ward, the patient required a further 97 days of hospital treatment and spent 63 days at the Intensive Care Unit. There, he underwent ECMO V-V therapy lasting 22 days, which resulted in the improvement of his arterial blood gas parameters and clinical condition.

We present 21 studies of cases of lung cancer in patients with situs inversus totalis (SIT) published worldwide. The first case was described in 1952. Thirteen patients were from Japan, 4 from Eastern Europe, including 2 Polish cases from the authors` center (Department of Thoracic Surgery, Pomeranian Medical University in Szczecin, Poland), 2 from Western Asia, 1 from the U.S. and 1 from Australia. Male patients (20/21) as well as left-sided lung cancer cases (14/21) and squamous cell carcinoma cases (8/21) dominated in the entire group. Thirteen patients underwent surgical treatment. There were 10 left-sided and 3 right-sided surgical interventions with uneventful intra- and postoperative course. Explorative thoracotomy was performed in one case only on the right side. Upper lobectomy was performed in 5 cases, pneumonectomy in 3 cases, lower bilobectomy and middle lobectomy in one case and lower lobectomy in two cases. Surgery was performed through thoracotomy in 10 cases, VATS-assisted approach in two cases and sternotomy in one case. Descriptions of the surgical anatomy confirmed mirror image of the anatomy in all cases and were consistent with the preoperative CT images. Preoperative diagnosis was discussed including the role of 3-D reconstruction of CT for improving perioperative safety in this group of patients. In conclusion, lung cancer/SIT cases despite inversed but regular anatomy can be operated on radically as cases with normal anatomy with preservation of intraoperative security level.

Powikłania płucne u biorców narządów cechują się trudnościami diagnostycznymi, poważnym rokowaniem i często słabą odpowiedzią na leczenie. Niektóre z nich wymagają diagnostyki inwazyjnej i leczenia operacyjnego, a inne długotrwałego leczenia farmakologicznego. Gruźlica, zakażenia Pneumocystis sp. i zakażenia grzybicze należą do grupy powikłań infekcyjnych. Pierwotne i wtórne nowotwory płuc powstające w niedalekim odstępie czasowym od transplantacji narządu litego noszą miano powikłań onkologicznych, a oba typy powikłań mają swoje podłoże w immunosupresji. Wymóg kontynuacji immunosupresji dotyczy także okresu leczenia wyżej wymienionych powikłań, stawiając podwyższone wymagania dla zespołów terapeutycznych. Przedstawiono grupę 5 chorych (2 kobiety i 3 mężczyzn) po przeszczepieniach narządów leczonych w ośrodku autorów z powodu nowotworów płuc. Czterech chorych przebyło transplantację wątroby, a jeden serca. Trzech chorych leczono z powodu pierwotnego raka płuca, z czego u 1 dodatkowo wystąpił przerzut raka płuca, u 2 chorych rozwinęły się zmiany przerzutowe raka wątrobowokomórkowego (HCC) z wszczepionej z tego powodu wątroby. Czterech chorych operowano. Wykonano 2 lobektomie i 1 segmentektomię, uzupełnione o limfadenektomię w grupie zmian pierwotnych, jedną obustronną resekcję przerzutów (HCC) i jedną resekcję przerzutu raka płuca wcześniej zoperowanego. Wszystkie przypadki pierwotnego raka płuca miały charakter raka płaskonabłonkowego. Opisano przebiegi okołooperacyjne, schematy immunosupresji oraz dodatkowe powikłania infekcyjne (gruźlica, zakażenie uogólnione i zakażenie dróg żółciowych, kandydoza przełyku), jakie miały miejsce w tej grupie chorych, choć powikłania te nie były związane z obecnym procesem leczenia. Podkreślono znaczenie nikotynizmu w tej grupie chorych, bowiem każdy z nich był palaczem tytoniu.

Przedstawiono przypadek 66-letniej chorej z guzkami pluc o średnicy do 1 cm obserwowanymi od 2 lat. Chora byla dializowana od wielu lat z powodu przewleklej niewydolności nerek, jednakze bez cech niewydolności oddechowej, z prawidlowymi stezeniami wapnia w surowicy. Drogą otwartej biopsji pluca pobrano kilka pojedynczych guzkow, a wynik histopatologiczny oceniono jako przerzutowe zwapnienia plucne (metastatic pulmonary calcification – MPC). Na podstawie przeglądu piśmiennictwa opisano kliniczne, morfologiczne i patofizjologiczne cechy MPC wraz z ich diagnostyką, z odniesieniem do prezentowanego przypadku. Slowa kluczowe: niewydolnośc nerek, guz pluca, zwapnienia przerzutowe. Abstract

Thoracic splenosis of the left lung and upper abdominal area was described. Left minithoracotomy was performed due to unclear results from a fine needle biopsy and following the suggestion to obtain a tissue sample. Clinical findings were similar to neoplasmatic disease; intraoperative extension of the disease was larger than CT view and correlated with postoperative assessment with 99mTc sulphur colloid. This confirmed the usefulness of scintigraphic assessment in preoperative diagnosis in order to avoid thoracotomy in such cases.

The surgeon's viewpoint on a patient with cystic fibrosis differs from that of a pediatrician or internist. The problems a cystic fibrosis specialist encounters are different from those faced by the surgeon who takes over the patient in a very advanced, often terminal stage of the disease. Hence, the main problem for the surgeon is the decision concerning the surgery (lung transplantation, pneumonectomy, lobectomy). It is, therefore, important to lay down fundamental and appropriate rules concerning the indications and contraindications for lung transplantation, especially in patients with cystic fibrosis.The aim of this study was to analyze the methods of qualifying and preparing patients for surgery, as well as carrying out the procedure of transplantation and postoperative short and long-term care.The investigation was carried out on 16 patients with cystic fibrosis. Three were operated on and 10 were on the waiting list for transplantation. Two patients on the waiting list died, one patient was disqualified from transplantation. During qualification for lung transplantation, strict indications, contraindications and other factors (such as blood type, patient's height, coexisting complications) were taken under consideration.All the 3 patients after lung transplantation are alive and under our constant surveillance. Ten patients await transplantation, though four of them are suspended due to hepatitis C infection. Two patients on the waiting list died: one from respiratory insufficiency and the other in the course of bridge to-transplant veno-venous extracorporeal membrane oxygenation due to hepatic failure. One patient has been disqualified because of cachexia.Since lung transplantation is the final treatment of the end-stage pulmonary insufficiency in cystic fibrosis patients, the number of such procedures in cystic fibrosis is still too low in Poland. The fast development of these procedures is highly needed. It is necessary to develop better cooperation between different disciplines and specialists, especially between pediatricians and surgeons. The correct choice of the suitable moment for lung transplantation is crucial for the success of the procedure.

Primary pulmonary lymphoma accounts only 0,5% of all primary lung neoplasms. Mucosa-associated lymphoid tissue (MALT) lymphoma is a low grade B-cell extranodal lymphoma. It is a quite infrequent entity, however it constitutes from 72% to 90% of all pulmonary lung lymphomas. Long-term stimulation of bronchus-associated lymphoid tissue by antigens, smoking, inflammatory disorders or autoimmune diseases are thought to be leading to the development of MALT lymphoma. We present the case of primary pulmonary mucosa-associated lymphoid tissue lymphoma. A 76-year-old man with a history of heavy smoking (22.5 pack years) was admitted to the hospital for a further diagnostics of an abnormal finding in the right lung visualized on the chest X-ray. The diagnostic process, including imagining studies did not reveal the etiology of a lesion in the right lung. The patient was qualified for surgical diagnostics. The histological finding confirmed extranodal marginal low-grade B-cell lymphoma of mucosa -associated lymphoid tissue.

Lung transplantation is an acceptable treatment option for various end-stage pulmonary diseases, but long-term survival currently lags behind that after transplantation of other solid organs. We hypothesized that gene transfer to grafts before transplantation may be a useful method to deliver antioxidant and/or anti-inflammatory genes to modulate these processes. For this purpose, we assessed the efficiency of gene transfer and effects on lung function of the synthetic polycation, linear polyethylenimine (PEI), after airway instillation to the lungs of Fischer rats. Twenty-four hours after gene delivery, reporter gene activity in DNA/PEI treated rats was approximately 12-fold higher than that in rats treated with naked DNA, but by 72 hours there was no significant difference between groups and activity had decreased by at least 85%. Function of the transfected left lung was assessed by measuring arterial PaO(2) levels and was found to be significantly lower at 24 and 72 hours after gene transfer in the PEI/DNA group compared with the naked DNA group. The deterioration in lung function correlated with histological findings. Rats treated with PEI alone and sacrificed after 72 hours showed an impairment in lung function similar to that seen with PEI/DNA treatment. Our studies highlight the importance of assessing the functional capacity of a graft after gene transfer to determine suitability for subsequent transplantation.

The case of a 43 year old male with giant chest wall tumor weighing 9.6 kg verified as chondrosarcoma is described. The patient was treated by multiple (six times) surgical procedures including left costopleuropneumonectomy and left subclavian artery end-to-end anastomosis between 1998 and 2005. Despite the palliative character of surgery, he achieved long-term survival but finally refused next surgery due to the risk of left upper limb amputation and died a few months later.