Lung Transplantation for Primary Ciliary Dyskinesia and Kartagener Syndrome: A Multicenter Study.

Primary ciliary dyskinesia, with or without situs abnormalities, is a rare lung disease that can lead to an irreversible lung damage that may progress to respiratory failure. Lung transplant can be considered in end-stage disease. This study describes the outcomes of the largest lung transplant population for PCD and for PCD with situs abnormalities, also identified as Kartagener's syndrome. Retrospectively collected data of 36 patients who underwent lung transplantation for PCD from 1995 to 2020 with or without SA as part of the European Society of Thoracic Surgeons Lung Transplantation Working Group on rare diseases. Primary outcomes of interest included survival and freedom from chronic lung allograft dysfunction. Secondary outcomes included primary graft dysfunction within 72 h and the rate of rejection ≥A2 within the first year. Among PCD recipients with and without SA, the mean overall and CLAD-free survival were 5.9 and 5.2 years with no significant differences between groups in terms of time to CLAD (HR: 0.92, 95% CI: 0.27-3.14, p = 0.894) or mortality (HR: 0.45, 95% CI: 0.14-1.43, p = 0.178). Postoperative rates of PGD were comparable between groups; rejection grades ≥A2 on first biopsy or within the first year was more common in patients with SA. This study provides a valuable insight on international practices of lung transplantation in patients with PCD. Lung transplantation is an acceptable treatment option in this population.

Recipient Comorbidities for Prediction of Primary Graft Dysfunction, Chronic Allograft Dysfunction and Survival After Lung Transplantation.

Since candidates with comorbidities are increasingly referred for lung transplantation, knowledge about comorbidities and their cumulative effect on outcomes is scarce. We retrospectively collected pretransplant comorbidities of all 513 adult recipients transplanted at our center between 1992-2019. Multiple logistic- and Cox regression models, adjusted for donor-, pre- and peri-operative variables, were used to detect independent risk factors for primary graft dysfunction grade-3 at 72 h (PGD3-T72), onset of chronic allograft dysfunction grade-3 (CLAD-3) and survival. An increasing comorbidity burden measured by Charleston-Deyo-Index was a multivariable risk for survival and PGD3-T72, but not for CLAD-3. Among comorbidities, congestive right heart failure or a mean pulmonary artery pressure >25 mmHg were independent risk factors for PGD3-T72 and survival, and a borderline risk for CLAD-3. Left heart failure, chronic atrial fibrillation, arterial hypertension, moderate liver disease, peptic ulcer disease, gastroesophageal reflux, diabetes with end organ damage, moderate to severe renal disease, osteoporosis, and diverticulosis were also independent risk factors for survival. For PGD3-T72, a BMI>30 kg/m2 was an additional independent risk. Epilepsy and a smoking history of the recipient of >20packyears are additional independent risk factors for CLAD-3. The comorbidity profile should therefore be closely considered for further clinical decision making in candidate selection.

Primary pulmonary meningioma: a case report.

An asymptomatic 68-year-old woman, with a history of breast cancer 19 years ago, was unexpectedly found to have primary pulmonary meningioma during medical evaluation. This discovery is exceedingly rare, with only about 70 cases reported worldwide. Following uncomplicated surgical removal of the mass, the patient was discharged in good health on the third day after the procedure. Notably, initial analysis of a frozen tissue sample indicated hamartoma, but subsequent immune-histochemical pathological examination confirmed the presence of meningioma. Given the uncommon nature of this tumor, it is essential to report such cases to raise awareness about pulmonary meningioma as a potential cause of solitary lung nodules. This awareness can help prevent unnecessary chemotherapy or surgical interventions.

The significance of a 'T shaped' incision for resection of giant mediastinal tumors: a case report.

A 37-year-old male, with a 5-year history of liposarcoma of the right thigh, was incidentally diagnosed with two huge thoracic metastases following a fall. One of these masses, measuring 22 cm, was located in the right chest apex, adjacent to a second 20 cm mass situated in the anterior mediastinum, partially invading the left chest. The patient underwent surgical intervention for mass resection that commenced with a hemi-clamshell incision, but was then extended by completing the lower median sternotomy in order to create a T shaped incision. This type of incision provides ample access for large mediastinal tumors that extensively extend into one side of the thoracic cavity, encompass the anterior mediastinum, and partially reach into the opposite cavity. It enhances visualization, facilitates access to vital organs, allows for precise surgical maneuvers, minimizes the risk of inadvertent tissue damage, and enables thorough oncological resection.

Lung transplantation in children.

Lung transplantation is a well-established treatment for children facing advanced lung disease and pulmonary vascular disorders. However, organ shortage remains highest in children. For fitting the small chest of children, transplantation of downsized adult lungs, lobes, or even segments were successfully established. The worldwide median survival after pediatric lung transplantation is currently 5.7 years, while under consideration of age, underlying disease, and peri- and posttransplant center experience, median survival of more than 10 years is reported. Timing of referral for transplantation, ischemia-reperfusion injury, primary graft dysfunction, and acute and chronic rejection after transplantation remain the main challenges.

A rare posterior mediastinal mass: chordoma.

A 72-year-old female presented with 2 years of pro-gradient pain in the upper thoracic spine radiating to the left arm and leg. MRI revealed a 2.7 × 2.0 × 12 cm paravertebral mass at T2/T3, extending into the foraminal and epidural nerves with extensive dural sac contact in the left hemithorax. The removed tumour was surprisingly soft for a schwannoma or chordoma. However, after the surgery, histopathology revealed the presence of brachyury protein (T-box transcription factor T), which is characteristic of a chordoma. While chordomas are extremely rare, it is important that they are kept in mind for the differential diagnosis of a posterior mediastinal mass. Successful treatment can only be achieved through a complete en bloc resection. This can often be complex due to their location along the spine. This case report aims to highlight the features and treatment of this rare disease.

[Surgery of old people-Thoracic surgery]. / Chirurgie des alten Menschen ­ Thoraxchirurgie.

BACKGROUND: The incidence of a large number of diseases relevant to thoracic surgery increases with age; however, old age is still frequently considered a contraindication per se for curative interventions and extensive surgical procedures. OBJECTIVE: Overview of the current relevant literature, derivation of recommendations for patient selection as well as preoperative, perioperative and postoperative optimization. MATERIAL AND METHODS: Analysis of the current study situation. RESULTS: Recent data show that for most thoracic diseases, age alone is not a reason to withhold surgical treatment. Much more important for the selection are comorbidities, frailty, malnutrition and cognitive impairment. A lobectomy or segmentectomy for stage I non-small cell lung cancer (NSCLC) in carefully selected octogenarians can provide acceptable to even comparably good short-term and long-term results as in younger patients. Selected > 75-year-old patients with stages II-IIIA NSCLC even benefit from adjuvant chemotherapy. With appropriate selection high-risk interventions, such as pneumonectomy in > 70-year-old patients and pulmonary endarterectomy in > 80-year-old patients can be performed without an increase in mortality rates. Even lung transplantation can lead to good long-term results in carefully selected > 70-year-old patients. Minimally invasive surgical techniques and nonintubated anesthesia contribute to risk reduction in marginal patients. DISCUSSION: In thoracic surgery the biological age rather than the chronological age is decisive. In view of the increasingly older population, further studies are urgently needed to optimize patient selection, type of intervention, preoperative planning and postoperative treatment as well as the quality of life.

[Surgery of old people-Thoracic surgery]. / Chirurgie des alten Menschen ­ Thoraxchirurgie.

Background: The incidence of a large number of diseases relevant to thoracic surgery increases with age; however, old age is still frequently considered a contraindication per se for curative interventions and extensive surgical procedures. Objective: Overview of the current relevant literature, derivation of recommendations for patient selection as well as preoperative, perioperative and postoperative optimization. Material and methods: Analysis of the current study situation. Results: Recent data show that for most thoracic diseases, age alone is not a reason to withhold surgical treatment. Much more important for the selection are comorbidities, frailty, malnutrition and cognitive impairment. A lobectomy or segmentectomy for stage I non-small cell lung cancer (NSCLC) in carefully selected octogenarians can provide acceptable to even comparably good short-term and long-term results as in younger patients. Selected > 75-year-old patients with stages II-IIIA NSCLC even benefit from adjuvant chemotherapy. With appropriate selection high-risk interventions, such as pneumonectomy in > 70-year-old patients and pulmonary endarterectomy in > 80-year-old patients can be performed without an increase in mortality rates. Even lung transplantation can lead to good long-term results in carefully selected > 70-year-old patients. Minimally invasive surgical techniques and nonintubated anesthesia contribute to risk reduction in marginal patients. Discussion: In thoracic surgery the biological age rather than the chronological age is decisive. In view of the increasingly older population, further studies are urgently needed to optimize patient selection, type of intervention, preoperative planning and postoperative treatment as well as the quality of life.

Extracorporeal cytokine adsorption reduces systemic cytokine storm and improves graft function in lung transplantation.

Objectives: Ischemia-reperfusion injury often coincides with a cytokine storm, which can result in primary graft dysfunction following lung transplantation. Our previous research has demonstrated allograft improvement by cytokine adsorption during ex vivo lung perfusion. The aim of this study was to investigate the effect of in vivo extracorporeal cytokine adsorption in a large animal model. Materials and Methods: Pig left lung transplantation was performed following 24 hours of cold ischemic storage. Observation period after transplantation was 24 hours. In the treatment group (n = 6), extracorporeal CytoSorb adsorption was started 30 minutes before reperfusion and continued for 6 hours. A control group (n = 3) did not receive adsorber treatment. Results: During adsorption, we consistently noticed a significant decrease in plasma proinflammatory interleukin (IL)-2, trends of less proinflammatory, tumor necrosis factor- α, IL-1α, and granulocyte-macrophage colony-stimulating factor as well as significantly reduced systemic neutrophils. In addition, a significantly lower peak airway pressure was detected during the 6 hours of adsorption. After 24 hours of observation, when evaluating the left lung allograft independently, we observed significantly improved CO2 removal, partial pressure of oxygen/inspired oxygen fraction ratio, and less acidosis in the treatment group. At autopsy, bronchoalveolar lavage results exhibited significantly lower recruitment of cells and less pro-inflammatory IL-1α, IL-1ß, IL-6, and IL-8 in the treatment group. Histologically, the treatment group had a strong trend, indicating less neutrophil invasion into the alveolar space. Conclusions: Based on our findings, cytokine adsorption during and after reperfusion is a viable approach to reducing posttransplant inflammation following lung transplantation. CytoSorb may increase the acceptance of extended criteria donor lungs, which are more susceptible to ischemia-reperfusion injury.

Ex Vivo Lung Perfusion with ß-Nicotinamide Adenine Dinucleotide (NAD+) Improves Ischemic Lung Function.

Ischemia-reperfusion injury compromises short- and long-term outcomes after lung transplantation. The scarce existing data on NAD+ suggest effects on hypoxia-induced vasoconstriction, on reactive oxygen species and on tampering inflammation. We exposed rat lungs to 14 h of cold ischemic storage and perfused them in a rat ex vivo lung perfusion (EVLP) system for 4 h. A control group (n = 6) was compared to groups receiving 100 µM (n = 6) or 200 µM NAD+ (n = 6) in the preservation solution and groups receiving 200 µM (n = 4) or 2000 µM (n = 6) NAD+ every 30 min in the perfusate, starting at 1 h of EVLP. Compared to the control, significant effects were only achieved in the 2000 µM NAD+ group. During the 4 h of EVLP, we monitored higher vascular flow, lower mean pulmonary arterial pressure and increased oxygenation capacity. Tissue inflammation estimated with the myeloperoxidase assay was lower in the 2000 µM NAD+ group. We observed higher levels of anti-inflammatory IL-10, higher anti-inflammatory IL-6/IL-10 ratios and lower levels of pro-inflammatory IL-12 and IL-18 as well as a trend of more anti-inflammatory IFNy in the 2000 µM NAD+ perfusate. In the bronchoalveolar lavage, the pro-inflammatory levels of IL-1α and IL-1ß were lower in the 2000 µM NAD+ group. NAD+ administered during EVLP is a promising agent with both anti-inflammatory properties and the ability to improve ischemic lung function.

Extracorporeal life support as a bridge to pulmonary retransplantation: prognostic factors for survival in a multicentre cohort analysis.

OBJECTIVES: Pulmonary retransplant (ReTx) is considered a controversial procedure. Despite literature reporting outcomes following ReTx, limited data exist in recipients bridged to their ReTx on extracorporeal life support (ECLS). The goal of this study was to investigate the outcomes of recipients bridged to a first-time ReTx by ECLS. METHODS: We performed a retrospective multicentre cohort analysis from 10 centres in Europe, Asia and North America. The primary outcome was overall survival. Risk factors were analysed using Cox regression models. RESULTS: ECLS as a bridge to a first-time ReTx was performed in 50 recipients (ECLS-ReTx). During the study period, 210 recipients underwent a first-time ReTx without bridging on ECLS (regular-ReTx) and 4959 recipients had a primary pulmonary transplant (index-Tx). The overall 1-year (55%) and 5-year (29%) survival was significantly worse for the ECLS-ReTx group.Compared to the index-Tx group, the mortality risk was significantly higher after ECLS-ReTx [hazard ratio 2.76 (95% confidence interval 1.94-3.91); P < 0.001] and regular-ReTx [hazard ratio 1.65 (95% confidence interval 1.36-2); P < 0.001].In multivariable analysis, recipient age ≥35 years, time interval <1 year from index-Tx, primary graft dysfunction as transplant indication, venoarterial-extracorporeal membrane oxygenation and Zurich donor score ≥4 points were significant risk factors for mortality in ECLS-ReTx recipients. CONCLUSIONS: Recipients for ECLS-ReTx should be carefully selected. Risk factors, such as recipient age, intertransplant interval, primary graft dysfunction as transplant indication and type of ECLS should be kept in mind before bridging these patients on ECLS to ReTx.