Validated Prognostic Scores to Predict Outcomes in ECLS-Bridged Patients to Lung Transplantation.

Selection of patients who may benefit from extracorporeal life support (ECLS) as a bridge to lung transplant (LTx) is crucial. The aim was to assess if validated prognostic scores could help in selecting patients who may benefit from ECLS-bridging predicting their outcomes. Clinical data of patients successfully ECLS-bridged to LTx from 2009 to 2021 were collected from two European centers. For each patient, we calculated Sequential Organ Failure Assessment (SOFA), Simplified Acute Physiology Score III (SAPS III), Acute Physiology and Chronic Health Evaluation II (APACHE II), before placing ECLS support, and then correlated with outcome. Median values of SOFA, SAPS III, and APACHE II were 5 (IQR 3-9), 57 (IQR 47.5-65), and 21 (IQR 15-26). In-hospital, 30 and 90 days mortality were 21%, 14%, and 22%. SOFA, SAPS III, and APACHE II were analyzed as predictors of in-hospital, 30 and 90 days mortality (SOFA C-Index: 0.67, 0.78, 0.72; SAPS III C-index: 0.48, 0.45, 0.51; APACHE II C-Index: 0.49, 0.45, 0.52). For SOFA, the score with the best performance, a value ≥9 was identified to be the optimal cut-off for the prediction of the outcomes of interest. SOFA may be considered an adequate predictor in these patients, helping clinical decision-making. More specific and simplified scores for this population are necessary.

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.

Impact of extended sinus surgery on allograft infection, allograft function and overall survival in cystic fibrosis lung transplant recipients.

BACKGROUND: Studies investigating the impact of sinus surgery for cystic fibrosis (CF) patients performed early after lung transplantation (Ltx) are scarce. Recent studies evaluating frequency of respiratory infections and graft outcomes are not available. OBJECTIVES/HYPOTHESIS: To determine whether there is a difference in allograft infection, allograft function and overall survival among CF lung transplant recipients with and without concomitant sinus surgery. STUDY DESIGN: Retrospective single-center study. METHODS: We examined 71 CF patients who underwent Ltx between 2009 and 2019 at our center. Fifty-nine patients had sinus surgery before or/and after transplantation and twelve did not undergo sinus surgery. We assessed the survival, the diagnosis of chronic allograft dysfunction (CLAD) and all elevated (> 5 mg/l) c-reactive protein episodes during the observed period. The infectious events of the upper and lower airways were categorized in mild infections (5-15 mg/l CRP) and severe infections (> 15 mg/l CRP). RESULTS: There was no difference in the long-time overall survival (p = 0.87) and no benefit in the short-term survival at 4 year post-transplant (p = 0.29) in both groups. There was no difference in both groups concerning CLAD diagnosis (p = 0.92). The incidence of severe upper and lower airway infections (CRP > 15 mg/l) was significantly decreased in the sinus surgery group (p = 0.015), whereas in mild infections there was a trend to decreased infections in the sinus surgery group (p = 0.056). CONCLUSIONS: CF patients undergoing Ltx benefit from extended endoscopic sinus surgery (eESS) in terms of frequency of severe infectious events of the upper and lower airways. There was no difference in overall survival and frequency of CLAD in the two groups.

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.

Survival After Lung Transplantation for Chronic Hypersensitivity Pneumonitis: Results From a Large International Cohort Study.

Repeated exposure to antigens via inhalation is the primary cause of hypersensitivity pneumonitis, a form of interstitial pneumonia. The chronic form of hypersensitivity pneumonitis leads to progressive loss of respiratory function; lung transplantation is the only therapeutic option for chronically ill patients. The ESTS Lung Transplantation Working Group conducted a retrospective multicentred cohort study to increase the body of knowledge available on this rare indication for lung transplantation. Data were collected for every patient who underwent lung transplant for hypersensitivity pneumonitis in participating centres between December 1996 and October 2019. Primary outcome was overall survival; secondary outcome was freedom from chronic lung allograft dysfunction. A total of 114 patients were enrolled from 9 centres. Almost 90% of patients were diagnosed with hypersensitivity pneumonitis before transplantation, yet the antigen responsible for the infection was identified in only 25% of cases. Eighty per cent of the recipients received induction therapy. Survival at 1, 3, and 5 years was 85%, 75%, and 70%, respectively. 85% of the patients who survived 90 days after transplantation were free from chronic lung allograft dysfunction after 3 years. The given study presents a large cohort of HP patients who underwent lung transplants. Overall survival rate is higher in transplanted hypersensitivity pneumonitis patients than in those suffering from any other interstitial lung diseases. Hypersensitivity pneumonitis patients are good candidates for lung transplantation.

Current status and further potential of lung donation after circulatory death.

Chronic organ shortage remains the most limiting factor in lung transplantation. To overcome this shortage, a minority of centers have started with efforts to reintroduce donation after circulatory death (DCD). This review aims to evaluate the experimental background, the current international clinical experience, and the further potential and challenges of the different DCD categories. Successful strategies have been implemented to reduce the problems of warm ischemic time, thrombosis after circulatory arrest, and difficulties in organ assessment, which come with DCD donation. From the currently reported results, controlled-DCD lungs are an effective and safe method with good mid-term and even long-term survival outcomes comparable to donation after brain death (DBD). Primary graft dysfunction and onset of chronic allograft dysfunction seem also comparable. Thus, controlled-DCD lungs should be ceased to be treated as marginal and instead be promoted as an equivalent alternative to DBD. A wide implementation of controlled-DCD-lung donation would significantly decrease the mortality on the waiting list. Therefore, further efforts in establishment of legislation and logistics are crucial. With regard to uncontrolled DCD, more data are needed analyzing long-term outcomes. To help with the detailed assessment and improvement of uncontrolled or otherwise questionable grafts after retrieval, ex-vivo lung perfusion is promising.

Surgical Outcomes and Risk Analysis of Primary Pulmonary Sarcoma.

BACKGROUND: Primary pulmonary sarcoma (PPS) is a rare malignant lung neoplasm, and there is very little medical evidence about treatment of PPS. The aim of this study is to clarify the clinical characteristics and therapeutic outcome of patients who underwent surgical resection for PPS. METHODS: We retrospectively reviewed the records of patients who underwent surgical resection for PPS in our institution between 1995 and 2014. Cases who only underwent biopsy were excluded. RESULTS: A total of 24 patients (18 males, 6 females), with a median age of 60 (interquartile range: 44-67) years, were analyzed. The surgical procedures performed in these patients were pneumonectomy (n = 10), lobectomy (n = 11), and wedge resection (n = 3). Complete resection was achieved in 16 patients. The pathological stages (tumor, node, metastases lung cancer classification, 8th edition) of the patients were I (n = 4), II (n = 12), III (n = 2), and IV (n = 5), and there were four cases of lymph node metastasis. The 5-year overall survival rate of the patients was 50% (95% confidence interval [CI]: 29-72). Adverse prognostic factors for overall survival were incomplete resection (hazard ratio [HR]: 4.4, 95% CI: 2.1-42), advanced pathological stage (HR 14, 95% CI: 2.8-66), higher pathological grade (HR 4.5, 95% CI: 1.2-17), and tumor size ≥ 7 cm (HR 4.7, 95% CI: 1.1-21). CONCLUSIONS: Our series of PPS revealed that incomplete resection, advanced pathological stage, higher pathological grade, and tumor size were unfavorable factors for long-term survival.

ECP as additional immunomodulation in idiopathic hyperammonemia and recurrent hypercapnic respiratory failure early post lung transplantation.

Extra-corporeal photopheresis (ECP) is known as safe ultimate treatment option for chronic lung allograft dysfunction (CLAD). Here, we report the first case of ECP as "second-line" immunomodulatory therapy early post-transplant in an adult patient undergoing lung transplantation for severe chronic thromboembolic pulmonary hypertension, complicated by impaired consciousness due to idiopathic hyperammonemia resulting in recurrent hypercapnic respiratory failure. ECP was initiated twice weekly on post-transplant day 25 and standard triple immunosuppression reduced. Within 2 weeks, the clinical status improved. ECP has been continued every 4 weeks after discharge. At 1 year post-transplant, ECP was stopped as maintenance immunosuppression was reached. We recommend to consider the immunomodulatory effect of ECP as "second line" immunomodulatory therapy in cases where standard immunosuppression causes severe collateral damage. ECP is able to assist prevention of allograft rejection in conjunction with reduced levels of standard immunosuppression, even in the early period following lung transplantation.

The Amide Local Anesthetic Ropivacaine Attenuates Acute Rejection After Allogeneic Mouse Lung Transplantation.

PURPOSE: Acute allograft rejection after lung transplantation remains an unsolved hurdle. The pathogenesis includes an inflammatory response during and after transplantation. Ropivacaine, an amide-linked local anesthetic, has been shown to attenuate lung injury due to its anti-inflammatory effects. We hypothesized that the drug would also be able to attenuate acute rejection (AR) after allogeneic lung transplantation. METHODS: Allogeneic, orthotopic, single left lung transplantation was performed between BALB/c (donors) and C57BL/6 (recipients) mice. Prior to explantation, lungs were flushed with normal saline with or without ropivacaine (final concentration 1 µM). Plasma levels of tumor necrosis factor-α and interleukins - 6 and - 10 were measured 3 h after transplantation by ELISA. Lung function was assessed on postoperative day five and transplanted lungs were analyzed using histology (AR), immunohistochemistry (infiltrating leukocytes) and Western blot (phosphorylation and expression of Src and caveolin-1). RESULTS: Ropivacaine pre-treatment significantly reduced AR scores (median 3 [minimum-maximum 2-4] for control vs. 2 [1-2] for ropivacaine, p < 0.001) and plasma levels of tumor necrosis factor-α (p = 0.01) compared to control, whereas plasma concentrations of interleukin - 6 (p = 0.008) and - 10 (p < 0.001) were increased by ropivacaine. The number of T-lymphocytes infiltrating the transplanted lung was attenuated (p = 0.02), while no differences in macrophage or B-lymphocyte numbers could be observed after ropivacaine pre-treatment. Caveolin-1 phosphorylation in ropivacaine-treated lungs was diminished (p = 0.004). CONCLUSIONS: Pre-treatment of donor lungs with the local anesthetic ropivacaine diminished histological signs of AR after orthotopic left lung transplantation in mice, most likely due to reduced infiltration of T-lymphocytes into the graft.

Lung donation after circulatory death.

PURPOSE OF REVIEW: The current review presents a concise update on published literature on donation after circulatory death (DCD) and lung transplantation (LTx). Worldwide an increasing need for lungs is evident, however the utilization rate of DCD lung donors is still considerably low. In this summary article, we reviewed both the experimental background and international clinical experience. RECENT FINDINGS: Our analysis confirmed satisfactory results for LTx from DCD donors, which equals the results from donation after brain death. Although most studies reported on short-term results, some confirmed these results on the long-term and development of chronic lung allograft dysfunction. Our review summarizes the different DCD categories and underlines the potential of the DCD V category. We analyze the barriers to implement a DCD program, discuss the more recent advances like ex-vivo lung perfusion and describe the future challenges. SUMMARY: Based on the current short-term and long-term clinical results, we believe that barriers for DCD utilization should be overcome, resulting in a safe implementation of more DCD LTx programs worldwide. VIDEO ABSTRACT.

Extracorporeal photopheresis as second-line treatment therapy in life-threatening primary graft dysfunction following lung transplantation.

ECP is an established "second-line" treatment for CLAD/BOS. Recently, ECP was used for the first time in an adolescent CF patient as a "second-line" treatment therapy in life-threatening primary graft dysfunction following lung transplantation who deteriorated despite extensive treatment including ECMO and ATG. Within 10 days after initiation of ECP twice weekly, allograft function and clinical status improved significantly and the patient was weaned from mechanical ventilation support. ECP has been continued every 2 weeks since. Two hundred days after lung transplantation, the patient has an acceptable allograft function (FEV1 67%) and no signs of allograft rejection. We advocate that use of ECP and its immunomodulatory effects should be evaluated in the early period following lung transplantation.

Sevoflurane preconditioning protects from posttransplant injury in mouse lung transplantation.

BACKGROUND: Although sevoflurane (Sevo) had been shown to ameliorate posttransplant injury in various organs, data available are inconsistent, particularly in the context of lung transplantation (Tx). We here investigated if preconditioning by Sevo can protect from posttransplant injury regarding both, primary graft dysfunction (PGD) and acute rejection (AR) after experimental lung Tx, thereby focusing on two important clinical outcome parameters. MATERIALS AND METHODS: Three experimental approaches were used: (1) BALB/c mice were preconditioned for 2 h with Sevo or a fentanyl cocktail (Control; n = 10); (2) syngeneic (Syn) mouse lung Tx (C57BL/6) with a Sevo-preconditioned graft followed by 18 h storage to mimic PGD (Syn-Tx, n = 12) versus controls (fentanyl cocktail); and (3) allogeneic (Allo) Tx (BALB/c, donor; C57BL/6, recipient) to mimic AR (Allo-Tx, n = 12) versus controls (fentanyl cocktail). Syn-Tx grafts were harvested on Day 1, Allo-Tx grafts on Day 3 and analyzed for histology, immunohistochemistry, blood gas analysis, and inflammatory cytokines (enzyme-linked immunosorbent assay or reverse transcription polymerase chain reaction). RESULTS: Evaluating the preconditioning effect of Sevo only showed significantly better oxygenation (P = 0.03) and a tendency toward lower levels of lung tissue messenger RNA for tumor necrosis factor-α. In Syn-Tx recipients, the Sevo group had histologically a tendency toward an attenuation of PGD and showed significantly lower levels of interleukin 6 (P = 0.01) in plasma, but higher levels of interleukin 10 (P < 0.01) in lungs. Allo-Tx grafts in Sevo Tx recipients showed attenuated AR with histologically significantly lower rejection scores (P = 0.03), fewer classical macrophages (F4/80+; P < 0.01), but more anti-inflammatory activated macrophages (M2, CD206+; P < 0.01). Functionally, the Sevo group had a tendency toward improved oxygenation. CONCLUSIONS: We demonstrated that Sevo preconditioning has protective effects on lung transplants in both, PGD and AR. The observed amelioration may be attributed to suppressed inflammatory cytokines during PGD and the induction of alternatively activated macrophages during AR. These promising data could set the base for using Sevo preconditioning in donor lungs for a human trial.

Ex vivo treatment with inhaled N-acetylcysteine in porcine lung transplantation.

BACKGROUND: We have shown the beneficial effects of N-acetylcysteine (NAC) on posttransplant lung function, when both donor and recipient were pretreated intravenously. However, systemic treatment of multiorgan donors may not be clinically relevant. Thus, we hypothesized that ex vivo treatment of donors with nebulized NAC would be adequate to prevent from ischemia-reperfusion injury after lung transplantation. METHODS: Lungs were retrieved from domestic pigs and stored at 4°C for 24 h followed by 2 h of ex vivo lung perfusion (EVLP) to administer 50 mg/kg of NAC via nebulization in the NAC group (n = 6). The control group received nebulized saline (n = 5). Left lungs were transplanted and isolated at 1 h of reperfusion by occluding the right main bronchus and pulmonary artery, followed by 5 h of observation. Physiological data during EVLP and after reperfusion were recorded. Inflammatory response, markers of oxidative stress, and microscopic lung injury were analyzed. RESULTS: There was a trend toward better oxygenation throughout reperfusion period in the treatment group, which was accompanied by inhibited inflammatory response related to reduction in myeloperoxidase activity during EVLP and nuclear factor-κB activation at the end of reperfusion. CONCLUSIONS: Ex vivo treatment of donor lungs with inhaled NAC reduced inflammatory response via its antioxidant activity in experimental porcine lung transplantation.

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.

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.

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.

Removal of a large symptomatic retrocardiac mediastinal lipoma.

Large mediastinal lipomas are rare. Complete surgical resection can be difficult due to the intricate anatomy in the mediastinum. We report the case of a 75-year-old man with worsened retrosternal pressure, decline in performance and syncope episodes. Computed tomography revealed a large retrocardiac low-attenuated mediastinal lesion measuring 10 × 8 cm, compressing the left atrium and pulmonary veins bilaterally. Surgical exploration was achieved through a right anterolateral thoracotomy with a successful en bloc resection without any intraoperative complications. The total operation time was 185 min with a total blood loss of <250 ml. Stand-by extracorporeal life support was present throughout the procedure, but its use was not required. The postoperative course was uneventful. The pathological examination revealed a mature mediastinal lipoma without any evidence of malignancy. In the 12-month control the patient was completely free of symptoms and in a good general condition.

A Multicenter Retrospective Case-Control Study on Simple vs Extended Sleeve Lobectomies.

BACKGROUND: Sleeve resection is currently the gold standard procedure for centrally located non-small cell lung cancer (NSCLC). Extended sleeve lobectomy (ESL) consists of an atypical bronchoplasty with resection of >1 lobe and carries several technical difficulties compared with simple sleeve lobectomy (SSL). Our study compared the outcomes of ESL and SSL for NSCLC. METHODS: This multicenter, retrospective, cohort study included 1314 patients who underwent ESL (155 patients) or SSL (1159 patients) between 2000 and 2018. The primary end points were 30-day and 90-day mortality, overall survival (OS), disease-free survival (DFS), and complications. RESULTS: No differences were found between the 2 groups in general characteristics and surgical and survival outcomes. In particular, there were no differences in early and late complication frequency, 30- and 90-day mortality, R status, recurrence, OS (54.26 ± 33.72 months vs 56.42 ± 32.85 months, P = .444), and DFS (46.05 ± 36.14 months vs 47.20 ± 35.78 months, P = .710). Mean tumor size was larger in the ESL group (4.72 ± 2.30 cm vs 3.81 ± 1.78 cm, P < .001). Stage IIIA was the most prevalent stage in ESL group (34.8%), whereas stage IIB was the most prevalent in SSL group (34.3%; P < .001). The multivariate analyses found nodal status was the only independent predictive factor for OS. CONCLUSIONS: ESL gives comparable short- and long-term outcomes to SSL. Appropriate preoperative staging and exclusion of metastases to mediastinal lymph nodes, as well as complete (R0) resection, are essential for good long-term outcomes.

Small animal models of experimental obliterative bronchiolitis.

Despite significant progress in the treatment of chronic lung allograft rejection, obliterative bronchiolitis (OB) remains the major limitation to long-term survival after lung transplantation. The use of animal models is critical to an understanding of the pathological mechanisms behind OB, and to develop therapeutic strategies for OB. For almost 20 years, the technique of heterotopic tracheal transplantation was the leading experimental model in OB research. To address the need for a more physiologic experimental setup, a variety of small animal models have been proposed during the past two decades, such as the orthotopic tracheal transplantation model or the intrapulmonary trachea implantation model. The recent introduction of the orthotopic lung transplantation model in the mouse fulfilled the criteria for a physiologic lung transplantation setup, and also presents the advantage of being genetically modifiable. Here we review the evolution of OB models and their applications, from their beginning to the rapidly emerging physiologic models of chronic lung allograft rejection.