Referral rates and barriers to lung transplantation based on pulmonary function criteria in interstitial lung diseases: a retrospective cohort study.

BACKGROUND: Interstitial lung diseases (ILD) unresponsive to medical therapy often require lung transplantation (LTx), which prolongs quality of life and survival. Ideal timing for referral for LTx remains challenging, with late referral associated with significant morbidity and mortality. Among other criteria, patients with ILD should be considered for LTx if forced vital capacity (FVC) is less than 80% or diffusion capacity for carbon monoxide (DLCO) is less than 40%. However, data on referral rates are lacking. OBJECTIVES: To evaluate referral rates for LTx based on pulmonary function tests (PFTs) and identify barriers associated with non-referral. DESIGN: A single-center retrospective cohort study. METHODS: The study consisted of ILD patients who performed PFT between 2014 and 2020. Patients with FVC < 80% or a DLCO < 40% were included in the study. Patients with absolute contraindications to LTx were excluded. Referral rates were computed, and a comparison was made between referred and non-referred subjects. RESULTS: Out of 114 ILD patients meeting criteria for referral to LTx, 35 were referred (30.7%), and 7 proceeded to undergo LTx. Median time from PFT to referral for assessment was 255 days [interquartile range (IQR) 35-1077]. Median time from referral to LTx was 89 days (IQR 59-143). Referred patients were younger (p = 0.003), had lower FVC (p < 0.001), DLCO (p < 0.001), and a higher rate of pulmonary hypertension (p = 0.04). Relatively better PFT, and older age, were significantly associated with non-referral of patients. CONCLUSION: There is under-referral of ILD patients who are eligible for LTx, which is associated with severe disease and missed opportunities for LTx. Further research is required to validate these findings.

Lung transplants: addressing referral gaps for lung disease patientsPatients with severe lung diseases that are unresponsive to medical treatments often require lung transplants to enhance their quality of life and survival. Determining the optimal timing for considering a transplant is challenging, as delaying it can lead to complications. Our study aimed to assess how frequently individuals with lung problems, particularly interstitial lung diseases, were referred for lung transplants based on lung function tests. We conducted a retrospective analysis of medical records for patients with lung diseases who underwent lung function tests between 2014 and 2020. We selected patients whose test results indicated impaired lung function, excluding those who were ineligible for lung transplants due to other medical reasons. Subsequently, we examined the number of patients referred for a lung transplant and compared them to those who were not referred. Our findings revealed that out of 114 patients eligible for a lung transplant, only 35 were referred, representing a referral rate of approximately 31%. Among these, only 7 patients actually underwent the transplant procedure. The time elapsed between the lung function test and the referral for a transplant assessment was notably long, averaging around 255 days. Additionally, once referred, patients waited an average of 89 days for the transplant assessment. Referred patients tended to be younger and had more severe lung disease, characterized by lower lung function test results and a higher likelihood of pulmonary hypertension. Conversely, patients who were not referred generally enjoyed better overall health and were older. This discrepancy highlights the missed opportunities for patients to improve their health and quality of life through lung transplantation. Further research is essential to verify the accuracy of these findings, but this study represents a crucial step toward ensuring that individuals with lung diseases receive the appropriate care they require.

Timing of Lung Transplant Referral in Patients with Severe COVID-19 Lung Injury Supported by ECMO.

Severe respiratory failure caused by COVID-19 often requires mechanical ventilation, including extracorporeal membrane oxygenation (ECMO). In rare cases, lung transplantation (LTx) may be considered as a last resort. However, uncertainties remain about patient selection and optimal timing for referral and listing. This retrospective study analyzed patients with severe COVID-19 who were supported by veno-venous ECMO and listed for LTx between July 2020 and June 2022. Out of the 20 patients in the study population, four who underwent LTx were excluded. The clinical characteristics of the remaining 16 patients were compared, including nine who recovered and seven who died while awaiting LTx. The median duration from hospitalization to listing was 85.5 days, and the median duration on the waitlist was 25.5 days. Younger age was significantly associated with a higher likelihood of recovery without LTx after a median of 59 days on ECMO, compared to those who died at a median of 99 days. In patients with severe COVID-19-induced lung damage supported by ECMO, referral to LTx should be delayed for 8-10 weeks after ECMO initiation, particularly for younger patients who have a higher probability of spontaneous recovery and may not require LTx.

Angiosarcoma of the main pulmonary artery-hand-made conduit reconstruction.

Pulmonary artery angiosarcoma is a rare malignant vascular tumour with a poor prognosis and a grim clinical course. Common clinical presentations include shortness of breath, coughing and haemoptysis. Differential diagnosis includes thromboembolism and lung carcinoma. Rarity of the tumour and the consequent lack of treatment guidelines further worsen the prognosis. We report a case of pulmonary artery angiosarcoma involving the main pulmonary artery and its bifurcation with emphasis on the surgical treatment.

Correction to: Trimodally treatment for stage IIIa NSCLC patients increases survival while not effecting surgical mortality or complexity.

The original article [1] contained an error whereby all authors' names were mistakenly inverted. This error has now been corrected.

Trimodally treatment for stage IIIa NSCLC patients increases survival while not effecting surgical mortality or complexity.

INTRODUCTION: Advanced non-small cell lung cancer (NSCLC) is still a therapeutic challenge as the 5-year survival is under 30%. The optimal treatment regimen is still under debate. HYPOTHESIS: Neo adjuvant (NA) treatment given pre-pneumonectomy does not increase surgical complexity or peri-OP mortality while it has a potential to increase long term survival. METHODS: We have conducted a retrospective study of 169 patients who underwent a pneumonectomy for NSCLC between January 2005 to December 2015 and focused on stage IIIa patients; a cohort of 51 patients, 30 which received neo adjuvant chemo-radiation (NA group) prior to pneumonectomy and 21 patients who had undergone pneumonectomy followed by adjuvant treatment (Adjuvant group). Surgical complexity and short- and long-term survival were evaluated. Surgical complexity was assessed by surrogates as surgery duration, hospitalization length and interdepartmental transfer. RESULTS: While no statistically significant differences were found in surgery duration, hospitalization length, morbidity in the 1st year post-OP and the peri-OP mortality; The long term beneficiary effect among the neo adjuvant patients was clear; while 30% of the NA patients were alive 8 years post-OP, there were no survivors in the adjuvant group 5.5 years post-OP. CONCLUSION: We conclude that while NA treatment has no effect on operation complexity, peri-OP mortality or post-OP morbidity; its impact on long term survival is protuberant, therefore, we believe that NA treatment should be considered as the treatment of choice in advanced NSCLC in need for pneumonectomy.

Intensity-modulated radiotherapy is a safe and effective treatment for localized malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare disease and management of localized disease is controversial. Radiotherapy has been shown to be useful after extrapleural pneumonectomy (EPP), as well as with less aggressive surgery. As no reports of the treatment of this disease have ever been published from Israel, we report our experience with MPM and intensity-modulated radiotherapy (IMRT). METHODS: The complete medical records of patients treated for MPM at the Rabin Medical Center from 1 August 2007 to 31 March 2016 were reviewed. Twenty-seven patients were treated with IMRT, either post-EPP or without EPP. Patients received 54 Gy in 2 Gy fractions using the restricted field IMRT technique. Chemotherapy was administered sequentially in 26% of patients. Patients were followed up from the date of diagnosis to death or treatment failure. RESULTS: Seventy-eight percent of patients had the epithelioid subtype. Nearly all patients were male (85%) and 90% of non-surgical patients were administered chemotherapy compared to 56% of post-EPP patients. All patients completed therapy and only 16% had grade 1-2 radiation pneumonitis, with no incidence of grade 3 or higher. The median follow-up was 22 months and the mean overall survival was 34.9 months. The mean time to progression following radiation therapy was 26.7 months. The mean time to local and distant failure was 19 and 16 months, respectively. CONCLUSIONS: IMRT for localized pleural mesothelioma is a tolerable and effective therapy both post-EPP or without surgery. These results suggest that future investigation in this area is required.

Stereotactic body radiotherapy for central lung tumors, yes we can!

BACKGROUND: SBRT is standard therapy for early stage lung cancer. Toxicity in central tumors has been a concern. RTOG 0813 showed that central SBRT is safe and effective. We report our experience with central SBRT. METHODS: We reviewed the records of patients treated with SBRT for central lung tumors (< 2 cm of the carina). Patients included primary lung cancer and recurrence following surgery and\ or conventional radiotherapy. All patients underwent 4DCT simulation and treatment planning was done with IMRT or VMAT techniques. Dose to the PTV was prescribed to the 95% isodose line. RESULTS: Seventy patients, between 5/09 and 4/13, were treated. Patients had early non-small cell lung cancer (n = 13) or locally recurrent lung cancer (n = 29) and pulmonary oligometastases (n = 28). Fifty-seven percent of the patients received BED of 132 with a schedule of 60Gy in 12 Gy fractions. Median follow up time was 18.3 months, 4/70 patients experienced local failure (6%). Median OS for the whole cohort was 4.6 years (CI 3-7 years). Ten patients had grade 1-2 radiation pneumonitis. One patient developed fatal bronchial bleeding. CONCLUSIONS: SBRT for central tumors is safe and effective in patients with central disease, reiradiation, recurrence following surgery and in oligometastes.

High-Dose Radiotherapy as Neoadjuvant Treatment in Non-Small-Cell Lung Cancer.

BACKGROUND: Trimodality therapy (chemoradiation followed by surgery) provides a benefit in progression-free survival but not overall survival. We sought to determine if a high dose of radiation could be delivered safely and provide a clinical benefit. METHODS: Consecutive patients with stage IIIA or IIIB non-small-cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy followed by surgery were reviewed with IRB approval. RESULTS: A total of 48 patients were treated from November 2007 to May 2014. Of these, 64% had stage IIIA disease while 36% had stage IIIB; 46% had adenocarcinoma, 34% squamous, and 23% NSCLC not otherwise specified. The median dose of chemoradiotherapy was 72 Gy (60-72). Overall, 86% of patients received cisplatin (50 mg/m2) and etoposide (50 mg/m2) concurrently with radiotherapy; 72% of patients underwent lobectomy following chemoradiotherapy and 28% underwent pneumonectomy. The 30- and 90-day mortality rates were 0%. The nodal downstaging rate was 82% and there was a 64% rate of pathologic complete response. The overall survival was 29.9 months (95% CI, 19-86 months). The median time to locoregional progression was 35.1 months and the median time to distant progression was 39.3 months. Locoregional failure was 8% and distant failure was 44%. CONCLUSION: High-dose preoperative chemoradiotherapy was safe and effective. This combination should be further considered.

Lung transplantation in cystic fibrosis patients in Israel: The importance of ethnicity and nutritional status.

OBJECTIVES: To assess the characteristics that correlate with better outcomes after lung transplantation for patients with cystic fibrosis (CF). METHODS: We retrospectively reviewed the charts of all patients with CF who underwent lung transplantation between 1996 and 2014 at Rabin Medical Center, Israel. RESULTS: Fifty patients with CF underwent 55 lung transplantations. Eighteen patients (36%) died during the study period. Actuarial survival was 83%, 68%, 62%, and 39% at 1, 3, 5, and 10 years, respectively. Better survival correlated with: BMI at 6 months and 1 year after transplantation (P = .002 and P = .003, respectively), ischemic time of less than 300 minutes (P = .023), absence of liver disease (P = .012), and Jewish compared to Arab ethnicity (P = .007). Freedom from bronchiolitis obliterans syndrome (BOS) was 87%, 75%, and 72% at 1, 3, and 5 years, respectively. BOS was more common and appeared earlier in the Arab than in the Jewish population (P = .012, P = .007). Additionally, prolonged time free of BOS correlated with male gender (P = .039), older age (P < .001), absence of liver disease (P = .012), and higher BMI 1 year after transplantation (P < .001). CONCLUSIONS: Clinically important determinants for survival include BMI pre- and 1-year post-transplantation and improved freedom from BOS. Arab ethnicity correlated with higher incidence and earlier onset of BOS compared to Jewish ethnicity in Israel.

Survival following lung transplantation for artificial stone silicosis relative to idiopathic pulmonary fibrosis.

BACKGROUND: Silicosis is a progressive lung disease resulting from the inhalation of respirable crystalline silica. Lung transplantation is the only treatment for end-stage silicosis. The aim of this study was to analyze the survival experience following lung transplantation among patients with silicosis. METHODS: We reviewed data for all patients who underwent lung transplantation for silicosis and a matched group undergoing lung transplantation for idiopathic pulmonary fibrosis (IPF) at a single medical center between March 2006 and the end of December 2013. Survival was followed through 2015. RESULTS: A total of 17 lung transplantations were performed for silicosis among 342 lung transplantations (4.9%) during the study period. We observed non-statistically significant survival advantage (hazard ratio 0.6; 95%CI 0.24-1.55) for those undergoing lung transplantation for silicosis relative to IPF patients undergoing lung transplantation during the same period. CONCLUSIONS: Within the limits of a small sample, survival in silicosis patients following lung transplantation was not reduced compared to IPF. Am. J. Ind. Med. 60:248-254, 2017. © 2017 Wiley Periodicals, Inc.

RET Fusion Lung Carcinoma: Response to Therapy and Clinical Features in a Case Series of 14 Patients.

BACKGROUND: RET (rearranged during transfection) fusions have been reported in 1% to 2% of lung adenocarcinoma (LADC) cases. In contrast, KIF5B-RET and CCDC6-RET fusion genes have been identified in 70% to 90% and 10% to 25% of tumors, respectively. The natural history and management of RET-rearranged LADC are still being delineated. MATERIALS AND METHODS: We present a series of 14 patients with RET-rearranged LADC. The response to therapy was assessed by the clinical response and an avatar model in 2 cases. Patients underwent chemotherapy, targeted therapy, and immunotherapy. RESULTS: A total of 14 patients (8 women; 10 never smokers; 4 light smokers; mean age, 57 years) were included. KIF5B-RET and CCDC6-RET variants were diagnosed in 10 and 4 cases, respectively. Eight patients had an early disseminated manifestation, seven with KIF5B-RET rearranged tumor. The features of this subset included bilateral miliary lung metastases, bone metastases, and unusual early visceral abdominal involvement. One such patient demonstrated an early and durable complete response to cabozantinib for 7 months. Another 2 patients treated with cabozantinib experienced a partial response, with rapid significant clinical improvement. Four patients with tumors harboring CCDC6-RET and KIF5B-RET fusions showed pronounced and durable responses to platinum-based chemotherapy that lasted for 8 to 15 months. Two patients' tumors showed programmed cell death ligand 1-positive staining but did not respond to pembrolizumab. The median overall survival was 22.8 months. CONCLUSION: RET-rearranged LADC in our series tended to occur as bilateral disease with early visceral involvement, especially with KIF5B fusion. Treatment with cabozantinib achieved responses, including 1 complete response. However, further studies are required in this group of patients.

Malignant Melanoma in Association With a Thymic Nevus in a Patient With a Giant Congenital Nevus.

Nevi and melanocytic proliferations are known to appear in multiple extracutaneous sites, including lymph nodes and meninges. We report a case of an anterior mediastinal mass in a patient with a giant congenital nevus and neurofibromatosis type I. Histologically, the tumor was found to be a malignant melanoma in the thymus arising in association with a nevus that involved most of the thymic tissue. There was no sign of cutaneous melanoma on skin examination. We suggest that the tumor originated from the benign nevus in the thymus, a rare extracutaneous location for nevi and malignant melanoma.

Limitations in exercise and functional capacity in long-term postpneumonectomy patients.

INTRODUCTION: Pneumonectomy results in impairments of pulmonary function and exercise intolerance associated with respiratory limitations. However, exercise capacity and functional capacity are less known at long-term followup. The aims of this study were to assess exercise tolerance and functional capacity among long-term postpneumonectomy patients and to identify the limiting factors in exercise related to comorbidities and which lung was involved. METHODS: Seventeen postpneumonectomy patients aged 59 ± 13 years and 5.5 ± 4.2 years postoperation were prospectively studied. Pulmonary function tests (PFTs), cardiopulmonary exercise test (CPET), Doppler-echocardiography, 6-minute walk test (6MWT) distance, and "senior fitness tests" (SFTs) were conducted with all patients. RESULTS: Exercise capacity and PFT were diminished ((Equation is included in full-text article.)O2 peak; 11.5 ± 3.3 mL·kg·min, 48 ± 17% predicted, forced vital capacity % predicted; 55 ± 13, FEV1% predicted; 46 ± 14, respectively). Most patients presented with low exercise cardiovascular parameters and normal breathing reserve (17 ± 12 L) during CPET. No significant differences were shown between right and left pneumonectomy and comorbidities related to exercise limitations (χ= 1.96, P = .376). Functional capacity in walking and SFTs were near normal (6MWT distance; 490 ± 15 m, 89 ± 25% predicted). Echocardiography showed normal left ventricle systolic function (ejection fraction, 60 ± 4%) with mildly elevated systolic pulmonary arterial pressure (38 ± 12 mm Hg). CONCLUSIONS: Long-term postpneumonectomy patients demonstrated decreased exercise capacity, limited primarily by the cardiovascular system regardless of lung resection side or comorbidities, although tests of functional capacity were near normal. Most patients can maintain near normal life in activities of daily living, but the long-term cardiopulmonary exercise function should be considered for meticulous evaluation and clinical care to preserve physiological reserves.

Efficacy of bronchoscopic closure of a bronchopleural fistula with amplatzer devices: long-term follow-up.

BACKGROUND: The development of a bronchopleural fistula (BPF) is associated with high rates of morbidity and mortality. We have developed a minimally invasive method of bronchoscopic BPF closure using Amplatzer devices (AD) and Amplatzer vascular plugs (AVP), with excellent short-term results. OBJECTIVES: The aim of the present report was to explore the long-term outcome of patients treated by Amplatzer occluders and the durability of this novel modality of BPF treatment. METHODS: A total of 31 central BPF in 31 patients (mean age 66.8 years, range 19-91) were sealed under moderate sedation bronchoscopically by either AD (n = 19) or AVP (n = 12). The average follow-up period was 17.6 months (range 1-68 months). RESULTS: The main etiology for BPF was surgery (n = 24), pneumonectomy (n = 14) or lobectomy/segmentectomy (n = 10). The underlying disease was either primary (n = 19) or metastatic (n = 2) lung cancer. The immediate success rate was 96% as symptoms related to BPF disappeared in 30 of the 31 patients. Short-term (<30 days) mortality was 13% (4 patients). At follow-up, 14 patients (45%) are still alive. Out of 12 patients with late mortality, in 5 patients (41%) the death was directly related to cancer relapse, and no patient died due to BPF recurrence. CONCLUSION: Endobronchial closure of BPF using both types of Amplatzer occluders (AD and AVP) is a minimally invasive effective modality of treatment with high safety profile and satisfactory long-term outcome considering the poor prognosis in this particular group of patients.

Metallic stents for airway complications after lung transplantation: long-term follow-up.

OBJECTIVES: Bronchial stenosis is still a significant source of morbidity and mortality following lung transplantation (LTX) and often mandating placement of a bronchial stent. It has been suggested that although self-expanding metal stents offer excellent early palliation, their long-term complication rates are unacceptably high, and hence, their usage in many transplantation centres has been nearly abandoned. The aim of the study was to assess short- and long-term complication rates and survival in LTX patients with bronchial stenosis treated with insertion of self-expanding metal stents. METHODS: From January 1997 to March 2013, 435 patients underwent LTX (325 single-LTX and 110 bilateral LTX). Of 503 actual anastomoses at risk (derived by subtracting the number of anastomoses in 30 patients who died within 30 days of LTX), 60 airway complications (11.9%) in 47 patients required self-expanding metal stent insertion. We assessed the early results and long-term outcomes and survival compared with LTX patients in whom stents were not required. RESULTS: The median follow-up period ranged from 1 to 132 (median 54) months. Immediate relief of symptoms was achieved in the vast majority of patients (95%). One-, three- and five-year survival in patients who required self-expanding metal stent placement were 77.7, 66.6 and 55.5%, respectively. The corresponding survival rates in LTX patients without stents were 69, 64.9 and 61.1% (P > 0.05). CONCLUSIONS: Self-expanding metal stents are safe and effective tools in the management of airway complications post-LTX and provide immediate improvement in symptoms and pulmonary function tests in the vast majority of cases. The long-term complication rate is low, and mortality is similar to that in LTX patients who did not require stent insertion.

Endobronchial closure of bronchopleural fistulas with Amplatzer vascular plug.

OBJECTIVE: Bronchopulmonary fistula (BPF) is a severe complication following lobectomy or pneumonectomy and is associated with a high rate of morbidity and mortality. We have developed a novel minimally invasive method of central BPF closure using Amplatzer vascular plug (AVP) device that was originally designed for the transcatheter closure of vascular structures in patients with small BPF. METHODS: Patients with BPFs were treated under conscious sedation by bronchoscopic closure of BPFs using AVP. After locating the fistula using bronchography, the self-expanding nitinol made AVP occluder to be delivered under direct bronchoscopic guidance over a loader wire into the fistula followed by bronchography to assure correct device positioning and sealing of the BPF. RESULTS: Six AVPs were placed in five patients, four males and one female, with a mean age of 62.3 years (range: 51-82 years). The underlying disorders and etiologies for BPF development were lobectomy (two patients), pneumonectomy for lung cancer (one patient), lobectomy due to necrotizing pneumonia (one patient), and post-tracheostomy tracheo-pleural fistula (one patient). In all the patients, the bronchoscopic procedure was successful and symptoms related to BPF disappeared following closure by the AVP. The results were maintained over a median follow-up of 9 months (range: 5-34 months). CONCLUSIONS: Endobronchial closure using the AVP is a safe and effective method for treatment of small postoperative BPF. The ease of their implantation by bronchoscopy under conscious sedation adds this novel technique to the armatorium of minimally invasive modalities for the treatment of small BPF.