Milton Saute

The Role of Open Lung Biopsy in the Management and Outcome of Patients With Diffuse Lung Disease

BACKGROUNDnOpen lung biopsy (OLB) has long been considered the gold standard for the diagnosis of parenchymal lung disease. With recent advances in computed tomographic imaging and diagnostic techniques (eg, bronchoscopy), we thought it necessary to reevaluate the role of OLB in the management of patients with interstitial lung disease.nnnMETHODSnWe carried out a retrospective analysis of 103 OLBs performed at Hadassah University Hospital, Jerusalem, and Carmel Medical Center, Haifa, between 1980 and 1994. Data gathered included demographic information, underlying condition, indications for biopsy, diagnosis before biopsy, final diagnosis, change in therapy, and mortality. Benefit was defined as a change in therapy resulting in survival.nnnRESULTSnThere were 45 immunocompetent patients (group 1), 39 immunocompromised patients (group 2), and 26 children (group 3), 7 of whom were included in group 2 for analysis. Overall, a diagnosis was reached after OLB in 85% of patients. An unexpected diagnosis was reached in 52%, and a change in therapy was instituted in 46%. The overall mortality rate was 20%. In group 1, the mortality rate was 13%, and benefit from OLB was reached in only 18%. In group 2, the mortality rate was 39%, and benefit was achieved in 46%, and in group 3, the mortality rate was 12% and benefit, 50%.nnnCONCLUSIONSnOpen lung biopsy is an excellent diagnostic technique. In immunocompetent patients, the benefit is relatively low, as therapy (corticosteroids) is frequently used after biopsy. In immunocompromised patients, therapy changes substantially after OLB, but mortality is high. Therefore, OLB should be reserved for patients in whom the diagnosis is likely to lead to a change in therapy and in patients in whom the underlying condition has a reasonable prognosis according to the clinical impression by the attending physician.

Lung transplantation in patients with scleroderma: case series, review of the literature, and criteria for transplantation

Abstract:u2002 Backgrounds:u2002 The use of lung transplantation (LTX) to treat respiratory failure because of scleroderma is controversial. We present our experience, review the current literature, and suggest specific criteria for LTX in scleroderma. Of the 174 patients who underwent LTX at our center, seven (4%) had scleroderma‐associated respiratory failure.

The use of surfactant in lung transplantation.

Background. Lung transplantation impairs surfactant activity, which may contribute to primary graft dysfunction (PGD). Prompted by studies in animals and a few reports in humans, this study sought to determine if the administration of surfactant during transplantation serves as an effective preventive measure. Methods. An open, randomized, controlled prospective design was used. Forty-two patients scheduled for single (n=38) or double (n=4) lung transplantation at a major tertiary medical center were randomly assigned to receive, or not, intraoperative surfactant treatment. In the treated group, bovine surfactant was administered at a dose of 20 mg phospholipids/kg through bronchoscope after the establishment of bronchial anastomosis. The groups were compared for oxygenation (PaO2/FiO2), chest X-ray findings, PGD grade, and outcome. Results. Compared with the untreated group, the patients who received surfactant were characterized by better postoperative oxygenation mean PaO2/FiO2 (418.8±123.8 vs. 277.9±165 mm Hg, P=0.004), better chest radiograph score, a lower PGD grade (0.66 vs. 1.86, P=0.005), fewer cases of severe PGD (1 patient vs. 12, P<0.05), earlier extubation (by 2.2 hr; 95% CI 1.1–4.3 hr, P=0.027), shorter intensive care unit stay (by 2.3 days; 95% CI 1.47–3.74 days, P=0.001), and better vital capacity at 1 month (61% vs. 50%, P=0.022). One treated and 2 untreated patients died during the first postoperative month. Conclusions. Surfactant instillation during lung transplantation improves oxygenation, prevents PGD, shortens intubation time, and enhances early posttransplantation recovery. Further, larger studies are needed to assess whether surfactant should be used routinely in lung transplantation.

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

OBJECTIVESnBronchial 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.nnnMETHODSnFrom 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.nnnRESULTSnThe 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).nnnCONCLUSIONSnSelf-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

OBJECTIVEnBronchopulmonary 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.nnnMETHODSnPatients 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.nnnRESULTSnSix 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).nnnCONCLUSIONSnEndobronchial 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.

Risk factors for death while awaiting lung transplantation in Israeli patients: 1997—2006

OBJECTIVEnPatients with end-stage lung disease very frequently die while awaiting lung transplantation. The aim of this study was to identify factors associated with mortality in patients referred for lung transplant assessment.nnnMETHODSnThe files of all consecutive patients listed for lung transplantation in Israel between 1997 and 2006 were reviewed and the data were compared statistically between those who survived to transplantation.nnnRESULTSnA total of 229 patients were listed for lung transplantation, of whom 42 (18.3%) died while awaiting transplantation. Comparison of the patients who survived to transplantation with those who did not using univariate analysis revealed that the died-waiting group was significantly older, used steroids to a greater extent, had more IPF patients and less emphysematous, and lower mean oxygen saturation at rest (p=0.005). There were no between-group differences in comorbid diseases or pulmonary function measurements. The 6 min walk distance was strongly and inversely correlated with risk of death before transplantation (p=0.005). On multivariate analysis, only oxygen saturation at rest was a significant independent risk factor for death while awaiting transplantation (OR 0.886; C.I. 0.805-0.974).nnnCONCLUSIONSnThere are several risk factors for death in the Israeli population listed for LTX, including age, steroid use, emphysematous patients and lower saturation at rest.

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. Micro‐Abstract Data are increasing regarding RET (rearranged during transfection) fusions in lung cancer. We present our experience with the natural history of this disease and its response to targeted therapy and standard chemotherapy in 14 patients. In our series, RET‐rearranged lung adenocarcinoma had an early disseminated presentation, especially with KIF5B fusion. Treatment with cabozantinib achieved responses, including 1 complete response.

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 ( O2 peak; 11.5 ± 3.3 mL−1·kg−1·min−1, 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 (&khgr;2= 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.

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

BACKGROUNDnSilicosis 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.nnnMETHODSnWe 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.nnnRESULTSnA 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.nnnCONCLUSIONSnWithin 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.

Primary Pulmonary Amyloidosis Due to Low-Grade B Cell Lymphoma

Pulmonary involvement is not an infrequent complication of systemic amyloidosis, although affected patients rarely have significant pulmonary symptoms. In contrast, localized (primary) pulmonary amyloidosis is rare. We report a case of pulmonary low-grade B cell lymphoma with amyloid production, causing localized pulmonary amyloidosis.