New paradigms have been recently proposed in the pathogenesis of both chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), evidencing surprising similarities between ...these deadly diseases, despite their obvious clinical, radiological and pathologic differences. There is growing evidence supporting a "double hit" pathogenic model where in both COPD and IPF the cumulative action of an accelerated senescence of pulmonary parenchyma (determined by either telomere dysfunction and/or a variety of genetic predisposing factors), and the noxious activity of cigarette smoke-induced oxidative damage are able to severely compromise the regenerative potential of two pulmonary precursor cell compartments (alveolar epithelial precursors in IPF, mesenchymal precursor cells in COPD/emphysema). The consequent divergent derangement of signalling pathways involved in lung tissue renewal (mainly Wnt and Notch), can eventually lead to the distinct abnormal tissue remodelling and functional impairment that characterise the alveolar parenchyma in these diseases (irreversible fibrosis and bronchiolar honeycombing in IPF, emphysema and airway chronic inflammation in COPD).
BACKGROUND Lung cancer (LC) is frequently associated with idiopathic pulmonary fibrosis (IPF). Despite this well-known association, the outcome of LC in patients with IPF is unclear. The objective of ...this study was to evaluate the impact of LC on survival of patients with associated IPF. METHODS A total of 260 patients with IPF were reviewed, and 186 IPF cases had complete clinical and follow-up data. Among these, five cases were excluded because LC was radiologically suspected but not histologically proven. The remaining 181 cases were categorized in two groups: 23 patients with biopsy-proven LC and IPF (LC-IPF) and 158 patients with IPF only (IPF). Survival and clinical characteristics of the two groups were compared. RESULTS Prevalence of histologically proven LC was 13%, and among those with LC-IPF cumulative incidence at 1 and 3 years was 41% and 82%. Patients with LC were more frequently smokers (91.3% vs 71.6%, P = .001), with combined pulmonary fibrosis and emphysema (52% vs 32%, P = .052). Survival in patients with LC-IPF was significantly worse than in patients with IPF without LC (median survival, 38.7 months vs 63.9 months; hazard ratio = 5.0; 95% CI, 2.91-8.57; P < .001). Causes of death in the study group were respiratory failure in 43% of patients, LC progression in 13%, and LC treatment-related complications in 17%. CONCLUSIONS In patients with IPF, LC has a significant adverse impact on survival. Diagnosis and treatment of LC in IPF are burdened by an increased incidence of severe complicating events, apparently as lethal as the cancer itself.
- Transbronchial cryobiopsy has recently been proposed as an alternative to surgical biopsy in the diagnosis of diffuse lung disease.
- To familiarize pathologists with transbronchial cryobiopsy, ...including what it is, how it is performed, how it compares to other techniques of lung biopsy in diffuse lung disease, what are the technical issues relating to it, what the complications are, how cryobiopsies should be interpreted, and the clinical usefulness of cryobiopsy.
- All the available literature on cryobiopsy in diffuse lung disease through May 2016, primarily in the last 5 years, was reviewed, and some unpublished data known to the authors were included.
- Cryobiopsies are considerably larger than forceps biopsies and allow pattern recognition approaching that of a surgical lung biopsy in many cases. Artifacts associated with cryobiopsy are minimal. In comparison with surgical lung biopsies, the diagnosis rate with cryobiopsies is lower, in the neighborhood of 80%, versus higher than 90% for surgical lung biopsies. Cryobiopsy is proposed as an alternative to surgical lung biopsy and a technique that may appreciably decrease the number of patients who require surgical lung biopsy for diagnosis. This is important because the mortality from cryobiopsy is very small (0.1% to date) compared with surgical lung biopsy (1.7% for elective procedures and considerably higher for nonelective procedures).
Surgical lung biopsy is often required for a confident multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF). Alternative, less-invasive biopsy methods, such as bronchoscopic lung ...cryobiopsy (BLC), are highly desirable.
To address the impact of BLC on diagnostic confidence in the multidisciplinary diagnosis of IPF.
In this cross-sectional study we selected 117 patients with fibrotic interstitial lung disease without a typical usual interstitial pneumonia pattern on high-resolution computed tomography. All cases underwent lung biopsies: 58 were BLC, and 59 were surgical lung biopsy (SLB). Two clinicians, two radiologists, and two pathologists sequentially reviewed clinical-radiologic findings and biopsy results, recording at each step in the process their diagnostic impressions and confidence levels.
We observed a major increase in diagnostic confidence after the addition of BLC, similar to SLB (from 29 to 63%, P = 0.0003 and from 30 to 65%, P = 0.0016 of high confidence IPF diagnosis, in the BLC group and SLB group, respectively). The overall interobserver agreement in IPF diagnosis was similar for both approaches (BLC overall kappa, 0.96; SLB overall kappa, 0.93). IPF was the most frequent diagnosis (50 and 39% in the BLC and SLB group, respectively; P = 0.23). After the addition of histopathologic information, 17% of cases in the BLC group and 19% of cases in the SLB group, mostly idiopathic nonspecific interstitial pneumonia and hypersensitivity pneumonitis, were reclassified as IPF.
BLC is a new biopsy method that has a meaningful impact on diagnostic confidence in the multidisciplinary diagnosis of interstitial lung disease and may prove useful in the diagnosis of IPF. This study provides a robust rationale for future studies investigating the diagnostic accuracy of BLC compared with SLB.
Current understanding of the complex pathogenesis of COVID-19 interstitial pneumonia pathogenesis in the light of biopsies carried out in early/moderate phase and histology data obtained at ...postmortem analysis is discussed. In autopsies the most observed pattern is diffuse alveolar damage with alveolar-epithelial type-II cell hyperplasia, hyaline membranes, and frequent thromboembolic disease. However, these observations cannot explain some clinical, radiological and physiopathological features observed in SARS-CoV-2 interstitial pneumonia, including the occurrence of vascular enlargement on CT and preserved lung compliance in subjects even presenting with or developing respiratory failure. Histological investigation on early-phase pneumonia on perioperative samples and lung biopsies revealed peculiar morphological and morpho-phenotypical changes including hyper-expression of phosphorylated STAT3 and immune checkpoint molecules (PD-L1 and IDO) in alveolar-epithelial and endothelial cells. These features might explain in part these discrepancies.
A diagnosis of interstitial lung diseases (ILDs) may include surgical lung biopsy (SLB), which is associated with significant morbidity and mortality and also appreciable costs. Transbronchial lung ...cryobiopsy (TBLC) is adopting an important role.
The aim of this study was to compare the diagnostic yield (DY) and safety of TBLC and SLB in a large cohort of patients and to perform a systematic review of the literature as well as a meta-analysis.
We performed a retrospective analysis of 447 cases with ILD undergoing TBLC and/or SLB and a systematic review of the literature (MEDLINE and Embase for all original articles on the DY and safety of TBLC in ILDs up to July 2015).
A total of 150 patients underwent SLB and 297 underwent TBLC. The median time of hospitalization was 6.1 days (SLB) and 2.6 days (TBLC; p < 0.0001). Mortality due to adverse events was observed for 2.7% (SLB) and 0.3% (TBLC) of the patients. Pneumothorax was the most common complication after TBLC (20.2%). No severe bleeding was observed. TBLC was diagnostic for 246 patients (82.8%), SLB for 148 patients (98.7%, p = 0.013). A meta-analysis of 15 investigations including 781 patients revealed an overall DY of 0.81 (0.75-0.87); the overall pooled probability of developing a pneumothorax, as retrieved from 15 studies including 994 patients, was 0.06 (95% CI 0.02-0.11).
Cryobiopsy is safe and has lower complication and mortality rates compared to SLB. TBLC might, therefore, be considered the first diagnostic approach for obtaining tissue in ILDs, reserving the surgical approach for cases in which TBLC is not diagnostic.
Standardization of trans-bronchial lung cryobiopsy in diffuse parenchymal lung diseases is imminent; however, the majority of published series on cryobiopsy include a limited number of patients and ...are characterized by several differences in procedural technical details.
This is an observational, retrospective cohort study. Aim of the study was to suggest some sampling strategies related to transbronchial cryobiopsy in the diagnostic work-up of patients with diffuse parenchymal lung diseases.
Six hundred ninety-nine patients with suspected diffuse parenchymal lung disease were recruited. A specific pathological diagnosis was achieved in 614/699 cases (87.8%) and a multidisciplinary diagnosis was obtained in 630/699 cases (90.1%). Diagnostic yield was significantly influenced by the number of samples taken (1 vs ≥ 2 biopsies, p < 0.005). In 60.4% of patients, biopsies were taken from one site and in 39.6% from different sites (in the same lobe or in two different lobes), with a significant increase in diagnostic yield, specifically in patients with fibrotic lung diseases (65.5% vs 93.4%, p < 0.0001). The 2.4 mm or 1.9 mm probes were used, with no differences in terms of diagnostic yield. Regarding safety, pneumothorax occurred in 19.2% and was influenced by baseline lung function; in all patients Fogarty balloon has been used and severe haemorrhage occurred in 0.7% of cases. Three patients (0.4% of cases) died within 30 days after the procedure.
We propose some sampling strategies of cryobiopsy which seem to be associated with a higher diagnostic yield and a favorable risk/benefit ratio: sampling at least two samples in different sites, using either the 2.4 mm or the 1.9 mm probe, intubating the patients and using bronchial blockers/catheters.
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