Despite the availability of antifibrotic therapies, many patients with idiopathic pulmonary fibrosis (IPF) will progress to advanced disease and require lung transplantation. International guidelines for transplant referral and listing of patients with interstitial lung disease are not specific to those with IPF and were published before the widespread use of antifibrotic therapy. In this review, we discussed difficulties in decision-making when dealing with patients with IPF due to the wide variability in clinical course and life expectancy, as well as the acute deterioration associated with exacerbations. Indeed, the ideal timing for referral and listing for lung transplant remains challenging, and the acute deterioration might be influenced after transplant outcomes. Of note, patients with IPF are frequently affected by multimorbidity, thus a screening program for occurring conditions, such as coronary artery disease and pulmonary hypertension, before lung transplant listing is crucial to candidate selection, risk stratification, and optimal outcomes. Among several comorbidities, it is of extreme importance to highlight that the prevalence of lung cancer is increased amongst patients affected by IPF; therefore, candidates’ surveillance is critical to avoid organ allocation to unsuitable patients. For all these reasons, early referral and close longitudinal follow-up for potential lung transplant candidates are widely encouraged.
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease characterized by irreversible scarring of the distal lung. IPF is best described by its histopathological pattern of usual interstitial pneumonia (UIP), characterized by spatial heterogeneity with alternating interstitial fibrosis and areas of normal lung, and temporal heterogeneity of fibrosis characterized by scattered fibroblastic foci (FF), dense acellular collagen and honeycomb changes. FF, comprising aggregated fibroblasts/myofibroblasts surrounded by metaplastic epithelial cells (EC), are the cardinal pathological lesion and their presence strongly correlates with disease progression and mortality. We hypothesized that the EC/FF sandwich from patients with UIP/IPF has a distinct molecular signature which could offer new insights into the crosstalk of these two crucial actors in the disease. Laser capture microdissection with RNAseq was used to investigate the transcriptome of the EC/FF sandwich from IPF patients versus controls (primary spontaneous pneumothorax). Differentially expressed gene analysis identified 23 up-regulated genes mainly related to epithelial dysfunction. Gene ontology analysis highlighted the activation of different pathways, mainly related to EC, immune response and programmed cell death. This study provides novel insights into the IPF pathogenetic pathways and suggests that targeting some of these up-regulated pathways (particularly those related to secreto-protein/mucin dysfunction) may be beneficial in IPF. Further studies in a larger number of lung samples, ideally from patients with early and advanced disease, are needed to validate these findings.
Background: The involvement of mediastinal great vessels is common in advanced stage thymic tumors, which makes their surgical resection challenging. Moreover, the impact of vascular involvement on the oncological prognosis is still unclear. The aim of this study is to investigate the surgical and oncological outcomes and the impact of vascular involvement in a population of patients operated for advanced stage thymic tumors. Methods: A retrospective analysis on four hundred and sixty-five patients undergoing resection for advanced stage (Masaoka III–IV) thymic tumors in a single high-volume center was performed. One hundred forty-four patients met the inclusion criteria and were eligible for the study. Patients were divided in two groups according to the presence or absence of vascular involvement. Results: the two groups did not differ for the baseline characteristics and showed comparable surgical outcomes. Vascular involvement was not associated with worse overall survival but with an increased recurrence rate (p = 0.03). Multivariable analysis demonstrated a higher risk of recurrence in patients without R0 resection (HR 0.11, 0.02–0.54, p = 0.006) and with thymic carcinoma (HR 2.27, 1.22–4.24, p = 0.01). Conclusions: resection of thymic tumors with vascular involvement can be performed with optimal surgical results in a high volume center. From the oncological point of view, the involvement of the great vessels seems to be associated with a higher recurrence rate without affecting long-term survival.
Purpose: Bronchial stenoses are challenging complications after lung transplantation and are associated with high rates of morbidity and mortality. We report a series of patients who underwent bronchoplasty or sleeve resection for bronchial stenoses that did not resolve with endoscopic treatment after lung transplantation. Methods: Between 1995 and 2020, 497 patients underwent lung transplantation at our Institution. 35 patients (7.0%) experienced bronchial stenoses with a median time from transplantation of 3 months. Endoscopic management was effective in 28 cases (5.6%) while 1 patient required re-transplantation. Six patients (1.2%) underwent bronchoplasty or sleeve resection. Results: The procedures of the six patients who underwent bronchoplasty or sleeve resection were as follows: lower sleeve bilobectomy (n = 3), wedge bronchoplasty of the bronchus intermedius (n = 1), isolated sleeve resection of the bronchus intermedius (n = 1), and isolated sleeve resection of the bronchus intermedius (n = 1), associated with a middle lobectomy. All patients were discharged after a median time of 11 days. At a median of 12 months from surgery, two patients remain alive with a preserved pulmonary function. Four patients died after a median time of 56 months from bronchoplasty of causes that were not related to surgery. Conclusions: Bronchial reconstructions are challenging procedures that can be performed in highly specialized centers. Despite this, they can be considered a good strategy to obtain a definitive resolution of stenosis after lung transplantation.
The histological diagnosis of pleural epithelioid mesothelioma can be difficult in the case of rare variants or in the definition of neoplasm origin in patients with previous or concomitant tumours. Currently, several immunohistochemical reactions are available in the surgical pathologist’s armamentarium that allow us to obtain a more sensitive and specific diagnosis of malignant pleural mesothelioma. However, in some cases, the final interpretation remains inconclusive. Historically, ultrastructural examination has represented a useful tool for the definition of the mesothelial nature of neoplastic cells due to their peculiar morphological characteristics. The recent international guidelines for pathological diagnosis of pleural mesothelioma suggest the use of electron microscopy when the immunohistochemical reactions are equivocal or when further support of a diagnosis of mesothelioma is needed. This paper presents three cases of pleural epithelioid mesothelioma whose diagnoses were finally supported by ultrastructural examination.