ABSTRACT
RATIONALE: Since the pathogenesis of chronic lung allograft dysfunction (CLAD) remains poorly defined with no known effective therapies, the identification and study of key events which increase CLAD risk is a critical step towards improving outcomes. We hypothesized that bronchoalveolar lavage fluid (BALF) CXCR3 ligand concentrations would be augmented during organizing pneumonia (OP) and that episodes of OP with marked chemokine elevations would be associated with significantly higher CLAD risk. METHODS: All transbronchial biopsies (TBBX) from patients who received lung transplantation between 2000 to 2010 were reviewed. BALF concentrations of the CXCR3 ligands (CXCL9, CXCL10 and CXCL11) were compared between episodes of OP and "healthy" biopsies using linear mixed-effects models. The association between CXCR3 ligand concentrations during OP and CLAD risk was evaluated using proportional hazards models with time-dependent covariates. RESULTS: There were 1894 bronchoscopies with TBBX evaluated from 441 lung transplant recipients with 169 (9%) episodes of OP and 907 (49%) non-OP histopathologic injuries. 62 (37%) episodes of OP were observed during routine surveillance bronchoscopy. Eight hundred thirty-eight (44%) TBBXs had no histopathology and were classified as "healthy" biopsies. There were marked elevations in BALF CXCR3 ligand concentrations during OP compared with "healthy" biopsies. In multivariable models adjusted for other injury patterns, OP did not significantly increase the risk of CLAD when BAL CXCR3 chemokine concentrations were not taken into account. However, OP with elevated CXCR3 ligands markedly increased CLAD risk in a dose-response manner. An episode of OP with CXCR3 concentrations greater than the 25th, 50th and 75th percentiles had HRs for CLAD of 1.5 (95% CI 1.0-2.3), 1.9 (95% CI 1.2-2.8) and 2.2 (95% CI 1.4-3.4), respectively. CONCLUSIONS: This study identifies OP, a relatively uncommon histopathologic finding after lung transplantation, as a major risk factor for CLAD development when considered in the context of increased allograft expression of interferon-γ inducible ELR- CXC chemokines. We further demonstrate for the first time, the prognostic importance of BALF CXCR3 ligand concentrations during OP on subsequent CLAD risk.
Subject(s)
Lung Transplantation , Lung/diagnostic imaging , Lung/physiopathology , Pneumonia/diagnostic imaging , Pneumonia/physiopathology , Receptors, CXCR3/immunology , Adult , Biomarkers/chemistry , Biomarkers/metabolism , Biopsy , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/immunology , Bronchoscopy , Chemokine CXCL10/genetics , Chemokine CXCL10/immunology , Chemokine CXCL11/genetics , Chemokine CXCL11/immunology , Chemokine CXCL9/genetics , Chemokine CXCL9/immunology , Female , Gene Expression , Humans , Ligands , Lung/immunology , Male , Middle Aged , Pneumonia/genetics , Pneumonia/immunology , Proportional Hazards Models , Receptors, CXCR3/genetics , Respiratory Function Tests , Retrospective Studies , Risk , Transplantation, HomologousABSTRACT
BACKGROUND Laparoscopic cholecystectomy is a commonly performed surgical procedure. In certain situations visualization of the Callot triangle can become difficult due to inflammation, adhesions, and sclerosing of the anatomy. Without being able to obtain the "critical view of safety" (CVS), there is increased risk of damage to vital structures. An alternative approach to the conventional conversion to an open cholecystectomy (OC) would be a laparoscopic subtotal cholecystectomy (LSC). CASE REPORT We present a case of a 56-year-old male patient with acute cholecystitis with a "difficult gallbladder" managed with LSC. Due to poor visualization of the Callot triangle due to adhesions, safe dissection was not feasible. In an effort to avoid injury to the common bile duct (CBD), dissection began at the dome of the gallbladder allowing an alternative view while ensuring safety of critical structures. CONCLUSIONS We discuss the potential benefits and risks of LSC versus conversion to OC. Our discussion incorporates the pathophysiology that allows LSC in this particular circumstance to be successful, and the considerations a surgeon faces in making a decision in management.
Subject(s)
Cholecystectomy, Laparoscopic/methods , Cholecystitis/surgery , Gallbladder/pathology , Cholecystectomy/methods , Cholecystitis/diagnosis , Chronic Disease , Dissection/methods , Fibrosis , Humans , Male , Middle Aged , Tissue Adhesions/surgery , Treatment OutcomeABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a specific form of chronic interstitial lung pneumonia associated with the histologic pattern of usual interstitial pneumonia (UIP). Although UIP is a distinct histologic lesion, this histologic pattern is not specific for IPF and can also be found in other diseases (e.g., connective tissue disease and asbestosis). Clinical features of IPF include progressive cough, dyspnea, restrictive ventilatory defect, and progressive fibrosis and destruction of the lung parenchyma. IPF is rare (13-42 cases/100,000), and primarily affects older adults (>50 years of age). The diagnosis of IPF often requires surgical lung biopsy, but the diagnosis can be affirmed with confidence in some patients provided the results of computed tomographic (CT) scans and clinical features are consistent. The clinical course is variable, but inexorable progression (typically over months to years) is typical. Mean survival from the onset of symptoms approximates 3 to 5 years. Medical treatment is only modestly effective, primarily by slowing the rate of disease progression. Lung transplantation is the best therapeutic option.
