Ramón Bordes

Smoking-related interstitial lung diseases: radiologic-pathologic correlation

Smoking-related interstitial lung diseases (SRILD) are a heterogeneous group of entities of unknown cause. These diseases include desquamative interstitial pneumonia (DIP), respiratory-bronchiolitis-related interstitial lung disease (RB-ILD), pulmonary Langerhans’ cell histiocytosis (LCH) and idiopathic pulmonary fibrosis (IPF). High-resolution CT is highly sensitive in the detection of abnormalities in the lung parenchyma and airways. Ground-glass attenuation can occur in DIP and RB-ILD. Whereas DIP is histologically characterized by intra-alveolar pigmented macrophages, RB-ILD shows alveolar macrophages in a patchy peribronchiolar distribution. LCH shows nodular infiltrates on histopathological examination containing varying amounts of characteristic Langerhans’ histiocytes. The HRCT findings are characteristically bilateral, symmetrical and diffuse, involving the upper lobe zones with sparing of the costophrenic angles. The most prominent CT features are nodules (sometimes cavitary) measuring 1 to 10xa0mm in diameter, cysts and areas of ground-glass attenuation. Pathologically, IPF is characterized by its heterogeneity with areas of normal clung, alveolitis and end-stage fibrosis shown in the same biopsy specimen. High-resolution CT findings consist of honeycombing, traction bronchiectasis and intralobular interstitial thickening with subpleural and lower lung predominance. Since coexisting lesions in the same cases have been observed, a better understanding of the different smoking-related interstitial lung diseases (SRILD) allows a more confident and specific diagnosis.

Evaluation of Biopsy Classification for Rejection: Relation to Detection of Myocardial Damage by Monoclonal Antimyosin Antibody Imaging

OBJECTIVESnThis study sought to compare the histologic grades of rejection in endomyocardial biopsy specimens with the global estimate of myocardial transplant-related cardiac damage detected by myocardial uptake of monoclonal antimyosin antibodies.nnnBACKGROUNDnThe diagnosis and treatment of acute cardiac allograft rejection is based on the interpretation of endomyocardial biopsies. Because allograft rejection is a multifocal process and biopsy is obtained from a small area of the right ventricle, sampling error may occur. Global assessment of myocardial damage associated with graft rejection is now possible with the use of antimyosin scintigraphy. The present study was undertaken to compare the histologic grades of rejection in endomyocardial biopsy specimens with the global assessment of transplant-related myocardial damage detected by antimyosin scintigraphy.nnnMETHODSnBiopsies (n=395) from 112 patients were independently interpreted by three pathologists in a blinded manner according to the original Stanford four-grade (normal, mild, moderate and severe) and the current International Society of Heart and Lung Transplantation (ISHLT) seven-grade (0, 1A, 1B, 2, 3A, 3B and 4) classifications. The results were correlated with 395 antimyosin studies performed at the time of the biopsies. The heart/lung ratio of antimyosin antibody uptake was used to assess the severity of myocardial damage.nnnRESULTSnIn the Stanford biopsy grade classification, significantly higher antimyosin uptake, indicating increasing degrees of myocardial damage, were associated with normal (1.78+/-0.26), mild (1.88+/-0.31) and moderate (1.95+/-0.38) biopsy classifications for rejection (p < 0.01). In the ISHLT classification, significant differences were detected only for antimyosin uptake associated with grades 0 (1.77+/-0.26) and 3A (1.98+/-0.39) but not for intermediate scores (1A, 1B and 2). In view of the similar intensity of antibody uptake among the various grades, ISHLT biopsy scores were regrouped: normal biopsies in grade A; 1A and 1B as grade B; and 2 and 3A as grade C. Antimyosin uptake in grades A, B and C was 1.78+/-0.26, 1.88+/-0.31, 1.95+/-0.38, respectively (p < 0.01).nnnCONCLUSIONSnThe current ISHLT seven-grade scoring system does not reflect the progressive severity of myocardial damage associated with heart transplant rejection. Because myocardial damage constitutes the basis of treatment for allograft rejection, there is a need to reevaluate the ISHLT grading system, given its importance for multicenter trials.

Efficacy of augmented immunosuppressive therapy for early vasculopathy in heart transplantation

OBJECTIVESnThe present study was undertaken to prospectively and comparatively evaluate the role of serial myocardial perfusion imaging and coronary angiography for the detection of early vasculopathy in a large patient population and also to determine the short- and long-term efficacy of augmented immunosuppressive therapy in the potential reversal of the early vasculopathy.nnnBACKGROUNDnAllograft vasculopathy is the commonest cause of death after the first year of heart transplantation. Anecdotal studies have reported the efficacy of augmented immunosuppressive therapy after early detection of vascular involvement. However, no prospective study has evaluated the feasibility of early detection and treatment of allograft vasculopathy.nnnMETHODSnIn 76 cardiac allograft recipients, 230 coronary angiographic and 376 scintigraphic studies were performed in a follow-up period of 8 years. Angiography was performed at 1 month and every year after transplantation, and thallium-201 scintigraphy at 1, 3, 6 and 12 months after transplantation and twice a year thereafter. Prospective follow-up of 76 patients showed that 18 developed either angiographic or scintigraphic evidence of coronary vasculopathy. All episodes were treated with 3-day methylprednisolone pulse and antithymocyte globulin.nnnRESULTSnTwenty-two episodes of vasculopathy were diagnosed and treated in these 18 patients. Of these 22 episodes, two were detected only by angiography, seven by both angiography and scintigraphy, four by scintigraphy and histologic evidence of vasculitis and nine episodes only by thallium-201 scintigraphy studies. Angiographic and/or scintigraphic resolution was observed in 15 of the 22 episodes (68%) with augmented immunosuppression. The likelihood of regression was higher when treatment was instituted within the first year of transplantation (92%) than after the first year (40%) (p = 0.033). Eighty percent of patients who responded to follow-up.nnnCONCLUSIONSnThe present study suggests that early detection of allograft coronary vasculopathy is feasible with surveillance myocardial perfusion or coronary angiographic studies. When identified early after transplantation, immunosuppressive treatment may result in regression of coronary disease.

Active myocardial damage without attending inflammatory response in dilated cardiomyopathy.

OBJECTIVESnThis study aimed to compare indium-111 (111In)-monoclonal antimyosin antibody uptake in patients with dilated cardiomyopathy before heart transplantation with the histologic findings in the explanted hearts.nnnBACKGROUNDnA high prevalence of 111In-monoclonal antimyosin antibody uptake has been described in patients with dilated cardiomyopathy, suggesting the presence of active, ongoing myocyte damage; however, no correlation between monoclonal antimyosin antibodies and histologic findings is available in these patients.nnnMETHODSnA consecutive series of 21 patients with dilated cardiomyopathy awaiting heart transplantation were studied with monoclonal antimyosin antibodies before the operation, and the results were compared with the histologic analysis of the explanted hearts. The interval between monoclonal antimyosin antibody studies and transplantation was 1 to 90 days (mean 58 +/- 31).nnnRESULTSnUsing a semiquantitative method (heart/lung ratio), monoclonal antimyosin antibody uptake was present in 15 (71%) of 21 patients, but active myocarditis in the explanted hearts was detected in only 7. In 11 patients, intense monoclonal antimyosin antibody uptake coexisting with absent myocyte damage or cellular infiltration of explanted hearts was noted. One patient who showed preoperative monoclonal antimyosin antibody uptake underwent transplantation 11 h later, and ex vivo diffuse myocardial antimyosin uptake was detected, but active myocarditis was seen only at cardiectomy in only a small area of the heart; the rest of the myocardium showed no signs of myocyte damage.nnnCONCLUSIONSnIn dilated cardiomyopathy, monoclonal antimyosin antibody uptake cannot be equated with the presence of an inflammatory response detected in the myocardium of the explanted heart.

Burden of myocardial damage in cardiac allograft rejection: Scintigraphic evidence of myocardial injury and histologic evidence of myocyte necrosis and apoptosis

BackgroundBecause myocardial damage determines morbidity and outcomes in heart transplant rejection, assessment of total burden of myocardial damage is highly desirable. In addition to myocyte necrosis, programmed cell death, or apoptosis, has recently been shown to contribute to cardiac allograft rejection. In the present study, we noninvasively determined myocardial damage by antimyosin scintigraphy and compared it with necrotic and apoptotic myocardial damage in endomyocardial biopsy (EMB) specimens.Methods and ResultsForty scintigraphic and histologic studies were simultaneously performed. Of these, 19 patients had no EMB evidence of allograft rejection (group I, International Society of Heart and Lung Transplantation [ISHLT] grade 0/4), 12 had mild rejection (group II, ISHLT grades 1A and 1B), and 9 had evidence of moderate allograft rejection (group III, ISHLT grades 2, 3A, and 3B). None of the biopsies demonstrated severe allograft rejection (ISHLT grade 4/4). The severity of global myocyte damage in 40 patients was assessed by antimyosin scintigraphy. Endomyocardial biopsies were performed in these patients within 48 hours of imaging study; biopsy specimens were characterized for presence of myocyte necrosis and apoptosis. Evidence of myocyte necrosis was observed in 9 (23%) of 40 EMB specimens. Nineteen EMB specimens of group I had no inflammation and no myocyte necrosis, 12 of group II specimens showed interstitial mononuclear cell infiltration (only) but no myocyte necrosis, and all 9 of group III specimens had evidence of cellular infiltration and myocyte damage. Myocyte necrosis was assessed by hematoxylin-eosin and trichrome staining of EMB specimens. On the other hand, apoptosis of myocytes, as assessed by TUNEL staining of DNA fragments, was seen in 22 (55%) of the 40 biopsy specimens: 47%, 58%, and 67% in groups I, II and III, respectively. Abnormal antimyosin scan findings, indicating presence of myocardial damage, were observed in 9 of the 19 patients in group I and in all patients in groups II and III. Although positive antimyosin scan results in group III patients are concordant with the presence of histologic myocardial necrosis, myocardial uptake of antimyosin antibodies in groups I and II (no apparent myocyte damage at light microscopic examination) could reflect either sampling error of the biopsy or ongoing apoptotic myocyte damage.ConclusionsApoptosis of myocytes is frequently observed during cardiac allograft rejection. The presence of apoptotic myocytes in the absence of histologic rejection activity in patients with antimyosin uptake suggests that apoptosis could be an additional mechanism of transplant-associated myocardial damage.

Membrane PKC-beta 2 protein expression predicts for poor response to chemotherapy and survival in patients with diffuse large B-cell lymphoma.

The protein kinase C (PKC) plays an important role in the activation and survival of B cells. The purpose of this study was to analyze the clinical significance of PKC-beta 2 protein expression in patients with diffuse large B-cell lymphoma (DLBCL). Tumors from 76 patients with DLBCL who received anthracycline-containing chemotherapy were examined for PKC-beta 2 protein expression by immunohistochemistry. Twenty-six cases (34%) were positive for PKC-beta 2 protein, and 50 (66%) were negative. Patients with PKC-beta-2-positive tumors showed a lower complete remission rate (31 vs 62%; P=0.015) and a lower 5-year disease-free survival (DFS) (30 vs 60%; P=0.03) than the PKC-beta-2-negative group. Overall survival (OS) was significantly lower in patients with the membranous staining pattern of PKC-beta 2 protein when compared to those with PKC-beta-2-negative tumors (14 vs 64%; P=0.005). In patients with low international prognostic index (IPI), those with tumors showing membrane expression of PKC-beta 2 had a significantly inferior DFS and OS (0 vs 79%, P=0.003; 25 vs 80%; P=0.01) compared to PKC-beta-2-negative tumors. In multivariate analysis for OS, the membrane staining of PKC-beta 2 is the strongest independent adverse prognostic factor (OR=3.4, P=0.011). Our results suggest that membrane expression of PKC-beta 2 protein on DLBCL predicts for poor survival, especially in patients with low IPI.

Changes in myocardial electrical impedance in human heart graft rejection

Monitoring of post‐transplant heart rejection is currently based on endomyocardial biopsy analysis. This study aimed to assess the effects of heart graft rejection on myocardial electrical impedance.

Dopamine treatment of locally procured donor hearts: relevance on postoperative cardiac histology and function☆

UNLABELLEDnAdministration of catecholamines can lead to myocyte damage. Dopamine treatment is often used in potential cardiac donors to attain hemodynamic stability. Donor hearts exposed to dopamine are rejected or selected for transplantation without clearly defined criteria. A prospective study was undertaken to analyze the clinical relevance of dopamine-induced myocardial lesions in 25 hearts (21 male, 4 female; 15-40 years, mean: 26 +/- 7) that were later used for transplantation. Donors were divided into those who had received dopamine and those who had not. Dopamine doses ranged from 2-12.5 micrograms/kg/min (mean: 6.3 +/- 3). Time of administration was 3-26 hours (mean: 16 +/- 8). Use of dopamine was unrelated to donor electrocardiographic findings, intra- or postoperative death, or difficulty coming off by-pass. Postoperatively, filling pressures were similar in both groups of patients at 2 and 10 days postoperatively. Left ventricular ejection fraction was similar in the two groups. Dopamine requirements were significantly higher in the dopamine-treated hearts (P = 0.05). Histologic findings at first biopsy revealed infiltration and cell damage in a similar proportion of patients in both groups.nnnIN CONCLUSIONndonor hearts exposed to dopamine can be accepted for transplantation if doses ranging from 2-12.5 micrograms/kg/min have been administered up to 24 hours.

Hydatid pulmonary embolism from a ruptured mediastinal cyst: high-resolution computed tomography, angiographic, and pathologic findings.

Hydatid disease is a parasitic infestation caused by the larval stage of a tapeworm of the genus Echinococcus. This report describes an extremely rare complication of echinococcal disease in which severe pulmonary hypertension developed after massive hydatid pulmonary embolism.