Robert Gosselin

Integrated FDG-PET/CT does not make invasive staging of the intrathoracic lymph nodes in non-small cell lung cancer redundant: a prospective study

Background: Staging of non-small cell lung cancer (NSCLC) is important for determining choice of treatment and prognosis. The accuracy of FDG-PET scans for staging of lymph nodes is too low to replace invasive nodal staging. It is unknown whether the accuracy of integrated FDG-PET/CT scanning makes invasive staging redundant. Methods: In a prospective study, the mediastinal and/or hilar lymph nodes in patients with proven NSCLC were investigated with integrated FDG-PET/CT scanning. Pathological confirmation of all suspect lymph nodes was obtained to calculate the accuracy of the fusion images. In addition, the use of the standardised uptake value (SUV) in the staging of intrathoracic lymph nodes was analysed. Results: 105 intrathoracic lymph node stations from 52 patients with NSCLC were characterised. The prevalence of malignancy in the lymph nodes was 36%. The sensitivity of the integrated FDG-PET/CT scan to detect malignant lymph nodes was 84% and its specificity was 85% (positive likelihood ratio 5.64, negative likelihood ratio 0.19). SUVmax, SUVmean and the SUVmax/SUVliver ratio were all significantly higher in malignant than in benign lymph nodes. The area under the receiver operating curve did not differ between these three quantitative variables, but the highest accuracy was found with the SUVmax/SUVliver ratio. At a cut-off value of 1.5 for the SUVmax/SUVliver ratio, the sensitivity and specificity to detect malignant lymph node invasion were 82% and 93%, respectively. Conclusion: The accuracy of integrated FDG-PET/CT scanning is too low to replace invasive intrathoracic lymph node staging in patients with NSCLC. The visual interpretation of the fusion images of the integrated FDG-PET/CT scan can be replaced by the quantitative variable SUVmax/SUVliver without loss of accuracy for intrathoracic lymph node staging.

Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in mesothelioma

Introduction: Soluble mesothelin (SM), megakaryocyte potentiating factor (MPF), and osteopontin (OPN) are blood biomarkers of mesothelioma. This study evaluates their use as markers of response to therapy and outcome. Methods: Sixty-two patients with malignant pleural mesothelioma were included in an observational multicenter study. Blood samples and matched computed tomography scans were collected at diagnosis and, when possible, during and after therapy. For each patient, the best overall radiological response was compared with the changes in serum SM, MPF, and plasma OPN levels across corresponding time points. Results: In five patients, blood sampling was done shortly before and after extrapleural pneumonectomy. SM and MPF levels markedly decreased after surgery, whereas OPN levels showed a median increase. Fifty-seven patients were surveilled during (and after) chemotherapy, of whom 27 (47%) had stable disease, 14 (25%) partial response, and 16 (28%) progressive disease. In patients with stable disease, SM and MPF levels did not change significantly across the corresponding time points, whereas OPN levels significantly decreased. In those with partial response, SM and MPF levels significantly decreased, whereas OPN levels showed no significant change. In patients with progressive disease, all three biomarker levels significantly increased. Patient responses correlated with a 15% change in all three biomarkers, although SM and MPF appeared more accurate than OPN. Low baseline OPN levels were independently associated with favorable progression-free survival and overall survival. Neither SM nor MPF showed prognostic value. Conclusions: SM and MPF levels were more closely associated with disease course than OPN and might prove useful in monitoring patient response in mesothelioma. Baseline OPN levels were an independent negative predictor of survival. These promising results require further validation.

Coagulation profile of liquid-state plasma.

BACKGROUND: Use of liquid plasma (LP) has been reported as early as the mid 1930s. Unlike fresh‐frozen plasma (FFP), LP is maintained at 1 to 6°C for up to 40 days after collection and processing. Despite its approved use by the US Food and Drug Administration, the coagulation profile of LP is incompletely described. In this study we evaluate the coagulation profile of LP stored up to 30 days.

Difficulties in the Interpretation of Chest Radiography

Reading chest X-rays is a difficult and challenging task, and is still important despite the development of powerful imaging techniques such as computed tomography, high-resolution computed tomography, and magnetic resonance. For a correct reading and interpretation of chest X-rays, it is necessary to understand the techniques, their limitations, basic anatomy and physiology, and to have a systematic system of scrutiny. However, we have to keep in mind that interpretation is submitted to perceptual and cognitive limitations and errors. In this chapter, chest X-ray will be discussed from prescription to report in all its facets.

Interstitial Lung Disease

Interstitial lung disease (ILD), also known as diffuse parenchymal lung disease, is a broad category of lung diseases that are grouped together because of their similar clinical, radiographic, physiologic, or pathologic manifestations. It includes more than 130 disorders characterized by scarring (i.e., “fibrosis”) and/or inflammation of the lungs. The traditional approach to radiographic assessement of ILD consists primarily of determining whether the pulmonary parenchymal process is located within the interstitium. This is often difficult, although radiographic criteria have been established over the past years. Therefore, radiologists use a more descriptive approach to analyze the predominant pulmonary pattern, lung volumes, lesion distribution, and the presence of associated findings. High-resolution computed tomography (HRCT) has been widely accepted as the imaging gold standard for ILD. This chapter reviews the different interstitial patterns seen on chest radiograph classified and based on their appearance patterns on HRCT.

The sound of the parasite. Diagnosing mediastinal cysts with endoscopic ultrasound techniques.

hepatic or cerebral involvement. Because the patient had a thoracotomy before, and thus anticipating diffi cult surgery, we treated him with albendazole. This resulted in a radiographic reduction in the size of the cyst after 2 and 4 months, and a stabilization after 6 months whereafter the patient was referred for resection. The intact cyst was sent for pathological examination ( fi g. 1 C). It was fi lled with a clear fl uid and its inner wall was covered with a white folded membrane. Microscopy showed that the outer part of the cyst wall or pericyst ( fi g. 1 D) consisted of a dense eosinophilic infi ltrate covering an acellular fi brinous exudate. This pericyst represents the infl ammatory reaction of the host. The inner part of the cyst wall ( fi g. 1 E) consisted of an exocyst (parasite-derived laminated membrane) and an endocyst (germinal layer), the latter barely detectable. The cyst lumen contained numerous scolices. This is the fi rst time a mediastinal echinococcosis was diagnosed by EUS, an elegant tool to investigate endothoracic cystic structures [3] which are hypoechogenic lesions that can be deformed by the ultrasound probe. The distal reinforcement of the ultrasound signal beyond the cyst is the hallmark of its fl uid content. In this case, the laminated hyperechogenic cyst wall and the presence of daughter cysts were the pathognomonic characteristics, not observed on the CT scan. Echinococcosis is caused by tapeworm infections (Echinococcus granulosis) and results in cyst formation mainly in the liver (70% of the cases) but also in the thorax, bone, spleen and brain. For the liver, there are a few cases indicating the high diagnostic value of abdominal ultrasonography [4] . Because of the risk of infection and parasite spreading, puncture of mediastinal cystic structures is not recommended [3, 5] . Patients with mediastinal cystic masses are often referred for surgery [6] . However, in case of parasitic disease, this includes the danger of parasitic spread in the thorax. Our fi ndings with EUS prompted us to treat the patient fi rst with albendazole in order to facilitate the surgical procedure. The management of patients with intrathoracic cystic structures is a challenge to pulmonologists. In adults, these symptomless structures are often discovered coincidentally on radiographs. However, an exact diagnosis is needed in view of the differential diagnoses including malignant mediastinal tumours. The main tool for imaging these structures is the CT scan, although MRI is sometimes advocated. However, these techniques do not always provide the clinician with an unequivocal diagnosis. Hence, patients are often referred to a surgeon for resection. Oesophageal endoscopic ultrasound (EUS) with a curved linear ultrasound probe is a fairly new diagnostic technique in pulmonary medicine for the investigation of the middle and posterior mediastinum. This outpatient technique allows ‘real time’ fi ne needle aspirations and is increasingly used for the diagnosis and staging of lung cancer. It signifi cantly decreases the number of mediastinoscopies and is thus cost effective [1, 2] . We show that EUS is a valuable technique for the investigation of mediastinal cystic structures, infl uencing clinical decisions. A 38-year-old Turk presented with mild thoracic pain. Three years ago, he underwent surgery for a mediastinal cyst. The diagnosis of echinococcosis was made on the resected specimen and positive serum antigens. On physical examination, no abnormalities were detected. A laboratory analysis including liver function tests and C reactive protein was normal. A contrast CT scan showed a mediastinal mass compatible with a para-atrial cyst ( fi g. 1 A) that could be approached closely with a curved linear oesophageal ultrasound probe. EUS showed a 50-mm cystic lesion reaching from the subcarinal to the retrocardial region ( fi g. 1 B). The cyst could be deformed with the ultrasound probe and a distal reinforcement of the echo-signal was observed. The cyst wall was hyper echogenic, irregular and showed the presence of different membranes. A heterogeneous content with membranes and daughter cysts (arrows in fi g. 1 B) were pathognomonic for echinococcosis. Fine needle aspiration was not performed. The CT scan excluded Published online: September 30, 2005

Lymphangioleiomyomatosis presenting with perirenal hemorrhage

Lymphangioleiomyomatosis (LAM) is a rare debilitating disease of unknown etiology, classically described as almost exclusively affecting women of childbearing age. The disease most commonly involves the lungs and is characterized by hamartomatous smooth muscle cell proliferations along blood vessels, airways and lymphatics. Most patients present with pulmonary symptoms, including shortness of breath, recurrent pneumothorax and pleural effusions. Extrapulmonary manifestations of LAM as the initial presentation of the disease are highly unusual. We present the case of a patient in whom LAM was incidentally discovered when the patient presented with retroperitoneal hemorrhage from a ruptured renal angiomyolipoma.

Semeiology of the Mediastinum

In the past, the mediastinum has been considered as the so-called “black-box” of thoracic radiology. Nowadays, CT and MRI nicely depict and explain “the who’s and the why’s” of the mediastinal lines in physiological as well in pathological conditions. The aim of this chapter is to emphasize on the important role of basic radiological findings in standard diagnostic chest XR interpretation and to correlate the radiological anatomy with cross-sectional imaging. The mediastinal lines can be defined as linear structures (reflections) visible on the conventional X-ray, formed by points of contact of the mediastinal soft tissues and the adjacent aerated lung or contact of pulmonary tissue by intervening soft tissue. Normal anatomic structures of the mediastinum may be altered by mediastinal disease. This alteration of normal anatomy and the accompanying displacement of the mediastinal lines and spaces may alert the radiologist to the presence of a mediastinal mass. Thus, familiarity with the appearance of normal mediastinal structures on chest radiography is the first crucial part in locating and identifying an abnormality. These elements will further on permit to narrow the differential diagnosis and possibly influence the choice of modality for further diagnostic imaging.

Soluble mesothelin, megakaryocyte potentiating factor, and osteopontin as markers of patient response and outcome in malignant pleural mesothelioma.

7086 Background: Radiological response evaluation is notoriously difficult in patients with malignant pleural mesothelioma, an asbestos-related malignancy. Soluble mesothelin (SM), megakaryocyte potentiating factor (MPF), and osteopontin (OPN) are blood biomarkers of mesothelioma. This study evaluates their use as markers of response to therapy and outcome. METHODS 62 patients with malignant pleural mesothelioma were surveilled in a Belgian observational multicenter study. Blood samples and CTs were collected at diagnosis and, when possible, during and after therapy, until disease progression or death. SM and MPF levels were measured in serum with the Mesomark ELISA and the non-commercial Human MPF ELISA, respectively. OPN levels were measured in plasma with the Human Osteopontin ELISA. For each patient, the best overall radiological response was compared with the change in serum SM, MPF and plasma OPN levels across the corresponding time points. Survival analysis was performed with Cox proportional hazard regression and log-rank statistics. RESULTS In five patients who underwent extrapleural pneumonectomy, SM and MPF markedly decreased after surgery, whereas OPN showed a median increase. Of the 57 patients who received chemotherapy, 27 (47%) had radiological stable disease (SD), 14 (25%) partial response (PR), and 16 (28%) progressive disease (PD). In patients with SD, biomarker levels did not change significantly (SM and MPF), or decreased (OPN). For PR and PD, biomarker levels typically decreased and increased, respectively. A change ≥15% in all three biomarkers significantly correlated with patient response, whereas SM and MPF appeared more accurate than OPN. Low baseline OPN levels were independently associated with favorable overall and progression free survival. Neither SM nor MPF were informative for patient outcome. CONCLUSIONS Relative changes in SM, MPF and OPN all three correlated with disease course, whereas SM and MPF appeared most suitable for monitoring of patients with mesothelioma. Baseline OPN levels were an independent negative predictor of survival. Further validation of these promising results remains mandatory.