Factors causing inaccurate staging of mediastinal nodal involvement in non-small cell lung cancer patients staged by positron emission tomography

Despite documented superiority of positron emission tomography over other investigative modalities in the preoperative staging of non-small cell lung cancer, a proportion of patients will have an inaccurate staging of their mediastinal nodes. The aim of this retrospective review is to analyse the clinicopathological factors responsible for inaccurate nodal staging by integrated PET-CT. A total of 100 consecutive patients with histologically proven non-small cell lung cancer underwent staging with PET-CT prior to lung resection. Thirty-three patients, inaccurately staged by PET-CT, were analysed. Univariate analysis identified the following as significant in causing inaccurate nodal staging: history of tuberculosis (P=0.039) and non-insulin dependant diabetes (P=0.014). In multivariate analysis, we have identified the following as independent factors in causing inaccurate staging of mediastinal lymph nodes: rheumatoid arthritis, non-insulin dependent diabetes, history of tuberculosis, presence of atypical adenomatous hyperplasia and pneumonia (P<0.05). The highest rate of inaccuracy in mediastinal nodal staging was in nodal station 4 (11%, P=0.01) followed by station 7 (10%, P=0.02) and station 9 (3.5%, P=0.01). Interpretation of PET-CT staging of the mediastinum in patients with a history of the above should be with caution, as the incidence of false upstaging and down staging in these subgroups is high. Vigilance of such factors may improve the accuracy of PET-CT in staging mediastinal lymph nodes. Histological confirmation should always be sought.     

Cardiac magnetic resonance imaging at 3.0 T

Cardiovascular magnetic resonance imaging (MRI) has gained widespread acceptance for the assessment of cardiovascular disease. Cardiac MRI requires fast data acquisition schemes because of constraints imposed by physiological motion of cardiac structures and blood flow, which dictate the suitable window of data acquisition. The ongoing improvement of MRI hardware and the development of tailored imaging techniques have been the cornerstones for rapid progress in cardiac MRI. Cardiac MRI at 3.0 T holds the promise to overcome some of the signal-to-noise (SNR) limitations, especially for techniques with borderline SNR at 1.5 T (eg, myocardial perfusion, assessment of viability, or imaging of coronary arteries). The improved SNR at 3.0 T can be used to increase the spatial resolution and/or reduce imaging time. It was shown that all applications of cardiac imaging at 1.5 T seem feasible also at 3.0 T and predominantly provide similar or improved image quality. Although specific absorption rate limitations and susceptibility effects remain a primary concern, the combination of high-field strength examinations with parallel imaging has increased the performance of techniques such as steady-state free-precession at 3.0 T. Therefore, the signal-to-noise and the contrast-to-noise ratios advantages at 3.0 T and the resulting potential benefit for an improved diagnostic value will constantly fuel further developments in this area and pave the way for novel, promising imaging techniques.     

Use of nasal potential difference and sweat chloride as outcome measures in multicenter clinical trials in subjects with cystic fibrosis.

One of the goals of current research in cystic fibrosis (CF) is to develop treatments that correct or compensate for defects in function of the cystic fibrosis transmembrane regulator (CFTR) gene. The use of outcome measures that assess CFTR function such as nasal potential difference (NPD) measurements and sweat chloride determinations will be required to evaluate the efficacy of such treatments in multicenter clinical trials. The purpose of this work was to identify the sources and magnitude of variability in NPD and sweat chloride measurements when performed at multiple centers. For the variance component analysis presented here, we used NPD and sweat chloride measurements from 37 subjects with CF participating in a phase I, four-center clinical trial of CPX (8-cyclopentyl-1,3-dipropylxanthine), a drug intended to enhance trafficking of Delta F508 CFTR to the cell membrane. The specific techniques used to measure these outcomes were not standardized, and varied between the four sites. Variability of both NPD measurements (baseline potential difference during infusion with Ringer's solution; change in response to addition of 0.1 mM amiloride; and subsequent change in response to perfusion with low chloride solution containing 0.1 mM amiloride and 0.01 mM isoproterenol) and sweat chloride measurements differed significantly between study sites. For change in NPD, one study site had significantly greater variability (lower reproducibility) of measurement than the other three sites. For sweat chloride measurements, reproducibility was lower at two of the sites relative to the other two sites. Sample size calculations showed that lower reproducibility at one or more sites can substantially reduce the power of studies using NPD or sweat chloride determinations as outcome measures. Standardization of measurement protocols, careful operator training and certification, and ongoing monitoring of individual operator performance may help to improve reliability in multicenter trials.     

Large‐cell transformation of chronic lymphocytic leukemia and follicular lymphoma during or soon after treatment with fludarabine–rituximab‐containing regimens: natural history‐ or therapy‐related complication?

Novel therapeutic regimens containing purine analogs and monoclonal antibodies have led to significant improvement in the course of indolent lymphoproliferative diseases (LPD). Complete clinical and even molecular remissions have been achieved in an increasing proportion of patients. In parallel to their tumor cytotoxic effect, these agents are inevitably associated with prolonged immunosuppression inherent to their mechanism of antilymphocytic activity. Until now, attention has been paid mainly to opportunistic infection occurring as a result of the above drug-induced immunosuppression and less to other possible complications, such as malignancy or tumor progression in the immunocompromised host. Here we briefly report nine patients with previously treated indolent LPD in whom the onset of large-cell transformation occurred during or shortly after the initiation of regimens containing these agents before transformation occurred. One patient had received rituximab alone, three fludarabine-containing regimens and five received sequential regimens containing both agents. This     

Retreatment with rituximab alone induces sustained remission in a patient with follicular lymphoma with multiple extranodal sites of involvement,relapsing soon after primary treatment with fludarabine-rituximab

Two recent studies have shown that retreatment of patients with relapsed indolent NHL with rituximab (RI) can be as effective as primary treatment, provided the lymphoma was initially responsive to primary RI therapy. From the available data, it remains unknown as to whether this approach is also effective for extranodal relapse. Here, we describe a 47-year-old male with stage 4B follicular lymphoma (FL), initially also involving skin, who achieved complete remission (CR) after a combination of fludarabine, cyclophosphamide and RI that lasted only 5 months. He soon relapsed with systemic disease and a number of extranodal sites including liver, lungs and bone marrow. After retreatment with RI alone (four cycles, 375 mg/m(2)), the patient achieved a second CR. Another four infusions of RI were given 6 months later as maintenance therapy. The duration of CR is already 18 months longer than the first CR. This case illustrates the fact that even in relapsed advanced FL, with multiple sites of extranodal disease, RI given as a single agent may be extremely effective in achieving an additional meaningful complete response.     

Lymph node staging by means of positron emission tomography is less accurate in non-small cell lung cancer patients with enlarged lymph nodes: analysis of 1,145 lymph nodes

BACKGROUND: Despite documented superiority of integrated positron emission tomography-computerized tomography (PET-CT) over computerized tomography (CT) in lymph node staging in non-small cell lung cancer, little is known about the sensitivity, specificity and accuracy of integrated PET-CT among enlarged lymph nodes. We sought to assess if PET-CT is uniformly accurate among enlarged and non-enlarged lymph nodes. METHODS: A retrospective review of 206 consecutive patients with histologically proven non-small cell lung cancer who underwent resection and/or mediastinoscopy in our centre over 30 months period was carried out. All these patients had pre-operative staging with integrated PET-CT as an adjunct to chest CT prior to resection and/or mediastinoscopy. Diabetic patients (BM>or=8.0 mmol/l) and those who received neo-adjuvant chemotherapy were excluded. The pathological results of all these cases were reviewed and correlated with those on CT and integrated PET-CT. RESULTS: The sensitivity, specificity, accuracy, positive and negative predictive values were higher in integrated PET-CT than CT alone in all lymph nodes, whether N1 or N2. When lymph nodes were stratified by size, the sensitivity of PET-CT was significantly higher among enlarged (>1cm) than non-enlarged (1cm) should be with caution as the specificity of PET-CT is lower and its ability to detect truly negative nodes become reduced. NSCLC patients with enlarged nodes by CT criteria who are PET-CT negative may require cervical mediastinoscopy to rule out metastatic spread to these nodes. Prospective studies are warranted.     

Strain‐encoded cardiac MR during high‐dose dobutamine stress testing: Comparison to cine imaging and to myocardial tagging

Purpose

To investigate regional strain response during high‐dose dobutamine stress cardiac magnetic resonance imaging (DS‐CMR) using myocardial tagging and Strain‐Encoded MR (SENC).

Materials and Methods

Stress induced ischemia was assessed by wall motion analysis, by tagged CMR and by SENC in 65 patients with suspected or known CAD who underwent DS‐CMR in a clinical 1.5 Tesla scanner. Coronary angiography deemed as the standard reference for the presence or absence of CAD (≥50% diameter stenosis) in all patients.

Results

SENC and conventional tagging detected abnormal strain response in six and five additional patients, respectively, who were missed by cine images and proved to have CAD by angiography (P < 0.05 for SENC versus cine, P = 0.06 for tagging versus cine and p = NS for SENC versus tagging). On a per‐vessel level, wall motion analysis on cine images showed high specificity (95%) but moderate sensitivity (70%) for the detection of CAD. Tagging and SENC yielded significantly higher sensitivity of 81% and 89%, respectively (P < 0.05 for tagging and P < 0.01 for SENC versus wall motion analysis, and p = NS for SENC versus tagging), while specificity was equally high (96% and 94%, respectively, P = NS for all).

Conclusion

Both the direct color‐coded visualization of strain on CMR images and the generation of additional visual markers within the myocardium with tagged CMR represent useful adjuncts for DS‐CMR, which may provide incremental value for the detection of CAD in humans. J. Magn. Reson. Imaging 2009;29:1053–1061. © 2009 Wiley‐Liss, Inc.     

Occult Carcinomas of the Lung

In 1974, we reported 26 patients with roentgenographically occult lung carcinomas. In 13 (50%) of them, the tumor was localized and treated by resection while the disease was still early (Stage I). These patients have done well, and the median survival has reached 8 years. We have added 21 patients to the series since our last report. Localization was by fiberoptic bronchoscopy in all 21. Fourteen of these patients had Stage I disease and were treated by resection.Of a total of 27 patients with early disease treated by resection, none has had recurrence after follow-up extending from 2 months to 20 years. However, in 21 of the entire 47 patients (45%) a second carcinoma developed, 15 (71%) of which were second lung carcinomas.