The cortical collecting duct (CCD) is a final site for regulation of K(+) homeostasis. CCD K(+) secretion is determined by the electrochemical gradient and apical permeability to K(+). Conducting secretory K(+) (SK/ROMK) and maxi-K channels are present in the apical membrane of the CCD, the former in principal cells and the latter in both principal and intercalated cells. Whereas SK channels mediate baseline K(+) secretion, maxi-K channels appear to participate in flow-stimulated K(+) secretion. Chronic dietary K(+) loading enhances the CCD K(+) secretory capacity due, in part, to an increase in SK channel density (Palmer et al., J Gen Physiol 104: 693-710, 1994). Long-term exposure of Ambystoma tigrinum to elevated K(+) increases renal K(+) excretion due to an increase in apical maxi-K channel density in their CDs (Stoner and Viggiano, J Membr Biol 162: 107-116, 1998). The purpose of the present study was to test whether K(+) adaptation in the mammalian CCD is associated with upregulation of maxi-K channel expression. New Zealand White rabbits were fed a low (LK), control (CK), or high (HK) K(+) diet for 10-14 days. Real-time PCR quantitation of message encoding maxi-K alpha- and beta(2-4)-subunits in single CCDs from HK animals was greater than that detected in CK and LK animals (P < 0.05); beta(1)-subunit was not detected in any CCD sample but was present in whole kidney. Indirect immunofluorescence microscopy revealed a predominantly intracellular distribution of alpha-subunits in LK kidneys. In contrast, robust apical labeling was detected primarily in alpha-intercalated cells in HK kidneys. In summary, K(+) adaptation is associated with an increase in steady-state abundance of maxi-K channel subunit-specific mRNAs and immunodetectable apical alpha-subunit, the latter observation consistent with redistribution from an intracellular pool to the plasma membrane.
PET may contribute to the management of patients with low-grade follicular NHL. For the other low-grade lymphoma subtypes, the role of PET is less evident. Further studies using PET to evaluate the results of treatment or to diagnose disease recurrence are warranted in low-grade follicular NHL.
A residual mass after treatment of lymphoma is a clinical challenge, because it may represent vital tumor as well as tissue fibrosis. Metabolic imaging by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) offers the advantage of functional tissue characterization that is largely independent of morphologic criteria. We compared18F-FDG PET to computed tomography (CT) in the posttreatment evaluation of 54 patients with Hodgkin’s disease (HD) or intermediate/high-grade non-Hodgkin’s lymphoma (NHL). Residual masses on CT were observed in 13 of 19 patients with HD and 11 of 35 patients with NHL. Five of 24 patients with residual masses on CT versus 1 of 30 patients without residual masses presented a positive18F-FDG PET study. Relapse occurred in all 6 patients (100%) with a positive 18F-FDG PET, 5 of 19 patients (26%) with residual masses on CT but negative 18F-FDG PET, and 3 of 29 patients (10%) with negative CT scan and18F-FDG PET studies (P ≤ .0001). We observed a higher relapse and death rate in patients with residual masses at CT compared with patients without residual masses at CT (progression-free survival at 1 year: 62 ± 10 v88 ± 7%, P = .0045; overall survival at 1 year: 77 ± 5 v 95 ± 5%, P = .0038). A positive18F-FDG PET study was even more consistently associated with poorer survival: compared with patients with a negative18F-FDG PET study, the 1-year progression-free survival was 0% versus 86% ± 5% (P < .0001) and the 1-year overall survival was 50% ± 20% versus 92% ± 4% (P < .0001). The detection of vital tumor by 18F-FDG PET after the end of treatment has a higher predictive value for relapse than classical CT scan imaging (positive predictive value: 100% v42%). This could help identify patients requiring intensification immediately after completion of chemotherapy. However,18F-FDG PET mainly predicts for early progression but cannot exclude the presence of minimal residual disease, possibly leading to a later relapse.
We performed this study in order to evaluate the diagnostic accuracy of whole-body fluorodeoxyglucose positron emission tomography (FDG PET) imaging and somatostatin receptor scintigraphy (SRS) for localizing primary carcinoid tumours and evaluating the extent of the disease. A secondary aim was to correlate those findings with the histological characteristics of the lesions. FDG PET was performed in 17 patients and SRS in 16. All patients had pathologically proven carcinoids. All lesions were verified by histopathological analysis or by follow-up. Ki-67 and p53 expression were assessed as an indicator of the tumours' aggressiveness. FDG PET correctly identified 4/7 primary tumours and 8/11 metastatic spreads, as compared to six and 10 respectively, for SRS. Most tumours were typical carcinoids with low Ki-67 expression. No correlation was found between the histological features and the tracer's uptake. We conclude that SRS remains the modality of choice for evaluating patients with carcinoid tumours, regardless of their proliferative activity. FDG PET should be reserved to patients with negative results on SRS.
A residual mass after treatment of lymphoma is a clinical challenge, because it may represent vital tumor as well as tissue fibrosis. Metabolic imaging by 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) offers the advantage of functional tissue characterization that is largely independent of morphologic criteria. We compared18F-FDG PET to computed tomography (CT) in the posttreatment evaluation of 54 patients with Hodgkin’s disease (HD) or intermediate/high-grade non-Hodgkin’s lymphoma (NHL). Residual masses on CT were observed in 13 of 19 patients with HD and 11 of 35 patients with NHL. Five of 24 patients with residual masses on CT versus 1 of 30 patients without residual masses presented a positive18F-FDG PET study. Relapse occurred in all 6 patients (100%) with a positive 18F-FDG PET, 5 of 19 patients (26%) with residual masses on CT but negative 18F-FDG PET, and 3 of 29 patients (10%) with negative CT scan and18F-FDG PET studies (P ≤ .0001). We observed a higher relapse and death rate in patients with residual masses at CT compared with patients without residual masses at CT (progression-free survival at 1 year: 62 ± 10 v88 ± 7%, P = .0045; overall survival at 1 year: 77 ± 5 v 95 ± 5%, P = .0038). A positive18F-FDG PET study was even more consistently associated with poorer survival: compared with patients with a negative18F-FDG PET study, the 1-year progression-free survival was 0% versus 86% ± 5% (P < .0001) and the 1-year overall survival was 50% ± 20% versus 92% ± 4% (P < .0001). The detection of vital tumor by 18F-FDG PET after the end of treatment has a higher predictive value for relapse than classical CT scan imaging (positive predictive value: 100% v42%). This could help identify patients requiring intensification immediately after completion of chemotherapy. However,18F-FDG PET mainly predicts for early progression but cannot exclude the presence of minimal residual disease, possibly leading to a later relapse.
Although positron emission tomography (PET) imaging is now recognized as a useful tool for staging intermediate and high-grade non-Hodgkin's lymphoma (NHL), few data are available regarding its accuracy in low grade NHL. We therefore studied 36 patients with histologically proven low-grade NHL. Whole-body 2-(fluorine-18) fluoro-2-deoxy-D-glucose (FDG) PET was performed at the time of initial diagnosis (n = 21) or for disease recurrence (n = 15) prior to any treatment. PET results were compared to those of physical examination and computed tomography (CT). PET studies were read without knowledge of any clinical data. Any focus of increased activity was described and given a probability of malignancy using a 5 point-scale (0: normal to 4: definitively malignant). An individual biopsy was available for a total of 31 lesions. The sensitivity and specificity were 87% and 100% for FDG-PET, 100% and 100% for physical examination and 90% and 100% for CT respectively. In addition, 42 of 97 peripheral lymph node lesions observed by FDG-PET were clinically undetected, whereas the physical examination detected 23 additional nodal lesions. PET and CT both indicated 12 extranodal lymphomatous localizations. FDG-PET showed 7 additional extranodal lesions while 5 additional unconfirmed lesions were observed on CT. Regarding bone marrow infiltration, PET and biopsy were concordant in 24 patients with 11 true positive (TP) and 13 true negative (TN). However PET was FN in 11 patients and no biopsy was performed in one patient. The combination PET/CT/physical examination seems to be more sensitive than the conventional approach for staging low grade NHL. Its sensitivity however is unacceptably low for diagnosing bone marrow infiltration.
Baseline CECs levels might be an early predictive biomarker for treatment efficacy in advanced NSCLC patients. Our results suggest the change in CECs count after chemotherapy as a prognostic factor for tumor response and PFS in NSCLC.
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