The predictive role of interim PET after the first chemotherapy cycle and sequential evaluation of response to ABVD in Hodgkin's lymphoma patients-the Polish Lymphoma Research Group (PLRG) Observational Study.

BACKGROUND: Interim PET after two ABVD cycles (iPET2) predicts treatment outcome in classical Hodgkin's lymphoma. To test whether an earlier assessment of chemosensitivity would improve the prediction accuracy, we launched a prospective, multicenter observational study aimed at assessing the predictive value of iPET after one ABVD (iPET1) and the kinetics of response assessed by sequential PET scanning. PATIENTS AND METHODS: Consecutive patients with newly diagnosed classical Hodgkin's lymphoma underwent interim PET scan after one ABVD course (iPET1). PETs were interpreted according to the Deauville score (DS) as negative (-) (DS 1-3) and positive (+) (DS 4, 5). Patients with iPET1 DS 3-5 underwent iPET2. RESULTS: About 106 early (I-IIA) and 204 advanced (IIB-IV) patients were enrolled between January 2008 and October 2014. iPET1 was (-) in 87/106 (82%) or (+) in 19/106 (18%) of early, and (-) in 133/204 (65%) or (+) in 71/204 (35%) of advanced stage patients, respectively. Twenty-four patients were excluded from response analysis due to treatment escalation. After a median follow-up of 38.2 (3.2-90.2) months, 9/102 (9%) early and 43/184 (23%) advanced patients experienced a progression-free survival event. At 36 months, negative and positive predictive value for iPET1 were 94% and 41% (early) and 84% and 43% (advanced), respectively. The kinetics of PET response was assessed in 198 patients with both iPETs. All 116 patients with iPET1(-) remained iPET2(-) (fast responders), 41/82 with IPET1(+) became iPET2(-) (slow responders), and the remaining 41 stayed iPET2(+) (non-responders); progression-free survival at 36 months for fast, slow and non-responders was 0.88, 0.79 and 0.34, respectively. CONCLUSION: The optimal tool to predict ABVD outcome in HL remains iPET2 because it distinguishes responders, whatever their time to response, from non-responders. However, iPET1 identified fast responders with the best outcome and might guide early treatment de-escalation in both early and advanced-stage HL.

Ethnicity-related variations of left ventricular remodeling in adolescent amateur football players.

Adult and adolescent elite black athletes display - as compared with their white counterparts - excessively increased left ventricle (LV) wall thickness (LVWT), mass (LVM), and relative wall thickness (RWT). To investigate such ethnicity-related differences in non-professional adolescent athletes, 138 male, amateur football players [age 14.0 ± 1.7 years, 42 West-African blacks (BA) and 96 Italian whites (WA)] underwent an echocardiographic study of LV diameters, LVWT, maximal wall thickness (MWT), LVM, and RWT as remodeling index. BA vs WA exhibited greater thickness of septum and posterior wall, higher MWT (10.3 ± 1.7 vs 8.8 ± 1.1 mm), and higher LVM (117 ± 27 vs 101 ± 20 g/m(2)) and RWT (0.44 ± 0.07 vs 0.35 ± 0.04). Age, systolic blood pressure, body mass index, and ethnicity predicted MWT and LVM, whereas ethnicity was the sole strong predictor of RWT. The greater MWT, LVWT, and LVM of 14-year-old, amateur-level BA vs WA indicates that ethnicity substantially affects LV structure in adolescent, non-professional athletes. In contrast with MWT and LVM, elevated RWT was predicted by black ethnicity only. We suggest that concentric-type LV remodeling is a peculiar LV phenotype in adolescent African athletes.

Diagnostic and prognostic role of PET/CT in patients with chronic lymphocytic leukemia and progressive disease.

In order to evaluate the predictive value of positron emission tomography-computed tomography (PET/CT) in discriminating the presence of a Richter's syndrome (RS) or a second malignancy (SM), as well as to evaluate its prognostic value in patients with chronic lymphocytic leukemia (CLL), we retrospectively analyzed the data of 90 patients who, in the suspicion of a RS or a SM, underwent PET/CT followed by the biopsy of the involved tissue. The median maximum Standardized Uptake Value (SUV max) in the presence of a CLL/small lymphocytic lymphoma, a diffuse large B-cell lymphoma (DLBCL), a Hodgkin lymphoma (HL), a SM were 3.5, 14.6, 7.0 and 6.3, respectively (P ⩽ 0.0001). A SUV max cutoff value ⩾ 5 showed a sensitivity, specificity, positive and negative predictive values of 88.2, 71.2, 51.3 and 94%, respectively, for the presence of a more aggressive disease (DLBCL, HL and SM). A SUV max ⩾ 5 identified also a subset of treatment naive patients with an inferior progression-free survival (P = 0.011) and overall survival (P = 0.067). These findings suggest that PET/CT may helpfully integrate the biologically-based prognostic stratification of CLL. Prospective clinical trials including larger cohorts of patients are needed to conclusively define the role and prognostic impact of PET/CT in the routine management of CLL patients.

Endothelin-A blockade attenuates systemic and renal hemodynamic effects of L-NAME in humans.

Eight Na-repleted volunteers underwent 3 separate 90-minute infusions of either N(G)-nitro-L-arginine methyl ester (L-NAME) 3.0 mg. kg(-1). min(-1) or endothelin-A receptor (ET-A) blocker BQ-123 (BQ) 0.125 nmol. kg(-1). min(-1) or both. Mean arterial pressure (MAP), glomerular filtration rate (GFR), renal blood flow (RBF), renal vascular resistances (RVR), and sodium excretion rate (UNaV) were measured at baseline (b) and from 0 to 45 minutes (period 1) and 45 to 90 minutes (period 2) of infusion. BQ alone had no effect. GFR declined by 4.9% (P<0.001 versus b) in period 1, to 9.9% (P<0. 001) in period 2 with L-NAME, and by 3.3% (P<0.01) to 6.6% (P<0.001) with L-NAME plus BQ (P=NS between L-NAME and L-NAME plus BQ). UNaV fell equally with L-NAME or L-NAME plus BQ. MAP rose significantly in period 2 with L-NAME (6.9%; P<0.001) but not with coinfused BQ (2. 1%; P=NA versus b, P=0.005 versus L-NAME alone). RBF declined by 12. 2% (P<0.001) to 18.3% (P<0.001) with L-NAME and by 4.6% (P<0.005) to 8.2% (P<0.001) with L-NAME plus BQ. These changes were smaller with L-NAME plus BQ (P<0.05 in period 1 and P<0.02 in period 2). Blunted changes were also seen for RVR (P<0.005 in period 1 and P<0.001 in period 2 between L-NAME alone and L-NAME plus BQ). These findings show that systemic and renal vasoconstriction due to L-NAME are attenuated by BQ, which suggests that an interaction between endogenous nitric oxide production and ET-A activity participates in the maintenance of baseline systemic and renal vascular tone in humans.

Dopamine blockade abolishes the exaggerated natriuresis of essential hypertension.

We studied natriuresis during central hypervolaemia by immersing eight normal subjects and eight patients with uncomplicated essential hypertension up to the neck in water, either in the absence (study 1) or presence (study 2) of dopamine blockade by metoclopramide. Water immersion without metoclopramide induced an exaggerated natriuresis in hypertensives compared with normotensives (P less than 0.001). This occurred in the presence of identical hormonal (plasma renin activity, plasma aldosterone and prolactin), renal (creatinine clearance) and pressor responses in both groups (study 1). The marked natriuresis seen during water immersion alone in normotensives was significantly blunted (P less than 0.02) but not abolished during water immersion with addition of metoclopramide. On the other hand, the exaggerated natriuresis found in hypertensives during water immersion alone was completely abolished during water immersion plus dopamine blockade by metoclopramide (study 2). Similar hormonal, renal and pressor changes were detected in both normotensive and hypertensive subjects during water immersion plus metoclopramide administration. Our data demonstrate that metoclopramide abolishes the exaggerated natriuretic response seen in hypertensives during volume expansion produced by water immersion, and suggest that dopamine may play a critical role in mediating the hypernatriuresis of essential hypertension.

Detection of suspected primary lung cancer by scintigraphy with indium-111-anti-carcinoembryonic antigen monoclonal antibodies (type F023C5)

Immunoscintigraphy with 111In-labeled anti-CEA-Mab (F023C5i) was carried out in 66 patients strongly suspected for a primary lung cancer and in 8 control patients suffering from different chest diseases. A sensitivity of 0.90, a specificity of 0.45 and an accuracy of 0.85 were calculated. False-negative results were mainly obtained in patients in whom the size of the lesion was below 2 cm and the tumor was centrally located. All patients affected by small-cell carcinoma were correctly identified. In 89% of the patients, a positive immunoscintiscan was associated with the presence of the antigen in the tumor. False-positive results were observed in control patients suffering from different chest diseases due to the nonspecific uptake of the tracer. The tumor definition was generally better after 120 hr than at an earlier time after injection due to the reduction of background activity. SPECT imaging defined the tumor better in each patient but did not reveal any tumor not seen on planar studies.

Nuclear medicine imaging in lung cancer.

The evaluation of the anatomical dissemination of lung cancer has a pivotal role in the choice of the most appropriate treatment modality. The techniques of nuclear medicine are founded on the use of different radiopharmaceuticals capable of exploiting the specific characteristics of malignant tissues. They may recognise diverse cell densities, growth rates, metabolic pathways, antigenic and surface receptor expressions. In the past, the use of Co-57-bleomycin and, then, of (67)Gallium has encountered a mixed acceptance among nuclear medicine specialists, with favourable reports claiming their utility, and others with more sceptical opinions. It is generally admitted that both Co-57-bleomycin and (67)Gallium scintigraphies are quite sensitive and rather accurate. Their use, however, is almost abandoned in favour of more innovative and encouraging approaches, including non-specific radio-tracers ((201)Thallium and Tc-99m-sestamibi), substances useful in particular clinical applications (the somatostatin analogues I-123-tyr(3) and the In-111 octreotide for neuronendocrine tumours), radio-labelled monoclonal antibodies, and the recently introduced positron emission tomography. Promising results with each of these techniques need to be further substantiated, before their entering into clinical practice. However, the abundance of choices offered by nuclear medicine might reasonably bring forward the ideal noninvasive test. We review the many scintigraphic methods investigated so far and their clinical significance.

Anti-CEA immunoscintigraphy might be more useful than computed tomography in the preoperative thoracic evaluation of lung cancer. A comparison between planar immunoscintigraphy, single photon emission computed tomography (SPECT), and computed tomography.

While a clinical, plain radiographic, and bronchoscopic assessment yields most of the essential information needed in lung cancer, computed tomography (CT) of the thorax provides diagnostic information previously unobtainable, potentially capable of reducing the number of explorative thoracotomies. In a few recent studies, immunoscintigraphy with anti-carcinoembryonic antigen (anti-CEA) monoclonal antibodies (MA) has shown remarkable staging potential. To compare the diagnostic accuracy of the two techniques, we photoscanned with indium-111 (111In)-labeled-F(ab')2 fragments of the murine anti-CEA MA FO23C5 45 patients, who were pathologically assessed for possible loco-regional extension of lung cancer. Both planar and single photo emission computed tomography (SPECT) images were obtained. Additionally, CT of the thorax (contiguous CT slices, 10 mm thick, from the lung apices to the upper abdomen), and other routine tests of preoperative evaluation were obtained. On the basis of 37 (N1, T3, and T4), 38 (N2), and 12 (N3) pathologically documented sites, an accuracy of 65, 76, 92, 78, and 86 percent (SPECT images), and 62, 68, 42, 78, and 84 percent (CT images) was calculated (figures are relevant to N1, N2, N3, T3, and T4 disease, respectively). Thus, both techniques shared a significant margin of error in almost all the categories of evaluation; however, immunoscintigraphy showed equivalent, and, in the lymph node assessment, superior results to CT. A marginal improvement of diagnostic accuracy was recorded combining the three techniques in one case (SPECT plus planar immunoscintigraphic images), while there was no benefit in any possible integration of CT and immunoscintigraphic images. In patients with peripheral nonsquamous cell cancers, the accuracy of anti-CEA immunoscintigraphy was of 90 percent or higher. Variations in the modality of performing immunoscintigraphy, such as changes in the dose of antibody fragments to be injected, in the percentage of radiolabeling, or in the time of imaging, affected the quality of immunoscintigraphic series, and the consequent interpretation of findings. At the present time, there are very few reliable tests capable of selecting patients to proceed directly to thoracotomy or to receive some intermediate surgical test, such as a prior mediastinoscopy. Traditionally, CT has been this type of "filter-test." If current findings will be confirmed in future studies, anti-CEA immunoscintigraphy might replace CT in the evaluation of particular subgroups of patients, such as patients with peripheral nonsquamous cell bronchogenic carcinoma.

Sodium homeostasis and hormonal responses during dopaminergic blockade in normal humans.

Six normal subjects were submitted to 2 h water immersion (WI) with and without pharmacological dopaminergic (DA) blockade with metoclopramide (MCP). Urinary sodium excretion showed a marked increase during WI alone while it was blunted during WI plus DA blockade. Plasma aldosterone was significantly suppressed by WI alone but remained unchanged during WI plus MCP. Plasma atrial natriuretic factor showed similar augmentation during WI alone and during WI plus MCP. The reduced sodium and 6-keto-PGF1 alpha excretion, observed during WI plus MCP administration, suggests that dopamine might induce prostacyclin synthesis in the kidney during WI.

A new diagnostic test for primary aldosteronism.

Isotonic-isooncotic central volume expansion by head-out water immersion was induced in six aldosterone-producing adenoma subjects and in six patients with idiopathic hyperaldosteronism. Plasma renin activity and plasma aldosterone levels did not significantly change during water immersion while serum cortisol was significantly suppressed (P less than .001) and the aldosterone-cortisol ratio increased (P less than .02) in aldosterone-producing adenoma patients. Water immersion also revealed the failure of plasma aldosterone levels to decrease below 10 ng/dL in these subjects, thus confirming previous results obtained during isotonic saline infusion. Otherwise, plasma renin activity and plasma aldosterone were significantly reduced (P less than .05 and P less than .01 respectively) by water immersion and plasma aldosterone invariably fell below 10 ng/dL in patients with idiopathic aldosteronism. In view of the diagnostic reliability of such a suppression test we conclude that water immersion is suitable for discriminating between the two forms of primary aldosteronism. We therefore suggest its use for assessing renin-aldosterone responsiveness in primary aldosteronism.

Calcium and sodium handling during volume expansion in essential hypertension.

To evaluate the actual role of extracellular fluid volume (ECFV) expansion per se in modulating the rate of urinary calcium excretion, a thermoneutral water immersion (WI) study was conducted in 10 normal subjects and 30 patients with essential hypertension. Central hypervolemia by 2 hours of WI caused a significant diuretic and natriuretic response (P < .005) in normal subjects; no significant changes were detected in urinary calcium and magnesium excretion. WI provoked either an appropriate or exaggerated natriuresis (P < .001) in 21 hypertensive patients; these subjects also exhibited a highly positive correlation between urinary sodium and calcium excretion during WI (P < .001). In the remaining nine hypertensive patients, WI produced a significant diuretic response, but a barely discernible (P = NS) natriuresis (inappropriate response). These subjects also exhibited a significant reduction of urinary calcium (P < .001) and magnesium (P < .01) excretion. The data indicate that (1) volume expansion per se may have a role in regulating calcium excretion in hypertensive subjects; (2) a calcium leak may be attributable to a close relationship between urinary sodium and calcium metabolism, and causally related to a disturbance of sodium and volume homeostasis in hypertension.

Regional expiratory flow limitation studied with Technegas in asthma.

Regional expiratory flow limitation (EFL) may occur during tidal breathing without being detected by measurements of flow at the mouth. We tested this hypothesis by using Technegas to reveal sites of EFL. A first study (study 1) was undertaken to determine whether deposition of Technegas during tidal breathing reveals the occurrence of regional EFL in induced bronchoconstriction. Time-activity curves of Technegas inhaled during 12 tidal breaths were measured in four asthmatic subjects at control conditions and after exposure to inhaled methacholine at a dose sufficient to abolish expiratory flow reserve near functional residual capacity. A second study (study 2) was conducted in seven asthmatic subjects at control and after three increasing doses of methacholine to compare the pattern of Technegas deposition in the lung with the occurrence of EFL. The latter was assessed at the mouth by comparing tidal with forced expiratory flow or with the flow generated on application of a negative pressure. Study 1 documented enhanced and spotty deposition of Technegas in the central lung regions with increasing radioactivity during tidal expiration. This is consistent with increased impaction of Technegas on the airway wall downstream from the flow-limiting segment. Study 2 showed that both methods based on analysis of flow at the mouth failed to detect EFL at the time spotty deposition of Technegas occurred. We conclude that regional EFL occurs asynchronously across the lung and that methods based on mouth flow measurements are insensitive to it.

Renin-angiotensin system unresponsiveness in phaeochromocytoma.

Water immersion to the neck is able to provoke a profound suppression of the renin-angiotensin system in several clinical conditions associated with hyper-reninaemia. Both hyper-reninaemia and secondary aldosteronism have sometimes been described in phaeochromocytoma. We report on two patients, with surgically proven phaeochromocytoma, in whom water immersion, performed before surgery, failed to induce any significant change in plasma renin activity.

Cutaneous, musculoskeletal and bone flow scintiscan by intravenous infusion of 99mTc-MDP (Diphosphonate) in the evaluation and control of patients treated with spinal cord stimulation for ischaemic pain.

In patients affected by unbearable pain secondary to peripheral vascular disorders beyond surgical repair such as thromboangitis obliterans, diabetic microangiopathy, arteriosclerosis obliterans, there is a need to establish the degree of micro-circulation functionality before proceeding with invasive pain therapy, such as Spinal Cord Stimulation (SCS). From our series some cases of refractory ischaemic pain subjected to nuclear medicine techniques assessment before and after SCS implant will be presented; these data suggest that the use of radionuclides for quantifying regional perfusion, in view of the information it offers us both in the dynamic angiographic phase and in the later static phase, constitutes a very valid aid in the diagnosis and treatment of chronic pain conditions of ischaemic origin. Cutaneous, musculoskeletal and bone flow scintiscan is a non-invasive procedure which allowed us to make an objective selection of patients who are candidates for prolonged conservative treatment thus limiting the incidence of ineffective permanent SCS implants.

[Acute cholecystitis. Early diagnostic study using cholescintigraphy with Tc99m-IDA]. / La colecistite acuta. Indagine diagnostica precoce con la colescintigrafia con IDA-99mTc.

34 patients admitted for suspected acute cholecystitis were evaluated using 99mTc IDA cholescintigraphy. The results of these studies are reviewed and compared with other diagnostic tests and the subsequent clinical diagnosis. Cholescintigraphy proved to be a safe, simple, highly accurate and sensitive technique. Therefore, 99mTc-IDA cholescintigraphy is proposed as the initial procedure of choice in the evaluation of patients with suspected acute cholecystitis.