Liver metastases from prostate cancer at 11C-Choline PET/CT: a multicenter, retrospective analysis.

AIM: During our daily clinical practice using 11C-Choline PET/CT for restaging patients affected by relapsing prostate cancer (rPCa) we noticed an unusual but significant occurrence of hypodense hepatic lesions with a different tracer uptake. Thus, we decided to evaluate the possible correlation between rPCa and these lesions as possible hepatic metastases. MATERIALS AND METHODS: We retrospectively enrolled 542 patients diagnosed with rPCa in biochemical relapse after a radical treatment (surgery and/or radiotherapy). Among these, patients with a second tumor or other benign hepatic diseases were excluded. All patients underwent 11C-Choline PET/CT during the standard restaging workup of their disease. We analyzed CT images to evaluate the presence of hypodense lesions and PET images to identify the relative tracer uptake. In accordance to the subsequent oncological history, five clinical scenarios were recognized [Table 1]: normal low dose CT (ldCT) and normal tracer distribution (Group A); evidence of previously unknown hepatic round hypodense areas at ldCT with normal rim uptake (Group B); evidence of previously known hepatic round hypodense areas at ldCT stable over time and with normal rim uptake (Group C); evidence of previously known hepatic round hypodense areas at ldCT, in a previous PET/CT scan, with or without rim uptake and significantly changing over time in terms of size and/or uptake (Group D); evidence of hepatic round hypodense areas at ldCT with or without rim uptake confirmed as prostate liver metastases by histopathology, triple phase ceCT, ce-ultra sound (CEUS) and clinical/biochemical evaluation (Group E). We evaluated the correlation with PSA level at time of scan, rim SUVmax and association with local relapse or non-hepatic metastases (lymph nodes, bone, other parenchyma). RESULTS: Five hundred and forty-two consecutive patients were retrospectively enrolled. In 140 of the 542 patients more than one 11C-choline PET/CT had been performed. A total of 742 11C-Choline PET/CT scans were analyzed. Of the 542 patients enrolled, 456 (84.1%) had a normal appearance of the liver both at ldCT and PET (Group A). 19/542 (3,5%) belonged to Group B, 13/542 (2.4%) to Group C, 37/542 (6.8%) to Group D and 18/542 (3.3%) to Group E. Mean SUVmax of the rim was: 4.5 for Group B; 4.2 for Group C; 4.8 for Group D; 5.9 for Group E. Mean PSA level was 5.27 for Group A, 7.9 for Group B, 10.04 for Group C, 10.01 for Group D, 9.36 for Group E. Presence of positive findings at 11C-Choline PET/CT in any further anatomical area (local relapse, lymph node, bone, other extra hepatic sites) correlated with an higher PSA (p = 0.0285). In both the univariate and multivariate binary logistic regression analyses. PSA, SUVmax of the rim, local relapse, positive nodes were not associated to liver mets (Groups D-E) (p > 0.05). On the contrary, a significant correlation was found between the presence of liver metG (group D-E) and bone lesions (p= 0.00193). CONCLUSION: Our results indicate that liver metastases in relapsing prostate cancer may occur frequently. The real incidence evaluation needs more investigations. In this case and despite technical limitations, Choline PET/CT shows alterations of tracer distribution within the liver that could eventually be mistaken for simple cysts but can be suspected when associated to high trigger PSA, concomitant bone lesions or modification over time. In this clinical setting an accurate analysis of liver tracer distribution (increased or decreased uptake) by the nuclear medicine physician is, therefore, mandatory.

Association of psoriasis and/or psoriatic arthritis with autoimmune diseases: the experience of two Italian integrated Dermatology/Rheumatology outpatient clinics.

BACKGROUND: The systemic nature of psoriasis and its association with arthropathy, metabolic syndrome and cardiovascular disease is well established. In contrast, the association between psoriatic disease and other autoimmune disorders is still a matter of debate and data available in the literature are scarce. OBJECTIVE: The aim of this study was to examine the association of common autoimmune diseases (ADs), specified a priori, in an Italian cohort of patients affected by psoriasis and/or psoriatic arthritis (PsA), referred to two integrated Dermatology/Rheumatology outpatient clinics, over a 3-year period. METHODS: Five hundred and two patients, affected by plaque psoriasis, PsA 'sine psoriasis' or a combination of psoriasis and PsA and with a diagnosis of at least one AD, were retrospectively evaluated. Univariate and multivariate binary logistic regression was employed to identify possible association between psoriasis, PsA, psoriasis-PsA and ADs, by calculating corresponding odds ratios and 95% confidence intervals. RESULTS: Patients with psoriasis or PsA may develop one or more autoimmune diseases during their lifetime, with a higher prevalence of most ADs in psoriasis subgroup. We demonstrated for the first time that the combination of psoriasis-PsA appears to be protective towards some autoimmune diseases. However, a gender effect should always be considered due to the different distribution of autoimmune disorders between males and females. CONCLUSION: The new concept of psoriatic disease, focusing on genetic and molecular aspects which are at the basis of the pathogenesis of psoriasis and its related manifestations, extended the traditional idea of a disease confined to skin and joints. In this context, the multidisciplinary assessment of patients in the combined Dermatology/Rheumatology outpatient clinics would allow to identify early clinical and laboratory abnormalities not limited to skin and joint.

miR-23a, miR-24 and miR-27a protect differentiating ESCs from BMP4-induced apoptosis.

Numerous studies have indicated that BMP4 signaling is involved in the regulation of the early steps of development. In mouse embryonic stem cells (ESCs), BMP4 is crucial to sustain pluripotency and blocks differentiation towards neural fate. Here, through a systematic analysis of miRNAs in ESCs, we establish that BMP4 signaling regulates miR-23a, 27a and 24-2, through the recruitment of phospho-Smads at the promoter of the gene encoding this miRNA cluster. Suppression of miR-23a/b, 27a/b and 24 does not affect self-renewal or pluripotency, but induces an evident change of ESC differentiation, with a significant increase of the cells undergoing apoptosis after the transition from ESCs to epiblast stem cells (EpiSCs). BMP4 has been previously reported to cause apoptosis during ESC differentiation. By blocking BMP4 signaling, we completely prevent the apoptosis induced by suppression of the miRs. This suggests that the effects of miR suppression are the result of enhanced BMP4 signaling. This hypothesis is further supported by the observation that Smad5, the transcription factor downstream of the BMP4 receptor, is targeted by the miRNAs of the 23a and 23b clusters. Altogether, our results highlight the existence of a regulatory loop, involving Smad5 and the miR-23a clusters, that modulates the apoptotic response of ESCs to BMP4.

Electrophysiologic effects and clinical efficacy of flecainide in children with recurrent paroxysmal supraventricular tachycardia.

The electrophysiologic effects of intravenous flecainide were evaluated in 16 patients aged 9 +/- 4 years: 15 with recurrent paroxysmal supraventricular tachycardia (SVT) and 1 with overt accessory pathway and history of syncope. Eleven patients had an accessory pathway; it was concealed in 2, overt in 9 and in 10 of these patients an orthodromic atrioventricular reentrant tachycardia was induced. Five patients without accessory pathway had an atrioventricular nodal reentrant tachycardia. After intravenous flecainide (1.5 mg/kg) the effective refractory period of the atrium and ventricle increased significantly; the anterograde and retrograde effective refractory periods of the atrioventricular node did not. Flecainide blocked retrograde conduction in the accessory pathway in 4 patients (effective refractory period 245 +/- 41 ms) and anterograde conduction in 8 of 9 patients (effective refractory period 284 +/- 57 ms). The mean cycle length of orthodromic reciprocating tachycardia and atrioventricular nodal reentrant tachycardia increased significantly. After flecainide tachycardia was noninducible in 6 patients with orthodromic reciprocating tachycardia and in 1 with atrioventricular nodal reentrant tachycardia. It was inducible but nonsustained (less than or equal to 30 seconds) in 1 patient with orthodromic reciprocating tachycardia and in 3 with atrioventricular nodal reentrant tachycardia. Fifteen patients continued oral flecainide treatment for 19 +/- 11 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis of unknown sarcoidosis associated to erythema nodosum with 18F-FDG PET/CT.

A 76-year-old woman was referred to our centre to perform (18)F-FDG PET/CT with the clinical suspicion of vasculitis. Whole body PET was negative for vasculitis but it depicted moderate hypermetabolism in several lymph nodes of the mediastinum and intense uptake of the tracer in the parotid glands. Since the patient referred skin lesion on both legs a particular acquisition of the lower extremities was performed which showed diffuse uptake on the perimalleolar region of both legs. On the basis of the PET/CT findings that were suggestive for sarcoidosis the patient performed bronchoalveolar lavage (BAL) and biopsy of a mediastinal lymph node which confirmed the suspicion of sarcoidosis.

Gliomas and seizures.

Glial neoplasms account for nearly 50% of all adult primary brain tumors. They originate from glial cells in the brain and/or spinal cord and include low-grade diffuse astrocytomas, anaplastic-astrocytomas, and glioblastomas. Of all brain tumors, glioblastoma multiforme (GBM) is the most aggressive and is characterized by rapid glial cell growth, resistance to radio- and chemo- therapies, and relentless infiltration and spreading throughout the central nervous system (CNS). In glioblastomas, primary tumor growth and CNS invasion are associated with the activation of complex structural molecular and metabolic changes within the tumor tissue, which profoundly affect the surrounding neuronal networks and may in part explain induction of epilepsy. In fact, epileptic seizures are very common among patients with glial tumors, reaching nearly 50% in glioblastoma patients and almost 90% in low-grade astrocytomas. The overall hypothesis presented here discusses the possibility that the aberrant tumor cell metabolism may act directly on neuronal network, and this leads to seizure susceptibility. Further invasion and growth of the malignant glial cells exacerbate this initial pathologic state which promotes recurrent seizures (epileptogenesis).

[18F]FDG-PET/CT monitoring early identifies advanced ovarian cancer patients who will benefit from prolonged neo-adjuvant chemotherapy.

AIM: The most accepted standard duration of neoadjuvant chemotherapy (na-CHT) before debulking surgery for advanced ovarian cancer (AOC) is 3 courses. However a percentage of patients could benefit from additional courses. [(18)F]FDG-PET/CT monitoring during na-CHT could predict early pathological response and allow the delivery of an optimal na-CHT duration. METHODS: Consecutive patients with AOC unsuitable for optimal up front surgery and fit for na-CHT were monitored by FDG-PET/CT at baseline and after 3 and 6 courses of carboplatin-paclitaxel CHT. At the end of na-CHT patients were re-evaluated to undergo definitive optimal surgery (i.e. without post-surgical residual disease). Percentage changes in maximal standardized uptake value (∆-SUVmax) were compared with the pathological response. Only patients with pathological complete response (pCR) or minimal residual disease (pMRD) were considered as pathological responders (pR), while all the other cases were considered non-responders (NR). RESULTS: Baseline FDG-PET/CT was abnormal in all 42 enrolled patients (median SUVmax 11, range 3-20). After 3 and 6 courses median SUVmax decreased to 3 (<2-21) and <2, i.e. value equal to normal surrounding tissues uptake (<2-17), respectively. After 3 courses, 17 (40%) patients presented ∆-SUVmax=100%, (i.e. SUVmax <2): 15 of them (88%) subsequently resulted pR and achieved no postsurgical residual disease at the end of na-CHT, while 2 (12%) were NR with postsurgical residual tumor ≤ 1cm. Out of 25 patients with ∆-SUVmax <100% after 3 courses, 6 (24%) were pR and 19 (76%) NR at the end of na-CHT. CONCLUSION: Patients with AOC who present normalization of SUVmax after 3 courses of na-CT have a high likelihood of benefiting from 3 additional courses in order to obtain pCR or pMDR and receiving optimal surgery.

Electrophysiological effects and clinical efficacy of propafenone in children with recurrent paroxysmal supraventricular tachycardia.

Twenty-four patients aged 10.1 +/- 4.5 (mean +/- SD) years with recurrent paroxysmal supraventricular tachycardia underwent an electrophysiological study. Eleven patients had an overt and seven had a concealed accessory connection; six patients had no accessory connection. An orthodromic reciprocating tachycardia was inducible in 17 of 18 patients with an accessory connection, and an atrioventricular nodal reentrant tachycardia was inducible in four of six patients without accessory connection. After administration of propafenone, the sinus cycle length decreased. Intra-arterial, intranodal, and His-ventricle intervals and QRS duration increased. The atrial and ventricular effective refractory periods and anterograde and retrograde effective refractory periods of the atrioventricular node increased. The cycle length at which nodal second-degree block occurred increased. Of 18 patients with accessory connection, propafenone prolonged retrograde conduction in all, blocked anterograde conduction in five, and prolonged it in six. The drug terminated the orthodromic reciprocating tachycardia in all 17 patients and the atrioventricular nodal reentrant tachycardia in three of four patients. In three of four patients with atrioventricular nodal reentrant tachycardia and in 15 of 17 patients with orthodromic reciprocating tachycardia, the tachycardia was no longer inducible or nonsustained after propafenone. A follow-up of 26 +/- 10 months revealed that the drug when orally administered to all patients prevented recurrences of tachycardia in 15 of 18 patients with and in four of six patients without accessory connection. The results of short-term drug testing with propafenone predict the response to long-term oral therapy with this drug.

[Electrophysiologic effects and clinical efficacy of propafenone in pediatric patients with paroxysmal supraventricular reentrant tachycardia]. / Effetti elettrofisiologici ed efficacia clinica del propafenone in pazienti di età pediatrica con tachicardia parossistica reciprocante sopraventricolare.

Twenty patients (pts) with recurrent paroxysmal supraventricular tachycardia (PSVT), 12 female and 8 male, aged 9.8 +/- 4.7 years, underwent an electrophysiologic study (EPS) in order to assess the effects of propafenone (Pf) administered intravenously (1.5 mg/Kg in 3'). Thirteen pts (Group I) had an accessory pathway (AP) which was concealed in 5 and overt in 8 and in 12 of them an orthodromic atrioventricular reentrant tachycardia (ORT) was induced. In 5 of 7 pts (Group II) without AP an idio-nodal reentrant tachycardia (AVNRT) was induced. After Pf the sinus cycle length decreased significantly from 668 +/- 165 to 612 +/- 109 msec and PA, AH, HV intervals and QRS duration increased significantly from 35 +/- 11, 71 +/- 18, 34 +/- 6 and 73 +/- 12 to 43 +/- 11, 87 +/- 15, 39 +/- 9 and 85 +/- 10 msec respectively. The atrial and ventricular effective refractory period (ERP) increased from 216 +/- 18 and 211 +/- 19 to 227 +/- 21 and 217 +/- 21 msec respectively. The anterograde and retrograde nodal ERP and anterograde and retrograde Wenckebach point increased from 240 +/- 48, 227 +/- 28, 278 +/- 37 and 287 +/- 38 to 270 +/- 58, 330 +/- 32, 340 +/- 59 and 408 +/- 37 msec respectively. Pf terminated the tachycardia (T) in all 12 pts of Group I after prolongation of the cycle length which increased from 299 +/- 46 to 383 +/- 69 msec.(ABSTRACT TRUNCATED AT 250 WORDS)

Flecainide single oral dose for management of paroxysmal supraventricular tachycardia in children and young adults.

The efficacy of a single oral dose of flecainide to terminate paroxysmal supraventricular tachycardia (PSVT) was evaluated in 25 children and young adults. The subjects were selected from a group of 35 patients with recurrent attacks of PSVT evaluated by means of electrophysiologic study and intravenous electropharmacologic testing with flecainide. In all 25 patients the induced PSVT was stopped by intravenous flecainide and was then no longer inducible or nonsustained. All patients had normal hearts. At least 48 hours after acute intravenous testing, 25 patients underwent electrophysiologic study with a transesophageal catheter and PSVT was induced in all of them: atrioventricular reentrant tachycardia in 16 and atrioventricular nodal reentrant tachycardia in nine. During stable tachycardia, a single oral dose of flecainide (2.9 +/- 0.3 mg/kg; 2.5 to 3.3 mg/kg) was administered. This approach was effective for termination of PSVT in 22 patients. The mean plasma level of flecainide at cessation of tachycardia was 277 +/- 92 ng/ml (150 to 500 mg/ml). All 22 patients who responded were given a single oral dose of flecainide for recurrences of PSVT during follow-up. During a period of 12 +/- 7 months (2 to 27 months) a total of 134 spontaneous episodes of PSVT were reported, and 127 of these episodes were terminated with periodic management. Thus oral periodic flecainide seems useful for management of PSVT in selected patients.

[Electrophysiological effects and clinical efficacy of flecainide in childhood patients with supraventricular reciprocating paroxysmal tachycardia]. / Effetti elettrofisiologici ed efficacia clinica della flecainide in pazienti di età pediatrica con tachicardia parossistica reciprocante sopraventricolare.

The electrophysiologic effects of intravenous (i.v.) flecainide were evaluated in 13 patients (pts) with recurrent paroxysmal supraventricular tachycardia (PSVT): 6 pts had an overt accessory pathway, 2 a concealed anomalous pathway and 5 had an idionodal reentrant tachycardia (AVNRT). Another patients with overt preexcitation underwent electrophysiologic testing as part of a diagnostic investigation for syncope. After flecainide the effective refractory period of the right atrium and retrograde AV node, and anterograde and retrograde Wenckebach point significantly increased. The drug blocked retrograde conduction on the accessory pathway in 3 pts whereas anterograde conduction was blocked in all 7 pts with overt anomalous pathway. The mean cycle length of the atrioventricular reentrant tachycardia (AVRT) and of the AVNRT increased respectively from 269 +/- 34 msec to 332 +/- 25 msec (P less than .005) and from 286 +/- 9 msec to 380 +/- 64 msec (P less than .05). After i.v. flecainide, reentrant supraventricular tachycardia was no longer inducible in pts with AVRT and 1 with AVNRT, inducible but non sustained (less than or equal to 30 seconds in duration) in 1 pt with AVRT and in 3 with AVNRT. Thirteen pts continued oral flecainide treatment for a mean of 7.2 +/- 3.6 months (range 3 to 12 months). Tachycardia recurred in all 3 pts whose arrhythmia remained inducible and sustained after i.v. flecainide, and in 1 of 10 pts whose re-entrant supraventricular tachycardia was suppressed (6 pts) or inducible but non sustained (4 pts). Thus flecainide is an highly effective and well tolerated drug for the control of PSVT in infancy. The electrophysiologic drug testing with flecainide predicts its efficacy during chronic therapy in most patients.