Mauro Liberatore

Scintigraphic evaluation of disease activity in rheumatoid arthritis: a comparison of technetium-99m human non-specific immunoglobulins, leucocytes and albumin nanocolloids

Technetium-99m-labelled, non-specific, polyclonal, human immunoglobulin G (99mTc-hIG) has been used to quantify synovial inflammation in rheumatoid arthritis. A comparison was carried out between the scintigraphic results obtained with this tracer, 99mTc-hexamethylpropylene amine oxime-labelled white blood cells (99mTc-WBC) and 99mTc-albumin nanocolloids (99mTc-NC). Twenty patients affected by rheumatoid arthritis and suffering from clinically active synovitis were studied with 99mTc-hIG. The number and sites of the involved joints had been previously assessed on the basis of the presence of pain and/or swelling. A radiological examination had already been carried out on all the joints. Two days after the 99mTc-hIG scan, 10 patients (group 1) underwent 99mTc-WBC scintigraphy and the other 10 (group 2) underwent a 99mTc-NC scan. The results show that the results of 99mTc-hIG and99m Tc-NC scans are in agreement with clinical examinations in the majority of cases. However, a certain number of positive joint scans corresponding to negative clinical examinations was found. The numerical distribution of these results according to the radiological stages seems to show that99m Tc-hIG is more useful than 99mTc-NC in the initial phases of the disease. The 99mTc-WBC scan was negative in a consistent percentage of the joints previously assessed as clinically and 99mTc-hIG scan positive.

CEUS Time Intensity Curves in the Differentiation Between Leydig Cell Carcinoma and Seminoma: A Multicenter Study

PURPOSE Ultrasound (US) is the main imaging technique in the assessment of testicular masses, as it has proved to be highly accurate in the visualization of these pathologies. Identification of a Leydig cell tumor is essential since the lesion is benign in 90% of cases. The aim of this multicenter study is to assess the effectiveness of contrast-enhanced ultrasound (CEUS) in differentiating Leydig cell tumors from seminoma using qualitative and quantitative features. MATERIALS AND METHODS From February 2011 to December 2013, 31 patients (mean age: 34 years; range: 25 - 52) were recruited for this prospective study. Three of them were monorchid. Therefore, a total of 59 testicles were assessed. All patients underwent grayscale US, color Doppler ultrasound (CDUS), CEUS and orchiectomy. The paired one-tailed Students t-test was carried out to differentiate between Leydig cell tumors and seminomas. RESULTS 31 lesions suspicious for malignancy were hypoechoic on grayscale US while they did not show a typical pattern on CDUS. CEUS qualitative analysis, based on contrast enhancement pattern, during the arterial and venous phases, did not allow discrimination of Leydig cell tumors from seminoma. Quantitative analysis of time-intensity curves (TICs) demonstrated that only three parameters presented statistical significance, i. e. wash-in rate (WiR) p = 0.014, peak enhancement (PE) p = 0.001 and time to peak (TTP) p = 0.003. CONCLUSION The vascular bed of a Leydig cell tumor is wider and the blood flow velocity is higher than that of a seminoma due to more regular neovascularization. In contrast, a seminoma presents large areas of necrosis due to irregular neovascularization. This explains the different PE and WiR values. Further studies involving larger patient populations are mandatory to confirm these encouraging preliminary results.

Microbial Targeting of 99mTc-Labeled Recombinant Human β-Defensin-3 in an Animal Model of Infection: A Feasibility Pilot Study

Human β-defensin-3 (HBD-3) is an antimicrobial peptide with bactericidal effects on many gram-positive and gram-negative bacteria and some yeast species and, if radiolabeled, might be used to distinguish bacterial infection from sterile inflammation. The goals of the present study were to develop methods for radiolabeling HBD-3 with 99mTc and to perform preliminary investigations on 99mTc-labeled HBD-3 as a means to evaluate induced infection in an animal model. To this purpose, Staphylococcus aureus–induced infection was used to evaluate the capability of 99mTc-HBD-3 to distinguish infection from aseptic inflammation in rats. Methods: Twenty to 40 μg of recombinant HBD-3 were labeled with 99mTc+ hexa-coordinated with 3 molecules of CO and H2O and separated by a column from free 99mTc. 99mTc-HBD-3 was added to cultures of a bacterial suspension of S. aureus and Escherichia coli to evaluate in vitro antibacterial activity. A bacterial suspension of S. aureus and a carrageenan solution were used to induce infection and sterile inflammation, respectively, in opposite thighs of 9 adult rats. Three separate experiments were performed on groups of 3 rats each. The animals received different doses of 99mTc-HBD-3 injected through a cannula into the jugular vein. After sacrifice of the animals, tissue samples were obtained from sites of infection, inflammation, and control muscle (left foreleg) at 1, 3, and 5 h after 99mTc-HBD-3 administration. Tissue samples were weighed and then counted in a well-counter. Simultaneously, 1 mL of a standard solution of 99mTc-HBD-3 corresponding to each administered dose was counted. Results: 99mTc-HBD-3 retained antibacterial activity. Radioactivity in tissue samples from the infected sites was significantly higher than that in samples of either induced inflammation or normal control muscle (ratio, ∼3:1) at 3 and 5 h after injection, whereas similar radioactivity counts were observed for tissue samples from aseptic inflammation sites and normal control muscle. Conclusion: In this investigation, 99mTc-HBD-3 retained antibacterial activity and successfully distinguished infection from aseptic inflammation in adult rats.

Sternal wound infection revisited

Abstract.Sternal wound infections (SWIs) can be subdivided into two types, superficial or deep, that require different treatments. The clinical diagnosis of superficial SWI is normally easy to perform, whereas the involvement of deep tissues is frequently difficult to detect. Therefore, there is a need for an imaging study that permits the assessment of SWIs and is able to distinguish between superficial and deep SWI. The present work was a prospective study aiming to evaluate the role of technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) labelled leucocyte scan in SWI management. Twenty-eight patients with suspected SWIs were included in the study. On the basis of clinical examination they were subdivided into three groups: patients with signs of superficial SWI (group 1), patients with signs of superficial SWI and suspected deep infection (group 2) and patients with suspected deep SWI without superficial involvement (group 3). Ten patients previously submitted to median sternotomy, but without suspected SWI, were also included in the study as a control group (group 4). All patients with suspected SWI had bacteriological examinations of wound secretion, if present. In addition 99mTc-HMPAO labelled leucocyte scan was performed in all patients. The patients of groups 1, 2 and 3 were treated on the basis of the clinical signs and microbiological findings, independently of the scintigraphic results. The patients of group 4 did not receive treatment. The final assessment of infection was based on histological and microbiological findings or on long-term clinical follow-up. Sensitivity, specificity, accuracy and positive and negative predictive values for scintigraphic and non-scintigraphic results were calculated. In the diagnosis of superficial and deep SWI, clinical and microbiological examination (combined) yielded, respectively, a sensitivity of 68.7% and 100%, a specificity of 77.3% and 80.8%, an accuracy of 73.7% and 86.8%, a positive predictive value of 68.7% and 70.6% and a negative predictive value of 77.3% and 100%. The scintigraphic results obtained in superficial SWI yielded a sensitivity of 56.2%, a specificity of 90.9%, an accuracy of 76.3%, a positive predictive value of 81.8% and a negative predictive value of 74.1%, while, by contrast, in deep SWI all of these values were 100%. Therefore, one can conclude that 99mTc-HMPAO labelled leucocyte scan permits accurate diagnosis of deep SWI, solving the main clinical problem in this field. In the present study the categorisation of patients without taking into account 99mTc-HMPAO labelled leucocyte planar scan findings caused a non-negligible number of cases of superficial SWI to be treated as though they were deep SWI. This ”overestimation” led to unnecessary surgery, increased and prolonged use of antibiotics with more (higher) toxicity and additional expense.

Tc-99m Exametazime-Labeled Leukocyte Scans in the Study of Infections in Skull Neurosurgery

Diagnosis and follow-up of skull infections are usually performed by neurologic examination, laboratory tests and instrumental diagnostic methods such as computed tomography (CT) and magnetic resonance imaging (MRI). These have, however, shown some limitations for specificity. The aim of the current study was to evaluate the overall contribution of Tc-99m exametazime-labeled leukocyte imaging scan Tc-99m hexamethylpropyleneamine (HMPAO) labeled white blood cells (WBC) in the diagnosis and management of infections in skull neurosurgery. Thirty-four patients were subdivided into 4 groups on the basis of the suspected pathology: intracerebral lesions on CT or MRI (group A, n = 20), suspected postsurgical infections (group B, n = 6), suspected deep infection of the surgical wound (group C, n = 4), and suspected infection of the ventriculoperitoneal shunt (group D, n = 4). All patients underwent CT, MRI, and Tc-99m HMPAO WBC imaging. Patients in group C also underwent bacteriologic and culture examinations of wound secretions if present. In positive cases in group A, Tc-99m HMPAO WBC imaging was repeated. The scintigraphic results were compared with histologic findings in patients who underwent surgery and with the results of a 12-month clinical follow-up in the remaining patients. Tc-99m HMPAO WBC scans correctly detected the infections in all groups. Furthermore, such imaging proved to be able to document recovery from the disease in all of the assessed cerebral abscesses. This study may have an important role both in the diagnosis and in the management of infections in skull neurosurgery, which, it is hoped, will be confirmed in the future.

Prostate-Specific Antigen Flare Phenomenon During 223Ra-Dichloride Treatment for Bone Metastatic Castration-Resistant Prostate Cancer: A Case Report

Clinical Practice Points Ra-dichloride is an alpha-emitting radionuclide recently approved for treatment of castration-resistant prostate cancer (CRPC) patients with symptomatic bone metastases. In this specific therapeutic setting, prostate-specific antigen (PSA) is not an objective biomarker in assessing Ra efficacy. We present a 79-year-old patient who was affected by CRPC and symptomatic bone metastases enrolled in the Ra-dichloride Early Access Program who presented a relevant rise in PSA levels after the fifth Ra administration. No radiological signs of disease progression were found, so this event was recognized as a PSA flare phenomenon and the last Ra infusion was administered. In clinical practice, PSA flare in the course of Ra treatment can be misinterpreted as a therapeutic failure with early withdrawal from a potentially effective therapy. During Ra treatment, PSA flare can be explained as a direct consequence of Ra cytotoxic effect on cancer cells. Further analysis should be conducted on large cohort to evaluate the clinical significance of PSA flare phenomenon during Ra treatment.

Sudden benzodiazepine-induced resolution of post-operative pediatric cerebellar mutism syndrome: a clinical-SPECT study

Post-operative pediatric cerebellar mutism syndrome (PPCMS) is a clinical syndrome arising from cerebellar injury and characterized by absence of speech and other possible symptoms and signs. Rare reports described some benefit after administration of dopamine agonist therapy, but no treatment has proven efficacy. In this paper, we report on the dramatic, sudden resolution of PPCMS induced by midazolam administration in a boy who underwent posterior fossa surgery for choroid plexus papilloma of the fourth ventricle. In addition to clinical improvement, post-midazolam single-photon emission computed tomography also demonstrated amelioration of brain perfusion.

Detection of small testicular masses in monorchid patients using US, CPDUS, CEUS and US-guided biopsy

PurposeTestis sparing surgery (TSS) is a well-known technique in the treatment of small testicular masses. Grayscale ultrasound (US), color/power Doppler US (CPDUS) and contrast-enhanced ultrasound (CEUS) are considered the best diagnostic imaging tools in those patients. Aim of this study was to assess the role of US imaging in the detection of small testicular masses in monorchid patients after orchiectomy for malignant neoplasm, and in guiding surgery to reach the target and also to differentiate lesions which presented vascular activity within the mass.MethodsFrom January 2011 to October 2014, 18 patients were enrolled in this study. They had previously undergone orchiectomy and were investigated for suspected contralateral disease. During routine follow-up, all patients underwent grayscale US. If findings were positive, CPDUS and CEUS were performed and eventually all patients underwent surgery. After exteriorization of the testis, the small mass was identified by intraoperative US, and a needle was placed under US guidance. After excision of the mass, frozen section examination was performed. When malignancy was found, radical orchiectomy was performed; if histological outcome was negative, the healthy testis was conserved.ResultsAll patients underwent grayscale US examination, which showed small hypoechoic masses. Each mass identified at US imaging was confirmed at surgery. All patients underwent CPDUS; 12/19 lesions showed blood flow while 7/19 showed absence of blood flow. At CEUS, 16/19 lesions showed enhancement and subsequent histological examination revealed that 8 were seminomas and 3 were Leydig cell tumors. In 5/19 cases CEUS showed the presence of lesions (focal inflammatory lesions) and in 3/19 cases CEUS was negative.ConclusionsTSS in monorchid patients may be a safe procedure leading to excellent results. We therefore consider it a valid alternative to radical orchiectomy, and US imaging is essential to guide the resection of non-palpable neoplasms and to exclude concomitant lesions.RiassuntoScopoLa testis sparing surgery (TSS) è una tecnica ben nota nel trattamento di piccole masse testicolari. L’ecografia in scala di grigi (US), il color/power Doppler (CPDUS) e l’ecografia con mezzo di contrasto (CEUS) sono considerati i migliori strumenti di diagnostica per immagini in questi pazienti. Scopo di questo studio è stato quello di valutare il ruolo dell’imaging ecografica nell’individuazione delle piccole masse testicolari nei pazienti monorchidi dopo orchiectomia per neoplasia maligna, nel ruolo di guida durante l’intervento chirurgico e nella differenziazione delle lesioni che presentavano attività vascolare dentro la massa.MetodiDa Gennaio 2011 a Novembre 2014, 18 pazienti (19 lesioni), orchiectomizzati per neoplasia, durante il follow-up di routine, sono stati sottoposti a ecografia. Se positivi, venivano sottoposti a CPDUS e CEUS ed ad intervento chirurgico. La piccola massa, era identificata e sotto guida ecografica marcata con ago. Dopo l’asportazione della massa, è stato eseguito l’esame istologico estemporaneo. In caso di malignità, veniva eseguita una orchiectomia radicale; se l’esito istologico era negativo, il testicolo sano veniva conservato.RisultatiIn tutti i pazienti l’ecografia ha mostrato 19 piccole masse ipoecogene confermate all’intervento chirurgico. Al CPDUS; 12/19 hanno mostrato presenza di flusso ematico, 7 hanno mostrato assenza di segnale. Alla CEUS, 16/19 sono risultate positive e l’esame istologico ha dimostrato 8 seminomi, 3 tumori a cellule di Leydig. In 5 casi la CEUS ha mostrato la presenza di lesioni (lesioni infiammatorie focali) e in 3 è stata negativa.ConclusioniLa TSS nei pazienti monorchidi può essere una procedura sicura che porta a eccellenti risultati. Tale tecnica può essere una valida alternativa all’orchiectomia radicale. L’imaging ecografico è essenziale per il riconoscimento e la caratterizzazione della lesione, per guidare la resezione delle neoplasie non palpabili e per escludere lesioni concomitanti.

99mTc-labeled White Blood Cell Scan as a Guide to Open Biopsy in the Management of Hip and Knee Prosthesis Infection: Preliminary Results

OBJECTIVE The aim of the present prospective study was to evaluate the usefulness of labeled leukocyte scan as a guide to open biopsy for the management of hip and knee prosthesis infection in patients without loosening of orthopedic device. METHODS Twenty-six patients with suspected hip (24) and knee (2) prosthesis infection underwent routine analysis of blood, plain radiography and 99mTc-HMPAO labelled leukocyte scan (WBCS). On these basis, patients were subdivided in the following groups: bone infection without loosening (n°=14), septic loosening (n°=8), superficial infection (n°=2), no infection (n°=2). Patients with septic loosening underwent empirical antibiotic therapy in order to avoid two-stage reimplantation. When the medical treatment was effective patients were submitted to one-stage operation. Patients without loosening of prosthesis but positive WBCS results underwent open biopsy: bone samples and periprosthetic tissues were taken from the regions showing pathological leukocyte uptake at the scan. Samples were submitted to microbiological examination and antibiotic treatments were undertaken in cases of bacterial growth. A 24-months clinical and instrumental follow-up was carried out in all patients. RESULTS WBCS showed 22 patients affected by bone infection, 2 by superficial infection and 2 not infected. Height out of the 22 patients affected by deep infection had a septic loosening. In these cases, the medical treatment was inadequate in 6 patients and effective in 2. Fourteen patients with bone infection without loosening were submitted to open biopsy: in 9 cases a complete remission of the disease was found. Two patients, without infection, underwent single-stage surgery for mechanical problems. Superficial infection was assessed and successfully treated in 2 patients. CONCLUSION The obtained results indicate that a multidisciplinary approach to infection of orthopedic prostheses, characterized by the combined use of open biopsy, WBC, and microbiological examination, produced positive outcome in 9 out of 14 patients.

The role of preoperative Tc-99m HMPAO-labeled leukocyte total-body scans in aortic prosthetic reconstruction.

Purpose This study was performed to evaluate the utility of Tc-99m HMPAO-labeled leukocyte total-body scans (TBLS) for detecting remote septic foci before operation in patients undergoing aortofemoral vascular surgery. Materials and Methods Fifty-eight patients were screened before operation for inflammatory or infective disease, and a clinical score was assigned to each patient. Each patient had TBLSs. The relation between the clinical score and the TBLS result was determined. Patients with positive results of the TBLSs were examined, and the causes of these findings were treated before surgery. Results Ten of the 58 (17%) patients had a positive result of TBLSs. Of 31 patients with a clinical score of zero, 3 had positive findings of TBLS. No TBLS was positive in the 13 patients with a clinical score of 1. TBLS findings were positive in 7 of 14 of the combined patients with clinical scores of 2, 3, or 4. None of the patients showed signs of prosthetic vascular graft infection during the postoperative follow-up period. Conclusions In conclusion, TBLSs can be used before aortofemoral vascular surgery, but only in patients with high clinical scores for inflammatory or infective disease to identify relevant infective foci that could cause vascular graft infection.