Lorenzo Preda

Multicenter surveillance of women at high genetic breast cancer risk using mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging (the high breast cancer risk italian 1 study): final results.

Objectives:To prospectively compare clinical breast examination, mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging (MRI) in a multicenter surveillance of high-risk women. Materials and Methods:We enrolled asymptomatic women aged ≥25: BRCA mutation carriers; first-degree relatives of BRCA mutation carriers, and women with strong family history of breast/ovarian cancer, including those with previous personal breast cancer. Results:A total of 18 centers enrolled 501 women and performed 1592 rounds (3.2 rounds/woman). Forty-nine screen-detected and 3 interval cancers were diagnosed: 44 invasive, 8 ductal carcinoma in situ; only 4 pT2 stage; 32 G3 grade. Of 39 patients explored for nodal status, 28 (72%) were negative. Incidence per year-woman resulted 3.3% overall, 2.1% <50, and 5.4% ≥50 years (P < 0.001), 4.3% in women with previous personal breast cancer and 2.5% in those without (P = 0.045). MRI was more sensitive (91%) than clinical breast examination (18%), mammography (50%), ultrasonography (52%), or mammography plus ultrasonography (63%) (P < 0.001). Specificity ranged 96% to 99%, positive predictive value 53% to 71%, positive likelihood ratio 24 to 52 (P not significant). MRI showed significantly better negative predictive value (99.6) and negative likelihood ratio (0.09) than those of the other modalities. At receiver operating characteristic analysis, the area under the curve of MRI (0.97) was significantly higher than that of mammography (0.83) or ultrasonography (0.82) and not significantly increased when MRI was combined with mammography and/or ultrasonography. Of 52 cancers, 16 (31%) were diagnosed only by MRI, 8 of 21 (38%) in women <50, and 8 of 31 (26%) in women ≥50 years of age. Conclusion:MRI largely outperformed mammography, ultrasonography, and their combination for screening high-risk women below and over 50.

Lung cancer screening with low-dose computed tomography: A non-invasive diagnostic protocol for baseline lung nodules

BACKGROUND Indeterminate non-calcified lung nodules are frequent when low-dose spiral computed tomography (LD-CT) is used for lung cancer screening. We assessed the diagnostic utility of a non-invasive work-up protocol for nodules detected at baseline in volunteers enrolled in our single-centre screening trial, and followed for at least 1 year. METHODS 5201 high-risk volunteers, recruited over 1 year from October 2004, underwent baseline LD-CT; 4821 (93%) returned for the first repeat LD-CT. Nodules <or=5mm underwent repeat LD-CT at 1 year; nodules 5.1-8mm underwent LD-CT 3 months later; lesions >8mm received combined CT-positron emission tomography (CT-PET). A subset of nodules >8mm was studied by CT with contrast. Protocol failures were delayed diagnosis with disease progression beyond stage I, and negative surgical biopsy. RESULTS 2754 (53%) volunteers presented one or more non-calcified nodules. Ninety-two lung cancers were diagnosed: 55 at baseline and 37 at annual screening (66% stage I). Among the 37 incident cancers, 17 had a baseline nodule that remained stage I, 7 had a baseline nodule that progressed beyond stage I, and 13 presented a new malignant nodule. Baseline and annual cancers were 79 (1.5%) and 13 (0.2%), respectively. In 15 of 104 (14%) invasive diagnostic procedures, the lesion was benign. Sensitivity, and specificity were 91 and 99.7%, respectively, for the entire protocol; 88 and 93% for CT-PET; and 100 and 59% for CT with contrast. CONCLUSIONS The protocol limits invasive diagnostic procedures while few patients have diagnosis delay, supporting the feasibility of lung cancer screening in high-risk subjects by LD-CT. Nevertheless further optimization of the clinical management of screening-detected nodules is necessary.

Spiral CT angiography and surgical correlations in the evaluation of intracranial aneurysms.

Abstract. We investigated the accuracy of spiral computed tomography angiography (CTA) in the detection and study of intracranial aneurysms by comparing CTA with selective angiograms and surgical findings. Twenty-six patients (9 men and 17 women; mean age 53.1 ± 1.8 years) with suspected intracranial aneurysms were submitted to CTA (1- to 2-mm slices, pitch 1:1, 24 s, RI = 1) after a conventional CT examination showing subarachnoid hemorrhage (SAH) in 19 cases and during neuroradiological investigations performed for other reasons in 7 cases. One hundred twenty to 150 ml iodate contrast agent (0.3–0.4 gI/ml) were injected intravenously at 5 ml/s rate and with 12- to 25-s delay calculated with a preliminary test bolus. Three-dimensional shaded surface display (3D SSD) and maximum intensity projection (MIP) reconstructions were obtained from axial images. Then, within 48 h, all patients were submitted to digital subtraction angiography (DSA), with separate assessment of CTA and DSA findings. Twenty-two aneurysms shown by CTA were confirmed at DSA and surgery (true positives), whereas the vascular lesion was not confirmed at DSA in 2 cases (false positives). The presence of intracranial aneurysms was excluded at both CTA and subsequent DSA in 7 cases (true negatives) and there were no false negatives; sensitivity was 100 %, specificity 77.8 %, and diagnostic accuracy 93.5 %. Computed tomography angiography aneurysm location was confirmed at surgery in all cases, with very high accuracy in assessing the presence of an aneurysm neck (100 %). Computed tomography angiography accurately depicted the aneurysm shape in 20 of 22 cases, but failed to depict its multilobed nature in 2 cases. The mean aneurysm diameter calculated at CTA was 0.99 ± 0.12 cm vs 1.09 ± 0.11 cm at surgery (p < 0.01). The present results suggest that the high sensitivity of CTA, if confirmed by further studies, might help in avoiding having to resort to arteriography after negative CTA in SAH patients.

CT perfusion in oncology: how to do it

Abstract Robust technique and accurate data analysis are required for reliable computed tomography perfusion (CTp) imaging. Multislice CT is required for high temporal resolution scanning; 16-slice (or 64-slice) scanners are preferred for adequate volume coverage. After tumour localization, the volume of CTp imaging has to be positioned to include the maximum visible area of the tumour and an adequate arterial vessel. Dynamic scans at high temporal resolution (at least 1-s gantry rotation time) are performed to visualize the first pass of contrast agent within the tumour; repeated scans with low temporal resolution can be planned for late enhancement assessment. A short bolus of conventional iodinated contrast agent, preferably with high iodine concentration, is power injected at a high flow rate (>4 ml/s) in the antecubital vein. The breath-hold technique is required for CTp imaging of the chest and upper abdomen to avoid respiratory motion; free breathing is adequate for CTp imaging of the head, neck and pelvis. Using dedicated software, a region of interest (ROI) has to be placed in an adequate artery (as arterial input) to obtain density–time curves; according to different kinetic models, colour maps of different CTp parameters are generated and generally overlaid on CT images. Additional ROIs can be positioned in the tumour, and in all other parts of the CTp volume, to obtain the values of the CTp parameters within the ROI.

Magnetic resonance mammography in the evaluation of recurrence at the prior lumpectomy site after conservative surgery and radiotherapy

IntroductionThe aim was to assess the value of magnetic resonance mammography (MRM) in the detection of recurrent breast cancer on the prior lumpectomy site in patients with previous conservative surgery and radiotherapy.MethodsBetween April 1999 and July 2003, 93 consecutive patients with breast cancer treated with conservative surgery and radiotherapy underwent MRM, when a malignant lesion on the site of lumpectomy was suspected by ultrasound and/or mammography. MRM scans were evaluated by morphological and dynamic characteristics. MRM diagnosis was compared with histology or with a 36-month imaging follow-up. Enhancing areas independent of the prior lumpectomy site, incidentally detected during the MRM, were also evaluated.ResultsMRM findings were compared with histology in 29 patients and with a 36-month follow-up in 64 patients. MRM showed 90% sensitivity, 91.6% specificity, 56.3% positive predictive value and 98.7% negative predictive value for detection of recurrence on the surgical scar. MRM detected 13 lesions remote from the scar. The overall sensitivity, specificity, positive predictive value and negative predictive value of MRM for detection of breast malignancy were 93.8%, 90%, 62.5% and 98.8%, respectively.ConclusionMRM is a sensitive method to differentiate recurrence from post-treatment changes at the prior lumpectomy site after conservative surgery and radiation therapy. The high negative predictive value of this technique can avoid unnecessary biopsies or surgical treatments.

Relationship between histologic thickness of tongue carcinoma and thickness estimated from preoperative MRI

Several studies have shown that the thickness of tongue carcinoma is related to prognosis and to the likelihood of cervical node metastases. We investigated whether preoperative estimates of tumor thickness and volume, as determined from magnetic resonance imaging (MRI), correlated with histologic thickness and might therefore predict the presence of neck metastases. We assessed relationships between histologic tumor thickness and MRI tumor thickness and volume in a retrospective series of 33 patients with squamous cell carcinoma of the tongue. Thicknesses were determined by direct measurement and by considering corrections for ulceration or tumor vegetation (reconstructed thickness). Relationships between MRI thickness and the presence or absence of homolateral and contralateral nodal metastases were also investigated. We found that MRI thicknesses correlated strongly and directly with histologic tumor thicknesses, although mean MRI thicknesses were significantly greater than histologic thicknesses. MRI thicknesses were significantly greater in patients with contralateral neck involvement than in those with no neck involvement. We conclude that MRI provides an accurate and reproducible means of estimating the thickness of tongue carcinomas, paving the way for further studies on more extensive series of patients to determine whether preoperatively determined MRI thickness can reliably predict homolateral and bilateral neck involvement.

Perfusion computed tomography for monitoring induction chemotherapy in patients with squamous cell carcinoma of the upper aerodigestive tract: correlation between changes in tumor perfusion and tumor volume.

Objective: The aim of this study was to assess the potential of perfusion computed tomography (CTp) for monitoring induction chemotherapy in patients with squamous cell carcinoma (SCCA) of the upper aerodigestive tract. Materials and Methods: Twenty-five patients with advanced SCCA underwent CTp and volumetric CT before and after induction chemotherapy. Perfusion CT parameters were calculated in the tumor, normal tissue, and muscles and correlated with tumor volume. Results: The blood flow (BF), blood volume (BV), and permeability surface were significantly higher, and the mean transit time was significantly lower in the tumor than in the normal tissue. The tumor BF and BV significantly decreased, and the mean transit time significantly increased after the therapy; decrease in BF and BV correlated with tumor volume reduction after chemotherapy. The baseline tumor BV was significantly lower in nonresponders compared with that in responders. Conclusions: In patients with SCCA, CTp showed potential for monitoring induction chemotherapy, reduction in tumor BF and BV correlated with reduction of tumor volume after chemotherapy, and baseline tumor BV may predict response to chemotherapy.

Perfusion CT in solid body-tumours part II. Clinical applications and future development

Perfusion computed tomography (CTP) has shown great potential in diagnosing tumours and evaluating and predicting treatment response and has been the subject of numerous experimental and clinical studies. Its increasing availability and simplicity allow it to be performed alongside morphological imaging to complete the evaluation of neoplastic lesions. The aim of this paper is to describe our personal experience and review the literature on the applications of CTP in tumours of different body regions, with particular regard to fields of development for new research. Increased clinical application is desirable, especially in relation to a wider use of antiangiogenic drugs. Additional and ideally multicentre studies are necessary to define the role of this technique.RiassuntoLa tomografia computerizzata perfusionale (TCp) ha dimostrato potenzialità nella diagnosi dei tumori, nella valutazione della risposta alla terapia e nella previsione di risposta ed è oggetto di numerosi studi sperimentali e clinici. La sua sempre più ampia disponibilità sul territorio e la semplicità di esecuzione la rendono una tecnica che affianca l’immagine morfologica e rende più completa la valutazione delle lesioni neoplastiche. Scopo di questo lavoro è descrivere i risultati personali e i dati descritti in letteratura sulle applicazioni della TCp nei tumori dei diversi distretti, con un particolare accento ai possibili campi di sviluppo per nuove ricerche in questo ambito. À auspicabile una sua applicazione clinica più estesa, soprattutto in relazione all’utilizzo sempre maggiore di farmaci antiangiogenetici. Ulteriori studi, possibilmente multicentrici, sono necessari per definire l’evidenza del ruolo di questa tecnica.

Difficulties encountered managing nodules detected during a computed tomography lung cancer screening program

OBJECTIVE The main challenge of screening a healthy population with low-dose computed tomography is to balance the excessive use of diagnostic procedures with the risk of delayed cancer detection. We evaluated the pitfalls, difficulties, and sources of mistakes in the management of lung nodules detected in volunteers in the Cosmos single-center screening trial. METHODS A total of 5201 asymptomatic high-risk volunteers underwent screening with multidetector low-dose computed tomography. Nodules detected at baseline or new nodules at annual screening received repeat low-dose computed tomography at 1 year if less than 5 mm, repeat low-dose computed tomography 3 to 6 months later if between 5 and 8 mm, and fluorodeoxyglucose positron emission tomography if more than 8 mm. Growing nodules at the annual screening received low-dose computed tomography at 6 months and computed tomography-positron emission tomography or surgical biopsy according to doubling time, type, and size. RESULTS During the first year of screening, 106 patients underwent lung biopsy and 91 lung cancers were identified (70% were stage I). Diagnosis was delayed (false-negative) in 6 patients (stage IIB in 1 patient, stage IIIA in 3 patients, and stage IV in 2 patients), including 2 small cell cancers and 1 central lesion. Surgical biopsy revealed benign disease (false-positives) in 15 cases (14%). Positron emission tomography sensitivity was 88% for prevalent cancers and 70% for cancers diagnosed after first annual screening. No needle biopsy procedures were performed in this cohort of patients. CONCLUSION Low-dose computed tomography screening is effective for the early detection of lung cancers, but nodule management remains a challenge. Computed tomography-positron emission tomography is useful at baseline, but its sensitivity decreases significantly the subsequent year. Multidisciplinary management and experience are crucial for minimizing misdiagnoses.

Risk factors for complications of CT-guided lung biopsies

PurposeThis study assessed the risk factors for pneumothorax and intrapulmonary haemorrhage after computed tomography (CT)-guided lung biopsies.Materials and methodsCT-guided lung biopsies performed between January 2007 and July 2008 were retrospectively evaluated to select the study cohort. Whenever possible, emphysema was quantified by using dedicated software. Features related to the patient, the lesion and the needle and its intrapulmonary path were recorded, along with the pathology findings and operators’ experience. The occurrence of pneumothorax and parenchymal haemorrhage was recorded. Univariate and multivariate statistical analyses were performed to assess the association between risk factors and complications. P values <0.05 were considered significant.ResultsIn 157/222 of the procedures considered, complications were associated with small lesion size and length of the intrapulmonary needle path. Transfissural course and type of needle were associated with pneumothorax using univariate analysis, whereas transfissural course was associated with intrapulmonary haemorrhage using both univariate and multivariate analysis. Emphysema, nodule type, patient position, access site and needle diameter were not significant. Fine-needle aspirates and operator experience were significantly correlated with inadequate biopsy samples.ConclusionsThe size of the lesion and the length of the intrapulmonary trajectory are risk factors for pneumothorax and parenchymal haemorrhage. The transfissural course of the needles is frequently related to pneumothorax and intrapulmonary haemorrhage, and the type of the needle is related to pneumothorax.RiassuntoObiettivoScopo del presente lavoro è stato valutare i fattori di rischio per l’insorgenza di pneumotorace e soffusione polmonare dopo biopsie polmonari guidate tramite tomografia computerizzata (TC).Materiali e metodiSono state valutate retrospettivamente le biopsie polmonari TC-guidate eseguite nel periodo gennaio 2007-luglio 2008. Ove possibile, è stato quantificato l’enfisema mediante software dedicato. Sono state valutate caratteristiche relative al paziente, alla lesione, all’ago e al tragitto intrapolmonare in relazione al risultato patologico e all’esperienza degli operatori, all’eventuale presenza post-bioptica di pneumotorace e di soffusione parenchimale. È stata eseguita un’analisi statistica univariata e multivariata. Valori di p<0,05 sono stati considerati significativi.RisultatiIn 157/222 procedure incluse, le complicanze sono state associate con lesioni piccole e lunghezza del tragitto intrapolmonare dell’ago. Tragitto trans-scissurale e tipo di ago sono associati allo pneumotorace nell’analisi univariata; il tragitto trans-scissurale è correlato alla soffusione polmonare sia nell’analisi univariata che multivariata. Quantificazione dell’enfisema, tipo di nodulo, posizione del paziente, accesso e diametro dell’ago non sono risultati significativi. Gli ago-aspirati e l’esperienza degli operatori sono correlati con l’inadeguatezza del campione bioptico.ConclusioniDimensione della lesione e lunghezza del tragitto intrapolmonare dell’ago sono fattori di rischio sia per pneumotorace che per soffusione parenchimale. Il tragitto trans-scissurale dell’ago è spesso associato con pneumotorace e soffusione, gli aghi citologici con pneumotorace.