Detection of noncalcified pulmonary nodules on low-dose MDCT: comparison of the sensitivity of two CAD systems by using a double reference standard.

PURPOSE: This study compared the sensitivity of two commercial computer-aided detection (CAD) systems in identifying noncalcified pulmonary nodules on low-dose multidetector computed tomography (MDCT) scans by using a double reference standard. MATERIALS AND METHODS: Three chest low-dose MDCT scans of patients who had undergone lung cancer screening were retrospectively analysed using two distinct commercial CAD systems: LungCAD VC10A, Siemens Medical Solutions (CAD1) and LungVCAR, GE Healthcare (CAD2). The exact location of each finding suggested by each system was recorded by an independent reader according to spatial coordinates (x, y, z). Two panels of experienced thoracic radiologists from two different institutions independently established two reference standards (RS1, RS2) by identifying the true positive findings with spatial coordinates without using CAD. Sensitivity of the two CAD systems, defined by lesionlevel analysis, was tested and sensitivities compared. RESULTS: RS1 identified 34 noncalcified pulmonary nodules, whereas RS2 identified 54. The total number of findings detected by the two CAD systems was 684. CAD1 correctly identified 13/34 nodules (sensitivity 38%) for RS1 and 17/54 (sensitivity 30%) for RS2, whereas CAD2 correctly identified 11/34 nodules (sensitivity 35%) for RS1 and 13/54 (sensitivity 23%) for RS2. Comparison between the two CAD systems did not show a statistically significant difference in terms of sensitivity (p<0.05) for both RS1 (p=0.42) and RS2 (p=0.33). CONCLUSIONS: The two commercial CAD systems had similar sensitivity in detecting noncalcified pulmonary nodules on low-dose MDCT of the chest.

Quantitative analysis of elastography images in the detection of breast cancer.

PURPOSE: The aim of this study was to develop a quantitative method for breast cancer diagnosis based on elastosonography images in order to reduce whenever possible unnecessary biopsies. The proposed method was validated by correlating the results of quantitative analysis with the diagnosis assessed by histopathologic exam. MATERIAL AND METHODS: 109 images of breast lesions (50 benign and 59 malignant) were acquired with the traditional B-mode technique and with elastographic modality. Images in Digital Imaging and COmmunications in Medicine format (DICOM) were exported into a software, written in Visual Basic, especially developed to perform this study. The lesion was contoured and the mean grey value and softness inside the region of interest (ROI) were calculated. The correlations between variables were investigated and receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic accuracy of the proposed method. Pathologic results were used as standard reference. RESULTS: Both the mean grey value and the softness inside the ROI resulted statistically different at the t test for the two populations of lesions (i.e., benign versus malignant): p<0.0001. The area under the curve (AUC) was 0.924 (0.834-0.973) and 0.917 (0.826-0.970) for the mean grey value and for the softness respectively. CONCLUSIONS: Quantitative elastosonography is a promising ultrasound technique in the detection of breast cancer but large prospective trials are necessary to determine whether quantitative analysis of images can help to overcome some pitfalls of the methodic.

The breast dynamic contrast enhanced MRI: preliminary results of a quantitative analysis.

The objective of our study was to apply a quantitative analysis to the dynamic contrast enhanced MR imaging of the breast. Automated criteria increase the objectivity and reproducibility of the diagnostic interpretation of the imaging for differentiating benign and malignant lesions. The validation of this applied method was evaluated by analysing the time- signal intensity curves and the performance of the extracted enhancement parameters. The performance of some extracted parameters was evaluated by ROC (Receiver Operating Characteristic) analysis. These parameters were found to be particularly accurate in differentiating lesions.

Oral cavity and base of the tongue tumors. Correlation between clinical, MRI and pathological staging of primary tumor.

The diagnosis of oral cavity and oropharyngeal tumors can be obtained through clinical examination and biopsy. CT and MRI can then be used to define the extension of the disease. The aim of this study was to define the accuracy of clinical and MRI T staging of oral cavity and base of the tongue tumors and correlate the results with pathological data. Mandibular involvement, in a subgroup of patients, was determined and sensitivity, specificity, accuracy and positive and negative predictive values were evaluated. Fifty-nine patients affected by squamous cell carcinoma and 1 case of adenoido-cystic carcinoma were examined by means of a superconductive MR unit, using SE T1, and fat-suppressed T2 weighted sequences before contrast medium infusion. SE T1 and T1 fat-suppressed sequences after gadolinium-DTPA infusion were used. T stage accuracy of both clinical examination and MRI were found to be respectively 62% (k 0.459) and 82% (k 0.775). The sensitivity, specificity and accuracy of MRI in the detection of mandibular involvement were 94.1%, 60% and 81.5%, while the positive and negative predictive values were 80% and 85.7%, respectively. The sensitivity, specificity and accuracy of clinical examination in the detection of mandibular involvement were 100%, 30% and 74.1%, while the positive and negative predictive values were 70.8% and 100%. In the present study, MRI was seen to be an adequate technique for the assessment of oral cavity malignancies, in the evaluation of depth invasion, presence and extension of mandibular involvement.

Early post-operative MRI: correlation with progression-free survival and overall survival time in malignant gliomas.

Forty-seven patients with Glioblastoma (42) and Anaplastic Astrocytoma (5) were studied with MR 24 hrs after surgery. In order to evaluate the role of early MR in defining the extent of surgical resection and its relation with the prognosis of malignant glioma patients, three categories of surgical resection were considered: gross total, sub-total and partial resection. The results were correlated with progression-free survival (PFS) and overall survival (ST). As demonstrated by early-MR, gross total resection was performed in 17 patients, sub-total and partial resection in 19 and 11 patients, respectively. The PFS was 6 months in gross total resection, 6 and 3 months in sub-total and in partial resection, respectively. The median survival time was 16 months in total resection patients, 13 months and 7 months in sub-total resection and partial resection patients, respectively. The study confirms that early-MR has to be considered an accurate technique for monitoring the extension of malignant glioma surgical resection and shows a good correlation between early-MR findings, PFS and ST.

Correlation between tumor necrosis factor-alpha and D-dimer levels in non-small cell lung cancer patients.

The present study was designed to investigate whether a correlation exists between IL-6, TNF-alpha and coagulation (Thrombin-antithrombin, TATc) or fibrinolysis (D-dimer) activation in non-small cell lung cancer (NSCLC) patients. One hundred thirty patients with NSCLC (n=65, 53 males, mean age 65 +/- 8, adenocarcinoma n=32, squamous cancer n=33) or chronic obstructive pulmonary disease (COPD) (n=65, 51 males, mean age 67 +/- 9) were studied. As control group 65 healthy donors (51 males, mean age 61 +/- 14) were also evaluated. The results obtained showed that median D-dimer levels were higher in NSCLC patients (3.0 microg/ml) compared either to COPD patients (1.1 microg/ml, P<0.05) or controls (0.3 microg/ml, P<0.0001). Positive TNF-alpha levels (>10 pg/ml) were found in 26% of NSCLC compared to 3% of COPD (P<0.002) and 5% of controls (P<0.0005). On the other hand, positive (>8.5 pg/ml) IL-6 levels were found in 53% of NSCLC and 21% of COPD patients, compared to 5% of control subjects (P<0.001). Median TATc levels were elevated in either NSCLC (6.9 microg/l) or COPD (5.7 microg/l) patients compared to controls (1.8 microg/l, P<0.0001). Elevated D-dimer levels were significantly associated to positive TNF-alpha levels in patients without distant metastasis (F=4.3, P<0.05). Moreover, TNF-alpha levels (P<0.01) were independently related to the presence of positive D-dimer levels in patients with non-metastatic NSCLC. These results suggest that increased levels of TNF-alpha might be responsible for an activation of fibrinolysis in patients with NSCLC.

Evaluation of hepatic metastases from colorectal carcinoma with MR-superparamagnetic iron oxide.

The purpose of this study was to compare the results obtained with superparamagnetic iron oxide-enhanced and unenhanced Magnetic Resonance at 1.5 T with that of spiral-computed tomography (CT) in order to select those patients suitable for liver resection; the intraoperative US (IOUS) comprised the gold standard. Thirty five candidates for liver resection with known colorectal neoplasm were studied; 26 patients underwent surgery, one patient underwent RF ablation and 8 of them were submitted to follow-up. MR examination was performed using a 1.5 T superconductive instrument, CT examination was performed on a Somatom-Plus (Siemens) scanner. Dimensions and number of the lesions were defined in all patients as well as the sensitivity of spiral CT and MR imaging, using either the plain technique or after Ferumoxides c.m.. In those patients submitted to surgery, results have been correlated to those of IOUS. From 26 patients, a total of 48 lesions were removed surgically. With CT, 34 lesions with 3 false positive cases were detected; 32 with plain MR imaging, while MR imaging with Ferumoxides detected 41 lesions. In the patients not submitted to surgery, MR iron-oxide imaging identified 15 lesions, while both plain MR imaging and CT showed 8 lesions. The smallest lesion was 6 mm. as shown by MR imaging with Ferumoxides. In the cases submitted to surgery, the CT sensitivity was 71%, plain MR imaging 66% and MR imaging with Ferumoxides 85%. In our experience, Ferumoxides-enhanced MR imaging of the liver shows increased sensitivity compared to plain and spiral-CT in the evaluation of hepatic metastases. We think that MR superparamagnetic iron oxide should be used in all patients selected for liver resection.

The Italian multi-centre project on evaluation of MRI and other imaging modalities in early detection of breast cancer in subjects at high genetic risk.

This report presents the preliminary results of the first phase (21 months) of a multi-centre, non-randomised, prospective study, aimed at evaluating the effectiveness of contrast-enhanced magnetic resonance imaging (MRI), X-ray mammography (XM) and ultrasound (US) in early diagnosis of breast cancer (BC) in subjects at high genetic risk. This Italian national trial (coordinated by the Istituto Superiore di Sanità, Rome) so far recruited 105 women (mean age 46.0 years; median age 51.0; age range 25-77 years), who were either proven BRCA1 or BRCA2 mutation carriers or had a 1 in 2 probability of being carriers (40/105 with a previous personal history of BC). Eight cases of breast carcinomas were detected in the trial (mean age 55.3 years, median age 52.5; age range 35-70 years; five with previous personal history of BC). All trial-detected BC cases (8/8) were identified by MRI, while XM and US correctly classified only one. MRI had one false positive case, XM and US none. Seven "MRI-only" detected cancers (4 invasive, 3 in situ) occurred in both pre- (n = 2) and post-menopausal (n = 5) women. With respect to the current XM screening programmes addressed to women in the age range 50-69 years, the global incidence of BC in the trial (7.6%) was over ten-fold higher. The cost per "MRI-only" detected cancer in this particular category of subjects at high genetic risk was substantially lower than that of an XM-detected cancer in the general women population. These preliminary results confirmed that MRI is a very useful tool to screen subjects at high genetic risk for breast carcinoma, not only in pre-, but also in post-menopausal age, with a low probability of false positive cases.

Primary cancer of the urinary bladder: CT evaluation of the T parameter with different techniques.

The evaluation of mural invasion (T) in primary urinary bladder carcinoma is important in the planning of an appropriate surgical or radiochemotherapeutic strategy. Previous investigators using computed tomography (CT) have evaluated the bladder filled with urine, urine opacified with iodinated contrast material, or air insufflation. The purpose of this trial was to establish which of these three techniques was the most accurate by comparing data obtained in postoperative staging (pT). Sixty-five patients with primary bladder cancer were enrolled, all of whom were studied by spiral CT with these three techniques. Patients were assigned to four stage groups: Ta-T1, T2-T3a, T3b, and T4. The results demonstrated total accuracies of 95% for the air-insufflated bladder, 90.5% for opacified urine, and 87% for noncontrast studies. In conclusion, the air-insufflated bladder is the more accurate technique in the evaluation of the T parameter in primary bladder cancer, especially in the first and third stage groups.

Bladder cancer within a direct inguinal hernia: CT demonstration.

We present a case of a urothelial neoplasm arising within a direct bladder hernia in the inguinal canal. Bladder hernias are rarely found preoperatively and are exceptional sites of neoplasm. Spiral computed tomography with gaseous insufflation of the bladder demonstrated the bladder hernia and the extension of the neoplasm in the inguinal canal more accurately than other computed tomographic techniques with nonopacified and iodinated urine.

[Renal carcinoma: effective modulation of low-dose interferon-alpha and interleukin-2 with medroxyprogesterone acetate and 13-cis retinoic acid]. / Carcinoma renale: efficace modulazione dell'interferone-alpha e dell'interleuchina 2 a basse dosi con medrossiprogesterone acetato e acido 13-cis retinoico.

We report a case history of a patient with clear renal carcinoma. After surgical treatment of primary tumor patient had been treated with medium-high doses IL-2 and alpha IFN for lung metastasis and paraaortic nodes, without significant response. Subsequently, low doses alpha IFN/IL-2 produced a response, and further response have been obtained by the combination of low-doses alpha IFN/IL-2 plus medroxyprogesterone acetate and cis-retinoic acid. We can therefore conclude that in immunogenic tumors, such as renal cancer, various immunologic strategies are justified, also employing in combination drugs not active as single agents, or modifying doses and schedules.

Retromolar trigone tumors: evaluation by magnetic resonance imaging and correlation with pathological data.

The aim of this study was to evaluate the diagnostic accuracy of magnetic resonance (MR) images to establish both the T stage and the relationships between the tumors and the surrounding structures in retromolar trigone tumors. Twenty-two patients with squamous cell carcinoma of the retromolar trigone were examined by MR with a superconductive scanner operating at 1.5T. The study was performed with spin-echo (SE) T1 and T2 and short SE T1 sequences (TR 180 ms, TE 15 ms) after the administration of 0.2 mmol/kg of gadolinium-DTPA (Gd-DTPA). The mandible was studied with SE T1 weighted sequences and GE sequences. The results were compared with the pathological data on the T stage (TNM classification) and the involvement of the surrounding structures. A positive correlation was found in 19 of the 22 patients with an accuracy of 86%. In one patient, the lesion was classified as T1 by MR which, at surgery, resulted being T4, given the infiltration of the cortical mandible (this infiltration was too limited). In another, the MR showed a T4 lesion because of the presence of low signal intensity in the mandibular marrow with enhancement after the Gd-DTPA injection without cortical erosion, while pathological data revealed a T2 lesion (this signal intensity was secondary to inflammation). In another case, the lesion was classified as T1 by MR which, at surgery, proved to be a T2 lesion. In assessing the involvement of the surrounding structures. MR showed a high accuracy, specificity and sensitivity (> 90%). Five false positive cases were observed: in two because of infiltration of the masseter muscle and in the other three, because of infiltration to the pterigoid muscle, mandible and tonsillar bed, respectively, due to the close contact between the tumors and the surrounding structures. Only one false negative case was observed with infiltration of the mandibular marrow. In evaluating the low signal intensity of the mandibular marrow, the accuracy of MR was 87% the specificity 77% and the sensitivity 100%. In one case, perineural spread along the mandibular nerve was found. In conclusion, MR proved to be highly accurate to study the T stage and examine the relationships between the surrounding structures in cases of retromolar trigone tumors.

Peripheral nervous system involvement in a patient with large T-cell lymphoma arising from a pre-existing mycosis fungoides.

A 29-year-old man was examined for disseminated erythematous scaling patches and plaques and reddish, partially ulcerated nodules. Histological examination showed a dense, diffuse, epidermotropic infiltrate located in the entire dermis to the subcutaneous tissue, composed mainly of large pleomorphic T lymphocytes. Immunohistochemistry revealed positivity of neoplastic cells for T-cell-associated markers, negativity for CD30 antigen and for B-cell markers. Polymerase chain reaction analysis detected a clonal amplification of T-cell receptor gamma. Based on clinicopathological and molecular findings, the diagnosis of large T-cell lymphoma (LCL) arising from a pre-existing mycosis fungoides was made. Seven months after primary diagnosis, meningeal and peripheral nervous system involvement developed with no other evidence of systemic disease. Despite chemotherapy and radiation therapy, the patient died 3 months after the diagnosis of nervous system involvement. In patients with cutaneous LCL, mild neurological symptoms may precede the complete diagnostic picture by some weeks. A rapid and fatal progression characterizes the clinical course of the disease.

[Gemcitabine in peritoneal mesothelioma: a case report]. / Gemcitabina nel mesotelioma peritoneale: presentazione di un caso clinico.

Malignant peritoneal mesothelioma is a rare tumor whose prognosis is poor. We report a case history of a 57-year old woman with large peritoneal masses and ascites refractory to several chemotherapeutic regimens. The patient benefited of a dramatic regression of disease with symptomatic improvement during chemotherapy with gemcitabine. Serum CA-125 values declined consensually to tumor regression. The duration of response was 12 months. The activity of gemcitabine in malignant mesothelioma has been already confirmed in phase II studies. Data are also available suggesting that better results can be obtained combining this agent with cisplatin, and a multicenter phase II study is now exploring the activity of this combination.

[Intracranial meningiomas in the elderly]. / Meningiomi endocranici dell'anziano.

BACKGROUND: Since the introduction of CT and then MRI in the clinical practice, the number of elderly patients with intracranial meningiomas observed in neurosurgical departments has increased to three/four times. Considering that some patients die because of their meningioma and others die with their meningioma, the neurosurgeon should not only be able to eradicate surgically the lesion, but also to decide if that benign tumor should be treated or not. MATERIALS AND METHODS: Forty-three patients with intracranial meningioma, aged over 65 were operated upon between 1989 and 1995. They constitute about one fourth of all the meningioma-patients operated upon in that period at our Department. Main symptoms were focal deficits, psychorganic syndrome, and seizures. Mean duration of symptoms was 15 months, with 30% of the histories lasting less than 3 months. Associate pathologies were those typical of the elderly population with hypertension and senile cardiopathy at the first places. Two patients had insulin-dependent diabetes, 2 prostatic carcinoma, and 8 were obese. MRI was useful either in depicting the location of the tumor or in helping the surgeon to give a correct operative indication and risk evaluation. MRI criteria for risk evaluation were severe edema and venous vascular infiltration. Forty-five operations were performed. Their duration was not a risk factor by itself, it only reflected the difficulty of the removal, due to the location of the tumor. Dissection of tumor remnants from main arteries or veins was never attempted in this group of patients; total removal was achieved in 75.5% of the cases. RESULTS: Immediate postoperative results were good in 71% of cases. Four patients died (9%). Long term results were evaluated in 29 patients (mean follow-up period: 35 months). Twenty-two patients (76%) had excellent or good results, 5 (17%) fair, and 2 (7%) had severe neurological dysfunctions and needed continuous assistance. CONCLUSIONS: Surgical risk factors typical of this age group were identified: cranio-spinal location, damage to the cortical or deep venous system, severe peritumoral edema, and poor neurological preoperative conditions. Systemic risk factors were insulin-dependent diabetes and obesity.

[Magnetic resonance features in cerebral primary lymphomas in non-immunocompromised subjects]. / Aspetti della Risonanza Magnetica nei linfomi primitivi cerebrali nei soggetti non immunocompromessi.

In the past few years, non-Hodgkin's lymphomas have been paid increasing attention to because of their recently increasing frequency. We reviewed the MR images of 17 patients with histologically proved primary CNS lymphoma, all of them immunocompetent at diagnosis. We studied the site, number and shape of the lesions, the presence and grade of edema and possible periventricular spread. The exams were performed with 0.5 T and 1.5 T MR units, using SE sequences on the sagittal, axial and coronal planes, before and after Gd-DTPA administration. The most typical neuroradiologic signs which may suggest the diagnosis of CNS lymphoma are deep or periventricular lesion site, diffuse and marked contrast enhancement, poorly defined borders, moderate edema surrounding the mass and a tendency to periventricular spread. MRI demonstrated 35 lesions in 17 patients. The lymphoma was unifocal in 9 cases (53%) and 7 lesions were localized in subtentorial site. Lesion size did not exceed 2 cm in 49% of cases, ranged 2-4 cm in 40% and exceeded 4 cm in 11% of cases only. These lesions and hypo- to isointense on T1-weighted images (97%) and their signal intensity varies on T2-weighted images, with mainly iso-/hypointense patterns (79%). All lesions enhanced after Gd-DTPA administration, 74% of them markedly and 26% moderately; enhancement was mostly homogeneous (80% of cases). Perilesional edema was observed in 74% of cases. In conclusion, MRI yields some useful information for the diagnosis of primary CNS lymphoma, but the clinical and radiologic signs of this lesion may exhibit aspecific signal features, meaning that no correct diagnosis can be made even in immuno-competent patients.

Prolonged infusion gemcitabine: a clinical phase I study at low- (300 mg/m2) and high-dose (875 mg/m2) levels.

Gemcitabine (GEM) is a novel nucleoside analogue with a unique mechanism of action. Preliminary studies have shown a mild, schedule-dependent toxic profile with a broad range of MTDs and promising antitumor activity in various solid tumors. This phase I study describes the infusion length-effect relationships of low- (300 mg/m2) and high-dose (875 mg/m2) GEM, administered on days 1, 8 and 15 at 4-week intervals in a step-wise escalation of duration (> or = 33%) at a starting level of 60 minutes. At least 3 patients entered each infusion-level step and 3 more cases were treated in the presence of significant toxicity. Conservative criteria for toxicity were employed, including treatment delay until recovery with infusion de-escalation in the subsequent course. Forty-seven patients (29 at low- and 18 at high-dose GEM levels) with various solid tumors, including 9 (taken as a reference) who had received the same dose levels over 30 min. entered the study. All but 9 patients (with pancreatic cancer) had been previously treated with chemotherapy and all had extensive visceral disease. A striking infusional-effect relationship was observed at both GEM dose levels. Four escalation steps were required to define the maximum tolerated infusion time (MTIT) at 6 hours for 300 mg/m2 GEM, with leucopenia being dose-limiting. At 875 mg/m2, although no limiting toxicity was observed (in spite of increased severity of leucopenia), no escalation was attempted following the 1-hour infusion, due to the limiting rate (58% of 12 patients) of toxic delay requiring shorter infusions. Toxicity was usually mild (no grade 4 event was recorded) showing the usual profile, although there was a trend towards increased non-hematologic toxicity (i.e. LFT abnormalities) as compared with the MTD previously defined using a 30-min. infusion schedule (1,370 mg/m2). Eight patients achieved a PR: 1 with NSCLC, 1 with gastric and 2 with bladder cancer at 300 mg/m2 (1 with a 3- and 3 with a 6-hour infusion) and 2 with pancreatic, 1 with cervical and another with bladder cancer at 875 mg/m2 (all but one with a 1-hour infusion). These data clearly suggest that the infusion duration is an important independent factor that influences the clinical effects of GEM. The present study not only defined the toxic profiles and the MTITs of the selected dose levels but demonstrated that GEM retained the antitumor activity at doses as small as 300 mg/m2 when given as a prolonged infusion. Further studies should clarify the underlying mechanism(s) responsible for the erratic dose-effect dose-effect relationships of GEM and establish the optimal dose-infusion level in the treatment of solid tumors.

111In-octreotide scintigraphy in pituitary adenomas.

This study reports on 111In-octreotide scintigraphy in 20 patients affected with pituitary adenomas, including tracer uptake ratios and in vitro immunohistochemical characterization of the matostatin receptor state. 111In-octreotide uptake was already observed at 4 hours in 7/8 GH-secreting adenomas, in 5/7 non-secreting adenomas and in 1/5 prolactinomas. Concordance between the scan and the histochemical results was observed in all cases. The uptake ratios evaluated at 24 hours ranged from 2.3 to 4.2. The following conclusions were drawn: 1) 111In-octreotide is a suitable tracer to evaluate the somatostatin receptor state of pituitary adenomas; 2) Semi-quantitative measures of tracer uptake can be easily obtained with static planar scanning, but more refined techniques are needed for receptor kinetics evaluation; 3) This nuclear technique is a promising non-invasive tool to identify patients with somatostatin receptor positive pituitary adenomas who might potentially benefit from pre- and/or post-surgery cold octreotide medical treatment.