[Cardiac arrest caused by anomalous origin and course of the right coronary artery]. / Arresto cardiaco causato da coronaria destra ad origine e decorso anomali.

The anomalous origin of the right coronary artery from the left sinus with interarterial course is a rare but life-threatening coronary abnormality. Coronary computed tomography is crucial in identifying this disease whose treatment, based on coronary artery bypass grafting, is recommended in symptomatic patients but is more controversial in asymptomatic patients. The case report presented offers an opportunity to discuss the pathophysiological, diagnostic and therapeutic aspects of this congenital coronary artery disease.

Bilateral breast metastases as the first manifestation of an occult pancreatic neuroendocrine tumor.

Breast metastases are uncommon findings compared to primary breast cancer and in particular bilateral secondary breast lesions from neuroendocrine tumor (NET)s are extremely rare with just less over 13 cases described in literature. We reported herewith the case of a 54-year-old woman who presented to our Breast Unit after noticing multiple, mobile, bilateral breast lumps. Imaging studies confirmed the presence of multiple, circumscribed, bilateral breast masses with slightly spiculated margins, classified as suspicious for malignancy (BI-RADS 4). A tru-cut biopsy was carried out on the largest lesion of each side and histopathologic and immunohistochemistry examination was consistent with metastases from pancreatic neuroendocrine tumor (PNET). Total-body CT revealed the presence of a mass located in the pancreatic body - tail with associated abdominal lymphadenopathies and multiple secondary nodules in bilateral breast and in the liver. Stage IV disease was diagnosed, patient did not undergo surgery and started LAR - octreotide therapy. Although rare, breast metastases from NETs represent an important diagnostic challenge for practitioners because of the difficulty to differentiate from a primary breast carcinoma or even from benign breast lesions. Clinicians should be aware of the possibility of bilateral breast metastases in differential diagnosis of breast lesions in order to ensure the correct diagnosis and the most appropriate management of these patients.

[Takotsubo syndrome complicated by ventricular thrombosis and pericarditis]. / Sindrome takotsubo complicata da trombosi ventricolare e pericardite.

Takotsubo syndrome is a heart disease characterized by transient ventricular dysfunction; although it is considered a benign pathology, it is not free from serious complications. Intraventricular thrombosis is a rare occurrence as well as pericarditis, and the simultaneous presence of both complications is very exceptional. Here we describe a case. Diagnosis and therapeutic management was successfully guided by multimodality imaging.

Radiological Wheeler staging system: a retrospective cohort analysis to improve the local staging of prostate cancer with multiparametric MRI.

BACKGROUND: The knowledge of tumor location and extension can allow a modulated radical prostatectomy in order to minimize positive surgical margins and reduce functional morbidity after surgery in patients with prostate cancer (PCa). Multiparametric (mp) magnetic resonance imaging (MRI) could allow the assessment of tumor extension and of its relationship with external structures. Aim of this study is to propose a new radiological Wheeler (rW) staging system applied to mp-MRI, based on the pathologic staging system (pW) for the local assessment of PCa. METHODS: This retrospective single-center multi-reader study included consecutive patients with PCa and preoperative mp-MRI, who underwent non-nerve sparing radical prostatectomy. Three radiologists reported on all examinations and classified each selected lesion according to imaging criteria following rW. Whole-mount histological sections were used as the reference standard. An experienced pathologist classified the extent of prostatic capsular invasion of each PCa according to the pW. Each histological section was scanned for comparison with mp-MRI findings. The rate of PCa correctly classified by radiologists using the pW was assessed. To evaluate the accuracy of mp-MRI in the discrimination between T2 and T3 PCa, the AUC was computed. RESULTS: One-hundred and five patients with a total of 195 PCa foci were included in the study. 130/195 tumors with a clear overlap between mp-MRI and surgical specimens were selected. The sensitivity of the most experienced reader was lower than that of the other two readers (48.6% vs. 68.6% and 62.9%, P>0.09) while specificity and PPV were higher (95.8% vs. 79.0% and 57.9%, P<0.001; 81.0% vs. 54.6% and 35.5%, P<0.041; respectively). The AUC values for the most and the intermediate experienced readers in the detection of extracapsular extension were in the range 0.72-0.74. CONCLUSIONS: The rW staging system has low accuracy in predicting each single pW class, while accuracy was over 80% for experienced readers in the identification of organ-confined (T2 stage class) tumors and non-organ confined cases (T3 stage class).

Multiparametric magnetic resonance imaging of the prostate with computer-aided detection: experienced observer performance study.

OBJECTIVES: To compare the performance of experienced readers in detecting prostate cancer (PCa) using likelihood maps generated by a CAD system with that of unassisted interpretation of multiparametric magnetic resonance imaging (mp-MRI). METHODS: Three experienced radiologists reviewed mp-MRI prostate cases twice. First, readers observed CAD marks on a likelihood map and classified as positive those suspicious for cancer. After 6 weeks, radiologists interpreted mp-MRI examinations unassisted, using their favourite protocol. Sensitivity, specificity, reading time and interobserver variability were compared for the two reading paradigms. RESULTS: The dataset comprised 89 subjects of whom 35 with at least one significant PCa. Sensitivity was 80.9% (95% CI 72.1-88.0%) and 87.6% (95% CI 79.8-93.2; p = 0.105) for unassisted and CAD paradigm respectively. Sensitivity was higher with CAD for lesions with GS > 6 (91.3% vs 81.2%; p = 0.046) or diameter ≥10 mm (95.0% vs 80.0%; p = 0.006). Specificity was not affected by CAD. The average reading time with CAD was significantly lower (220 s vs 60 s; p < 0.001). CONCLUSIONS: Experienced readers using likelihood maps generated by a CAD scheme can detect more patients with ≥10 mm PCa lesions than unassisted MRI interpretation; overall reporting time is shorter. To gain more insight into CAD-human interaction, different reading paradigms should be investigated. KEY POINTS: • With CAD, sensitivity increases in patients with prostate tumours ≥10 mm and/or GS > 6. • CAD significantly reduces reporting time of multiparametric MRI. • When using CAD, a marginal increase of inter-reader agreement was observed.

Detection of prostate cancer index lesions with multiparametric magnetic resonance imaging (mp-MRI) using whole-mount histological sections as the reference standard.

OBJECTIVE: To evaluate the sensitivity of multiparametric magnetic resonance imaging (mp-MRI) for detecting prostate cancer foci, including the largest (index) lesions. PATIENTS AND METHODS: In all, 115 patients with biopsy confirmed prostate cancer underwent mp-MRI before radical prostatectomy. A single expert radiologist recorded all prostate cancer foci including the index lesion 'blinded' to the pathologist's biopsy report. Stained whole-mount histological sections were used as the reference standard. All lesions were contoured by an experienced uropathologist who assessed their volume and pathological Gleason score. All lesions with a volume of >0.5 mL and/or pathological Gleason score of >6 were defined as clinically significant prostate cancer. Multivariate analysis was used to ascertain the characteristics of lesions identified by MRI. RESULTS: In all, 104 of 115 index lesions were correctly diagnosed by mp-MRI (sensitivity 90.4%; 95% confidence interval [CI] 83.5-95.1%), including 98/105 clinically significant index lesions (93.3%; 95% CI 86.8-97.3%), among which three of three lesions had a volume of <0.5 mL and Gleason score of >6. Overall, mp-MRI detected 131/206 lesions including 13 of 68 'insignificant' prostate cancers. The multivariate logistic regression modelling showed that pathological Gleason score (odds ratio [OR] 11.7, 95% CI 2.3-59.8; P = 0.003) and lesion volume (OR 4.24, 95% CI 1.3-14.7; P = 0.022) were independently associated with the detection of index lesions at MRI. CONCLUSIONS: This study shows that mp-MRI has a high sensitivity for detecting clinically significant prostate cancer index lesions, while having disappointing results for the detection of small-volume, low Gleason score prostate cancer foci. Thus, mp-MRI could be used to stratify patients according to risk, allowing better treatment selection.

A fully automatic method to register the prostate gland on T2-weighted and EPI-DWI images.

Prostate adenocarcinoma (PCa) is the most frequent noncutaneous cancer among men in developed countries. Magnetic Resonance (MR) has been used to detect PCa and several clinical trials report on the accuracy of the test. Multiparametric MR imaging (mpMRI) is defined as the integration of information from different morphological and functional datasets. mpMRI could be used to increase the performances of prostate MR, therefore allowing a more accurate assessment of the tumor gland extent, while reducing reporting time and interobserver variability. The first step to perform such a multiparametric analysis is to correct for voluntary and involuntary movements during the acquisitions, as well as for image distortion in the Diffusion Weighted (DWI) images. The aim of this work is to present a fully automatic registration algorithm between T2w and DWI images, able to realign the images and to correct the distortions in the DWI. Results showed a good overlap after registration and a strong decrease of mean surface distance in both the central gland and peripheral zone. These promising results suggest that the algorithm could be integrated in a CAD system which will combine the pharmacokinetic parameters derived from DCE-MRI, T2w MRI and DWI MR to generate one comprehensive value assessing the risk of malignancy. However to perform such a multiparametric analysis, it is necessary to correct for voluntary and involuntary (breathing, heart beating) movements during the DCE-MRI acquisition, and to realign also the DCE-MRI sequence to the T2w sequence.

Technical limits of comparison of step-sectioning,immunohistochemistry and RT-PCR on breast cancer sentinel nodes: a study on methacarn-fixed tissue.

The optimal pathological assessment of sentinel nodes (SLNs) in breast cancer is a matter of debate. Currently, multilevel histological evaluation and immunohistochemistry (IHC) are recommended, but alternative RT-PCR procedures have been developed. To assess the reliability of these different procedures, we devised a step-sectioning protocol at 100 micron-intervals of 74 SLNs using methacarn fixation. mRNA was extracted from sections collected from levels 4 to 5. Mammaglobin, CEA and CK19 were used for RT-PCR. mRNA extraction was successful in 69 SLNs. Of these, 7 showed macrometastases (>2mm), 2 showed micrometastases (<2 mm) and 7 showed isolated tumour cells (ITC) by IHC. RT-PCR was positive for the three markers in 6 of 7 macrometastases and in 1 of 2 micrometastases. In the 2 RT-PCR negative cases, metastases were detected only on sections distant from those analysed by RT-PCR. CEA and/or CK19 were positive by RT-PCR in 3 of 7 ITC and in 23 morphologically negative SLNs. In conclusion, the main goal of our study was to show that the use of alternate sections of the same sample for different procedures is the key reason for the discrepancies between molecular and morphological analyses of SLN. We believe that only prospective studies with quantitative mRNA analysis of specific metastatic markers on the whole lymph node can elucidate the utility of molecular assessments of SLN.

Predicting gefitinib responsiveness in lung cancer by fluorescence in situ hybridization/chromogenic in situ hybridization analysis of EGFR and HER2 in biopsy and cytology specimens.

In non-small cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) mutational analysis is an excellent predictor of responsiveness to treatment with tyrosine kinase inhibitors, such as gefitinib. In up to 80% of NSCLCs, cytologic samples or endoscopic biopsies are the only specimens available for molecular analysis, but PCR amplification of DNA from small fixed and paraffin-embedded samples may create artifactual mutations. Fluorescence in situ hybridization (FISH) of EGFR and HER2 has been proposed as an alternative method of analysis. This project aimed to determine the optimal scoring method for FISH or chromogenic in situ hybridization (CISH) assays when analyzing small NSCLC samples to predict response. FISH or CISH analysis of EGFR and HER2 genes was done on 42 small samples derived from NSCLC patients treated with gefitinib. EGFR mutational analysis was done after quantity and quality controls of DNA. In seven of seven cases, a balanced increase in EGFR gene and chromosome 7 number was found to correlate with the presence of specific EGFR mutations. In addition, seven of seven cases with balanced EGFR/HER2 polysomy and two of three cases with balanced EGFR/HER2 trisomy responded to gefitinib (75% of responders). Instead, the EGFR mutations predicted only 7 of 12 (58%) of gefitinib-responsive patients. When only endoscopic biopsies or cytologic specimens are available, we propose using FISH/CISH for EGFR and HER2 as the test of choice for selecting patients for treatment with gefitinib and to consider as negative predictive factor the absence of EGFR/HER2 gene gain.

CD157, the Janus of CD38 but with a unique personality.

CD157 is a pleiotropic ectoenzyme which belongs to the CD38 family and to the growing number of leukocyte surface molecules known to act independently as both receptors and enzymes. A 45-kDa surface structure with a GPI anchor, the CD157 molecule displays two distinct domains in its extracellular component. The first is implicated in the enzymic activities of the molecule and the second features adhesion/signalling properties. CD157 shares several characteristics with CD38, including a similar amino acid sequence and enzymic functions. Both molecules are involved in the metabolism of NAD(+), and the CD157 gene is synthenic on 4p15 with CD38, with which it also shares a unique genomic organization. Their conservation in phylogeny is striking evidence for their relevance in the life and death cycle of the cell.