Lung visualisation on PET/MRI: implementing a protocol with a short echo-time and low flip-angle volumetric interpolated breath-hold examination sequence.

AIM: To assess the diagnostic performance in detecting lung lesions of a short echo-time (TE) and low flip-angle (FA) volumetric interpolated breath-hold examination (VIBE) sequence included in the integrated positron-emission tomography (PET)/magnetic resonance imaging (MRI) protocol. METHOD AND MATERIALS: Thirty-seven oncological patients who underwent computed tomography (CT) and PET/MRI, including both a dedicated short TE, low FA VIBE (modified VIBE) and a standard VIBE of the lung, were enrolled. Modified VIBE images were reviewed retrospectively and independently by three raters, to detect pulmonary nodules, parenchymal consolidation, and bands. Three other groups examined standard VIBE, PET, and CT images. MRI and PET findings were compared to CT using Krippendorff's alpha using patient-based and a lesion-based analysis. Krippendorff's alpha was calculated to assess the interobserver agreement among the three raters of the modified VIBE. RESULTS: In the patient-based analysis (positivity ≥1 lesion), the comparison of modified VIBE with CT showed an alpha of 0.54 for nodules <6 mm (versus 0.41 for standard VIBE and 0.09 for PET) and an alpha of 0.88 for nodules ≥6 mm (versus 0.74 for standard VIBE and 0.42 for PET). On a lesion-based analysis (presence/absence of each lesion), modified VIBE compared to CT showed an alpha of0.58 for nodules <6 mm (versus 0.44 for standard VIBE and 0.09 for PET) and an alpha of 0.90 for nodules ≥6 mm (versus 0.79 for standard VIBE and 0.50 for PET). The alpha value for the interobserver agreement was 0.90 for nodules <6 mm, 0.91 for nodules ≥6 mm, 1.00 for consolidations, and 0.95 for bands in the patient-based analysis and 0.89, 0.93, 1.00, and 0.95 in the lesion-based analysis. CONCLUSIONS: Modified VIBE proved to be reproducible, showed better accuracy than standard VIBE and PET, and very good concordance with CT in assessing lung nodules ≥6 mm, whereas the agreement was less satisfactory for smaller nodules.

Risk factors including the presence of inflammation at the resection margins for colorectal anastomotic stenosis following surgery for diverticular disease.

AIM: The aim of this study was to investigate risk factors for anastomotic stenosis in patients operated on for diverticular disease. Histological inflammation and diverticula at the resection margins were also considered. METHOD: Patients' characteristics, the surgical technique and postoperative complications were collected from the medical records. Anastomotic stenoses were evaluated prospectively by rigid sigmoidoscopy during follow-up examination. Histological specimens were examined by a single pathologist who investigated inflammation and diverticula at the resection margins. Twenty patients with anastomotic colorectal stenosis from a single tertiary centre were compared with 24 consecutive patients without stenosis. They were all operated on for diverticular disease over a specified time period. RESULTS: Histological inflammation and diverticula were found in 25% and 30% of the resection margins respectively. Univariate analysis showed that age > 71 years (P = 0.0002), female gender (P = 0.0069) and anastomoses located below 12 cm from the anal verge (P = 0.020) were risk factors for stenosis. No correlation was found between anastomotic stenosis and the presence of histological inflammation or diverticula at the resection margins. By multivariate analysis, only age > 71 years was found to be a statistically significant risk factor for stenosis (P = 0.0003, OR = 60.8, 95% CI: 6.4-575.5). CONCLUSION: Anastomotic stenosis is a frequent, long-term complication following surgery for diverticular disease. An analysis demonstrated that age is a risk factor for colorectal stenosis and that histological inflammation and the presence of diverticula near/at the resection margins have no effect on the incidence of stenosis.

First-line screening tests for Cushing's syndrome in patients with adrenal incidentaloma: the role of urinary free cortisol measured by LC-MS/MS.

INTRODUCTION AND AIM: Patients with adrenal incidentaloma present a wide range of cortisol secretion, which is not always properly defined by first-line screening tests recommended to rule out Cushing's syndrome (CS), such as 1-mg dexamethasone suppression test (1-mg DST), late night salivary cortisol (LNSC), or 24-h urinary free cortisol (UFC). Therefore, we examined the diagnostic performance of each screening test in patients with adrenal incidentaloma. MATERIALS AND METHODS: In a series of 164 consecutive patients with adrenal incidentaloma, we measured serum cortisol after 1-mg DST, LNSC, and UFC (with LC-MS/MS). Medical history was investigated for cardiovascular events (CVE) in a subgroup of 93 patients with at least 2 years of follow-up. RESULTS: Serum cortisol <50 nmol/L after 1-mg DST presented the highest sensitivity (100%) to rule out CS, despite a low specificity (62%). UFC > 170 nmol/24 h achieved the highest diagnostic accuracy (sensitivity 98%, specificity 91%, and negative/positive likelihood ratios of 0.02/10.83, respectively). The prevalence of CVE was higher in patients with non-suppressed cortisol after 1-mg DST and high UFC levels (p = 0.018). Traditional cardiovascular risk factors (hypertension, diabetes mellitus, dyslipidemia, BMI > 30 kg/m2, smoke or high gender-based waist circumference) were not associated with CVE. CONCLUSIONS: The 1-mg DST at its lowest threshold presented high sensitivity in identifying CS, but its low specificity encourages us to consider UFC levels, measured with LC-MS/MS, to reduce false-positive test results. High UFC levels could also be considered as markers to stratify cardiovascular risk in patients with adrenal incidentaloma.

Calculating regional tissue volume for hyperthermic isolated limb perfusion: Four methods compared.

INTRODUCTION: Hyperthermic isolated limb perfusion (HILP) can be performed as an alternative to amputation for soft tissue sarcomas and melanomas of the extremities. Melphalan and tumor necrosis factor-alpha are used at a dosage that depends on the volume of the limb. Regional tissue volume is traditionally measured for the purposes of HILP using water displacement volumetry (WDV). Although this technique is considered the gold standard, it is time-consuming and complicated to implement, especially in obese and elderly patients. AIM: The aim of the present study was to compare the different methods described in the literature for calculating regional tissue volume in the HILP setting, and to validate an open source software. METHODS: We reviewed the charts of 22 patients (11 males and 11 females) who had non-disseminated melanoma with in-transit metastases or sarcoma of the lower limb. We calculated the volume of the limb using four different methods: WDV, tape measurements and segmentation of computed tomography images using Osirix and Oncentra Masterplan softwares. RESULTS AND CONCLUSION: The overall comparison provided a concordance correlation coefficient (CCC) of 0.92 for the calculations of whole limb volume. In particular, when Osirix was compared with Oncentra (validated for volume measures and used in radiotherapy), the concordance was near-perfect for the calculation of the whole limb volume (CCC = 0.99). With methods based on CT the user can choose a reliable plane for segmentation purposes. CT-based methods also provides the opportunity to separate the whole limb volume into defined tissue volumes (cortical bone, fat and water).

Inflammatory cell burden and phenotype in endomyocardial biopsies with antibody-mediated rejection (AMR): a multicenter pilot study from the AECVP.

This multicenter case-controlled pilot study evaluated myocardial inflammatory burden (IB) and phenotype in endomyocardial biopsies (EMBs) with and without pathologic antibody-mediated rejection (pAMR). Sixty-five EMBs from five European heart transplant centers were centrally reviewed as positive (grade 2, n = 28), suspicious (grade 1, n = 7) or negative (n = 30) for pAMR. Absolute counts of total, intravascular (IV) and extravascular (EV) immunophenotyped mononuclear cells were correlated with pAMR grade, capillary C4d deposition, donor specific antibody (DSA) status and acute cellular rejection (ACR). In pAMR+ biopsies, equivalent number of IV CD3+ T lymphocytes (23 ± 4/0.225 mm(2) ) and CD68+ macrophages (21 ± 4/0.225 mm(2) ) were seen. IB and cell phenotype correlated with pAMR grade, C4d positivity and DSA positivity (p < 0.0001). High numbers of IV T lymphocytes were associated with low grade ACR (p = 0.002). In late-occurring AMR EV plasma cells occurring in 34% of pAMR+ EMBs were associated with higher IB. The IB in AMR correlated with pAMR+, C4d positivity and DSA positivity. In pAMR+ equivalent numbers of IV T lymphocytes and macrophages were found. The presence of plasma cells was associated with a higher IB and occurrence of pAMR late after transplantation.

Assessing response using 99mTc-MIBI early after interstitial chemotherapy with carmustine-loaded polymers in glioblastoma multiforme: preliminary results.

Introduction. Early signs of response after applying wafers of carmustine-loaded polymers (gliadel) are difficult to assess with imaging because of time-related imaging changes. (99m)Tc-sestamibi (MIBI) brain single-photon emission tomography (SPET) has reportedly been used to reveal areas of cellularity distinguishing recurrent neoplasm from radionecrosis. Our aim was to explore the role of MIBI SPET in assessing response soon after gliadel application in glioblastoma multiforme (GBM). Methods. We retrospectively reviewed the charts on 28 consecutive patients with a radiological diagnosis of GBM who underwent MIBI SPET/CT before surgery (with intracavitary gliadel placement in 17 patients), soon after surgery, and at 4 months. The area of uptake was selected using a volume of interest that was then mirrored contralaterally to obtain a semiquantitative ratio. Results. After adjusting for ratio at the baseline, the effect of treatment (gliadel versus non-gliadel) was not statistically significant. Soon after surgery, however, 100% of patients treated with gliadel had a decreased ratio, as opposed to 62.5% of patients in the non-gliadel group (P = 0.0316). The difference between ratios of patients with radical versus partial resection reached statistical significance by a small margin (P = 0.0528). Conclusions. These data seem to suggest that the MIBI ratio could be a valuable tool for monitoring the effect of gliadel early after surgery.

Is resectable hepatocellular carcinoma a contraindication to liver transplantation? A novel decision model based on "number of patients needed to transplant" as measure of transplant benefit.

BACKGROUND & AIMS: Number-needed-to-treat is used in assessing the effectiveness of a health-care intervention, and reports the number of patients who need to be treated to prevent one additional bad outcome. Although largely used in medical literature, there are no studies measuring the benefit of liver transplantation (LT) over hepatic resection (HR) for hepatocellular carcinoma (HCC) in terms of "Number of patients needed to transplant (NTT)." EXCLUSION CRITERIA: Child-Turcotte-Pugh (CTP) Classes B-C, very large (>10 cm) and multi-nodular (>2 nodules) tumours, macroscopic vascular invasion and extra-hepatic metastases. STUDY POPULATION: 1028 HCC cirrhotic patients from one Eastern (n=441) and two Western (n=587) surgical units. Patient survival observed after HR by proportional hazard regression model was compared to that predicted after LT by the Metroticket calculator. The benefit obtainable from LT compared to resection was analysed in relationship with number of nodules (modelled as ordinal variable: single vs. oligonodular), size of largest nodule (modelled as a continuous variable), presence of microscopic vascular invasion (MVI), and time horizon from surgery (5-year vs. 10-year). RESULTS: 330 patients were beyond the Milan criteria (32%) and 597 (58%) had MVI. The prevalence of MVI was 52% in patients within Milan criteria and 71% in those beyond (p<0.0001). In the 5-year transplant benefit analysis, nodule size and HCC number were positive predictors of transplant benefit, while MVI had a strong negative impact on NTT. Transplantation performed as an effective therapy (NTT <5) only in oligonodular HCC with largest diameter >3cm (beyond conventional LT criteria) when MVI was absent. The 10-year scenario increased drastically the transplant benefit in all subgroups of resectable patients, and LT became an effective therapy (NTT <5) for all patients without MVI whenever tumor extension and for oligonodular HCC with MVI within conventional LT criteria. CONCLUSIONS: Based on NTT analysis, the adopted time horizon (5-year vs. 10-year scenario) is the main factor influencing the benefit of LT in patients with resectable HCC and Child A cirrhosis.

Potential use of contrast-enhanced ultrasound (CEUS) in the detection of metastatic superficial lymph nodes in melanoma patients.

PURPOSE: Malignant melanoma represents a significant and growing public health burden worldwide. Ultrasonography is the most useful diagnostic modality for regional lymph nodal staging. Because any focal areas of cortical lobulation or thickening-swelling should also be considered as a sign of metastases, we are going to report the usefulness of contrast-enhanced ultrasonography (CEUS) in the differential diagnosis of benign or malignant lymph nodes in patients with malignant melanoma based on blood stream patterns and investigate the diagnostic capability. PATIENTS AND METHODS: After the excision of cutaneous melanoma with positive excision margins but with negative sentinel lymph node, 540 patients underwent US of superficial lymph nodes. The inclusion criteria for CEUS consisted of both major signs (absence of the echogenic hilus, round shape, and peripheral capsular vascularity) and minor ones (the presence of focal cortical thickening). The diagnostic capability was evaluated by comparing the cytological findings with the enhancement pattern on CEUS.  RESULTS: US in combination with CEUS correctly classified 534/540 patients. CEUS applied to lymph nodes with focal cortical thickening on grayscale US confirmed great sensitivity (0.98) and specificity (0.99) but above all, it showed a markedly improved accuracy of 0.99. The likelihood ratios confirmed the good performance of the methods used. CONCLUSION: CEUS increases the diagnostic accuracy of US in the differential diagnosis of benign and malignant LNs but it also allows us, when possible, to avoid unnecessary invasive operations such as LN FNAC. Moreover, CEUS may guide FNAC in the case of focal cortical thickening on the basis of hypoperfusion, with a reduction in the number of false negatives and much earlier detection of nodal metastatic foci.

Human olfactory sensitivity for bourgeonal and male infertility: a preliminary investigation.

Olfactory receptor (OR) expression is also present in the sperm cells and could mediate sperm chemotaxis. OR1D2 was the first OR expressed in the testis demonstrated to be involved in chemotaxis and to be expressed also in the nose with a similar behavior. Bourgeonal is the OR1D2 most potent known agonist. Infertility affects ~15 % of couples in western countries and sometimes it is unexplained. This pilot study compared the bourgeonal olfactory thresholds, the ability of sperm to sense the bourgeonal and the frequency of 13 single nucleotide polymorphisms (SNPs) of OR1D2 gene in nine males suffering of unexplained infertility with a control group of 15 healthy males. The mean olfactory threshold for bourgeonal was statistically different between the study group (10.5 ± 3.7; median 12.3) and the control group (14.0 ± 2.8; median 15.5) (p = 0.006). Statistical analysis showed a significantly higher percentage of spermatozoa that migrated toward the capillaries filled with bourgeonal in the control group compared to the study group (p < 0.0001). Sperm migration was equally inhibited in both groups of subjects when, together with bourgeonal, capillaries were filled with undecanal, a strong bourgeonal inhibitor (p = 0.42). The 13 SNPs of OR1D2 revealed a statistically significant difference for allele and genotype frequency of rs769423 in study group versus control group (p = 0.02). The present preliminary study seems to confirm the important role of OR1D2 both in nose and spermatozoa and may explain the idiopathic infertility of the study group. Further studies on larger series are mandatory to confirm our preliminary evidence.

Risk factors for colorectal anastomotic stenoses and their impact on quality of life: what are the lessons to learn?

AIM: The aim of the study was to analyse the incidence of benign colorectal anastomotic stenoses in consecutive patients operated on in a single institution and to assess risk factors for their development. Their impact on quality of life was also evaluated. METHOD: Patient characteristics, indications for surgery, surgical technique and postoperative complications were prospectively recorded. Stenosis was evaluated by rectoscopy at regular intervals, and patients were treated only if symptomatic. After at least 6 months following surgery, patients were asked to respond to the Short Form 36-item quality-of-life questionnaire during a telephone interview. RESULTS: Of the original 211 patients considered, 195 underwent a follow-up rectoscopy and were included in the study. Benign stenosis were found in 26 (13%), and 19 (73%) symptomatic patients were treated successfully (15 with endoscopic dilatation and four with radial diathermic surgical incisions). Risk factors for anastomotic stenosis according to univariate analysis were female sex, diverticulitis, mechanical anastomosis, and anastomosis located between 8 and 12 cm from the anal verge. The significant risk factors identified by multivariate analysis were diverticulitis (OR 5, P=0.002) and mechanical anastomosis (OR 9, P=0.04). The self-perceived quality of life of patients with stenosis was significantly worse compared with controls. CONCLUSION: Since diverticulitis and mechanical anastomosis are risk factors for anastomotic stenosis, surgeons should take this into account when they are considering what type of anastomotic technique to utilize.

Microangiopathy is independently associated with presence, severity and composition of carotid atherosclerosis in type 2 diabetes.

BACKGROUND AND AIMS: Common mechanisms for the development of micro- and macroangiopathic diabetic complications have been suggested. We aimed to cross-sectionally investigate strength and characteristics of the association between carotid atherosclerosis and microangiopathy in type 2 diabetic patients. METHODS AND RESULTS: Common carotid artery intima-media thickness (cIMT), carotid plaque (CP) type and degree of stenosis were evaluated by ultrasound, along with the determination of anthropometric parameters, HbA1c, lipid profile, assessment of diabetic retinopathy and nephropathy, in 662 consecutive patients with type 2 diabetes mellitus (T2DM). Patients were divided according to high/low cIMT, presence/absence of CP and of retinopathy and nephropathy. Patients with CP were older, more prevalently males, past smokers, had longer diabetes duration, significantly lower HDL cholesterol and more prevalent ischemic heart disease (all p<0.05) as compared to those with cIMT < 1 mm. Microangiopathies were more prevalent in patients with CP than in those without. At multivariate logistic regression, factors independently associated with the presence of CP were age, past smoke, HDL cholesterol, retinopathy and retinopathy plus nephropathy. A significant independent correlation of CP stenosis with stage of retinopathy and nephropathy was found. Finally, echolucent CPs were associated with a lower prevalence of proliferative retinopathy than CP containing calcium deposits. CONCLUSION: In T2DM, retinopathy, alone or in combination with nephropathy, is independently associated to CP, and severity of microangiopathy correlates with severity of carotid atherosclerosis. These observations, together with the different prevalence of proliferative retinopathy according to CP types, point to possible common pathogenic mechanisms in micro- and macrovascular complications.

Predictors of survival and toxicity in patients on adjuvant therapy with 5-fluorouracil for colorectal cancer.

The present study aimed at investigating whether the simultaneous evaluation of pharmacokinetic, pharmacogenetic and demographic factors could improve prediction on toxicity and survival in colorectal cancer patients treated with adjuvant 5-fluorouracil (5FU)/leucovorin therapy. One hundred and thirty consecutive, B2 and C Duke's stage colorectal cancer patients were prospectively enrolled. 5FU pharmacokinetics was evaluated at the first cycle. Thymidylate synthase (TYMS) 5'UTR and 3'UTR polymorphisms and methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms were assessed in peripheral leukocytes. Univariate and multivariate analyses were applied to evaluate which variables could predict chemotherapy-induced toxicity, disease-free survival (DFS) and overall survival (OS). Multivariate analysis showed that: (a) low 5FU clearance was an independent predictive factor for severe toxicity (OR=7.32; P<0.0001); (b) high-5FU clearance predicted poorer DFS (HR=1.96; P=0.041) and OS (HR=3.37; P=0.011); (c) advanced age was associated with shorter DFS (HR=3.34; P=0.0008) and OS (HR=2.66; P=0.024); (d) the C/C genotype of the MTHFR C677T polymorphism was protective against grade 3-4 toxicity (P=0.040); (e) none of the TYMS polymorphisms could explain 5FU toxicity or clinical outcome.