L.V. Forzenigo

The diagnostic and economic impact of contrast imaging techniques in the diagnosis of small hepatocellular carcinoma in cirrhosis

Background Contrast-enhanced ultrasound (CE-US), contrast CT scan and gadolinium dynamic MRI are recommended for the characterisation of liver nodules detected during surveillance of patients with cirrhosis with US. Aim To assess the sensitivity, specificity, diagnostic accuracy and economic impact of all possible sequential combinations of contrast imaging techniques in patients with cirrhosis with 1–2 cm liver nodules undergoing US surveillance. Patients/methods 64 patients with 67 de novo liver nodules (55 with a size of 1–2 cm) were consecutively examined by CE-US, CT, MRI, and a fine-needle biopsy (FNB) as diagnostic standard. Undiagnosed nodules were re-biopsied; non-malignant nodules underwent enhanced imaging follow-up. The typical radiological feature of hepatocellular carcinoma (HCC) was arterial phase hypervascularisation followed by portal/venous phase washout. Results HCC was diagnosed in 44 (66%) nodules (2, <1 cm; 34, 1–2 cm; 8, >2 cm). The sensitivity of CE-US, CT and MRI for 1–2 cm HCC was 26, 44 and 44%, with 100% specificity, the typical vascular pattern of HCC being identified in 22 (65%) by a single technique versus 12 (35%) by at least two techniques carried out at the same time point (p=0.028). Compared with the cheapest dual examination (CE-US+CT), the cheapest single technique of stepwise imaging diagnosis of HCC was equally expensive (€26 440 vs €28 667), but led to a 23% reduction of FNB procedures (p=0.031). Conclusions In patients with cirrhosis with a 1–2 cm nodule detected during surveillance, a single imaging technique showing a typical contrast pattern confidently permits the diagnosis of HCC, thereby reducing the need for FNB examinations.

Antibodies to Neutrophil Cytoplasm in Italian Patients with Ulcerative Colitis: Sensitivity, Specificity and Recognition of Putative Antigens

We studied the prevalence of perinuclear antineutrophil cytoplasmic antibody (p-ANCA), as detected by immunofluorescence, in 290 Italian subjects. One hundred and two were affected by ulcerative colitis, 48 by Crohns disease, 40 by gluten-sensitive enteropathy and 100 were normal subjects. The prevalence of p-ANCA was significantly higher in ulcerative colitis patients (45.1%) as compared to Crohns disease patients (4.8%), gluten-sensitive enteropathy (0%) and normal subjects (1%; p < 0.0001 ulcerative colitis vs. all other groups). In this setting, the overall specificity of the test was 98.1% with a sensitivity of 45.1%. The specificity slightly decreased to 95.1% when ulcerative colitis patients were compared to patients with Crohns colitis. In our series, p-ANCA appeared to be more prevalent in ulcerative colitis patients with more aggressive disease. ELISA experiments performed in order to identify the putative antigen(s) recognized by p-ANCA-positive sera showed that 8 of 12 sera positive at immunofluorescence reacted with at least one of the neutrophil preparations tested. The reactivities were directed towards various neutrophil preparations. Preabsorption with the specific antigen recognized by ELISA significantly inhibited the p-ANCA immunofluorescence reactivity indicating that p-ANCA reactivity might derive from the recognition of heterogeneous neutrophil-associated antigens.

Diagnosis of Hepatocellular Carcinoma in Cirrhosis by Dynamic Contrast Imaging: The Importance of Tumor Cell Differentiation

Dynamic contrast imaging techniques are considered the standard of care for the radiological diagnosis of hepatocellular carcinoma (HCC) in cirrhosis. However, the accuracy of radiological diagnosis depends largely on the degree of arterial hypervascularization, which increases with tumor size. Owing to the interplay and prognostic relevance of tumor vascularization and cell differentation, we asked ourselves whether tumor grade also affects the outcome of radiological diagnosis. Sixty‐two HCCs (47 of which measured 1‐2 cm) were consecutively detected in 59 patients with compensated cirrhosis under surveillance with ultrasound and confirmed by way of echo‐guided biopsy and concurrent investigations with contrast‐enhanced ultrasound (CE‐US), computed tomography (CT), and gadolinium magnetic resonance imaging (MRI). Tumor cell differentiation was evaluated using Edmondson‐Steiner criteria in liver cores of 0.9‐5.0 cm (median 1.6 cm). Eighteen (29%) HCCs were grade I (1.5 cm), 28 (45%) were grade II (1.5 cm), 16 (26%) were grade III (1.8 cm), and none were grade IV. Contrast wash‐in and wash‐out were concurrently demonstrated in 21 (34%) tumors by way of CE‐US, including three (16%) grade I and 18 (41%) grade II‐III (P = 0.08); in 32 (52%) tumors by way of CT, including three (16%) grade I and 29 (66%) grade II‐III (P = 0.0006); and 28 (47%) tumors by way of MRI, including three grade I (16%) and 25 (57%) grade II‐III (P = 0.01). Among 1‐ to 2‐cm tumors, the radiological diagnosis was achieved in two of 16 grade I and 17of 31 grade II‐III tumors (P = 0.006). Conclusion: Tumor grade, a relevant predictor of disease severity, influences the accuracy of dynamic contrast techniques in the diagnosis of HCC. HEPATOLOGY 2010

Contrast enhanced CT-scan to diagnose intrahepatic cholangiocarcinoma in patients with cirrhosis

BACKGROUND & AIMS Contrast enhanced computed tomography (CT-scan) is a standard of care for the radiological diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis. This technique, however, is not validated to exclude intrahepatic cholangiocarcinoma (ICC) which may develop in patients with cirrhosis, as well. METHODS To assess the features of contrast CT-scan in the diagnosis of ICC, we reviewed all CT-scan films obtained in cirrhotic patients with a histologically documented ICC, taking in consideration the pattern and dynamics of the arterial, portal venous and delayed phases of contrast uptake. RESULTS Thirty-two patients had 40 nodules of ICC (22 male; median age 62years; 13 hepatitis C) that were identified either during surveillance with abdominal ultrasound (21 patients, 66%) or incidentally (11 patients, 34%). ICC was either multifocal or ≥ 30 mm in 11 of the former and 10 of the latter group (52% vs. 91%, p<0.05). Two nodules (5%) escaped detection by CT-scan, while the remaining 38 showed a heterogeneous contrast enhancement pattern, being the arterial peripheral-rim enhancement present in 19 (50%) cases and a progressive homogeneous contrast uptake in 16 (42%) cases during the three vascular phases, with no relation to tumor size. Importantly, all nodules lacked the radiological hallmark of HCC, the only ICC nodule showing a homogeneous wash-in during the arterial phase followed by a wash-out in the delayed venous phase, however showing a homogeneous wash-in during the portal phase too. CONCLUSIONS ICC in cirrhotic patients displays distinct vascular patterns at CT-scan that allow for differentiation from HCC.

Correlation between IgA antiendomysial antibodies and subtotal villous atrophy in dermatitis herpetiformis

Serum IgA antiendomysial antibodies (EmA) were present in 20 (64.5%) of 31 patients with dermatitis herpetiformis (DH) on a normal diet. A significant correlation was found between these antibodies and the severity of gluten-induced jejunum damage. IgA EmA were positive in 19 (86%) of the 22 DH patients with subtotal villous atrophy, in comparison with the positivity of only one (11%) of the nine DH patients with less severe intestinal involvement (partial villous atrophy or mild abnormalities). The specificity of this test for gluten-sensitive enteropathy was 100%, these antibodies being consistently negative in biopsied disease controls showing a normal jejunal mucosa. Moreover, IgA EmA proved to be useful in monitoring the response to gluten withdrawal in DH patients, as these antibodies always disappeared in all the DH cases studied after 1 year of gluten-free diet together with the regrowth of jejunal villi. The strict relationship between IgA EmA and subtotal villous atrophy is more helpful still since the enteropathy present in DH is usually symptomless and therefore difficult to suspect.

Computer-assisted evaluation of perianal fistula activity by means of anal ultrasound in patients with Crohn's disease

OBJECTIVES:Assessment of the activity of perianal fistulas may be of clinical relevance in patients with Crohns disease. Fistula activity is currently evaluated by means of magnetic resonance imaging; anal ultrasound can also be used, but its diagnostic performance in this setting remains to be defined. Our aims were to evaluate the agreement between clinical examination, magnetic resonance imaging, and anal ultrasound in assessing perianal fistula activity, and to apply computerized analysis to improve the assessment of ultrasound images.METHODS:Thirty-one consecutive patients with Crohns perianal fistulas underwent clinical examination, and magnetic resonance and anal ultrasound imaging. Active fistulas were defined as the presence of active drainage or signs of local inflammation on clinical examination, and the definition was confirmed by surgical examination. Activity was assessed on the basis of T2 hyperintensity on magnetic resonance imaging and the degree of hypoechogenicity on anal ultrasound; the anal ultrasound images were also analyzed using dedicated computer image-analysis software.RESULTS:Twenty-five patients had an active fistula at clinical examination. The agreement between clinical examination and magnetic resonance imaging was good (k-value = 0.739), whereas that with anal ultrasound was only fair (k-value = 0.266–0.294); computer-assisted analysis of the anal ultrasound images improved the agreement from fair to good (k-value = 0.608–0.670).CONCLUSIONS:Anal ultrasound can be used to assess fistula track activity in patients with Crohns disease. The diagnostic performance of the technique can be improved to values comparable with those of magnetic resonance imaging by using a computer-assisted evaluation of the anal ultrasound images.

Impact of hemodynamics on lumen boundary displacements in abdominal aortic aneurysms by means of dynamic computed tomography and computational fluid dynamics

The aim of the present work is to quantitatively assess the three-dimensional distributions of the displacements experienced during the cardiac cycle by the luminal boundary of abdominal aortic aneurysm (AAA) and to correlate them with the local bulk hemodynamics. Ten patients were acquired by means of time resolved computed tomography, and each patient-specific vascular morphology was reconstructed for all available time frames. The AAA lumen boundary motion was tracked, and the lumen boundary displacements (LBD) computed for each time frame. The intra-aneurysm hemodynamic quantities, specifically wall shear stress (WSS), were evaluated with computational fluid dynamics simulations. Co-localization of LBD and WSS distributions was evaluated by means of Pearson correlation coefficient. A clear anisotropic distribution of LBD was evidenced in both space and time; a combination of AAA lumen boundary inward- and outward-directed motions was assessed. A co-localization between largest outward LBD and high WSS was demonstrated supporting the hypothesis of a mechanistic relationship between anisotropic displacement and hemodynamic forces related to the impingement of the blood on the lumen boundary. The presence of anisotropic displacement of the AAA lumen boundary and their link to hemodynamic forces have been assessed, highlighting a new possible role for hemodynamics in the study of AAA progression.

No Relative Increase in Intra-Abdominal Adipose Tissue in Healthy Unstressed Preterm Infants at Term

Background: Preterm infants may be at risk for altered adiposity, a known risk factor for unfavorable metabolic and cardiovascular outcomes. Objectives: The aim was to compare body composition (total body fat mass (FM), subcutaneous and intra-abdominal adipose tissue (AT)) between infants born preterm and at term. Methods: We conducted an observational, cross-sectional study that involved 50 infants born preterm free from major co-morbidities and 34 term healthy breastfed infants. Anthropometric measurements, body composition (total body FM, subcutaneous and intra-abdominal AT) were assessed at 40-42 weeks postconceptional age for preterm infants and within 15 days of birth for term infants. Total body FM was assessed by an air displacement plethysmography system and subcutaneous abdominal and intra-abdominal AT were assessed by magnetic resonance imaging using a commercially available software program. Results: Compared to term infants, mean (SD) total body FM (g) (636.7 (247) vs. 418.4 (253), p < 0.0001) and mean (SD) subcutaneous abdominal AT (g) (123 (36) vs. 98.9 (22), p < 0.001) were significantly higher in preterm infants but mean (SD) fat-free mass (g) (2,530 (420) vs. 2,965 (389), p < 0.0001) and mean (SD) intra-abdominal AT (10.9 (5.2) vs. 18.2 (13.2), p = 0.001) were significantly lower. Conclusions: In the absence of severe illness during the hospital stay, prematurity, although associated with increased total body FM, does not appear to be associated with a relative increase in intra-abdominal AT compared to term infants.

Transarterial embolization with microspheres in the treatment of monofocal HCC

BACKGROUND Transarterial embolization using one permanent embolic agent alone enhances tumour ischaemia and spares patients with hepatocellular carcinoma form toxic chemotherapeutic drugs. PURPOSE We assessed feasibility, tolerability and efficacy of transarterial embolization with microspheres in patients with a single node hepatocellular carcinoma. MATERIALS AND METHODS Eighteen consecutive patients with compensated cirrhosis, hypervascularized single hepatocellular carcinoma, in whom liver transplantation was indicated (no.=3), or excluded from radical therapies (no.=15), received selective transarterial embolization with microspheres. Treatment was repeated every other month until complete devascularitazion was demonstrated by computed tomography, for a maximum of 3 cycles. RESULTS Fifty transarterial embolization courses (mean: 2.8 courses, range 1-6) were administered, corresponding to a 100% applicability rates. Initial complete response was achieved in 16 (89%) patients and confirmed by histology in 2 transplanted patients. During 21-month follow-up (range 8-36), hepatocellular carcinoma recurred in 10 (62%) patients who achieved initial complete response, and de novo tumour nodes developed in 10 (56%). No patient required analgesics and none had liver function deteriorated following transarterial embolization. CONCLUSIONS Transarterial embolization is a well-tolerated treatment for patients with early or intermediate hepatocellular carcinoma who are not suitable for radical treatment or await liver transplantation, but it allows to achieve a sustained complete response in a minority of patients.

Structural Fat Grafting to Improve Outcomes of Vocal Folds’ Fat Augmentation: Long-term Results

Objective Evaluating the long-term outcomes of vocal fold structural fat grafting. Study Design Case series with chart review. Setting University hospital. Subjects and Methods Seventy-nine dysphonic patients (16-82 years; 55 with unilateral laryngeal paralysis and 24 with vocal fold scarring) underwent vocal fold fat injection. Fat was harvested by low-pressure liposuction and then processed by centrifugation. Refined fat aliquots were placed in the vocal fold and paraglottic space in multiple tunnels to enhance graft neovascularization. All patients were followed for 12 months, 15 for 3 years, and 5 for 10 years with videolaryngostroboscopy, maximal phonation time (MPT) measurement, Voice Handicap Index (VHI) questionnaire, and GRBAS (grade, roughness, breathiness, asthenia, strain) perceptual evaluation. Laryngeal computed tomography (CT) and/or magnetic resonance imaging (MRI) studies were performed in 16 patients 3 to 28 months postoperatively; MRI was repeated in 5 cases 12 to 18 months after the first radiological study. Results The voice quality of all patients improved after surgery, and long-term stability was confirmed by MPT, GRBAS, and VHI (P ranging between .004 and <.001). The results achieved 1 year postoperatively remained stable at 3 and 10 years. Videolaryn-gostroboscopy showed improved glottic closure in all patients despite a limited amount of fat resorption. CT and MRI demonstrated survival of the fat grafts in all of the 16 examined cases. Serial MRI scans showed no change in graft size over time. Conclusions The reported clinical and radiological data demonstrate that fat is an effective filler for permanent vocal fold augmentation if the refined micro-aliquots are placed in multiple tunnels.