Sara Massironi

Accuracy of Ultrasonography, Spiral CT, Magnetic Resonance, and Alpha-Fetoprotein in Diagnosing Hepatocellular Carcinoma: A Systematic Review

BACKGROUND AND AIM:In patients with chronic liver disease, the accuracy of ultrasound scan (US), spiral computed tomography (CT), magnetic resonance imaging (MRI), and alpha-fetoprotein (AFP) in diagnosing hepatocellular carcinoma (HCC) has never been systematically assessed, and present systematic review was aimed at this issue.METHODS:Pertinent cross-sectional studies having as a reference standard pathological examinations of the explanted liver or resected segment(s), biopsies of focal lesion(s), and/or a period of follow-up, were identified using MEDLINE, EMBASE, Cochrane Library, and CancerLit. Pooled sensitivity, specificity, and likelihood ratios (LR) were calculated using the random effect model. Summary receiver operating characteristic (SROC) curve and predefined subgroup analyses were made when indicated.RESULTS:The pooled estimates of the 14 US studies were 60% (95% CI 44–76) for sensitivity, 97% (95% CI 95–98) for specificity, 18 (95% CI 8–37) for LR+, and 0.5 (95% CI 0.4–0.6) for LR−; for the 10 CT studies sensitivity was 68% (95% CI 55–80), specificity 93% (95% CI 89–96), LR+ 6 (95% CI 3–12),and LR− 0.4 (95% CI 0.3–0.6); for the nine MRI studies sensitivity was 81% (95% CI 70–91), specificity 85% (95%CI 77–93), LR+ 3.9 (95%CI 2–7), and LR− 0.3 (95% CI 0.2–0.5). The sensitivity and specificity of AFP varied widely, and this could not be entirely attributed to the threshold effect of the different cutoff levels used.CONCLUSIONS:US is highly specific but insufficiently sensitive to detect HCC in many cirrhotics or to support an effective surveillance program. The operative characteristics of CT are comparable, whereas MRI is more sensitive. High-quality prospective studies are needed to define the actual diagnostic role of AFP.

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.

Plasma chromogranin a in patients with inflammatory bowel disease.

Background: Circulating chromogranin A (CgA) levels, a marker for neuroendocrine tumors including carcinoids, have recently been found elevated in some patients with inflammatory bowel disease (IBD), although their significance is unclear. Therefore, we aimed to evaluate CgA levels and their possible relationship with clinical and biochemical disease activity indexes in 119 IBD patients. Methods: The study groups comprised 75 patients with ulcerative colitis, 44 with Crohns disease, in both active and quiescent phases, and 85 controls. Results: Mean CgA levels were significantly higher in IBD patients than in controls (20.4 ± 14.0 [SD] versus 11.3 ± 4.3 U/L, P < 0.001), without any statistical significant difference among the IBD subgroups. However, CgA levels were above the normal range (20 U/L) in 25/45 patients with active IBD (55%; 95% confidence interval [CI]: 40%–70%) and in 18/74 patients with remission IBD (24%; 95% CI: 15%–36%) (P < 0.001, Fishers test). Among biochemical parameters, CgA correlated with serum TNF‐&agr; levels (rs = 0.398, P < 0.001). Conclusions: High CgA levels can occur in IBD. The disease activity and TNF‐&agr; levels seem to influence the CgA pattern, which could reflect the neuroendocrine system activation in response to inflammation. From a clinical point of view, the possibility of high CgA levels in IBD should be taken into consideration when a carcinoid is suspected in such patients, since this event seems to be more frequent than previously considered. Indeed, revision of our 83 patients with gastrointestinal carcinoids, studied between 1997 and 2006, showed that 4 patients had IBD, with a prevalence of 4.8%, which is markedly higher than that of the general population.

Sporadic and MEN1-related primary hyperparathyroidism: differences in clinical expression and severity.

Primary hyperparathyroidism (PHPT) is a common endocrine disease that is associated with multiple endocrine neoplasia type 1 (MEN1) in ∼2% of PHPT cases. Lack of a family history and other specific expressions may lead to underestimated MEN1 prevalence in PHPT. The aim of this study was to identify clinical or biochemical features predictive of MEN1 and to compare the severity of the disease in MEN1‐related versus sporadic PHPT (sPHPT). We performed a 36‐mo cross‐sectional observational study in three tertiary referral centers on an outpatient basis on 469 consecutive patients with sporadic PHPT and 64 with MEN1‐related PHPT. Serum calcium, phosphate, PTH, 25(OH)D3, and creatinine clearance were measured, and ultrasound examination of the urinary tract/urography was performed in all patients. In 432 patients, BMD was measured at the lumbar spine (LS) and femoral neck (FN). MEN1 patients showed lower BMD Z‐scores at the LS (−1.33 ± 1.23 versus −0.74 ± 1.4, p = 0.008) and FN (−1.13 ± 0.96 versus −0.6 ± 1.07, p = 0.002) and lower phosphate (2.38 ± 0.52 versus 2.56 ± 0.45 mg/dl, p = 0.003) and PTH (113.8 ± 69.5 versus 173.7 ± 135 pg/ml, p = 0.001) levels than sPHPT patients. Considering probands only, the presence of MEN1 was more frequently associated with PTH values in the normal range (OR, 3.01; 95% CI, 1.07–8.50; p = 0.037) and younger age (OR, 1.61; 95% CI, 1.28–2.02; p = 0.0001). A combination of PTH values in the normal range plus age <50 yr was strongly associated with MEN1 presence (OR, 13.51; 95% CI, 3.62–50.00; p = 0.0001). In conclusion, MEN1‐related PHPT patients show more severe bone but similar kidney involvement despite a milder biochemical presentation compared with their sPHPT counterparts. Normal PTH levels and young age are associated with MEN1 presence.

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

Nutritional deficiencies in inflammatory bowel disease: therapeutic approaches.

BACKGROUND & AIMS Malnutrition is common in inflammatory bowel diseases (IBD), mainly in Crohns disease (CD) because the small bowel is primarily affected. We reviewed the literature to highlight the importance of proper nutrition management. METHODS A PubMed search was performed for English-language publications from 1999 through 2012. Manuscripts comparing nutritional approaches for IBD patients were selected. RESULTS We identified 2025 manuscripts: six meta-analyses, 170 clinical-trials, 692 reviews. The study findings are discordant. In adult CD, enteral nutrition plays a supportive role, steroid therapy remaining the first choice treatment. In CD children enteral nutrition may represent the primary therapy. As regards parenteral nutrition, there are no large randomized studies, although mild improvements in morbidity have been described as a result of parenteral nutrition in malnourished surgical IBD patients. Specific micronutrient deficiencies are common in IBD. A number of factors may contribute to micronutrient deficiencies, and these include: dietary restriction, disease activity and surgery. The possible therapeutic roles of omega-3 fatty-acids, probiotics and prebiotics have been studied, but the results are still preliminary. CONCLUSION Protein-energy malnutrition and micronutrient depletion are clinical concerns in IBD patients. Enteral nutrition, parenteral nutrition and micronutrient supplementation are cornerstone of the multidisciplinary management of IBD patients.

Dual cut-off transient elastography to assess liver fibrosis in chronic hepatitis B: a cohort study with internal validation.

Aliment Pharmacol Ther 2011; 34: 353–362

Plasma Chromogranin A Response to Octreotide Test: Prognostic Value for Clinical Outcome in Endocrine Digestive Tumors

OBJECTIVES:Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) expressing somatostatin receptors may be treated with somatostatin analogs (SSAs). Selection criteria are a positive Octreoscan or a >50% hormone level decrease after octreotide subcutaneous (s.c.) injection (octreotide test) (OT). Plasma chromogranin A (CgA) is the best general GEP-NET marker, but data on CgA response to OT are scanty. Thus, we evaluated whether plasma CgA response to OT could predict the clinical response to SSAs.METHODS:At diagnosis, 38 GEP-NET patients received octreotide 200 μg s.c., with plasma CgA determination at 0, 3, and 6 h. Long-term SSA treatment was then given by monitoring symptomatic, biochemical, and objective responses, and survival.RESULTS:Basal plasma CgA levels were significantly higher in patients with functioning than non-functioning tumors (median (range): 220 (18–2,230) vs. 46 (25–8,610) U/l, P=0.03) and in those with than without metastases (171 (18–8,610) vs. 43 (28–220) U/l, P=0.04). CgA levels significantly correlated with WHO classification, clinical TNM staging, and Ki-67 proliferative index. After OT, CgA levels decreased from 146 (18–8,610) to 61 (10–8,535) U/l (basal and nadir values), P<0.001. In patients responsive to OT, a successful objective response occurred in 21/31 patients (68%). Successful symptomatic response occurred in 13/18 patients (72%), biochemical response in 25/31 (81%), and objective response in 21/31 (68%). In the remaining seven unresponsive cases, with CgA decrement <30%, disease progressed to death in six (86%). Median survival from enrollment was 48 months (6–138) in responsive and 6 (6–30) in unresponsive patients (P=0.0005).CONCLUSIONS:In GEP-NETs, plasma CgA is a reliable marker, and a >30% decrease after OT has a relevant prognostic meaning allowing the identification of the subgroup of patients most likely to be responsive to chronic SSAs.

Circulating ghrelin levels in patients with inflammatory bowel disease

Ghrelin, the gut-brain peptide recently identified as the natural endogenous ligand for growth hormone secretagogue receptors, exerts various endocrine and non-endocrine effects, including control of food intake and energy homeostasis.1 It could also play a role in modulating immune responses and inflammatory processes.1 Indeed, ghrelin exerts potent anti-inflammatory effects in vitro and in vivo,1–5 and high circulating ghrelin levels have been found in rats with septic shock, cysteamine induced duodenal ulcers, and adjuvant induced arthritis.4–6 Also, we have recently demonstrated that in patients with newly diagnosed coeliac disease, circulating ghrelin levels are abnormally high, correlate positively with intestinal mucosal lesion severity, and normalise in successfully gluten free diet treated patients.7 However, normal or even decreased ghrelin levels have been found in other inflammatory diseases, including rheumatoid arthritis and Helicobacter pylori associated …

Transient elastography assessment of the liver stiffness dynamics during acute hepatitis B

Background and aims The diagnostic accuracy of transient elastography (TE) for assessment of hepatic fibrosis is hampered by several factors, including acute parenchymal injury. Evaluation of liver stiffness (LS) using TE during acute hepatitis B may help to assess chronic hepatitis B patients with flares. Patients and methods Twelve patients consecutively referred for acute hepatitis B, underwent sequential examinations with TE and laboratory examinations for 24 weeks. Results On admission, aminotransferase ranged from 487 to 6067 IU/l (median=2590 IU/l) and LS ranged from 7.1 to 57 kPa (median=15.6 kPa) with nine (75%) patients showing LS greater than 11.9 kPa, that is, the predictive cutoff for cirrhosis. LS levels correlated significantly with bilirubin, only (r=0.58, P<0.05). During follow-up, LS declined from 15.6 to 5.2 kPa at week 24, with a significant reduction being observed at week 2 for aminotransferase (from 2590 to 452 IU/l, P<0.0001) and at week 6 for both LS (from 15.6 to 6.0 kPa, P=0.008) and bilirubin (from 10.7 to 0.95 mg/dl, P<0.01). Median decline of LS significantly correlated with bilirubin decline (rs=0.70, P<0.05). At week 24, 10 (83%) patients showed LS of less than 7.9 kPa and two (17%) patients had LS values between 7.9 and 11.9 kPa, including the only patient who developed chronic hepatitis B. Conclusion In patients with acute hepatitis B, the initial high values of LS mimicking LS cutoff of cirrhosis, likely reflect the liver cell inflammation, oedema and swelling as they progressively taper down during hepatitis resolution.