Non-functioning parathyroid cystic tumour: malignant or not? Report of a case.

Parathyroid carcinoma (PC) is a very rare endocrine tumour, usually characterized by symptoms such as a neck mass, dysphonia, severe hypercalcemia exceeding 140 mg/L and elevated serum parathyroid hormone levels, even more than 5 times the upper limit of normal. Non-functioning parathyroid cancer is extremely rare and, in this case, its pre-operative diagnosis is often difficult. A 54-year old female patient, referring dysphagia and dysphonia, underwent neck ultrasound and neck CT. A left thyroid nodule, probably cystic, was found. It presented caudal extent on anterior mediastinum causing compression of the left lateral wall of the trachea. The preoperative calcemia was into the normal range. The patient underwent left thyroid lobectomy. Histological exam showed a cystic lesion, immunohistochemically originating from parathyroid that oriented for carcinoma. The 18 months follow-up did not show a residual-recurrent disease. The parathyroid origin of a neck lesion could not be suspected before surgery when specific laboratory tests are not available and clinical effects of hyperparathyroidism syndrome are not present. Histological features are not always sufficient for the differential diagnosis between the parathyroid adenoma and carcinoma. The immunohistochemistry is an useful tool that can aid to reach the definite diagnosis.

Sarcopenia is associated with severe liver fibrosis in patients with non-alcoholic fatty liver disease.

BACKGROUND: Sarcopenia recognises insulin resistance and obesity as risk factors, and is frequently associated with cardiometabolic disorders, including non-alcoholic fatty liver disease (NAFLD). AIM: To test the prevalence of sarcopenia and its relation with the severity of fibrosis (main outcome) and the entire spectrum of liver histology in patients with NAFLD. METHODS: We considered 225 consecutive patients with histological diagnosis of NAFLD (Kleiner score). The skeletal muscle index (%) (total appendicular skeletal muscle mass (kg)/weight (kg) × 100), a validated measure of sarcopenia, was assessed by bioelectrical impedance analysis. Sarcopenia was defined as a skeletal muscle mass index ≤37 in males and ≤28 in females. RESULTS: The prevalence of sarcopenia showed a linear increase with the severity of fibrosis, and severe fibrosis (F3-F4) was more than doubled in sarcopenia (48.3% vs. 20.4% in fibrosis ≤F2, P < 0.001). After adjusting for confounders, the association of sarcopenia with severe fibrosis was maintained (OR 2.36, CI 1.16-4.77, P = 0.01), together with age > 50 (OR 6.53, CI 2.95-14.4, P < 0.001), IFG/Diabetes (OR 2.14, CI 1.05-4.35, P = 0.03) and NASH (OR 13.3, CI 1.64-108.1, P = 0.01). Similarly, a significant association was found between sarcopenia and NASH (P = 0.01), steatosis severity (P = 0.006), and ballooning (P = 0.01), but only the association with severe steatosis was maintained (OR 2.02, CI 1.06-3.83, P = 0.03) after adjusting for confounders. CONCLUSIONS: In Western patients with NAFLD, with high prevalence of metabolic disorders and advanced liver disease, sarcopenia was associated with the severity of fibrosis and steatosis, independently of hepatic and metabolic risk factors. Studies are needed to assess the impact of interventions to reduce sarcopenia on NAFLD progression.

D2-40 negative pyogenic granuloma-like Kaposi's sarcoma: Diagnostic features and histogenetic hypothesis of an uncommon skin tumor in HIV-negative patients.

Pyogenic granuloma-like Kaposi's sarcoma (PGLKS) is a recently described skin tumor showing features both of pyogenic granuloma (PG) and Kaposi's sarcoma (KS). The differential diagnosis is often challenging. We reviewed a series of 50 PG and 23 Ks located on distal extremities with the aid of an immunohistochemical panel comprising CD34, CD31, FVIII, SMA, D2-40, HHV8. After revision, 6/50 PG lesions previously diagnosed as PG, showed positive immunostaining for LNA1-HHV8 and focal positivity for CD31 and FVIII in the endothelial cells of the proliferating vessels, with some SMA positive pericytes. D2-40, a marker of lymphatic endothelium positive in KS, stained negatively. These lesions were renamed PGLKS. Of note, in our series, PGLKS represented the only form of KS localized in the hand; all the patients were HIV-negative, older than PG patients, with a prevalence for male gender. PGLKS and PG need a different management and a follow-up is advisable for PGLKS, as for the other variants of KS. To date, D2-40 negative immunostaining has not yet been reported in PGLKS and should not lead to a misdiagnosis of PG. The morphological similarities with PG and the immunohistochemical findings, showing a defective phenotype of the neoplastic cells, suggest a histogenetic hypothesis in which D2-40 negative PGLKS could represent an early stage of HHV8 infection of a pre-existing PG, whose vessels loose progressively their blood vascular markers but have not still acquired the lymphatic ones.

PNPLA3 rs738409 I748M is associated with steatohepatitis in 434 non-obese subjects with hepatitis C.

BACKGROUND: The PNPLA3/Adiponutrin rs738409 C/G single nucleotide polymorphism is associated with the severity of steatosis, steatohepatitis and fibrosis in patients with non-alcoholic fatty liver disease, as well as the severity of steatosis and fibrosis in patients with chronic hepatitis C (CHC). AIM: To test in genotype 1(G1)-CHC patients, the putative association between the PNPLA3 variant and histological features of steatohepatitis, as well as their impact on the severity of fibrosis. METHODS: Four hundred and thirty-four consecutively biopsied Caucasian G1-CHC patients were genotyped for PNPLA3 rs738409, its effect evaluated by using an additive model. Histological features of steatohepatitis in CHC were assessed using the Bedossa classification. Hepatic expression of PNPLA3 mRNA was evaluated in 63 patients. RESULTS: The prevalence of steatohepatitis increased from 16.5% in patients with PNPLA3 CC, to 23.2% in CG and 29.2% in the GG genotype (P = 0.02). By multiple logistic regression, PNPLA3 genotype (OR 1.54, 95% CI 1.03-2.30, P = 0.03), together with age (OR 1.03, 95% CI 1.00-1.05, P = 0.02), BMI ≥ 30 (OR 2.06, 95% CI 1.04-4.10, P = 0.03) and homoeostasis model assessment (HOMA, OR 1.18, 95% CI 1.04-1.32, P = 0.006) were independently linked to steatohepatitis. When stratifying for obesity, PNPLA3 was associated with NASH in non-obese patients only (12.0% in CC vs. 18.3% in CG vs. 27.3% in GG, P = 0.01), including after correction for metabolic confounders (OR 2.06, 95% CI 1.26-3.36, P = 0.004). We showed an independent association between steatohepatitis (OR 2.05, 95% CI 1.05-4.02, P = 0.003) and severe fibrosis. Higher liver PNPLA3 mRNA was associated both with the severity of steatosis (adjusted P = 0.03) and steatohepatitis after adjusting for gender, age, BMI and HOMA (P = 0.002). CONCLUSION: In patients with genotype 1 hepatitis C, the PNPLA3 G variant is associated with a higher risk of steatosis severity and steatohepatitis, particularly among non-obese subjects.

Quantification of fibrosis by collagen proportionate area predicts hepatic decompensation in hepatitis C cirrhosis.

BACKGROUND: It is unclear whether the course of cirrhosis and its prognosis are related to the amount of collagen in the liver. AIM: To determine whether fibrosis, assessed by collagen proportionate area (CPA) in patients with compensated cirrhosis, is associated with the presence of oesophageal varices, and predict disease decompensation during the follow-up period. METHODS: We prospectively evaluated 118 consecutive patients with compensated cirrhosis to correlate fibrosis, assessed by CPA in liver biopsies, with the presence of oesophageal varices (OV) and with the rate of liver decompensation (LD) development during a median follow-up of 72 months. RESULTS: At baseline 38 (32.2%) patients had OV and during the follow-up (median 72 months, IQR 47-91), 17 patients (14.4%) developed LD. The mean CPA value was different in patients with and without OV (14.8 ± 5.9% vs. 21.6 ± 9.5%, P < 0.001). The best CPA cut-off for OV by area under the receiver operating characteristic (AUROC) was ≥14% and with multivariate logistic analysis CPA was the only variable associated with OV (OR: 28.32, 95% CI: 6.30-127.28; P < 0.001). By AUROC analysis the best CPA cut-off to predict LD was 18.0%. By Cox regression multivariate analysis CPA ≥18% (HR: 3.99, 95% CI: 1.04-11.45; P = 0.036), albumin (HR: 0.12, 95% CI: 0.04-0.43; P = 0.001) and presence of OV (HR: 8.15, 95% CI: 2.31-28.78; P = 0.001) were independently associated with LD. CONCLUSION: Quantification of fibrosis by collagen proportionate area allows identification of patients with compensated HCV cirrhosis with a higher likelihood of clinically relevant portal hypertension and a higher risk of decompensation.

Immunohistochemical/histochemical double staining method in the study of the columnar metaplasia of the oesophagus.

Intestinal metaplasia in Barrett's oesophagus (BO) represents an important risk factor for oesophageal adenocarcinoma. Instead, few and controversial data are reported about the progression risk of columnar-lined oesophagus without intestinal metaplasia (CLO), posing an issue about its clinical management. The aim was to evaluate if some immunophenotypic changes were present in CLO independently of the presence of the goblet cells. We studied a series of oesophageal biopsies from patients with endoscopic finding of columnar metaplasia, by performing some immunohistochemical stainings (CK7, p53, AuroraA) combined with histochemistry (Alcian-blue and Alcian/PAS), with the aim of simultaneously assess the histochemical features in cells that shows an aberrant expression of such antigens. We evidenced a cytoplasmic expression of CK7 and a nuclear expression of Aurora A and p53,  both in goblet cells of BO and in non-goblet cells of CLO, some of which showing mild dysplasia. These findings suggest that some immunophenotypic changes are present in CLO and they can precede the appearance of the goblet cells or can be present independently of them, confirming the conception of BO as the condition characterized by any extention of columnar epithelium. This is the first study in which a combined immunohistochemical/histochemical method has been applied to Barrett pathology.

HER2 status in advanced gastric carcinoma: A retrospective multicentric analysis from Sicily.

According to the ToGA trial, HER2 has been shown to be predictive for the success of treatment with trastuzumab in advanced gastric cancer (AGC). A number of studies have analyzed HER-2/neu overexpression in gastric carcinoma and identified the rate of HER2 positivity to be markedly varied. To date, the prevalence of HER2 overexpression in Sicilian people with AGC is unknown. Therefore, in the present study, a retrospective immunohistochemical analysis of HER2 was performed in a cohort of 304 AGC samples that were obtained from the archives of 10 Sicilian anatomopathological diagnostic units in order to verify the positive rate of HER2-positive cases. Furthermore, the characteristics of histotype, grade, stage and Ki-67 expression were also analyzed. HER2 overexpression was encountered in 17.43% of all the gastric adenocarcinomas, which was consistent with the results that have been reported elsewhere in the literature. A progressive increase in HER2 overexpression was observed, from the poorly cohesive histotype to the tubular adenocarcinomas and gastric hepatoid adenocarcinomas. HER2 overexpression was significantly associated with a high grade, advanced stage and high Ki-67 labeling index. Further investigations performed jointly by pathologists and oncologists within the geographical area of the present study should confirm that the association of trastuzumab with chemotherapy results in an improvement of survival in patients with AGC.

Recurrent ossifying fibroma of the maxillary sinus in an adult patient.

In some aspects, the terminology of fibro-osseous lesions of the head remain equivocal. The WHO classification suggested to group cemento-ossifying fibroma and ossifying fibroma under the term "ossifying fibroma". Based on the different age of onset, localization and risk of recurrence, two types have been described: "juvenile ossifying fibroma", with early age of onset, which needs to be treated with wide surgical resection due to the high risk of recurrence; and "adult ossifying fibroma", arising in adult patients, with low recurrence rate, properly treated by conservative surgery. We describe a case of an "adult ossifying fibroma" of a 57-year-old woman with several relapses, for whom conservative therapy was inadequate. We think that the "early" age of onset should not be included among the essential characteristics of ossifying fibroma with a high risk of recurrence.

Association of vitamin D serum levels and its common genetic determinants, with severity of liver fibrosis in genotype 1 chronic hepatitis C patients.

Lower 25-hydroxyvitamin D [25(OH)D] serum levels have been associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients (G1CHC). In addition, a recent genome-wide study identified genetic variants (rs12785878, near dehydrocholesterol reductase, DHCR7; rs10741657, near CYP2R1; and rs7041, near vitamin D-binding protein, GC) affecting 25(OH)D serum levels in healthy populations. We aimed to assess the association between vitamin D serum levels and its genetic determinants, with the severity of liver fibrosis. Two hundred and sixty patients with biopsy-proven G1CHC were consecutively evaluated. The 25(OH)D serum levels were measured by high-pressure liquid chromatography. All patients were genotyped for DHCR7 rs12785878, CYP2R1 rs10741657 and GC rs7041 single nucleotide polymorphisms. DHCR7 GG genotype (P = 0.003) and the severity of fibrosis (P = 0.03) were independent factors associated with lower 25(OH)D serum levels in multiple linear regression analysis. Interestingly, 53.8% (7/13) of patients with DHCR7 GG genotype had severe liver fibrosis, compared to 27.1% (67/247) of those with DHCR7 TT/TG genotype (P = 0.03). By multivariate logistic regression analysis, severe fibrosis was independently associated with older age (OR, 1.056; 95% CI, 1.023-1.089, P = 0.001), low cholesterol (OR, 0.984; 95% CI, 0.974-0.994, P = 0.002), high triglycerides (OR, 1.008; 95% CI, 1.002-1.015, P = 0.01), low 25(OH)D (OR, 0.958; 95% CI, 0.919-0.999, P = 0.04), DHCR7 GG genotype (OR, 4.222; 95% CI, 1.106-16.120; P = 0.03), moderate-severe steatosis (OR, 2.588; 95% CI, 1.355-4.943; P = 0.004) and moderate-severe necroinflammatory activity (grading) (OR, 2.437; 95% CI, 1.307-4.763; P = 0.001). No associations were found between liver fibrosis and both CYP2R1 and GC genotypes. In patients with G1CHC, GG homozygosis for DHCR7 gene and lower 25(OH)D levels are independently associated with the severity of liver fibrosis.

High sCD36 plasma level is associated with steatosis and its severity in patients with genotype 1 chronic hepatitis C.

Soluble CD36 (sCD36) plasma levels, a known marker of cardiometabolic disorders, are associated with surrogate markers of steatosis, while experimental and human studies show a link between CD36 expression in the liver and steatosis. In a cohort of patients with genotype 1 chronic hepatitis C (G1 CHC), we tested the association of sCD36 plasma levels with host and viral factors and sustained virological response (SVR). One hundred and seventy-five consecutive biopsy-proven patients were studied. sCD36 plasma levels were assessed by an in-house ELISA. All biopsies were scored by one pathologist for staging and grading (Scheuer) and graded for steatosis, which was considered moderate-severe if ≥20%. Patients underwent standard of care therapy with pegylated interferon and ribavirin. The severity of steatosis progressively increased according to sCD36 quartiles (P = 0.02); total and low-density lipoprotein (LDL) cholesterol levels were significantly higher in patients in the lower quartile compared to all the others. Gamma-glutamyl transferase (P = 0.02), homoeostasis model assessment (HOMA) score (P = 0.002) and sCD36 (P = 0.04) were independently associated with the severity of steatosis as continuous variable. Multivariate logistic regression analysis showed that HOMA (OR 1.243, 95% CI 1.04-1.484, P = 0.01) and sCD36 (OR 1.445, 95%CI 1.135-1.839, P = 0.003) were independently linked to steatosis ≥20%. No association was found between sCD36 and SVR. CD36 is linked to steatosis and insulin resistance in patients with G1 CHC, but does not predict response to treatment. The potential of sCD36 as a surrogate marker of steatosis should be further investigated.

The molecular changes driving the carcinogenesis in Barrett's esophagus: which came first, the chicken or the egg?

Esophageal adenocarcinoma originates from columnar metaplastic epithelium of the distal esophagus. Various steps for this carcinogenetic process are known. Before the onset of high-grade dysplasia and adenocarcinoma, endoscopic surveillance is possible. However, because of the high cost of long-term surveillance, predictive factors for cancer are being evaluated to identify subjects with metaplasia who have a higher risk of developing malignancy. Molecular changes seem suitable for this purpose, but could require a high resource expenditure. While trying to identify the best predictive factors for cancer risk, molecular changes and differences in miRNA expression profile between the various steps leading to cancer could help to clarify Barrett's carcinogenesis. In this attempt to find a molecular explanation for the onset of esophageal adenocarcinoma, it is still difficult to understand whether the molecular changes are causes or effects of the neoplastic phenotypic modifications.

Methylenetetrahydrofolate reductase homozygosis and low-density lipoproteins in patients with genotype 1 chronic hepatitis C.

Methylenetetrahydrofolate reductase status, homocysteine and lipoproteins levels have been associated with severity of disease and both rapid and sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C (CHC). We aimed to assess the association of homocysteine and MTHFR status with serum cholesterol levels and their potential links to both histological findings and virological response, in patients with genotype 1 hepatitis C virus (HCV). A total of 119 consecutive patients were evaluated by biopsy and metabolic measurements. A total of 103 healthy blood donors were used as controls. Serum homocysteine and MTHFR C677T mutation were also evaluated. All patients underwent antiviral therapy with PEG-IFN alfa-2a plus ribavirin. HCV-RNA was assessed at baseline, week 4, week 12, at the end of therapy and after 6 months of follow-up. Mean serum values of homocysteine were higher in patients than in controls (15.8 ± 5.8 µg/L vs 12.5 ± 5.8 µg/L; P < 0.001), with a similar CC, CT and TT MTHFR distribution (23.6%, 48.7% and 27.7% in G1-CHC vs 34%, 48.5% and 17.5% in controls; P = 0.14). In genotype 1, HCV MTHFR TT homozygosis was independently linked to higher LDL (OR 1.016; CI 1.002-1.031; P = 0.03), but not to homocysteine. No association were found between homocysteine, MTHFR and histological features or both rapid virological response (RVR) and SVR. Low cholesterol (OR 0.988, 95%CI 0.975-0.999, P = 0.04) was independently linked to severe fibrosis, and high LDL was the only independent positive predictors of both RVR and SVR (OR 1.036; 95%CI 1.017-1.055; P < 0.001; and OR 1.016; 95%CI 1.001-1.031; P = 0.04 respectively). In patients with genotype 1 hepatitis C, showing higher homocysteine serum levels than controls, MTHFR C677T homozygosis, via modulating cholesterol levels, could interfere with liver fibrosis and response to antiviral therapy.

Morphological and biomolecular characteristics of subcentimetric invasive breast carcinomas in Sicily: A multicentre retrospective study in relation to trastuzumab treatment.

Little information from clinical trials is available regarding the efficacy of trastuzumab treatment in subcentimetric breast carcinomas (BCs). The aim of this study was to verify the existence of correlations between HER2 and hormone receptor status, Ki67 values, grade, histotype and node involvement in a cohort of pT1a,b BCs from an area not widely covered by screening campaigns. A total of 410 pT1a,b BC formalin-fixed paraffin-embedded samples collected from eight Sicilian Anatomo-Pathological Units (APUs) were classified according to the WHO classification and tumour grading was established. Estrogen and progesterone receptor status, Ki67 labelling index and HER2 status were available. Relationships between immunohistochemical data and clinicopathological characteristics were investigated using the Chi-square test; the cohort was analysed with respect to pT1a and pT1b BC as well as to node status. Ductal infiltrating carcinoma was the prevalent histotype in the pT1a and pT1b stages; G2 was a more common tumour grade, with a range between 64.6% and 70% of pT1a and pT1b, respectively. Taking into consideration the lymph node involvement of pT1a,b BC, only 17.1% cases were node-positive without a relevant difference between pT1a and pT1b. No significant differences between pT1a and pT1b BC cases emerged in relation to Ki67 LI, hormone receptors and HER2 status. T1a,b BC cases were stratified by node involvement and a significant relationship was observed with grade as well as with HER2 status. A significant relationship for pT1a cases emerged only for tumour grade, while pT1b cases showed a significant correlation exclusively with HER2 status. Our data clearly support the operative guidelines of the National Comprehensive Cancer Network. Therefore, the combined treatment with trastuzumab plus chemotherapy should be administered only to patients with pT1b or larger BCs. In small HER2-positive pT1a or microinvasive BC, this therapy should be considered on a case-by-case basis, considering tumour grade as the first characteristic.

Visceral adiposity index is associated with significant fibrosis in patients with non-alcoholic fatty liver disease.

BACKGROUND: Metabolic factors have been associated with liver damage in patients with non-alcoholic fatty liver disease (NAFLD). AIMS: To test a new marker of adipose dysfunction, the visceral adiposity index (VAI), in NAFLD patients to assess whether or not it is associated with host factors, and to investigate a potential correlation with histological findings. METHODS: One hundred and forty-two consecutive NAFLD patients were evaluated by liver biopsy, and clinical and metabolic measurements, including insulin resistance with the homeostasis model assessment (HOMA), and VAI by using waist circumference, body mass index, triglycerides and HDL. Serum levels of TNFα, IL-6, adiponectin and leptin were also assessed. All biopsies were scored for NAFLD activity score (NAS) and its components, and for staging (Kleiner). RESULTS: By multiple linear regression analysis, VAI was independently associated with higher HOMA (P = 0.04), and fibrosis (P = 0.04). In addition, an independent association was found between higher VAI and lower adiponectin levels (P = 0.002). Higher HOMA (OR 1.149, 95% CI 1.003-1.316, P = 0.04), higher VAI (OR 1.446, 95% CI 1.023-2.043, P = 0.03), lobular inflammation (OR 3.777, 95% CI 1.771-8.051, P = 0.001), and ballooning (OR 2.884, 95% CI 1.231-6.757, P = 0.01) were correlated with significant fibrosis (F2-F4) on multiple logistic regression analysis. In particular, the prevalence of significant fibrosis progressively increased from patients with a VAI ≤ 2.1 and HOMA ≤ 3.4 (26%) to those with a VAI > 2.1 and HOMA > 3.4 (83%). CONCLUSIONS: In NAFLD patients, visceral adiposity index is an expression of both qualitative and quantitative adipose tissue dysfunction and, together with insulin resistance, is independently correlated with significant fibrosis.

Hyperuricemia is associated with histological liver damage in patients with non-alcoholic fatty liver disease.

BACKGROUND: Hyperuricemia has been associated with metabolic disorders. In this line recent studies observed an independent link between higher uric acid serum levels and clinical diagnosis of non-alcoholic fatty liver disease (NAFLD). AIMS: We aimed to assess the potential association between uric acid serum levels and histological liver damage in a homogeneous cohort of biopsy-proven NAFLD patients. METHODS: Consecutive NAFLD patients (n = 166), assessed by liver biopsy (Kleiner score), anthropometric, biochemical and metabolic features, were included. Enzymatic colorimetric test was used for serum uric acid assays (Roche Diagnostics GmbH, Mannheim, Germany). Hyperuricemia was diagnosed when uric acid serum levels were > 7 mg/dL in men, and > 6 mg/dL in women. RESULTS: Mean uric acid serum level was 5.75 mg/dL, and about 20% of patients had hyperuricemia, that was independently associated with younger age (OR 0.951, 95% CI 0.918-0.984, P = 0.004), lobular inflammation (OR 2.144, 95% CI 1.055-4.357, P = 0.03) and steatosis grade (OR 1.859, 95% CI 1.078-3.205, P = 0.02), by multivariate logistic regression analysis. Female gender (OR 2.656, 95% CI 1.190-5.928, P = 0.01), higher HOMA index (OR 1.219, 95% CI 1.043-1.426, P = 0.01), and hyperuricemia (OR 4.906, 95% CI 1.683-14.296, P = 0.004) were linked to NAFLD activity score (NAS) ≥ 5 by multiple logistic regression analysis. Conversely, higher HOMA index (OR 1.140, 95% CI 1.001-1.229, P = 0.04), and NAS (OR1.954, 95% CI 1.442-2.649, P < 0.001) were independently associated with significant fibrosis by logistic regression analysis. CONCLUSIONS: In NAFLD patients, hyperuricemia is independently associated with the severity of liver damage, representing, in this setting of patients, together with insulin resistance, a potential new therapeutic target in future intervention trials.

TyG index, HOMA score and viral load in patients with chronic hepatitis C due to genotype 1.

The triglycerides × glucose (TyG) index is a recently proposed surrogate marker of insulin resistance (IR), calculated from fasting plasma triglyceride and glucose concentrations. We tested the host and viral factors associated with Tyg and homeostasis model assessment (HOMA) scores, comparing their associations with histological features and with sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C(G1CHC). Three hundred and forty consecutive patients with G1CHC were considered. All had a liver biopsy scored by one pathologist for staging and grading (Scheuer), and graded for steatosis, which was considered moderate-severe if ≥30%. Anthropometric and metabolic measurements, including IR measured by both HOMA and TyG, were registered. By linear regression analysis, TyG was independently associated with waist circumference (WC), total cholesterol, presence of arterial hypertension, Log10 HCV-RNA and steatosis. Similarly, WC and steatosis were significantly associated with HOMA. Older age (OR, 1.036; 95%CI, 1.004-1.070, P = 0.02), higher WC (1.031; 1.004-1.060; P = 0.02) and higher TyG (11.496; 3.163-41.784; P < 0.001) were linked to moderate-to-severe steatosis (≥30%) by multiple logistic regression analysis. When TyG was replaced by HOMA-IR in the model, the latter remained significantly associated with steatosis ≥30% (1.237; 1.058-1.448; P = 0.008). Receiver operating characteristic curves showed a similar performance of TyG (AUC 0.682) and HOMA-IR (AUC 0.699) in predicting moderate-severe steatosis. No independent associations were found between both TyG and HOMA and fibrosis or SVR. In patients with G1CHC , TyG, an easy-to-calculate and low-cost surrogate marker of IR, is linked to liver steatosis and shows an independent association with viral load.

Reliability of liver stiffness measurement in non-alcoholic fatty liver disease: the effects of body mass index.

BACKGROUND: Liver stiffness measurement (LSM) using transient elastography (TE) is used to stage fibrosis in patients with liver disease, diagnostic reliability and the factors affecting its performance in patients with non-alcoholic fatty liver disease (NAFLD) are incompletely understood. AIM: To assess LSM. METHODS: Consecutive NAFLD patients (n = 169), assessed by liver biopsy (Kleiner score), anthropometrical, biochemical and metabolic features, underwent LSM using TE with standard M probe. RESULTS: Liver stiffness measurement was not reliable in 23 patients (14%) due to obesity. Among patients with a reliable TE, a LSM value >7.25 kPa was the best cut-off for predicting significant fibrosis at biopsy (AUC 0.794); however, this cut-off still failed to rule out F2-F4 fibrosis in 31% (false-negative rate) or rule in F3-F4 in 29% (false-positive rate). Similarly a LSM value >8.75 kPa was the best cut-off for severe fibrosis (F3-F4) (AUC 0.870), with a rate of false-negatives 24% and of false-positives 2%. Body mass index was the major determinant of these diagnostic errors in predicting significant and severe fibrosis both by overestimating or underestimating the stage of fibrosis. CONCLUSIONS: In NAFLD patients, even when liver stiffness measurement is feasible, high BMI values negatively affect the diagnostic reliability. Improved performance of transient elastography could be obtained using specifically designed probes.

Relationship between thymidylate synthase and p53 and response to FEC versus taxane adjuvant chemotherapy for breast carcinoma.

Many drugs can be used for adjuvant therapy of breast cancer, including anthracyclines, cyclophosphamide, 5-fluorouracil (5-fU) and, recently, taxanes (TXT) have shown promising results. 5-FU blocks thymidylate synthase (TS) which cross-links p53 mRNA, inhibiting its synthesis. TS overexpression is one of the main mechanisms involved in 5-FU drug resistance. Enough p53 mutations can confer resistance to chemotherapy using anthracyclines and 5-FU, while are associated with improved responses to TXT. The aim of this study was to examine the TS and p53 levels in tumor samples and to compare the efficacy of FEC (5-FU, epirubicin, cyclophosphamide) and TXT chemotherapy in a group of patients with differing TS and p53 status. We examined 84 breast tumor samples using immunohistochemistry. TS and p53 levels were inversely related, and TS and p53 positivity was significantly associated with the failure of FEC treatment and with a good response to TXT therapy (p <0.001). This confirms the predictive role of these two markers, which should be considered when choosing the appropriate adjuvant therapy for breast cancer.