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Biomedical subjects

Maurizio Soresi

Publications and source records attributed to Maurizio Soresi.

13 recordsLinked to original sources

Interleukin-6 and its soluble receptor in patients with liver cirrhosis and hepatocellular carcinoma.

AIM: To evaluate the immunohistochemical localization of interleukin-6 (IL-6) and IL-6 receptor (IL-6R) on tumor tissue specimens from patients with hepatocellular carcinoma (HCC) and the serum levels of IL-6 and sIL-6R in a group of patients with HCC as well as liver cirrhosis (LC) in a group of patients with LC alone and in a control group. METHODS: Three groups of subjects were studied: group I (n = 83) suffering from HCC and LC, group II (n = 72) suffering from LC alone and group III (n = 42) as healthy controls. All patients had hepatitis C virus infection. Serum IL-6 and IL-6R levels were determined using a commercially available ELISA kit. Immunohistochemistry was performed using the streptavidin-biotin complex and rabbit polyclonal antibodies against IL-6 and IL-6R. RESULTS: Immunohistochemistry analysis showed a medium to strong cytoplasmic and membrane reactivity for IL-6 and IL-6R respectively, in at least 40% of cases of HCC, whereas liver cirrhosis patients and controls were negative for IL-6 or showed a very mild and focal dot-like cytoplasmic reaction for IL-6R. Serum IL-6 levels in HCC group were significantly higher than those in LC and control groups (P < 0.0001). There was no significant difference in sIL-6R concentrations among 3 groups. When the patients with HCC were divided into groups according to Okuda's classification, a significant serum increase of IL-6 and sIL-6R level was observed from stage I to stage III (P < 0.02, P < 0.0005). When HCC and LC patients were divided into 3 classes of cirrhosis severity according to Child-Pugh, values in HCC patients were significantly higher than those in LC patients for each corresponding class (P < 0.01). CONCLUSION: IL-6 serum levels in HCC patients are higher than those in LC patients and controls, suggesting an increased production of this cytokine by neoplastic cells. sIL-6R values are similar in all groups, increasing only in stage III HCC patients. These data suggest that they have a closer relationship with the neoplastic mass rather than with the residual functioning hepatic mass.

Adult↗

Unexplained elevated serum pancreatic enzymes: a reason to suspect celiac disease.

BACKGROUND & AIMS: The frequency of elevated serum pancreatic enzymes in patients with celiac disease (CD) is unknown. The aim of this study was to evaluate the serum levels of pancreatic enzymes in CD patients. METHODS: Serum pancreatic isoamylase and lipase levels were assayed in 90 adult and 112 pediatric consecutive CD patients at diagnosis and after 12 months of gluten-free diet (GFD). Serum elastase and trypsin levels were assayed in a subgroup of adult CD patients. Pancreatic ultrasonography was also performed. RESULTS: Twenty-six adult (29%) and 29 pediatric (26%) CD patients exhibited elevated values of serum pancreatic amylase and/or lipase; trypsin was elevated in 69% and elastase in 19%. The frequency of elevated serum pancreatic enzymes observed was identical in the patients with "typical" and "atypical" CD symptoms and in the asymptomatic patients. Most of the elevated values were lower than 2-fold the threshold limits. Elevated pancreatic enzymes were not associated with alcohol consumption, drug use, presence of abdominal pain, or diabetes mellitus. Abdominal ultrasound scan showed no abnormal findings in the pancreatic region in any of the CD patients. After 12 months of GFD, pancreatic amylase was elevated in 3 cases and lipase in 2 cases; these patients had not strictly adhered to the GFD. CONCLUSIONS: We demonstrated a frequency of about 25% of elevated pancreatic enzymes values in CD patients, including subjects without gastrointestinal manifestations and apparently asymptomatic subjects. The finding of elevated serum amylase or lipase level, in the absence of signs of pancreatic disease, would appear to suggest a need to screen for celiac disease.

Adolescent↗

Food intolerance and chronic constipation: manometry and histology study.

BACKGROUND: Chronic constipation in children can be caused by cows' milk intolerance (CMI), but its pathogenesis is unknown. AIMS: To evaluate the histology and manometry pattern in patients with food intolerance-related constipation. PATIENTS AND METHODS: Thirty-six consecutive children with chronic constipation were enrolled. All underwent an elimination diet and successive double-blind food challenge. All underwent rectal biopsy and anorectal manometry. RESULTS: A total of 14 patients were found to be suffering from CMI and three from multiple food intolerance. They had a normal stool frequency on elimination diet, whereas constipation recurred on food challenge. The patients with food intolerance showed a significantly higher frequency of erosions of the mucosa, and the number of intra-epithelial lymphocytes and eosinophils. The rectal mucous gel layer showed that the food-intolerant patients had a significantly lower thickness of mucus than the other subjects studied. Manometry showed a higher anal sphincter resting pressure and a lower critical volume in food intolerance patients than in the others suffering from constipation unrelated to food intolerance. Both histology and manometry abnormalities disappeared on the elimination diet. CONCLUSIONS: Food intolerance-related constipation is characterized by proctitis. Increased anal resting pressure and a reduced mucous gel layer can be considered to be contributory factors in the pathogenesis of constipation.

Anal Canal↗

Correlation between expression of cyclooxygenase-2 and the presence of inflammatory cells in human primary hepatocellular carcinoma: possible role in tumor promotion and angiogenesis.

AIM: To investigate the association of cyclooxygenase-2 (COX-2) expression with angiogenesis and the number and type of inflammatory cells (macrophages/Kupffer cells; mast cells) within primary hepatocellular carcinoma (HCC) tissues and adjacent non-tumorous (NT) tissues. METHODS: Immunohistochemistry for COX-2, CD34, CD68 and mast cell tryptase (MC(T)) was performed on 14 well-characterized series of liver-cirrhosis-associated HCC patients. COX-2 expression and the number of inflammatory cells in tumor lesions and surrounding liver tissues of each specimen were compared. Moreover, COX-2, CD34 staining and the number of inflammatory cells in areas with different histological degrees within each tumor sample were comparatively analyzed. RESULTS: The percentage of COX-2 positive cells was significantly higher in NT tissues than in tumors. COX-2 expression was higher in well-differentiated HCC than in poorly-differentiated tissues. Few mast cells were observed within the tumor mass, whereas a higher number was observed in the surrounding tissue, especially in peri-portal spaces of NT tissues. Abundant macrophages/Kupffer cells were observed in NT tissues, whereas the number of cells was significantly lower in the tumor mass. However, a higher cell number was observed in the well-differentiated tumor and progressively decreased in relation to the differentiation grade. Within the tumor, a positive correlation was found between COX-2 expression and the number of macrophages/Kupffer cells and mast cells. Moreover, there was a positive correlation between CD34 and COX-2 expression in tumor tissues. Comparison between well- and poorly-differentiated HCC showed that the number of CD34-positive cells decreased with dedifferentiation. However, COX-2 was the only independent variable showing a positive correlation with CD34 in a multivariate analysis. CONCLUSION: The presence of inflammatory cells and COX-2 expression in liver tumor suggests a possible relationship with tumor angiogenesis. COX-2 expressing cells and the number of macrophages/Kupffer cells and mast cells decrease with progression of the disease.

Aged↗

Perihepatic lymph nodes and antiviral response in chronic HCV-associated hepatitis.

To identify predictive factors of response to interferon alpha (IFN-alpha) plus ribavirin therapy in patients with chronic hepatitis C (CHC), the presence of lymphadenopathy (LyA) of the hepatoduodenal ligament and other variables were investigated. A total of 110 patients with histologically proven CHC were enrolled in this study. Ultrasound (US) was performed at the start and end of therapy and 6 months after stopping therapy. At baseline, LyA was present in 35 (43.7%) of 80 patients with alanine aminotransferase (ALT) values and grading was significantly higher than in the LyA-negative group. LyA was more frequent in nonresponders (nonR) than in relapsers (relR) or sustained responders (susR). Lymph node volume (LyV) was significantly lower in susR than in nonR or relR (p < 0.05). Under antiviral treatment, the reduction in LyV was significantly higher in nonR (p < 0.01); in susR and relR, it was not significantly reduced. LyA totally disappeared in two patients of the susR group. Logistic regression analysis confirmed only a positive association of susR with grading and a negative association with staging (p < 0.02 and p < 0.006). In conclusion, this study suggests that US evidence of LyA is useful in evaluating the severity of a given chronic hepatitis C, but it cannot be proposed as a predictive index of response to antiviral treatment.

Adult↗

Prevalence of biliary lithiasis in a Sicilian population of chronic renal failure patients.

BACKGROUND: The aim of this study was to evaluate the prevalence of biliary lithiasis (BL) and associated risk factors in a population of undialysed patients with chronic renal failure (CRF), and to compare these with findings we had obtained previously in chronic haemodialysis (HD) patients and in subjects from the general population located in the same geographic region. METHODS: A total of 118 CRF patients on conservative treatment were included in the study. In all subjects, we measured several clinical and humoral parameters potentially correlated with BL. Liver and biliary tract ultrasonography was performed with a 3.5 MHz linear probe after at least 12 h of fasting. RESULTS: The prevalence of BL in CRF patients was 22%, which was higher than in the general population (chi(2) = 9.4, P < 0.002) but lower than in HD patients (chi(2) = 25.9, P < 0.0001). Age was similar in the three groups. Body mass index (BMI) was significantly higher in the CRF group than in both HD patients (P < 0.0001) and the general population (P < 0.0001). When the CRF group was divided into subjects with or without BL, the only difference was lower serum calcium levels in the subgroup with BL (P < 0.04). CONCLUSIONS: The prevalence of BL in a Sicilian population of CRF patients was higher than in the general population, but lower than in patients with CRF on chronic HD. Apart from BMI, none of the risk factors traditionally associated with BL in the general population were related to BL in the CRF patients. These data suggest that other factors inherent to kidney pathology contribute to the high prevalence of BL in CRF patients.

Aged↗

Circulating intercellular adhesion molecule-1 in chronic hepatitis C patients with normal or elevated aminotransferase before and after alpha-interferon treatment.

OBJECTIVES: Intercellular adhesion molecule-1 (ICAM-1) plays a fundamental role during liver inflammation. In fact, weak ICAM-1 expression is physiologically restricted to the endothelium of portal vessels and to sinusoidal lining cells, but it becomes markedly evident on sinusoidal lining cells and at the surface of hepatocytes during inflammatory liver diseases. The aim of this study was to evaluate the behaviour of soluble ICAM-1 (sICAM-1) in chronic hepatitis C (CH-C) patients with persistently normal aminotransferase in comparison with patients with CH-C and elevated aminotransferase, and its changes during alpha-interferon (IFN) therapy. Immunohistochemical localization of ICAM-1 was also performed on liver tissue specimens of both groups. METHODS: Sixty subjects were divided into 3 groups: group A included 19 patients with CH-C and persistently normal aminotransferase; group B included 21 patients with CH-C and persistently elevated aminotransferase levels, and group C included 20 healthy subjects representing the control group. The first two groups were treated with recombinant alpha-IFN 2b at a dose of 6 MU 3 times a week for 3 months and followed up with 3 MU 3 times a week for another 3 months. RESULTS: Baseline values of serum ICAM-1 in groups A and B were significantly higher than those in group C (p < 0.0001). The median baseline value of sICAM-1 in group A (525.0 ng/ml) was lower than that of group B (561.0 ng/ml), but the difference was not statistically significant. Furthermore, there was a trend toward higher ICAM-1 values as histological severity increased (Mantel-Haenszel chi(2) 8.8, p < 0.003). Post-treatment sICAM-1 serum values showed a marked decrease in both groups, but only among responder patients, while ICAM-1 levels were unchanged in non-responders. Immunohistochemical localization showed no staining for ICAM-1 in normal liver specimens, while there was a quite similar staining for ICAM-1 in the two groups of patients, consistent with an inflammatory process. CONCLUSIONS: This study shows that circulating ICAM-1 levels in most patients with CH-C and persistently normal aminotransferase are higher than those in a control group and the fact that ICAM-1 molecules are also expressed on the hepatocyte membrane suggests that they could play an important role, in association with other molecules, in the intercellular adhesion processes during the induction and maintenance phases of the immune response. In both groups, only patients responding to alpha-IFN therapy showed a marked decrease in serum ICAM-1 below baseline values.

Adult↗

Leucocyte interferon-alpha for patients with chronic hepatitis C intolerant to other alpha-interferons.

BACKGROUND: Alpha-interferon (alpha-IFN) is the treatment of choice for chronic hepatitis C but most patients experience adverse effects which sometimes lead to the suspension of therapy. Recently, higher doses of alpha-IFN or prolonged therapy have increased the number of cases of intolerance. STUDY DESIGN: In this open study we evaluated the efficacy and safety of leucocyte interferon-alpha (IFNalpha) [6MU three times a week] in 43 patients with chronic hepatitis C who had been intolerant to previous treatment courses with recombinant or lymphoblastoid IFNalpha. All patients were treated for 6 months and followed-up for an additional 6 months.End of treatment responders were patients in whom hepatitis C virus (HCV)-RNA had been eradicated from the blood by the end of treatment, sustained responders were those patients who maintained negative HCV-RNA at the end of follow-up, and the remaining patients were considered non-responders. Adverse effects were monitored by interviews, laboratory and clinical examinations. RESULTS: Five patients (11.6%) discontinued the treatment, four due to the reappearance of previous adverse effects, and one due to an ex novo adverse effect. In six patients the dose had to be halved. At the end of treatment 11 patients (25.6%) had negative serum HCV-RNA. After discontinuation of therapy, disease flared in four patients, thus seven patients were sustained responders. CONCLUSIONS: This study shows that leucocyte IFNalpha at a dose of 6MU three times a week is well tolerated in patients previously intolerant to recombinant or lymphoblastoid IFNalpha, allowing a high percentage of them to complete a course of treatment in terms of duration and dose.

Antiviral Agents↗

[Predictive value of serological tests in the diagnosis of celiac disease].

In the diagnostic work-up of celiac disease (CD) the simpler enzyme-linked immunosorbent assay (ELISA) for the identification of serum anti-transglutaminase (tTG) autoantibodies could substitute the immunofluorescence technique used for the detection of anti-endomysial antibodies (EmA). However, most of the studies on anti-tTG assay have considered pre-selected groups of patients and not consecutive subjects with suspected CD. The aim of this study was to compare the sensitivity, specificity and predictive value of anti-gliadin antibodies (AGA), EmA and two anti-tTG ELISAs, one based on guinea pig (gp)-tTG and the other on human (h)-tTG as antigens, in consecutive patients investigated for suspected CD. The study included 130 consecutive patients (age range 16-84 years), who underwent intestinal biopsy for suspected CD. They presented with one or more of the following symptoms: weight loss, anemia, chronic diarrhea, abdominal pain, dyspepsia, alternating bowel habits and constipation. At the time of admission in the study, an intestinal biopsy was performed and a serum sample was taken for immunoglobulin (Ig) G and IgA AGA, IgA EmA, anti-gp-tTG and anti-h-TG determination. Intestinal histology revealed that 15 patients had partial or total villous atrophy. In these patients the diagnosis of CD was confirmed at subsequent follow-up. The remaining 115 patients included in the study had an intestinal histology characterized by a normal villi/crypts ratio and were considered as controls. Serum EmA, anti-gp-tTG, and anti-h-tTG were positive in all the 15 CD subjects, whereas IgG and IgA AGA were positive in 10/15; in the control group, none were positive for serum EmA, but 11/115 (10%) were positive for anti-gp-tTG and 6/115 (5%) were positive for anti-h-tTG. The sensitivity was 100% for EmA, gp-tTG and h-tTG and 66% for IgA and IgG AGA. The specificity was 100% for EmA, 90% for anti-gp-tTG, 95% for anti-h-tTG, 74% for IgG AGA and 87% for IgA AGA. The negative predictive value was 100% for EmA, anti-h-tTG and anti-gp-tTG, 94% for IgG AGA and 95% for IgA AGA. The positive predictive value was 100% for EmA, 71% for anti-h-tTG (p = 0.03 vs EmA) and 58% for anti-gp-tTG (p = 0.003 vs EmA). Most of the patients who were false positive for anti-tTG had Crohn's disease or chronic liver disease. In conclusion, although both the anti-tTG ELISAs evaluated in the present study showed an optimum sensitivity, their low specificity determined positive predictive values which were significantly lower than those of EmA assay. Besides, the positive predictive value of gp-tTG was too low to warrant submitting a patient to intestinal biopsy for suspected CD.

Adolescent↗

Diagnosis of focal nodular hyperplasia. Role of imaging techniques.

Focal nodular hyperplasia (FNH) is a rare benign liver lesion which is difficult to differentiate from other benign liver pathologies and hepatocellular carcinoma. However, with appropriate new imaging techniques it is, at present, possible to diagnose this lesion with certainty thus avoiding invasive tests. Patient follow-up is also facilitated. It is often incidentally discovered during an abdominal ultrasound for other pathologies. Color power Doppler allows, in most cases, one to distinguish it from other focal liver lesions. However, in doubtful cases contrast-enhanced computed tomography and magnetic resonance imaging can help us to define the exact nature of the lesion. It is only occasionally necessary to perform an ultrasound-guided liver biopsy of the nodule and anyhow, once a correct diagnosis has been made, in most cases there is no indication for surgery. In spite of the contradictory results in the literature on the effects of oral contraceptives and pregnancy on the evolution of FNH, it now seems that they do not condition the appearance or the size of FNH and that in a woman with FNH pregnancy should not only be discouraged, but rather favored and closely monitored.

Biopsy↗

Usefulness of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma.

With the widespread use of ultrasonography (US) and computerized tomography (CT), the usefulness of alpha-fetoprotein assay in the diagnosis of hepatocellular carcinoma (HCC) has decreased. The aim of our study was to evaluate the best cut-off value for serum alpha-fetoprotein to discriminate between liver cirrhosis (LC) and HCC and the factors influencing levels in a Sicilian population. Three hundred and seventy-two patients with LC and 197 with HCC-associated LC were studied. The etiology was: HCV in 288 cases (77.4%) of LC and 147 cases (75%) of HCC; HBV in 31 cases (8.3%) of LC and 15 cases (7.6%) of HCC; HCV/HBV in 21 cases (5.6%) of LC and 6 cases (3.0%) of HCC; non-viral in 32 cases (8.6%) of LC and 29 cases (15%) of HCC. Hepatic function was estimated by the Child-Pugh's score; the TNM classification was used in HCC. The area under the ROC curve was 0.81 +/- 0.02; the best discriminant cut-off value, calculated as the value of the maximized likelihood ratio, was 30 ng/ml. At this level sensitivity (SE) was 65%, specificity (SP) 89%, positive predictive value (PPV) 74% and negative predictive value (NPV) 79%. When the patients were divided at this cut-off point into two groups according to viral or non-viral etiology, PPV was 70% versus 94%, respectively (p < 0.05). In the non-viral diseases PPV reached 100% for AFP serum levels of 100 ng/ml, while in the viral diseases PPV was 100% when AFP was greater than 400 ng/ml. There were no significant differences in SE, SP or NPV between viral and non-viral liver diseases. Child's classes B and C were more frequent in HCC (chi 2 of MH 7.7, p < 0.0001). There was a correlation between AFP serum values and TNM classification (p < 0.02) and on multiple logistic regression AFP levels > 30 ng/ml correlated positively only with the TNM stage (p < 0.0001). In conclusion, the best cut-off value for serum AFP in our study population was 30 ng/ml, but at this level sensitivity was low. This cut-off value was more useful in detecting non-viral HCC, because PPV was significantly higher than in viral HCC; therefore, our data confirm that the usefulness of AFP in the diagnosis of HCC of viral etiology is limited, being more useful in HCC of non-viral etiology.

Aged↗

[Radiofrequency thermoablation in the treatment of primary and secondary liver tumours].

Radiofrequency thermoablation is a locoregional procedure based on the use of electromagnetic waves that induce movement and consequently the production of heat. This is the basis for the coagulative necrosis produced in the tissues. The method, experimented with and developed in the '90s, is today extensively used in the treatment of focal hepatic lesions, both primary and secondary. The factors that condition the procedure are related essentially to the characteristics of the tumours and to the possibility of obtaining a predictable area of necrosis that guarantees the radicality of the treatment. As regards primary neoplasms, it should be stressed that the treatment for hepatocellular carcinoma is implemented only in a small percentage of cases due to both the stage of the cirrhosis and because a wide resection is not justified for small-sized lesions or for recurrences after resection. As far as liver metastases are concerned, particularly those from the colon-rectum, surgery is becoming increasingly indicated. Obviously the conditions are decidedly less demanding than those of surgery in liver parenchyma with cirrhosis. Radiofrequency thermal ablation, even in this condition, has a place as an alternative or in combination with liver resection, particularly during recurrences or in cases of multiple metastases that require extensive extirpative operations. The authors present their experience over the period from February 1999 to December 2002 in 82 patients, 71 with hepatocellular carcinoma and 11 with metastases, treated with radiofrequency thermoablation. Depending upon the site, the number of lesions and the Child-Pugh functional classes in patients with cirrhosis, 117 treatments were carried out: the percutaneous approach was used in 77 cases and the open procedure in 36, while the thermoablation was combined with surgical resection in 4 cases. The results are examined on the basis of perioperative morbidity and mortality and local recurrence, and the time of hospitalisation is compared in the different patient groups. The authors conclude favourably for this procedure, which is associated with an extremely low percentage of complications and with an almost total lack of perioperative mortality, and in some cases may be a valid alternative and in other cases a useful complement to resection treatment.

Adult↗