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Biomedical subjects

W Grigioni

Publications and source records attributed to W Grigioni.

At least 19 recordsLinked to original sources
PubMed1998

Reversal of fundic atrophy after eradication of Helicobacter pylori.

OBJECTIVES: We sought to evaluate the effect of Helicobacter pylori eradication in patients with fundic atrophic gastritis. METHODS: Acid secretion, gastric emptying, and histology were evaluated in 20 patients with fundic atrophic gastritis and H. pylori infection. After investigation, 10 patients (Group 1) received an eradicating treatment and 10 (Group 2) did not receive any treatment. One year later, the baseline investigations were repeated. Subsequently, patients in Group 2 received the same treatment given to patients in Group 1 and were reevaluated 12 months later. A further follow-up was performed in both groups 36 months after the treatment. RESULTS: At 1-yr follow-up, all the patients in Group 1 were H. pylori negative whereas all the patients in Group 2 were still infected. In Group 1, there was a significant improvement of both fundic atrophy and acid secretion, compared with baseline (p < 0.01). In Group 2, no substantial modification of either histological or functional parameters was observed at the first follow-up; conversely, a significant (p < 0.01) improvement of fundic atrophy and acid secretion was detected in these patients 12 months after eradication of the bacterium. Histological pattern remained unchanged at 36 months of follow-up in both groups. Gastric emptying remained, on the average, unaffected by the treatment; however, three patients with delayed gastric emptying at entry had normal gastric emptying after eradication of H. pylori. CONCLUSIONS: Our data suggest that mucosal atrophy can be reduced or even reversed by the eradication of H. pylori, and this is associated with a recovery of gastric function.

Amoxicillin↗
PubMed1997

What is the criterion for differentiating chronic hepatitis from compensated cirrhosis? A prospective study comparing ultrasonography and percutaneous liver biopsy.

BACKGROUND/AIMS/METHODS: The diagnosis of cirrhosis is currently based on percutaneous liver biopsy, although this procedure may give rise to false negative results. This prospective study blindly investigates the accuracy of an ultrasonographic score, derived from liver, spleen and portal vein features, in predicting the final diagnosis in 212 patients with compensated chronic liver disease undergoing percutaneous liver biopsy. RESULTS: Taking biopsy as the standard, the ultrasonographic score differed significantly between chronic hepatitis (39+/-33) and cirrhosis (100+/-35) (p<0.0001). Discriminant analysis with stepwise forward selection of the variables identified liver surface nodularity and portal flow velocity as independently associated with the diagnosis of cirrhosis (p<0.005), and a score based on these two variables correctly identified cirrhosis in 82.2% of cases. One or both of these abnormalities were also found in 27/32 patients who were diagnosed as having cirrhosis at ultrasound, but were not cirrhotic histologically. Eight of these 32 cases developed signs of decompensated liver disease and/or portal hypertension in the subsequent 6-month follow-up, thus supporting the diagnosis of cirrhosis. CONCLUSIONS: Our data suggest that ultrasound is accurate in predicting the final diagnosis in patients with compensated chronic liver disease and may identify cirrhosis even in the absence of a typical histopathological pattern. However, neither percutaneous liver biopsy nor ultrasonography can be assumed to be the definitive criterion for the diagnosis of compensated cirrhosis.

Adolescent↗
PubMed1996

Qualitative and quantitative analysis of AgNOR proteins in chemically induced rat liver carcinogenesis.

A qualitative and quantitative analysis of silver-stained nuclear organizer regions (AgNOR) proteins was performed during hepatocarcinogenesis induced in rats initiated by diethylnitrosamine (DENA) using the resistant-hepatocyte model. Nuclear proteins from control hepatocytes, hyperplastic nodules, and hepatocellular carcinomas (HCC) separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis were transferred to nitrocellulose membranes and specifically silver-stained for AgNOR proteins. No difference was observed in the distribution pattern of the silver-stained bands among control, hyperplastic, or cancer cells. The same was true if human cirrhosis and HCC were compared. The evaluation of individual AgNOR protein amounts by computerized densitometric analysis showed that 1) the integrated optical density value of the total AgNOR proteins was greatest in cancer cells, lesser in hyperplastic hepatocytes, and lowest in control hepatocytes, and 2) the amount of the two major silver-stained proteins, nucleolin (105 kd) and protein B23 (39 kd), was always a constant percentage of total AgNOR proteins. An experiment using bromodeoxyuridine incorporation showed that, during hepatocarcinogenesis, AgNOR protein quantity progressively increased and was significantly related to the increased hepatocyte labeling index. These results show that AgNOR protein distribution changes during hepatocarcinogenesis are caused neither by the synthesis of new AgNOR proteins nor by an unbalanced synthesis of individual AgNOR proteins, but to an increased synthesis of nucleolin and protein B23, which is associated with a progressive increased hepatocyte proliferation rate.

Animals↗
PubMed1996

Hepatocyte proliferative activity in chronic liver damage as assessed by the monoclonal antibody MIB1 Ki67 in archival material: the role of etiology, disease activity, iron, and lipid peroxidation.

Hepatitis B virus (HBV)- and hepatitis C virus (HCV)-related liver damage is linked to an increased risk of hepatocellular carcinoma, but the mechanisms underlying hepatitis C viral activity are not known. We therefore compared hepatocellular proliferative activity in chronic C virus-related hepatitis and in liver damage of other etiology. Hepatocyte proliferation rate was investigated in 56 patients with chronic hepatitis using the Ki67 MIB1 monoclonal antibody in archival material. According to etiology, the patients were subgrouped as follows: HCV (34), HBV (11), Alcohol (4), HCV + Alcohol (4), and Hemochromatosis (3). Proliferation rate was correlated with age, sex, etiology, disease activity, liver iron storage, free-radical production, and glutathione levels by regression and discriminant analysis. HCV-positive patients had significantly more MIB1-positive hepatocytes in the periportal area (P < .011) and in the low-proliferating perivenular area (zones 2 and 3) (P < .05). The number of MIB1-positive cells correlated directly with alanine transaminase (ALT) levels, Knodell index (KI), and, inversely, with iron saturation. By stepwise discriminant analysis, ALT levels and etiology were identified as single independent variables. These data suggest that HCV infection induces increased and abnormal hepatocyte proliferation, which might be related to the increased risk of hepatocellular carcinoma in patients with HCV-related liver damage.

Adult↗
PubMed1996

Expression of mitogen-activated protein kinase phosphatase-1 in the early phases of human epithelial carcinogenesis.

Many mitogens and human oncogenes activate extracellular regulated kinases (ERKs), which in turn convey proliferation signals. ERKs or mitogen-activated protein (MAP) kinases are inactivated in vitro by MAP kinase phosphatases (MKPs). The gene encoding one of these MKPs, MKP-1, is a serum-inducible gene and is transcriptionally activated by mitogenic signals in cultured cells. As MKP-1 has been shown to block DNA synthesis by inhibiting ERKs when expressed at elevated levels in cultured cells, it has been suggested that it may act as a tumor suppressor. MKP-1 mRNA and MAP kinase (ERK-1 and -2) protein expression was assessed in 164 human epithelial tumors of diverse tissue origin by in situ hybridization and immunohistochemistry. MKP-1 was overexpressed in the early phases of prostate, colon, and bladder carcinogenesis, with progressive loss of expression with higher histological grade and in metastases. In contrast, breast carcinomas showed significant MKP-1 expression even when poorly differentiated or in late stages of the disease. MKP-1, ERK-1, and ERK-2 were co-expressed in most tumors examined. In a subset of 15 tumors, ERK-1 enzymatic activity as well as structural alterations that might be responsible for loss of function of MKP-1 during tumor progression, were examined. ERK-1 enzymatic activity was found to be elevated despite MKP-1 overexpression. No loss of 5q35-ter (containing the MKP-1 locus) was detected by polymerase chain reaction in metastases compared with primary tumors. Finally, no mutations were found in the catalytic domain of MKP-1. These data indicate that MKP-1 is an early marker for a wide range of human epithelial tumors and suggest that MKP-1 does not behave as a tumor suppressor in epithelial tumors.

Biomarkers, Tumor↗
PubMed1995

HCV-associated liver cancer without cirrhosis.

Chronic infection with hepatitis C virus (HCV) is regarded as a risk factor for hepatocellular cancer, mostly in patients with liver cirrhosis. We looked for HCV genomes in the livers of patients with hepatocellular cancer who did not have cirrhosis to see whether HCV was directly oncogenic. Cancerous and non-cancerous liver tissue, and serum samples from 19 patients negative for hepatitis B surface antigen were analysed by polymerase chain reaction for the presence of HCV genome, HCV replication, HCV genotyping, and HBV genome. 13 of 19 patients were HCV RNA-positive in cancerous and non-cancerous liver tissue; 8 of 17 tested were anti-HCV positive. Among the 13 HCV RNA-positive patients, 11 had genotype 1b and 2 had genotype 2a. 7 of 13 serum samples were HCV RNA positive. 7 of 19 patients were HBV DNA positive in cancerous and non-cancerous liver tissue, 5 of them anti-HBc positive. 4 patients were both HCV RNA and HBV DNA positive and 3 were both HCV RNA and HBV DNA negative. Our results provide evidence for the association of HCV, mostly genotype 1b, with hepatocellular cancer without the intermediate step of cirrhosis.

Adult↗
PubMed1995

p53 protein accumulation in European hepatocellular carcinoma is not always dependent on p53 gene mutation.

BACKGROUND/AIMS: Immunohistochemical reactivity for p53 protein is common in various human malignancies and often related to p53 gene mutation. However, in some tumor types, accumulation of wild-type p53 has been shown. Previously, we analyzed 96 European hepatocellular carcinomas using immunohistochemistry and found that 31% of these tumors overexpressed p53 in the cell nucleus. The aim of the present study was to establish whether p53 positivity correlates with the presence of structural p53 gene abnormalities in European hepatocellular carcinoma. METHODS: DNA from 20 tumors, 10 with strong immunostaining and 10 with undetectable staining for p53, was extracted from frozen sections, and the entire coding portion of the p53 gene was sequenced. RESULTS: Five of the 10 tumors containing high levels of p53 protein showed missense point mutations. The remaining 5 tumors with high p53 levels showed the wild-type coding sequence. One of the 10 tumors containing undetectable levels of p53 protein had a 1-base pair deletion in the splice acceptor site of intron 4. CONCLUSIONS: The results strongly suggest that, in European hepatocellular carcinomas, stabilization of the p53 protein depends on factors other than p53 gene mutation, such as binding to other molecules of cellular or viral origin.

Adult↗
PubMed1995

Alcoholic liver disease in alcoholic chronic pancreatitis: a prospective study.

The prevalence and characteristics of alcoholic liver disease (ALD) in patients with alcohol-induced chronic pancreatitis (AICP) are not well defined. Fifty consecutive patients undergoing surgery for AICP were investigated for evidence of ALD. In addition to preoperative functional and imaging assessment of the liver, all had liver biopsy during surgery. Hepatic biopsy results were as follows: 12 patients had normal liver and 10 minimal aspecific changes; of the remaining 28 patients, 7 had liver cirrhosis, 11 showed features of alcoholic hepatitis, 2 had moderate steatosis, 6 extrahepatic cholestasis, and the remaining 2 had a combination of alcoholic hepatitis and cholestasis. Of the 7 patients with cirrhosis, 3 had oesophageal varices and 2 of these developed ascites in the postoperative period; in the remaining patients with ALD, this disease was subclinical. Patients with ALD consumed significantly (p < 0.005) more alcohol than those without ALD. In patients with cirrhosis, the duration of alcohol consumption (mean 27.6 years, range 18-42 years) was significantly longer (p < 0.05) than in patients without ALD (mean 19.7 years, range 8-36 years). The association of ALD with AICP is much more common than previously believed. The fact that AICP occurs earlier than liver cirrhosis and the fact that many patients stop alcohol consumption after the first attacks of pancreatic pain may explain, at least in part, the apparent rarity with which this association has been indicated by previous studies.

Adolescent↗
PubMed1993

Biological markers in hepatocellular carcinoma: potential clinical implications.

The assessment of biological markers as potential indicators of disease aggressiveness is still an open problem in hepatocellular carcinoma. Cell proliferation and extracellular matrix (ECM)-associated antigens and tumor-cell products can be associated with clinical aggressiveness in this tumor type, as has already been demonstrated for others. Cell proliferation, expressed as the in vitro [3H]thymidine labeling index, and ECM-associated antigens, such as type IV collagenase and laminin receptors, were assessed on the same paraffin-embedded samples. A strong association (P = 0.0001) was observed between the expression of collagenase and laminin receptors, with a correlation coefficient (rs) of 0.68. No relationship was found between cell proliferation and ECM-associated antigens. Moreover, the biological markers were generally independent of clinicopathologic features, except for a higher number of collagenase- and laminin receptor-positive cells in large (> or = 5 cm) compared with small (< 5 cm) tumors. In the present series of hepatocellular carcinoma patients, the 3-year clinical outcome was significantly affected by cell proliferation and ECM-associated antigens.

Antigens, Neoplasm↗
PubMed1992

Natural history of small untreated hepatocellular carcinoma in cirrhosis: a multivariate analysis of prognostic factors of tumor growth rate and patient survival.

We analyzed the growth pattern of tumor masses and the survival of 39 asymptomatic Italian patients with a total of 59 small (less than or equal to 5 cm in diameter) hepatocellular carcinomas arising from cirrhosis. The total length of the observation period ranged from 90 to 962 days, with an average of 364 +/- 229 (mean +/- S.D.). Doubling time ranged from 27.2 to 605.6 days (mean +/- S.D., 204.2 +/- 135; median = 171.6 days). Three different growth patterns were recognized: (a) tumors with no or very slow initial growth pattern (doubling time greater than 200 days), 10 cases (37%); (b) tumors with declining growth rate over time, 9 cases (33.4%); and (c) tumors with almost constant growth rate, 8 cases (29.6%). Using the stepwise discriminant analysis, we found a score based on albumin, alcohol intake, number of nodules, echo pattern and histological type that allowed a correct prediction of short doubling time (less than or equal to 150 days) in 55.6%, medium doubling time (151 to 300 days) in 60% and long doubling time (greater than 300 days) in 100% of cases. The estimated survival rate of the 39 patients, calculated by the Kaplan-Meier method was 81% at 1 yr, 55.7% at 2 yr and 21% at 3 yr. Stepwise discriminant analysis showed that a score based on sex, HBsAg status, alcohol consumption, ascites, gamma-glutamyltranspeptidase, prothrombin time, Child-Pugh class and all the sonographical parameters could predict 2-yr survival in 100% of cases. We conclude that great variability of growth patterns exists among and within small hepatocellular carcinomas. Prediction of subsequent growth rate is unreliable in most cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMed1992

Pancreatic exocrine carcinoma producing adrenocorticotropic hormone.

A rare case of pancreatic exocrine carcinoma with an endocrine component secreting adrenocorticotropic hormone (ACTH) is reported and discussed in relation to other cases previously published. The patient initially presented with a severe form of diabetes, which was treated accordingly. Persistence of hyperglycemia, along with other metabolic alterations and marked hypokalemia, led to the suggestion of abnormal ACTH secretion. In this patient, however, a florid Cushing's syndrome was not observed. The patient also developed hematological alterations, mainly leukopenia and thrombocytopenia, whose origins were unclear. At autopsy, a poorly-defined mass was discovered between the body and tail of the pancreas. Standard histology showed a moderately-differentiated adenocarcinoma. Immunohistochemical analysis of the tumor specimen demonstrated the presence of some neoplastic cells immunoreactive for chromogranin A, neuron-specific enolase and ACTH. These findings are consistent with the existence of an endocrine component within the exocrine carcinoma with ACTH differentiation.

ACTH Syndrome, Ectopic↗
PubMed1990

Percutaneous alcohol injection of portal thrombosis in hepatocellular carcinoma: a new possible treatment.

Hepatocellular carcinoma (HCC) with portal thrombosis is usually regarded as a contraindication for surgery and for percutaneous alcohol injection (PAI). For palliative purposes we used PAI in 4 patients with infiltrative HCC and segmental portal thrombosis. Ethanol, injected directly into the thrombus, diffused mostly along it. No complications emerged after 20 injections. In the first patient, who later received a liver transplant, the thrombus was completely necrotic. In the other patients, biopsies yielded only necrotic material: in two cases, progression of the thrombus was stopped at 4 and 12 months of follow-up, and in one case the thrombus shrank and remained as such 13 months later. This preliminary experience might broaden the scope of treatment for HCC.

Carcinoma, Hepatocellular↗
PubMed1990

Polymerase chain reaction to detect hepatitis B virus DNA and RNA sequences in primary liver cancers from patients negative for hepatitis B surface antigen.

BACKGROUND AND METHODS: The role of hepatitis B virus (HBV) in the course of patients with primary liver cancer who are negative for hepatitis B surface antigen has been debated. We used the polymerase chain reaction to evaluate 28 such patients for the presence of DNA and RNA sequences of the virus; 22 of these patients had associated cirrhosis. The patients were from areas with different prevalences of HBV infection (South Africa, Italy, France, and Japan). RESULTS: Antibodies to the surface and core antigens of HBV were detected in 10 of the 23 patients tested. HBV DNA sequences were detected in 17 of the 28 patients, including 8 of the 10 with HBV antibodies and 6 of 13 without HBV serologic markers. HBV RNA molecules were found in four of five tumors tested. CONCLUSIONS: Our investigation indicates that transcriptionally active HBV genomes are present in various geographic areas among patients with liver cancer who are negative for hepatitis B surface antigen. This observation is consistent with an etiologic role for the virus in the development of these tumors.

Adult↗
PubMed1990

Relationship between alpha-fetoprotein serum levels, tumour volume and growth rate of hepatocellular carcinoma in a western population.

In order to detect a possible relationship between alpha-fetoprotein (AFP) levels, total tumour volume at the moment of the discovery and the tumour volume doubling time, we studied a population of 138 patients, affected by Hepatocellular Carcinoma (HCC) discovered at abdominal ultrasound (US) examination and confirmed by liver biopsy in all cases. In each patient the serum AFP level was determined within a week before or after the US examination. A small therapy-free subgroup of 23 patients, was also serially observed for a mean period of 4 months, so making possible the evaluation of the tumour volume doubling time and its relationship with the initial value of AFP. In 81 patients (58.7%) the serum AFP resulted less than 20 ngr/ml in 21 (15.2%), between 20 and 200 and in 36 (26.1%) greater than 200ngr/ml. No statistical correlation was found between the tumour volume calculated on the basis of the US image at the moment of the discovery and the AFP level, even though very high levels (greater than 3000) were found only in large tumours. Furthermore the tumour doubling time was not correlated with the initial value of AFP.

Adult↗
PubMed1989

Search for human papillomavirus, herpes simplex virus and c-myc oncogene in human genital tumors.

We tested grade III cervical intra-epithelial neoplasms (CIN III), genital invasive carcinomas and healthy genital tissues for the presence of a number of viral and cellular parameters, considered to be risk factors in genital oncogenesis. The results show that: (I) about 30% of genital tumors had homology to HSV-2 BglII N and/or BamHI E DNA fragments; (2) positivity to HSV-2-specific protein ICP10, encoded by sequences within the HSV-2 BamHI E DNA fragment, was detected in 29/55 neoplastic genital tissues but not in healthy genital tissues or tumors at other sites; (3) HPV-16 DNA was found in about 50% of tumor samples, but none of the positive tissues reacted to HPV capsid protein or to the protein encoded by the HPV-16 E6 ORF; (4) 6/8 tumor samples showing homology to HSV-2 DNA fragments also hybridized to HPV-16 DNA; (5) c-myc amplification was not detected in any of the analyzed samples, but tissues from 4 patients were positive for c-myc expression. None of the considered factors was present in all the analyzed samples; nevertheless, some tissues showed the simultaneous involvement of several parameters, suggesting that a number of risk factors may be involved in different steps of human genital oncogenesis.

Adenocarcinoma↗
PubMed1988

Clinical experience with hepatic resections for hepatocellular carcinoma in patients with cirrhosis.

The results of 31 resections of the liver performed upon patients with cirrhosis and hepatocarcinoma are reported herein. The lesions were discovered mainly during routine echographic surveillance. Twenty-five of these patients with small tumors underwent a segmentary or subsegmentary resection. Intraoperative ultrasonography proved to be of paramount importance in these instances as it helped to recognize the lesion and outline the limits of the resection. In another 11 instances of primary tumors of the liver in patients with cirrhosis who underwent laparotomy, findings from intraoperative ultrasonography advised against exeretic operation because other intrahepatic lesions or neoplastic thrombi in portal branches were detected. The operative mortality rate in the 31 patients who underwent resection of the liver was 12.9 per cent. The actuarial three year survival rate is 58 per cent. The presence of an intact peritumoral capsule seems to be the best prognostic factor.

Adult↗
PubMed1987

Primary gastric lymphoma versus gastric carcinoma: endoscopic US evaluation.

Endoscopic ultrasonography (US) enables high-resolution imaging of the stomach and can demonstrate the different layers of the gastric wall. It has therefore been proposed for use in evaluating the extension of gastric neoplasms. It was performed in nine patients with primary gastric non-Hodgkin lymphoma and in 36 with gastric carcinoma. The US and pathologic findings were correlated in three surgical specimens of gastric lymphoma. Three different US patterns were found in gastric lymphomas: a polypoid pattern (two cases), localized (two cases) or extended (five cases) hypoechoic infiltration, and thickening with superficial ulcerations. Infiltration was confined to the second and third layers of the gastric wall in six cases and was transmural in three. The study of the gastric lymphoma specimens confirmed the accuracy of US in demonstrating the extent of infiltration. Gastric carcinomas had a more echogenic pattern and a different trend of diffusion, with no extended longitudinal hypoechoic infiltration of the superficial layers or extended hypoechoic transmural infiltration.

Adult↗