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Biomedical subjects

M Rugge

Publications and source records attributed to M Rugge.

At least 109 records · Page 6Linked to original sources

Pathology and ploidy in the prognosis of gastric cancer with no extranodal metastasis.

BACKGROUND: The prognostic relevance of morphology in advanced gastric cancer is well known. Data on tumor cell DNA content are still inadequate and contradictory. METHODS: Morphologic parameters and DNA ploidy were evaluated in 76 gastric cancer patients with no extranodal metastases (Stage I, 10 cases; Stage II, 20 cases; and Stage III, 46 cases), using formalin-fixed paraffin-embedded tissue. All cases were followed for at least 6 years after surgery or until death. RESULTS: Among the potential prognostic factors analyzed by Mantel-Cox and generalized Wilcoxon statistics, male sex (P = 0.02), cardiac location of neoplasia (P = 0.02), deeper infiltration of the gastric wall (P = 0.001), vascular neoplastic invasion (P = 0.006), metastatic lymph nodes (P = 0.001), pathologic stage (P = 0.0001), and aneuploidy (P = 0.01) were significantly associated with lower survival rate. Testing of all of the above-mentioned variables by the Cox stepwise multiple regression model disclosed that factors independently associated with survival were stage (P = 0.0001), ploidy (P = 0.0006), and vascular carcinomatous invasion (P = 0.01). CONCLUSIONS: In gastric cancer with no extranodal metastases, DNA ploidy was found to be the most significant prognostic parameter after pathologic stage.

Aged↗

A new method for detecting anti Helicobacter pylori antibodies: an analytical and clinical evaluation.

The diagnosis of Helicobacter pylori (Hp) infection is an important goal in clinical practice. In this paper we evaluated 1. the analytical reliability of a new second-generation antigen based enzyme immunoassay (Cobas Core Anti Helicobacter pylori EIA) in detecting anti-Hp IgG antibodies, and 2. the behaviour of anti-Hp IgG in patients with chronic atrophic and non-atrophic gastritis as compared to healthy controls. The findings from the dilution curve, the values of intra and inter assay coefficients of variations (never above 10%) and of the recovery test (between 96 and 109%), confirm that the method is reliable. Serum IgG anti-Hp levels were found to be significantly higher in patients with histologically identified Hp infection, than in those negative at histology. Furthermore, the grade of histological positivity was correlated with serum IgG levels. However, we found a discrepancy between a low prevalence of Hp staining and a high prevalence of Hp seropositivity in patients with chronic atrophic or non-atrophic gastritis, but not in controls. This suggests that IgG serum determination may be more useful than histology in determining a present or previous infection in patients with chronic atrophic or non-atrophic gastritis.

Adult↗

Are tryptase and cathepsin D related to Helicobacter pylori infection and mucosal gastrin in peptic ulcer?

The pathogenesis of peptic ulcer is a complex phenomenon and several factors are thought to be involved in this process. Among others, Helicobacter pylori infection, hypergastrinaemia and some proteases seem to play an essential role in inducing peptic ulceration. We investigated whether tryptase (a serine endoprotease released by mast cells) and cathepsin D (a lysosomal hydrolase which seems able to derange the extracellular matrix) play a part in peptic ulcer disease and whether they are linked to Helicobacter pylori infection and mucosal content of gastrin. We studied 13 controls, 25 patients with gastric ulcer, 47 with duodenal ulcer and 11 with duodenitis. Tryptase and cathepsin D were measured in mucosal biopsy specimens (body and antrum of the stomach and duodenum) using IRMA methods. Gastrin was assayed in the antral mucosa by means of a RIA method. Helicobacter pylori infection was histologically evaluated (Giemsa). Tryptase and cathepsin D levels were higher (25%) in patients with active peptic ulcer, whether gastric or duodenal. The mucosal content of cathepsin D, but not that of tryptase, was associated with Helicobacter pylori infection. Tryptase, on the other hand, was related to gastrin content. No correlation was found between the two enzymes. It is concluded that tryptase and cathepsin D probably reflect different pathophysiological modifications in ulcer disease. Cathepsin D seems to be mainly related to the phlogistic reaction of the mucosa to Helicobacter pylori infection; tryptase may reflect and indirect link between the action of gastrin and the function of mast cells.

Adult↗

Gastric epithelial dysplasia in the natural history of gastric cancer: a multicenter prospective follow-up study. Interdisciplinary Group on Gastric Epithelial Dysplasia.

BACKGROUND/AIMS: Because the precancerous significance of gastric epithelial dysplasia (GED) is still under debate, this study attempts to ascertain whether a prospective follow-up of GED can contribute to clarifying its clinical and pathological relationships with gastric cancer (GC). METHODS: One hundred twelve patients with mild (G1), moderate (G2), and severe (G3) GED or diagnosed as indefinite for dysplasia were prospectively followed up with a standardized endoscopic and bioptic protocol. RESULTS: Evaluation of GED outcome refers only to 93 patients with a follow-up period longer than 12 months. Regression of dysplasia was documented in 36%, 27%, and 0% of G1, G2, and G3 GED cases, respectively. Progression to more severe dysplasia or evolution into GC was detected in 21%, 33%, and 57% of G1, G2, and G3 GED cases, respectively. Evolution into GC was documented for all grades of dysplasia and correlated significantly with high-grade atrophic gastritis. A high prevalence of early GC (86.9%) was also observed. CONCLUSIONS: GED is a pre-invasive lesion, and carcinomatous evolution increases proportionally with its histological grade. Bioptical follow-up is mandatory for all histological grades of GED and significantly increases the likelihood of GC being detected in its early stages.

Biopsy↗

Human immunodeficiency virus infection and hepatitis C pathology.

To investigate the possible influence of human immunodeficiency virus (HIV) infection on hepatitis C virus-related liver disease, liver morphology was evaluated in 160 HBsAg-negative patients with chronic hepatitis C, including 68 HIV-positive and 92 HIV-negative cases. No differences were detected in the severity of necro-inflammatory hepatic lesions between HIV-negative and HIV-positive patients when the CD4+ lymphocytes count exceeded 400 cells/mm3. In contrast, HIV-positive patients with CD4+ lymphocytes below 400 cells/mm3 showed a significantly lower grade of portal inflammation and piecemeal necrosis. These results suggest that liver lesions in hepatitis C may largely depend on immunomediated mechanisms.

Adult↗

Treatment of chronic hepatitis C with recombinant human interferon-alpha 2a: results of a randomized controlled clinical trial.

Sixty consecutive patients with chronic hepatitis C were included in a randomized controlled trial of recombinant human interferon-alpha 2a vs. no treatment. Treated patients received tapering doses of interferon thrice weekly for 1 yr. Twenty treated cases (66.7%) normalized serum aminotransferase levels within the first 4 mo of treatment, but reactivation or breakthrough frequently occurred afterward (20% in both cases). Only one of the untreated patients showed spontaneous normalization of serum aminotransferase levels. Liver histology did not improve in patients without a biochemical response or with breakthrough during therapy, whereas it did not worsen in long-term responders and reactivating patients. Lack of response does not appear to be related to serum interferon antibodies, although their early appearance is more frequent in patients who showed reactivation later on. No biochemical parameter was found to be predictive for positive response to treatment. Antibody to c100 became negative in 62.5% of long-term responders, whereas no change was recorded in other treated patients or controls. Reactivation and breakthrough often occur during treatment, and further studies are needed to determine the most effective schedule (dose and time) of interferon treatment. Loss of c100 antibody during therapy may be a marker of long-term maintenance of response to interferon therapy.

Adult↗

Percutaneous CT-guided fine needle aspiration cytology in the differential diagnosis of pancreatic lesions.

Cytologic results were retrospectively evaluated in 83 patients who underwent CT-guided fine-needle aspiration of pancreatic lesions during a 5-year period. Sixty seven patients had malignant disease and 16 benign disease. The sensitivity, specificity, positive and negative predictive values, and diagnostic efficiency of fine-needle aspiration (FNA) cytology in detecting malignancy were 91%, 100%, 100%, 73%, and 93%, respectively. In solid pancreatic masses the sensitivity of FNA cytology rose to 98%, while in cystic pancreatic masses sensitivity fell to 62%. In 18 patients with cystic lesions (12 benign and 6 malignant), the cystic fluid was analyzed for amylase, CEA and CA 19-9 content. Amylase levels were high in pseudocysts and in 4/6 malignant cysts. CEA levels were low in benign cysts, and high in all malignant cysts. CA 19-9 levels were high in one pseudocyst and in all malignant cysts. Tumour marker content analysis enhanced the sensitivity of the cytologic diagnosis of malignant cysts to 92%. FNA cytology is a simple and highly accurate method in the differential diagnosis of solid pancreatic lesions. In cystic lesions, tumour marker fluid content determination increases the sensitivity of FNA cytology.

Biomarkers, Tumor↗

p53 alteration in gastric precancerous lesions.

It has been postulated that chronic atrophic gastritis, intestinal metaplasia, and dysplasia are precancerous stages of stomach tumorigenesis. We investigated the timing of p53 alterations in these events of gastric tumorigenesis. Each of 12 cases of archived tissue containing precancerous and cancerous lesions were selected for the detection of p53 alterations. Accumulation of p53 protein was detected by immunohistochemistry. Exons 5 to 8 of p53 gene were examined for mutations by polymerase chain reaction-single strand conformation polymorphism and DNA sequencing. p53 immunoreactivity was detected in 60% of the dysplasia cases and in 60% of the cases with carcinomas. p53 gene alterations were found in 37.5% of the metaplasia cases, 58.3% of the dysplasia cases, and 66.7% of the cases with carcinomas. In 71% of the cases, mutations were shown as G:C-->A:T transition. We conclude that mutation of the p53 gene is an early event in stomach tumorigenesis.

Base Sequence↗

Ductal adenocarcinoma of the pancreas: clinicopathologic features and survival.

AIMS AND BACKGROUND: The prognosis after surgical resection for pancreatic cancer has not been clearly defined because conflicting results have been reported. METHODS: Fifty-five patients who underwent surgical resection for pancreatic carcinoma between 1970 and 1987 were retrospectively reviewed to determine factors influencing long-term survival. RESULTS: The actuarial 5-year survival rate for all 55 patients was 12.5%. Type of operation, tumor stage, direct extension into adjacent organs, grading and lymph node involvement were found to significantly influence survival. Age, sex, tumor site, size, invasion into peripancreatic tissue, invasion of lymphatic vessels and small veins, perineural infiltration, tumor necrosis, round cell infiltrate at the tumor margin, associated chronic pancreatitis, and atypia of pancreatic ductal epithelium demonstrated no predictive capacity. No 5-year survival was observed among the patients who underwent vascular resection. Three of 9 patients who underwent left-sided pancreatectomy for cancer of the tail of the pancreas survived more than 5 years. Multivariate analysis confirmed that lymph node involvement, moderate-poor histologic tumor differentiation, and treatment with total pancreatectomy were significantly associated with a worse prognosis. CONCLUSIONS: Lymph node status, grading of the tumor and type of operation have a significant impact on prognosis in resected pancreatic cancer.

Adult↗

Early and advanced gastric cancer in the follow-up of moderate and severe gastric dysplasia patients. A prospective study. I.G.G.E.D.--Interdisciplinary Group on Gastric Epithelial Dysplasia.

The role of gastric epithelial dysplasia (GED) as a biological and morphological precursor of gastric cancer has been widely investigated, but few studies have prospectively evaluated the risk of its evolution into gastric cancer. In 1985, a prospective multicenter follow-up study was undertaken on patients with high-grade (moderate or severe) GED. The study involved 49 patients, with a follow-up currently averaging 18.8 months (range: 1-70) and a mean number of 4 endoscopies (range: 2-10). Follow-up was abandoned when 2 subsequent control endoscopies and a 1-year period were negative for GED, or when neoplasia was detected. Gastric cancer was diagnosed in 16 cases (33%). The cancer was detected at an early stage in 10 patients (62%). Eleven cases (59%) were diagnosed within 1 year of follow-up and 5 cases after 13, 18, 21, 24 and 39 months, respectively. Cancer was associated with 36% of moderate GED cases and with 80% of severe cases. Dysplastic changes were no longer detectable at follow-up in 27% of the moderate cases and in 10% of the severe cases. The relative risks for the two lesions being associated with or evolving into gastric cancer were 26 and 132, respectively. In conclusion, high-grade (moderate or severe) GED is frequently associated with or evolves into gastric cancer. The follow-up of patients considerably enhances the chances of diagnosing gastric cancer in its early stages, thus making such an approach mandatory.

Female↗

Prevalence of Helicobacter pylori infection in patients with precancerous changes and gastric cancer.

Several papers suggested a role for H. pylori infection in gastric cancer. We evaluated the prevalence of H. pylori infection in an endoscopic population of patients with gastric precancerous conditions and lesions by studying biopsies from 252 patients and recording the presence and degree of H. pylori infection. Patients were subgrouped as follows: chronic non-atrophic gastritis (CG), chronic atrophic gastritis (CAG), intestinal metaplasia (IM), epithelial dysplasia (ED) and gastric cancer (K). As control populations, patients with duodenal ulcer (DU) and patients with no endoscopic and histologic damage (CO) were investigated. H. pylori infection rate increased with age, but became significantly lower (P < 0.001) with the progression of gastric mucosal damage: DU 85%, CG 72%, CAG 58%, particularly in the antral type (39%), IM 63% overall, ED 44% and K 35%. The density of colonization showed the same trend (P < 0.001). Of the K patients, only 36% were H. pylori positive in the adjacent mucosa. Anti-H. pylori antibodies (IgG, IgA and IgM) were also tested. A concordance in the diagnosis between histology and serology was obtained in 82% of the cases. In our experience, H. pylori infection correlates inversely with the presence of gastric precancerous changes and cancer. A cautious interpretation of the epidemiological data regarding H. pylori infection and gastric cancer is therefore, in our opinion, mandatory.

Adolescent↗

Pathology of the gastric antrum and body associated with Helicobacter pylori infection in non-ulcerous patients: is the bacterium a promoter of intestinal metaplasia?

A series of 115 consecutive, non-ulcerous, dyspeptic patients were examined for Helicobacter pylori (H. pylori) colonization in the gastric antral and/or body mucosa using Giemsa staining. Findings were correlated with the presence and degree of activity of superficial gastritis, deep gastritis, atrophic gastritis and with the presence of intestinal metaplasia. The prevalence of H. pylori positivity was 61.7%. In 59 of the 71 positive patients (83%), H. pylori was detected in the antrum or in both the antral and oxyntic mucosa. In the remaining 12 positive patients, H. pylori was detected only in the oxyntic mucosa nad in all these cases, the antrum showed intestinal metaplasia associated with atrophic gastritis (25%). In both antral and oxyntic mucosa, the activity of the gastritis was significantly correlated with H. pylori colonization. Linear logistic regression analysis showed that in patients with intestinal metaplasia the presence of H. pylori infection was significant in predicting the presence of more extensive intestinal metaplasia after adjusting for age. The prevalence of intestinal metaplasia types II and III was 65.5% in the H. pylori positive and 25% in the H. pylori negative patients. The antral mucosa is thought to be the elective site for H. pylori related histological lesions. At a later stage, H. pylori can be detected only in the oxyntic area while the antral mucosa shows extensive metaplastic or atrophic lesions. We would suggest that H. pylori plays a promotional role in the morphogenesis of intestinal metaplasia.

Adolescent↗

Oesophagitis and pH of refluxate: an experimental and clinical study.

This experimental and clinical study examined the relationship between oesophageal damage and optimal pH of refluxate, and whether 24-h pH monitoring at optimal pH could discriminate the severity of oesophagitis. The rabbit oesophagus was perfused in vivo with pepsin and hydrochloric acid solutions of differing pH for 60 min. Maximal oesophageal damage coincided with peptic solutions at pH 1.5-2.5. Fifty-nine patients with proven gastro-oesophageal reflux disorders were tested for manometric features of the lower oesophageal sphincter (pressure, overall length and abdominal length) and oesophageal exposure to different pH levels. They were classified into four groups according to the endoscopically demonstrated severity of oesophagitis. Supine exposure at the optimal pH level for pepsin activity (pH 1.5-2.5) and overall sphincter length were found to discriminate the severity of oesophagitis reliably in 75 per cent of cases.

Adolescent↗

A randomized controlled trial of lymphoblastoid interferon-alpha in patients with chronic hepatitis B lacking HBeAg.

Ongoing hepatitis B virus replication in the presence of antibody to HBeAg can be observed in patients with active liver disease. These forms of chronic hepatitis B have been described as having a poor prognosis. We have conducted a randomized controlled trial to assess the efficacy of lymphoblastoid interferon-alpha in 60 patients with antibody to HBeAg and hepatitis B virus DNA-positive chronic hepatitis. Patients received 5 million U/m2 interferon three times a week for 6 mo, or no treatment. Final evaluation 18 mo after randomization showed hepatitis B virus DNA negativity and ALT normalization in 53% of treated patients and in 17% of controls (p less than 0.01). The probability of sustained hepatitis B virus DNA loss was significantly higher in treated patients than in controls (p less than 0.005). Blinded histological assessment revealed improvement in 50% of treated patients compared with 33% of controls. Pretreatment hepatitis B virus DNA and aminotransferase levels and histological appearance were not predictive of response. The results of this trial indicated that marked reduction of viral replication in serum and remission of liver damage can be obtained with lymphoblastoid interferon in about 50% of patients with HBeAg antibody- and HBV DNA-positive chronic hepatitis. This rate of response is higher than that reported previously.

Adult↗

Primary carcinoid tumor of the cystic and common bile ducts.

We report a case of primary carcinoid tumor arising at the confluence of the cystic and common bile ducts. The patient was a 64-year-old woman who developed a sudden onset of biliary colic and jaundice. Computerized tomography and nuclear magnetic resonance showed a mass lesion close to the head of the pancreas. At laparotomy a nodular lesion was found at the confluence of the cystic and common bile ducts. Microscopic observation revealed a type B-C carcinoid (Soga's classification) with positive immunoreactivity to chromogranin and cytokeratin. The presence of neurosecretory intracytoplasmic granules was demonstrated by electron microscopy. Flow cytometry showed diploid DNA content of the neoplastic cells with less than 5% of the nuclei in the S-phase region.

Bile Duct Neoplasms↗

Double fatal inhalation of dichloromethane.

1 Two cases of lethal poisoning following acute inhalation of extremely high concentrations of dichloromethane (DCM) are reported. The concentrations of the solvent found in the blood of the two subjects collected at autopsy and analysed by gas chromatography/mass spectrometry (572 and 601 mg l-1) were compatible with those measured in the air a few hours after the discovery of the bodies (up to 168,000 ppm). 2 Extensive brain and lung oedema and congestion, microhaemorrhagic changes of the stomach and congestion in other organs were observed on macroscopic and microscopic examination of both subjects. In addition, and in both cases, high but not lethal carboxyhaemoglobin (COHb) levels (30%) were found in the blood collected at autopsy. 3 Narcosis and respiratory depression due to the effect of DCM on the central nervous system (CNS) appear to have played a critical role in the death of the two men. However, biotransformation of the solvent to toxic metabolites, including carbon monoxide (via oxidative dehalogenation by the cytochrome P450-dependent mixed function oxidase system) or formaldehyde, formic acid, inorganic chloride and carbon dioxide (via the glutathione-S-transferase pathway) may have also contributed significantly to fatal toxicity.

Administration, Inhalation↗

Leukemia and liver disease in childhood: clinical and histological evaluation.

Seventy-two consecutive patients with acute lymphocytic leukemia (ALL) who had undergone liver biopsy within 3 months of completing chemotherapy were studied to evaluate histological features after 2 to 3 years of chemotherapy and to correlate liver disease to the treatment schedule, the number of transfused blood units, and the identified etiology. Fibrosis due to antiblastic drugs was the most frequent histological finding. Histological liver disease was not related either to the chemotherapy schedule or the number of transfused blood units. HBV with or without delta virus and HCV infections were related to a more severe histological liver disease. In about 40% patients with chronic liver disease, no etiology was demonstrated. Immunohistochemistry revealed HBcAg in the liver of 3 HBsAg-negative patients. In conclusion, liver biopsy could be useful in patients with persistent abnormal liver function tests after the completion of chemotherapy and in patients with markers for hepatotropic virus infection.

Alanine Transaminase↗