Monoethyl glycine xylidide (MEGX) test evaluation in primary biliary cirrhosis: comparison with Mayo score.

OBJECTIVE: To evaluate the clinical and prognostic value of the monoethyl glycine xylidide (MEGX) test in patients with primary biliary cirrhosis (PBC) in comparison with the Mayo score (Mayo). DESIGN: A prospective study. METHODS: MEGX determinations at enrolment were compared to the Mayo score as well as to conventional clinical and laboratory parameters in 92 patients with PBC. RESULTS: The MEGX test yielded higher basal values in long-term survivors compared to patients that were transplanted or died during the follow up; patients belonging to the last two groups displayed significantly higher Mayo scores at baseline. Although values for prothrombin time, serum albumin, alkaline phosphatase, cholesterol, cholinesterase, and gamma-glutamyltranspeptidase were significantly different in survivors compared to either transplanted or dead patients at univariate analysis, the multivariate analysis demonstrated an independent prognostic value for the MEGX and the Mayo score solely. The best discrimination between probability of death or survival was achieved with a cutoff value of 25 ng/ml for the MEGX test and of 6 for the Mayo score. When plotting both MEGX test and Mayo score, the point distribution displayed a bimodal trend, and the wide range of values given by the MEGX test was observed to supply a more precise assessment of liver reservoir and a better discrimination of progressive changes in liver function; the limited range of the Mayo score for values below 6 could only identify gross deteriorations. CONCLUSION: Our data show that the asymptomatic progressive functional deterioration occurring during the natural history of PBC can be monitored by the MEGX test because it appears to be able to identify abnormalities prior to the onset of alterations in conventional laboratory and/or clinical parameters which are likely to affect the Mayo score.

Monoethylglicinexylidide test: a prognostic indicator of survival in cirrhosis.

The aim of this study was to assess the value of the monoethylglicinexylidide assay, a dynamic liver function test based on the determination of the serum concentration of lidocaine major metabolite, as a predictor of survival in cirrhosis. For this purpose, the predictive value of monoethylglicinexylidide was evaluated in comparison with the Pugh score, ascites, encephalopathy and a number of different biochemical parameters as collected from the prospective follow-up of 118 patients with cirrhosis. A stepwise regression analysis was performed on the variables of prognostic value according to the Cox model and with respect to 1-yr survival; because Pugh score and monoethylglicinexylidide were the sole variables selected, they were proved to supply independent prognostic information. The most reliable cutoff values for discrimination between death and survival were 25 ng/ml or less for monoethylglicinexylidide and less than 9 for the Pugh score. In 74 patients without overt signs of liver failure (i.e., Pugh < or = 9), monoethylglicinexylidide provided a wide range of results (i.e., 4 to 77 ng/ml), namely values ranging from very low to elevated. Of the 38 patients with satisfactory Pugh scores (< or = 9) but poor monoethylglicinexylidide values (< or = 25), 11 died during follow-up and 3 underwent liver transplantation, despite having shown no clinical signs of liver failure at entry. On the bases of discriminant levels, the monoethylglicinexylidide test is suitable for adoption as a reliable and sensitive indicator of survival in patients with cirrhosis because it supplies more accurate prognostic information compared with the Pugh score.(ABSTRACT TRUNCATED AT 250 WORDS)

[Eosinophilic gastroenteritis and ascites. Clinical case]. / Gastroenterite eosinofila ed ascite. Caso clinico.

We report the case of a patient with recurrent subocclusive episodes and diarrhea (no malabsorption) associated with ascites, in the absence or liver, kidney or heart disease. The demonstration of hypereosinophilia in the peripheral blood and in the ascites fluid and the failure to identify parasitic or haematological disorders have led to a through examination of the stomach (Endoscopy, Echoendoscopy), small bowel (X-rays and Computerized Axial Tomography) and colon (colonoscopy) in a search for parietal lesions. The absence of segmental lesions and the observation of CAT images of diffuse, regular thickening of the ileum and of the mesentery, coupled with the monotonous clinical history spanning over three decades, have led to a diagnosis of eosinophilic gastroenteritis with involvement of the serosal layer. Serosal involvement is rare in eosinophilic disease of the gut; in analogy with other cases reported in the literature, steroids have improved clinical symptoms and normalized the hematological picture.

[Intestinal ischemia: nosographic framework and risk factors]. / Ischemia intestinale: inquadramento nosografico e fattori di rischio.

The diagnosis of intestinal ischaemia still presents numerous problems in terms of nosography, epidemiology, diagnosis and treatment with the result that it is more often excluded than diagnosed. The aim of the present study was to discover whether intestinal ischaemia was clinically identifiable by any specific early signs and symptoms and whether there were any concomitant risk factors. The medical reports on 44 patients consecutively admitted to the San Giovanni Battista Hospital, Turin in 1985-86 with suspected intestinal ischaemia were therefore examined. It was found that intestinal ischaemia was only occasionally (30% of cases) diagnosed at the onset of clinical symptoms. In the 10 patients with ischaemic colitis, the risk factor linked to the causes of the disease was systemic hypovolaemia arising in diffuse atherosclerosis. In the 8 cases of chronic ischaemia and the 26 of intestinal infarction the remote anamnesis revealed symptoms that should have aroused suspicion of intestinal ischaemia partly because the patients were suffering from widespread atherosclerosis. In fact a review of the risk factors for the onset of atherosclerosis (i.e. high blood pressure, smoking, dyslipidemia, obesity and age over 65) revealed that about 60% of the patients under study presented 3 or 4 them simultaneously. To conclude, the data emerging from the study indicate the existence of symptoms and risk factors to diffuse atherosclerosis that should permit the early diagnosis of intestinal ischaemia.

Alpha-fetoprotein in hepatic pathology and hepatocarcinoma.

We have examined a population of 1099 patients, suffering of HCC and chronic hepatitis of different nature, to determine the frequency and significance of alpha-fetoprotein elevation. Moreover we have followed up a group of 206 patients with liver cirrhosis referred to our department of hepatology in Turin, from January 1981 through April 1989. The AFP test with a cut-off of 50 ng/ml, is positive in 67.2% of tumor patients and in 12.9% of chronic hepatitis. No differences exist in patients carriers of hepatitis B virus versus alcoholic or criptogenetic subjects. Twenty-one out of 206 cirrhotic patients followed-up have developed HCC during the observation period (36.5 +/- 22.4 months). Fifteen out 21 patients (71%) showed an increase of AFP values. In 14 patients the HCC was graded as small (less than 4 cm of diameter at US) and in other 7 as advanced or multifocal. The underlying cirrhosis was alcoholic in 11 (53.3%), cryptogenic in 5 (23.8%), and hepatitis B chronic infection related in 5 (23.8%). Serological surveillance has led, to the identification of 71% of the tumors developing during this study. Using the time-course of AFP as the diagnostic parameter of the risk of HCC, we obtained the best performance in term of sensitivity, specificity and diagnostic accuracy. Screening patients at risk of HCC, using abdominal US and AFP testing, is an effective way of determinating small lesions, but how much early determination of HCC in a cirrhotic patient will improve the prognosis remain to be defined.

Canrenone and androgen receptor-active materials in plasma of cirrhotic patients during long-term K-canrenoate or spironolactone therapy.

Plasma levels of canrenone and androgen receptor-active materials (ARM) were determined during long-term oral K-canrenoate or spironolactone therapy in cirrhotics with chronic recurrent ascites. Mean plasma canrenone level was approximately 3 times higher under K-canrenoate than under spironolactone treatment; moreover, the levels were not dose related. Either type of treatment did not affect plasma aldosterone and testosterone concentrations. Plasma ARM during K-canrenoate treatment did not change, whereas in the spironolactone group a 3-fold increase of ARM occurred (p less than 0.05). No dose-related effect was evident with the latter treatment. The lower incidence of gynecomastia in the K-canrenoate group was not correlated with values of plasma canrenone or ARM (p greater than 0.05). Our study questions the traditional view that the mode of action of spironolactone is via its metabolite canrenone. The two antialdosterone drugs, although equally effective in clearing ascites from cirrhotics, appear to act through partially different metabolites. The lower incidence of antiandrogenic or estrogen-like side effects during K-canrenoate seems to be related to metabolites other than canrenone itself.

Pattern analysis of serum alpha-fetoprotein in the early diagnosis of hepatocellular carcinoma in liver cirrhosis.

In a surveillance program for hepatocellular carcinoma (HCC), serum alpha-fetoprotein (AFP) was determined every 4 months in 164 patients with liver cirrhosis. Ultrasonography (US) was performed yearly or as dictated by abnormal AFP levels. During a follow-up of 32.5 +/- 20.8 months HCC was identified by US in 16 patients. In 9 of them the AFP levels rose steadily over 4 months, increasing 7, 8 and 12 months in 3 cases before the lesion became detectable by US. In 4 patients tumors developed despite persistently normal AFP levels. Nine more patients showed abnormal fluctuations of AFP but HCC was not detected. AFP sensitivity was higher at a low cut-off point (40 ng/ml) while specificity of the test appeared higher at the 200 ng/ml cut-off point. An AFP value rising steeply over a few months appeared more reliable than a fixed preset threshold in indicating carcinomatous transformation. Screening for AFP can be expected to uncover about 3/4 of HCC developing in cirrhotics with few false-positive reactions. The test may have a unique role in identifying a subset of liver tumors whose early expression is AFP production.

[Prevalence of peptic ulcer in patients with various hepatopathies]. / Prevalenza della malattia peptica in pazienti con differenti epatopatie.

Aim of this study was to re-evaluate the overall prevalence of a peptic disease in 350 patients with liver diseases of different etiology and severity. A normal endoscopic picture was found in 82% of cases. Peptic lesions were found in 18% of total cases and were located in the duodenal (10.9%) and gastric (7.1%) wall. On the basis of the 15-20% rate, which most Authors think to be a reasonable estimate of the overall ulcer prevalence in normal population, the prevalence rate in this survey would suggest that there is no association between ulcer and liver disease. Ulcers were more commonly present in cirrhotic than in noncirrhotic patients. Both alcohol intake and cigarette smoking were identified as two ulcerogenic events in these patients while portal hypertension and etiology of liver disease were irrelevant factors. The contemporary occurrence of the three ulcerogenic factors (cirrhosis, smoking, and alcohol intake) in a given patient seems to potentiate each others as ulcerogenic event. It is concluded that patients with liver diseases share the same risk of developing a peptic disease as the general population.

CA 19-9 assay in differential diagnosis of pancreatic carcinoma from inflammatory pancreatic diseases.

Levels of a new carbohydrate antigen CA 19-9, which is a monosialoganglioside identified by a monoclonal antibody raised against colorectal carcinoma cells, were compared to carcinoembryonic antigen and tissue polypeptide antigen assays in 250 sera from patients with different pancreatic diseases including acute pancreatitis, chronic pancreatitis, and pancreatic cancer. All three tumoral markers were elevated at the onset of an acute pancreatic attack in a few patients. All but five patients with chronic pancreatitis displayed normal levels with each of the three markers; in two of these five cases an extraintestinal cancer was later discovered. CA 19-9 displayed higher sensitivity and predictive value of a negative result than the other two markers. The best operational characteristic of CA 19-9 was its high predictive value for a positive test which suggests a "ruling in" usage of it for pancreatic cancer diagnosis. CA 19-9 assay was of extreme value in disclosing both localized and metastatic pancreatic cancer while the other two markers were more often positive in the latter case. Of 71 cancer patients with positive markers, only four would have escaped a right diagnosis by assaying CA 19-9 alone.

Prospective evaluation of the diagnostic efficacy of CA 19-9 assay as a marker for gastrointestinal cancers.

Levels of a new carbohydrate antigen, CA 19-9, which is a monosialoganglioside identified by a monoclonal antibody raised against colorectal carcinoma cells, were compared to conventional CEA assays in 615 sera from healthy controls, patients with benign gastrointestinal disorders, and patients with cancers of gastrointestinal or extragastrointestinal origin. Whereas CEA levels were higher in smokers, CA 19-9 values were independent of the smoking history. CA 19-9 was undetectable in lymphoma and myeloma patients, but some patients with extraintestinal epithelial cancers expressed this antigen in serum. For benign and malignant gastrointestinal diseases, CA 19-9 displayed higher sensitivity, specificity, and predictive values than CEA. CA 19-9 was elevated as frequently as CEA in patients with metastatic pancreatic cancer, but in patients with localized disease, CA 19-9 was elevated more often than was CEA. In colorectal cancer, patients with and without metastases were detected at similar rates by both assays. It is concluded that CA 19-9 is a marker of epithelial cancers, does not vary with the smoking status, and is superior to CEA in detecting gastrointestinal malignancies, especially those arising from the pancreatic gland.