Diagnostic accuracy of portal-phase CT and MRI with mangafodipir trisodium in detecting liver metastases from colorectal carcinoma.

AIM: To compare the diagnostic accuracy of single section spiral computed tomography (CT) and magnetic resonance imaging (MRI) with tissue-specific contrast agent mangafodipir trisodium (MnDPDP) in the detection of colorectal liver metastases. MATERIAL AND METHODS: One hundred and twenty-five consecutive patients undergoing surgery for primary and/or metastatic disease were evaluated using CT (5 mm collimation and reconstruction interval, pitch 2), two-dimensional fast spoiled gradient echo (2D FSPGR) T1 and single shot fast-spin echo (SSFSE) T2 weighted breath-hold MRI sequences, performed before and after intravenous administration of MnDPDP. The reference standards were intraoperative ultrasound and histology. RESULTS: The per-patient accuracy of CT was 72.8 versus 78.4% for unenhanced MRI (p = 0.071) and 82.4% for MnDPDP-enhanced MRI (p = 0.005). MnDPDP-enhanced MRI appeared to be more accurate than unenhanced MRI but this was not significant (p = 0.059). The sensitivity of CT was 48.4% versus 58.1% for unenhanced MRI (p = 0.083) and 66.1% for MnDPDP-enhanced MRI (p = 0.004). The difference in specificity between procedures was not significant. The per-lesion sensitivity was 71.7, 74.9 and 82.7% for CT, unenhanced MRI, and MnDPDP-enhanced MRI, respectively; the positive predictive value of the procedures was respectively 84.0, 96.0 and 95.8%. MnDPDP-enhanced MRI provided a high level diagnostic confidence in 92.5% of the cases versus 82.5% for both unenhanced MRI and CT. The kappa value for inter-observer variability was >0.75 for all procedures. CONCLUSIONS: The diagnostic accuracy and sensitivity of MnDPDP-enhanced MRI is significantly higher than single section spiral CT in the detection of colorectal cancer liver metastases; no significant difference in diagnostic accuracy was observed between unenhanced MRI and MnDPDP-enhanced MRI.

CT colonography: screening in individuals at high risk for colorectal cancer.

The use of computed tomographic colonography (CTC) as a screening test for colorectal cancer is being advocated with growing enthusiasm by physicians and the public as stronger evidence of its validity and limited invasiveness emerges from the literature. Because the approach to surveillance of colorectal cancer depends on an individual's degree of risk category, which depends on familial and personal histories, it seems logical that the diagnostic performance and cost efficacy of screening CTC may differ according to the characteristics of the target population. Although CTC seems a valid option in low- to average-risk populations, pending a careful assessment of its cost and estimates of its cost efficacy, there are some important issues that should be addressed when it comes to considering its use in high-risk patients. The expected larger number of induced colonoscopies and higher false-positive rates are likely to have a great influence on CTC costs, but if its implementation causes a dramatic increase in the number of patients willing to undergo screening, thanks to its acceptability, then the cost efficacy ratio may ultimately become competitive with all other screening strategies for colorectal cancer. We strongly feel that large and well-conducted trials are needed to clarify the role of CTC in screening patients at increased risk of developing colorectal cancer.

Serum bile acids, programmed cell death and cell proliferation in the mucosa of patients with colorectal adenomas.

BACKGROUND: Deoxycholic acid induced programmed cell death and an imbalance with cell proliferation may favour colorectal tumourigenesis according to 'in vitro' studies, but information is lacking on the relationships occurring 'in vivo' in humans. AIMS: To evaluate whether serum deoxycholic acid is associated with programmed cell death and cell proliferation in colonic mucosa. METHODS: In 10 patients with colorectal adenomas, we measured fasting serum levels of bile acids; and, in normal colonic mucosa, programmed cell death by the TUNEL technique and cell proliferation by immunohistochemical staining with anti-Ki67. Total and compartmental indices for both activities were calculated. RESULTS: Among serum bile acids, only total deoxycholic acid (median: 0.89 micromol/L +/- 0.54 95% CI), showed a significant positive correlation with the total and basal compartments PCD Index (r = 0.68, p < 0.05). Total proliferation index showed no correlation with either total PCD Index, or bile acids. Within the median compartment of the crypt, cell proliferation was negatively associated with all unconjugated bile acids. CONCLUSIONS: The positive association between deoxycholic acid and programmed cell death in the basal compartment of the crypt, and the negative association of cell proliferation and unconjugated bile acids in the median compartment, do not seem to support the co-carcinogenic effect of deoxycholic acid.

Ileocecal valve imaging on computed tomographic colonography.

BACKGROUND: The aim of our study was to describe the visualization, normal anatomy, and variations of the ileocecal valve with computed tomographic (CT) colonography to provide information about its optimal imaging. METHODS: We analyzed data in two- and three-dimensional rendering mode in 71 consecutive patients who underwent routine CT colonoscopy followed by conventional colonoscopy for confirmation of the radiologic findings. RESULTS: Complete visualization of the ileocecal valve was better achieved in the supine than in the prone position (82% vs. 62%, respectively); the ileocecal valve appeared in 64% of cases in the supine position when it was invisible in prone position (p < 0.0001). Partial visualization of the ileocecal valve was possible in 94% of cases. The ileocecal valve was of labial type in 76%, papillary type in 21%, and lipomatous in 3% of cases. The orifice was identified in 53% of ileocecal valves; in two cases of cecal carcinoma, the normal ileocecal valve morphology was grossly disrupted. CONCLUSION: The ileocecal valve was at least partly visualized by CT colonoscopy in 94% of cases, more frequently in the supine position. Its most common normal morphology is the labial type. The absence of orifice visualization alone is not a specific sign for neoplasia, but its presence helps distinguish physiologic bulging from neoplasia.

Coeliac disease associated with Sjögren's syndrome, renal tubular acidosis, primary biliary cirrhosis and autoimmune hyperthyroidism.

Although coeliac disease may occur in patients affected by another immune-mediated disorder, its coexistence with multiple autoimmune diseases is not frequently described. We report here the case of a 45-year-old woman referred to our centre because of diarrhoea and weight loss, who had already received a diagnosis of primary biliary cirrhosis, Sjögren's syndrome and renal tubular acidosis. Following the development of diarrhoea we established the diagnosis of coeliac disease, based on the presence of anti-endomysium antibodies and a compatible duodenal biopsy. Despite gluten withdrawal she went on to develop an autoimmune hyperthyroidism. The patient tested positive for HLA DRB1*03 and DQB1*02. The association is unlikely to be casual and may be explained by autoimmune mechanisms, genetic susceptibility and favouring environmental factors commonly shared by the diseases of our patient.

Outcome of surgical treatment for chronic calcifying pancreatitis.

OBJECTIVE: To evaluate the short and long-term results of surgical treatment of calcifying chronic pancreatitis in our center. PATIENTS AND METHODS: We studied 55 consecutive patients operated on for chronic calcifying pancreatitis during a period of 12 years. The mean follow-up period was 6.2 years. Main outcome measures were operative mortality and morbidity, degree of pain control, diabetes onset, survival, and causes of death. RESULTS: The etiology was alcoholic in 48 patients and idiopathic in seven patients. A resection was performed in 78% of cases and a by-pass procedure was performed in 22%. Operative mortality was 3.6%; morbidity was 21.8%. A ductal adenocarcinoma was found in 3.6% of cases. The alcohol withdrawal rate was 78%. Complete pain control was achieved in 71.4% of the patients. Among diabetes, cirrhosis, type of surgery, smoking and alcohol abuse history, only alcohol withdrawal was associated with pain control (p < 0.03). A late reintervention was needed in only one patient in the by-pass group. Five and 10-year survival rates for the entire population were 80% and 61%, respectively. Among alcohol, cirrhosis, diabetes, and type of surgery, only the former was associated with survival (p < 0.003). Five-year actuarial survival was 55.6% for patients who continued drinking compared with 86.3% for ex-alcoholics. CONCLUSIONS: Surgical resection should be performed when required by the anatomical conditions because it was associated with good long-term pain control and low postoperative and late morbidity. Alcohol withdrawal has a key role for effective control of pain and prolonged survival.

Spontaneous rupture of hepatocelluar carcinoma: surgical resection and long-term survival.

AIMS: Spontaneous rupture of hepatocellular carcinoma (HCC) is a life-threatening event, particularly in patients with associated cirrhosis. We present our experience of hepatic resection of ruptured HCC. METHODS: We performed 199 resections of hepatocellular carcinoma between January 1984 and December 1999. Six (3%) of these patients were operated on as an emergency because of haemoperitoneum: in five the liver was cirrhotic. RESULTS: The mean duration of the operation was 195+/-101 min; all the patients received blood transfusions. The overall morbidity was 50%, with a mortality rate of 16.5%. Three patients were alive at 50, 80 and 116 months respectively; two had an intrahepatic recurrence treated by chemoembolization. CONCLUSIONS: Non-surgical treatment of spontaneously ruptured hepatocarcinoma should be performed only in patients with contraindication to surgery. Hepatic resection should be the treatment of choice since, according to our experience, long-term results are similar to those of elective surgery.

Liver function and encephalopathy after partial vs direct side-to-side portacaval shunt: a prospective randomized clinical trial.

BACKGROUND: The aim of this study was to determine, in a prospective randomized clinical trial, whether the partial portacaval shunt offers any advantage in terms of liver function and encephalopathy rate when compared with direct side-to-side direct portacaval shunt. METHODS: Forty-six "good risk" patients with cirrhosis and with documented variceal hemorrhage were randomly assigned to either a partial shunt procedure (achieved by 10-mm diameter interposition portacaval H-graft) or direct small-diameter side-to-side portacaval anastomosis. RESULTS: Operative mortality was zero in both groups. During the follow-up period, encephalopathy developed in 3 patients in the partial shunt group and 9 in the direct shunt group (P =.04). Kaplan-Meier analysis demonstrated that encephalopathy-free survival was significantly longer in the partial shunt group (P =.025). Direct shunt patients had significant hepatic functional deterioration postoperatively compared with the partial shunt group. CONCLUSIONS: The partial portacaval shunt effectively controls variceal hemorrhage. Compared with direct side-to-side portacaval shunt, partial shunt preserves long-term hepatic function and minimizes postoperative encephalopathy. We conclude that the partial portacaval shunt is the preferred approach over direct shunts for patients with cirrhosis and with variceal bleeding.

[Use of virtual endoscopy with computerized tomography in the identification of colorectal neoplasms. Prospective study with symptomatic patients]. / Impiego dell'endoscopia virtuale con Tomografia Computerizzata nell'identificazione delle neoplasie colorettali. Studio prospettico in pazienti sintomatici.

INTRODUCTION: Aim of this study was to evaluate the sensitivity of virtual colonoscopy (CT colonography) in the identification of colorectal cancer and to define the limitations and the advantages of this imaging modality, as well as indications to the examination. MATERIAL AND METHODS: We examined prospectively 62 symptomatic patients aged 36 to 82 years (28 women and 34 men). All patients underwent both conventional and virtual colonoscopy on the same day; the conventional examination allowed exploration of the entire colon. RESULTS: Conventional colonoscopy identified 89 lesions 3-50 mm in diameter, namely 84 benign and 5 malignant lesions. No lesions were identified in 12 patients. CT colonography identified 52 of the 89 lesions, with 57.1% diagnostic accuracy. There were 11 false positives (82.5% positive predictive value and 52.2% specificity) and 37 false negatives (24.5% negative predictive value and 58.4% sensitivity). Sensitivity was significantly higher (85.7%) for polyps > or = 1 cm. CONCLUSIONS: Virtual colonoscopy is an imaging modality with good diagnostic yield, well tolerated by patients and with great potentials for further development. We suggest that the examination be performed in symptomatic patients who cannot undergo total colonoscopy or refuse the other imaging modalities. Further studies are warranted in larger series of patients, possibly introducing it in screening programs.

Biliary bile acid composition in gastric cancer.

Bile reflux into the stomach has been considered carcinogenic. Secondary bile acids, and in particular deoxycholic acid, have been shown to act experimentally as co-carcinogens in the colon and are increased in patients with colorectal adenocarcinoma. No information is available with respect to biliary bile acid composition in patients with gastric cancer. We studied biliary bile acid composition in 11 patients with gastric cancer and 23 healthy controls. Bile acids were measured using high-performance liquid chromatography. The site of gastric cancer was the antrum in 6 patients and body in 5. There were 6 intestinal-type and 5 diffuse adenocarcinomas. Only 2 patients had Helicobacter pylori infection. Deoxycholic acid constituted 24% +/- 2% of biliary bile acid in gastric cancer patients versus 22% +/- 2% in healthy controls (NS). Similarly, no differences were found between the two groups for all other bile acids. Deoxycholic acid constituted 23% +/- 3% of biliary bile acid (NS vs. controls) in patients with antral adenocarcinoma and 25% +/- 2% (NS vs. controls) in patients with intestinal-type gastric adenocarcinoma. Gastric adenocarcinoma is not associated with an increase in the more-toxic secondary bile acids, and deoxycholic acid in particular. This reduces the importance of bile acid composition as a promotor in gastric carcinogenesis.

Effect of colectomy with ileo-anal anastomosis on the biliary lipids.

Total colectomy with ileo-anal anastomosis is an effective treatment for ulcerative colitis and familial adenomatous polyposis. The absence of the colon and the coexistence of bile acid malabsorption may increase bile lithogenicity, but data on biliary lipid composition in patients with this operation is lacking. Our aim was to assess bile lithogenicity, bile composition and mass of biliary lipids within the gallbladder. We studied 11 patients with total colectomy and ileo-anal anastomosis and 16 healthy controls. We measured the percentage composition of conjugated bile acids and the masses within the gallbladder of the three main biliary lipids. This method, in contrast with measurement of cholesterol saturation index, can determine the cause of bile lithogenicity in terms of absolute modifications of the biliary lipids. There was no difference in the cholesterol saturation index between patients and controls. Colectomy patients had reduced masses of all three biliary lipids (medians and ranges, mmol): cholesterol 0.11 (0.03-0.24) vs. 0.36 (0.02-0.96), P < 0.02; bile acid 1.62 (0.75-5.21) vs. 3.95 (1.27-8.70), P < 0.01; phospholipids 0.35 (0.07-0.69) vs. 1.14 (0.14-3.00), P < 0.002. They also had reduced per cent deoxycholic acid: 3.8 (0.0-27.6) vs. 17.4 (6.4-44.7), P < 0.005, and increased percent cholic acid: 44.9 (23.3-71.4) vs. 34.3 (19.2-57.9), P < 0.05. We conclude that, despite having bile acid malabsorption, patients with colectomy and ileo-anal anastomosis have a normal cholesterol saturation index, caused by a concomitant reduction in the masses of all three biliary lipids. The reduced per cent biliary deoxycholic acid may help explain the reduced cholesterol and phospholipid masses in these patients. Total colectomy with ileo-anal anastomosis does not seem to predispose to the formation of cholesterol gallstones.

The effect of drinking coffee and smoking cigarettes on the risk of cirrhosis associated with alcohol consumption. A case-control study. Provincial Group for the Study of Chronic Liver Disease.

In order to assess the interaction between alcohol intake, tobacco smoking and coffee consumption in determining the risk of liver cirrhosis we carried out a hospital-based case-control study involving 115 patients at their first diagnosis of cirrhosis and 167 control patients consecutively enrolled in the General Hospitals of the Province of L'Aquila (Central Italy). The mean life-time daily alcohol intake (as g ethanol consumed daily) was measured by direct patient interviews, whose reproducibility was > 0.80 and similar for cases and controls, as checked by interviewing the relatives of a sample of 50 cases and 73 controls. During the same patient's interview we also measured the mean consumption of coffee (daily number of cups of filtered coffee) and tobacco (life-time daily number of cigarettes smoked). A dose-effect relationship on the risk of cirrhosis was present both for alcohol intake--for which the risk was significantly increased above 100 g of daily intake--and for cigarette consumption. The latter did not however improve the goodness-of-fit of a logistic regression model including alcohol intake as covariate. By contrast, coffee consumption had a protective effect on the risk of cirrhosis and significantly improved the goodness-of-fit of such a model. Abstaining from coffee consumption determined both a significantly increased risk of cirrhosis, even for daily alcohol intake below 100 g, and a multiplicative effect with alcohol intake on this risk. In patients drinking > or = 101 g ethanol daily the relative risk increased from 5.5 (95% confidence interval: 1.4-22.0) for coffee consumers to 10.8 (95% confidence interval: 1.3-58.1) for coffee abstainers.(ABSTRACT TRUNCATED AT 250 WORDS)

Serological screening of coeliac disease: choosing the optimal procedure according to various prevalence values.

The aim of this study was to select the best approach for screening coeliac disease patients among populations with different grades of disease prevalence. The diagnostic performance was assessed of class A and G antigliadin antibodies and class A antiendomysium antibodies in 93 consecutive outpatients with suspected malabsorption, 44 of whom (47%) had coeliac disease according to duodenal histological tests. Class G antigliadin antibodies provided the worst diagnostic values, whereas a high diagnostic validity was found for the other two tests. The positive predictive value corrected for the disease prevalence expected in coeliac disease relatives (5%) and the general population (0.2%) fell to 30% and < 2% respectively for class A antigliadin antibodies, whereas it remained 100% for antiendomysium antibodies in both situations, providing an optimal value for their use as a screening test and as a valid alternative to duodenal biopsy when this is not feasible. The high cost of anti-endomysium antibodies and the invasive nature of duodenal biopsy prevent them being used widely as screening procedures. A cost effective two step approach was simulated measuring class A antigliadin antibodies in all subjects of the target population (first step), and performing a confirmation test (antiendomysium antibodies or duodenal biopsy) only in subjects positive for antigliadin antibodies. The results show that such a procedure should be recommended only for subjects with an expected low disease prevalence--that is, 5% for coeliac disease relatives and 0.2% for the general population--as the positive predictive value was always 100% with an acceptable false negative rate (6% and 11% respectively), irrespective of which of the two confirmation tests was used. This approach avoids the use of the confirmation test in 63% and 89% of subjects respectively for the two levels of prevalence, resulting in a considerable reduction of the cost. Patients seen for suspected malabsorption with an expected high prevalence of coeliac disease should not have such a serological screening procedure. In conclusion, antigliadin antibodies are useful to screen for asymptomatic coeliac disease in non-hospital communities if antiendomysium anti-bodies are used as a confirmation test: the latter is reasonable valid alternative to duodenal biopsy.

A strong negative association between alcohol consumption and the risk of hepatocellular carcinoma in cirrhotic patients. A case-control study.

We carried out a hospital-based, case-control study to assess the association of both the Hepatitis B Virus (HBV) infection and the lifetime daily alcohol intake with the risk of developing hepatocellular carcinoma (HCC) in patients with liver cirrhosis (LC). Cases were 62 consecutive inpatients of a Gastroenterology Division in whom a first diagnosis of HCC superimposed on LC was made. Two control groups were used: 310 patients without liver disease, matched 1:5 with cases and randomly selected from inpatients of the same hospital, and 97 consecutive asymptomatic inpatients in whom the first diagnosis of LC was made. Alcohol intake was quantified in all subjects by a standardized questionnaire. HBV infection was associated with HCC development in cirrhotics (odds ratio = 6.8; 95% confidence interval = 1.4-32.3), whereas we observed a trend towards a decreased HCC risk at increased alcohol intake values (odds ratio from 1 for lifetime abstainers to 0.2 for drinkers of 175 g/day or more). Our results suggest that alcohol intake is not a direct determinant of HCC, but its role is mediated by LC. Cirrhotics with high alcohol intake do not usually survive long enough to develop HCC.

Non-invasive diagnosis of liver cirrhosis: a comparison between four discriminant functions.

We assessed the performance of 4 methods of discriminant analysis using as independent variables the age and 16 serum tests, for correctly identifying patients with liver cirrhosis among hospitalized patients affected by chronic liver disease without signs of liver failure; 290 patients entered this study: on the basis of laparoscopy with or without liver biopsy, 152 patients had a diagnosis of liver cirrhosis and 138 were classified as chronic hepatitic patients. Due to the non-multinormal distribution of the variables used and to the unequality of the variance-covariance matrices, we compared the following 4 methods: linear discriminant function, quadratic discriminant function, non-parametric discriminant function and logistic regression. The Receiver Operating Characteristic (ROC) analysis was used to compare diagnostic ability of the assessed methods: the quadratic discriminant function was the best performing method. The predictive ability of this function was compared to that reported for percutaneous liver biopsy, showing that this simple statistical method using age and biochemical tests can efficiently identify liver cirrhosis in the setting of chronic liver disease, reducing the need for invasive diagnostic procedures.

Measurement of bile acid half-life using [75Se]HCAT in health and intestinal diseases. Comparison with [75Se]HCAT abdominal retention methods.

The diagnostic values in detecting terminal ileum dysfunction using [75Se]HCAT have been assessed for two different scintigraphic techniques in 58 subjects. The measurement of [75Se]HCAT T1/2 in the enterohepatic circulation by daily gallbladder scintigraphy showed 78% sensitivity, 96% specificity, 96% positive predictive value, and 78% negative predictive value at the optimal cutoff level of 2.0 days; lower--but not significantly different--figures were observed for [75Se]HCAT total abdominal retention four and seven days after isotope administration, at the optimal cutoff levels of 40% and 22%, respectively. [75Se]HCAT T1/2 was then evaluated in 60 patients with various intestinal diseases. Sixty-nine percent (9/13) of patients with diarrhea of obscure origin showed abnormal [75Se]HCAT T1/2. Bile acid malabsorption using [75Se]HCAT can be investigated by the noninvasive measurement of its enterohepatic T1/2 and may play a pathogenetic role in patients with diarrhea of obscure origin.

Alcohol consumption and non-cirrhotic chronic hepatitis: a case-control study.

We carried out a hospital-based case-control study to assess the association of both the daily amount and the duration of alcohol intake with the risk of developing non-cirrhotic chronic liver disease (chronic hepatitis) in 121 chronic hepatitis patients diagnosed by laparoscopy and liver biopsy, and in 242 matched 'controls' randomly selected from inpatients of the same hospital. Alcohol intake was quantified in all subjects using a standardized questionnaire administered by two doctors unaware of the aim of the study. The odds ratio (OR) for chronic hepatitis was estimated by conditional logistic regression and increased exponentially from 1.0 for non-drinkers to 11.4 for daily alcohol intake of 325 g or more. Considering duration of alcohol consumption from up to 10 to up to 30 years, the ORs for chronic hepatitis consistently decreased for the daily alcohol intake categories of 25-50 g (from 74.1 to 0.7 respectively), 75-100 g (from 149.7 to 0.7 respectively) and 125 g or more (from 212.0 to 1.8 respectively). Our results suggest the existence of a dose-dependent individual susceptibility to the damaging effect of alcohol on the liver.

Acute pancreatitis during oral 5-aminosalicylic acid therapy.

Therapy with oral 5-aminosalicylic acid for inflammatory bowel disease has been reported as effective and safe. We report two cases of biochemically proven mild acute pancreatitis occurring 2 and 14 days, respectively, after oral 5-aminosalicylic acid therapy was instituted for inflammatory bowel disease. A hypersensitivity mechanism might be involved, owing to possible erratic systemic absorption of the drug. We suggest clinical and biochemical monitoring for patients undergoing oral 5-aminosalicylic acid therapy in order to confirm its possible association with acute pancreatitis and to assess the actual incidence of such an adverse reaction.