The morphological and histopathological assessment of Alagille syndrome with extrahepatic bile duct obstruction: the importance of the differential diagnosis with subgroup "o" biliary atresia.

PURPOSE: The differential diagnosis between Alagille syndrome (AGS) with extrahepatic bile duct obstruction (EHBDO) and biliary atresia (BA) is difficult. We report a case series of AGS with EHBDO with detailed validation of the morphological and histopathological features for the differential diagnosis of BA. METHODS: Six liver transplantations (LTs) were performed for AGS with EHBDO. All patients were diagnosed with BA at the referring institution and the diagnosis of AGS was then confirmed based on a genetic analysis before LT. We verified the morphological and histopathological findings of the porta hepatis and liver at the diagnosis of BA and at LT. RESULTS: All patients had acholic stool in the neonatal period and were diagnosed with BA by cholangiography. The gross liver findings included a smooth and soft surface, without any cirrhosis. The gross findings of the porta hepatis included aplasia of the proximal hepatic duct, or subgroup "o", in five patients. The histopathological examination of the EHBD also revealed obstruction/absence of the hepatic duct. There were no patients with aplasia of the common bile duct. CONCLUSIONS: Aplasia of the hepatic duct and the macroscopic liver findings may help in to differentiate between AGS with EHBDO and BA.

Predictive value of assessment of different modalities in the diagnosis of infantile cholestasis.

This study investigated the relative accuracy and roles of abdominal ultrasonography, hepatobiliary scintigraphy and liver biopsy in the diagnosis of infantile cholestasis. A total of 50 infants (27 females) aged 1 - 12 months were classified into those with intrahepatic causes of cholestasis (n = 22) and those with extrahepatic causes (n = 28). Cholestasis is caused by a wide range of conditions and diagnosis requires meticulous history taking, thorough clinical examination and many laboratory tests. The most common cause of intrahepatic cholestasis was found to be idiopathic neonatal hepatitis (54.5%), followed by infectious hepatitis (9.1%), metabolic liver diseases (9.1%), intrahepatic biliary atresia (9.1%) and Alagille syndrome (4.5%). The most common cause of extrahepatic cholestasis was extrahepatic biliary atresia (96.4%). The incidence of choledochal cyst was low (3.6%). The cornerstone of the diagnosis of infantile cholestasis was found to be liver biopsy, which was associated with a high degree of accuracy.

Comparison of accessory performance using a novel ERCP mechanical simulator.

BACKGROUND AND STUDY AIMS: There is a paucity of in vitro methods for evaluating ERCP accessories. We hypothesize that the time taken to perform a simulated single stent or multiple stents placement is different for stenting systems with or without the capability of intraductal ductal release (IDR) of the guide wire. PATIENTS AND METHODS: We conducted an un-blinded in vitro comparison of ERCP accessories using a mechanical simulator during hands-on ERCP practice workshops. A total of 21 U.S. participants and 20 Chinese participants with various level of ERCP experience took part in the different practice workshops. Accessories with and without the capability of intraductal release of guide wire were compared. Total time required for completing a simulated stenting procedure with single or multiple stents and the respective simulated fluoroscopy time were recorded. RESULTS: There was no significant difference in the time taken for placement of a single stent using either stenting systems. Stenting system capable of intraductal release of the guide wire required significantly shorter time to complete placement of three stents. CONCLUSIONS: Using time required to complete a specific task, i. e. biliary stenting, the mechanical simulator permits the performance of different accessories by the same group of operators to be evaluated objectively.

Intraductal US in the assessment of tumor involvement to the orifice of the cystic duct by malignant biliary obstruction.

BACKGROUND: Tumor involvement to the orifice of the cystic duct (OCD) is a risk factor for cholecystitis after metallic stent (MS) placement. OBJECTIVE: ERCP and intraductal US (IDUS) were used to assess tumor involvement to the OCD. DESIGN: A prospective consecutive study. SETTING: The University of Tokyo Hospital, Japan. PATIENTS AND INTERVENTIONS: Between January 2003 and May 2007, 34 patients with resectable malignant biliary obstruction underwent an ERCP and an IDUS before preoperative biliary drainage. MAIN OUTCOME MEASUREMENTS: ERCP and IDUS findings were confirmed via a histopathologic analysis of surgical specimens. RESULTS: An ERCP showed that the cystic duct was opacified in 22 of 34 patients (64.7%). Eight patients were diagnosed with OCD tumor involvement. In the remaining 12 patients, tumor involvement was impossible to evaluate via an ERCP. An IDUS identified tumor involvement to the OCD in all 34 patients. Tumor involvement to the OCD was diagnosed in 12 patients, including 4 patients with previously negative results during an ERCP. Tumor involvement was confirmed by histopathology of surgical specimens. The sensitivity and specificity of detection were 66.7% (8/12) and 63.6% (14/22), respectively, via ERCP, and 100% (12/12) and 100% (22/22), respectively, via IDUS. LIMITATION: The small sample size. CONCLUSIONS: IDUS, in addition to ERCP, provides an accurate evaluation of tumor involvement to the OCD in patients with malignant biliary obstruction.

Magnetic resonance cholangiopancreatography in cholestatic diseases.

BACKGROUND/AIMS: To evaluate the usefulness of magnetic resonance cholangiopancreatography in cholestasis. METHODOLOGY: Sixty-seven patients with cholestasis underwent ultrasound and magnetic resonance cholangiopancreatography, subsequently. The results of ultrasound and magnetic resonance cholangiopancreatography were interpreted by two independent radiologists. RESULTS: According to ultrasonographic findings intra- and extrahepatic cholestasis were diagnosed in 62.7% and 37.3% of patients, respectively. Magnetic resonance cholangiopancreatography revealed intra- and extrahepatic cholestasis in 52.2% and 47.8% of patients at the same group, respectively (p=0.016, kappa=0.789). Endoscopic retrograde cholangiopancreatography was indicated in 37.3% of patients (22.4% diagnostic, 14.9% therapeutic) according to ultrasonographic findings. However, 41.8% of patients had indication for endoscopic retrograde cholangiopancreatography following magnetic resonance cholangiopancreatography in the same group. In 20% of patients who needed diagnostic endoscopic retrograde cholangiopancreatography according to ultrasonographic findings, endoscopic retrograde cholangiopancreatography wasn't indicated after magnetic resonance cholangiopancreatography. Similarly, 8.9% of patients who didn't have indication for endoscopic retrograde cholangiopancreatography according to ultrasonographic findings underwent endoscopic retrograde cholangiopancreatography (p=0.508, kappa=0.72). CONCLUSIONS: Magnetic resonance cholangiopancreatography is valuable in diagnosis of extrahepatic cholestasis in patients suspected with intrahepatic cholestasis according to ultrasonographic findings. Magnetic resonance cholangiopancreatography does not prevent endoscopic retrograde cholangiopancreatography requirement significantly in patients who need diagnostic endoscopic retrograde cholangiopancreatography following ultrasonography.

Usual and unusual causes of extrahepatic cholestasis: assessment with magnetic resonance cholangiography and fast MRI.

Cholestasis may result from hepatocellular (intrahepatic) disease or biliary tract (extrahepatic) abnormalities. Etiologies causing extrahepatic cholestasis are extremely diverse and invasive procedures, such as endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC), were previously required to establish the diagnosis. Due to refinements of magnetic resonance imaging (MRI) techniques, the patient with extrahepatic cholestasis currently can be evaluated noninvasively, and the information revealed frequently exceeds the findings obtained by ERCP and PTC. In this essay, we illustrate the classic MR cholangiographic (MRC) and MRI features of a variety of disorders causing extrahepatic cholestasis, including non-neoplastic disorders of the biliary tract (congenital abnormalities, infectious processes, iatrogenic disorders, and postsurgical complications) and neoplastic conditions (e.g., tumors of the pancreas, biliary tree, liver, ampulla, and regional lymph nodes). In most cases, familiarity with the key MRC features in addition to information obtained via cross-sectional MR images provide sufficient information for adequate lesion characterization.

The value of clinical assessment in the diagnosis of icterus and cholestasis.

We studied the reliability of the clinical assessment and the discriminatory value of different symptoms and signs in diagnosing obstructive and non-obstructive diseases causing icterus and/or cholestasis. During a period of two-and-a-half years, clinical assessment done by both physicians-in-training and by senior physicians was completed for 266 patients, and the usefulness of different symptoms and signs was tested in 220 of these. Clinical assessment was found to be a reliable method in distinguishing between obstructive and non-obstructive conditions causing icterus, with the sensitivity of 92% and specificity of 86%. In cases of anicteric cholestasis, the sensitivity and specificity of clinical assessment were 74% and 80%, respectively. Abdominal pain and abdominal tenderness were significantly (p less than 0.01) associated with obstructive diseases, whereas an enlarged liver, fever and excessive consumption of alcohol were associated with non-obstructive diseases (p less than 0.01, p less than 0.05, p less than 0.05, respectively). Itching, vomiting, intolerance to fatty foods, previous cholecystectomy, abdominal tumour and clinical icterus had no discriminatory value. Clinical evaluation is a reliable method in the diagnostic workup of a patient with icterus or anicteric cholestasis, and it is still of crucial importance in directing further investigations.

Bedside ultrasonography. A low-cost definitive diagnostic procedure in obstructive jaundice.

We evaluated real-time ultrasonography carried out by gastroenterologists for its diagnostic accuracy in 89 patients with obstructive jaundice. The positive predictive values for the site and nature of the obstruction were 94.3 and 89.9%, respectively. The advanced stage of disease in our patients and the clinical background of the investigators may have contributed to the high diagnostic accuracy of ultrasonography in this study. Nevertheless, we recommend that gastroenterologists themselves perform bedside ultrasonography for a definitive diagnosis in patients with obstructive jaundice. The high degree of precision achieved by ultrasound in our setting makes more expensive investigations unnecessary as routine procedures.

The influence of uninterpretability on the assessment of diagnostic tests.

A frequent problem faced by physicians utilizing diagnostic tests is the occurrence of uninterpretable test results. Such results, if they occur commonly, can seriously impair the diagnostic performance of the test. Moreover, in assessing the characteristics of the test, i.e. sensitivity, specificity, etc. failure to consider the impact of uninterpretability will artificially inflate the test characteristics. In this paper we explore the implications of this issue. We observe that a relevant factor is the potential repeatability of the test, i.e. whether the cause of uninterpretability is a transient phenomenon or an inherent property of the subject. We distinguish uninterpretable results, in which no result is obtained, from indeterminate results, in which the result is equivocal, or for which predisposing concomitant factors limit the interpretability of the result. Our results demonstrate that the naive approach of ignoring uninterpretable results in test assessments may indeed be unbiased in certain circumstances. However, if the cause of uninterpretability is related to disease status or to the potentially observable test result, then this approach will lead to bias. In either case, the frequency of uninterpretability is an important consideration in the cost-effectiveness of the test.

Decision analysis for the practicing gastroenterologist. 2. Insights into the efficacy of diagnostic strategies using decision analysis.

Decision analysis is a valuable tool for studying diagnostic strategies in gastroenterology. Multiple comprehensive patient management strategies can be compared in hypothetical populations of patients with varying characteristics reflecting real clinical situations which could not be readily empirically studied. Measures of clinical outcome can be compared and cost effectiveness ratios calculated. Analyses of the diagnostic approaches to suspected obstructive jaundice and pancreatic cancer presenting as abdominal pain are discussed as examples. A useful decision analysis combines the best data available in a clinically relevant fashion. Although decision analysis cannot replace empiric research, it helps clarify reasons for the uncertainty so common in clinical practice and provides insight into the diagnostic process that might otherwise be elusive.

Suspected obstructive jaundice: a decision analysis of diagnostic strategies.

Clinical decision analysis and a computer model were used to evaluate ten diagnostic strategies for the diagnosis of extrahepatic obstructive jaundice. The sensitivity, specificity, complications, and costs of currently used individual tests were used to determine the overall sensitivity, specificity, complications, and costs of each strategy at different disease prevalences. In patients with a low probability of extrahepatic obstructive jaundice (less than or equal to 20%), the optimal strategy begins with ultrasonography, followed by a cholangiogram when dilated ducts are present. When dilated ducts are not present, patients may be observed clinically and endoscopic retrograde cholangiopancreatography is done if the jaundice does not resolve. In patients with a higher probability of extrahepatic obstructive jaundice, a cholangiogram is needed for an accurate diagnosis. In patients with a low probability of extrahepatic obstructive jaundice, the optimal strategy has an overall sensitivity of 92% and a specificity of 99%. About 40% of patients need a cholangiogram at an average cost of $1000 per patient. In patients with a higher probability of extrahepatic obstructive jaundice, the optimal strategy has an overall sensitivity of 97%, specificity of 98%, and cost of $1000 to $1200 per patient.

[Critical evaluation of echography in the diagnosis of cholestatic jaundice]. / Valoración crítica de la ecografía en el diagnóstico de la ictericia colestática.

Seventy one patients affected by cholestasis and jaundice were studied by means of ultrasound between september 1980 and february 1983 in order to evaluate the accuracy of this procedure in the investigation of the site of obstruction and its ethiology. The ultrasound findings were correlated with those obtained by opacification of the bile ducts, either endoscopic or percutaneous, and by surgery. The sonographic diagnosis of cholestatic jaundice was based on the size of the biliary tract taking in account that the intrahepatic branches are not evident in normal conditions and considering 4-5 mm and 7-8 mm as the upper limits for the proximal and distal segments of the common bile duct respectively. The accuracy of ultrasound in establishing the common bile duct size was 98%. Forty eight patients had extrahepatic obstruction, 45 of whom had a dilated common bile duct (94%), while 3 were normal (6%). Twenty two patients had an intrahepatic cholestasis, 20 of whom had a normal size of the common bile duct (91%) while 2 showed a dilatation (9%). Thus, the sensitivity was 95.7% and the specificity 86.9%. The ethiologic diagnosis was available in 31 patients with extrahepatic obstruction (65%) and in 7 with intrahepatic cholestasis (32%). Dilated common bile duct with stones and pancreas and gallbladder carcinoma were the most common causes of obstructions we have found in this group of patients. In patients with cholestasis and jaundice the ultrasonic diagnosis should establish the site of obstruction and, if it is possible, the ethiology.

Decision theory as an aid in the diagnosis of cholestatic jaundice.

Current literature was reviewed for studies on diagnostic value and risk to the patient of different diagnostic techniques in jaundice. It was found that few studies of diagnostic techniques were in fact prospective trials and that many materials were highly selected. Reported figures were used for calculating expected risks and benefits of different investigative strategies. Decision analysis, here applied to a problem not as yet studied with this technique, enable us to compare the outcomes of different strategies and to construct a simple plan for the rational choice of investigative procedures in patients with cholestatic jaundice. According to this plan, following history-taking, physical examination and simple laboratory tests, the investigation should proceed directly with fine-needle PTC whenever the probability of extrahepatic cholestasis is judged to be greater than 87%, and with liver biopsy if this probability is judged to be lower than 2%. In all other cases further investigations should start with ultrasonography.