[A 3-week history of intestinal symptoms in a 67-year-old male patient with chronic arthralgia]. / Seit 3 Wochen bestehende intestinale Beschwerden bei einem 67-jährigen Patienten mit chronischen Arthralgien.

Whipple disease is an infection caused by the bacterium Tropheryma whipplei. Due to its unspecific clinical symptoms, it is difficult to diagnose and often remains undetected for a long time. The case of a patient who presented with acute intestinal symptoms to the authors' department is reported. The diagnosis of classic Whipple disease was established. The symptoms subsided under antibiotic therapy. Complications in the form of immune reconstitution inflammatory syndrome (IRIS) occurred, requiring immunosuppressive treatment.

Incidence of bleeding in 8172 percutaneous ultrasound-guided intraabdominal diagnostic and therapeutic interventions - results of the prospective multicenter DEGUM interventional ultrasound study (PIUS study).

PURPOSE: To analyse the incidence of bleeding after percutaneous ultrasound guided diagnostic and therapeutic intraabdominal interventions in a prospective multicentre study (DEGUM percutaneous interventional ultrasound study). MATERIALS AND METHODS: Within a time period of 2 years diagnostic and therapeutic intraabdominal interventions (with the exclusion of ascites paracentesis) performed percutaneously under continuous ultrasound (US) guidance were prospectively assessed using a pseudonymized standardized web site entry form. Number and type of intervention, operator experience, patient characteristics, medication, lab data as well as technical aspects of the procedure and bleeding complications were analysed according to the interventional radiology standards. RESULTS: 8172 US-guided intraabdominal interventions (liver n = 5903; pancreas n = 501, kidney n = 434, lymph node = 272, biliary system n = 153, spleen n = 63, other abdominal organs and extra-organic targets n = 999) were analysed in 30 hospitals. The majority were diagnostic biopsies including 1780 liver parenchyma, 3400 focal liver lesions and 404 pancreatic lesions. 7525 interventions (92.1 %) were performed in hospitalized patients (mean age 62.6 years). Most operators were highly experienced in US-guided interventions (> 500 interventions prior to the study n = 5729; 70.1 %). Sedation was administered in 1131 patients (13.8 %). Needle diameter was ≥ 1 mm in 7162 punctures (87.9 %) with main focus on core needle biopsies (18 G, n = 4185). Clinically relevant bleeding complications with need of transfusion (0.4 %), surgical bleeding control (0.1 %) and radiological coiling (0.05 %) were very rare. Bleeding complications with fatal outcome occurred in four patients (0.05 %). The frequency of major bleeding complications was significantly higher in patients with an INR > 1.5 (p < 0.001) and patients taking a medication potentially interfering with platelet function or plasmatic coagulation (p < 0.0333). CONCLUSION: This prospective multicentre study confirms the broad spectrum of percutaneous US-guided intraabdominal interventions. However diagnostic liver biopsies dominate with the use of core needle biopsies (18 G). Percutaneous US-guided interventions performed by experienced sonographers are associated with a low bleeding risk. Major bleeding complications are very rare. A pre-interventional INR < 1.5 and individual medication risk assessment are recommended.

Assessment of spleen stiffness using acoustic radiation force impulse imaging (ARFI): definition of examination standards and impact of breathing maneuvers.

PURPOSE: Spleen elastography is a promising method for the characterization of portal hypertension in cirrhotic individuals. However, standardized examination procedures for spleen stiffness measurement have not been defined yet. We analyzed the distribution characteristics of spleen shear-wave velocity (ARFI) and assessed the influence of the respiratory position on spleen stiffness measured by ARFI. MATERIALS AND METHODS: 25 healthy probands and 25 patients with Child A liver cirrhosis were prospectively characterized with conventional ultrasound, transient elastography, liver ARFI, and underwent spleen ARFI in two respiratory positions: breath hold after expiration (exp) and deep inspiration (insp). For each position 20 single measurements were performed. The distribution of spleen ARFI values was analyzed for normality and the appropriate number of measurements for spleen stiffness estimation was investigated. RESULTS: Spleen ARFI results were normally distributed in > 95 % of cases. Performing 20 instead of 10 single measurements resulted in < 5 % deviation from the mean value after 20 measurements in the majority of cases. Cirrhotic patients had a higher spleen stiffness compared to healthy probands (exp: 3.25 ±â€Š0.58 vs. 2.46 ±â€Š0.35 m/s; p < 0.001). Deep inspiration caused an overall increase in spleen stiffness in both groups: probands 2.46 ± 0.35 m/s (exp) vs. 2.66 ±â€Š0.36 m/s (insp), p = 0.01; cirrhotics 3.25 ±â€Š0.58 m/s (exp) vs. 3.46 ±â€Š0.38 m/s (insp), p = 0.03. However, cases with high spleen stiffness values (exp) show decreasing ARFI values in deep inspiration. CONCLUSION: ARFI values of the spleen are normally distributed and the mean of 10 valid measurements can be used as a representative value. Deep inspiration significantly modulates spleen stiffness. Therefore, the respiratory position needs careful standardization.

How perfect are you with defective probes? Information on the results of the mini-trial on technical quality assurance during the "Ultraschall 2012" conference in Davos.

This article deals with the technical quality assurance of ultrasound B-systems. As part of a mini-trial during the Dreiländertreffen in Davos "Ultrasound 2012", we addressed the question as to whether physicians can detect faulty probes spontaneously during live scanning B-mode. For this purpose a special diagnostic device had been prepared so that groups of piezoelectric elements in the array were without function. Then the images had to be characterized by test persons without knowledge of the faulty elements. The results show that a deterioration of the image could be detected starting at five disabled elements. Due to the small number of test persons, our statements are only preliminary.

Acoustic radiation force impulse (ARFI) elastography in acute liver failure: necrosis mimics cirrhosis.

Acoustic radiation force Impulse (ARFI) technology correlates shear-wave velocity with fibrosis. It can differentiate between advanced fibrosis and normal tissue in chronic liver disease. However, specificity is impaired by cholestasis, inflammation or oedema in acute hepatitis. In patients with acute liver failure (ALF) necessitating liver transplantation ARFI has not been evaluated yet. We investigated 3 patients with ALF and compared their ARFI results to those of healthy controls (n = 33) and cases with liver cirrhosis (n = 21). In the 3 ALF patients shear-wave velocities were 3.0, 2.5, and 2.7 m/s, respectively. These results were significantly increased compared to those of healthy controls (median: 1.13 m/s; p < 0.001) and similar to those of cirrhotic individuals (median: 2.93 m/s). Two individuals underwent liver transplantation. Explants showed massive necrosis, but no signs of chronic liver disease. Patient 3 recovered spontaneously and showed decreasing ARFI results during follow-up. In conclusion, hepatic necrosis can mimic liver cirrhosis at ARFI evaluation in ALF patients and this impairs the specificity of ARFI.

Impact of controlled attenuation parameter on detecting fibrosis using liver stiffness measurement.

BACKGROUND: Liver fibrosis is often accompanied by steatosis, particularly in patients with non-alcoholic fatty liver disease (NAFLD), and its non-invasive characterisation is of utmost importance. Vibration-controlled transient elastography is the non-invasive method of choice; however, recent research suggests that steatosis may influence its diagnostic performance. Controlled Attenuation Parameter (CAP) added to transient elastography enables simultaneous assessment of steatosis and fibrosis. AIM: To determine how to use CAP in interpreting liver stiffness measurements. METHODS: This is a secondary analysis of data from an individual patient data meta-analysis on CAP. The main exclusion criteria for the current analysis were unknown aetiology, unreliable elastography measurement and data already used for the same research question. Aetiology-specific liver stiffness measurement cut-offs were determined and used to estimate positive and negative predictive values (PPV/NPV) with logistic regression as functions of CAP. RESULTS: Two thousand and fifty eight patients fulfilled the inclusion criteria (37% women, 18% NAFLD/NASH, 42% HBV, 40% HCV, 51% significant fibrosis ≥ F2). Youden optimised cut-offs were only sufficient for ruling out cirrhosis (NPV of 98%). With sensitivity and specificity-optimised cut-offs, NPV for ruling out significant fibrosis was moderate (70%) and could be improved slightly through consideration of CAP. PPV for significant fibrosis and cirrhosis were 68% and 55% respectively, despite specificity-optimised cut-offs for cirrhosis. CONCLUSIONS: Liver stiffness measurement values below aetiology-specific cut-offs are very useful for ruling out cirrhosis, and to a lesser extent for ruling out significant fibrosis. In the case of the latter, Controlled Attenuation Parameter can improve interpretation slightly. Even if cut-offs are very high, liver stiffness measurements are not very reliable for ruling in fibrosis or cirrhosis.

Human pancreatitis-associated protein. Messenger RNA cloning and expression in pancreatic diseases.

A human pancreatic cDNA library was screened with the cDNA encoding rat "pancreatitis-associated protein" (PAP). The selected clone encoded a secretory protein structurally related to rat PAP. The protein had the same size as rat PAP and showed 71% amino acid identity, the six half-cystines being in identical positions. Domains of the proteins showing homologies with calcium-dependent lectins were also conserved. In addition, expression in pancreas of the genes encoding the human protein and rat PAP showed similar characteristics: both were expressed at very low levels in control tissue and overexpressed during the acute phase of pancreatitis, contrary to most secretory products. The human protein was therefore named human pancreatitis-associated protein (PAP-H). Antibodies raised to a synthetic peptide of PAP-H detected a single band with an M(r) compatible with PAP-H in Western blot analysis of proteins extracted from a pancreas presenting with acute pancreatitis. In that tissue, the protein could be immunolocalized to the apical regions of acinar cells. An immunoassay was also constructed to quantify the protein in serum. Elevated PAP-H levels were observed in patients with acute pancreatitis and in some patients with chronic pancreatitis. Values were close to background in healthy subjects and in patients with other abdominal diseases. These results confirm that PAP-H synthesis increases during inflammation and suggest a possible use of the protein as biological marker of acute pancreatitis.

ESPEN Guidelines on Enteral Nutrition: Pancreas.

The two major forms of inflammatory pancreatic diseases, acute and chronic pancreatitis, require different approaches in nutritional management, which are presented in the present guideline. This clinical practice guideline gives evidence-based recommendations for the use of ONS and TF in these patients. It was developed by an interdisciplinary expert group in accordance with officially accepted standards and is based on all relevant publications since 1985. The guideline was discussed and accepted in a consensus conference. In mild acute pancreatitis enteral nutrition (EN) has no positive impact on the course of disease and is only recommended in patients who cannot consume normal food after 5-7 days. In severe necrotising pancreatitis EN is indicated and should be supplemented by parenteral nutrition if needed. In the majority of patients continuous TF with peptide-based formulae is possible. The jejunal route is recommended if gastric feeding is not tolerated. In chronic pancreatitis more than 80% of patients can be treated adequately with normal food supplemented by pancreatic enzymes. 10-15% of all patients require nutritional supplements, and in approximately 5% tube feeding is indicated.

Two transcripts are generated from the pancreatitis associated protein II gene by alternative splicing in the 5' untranslated region.

We have previously reported the coding sequence of the rat PAP II mRNA. We show in this paper the existence in rat pancreas of two forms of PAP II mRNA with identical coding sequence but a different 5'-untranslated region. We demonstrate that this is the result of a differential splicing.

Genetics of pancreatitis.

There was some recent progress in the understanding of genetic risk factors in chronic pancreatitis. Due to this progress some of the traditional views of the subject will change. Today, genetic risk factors are attributed a much more important role that in the past. The frequency and strength of mutations were higher than expected. Strong variants were the rare autosomal-dominant mutations N29I and R122H of PRSS1 (cationic trypsinogen) and homozygous N34S of SPINK1 (pancreatic secretory trypsin inhibitor). Other mutations (heterozygous N34S, CFTR) were of lower relevance but still mediate a higher risk than alcohol consumption. The course of genetically determined pancreatitis is rather mild. In the long term pancreas cancer was found in some patients but apart from non-smoking no adequate prophylactic strategy is available up to now.

Clinical characterization of patients with hereditary pancreatitis and mutations in the cationic trypsinogen gene.

PURPOSE: We determined the clinical manifestations of hereditary pancreatitis in nearly 30 families. PATIENTS AND METHODS: The two trypsinogen mutations N29I and R122H were identified in a group of 550 patients with chronic pancreatitis of unclear origin. The following criteria were used to characterize the severity of chronic pancreatitis (one point each): calcifications, cysts, dilation of the pancreatic duct, diabetes, hospital treatment, and operation. Stages were defined as stage 0 (no points), stage 1 (one to two points), stage 2 (three to four points), and stage 3 (more than four points). Smoking and drinking habits were also recorded. RESULTS: Six families with the N29I mutation (25 subjects with the mutation) and 21 families with the R122H mutation (76 subjects with the mutation) were identified. The median ages for the onset of disease were 11 years in N29I and 10 years in R122H patients. The severity of chronic pancreatitis and symptoms were similar for both mutations. About 26% (n = 26) of the 101 subjects carrying a mutation were asymptomatic, and 42% (n = 42) had mild disease (stage 1). Twenty-nine percent (n = 29) had moderate disease (stage 2), and only 4% (n = 4) had severe disease (stage 3). CONCLUSIONS: Symptoms of patients with the N29I or R122H trypsinogen mutation were generally similar. The majority of subjects with trypsinogen mutations had mild disease or was asymptomatic.

C282Y and H63D mutation of the hemochromatosis gene in German porphyria cutanea tarda patients.

BACKGROUND AND AIMS: Patients with porphyria cutanea tarda (PCT) have a susceptibility to reversible inactivation of hepatocyte uroporphyrinogen decarboxylase, which can be triggered by alcohol, hepatitis C virus, and other agents. Inherited factors that may predispose to PCT include the C282Y mutation in the hemochromatosis (HFE) gene. METHODS: We analyzed the hemochromatosis mutations C282Y and H63D in liver biopsies and serum samples of 190 German patients (mean age 48+/-12.5 years) with sporadic PCT. The hepatic iron concentration was determined within the liver tissue. Age-matched healthy blood donors (115 donors) served as controls. RESULTS: The C282Y and H63D mutations were found in 75 (39%) and 85 (45%) of 190 patients with PCT, respectively. Twenty-two patients (12%) were homozygous for the C282Y mutation, and eighteen patients (9%) were compound heterozygotes, displaying both the C282Y and the H63D mutation. Within the control group, 3 of 115 patients were heterozygous for C282Y (3%) and 12 for H63D (10%). Serum and hepatic iron, ferritin, transferrin saturation, or liver enzymes did not differ significantly between patients with or without HFE mutations. CONCLUSIONS: The high frequency of homo- and heterozygosity for the C282Y and H63D alleles strongly suggests that these mutations are important predisposing factors for PCT in German patients.

Octreotide treatment in patients with necrotizing pancreatitis and pulmonary failure.

OBJECTIVE: To determine the efficiency of intravenous infusion of octreotide in the treatment of patients with severe pancreatitis and pulmonary failure. DESIGN: Prospective, case-control study. SETTING: Intensive care unit of a university hospital. PATIENTS: Treatment group: 39 patients with necrotizing pancreatitis were selected for the study. In all, pulmonary failure developed under conservative treatment and surgical intervention had been necessary because of local (abscess, necrosis) or systemic (systemic inflammatory response syndrome) complications. The outcome was prospectively followed up until death or discharge from the hospital. CONTROL GROUP: 54 case-control matched patients with acute necrotizing pancreatitis and pulmonary failure, who had not been treated with octreotide. INTERVENTION: Each patient in the treatment group received 100 micrograms intravenous octreotide three times daily for 10 days, in addition to the standard intensive care therapy. RESULTS: The groups (octreotide group, control group) were highly comparable with regard to age (mean age: 54, 51 years), sex, severity of illness (Acute Physiology and Chronic Health Evaluation II score: 27, 27), etiology of pancreatitis, and pretreatment at the time of admission to the intensive care unit. There was no difference in the development of renal, hepatic, gastrointestinal, hemostatic, neurologic, or local complications. But the frequency of the adult respiratory distress syndrome (18 vs 40%; p < 0.05) and circulatory shock (51 vs 87%; p < 0.05) was significantly lower in the treatment group. Furthermore, mortality was 26% (10 of 39 patients) in the octreotide group and 61% (33 of 54 patients) in the control group (p < 0.01). CONCLUSION: The results of our case-control study showed a beneficial effect of octreotide in patients with severe necrotizing pancreatitis and pulmonary failure. Based on these data, a prospective, double-blind, placebo-controlled study should be performed to evaluate these results.

Influence of secretagogues on asynchronous secretion of newly synthesized pancreatic proteins in the conscious rat.

The secretion of newly synthesized pancreatic enzymes was studied in pancreatic duct cannulated rats after intravenous injection of 100 microCi of [35S]methionine. Secretion rate was stimulated by intravenous infusion of either cerulein (0.2 microgram/kg h) or carbachol (10 nmol/kg h) starting simultaneously with or 180 min before the injection of the labeled methionine. Secretory proteins were analyzed by sodium dodecyl sulfate (SDS) gel electrophoresis or by nondenaturing gel electrophoresis followed by determination of the radioactivity associated with the individual proteins. Similar to unstimulated controls in all experiments, an early secretion of newly synthesized trypsinogen and chymotrypsinogen was found, whereas amylase and lipase were secreted only after a certain lag period. The results suggest that the intracellular transit of endoproteases is faster than that of other enzymes, irrespective of whether or not secretagogues were applied.

Identification of rat pancreatic secretory proteins after separation by high-performance liquid chromatography.

In the present study an improved method of reversed-phase high-performance liquid chromatography (HPLC) for separation of rat pancreatic juice proteins is introduced. Aliquots of pancreatic juice were saved from conscious rats during basal secretion. The secretory proteins were separated on a wide-pore silica column by use of a multistep acetonitrile/water gradient. Up to 14 individual peaks could be separated by one run. Molecular weight analysis by sodium dodecyl sulfate (SDS)-gels allowed identification of peaks representing amylase, lipase, procarboxypeptidases, proelastase, chymotrypsinogen, and trypsinogen. Injection of pure rat amylase increased one specific peak which was assumed to represent amylase in the juice profile. Small amounts of residual enzymatic activities were measured for amylase, trypsin, and chymotrypsin in material of certain peaks. Activities of lipase, ribonuclease, and carboxypeptidases were not found, which reflected degradation of these enzymes by the separation procedure. High activities of phospholipase A2 were detected in one specific, early-eluting peak. Reversed-phase HPLC offers precise, reproducible, and rapid separation of the major proteins of rat pancreatic juice.

Resolution of human exocrine pancreatic juice proteins by reversed-phase high performance liquid chromatography (HPLC).

Exocrine proteins contained in human pancreatic juice were analyzed by reversed-phase high performance liquid chromatography (RP-HPLC). Pancreatic juice was saved by endoscopic retrograde cannulation of the main pancreatic duct in 17 persons: 12 without pancreatic disease, 3 patients suffering from recurrent acute pancreatitis probably due to pancreas divisum, 1 patient with a carcinoma of the pancreas, and 1 patient with chronic calcified pancreatitis. The juice proteins were separated on a silica column (Nucleosil 300-7 RP) by use of a multistep acetonitrile/water gradient (+0.1% trifluoroacetic acid). Up to 18 individual peaks could be separated by one analytical run (60 min). Molecular weight analysis by sodium dodecyl sulfate-gel electrophoresis indicated the presence of enzymes such as amylase, prophospholipase A2, procarboxypeptidases, trypsinogens, and chymotrypsinogens in certain peaks. Small residual enzymatic activities correlating with certain peaks were detected for amylase and chymotrypsin, and high residual activities were found for phospholipase A (recovery of enzymatic activity compared with the original sample amounted to 65%). Significant amounts of cathodic trypsin-like immunoreactivity were found in two certain peaks. By always loading 350 micrograms of protein/injection on the column the profiles of various samples showed similar patterns. Repeated injections of aliquots revealed highly reproducible profiles. RP-HPLC offers precise, reproducible, and rapid separation of the major proteins of human pancreatic juice.

Rat pancreatitis-associated protein is expressed in relation to severity of experimental pancreatitis.

To study the relation between expression of the pancreatitis-associated protein (PAP) and severity of pancreatitis in rats, different degrees of experimental pancreatitis were induced by a 1-, 3-, or 5-h cerulein infusion (5 micrograms kg-1 h-1). This treatment decreased pancreatic volume secretion to below 10%. Immediately after infusion, the secretion rate increased to approximately 50% of control. Within 1 day, volume and bicarbonate secretion rates were not different from controls. At this point, protein secretion amounted to 30% of control, but only in animals receiving the 3- or 5-h dose. The values increased to 40-60% within 3 days. In all groups, the isoenzyme pattern was not influenced by the cerulein treatment. One day after induction of pancreatitis, the PAP was found in pancreatic juice in concentrations related to the dose of cerulein given. By immunohistochemical techniques, the protein was localized over acinar cells, but was not detectable in interstitial tissue, islets, or in the healthy exocrine pancreas. Pathomorphologic alterations in the pancreas were quantified by a scoring system. One and 2 days after the treatment, a more severe pancreatitis and more elevated levels of PAP were found in animals treated with the higher dose of cerulein. It is concluded that PAP is expressed in the pancreas in relation to the severity of cerulein-induced pancreatitis.

A comparison of lipase and amylase in the diagnosis of acute pancreatitis in patients with abdominal pain.

The clinical value of amylase and lipase measurement for the diagnosis of acute pancreatitis was evaluated in 253 patients presenting with acute abdominal pain. Acute pancreatitis was detected in 32 patients by computed tomography or ultrasound. In the serum samples collected on days 0-1 after the onset of symptoms, lipase was elevated in 100% and amylase in 95%. A 95% sensitivity/specificity was reached at a lipase cutoff near twofold above normal. The receiver-operating characteristics (ROC) showed similar curves for both enzymes, lipase being slightly superior to amylase. The ROC curves from days 2-3 demonstrated a much lower sensitivity/specificity of both enzymes. Lipase, however, was notably superior to amylase: at a sensitivity of 85% the specificity of lipase (amylase) was 82% (68%). In samples from days 4-5 the accuracy of the enzyme assays was even worse; at a sensitivity of 60% the specificity did not increase above 70%. The diagnostic value of simultaneous measurement of amylase and lipase was tested at different cutoffs in two groups: the OR group, in which one of the two parameters had to be elevated, and the AND group, in which both parameters had to be above normal. Combination of both parameters mainly improved the specificity of the assay (from 91 to 98% on days 2-3 and from 93 to 97% on day 4-5) but only when, in the OR group, twofold elevated amylase was combined with lipase. We conclude that the simultaneous determination of serum lipase and amylase marginally improved the diagnosis of acute pancreatitis in patients with acute abdominal pain, however, the sensitivity of the assay with samples collected 4-5 days after onset of the disease remained low.

The pancreatitis-associated protein in hereditary and chronic alcoholic pancreatitis.

The pancreatitis-associated protein (PAP) was investigated in patients with hereditary and chronic alcoholic pancreatitis. Blood levels of pancreatic enzymes and PAP were measured in nine families with hereditary pancreatitis; in three of them, the mutation N21I, and in six, the R117H variant of the cationic trypsinogen were present. In all family members, similar to controls, only normal values of the PAP were found. There was no evidence for polymorphism of the PAP gene in patients with hereditary or alcoholic pancreatitis. Immunohistochemically PAP was detected in the apical parts of the acinar cells but not in ducts, interstitial tissue, islets, or blood vessels. Intensity of PAP labeling was directly related to the deterioration of the acinar units, and its concentration was inversely related to chymotrypsinogen immunoreactivity in the same tissue. Similar immunohistochemical findings were present in chronic alcoholic and hereditary pancreatitis. We conclude that there is a lack of PAP polymorphism in hereditary and alcoholic pancreatitis and that expression of the PAP in both groups of patients is related to the degree of cellular damage of the pancreas.