[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.

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.

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.

Value of liver elastography and abdominal ultrasound for detection of complications of allogeneic hemopoietic SCT.

Hepatic complications contribute to morbidity and mortality after allogeneic hemopoietic SCT. Liver Doppler ultrasound and elastography represent promising methods for pretransplant risk assessment and early detection of complications. Ultrasound (liver and spleen size, liver perfusion) and elastography (transient elastography (TE); right liver lobe acoustic radiation force impulse imaging (r-ARFI); left liver lobe ARFI (l-ARFI)) were prospectively evaluated in patients with indications for allo-SCT. Measurements were performed before and repeatedly after SCT. Results were compared with the incidence of life-threatening complications and death during the first 150 days after SCT. Of 59 included patients, 16 suffered from major complications and 9 of them died within the follow-up period. At baseline, liver and spleen size, liver perfusion, TE and r-ARFI did not differ significantly between patients with and without severe complications. In contrast, l-ARFI was significantly elevated in patients who later developed severe complications (1.58±0.30 m/s vs 1.37±0.27 m/s, P=0.030). After SCT, l-ARFI values remained elevated and TE showed increasing liver stiffness in patients with complications. The value of conventional liver ultrasound for prediction of severe SCT complications is limited. Increased values for TE and l-ARFI are associated with severe SCT complications and demand further evaluation.

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.

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.

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.

[Chronic pancreatitis--pancreas cancer: influence of genetic factors]. / Chronische Pankreatitis-- Pankreaskarzinom: Einfluss genetischer Faktoren.

Chronic pancreatitis: Only recently mutations in several genes were found in patients with chronic pancreatitis. In those with a familial chronic pancreatitis mutations of the cationic trypsinogen were identified and the variants N29I and R122H lead to an autosomal dominant disease. In this group of patients the mutation N34S of the trypsin inhibitor SPINK1 was detected. In so-called idiopathic pancreatitis both variants of the SPINK1 and of the CFTR (cystic fibrosis transmembrane conductance regular) were identified. Alterations in both genes were also found in patients with alcoholic chronic pancreatitis. The strongest risk factor for chronic pancreatitis were trypsinogen mutations N29I and R122H mutations. However, both SPINK1 and CFTR increased the risk for chronic pancreatitis to a higher level than alcohol consumption. A genetic investigation should be performed in familial disease and younger age, but also in patients without family history and higher age a mutation could be found. Pancreas cancer: In 10% of the patients with pancreas cancer other members of the family were affected from the disease. Some of them belong to well characterized familial syndroms like HNPCC or Peutz-Jeghers-syndrom. In a minority of the others a genetic factor may be found, too. In sporadic disease the development of the tumor is characterized by continued acquirement of genetic alterations described by the PanIN model (pancreatic intraepithelial neoplesia). This means that the evolution of the neoplasia progresses from normal tissue via epithelial hyperplasy (PanIN 1A), papillary hyperplasy without (PanIN 1B) and with dysplasy (PanIN 2) and carcinoma in situ (PanIN 3) to invasive pancreas cancer. The progression is associated with genetic alterations of the cells (mutations of ki-ras, p16, p53 etc.). This results in deterioration of control of the cell cycle and the apoptosis and explains the malignancy of the disease. These findings may be used in the future to develop newer therapeutic principles in order to improve the dismal prognosis of this disease.

[Diagnosis and treatment of acute pancreatitis]. / Diagnostik und Therapie der akuten Pankreatitis.

In patients with abdominal pain, an acute pancreatitis is likely when lipase is elevated more than 3-fold above normal. The diagnosis should be confirmed by an imaging technique (either sonography or CT). The determination of the severity is difficult as all methods (laboratory values, imaging systems, scores) exhibit a significant uncertainty. The regular clinical investigation of the patients is still needed. In contrast to a severe course, in mild or moderate disease the treatment of the patient in an intensive care unit is not obligatory. In biliary pancreatitis the extraction of biliary stones after papillotomy is indicated and in severe disease the procedure should be done without delay. Meanwhile enteral nutrition is standard treatment although the data are not completely convincing. Further measures are administration of pain killers, volume substitution and treatment of pulmonary and renal failure. Although data are not completely clear the prophylactic administration of antibiotics in necrotizing pancreatitis is routine. Puncture of the necrosis may be used to detect the responsible microorganisms. In patients with infected necrosis who deteriorate during conservative treatment, necrosectomy may be an option. There is a tendency to postpone the operation until the necrosis can be clearly separated from non-necrotic tissue. Although a specific pharmacological agent for the treatment of pancreatitis is still not available, the above procedure has led to a significant reduction of mortality in patients with severe acute pancreatitis.

[Clinical implications of genetic risk factors of chronic pancreatitis]. / Chronische Pankreatitis Klinische Bedeutung genetischer Risikofaktoren.

The identification of a specific mutation in the human cationic trypsinogen gene in large kindreds with hereditary pancreatitis was the key to understand the genetic background of chronic pancreatitis. Rapidly, other variants within the same gene were identified-even in small families with a minority of patients. Later, mutations of the most important intrapancreatic trypsin inhibitor SPINK1 were found with high prevalence in patients with idiopathic, tropical and alcoholic chronic pancreatitis. We summarize interesting genetic and biochemical findings, point to clinical features and review recommendations for genetic analysis, follow-up and cancer prevention.

[Therapy of acute pancreatitis]. / Therapie der akuten Pankreatitis.

Despite our increasing knowledge in the pathophysiology of acute pancreatitis therapeutic strategies based on this knowledge, such as inhibition of proteases, are not convincing. It is most likely that these strategies are initiated to late after the onset of pancreatitis. It is of utmost importance to clarify the severity of the disease for planning interdisciplinary approaches: therapy of pain, enteral nutrition via a jejunal tube, as well as treatment of extrapancreatic complications, such as respiratory insufficiency, coagulopathy, and renal insufficiency. A key role plays the exact balance of potential high fluid losses. Prophylactic application of antibiotics such as imipenem in cases of necrotizing pancreatitis to prevent infection is widely used. Infected necroses are an indication for surgery. In biliary pancreatitis one has to remove impacted bile duct stones via ERCP and papillotomy followed by elective cholecystectomy.

[Therapy of chronic pancreatitis]. / Therapie der chronischen Pankreatitis.

Treatment of chronic pancreatitis is dependend on the stage of the disease and its complications. Pain therapy should be based on the knowledge of various causes of pain. In therapy of complications such as bile duct or pancreatic duct strictures interventional endoscopy is usually the first choice followed by surgery. Exocrine insufficiency is treated by porcine pancreatic extracts, endocrine insufficiency by insulin. One has to apply various imaging procedures such as sonography, MRCP, ERCP, endosonography, CT for exact diagnosis of complications and planning various therapeutic strategies. Pseudocysts may be drained via the transgastric, transduodenal, transpapillary or transcutaneous route. Distal prepapillary stenosis of the main pancreatic duct and bile duct stenoses can be drained by stents. Pancreatic duct stones can be desintegrated by shock waves and removed by endoscopy. Early diagnosis of pancreatic carcinoma as a potential complication of long standing inflammation of the pancreas remains an unsolved problem.

Relevance of variants in serum antiproteinases for the course of chronic pancreatitis.

BACKGROUND: Mutations of the pancreatic serine protease inhibitor, Kazal type 1 (SPINK1), the cationic trypsinogen (PRSS1) and the cystic fibrosis transmembrane conductance regulator (CFTR) were reported to be genetic risk factors of chronic pancreatitis (CP). The aim of this study was to determine the role of genetic variants of the main serum antiproteinases alpha-1-antitrypsin (AAT) and alpha-2-macroglobulin (A2M) for the course of chronic pancreatitis. METHODS: 124 patients with non-alcoholic chronic pancreatitis (with PRSS1 or SPINK1 mutations or idiopathic pancreatitis) and 64 healthy controls were investigated for the AAT mutations PiS and PiZ, and the PiM determining variants R101H, V213A, E376D. In 101 subjects, the 'bait region' of A2M was sequenced. A pentanucleotide deletion in the bait region of A2M was analysed in 147 chronic pancreatitis (CP) patients and 87 controls. RESULTS: The lowest prevalences of V213A and E376D were found in PRSS1 patients, whereas an increased rate of these mutations was present in the SPINK1 group, and the highest prevalence was found in patients with idiopathic pancreatitis. The prevalence of PiM variants was higher in patients with early onset CP than in late onset (P < 0.05 for E376D). The coding region of the bait region of A2M was of wild type in all investigated subjects. The A2M pentanucleotide deletion showed a homogenous distribution in patients and controls. CONCLUSIONS: Our study suggests a moderating, but not predominant, role of AAT variants in the course of chronic non-alcoholic pancreatitis.