Michael Hocke

The EFSUMB guidelines and recommendations on the clinical practice of contrast enhanced ultrasound (CEUS): Update 2011 on non-hepatic applications

Authors F. Piscaglia1, C. Nolsøe2, C. F. Dietrich3, D. O. Cosgrove4, O. H. Gilja5, M. Bachmann Nielsen6, T. Albrecht7, L. Barozzi8, M. Bertolotto9, O. Catalano10, M. Claudon11, D. A. Clevert12, J. M. Correas13, M. D’Onofrio14, F. M. Drudi15, J. Eyding16, M. Giovannini17, M. Hocke18, A. Ignee19, E. M. Jung20, A. S. Klauser21, N. Lassau22, E. Leen23, G. Mathis24, A. Saftoiu25, G. Seidel26, P. S. Sidhu27, G. ter. Haar28, D. Timmerman29, H. P. Weskott30

Improved Differentiation of Pancreatic Tumors Using Contrast-Enhanced Endoscopic Ultrasound

BACKGROUND & AIMS Endoscopic ultrasound is a widely accepted imaging method for staging of ductal adenocarcinoma and the localization of neuroendocrine tumors of the pancreas. We prospectively evaluated conventional color Doppler imaging and contrast-enhanced endoscopic Doppler ultrasound (CE-EDUS) as a new imaging technique for further characterization and differentiation of solid pancreatic tumors. METHODS From 300 patients with pancreatic lesions investigated using contrast-enhanced endoscopic ultrasound we could finally include 93 patients with an undetermined, solitary, predominantly solid, lesion 40 mm or less, and a definite histologically proven diagnosis. After bolus injection of the contrast agent SHU 508A 4 g (400 mg/dL) the vascular pattern of the lesion during the arterial phase was compared with the vascularity of the residual pancreatic parenchyma. RESULTS Color Doppler imaging did not reveal vascularity of the pancreatic parenchyma in any of the patients, and therefore tumor hypovascularity could not be determined in contrast to all CE-EDUS-examined patients revealing at least some degree of parenchymal vascularity. Fifty-seven of 62 patients with ductal adenocarcinoma of the pancreas showed a hypovascularity of the tumor using CE-EDUS. All other pancreatic lesions revealed an isovascular or hypervascular pattern using contrast-enhanced endoscopic ultrasound (20 neuroendocrine tumors, 10 serous microcystic adenomas, and 1 teratoma). Hypovascularity as a sign of malignancy in contrast-enhanced endoscopic ultrasound obtained 92% (82%-97%) sensitivity and 100% specificity (89%-100%). CONCLUSIONS Contrast-enhanced endoscopic ultrasound is effective in differentiating small solid pancreatic tumors of different origin in most cases. Hypovascularity indicates malignancy of pancreatic tumors.

Accuracy of endoscopic ultrasound elastography used for differential diagnosis of focal pancreatic masses: a multicenter study.

BACKGROUND AND STUDY AIMS Endoscopic ultrasound (EUS) elastography represents a new imaging procedure that might characterize the differences of hardness and strain between diseased tissue and normal tissue. The aim of this study was to assess the efficiency of EUS elastography for the differentiation of focal masses in chronic pancreatitis and pancreatic cancer. PATIENTS AND METHODS The study group comprised 258 patients with focal pancreatic masses included prospectively at 13 participating centers. Qualitative analysis of the diagnoses made by two expert doctors using all recorded video clips was performed in order to test the interobserver variability. A post-processing software analysis was used to examine the EUS elastography videos by calculating average-hue histograms of individual elastography images. The quantitative information was used to calculate intra-observer variability and the accuracy of the method. RESULTS Qualitative analysis of the recorded videos revealed a kappa value of 0.72. Intra-observer variability analysis revealed that the single measure intraclass correlation ranged between 0.86 and 0.94. The average-hue histogram analysis of the data indicated a sensitivity of 93.4 %, a specificity of 66.0 %, a positive predictive value of 92.5 %, a negative predictive value of 68.9 %, and an overall accuracy of 85.4 %, based on a cut-off value of 175. Area under the receiver operating characteristic curve (AUROC) was 0.854 ( P < 0.0001) with a confidence interval of 0.804 - 0.894. CONCLUSION The value of quantitative analysis of EUS elastography recordings was proven by good reproducibility of the videos, as well as good parameters of the AUROC analysis. (Clinical Trials.gov identifier: CT00909103).

Efficacy of an Artificial Neural Network–Based Approach to Endoscopic Ultrasound Elastography in Diagnosis of Focal Pancreatic Masses

BACKGROUND & AIMS By using strain assessment, real-time endoscopic ultrasound (EUS) elastography provides additional information about a lesions characteristics in the pancreas. We assessed the accuracy of real-time EUS elastography in focal pancreatic lesions using computer-aided diagnosis by artificial neural network analysis. METHODS We performed a prospective, blinded, multicentric study at of 258 patients (774 recordings from EUS elastography) who were diagnosed with chronic pancreatitis (n = 47) or pancreatic adenocarcinoma (n = 211) from 13 tertiary academic medical centers in Europe (the European EUS Elastography Multicentric Study Group). We used postprocessing software analysis to compute individual frames of elastography movies recorded by retrieving hue histogram data from a dynamic sequence of EUS elastography into a numeric matrix. The data then were analyzed in an extended neural network analysis, to automatically differentiate benign from malignant patterns. RESULTS The neural computing approach had 91.14% training accuracy (95% confidence interval [CI], 89.87%-92.42%) and 84.27% testing accuracy (95% CI, 83.09%-85.44%). These results were obtained using the 10-fold cross-validation technique. The statistical analysis of the classification process showed a sensitivity of 87.59%, a specificity of 82.94%, a positive predictive value of 96.25%, and a negative predictive value of 57.22%. Moreover, the corresponding area under the receiver operating characteristic curve was 0.94 (95% CI, 0.91%-0.97%), which was significantly higher than the values obtained by simple mean hue histogram analysis, for which the area under the receiver operating characteristic was 0.85. CONCLUSIONS Use of the artificial intelligence methodology via artificial neural networks supports the medical decision process, providing fast and accurate diagnoses.

Improved characterisation of solitary solid pancreatic tumours using contrast enhanced transabdominal ultrasound

BackgroundContrast enhanced ultrasound (CEUS) is a new imaging method for detection and characterisation of liver tumours. The role of CEUS in pancreatic disease is less obvious. We prospectively evaluated CEUS for characterization of undetermined solid pancreatic lesions (gold standard histology).Patients and methodsA total of 112 solitary undetermined pancreatic masses (70 ductal adenocarcinoma and 42 neoplastic nodules of other origin) were prospectively examined in patients without metastatic disease using transabdominal ultrasound. Tumour enhancing features were analyzed in comparison to the surrounding pancreatic parenchyma in patients with adequate visualisation.ResultsThe sign of iso-hypervascularity as a sign of non-ductal adenocarcinoma showed a sensitivity of 100%, specifity of 90% and accuracy of 93.8%. The sign of hypovascularity as a sign of ductal adenocarcinoma showed a sensitivity of 90%, specifity of 100% and an accuracy of 93.8%.ConclusionCEUS allows differential diagnosis of ductal adenocarcinoma and non-ductal adenocarcinoma (mainly neuroendocrine tumours and (microcystic) serous pancreatic adenoma) in the most of cases.

Pitfalls and Artefacts using Contrast Enhanced Ultrasound

Ultrasound is the method of choice in the detection and characterization of diffuse and focal organic diseases. For B-mode and colour (power) Doppler ultrasound, besides manual skills, (hands-on) a technical knowledge about ultrasound images is of the upmost importance for the investigator. Contrast enhanced ultrasound (CEUS) has become an important diagnostic tool for hepatic, renal, pancreatic indications and several others due to: (a) an increasing rate of studies resulting in sufficient evidence especially in hepatic indications, (b) a rate of adverse events close to zero (1:10,000 in comparison to iodinated contrast agents from 1-12:100) enabling the application of CEUS in patients with severe renal insufficiency or thyroid gland autonomy, and (c) a reasonable price (depends on the country and influence of the health-care system [reimbursement]) and the dosage used. Mini-doses from 0.1 to 0.4 mL are used depending on the contrast agent and applied indication. Therefore a well founded knowledge concerning the technical aspects of CEUS is important for the investigator to avoid misinterpretation especially when artefacts specific for CEUS occur. Special literature is rare. In the presented article we present pitfalls concerning CEUS. The following aspects are considered and illustrated by images: (i) acoustic power (mechanical index) and other aspects resulting in micro bubble destruction, (ii) the possibility of false positive contrast signals in non-vascularized areas, (iii) attenuation caused by too high contrast agent dose, (iv) influence of the frame rate on the spatial resolution, (v) dealing with deep located lesions, (vi) differences in focus positioning in detection and characterization studies, (vii) advantages and disadvantages of replenishment studies, (viii) reliability of contrast enhanced spectral Doppler measurements.

Transgastral Retroperitoneal Endoscopy in Septic Patients with Pancreatic Necrosis or Infected Pancreatic Pseudocysts

OBJECTIVE Peripancreatic fluid collections are common complications of acute pancreatitis or acute exacerbations of chronic pancreatitis. Surgery is required when these fluid collections become infected or cause obstruction or pain. However, morbidity and mortality after surgery in these cases are still too high, therefore minimally invasive approaches have been encouraged. The aim of this study was to evaluate the feasibility of endoscopic ultrasound-guided transmural drainage with intracystic endoscopy and necrosectomy. MATERIAL AND METHODS From 2000 to 2006 30 patients (age: 57 +/- 10 years, range: 34 - 74 years) with an infected pancreatic pseudocyst or infected pancreatic necrosis were included in the study. The diagnosis of infection in patients who had fever despite an adequate antibiotic regime was confirmed by endoscopic fine needle aspiration with a positive bacterial or mycological result. The mean C-reactive protein value before treatment was 202 +/- 58 mg/L and the mean leukocyte count was 13.25 +/- 4.75 GPt/L. Transgastric cyst drainage was performed using a therapeutic endoscopic ultrasound probe (Pentax 38 UX or Olympus GF UCT 140) with insertion of an 8-Fr double pigtail prosthesis. After balloon dilatation (12 mm) a normal gastroscope was inserted into the cavity and all the fluid and easy removable necrosis were removed. The prosthesis was removed 4 weeks after the end of the endoscopic treatment. Clinical and ultrasound follow-up were carried out 3 and 6 months after removal of the prosthesis. The mean follow-up was 60 weeks. RESULTS The technical success of the procedure was 96.7 %, the long-term success was 83.4 %. On average 2.7 (range: 1 - 16) procedures were necessary for complete removal of necrosis and the remaining fluid. Major complications (bleeding, perforation, fistulation) occurred in 10 %. In 10 % a secondary operation was necessary. The overall mortality rate was 6.6 %. DISCUSSION Endoscopic treatment of infected pseudocysts and infected postacute pancreatic necrosis using transgastral retroperitoneal endoscopy with fluid and necrosis removal is a minimally invasive and effective procedure in patients with acute pancreatitis or acute exacerbation of chronic pancreatitis. However, the mortality rate of 6.6 % has to be taken into account.

Contrast-enhanced endoscopic ultrasound in the diagnosis of autoimmune pancreatitis.

Autoimmune pancreatitis is a rare condition which can mimic pancreatic carcinoma. We report the cases of 10 patients with autoimmune pancreatitis investigated in two different centers using contrast-enhanced endosonography. In these patients, contrast-enhanced endosonography showed a unique vascularization pattern which makes it easy to discriminate between autoimmune pancreatitis and lesions caused by pancreatic cancer. Lesions caused by autoimmune pancreatitis and the surrounding pancreas typically showed hypervascularization, whereas lesions caused by pancreatic cancer were hypovascularized. This was true for all patients with the exception of one who showed a normal vascularization pattern in comparison with normal patients and no signs of hypovascularization. Final diagnosis was achieved either by transcutaneous biopsy or a combination of endoscopic fine-needle aspiration with IgG4 immunostaining of the sample. All patients were followed up over a period of at least 12 months to rule out pancreatic carcinoma.

The IL‐10 gene is not involved in the predisposition to inflammatory bowel disease

Although genetic predisposition for inflammatory bowel disease (IBD) is well established, little is known about the accountable genes. The pathogenesis of IBD is characterized by an imbalanced activation of Th1‐ and Th2‐lymphocytes. IL‐10 represents an anti‐inflammatory cytokine which downregulates the production of Th1‐derived cytokines. To evaluate the role of the IL‐10 gene in IBD, two polymorphisms in the promoter region (G/A at position —1082 and C/A at position —592) were genotyped in 142 patients with Crohns disease (CD), 104 patients with ulcerative colitis (UC), and 400 healthy controls. Significant differences were not apparent, neither in the allele frequencies of either polymorphism, nor in the haplotype frequencies. Screening of the coding region of the IL‐10 gene by polymerase chain reaction — single strand conformation polymorphism (PCR‐SSCP) analysis revealed a rare sequence variation in exon 1 leading to an amino acid exchange (G→A; G15R) in two patients with CD and five healthy controls. Therefore, polymorphisms of the IL‐10 gene are not demonstrably involved in the predisposition of IBD in our cohorts of patients.

EFSUMB Guidelines on Interventional Ultrasound (INVUS), Part III – Abdominal Treatment Procedures (Short Version)

The third part of the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) Guidelines on Interventional Ultrasound assesses the evidence for ultrasound-guided and assisted interventions in abdominal treatment procedures. Recommendations for clinical practice are presented covering indications, contraindications, safety and efficacy of the broad variety of these techniques. In particular, drainage of abscesses and fluid collections, interventional tumor ablation techniques, interventional treatment of symptomatic cysts and echinococcosis, percutaneous transhepatic cholangiography and drainage, percutaneous gastrostomy, urinary bladder drainage, and nephrostomy are addressed (short version; a long version is published online).