Tim O. Hirche

Indications and limitations of endoscopic ultrasound elastography for evaluation of focal pancreatic lesions

BACKGROUND AND STUDY AIM Endoscopic-ultrasound-guided elastography (EUS-elastography) is a recently introduced imaging procedure that distinguishes tissues on the basis of their specific consistency. The aim of this prospective study was to investigate the role of this new technique in the characterization and differentiation of focal pancreatic lesions. PATIENTS AND METHODS This prospective study enrolled 70 patients with unclassified solid lesions of the pancreas and 10 controls with a healthy pancreas. In all patients elastography recordings were compared with cytology/histology findings as the gold standard. RESULTS Adequate EUS-elastography of the pancreas was performed in all healthy controls but in only 56 % of patients with solid pancreatic lesions. The main limitation of elastographic image acquisition was incomplete delineation of the border of lesions greater than 35 mm in diameter (39 %) or of lesions at some distance from the transducer (10 %). Elastographic recordings were also hampered by the fact that the surrounding tissue, which is used as an internal reference standard for strain calculation, was insufficiently displayed in the case of larger lesions. The reduced ratio of target to surrounding tissue resulted in the formation of color artifacts and in impaired reproducibility. In contrast, the majority of lesions smaller than 35 mm in diameter were adequately and reproducibly evaluated by EUS-elastography (91 %). The clinical use for differential diagnosis, however, seems limited, since strain images from all kinds of pancreatic masses were found to be harder than the surrounding tissues, irrespective of the underlying nature of the lesion (i. e., malignant vs. benign). EUS-elastography predicted the nature of pancreatic lesions with poor diagnostic sensitivity (41 %), specificity (53 %), and accuracy (45 %). CONCLUSION EUS-elastography of the pancreas has the potential to obtain some complementary information that would improve tissue characterization. Its clinical utility, however, remains questionable, and it seems unlikely that the information provided will obviate the necessity of obtaining tissue samples for confirmation of a final pathologic diagnosis.

Real-time tissue elastography in the diagnosis of autoimmune pancreatitis.

Endoscopic ultrasound (EUS) elastography distinguishes tissues on the basis of their specific consistency. The preoperative diagnosis of autoimmune pancreatitis (AIP) is of the utmost importance in order to avoid surgery. The aim of this prospective evaluation of five patients was to investigate the role of this new technique in the characterization of mass lesions caused by AIP, with histology as the gold standard. All five patients with AIP presented with a characteristic stiff elastographic pattern not only of the mass lesion but also of the surrounding pancreatic parenchyma, which was not found in 17 patients with ductal adenocarcinoma and 10 healthy subjects. EUS elastography of the pancreas shows a typical and unique finding with homogenous stiffness of the whole organ, and this distinguishes AIP from the circumscribed mass lesion in ductal adenocarcinoma.

The value of routinely performed ultrasonography in patients with Crohn disease.

Background: In active Crohn disease (CD), abdominal ultrasound can demonstrate morphological changes in the bowel wall. By contrast, the role of ultrasonography in periods with no disease activity has never been evaluated. In this prospective study we investigated the outcome of routinely performed abdominal ultrasonography in CD patients irrespective of symptoms and disease activity. Methods: 255 consecutive patients with chronic CD (117 M, 138 F, mean age ( ± s ) 38 ± 14) were evaluated by high-resolution ultrasonography of the bowel wall and abdomen. The findings were graded with respect to further diagnostic and/or therapeutic implications. In addition, the CD activity index (CDAI) was determined. In patients with pathological sonographic findings, complementary procedures (e.g. endoscopy, computed tomography, biopsy or operation) were performed to validate the suspected diagnosis. Results: In 46/255 (18%) patients with CD, the diagnosis of a transmural inflammatory reaction (TMR) with or without fistula was made by ultrasonography. In respect of CDAI, 29/46 (63%) of these patients were graded as active disease (CDAI >150) and 17/46 (37%) as inactive disease (CDAI h 150). Of the 17 patients with a TMR and CDAI h 150, 4 patients revealed interenteric fistula, 7 patients mesenteric or perirectal fistula, whereas 6 patients presented with a transmural mesenteric inflammatory reaction without fistula. All fistulae were confirmed by radiography. Ultrasonography of the remaining abdominal organs revealed pathological findings with further diagnostic implications in 25/255 (10%) patients and with therapeutic implications in 9/255 (4%) patients. Conclusion: Routinely performed ultrasonography of the abdomen reveals pathological findings with therapeutic implications not only in symptomatic but also in asymptomatic patients with CD. It can therefore be recommended as a screening tool for this group of patients.

Sonographic findings of the hepatobiliary-pancreatic system in adult patients with cystic fibrosis

Sonography of the liver, biliary system, and pancreas in adult patients with cystic fibrosis is by far less systematically documented than in pediatric patients with cystic fibrosis. In this prospective study, duplex sonographic findings of the liver, biliary system, and pancreas in adult patients with cystic fibrosis were compared with those of healthy control subjects.

Sonographic detection of perihepatic lymphadenopathy is an indicator for primary sclerosing cholangitis in patients with inflammatory bowel disease

AimPrimary sclerosing cholangitis (PSC) is a frequent complication in patients with inflammatory bowel disease (IBD). While hyperplasia of the perihepatic lymph nodes has been described in patients with PSC, its prevalence and cause in IBD patients remains obscure. In the present study we address the question of whether ultrasound (US) examination is useful to detect perihepatic lymphadenopathy and improve the diagnostic accuracy for PSC in patients with underlying IBD.MethodsA total of 310 consecutive IBD patients were prospectively evaluated by US for enlarged perihepatic lymph nodes, as well as serologic testing for cholestasis-indicating enzymes. In patients with positive test results, viral or autoimmune liver disorders were excluded by serum testing. Next, the presence of PSC was confirmed/excluded by endoscopic retrograde cholangiography (ERC).ResultsPerihepatic lymphadenopathy was detected by US in 27 of 310 (9%) patients. In 9 (33%) of those, serologic testing identified an underlying autoimmune or viral hepatitis. In the remaining 18 patients, ERC confirmed PSC in 17 (94%) and excluded it in 1. Elevated cholestasis parameters were found in 43 of 310 (14%) patients and 5 (12%) of those were diagnosed with autoimmune or viral hepatitis. In the remaining 38 patients, ERC confirmed PSC in 15 (39%) and excluded it in 23 (61%). Therefore, when autoimmune or viral hepatitis was excluded, enlarged lymph nodes in US predicted PSC more accurately than conventional serum parameters alone (PPV 94 and 39%, respectively [ P<0.001]), and the sensitivity ratio increased by a factor of 1.13 in favor of the US examination.ConclusionIn patients with IBD, detection of enlarged perihepatic lymph nodes is a highly predictive indicator for the presence of PSC. Alternative causes of perihepatic lymphadenopathy have to be excluded.

ULTRASOUND OF THE PLEURAE AND LUNGS

The value of ultrasound techniques in examination of the pleurae and lungs has been underestimated over recent decades. One explanation for this is the assumption that the ventilated lungs and the bones of the rib cage constitute impermeable obstacles to ultrasound. However, a variety of pathologies of the chest wall, pleurae and lungs result in altered tissue composition, providing substantially increased access and visibility for ultrasound examination. It is a great benefit that the pleurae and lungs can be non-invasively imaged repeatedly without discomfort or radiation exposure for the patient. Ultrasound is thus particularly valuable in follow-up of disease, differential diagnosis and detection of complications. Diagnostic and therapeutic interventions in patients with pathologic pleural and pulmonary findings can tolerably be performed under real-time ultrasound guidance. In this article, an updated overview is given presenting not only the benefits and indications, but also the limitations of pleural and pulmonary ultrasound.

Myeloperoxidase-dependent Inactivation of Surfactant Protein D in Vitro and in Vivo

Surfactant protein D (SP-D) plays diverse and important roles in innate immunity and pulmonary homeostasis. Neutrophils and myeloperoxidase (MPO) colocalized with SP-D in a murine bacterial pneumonia model of acute inflammation, suggesting that MPO-derived reactive species might alter the function of SP-D. Exposure of SP-D to the complete MPO-H2O2-halide system caused loss of SP-D-dependent aggregating activity. Hypochlorous acid (HOCl), the major oxidant generated by MPO, caused a similar loss of aggregating activity, which was accompanied by the generation of abnormal disulfide-cross-linked oligomers. A full-length SP-D mutant lacking N-terminal cysteine residues and truncation mutants lacking the N-terminal domains were resistant to the oxidant-induced alterations in disulfide bonding. Mass spectroscopy of HOCl-treated human SP-D demonstrated several modifications, but none involved key ligand binding residues. There was detectable oxidation of cysteine 15, but no HOCl-induced cysteine modifications were observed in the C-terminal lectin domain. Together, the findings localize abnormal disulfide cross-links to the N-terminal domain. MPO-deficient mice showed decreased cross-linking of SP-D and increased SP-D-dependent aggregating activity in the pneumonia model. Thus, MPO-derived oxidants can lead to modifications of SP-D structure with associated alterations in its characteristic aggregating activity.

Clinical Relevance of Perihepatic Lymphadenopathy in Acute and Chronic Liver Disease

Background and Goal In chronic virus hepatitis C the total perihepatic lymph node volume reflects the underlying liver histology, viral load, and the hosts immunologic response. Assessment of the perihepatic lymph node volume may represent an important diagnostic tool, and may help streamline the patients further management. The purpose of this study was to prospectively assess whether perihepatic lymphadenopathy is associated with the etiology of acute (and chronic) hepatitis. Study In 40 consecutive patients with transaminases >500 U/L without known liver disease the total perihepatic lymph node volume was assessed and compared with the ultrasound findings in 263 patients with known chronic liver disease and also 49 healthy controls. Results Thirty-one out of 40 patients were diagnosed with an acute viral hepatitis, whereas 9/40 patients were diagnosed with a toxic cause, resulting in acute liver damage. In all sonographically evaluated patients with acute viral hepatitis (29/31, 94%) perihepatic lymphadenopathy was found, whereas none of the patients with a toxic cause demonstrated lymphadenopathy. In chronic liver disease, perihepatic lymphadenopathy was present in 86% of viral, in 90% of autoimmune hepatitis, in 100% of primary sclerosing cholangitis, in 97% of primary biliary cirrhosis, but only in 6% of hemochromatosis, in 1% of fatty liver disease, and in 4% of cholecystolithiasis. Conclusions Perihepatic lymphadenopathy is found in infectious and autoimmune liver diseases, but not in metabolic or toxic liver damage. The absence of perihepatic lymph nodes in acute liver failure should lead to intensive search for a toxic or metabolic cause.

Increased frequency of regulatory T Cells and selection of highly potent CD62L+ cells during treatment of human lung transplant recipients with rapamycin

The currently available immunosuppressive agents applied in human transplantation medicine are highly potent in the protection from acute allograft rejection. However, long‐term allograft survival is still poor as these drugs fail to sufficiently prevent chronic allograft rejection. Naturally occurring regulatory T cells have been postulated as the key players to establish long‐lasting transplantation tolerance. Thus, the development of immunosuppressive regimens which shift the pathological balance of cytopathic versus regulatory T cells of human allograft recipients towards a protective T‐cell composition is a promising approach to overcome limitations of current transplantation medicine. Thirty‐three patients that received rapamycin (RPM) or calcineurin inhibitor treatment following lung transplantation were included and their T‐cell compartments analysed. Twelve healthy volunteers without history of lung disease served as controls. In this article, we show that treatment of human lung transplant recipients with RPM is associated with an increased frequency of regulatory T cells, as compared with treatment with calcineurin inhibitors or to healthy controls. Moreover, regulatory T cells during treatment with RPM were CD62Lhigh, a phenotype that displayed an enhanced immunosuppressive capacity ex vivo. Our data support the use of RPM in human lung transplant recipients and undertaking of further prospective studies evaluating its impact on allograft and patient survival.

Indications and limitations of perineal ultrasound examination

TO THE EDITOR: Perineal or perianal ultrasound (PNUS) is an effective, inexpensive, easily available and not painful but as of now rarely applied diagnostic tool important in the hands of gastroenterologists. PNUS is helpful in detecting a variety of pathological conditions of the rectum and perineum, such as transmural inflammation, fistula and abscesses in patients with inflammatory bowel disease. It is more flexible to apply than endorectal ultrasound (ERUS), particularly when oblique processes of transsphincteric fistulas are to be examined [1]. Indications for PNUS are perianal complaints as well as lesions of the entire perianal region [2,3]. It is particularly useful if clinical examination, ERUS or magnetic resonance imaging (MRI) cannot be performed (e.g., due to severe pain when introducing the probe into the anus, particularly in children) [4]. Indications are summarized in Table I. High frequency probes allow discrimination and differentiation of subtle tissue structures that are in close proximity to the surface. Lesions within in deeper tissues can also be visualized. The complete evaluation of the sphincter for diagnostic work-up of incontinence remains the domain of ERUS, however, PNUS can add additional information on extrasphincteric complications (e.g., fistula, abscesses) [5]. The most frequent causes for perianal and pararectal fistula as well as abscesses are crypto-glandular inflammations, that expand into the sphincteric region, as well as inflammatory bowel diseases [6,7]. In addition, venereal and neoplastic diseases can also cause fistula and abscess formation. Complex fistula that involve the M. sphincter ani externus, M. levator ani and/or M. obturatorius can not be assessed by conventional PNUS alone [8]. However, discrimination of the fistula by PNUS can be greatly enhanced by instillation of contrast agents over the external ostium of the fistula, e.g. using SonoVue. Hydrogen peroxide or sparkling mineral water can be used as more economical ultrasound contrast agents [9]. For staging of perirectal tumours, PNUS can be used complimentary to conventional ERUS. The PNUS examination allows a detail resolution of < 1 mm, which improves recognition of the depth of tumour infiltration. Due to the improved detail resolution by ultrasound imaging a revision of the UICC classification for anal carcinoma has been suggested including analysis of the infiltration of the different portions of the sphincter musculature [10]. A very valuable extension of the diagnostic application of PNUS is its supportive role during invasive interventions, such as drainage of fluids or targeted puncture of lesions. For this purpose, specialized transducers with a built in needle holder are available. However, conventional curved array probes can be used for free hand punctures, particularly if the lesion of interest is close to the surface and large enough. A condition sine qua non for interventions in the very sensitive perineal region is the appropriate use of local anaesthesia or analgo-sedation [11].