[Endovascular Therapy of Splanchnic Artery Aneurysms: For Each and Every Aneurysm?] / Endovaskuläre Therapie von Viszeralarterienaneurysmata ­ geht das immer?

True visceral artery aneurysms (VAA) and visceral artery pseudoaneurysms (VAPA) are located in the celiac trunk, the superior mesenteric artery and inferior mesenteric artery. In addition to surgical treatment, endovascular embolisation therapy of visceral aneurysms and pseudoaneurysms is an alternative interventional method that has developed precipitously over the last two decades and is considered a first-choice method in many centres. The procedure is characterised by a high technical success rate with a low complication rate. This article presents the basic principles of endovascular treatment and discusses the indications and limitations of the procedure.

HMGA1 and HMGA2 protein expression correlates with advanced tumour grade and lymph node metastasis in pancreatic adenocarcinoma.

AIMS: Pancreatic ductal adenocarcinoma follows a multistep model of progression through precursor lesions called pancreatic intraepithelial neoplasia (PanIN). The high mobility group A1 (HMGA1) and high mobility group A2 (HMGA2) proteins are architectural transcription factors that have been implicated in the pathogenesis and progression of malignant tumours, including pancreatic cancer. The aim of this study was to explore the role of HMGA1 and HMGA2 in pancreatic carcinogenesis. METHODS AND RESULTS: HMGA1 and HMGA2 expression was examined in 210 ductal pancreatic adenocarcinomas from resection specimens, combined on a tissue microarray also including 40 examples of PanIN and 40 normal controls. The results were correlated with the clinicopathological parameters of the tumours and the outcome of the patients. The percentage of tumour cells showing HMGA1 and HMGA2 nuclear immunoreactivity correlated positively with increasing malignancy grade and lymph node metastasis. Moreover, HMGA1 and HMGA2 expression was significantly higher in invasive carcinomas than in PanINs. No, or very low, expression was found in normal pancreatic tissue. CONCLUSIONS: Our results suggest that HMGA1 and HMGA2 are implicated in pancreatic carcinogenesis and may play a role in tumour progression towards a more malignant phenotype.

Excimer laser atherectomy in complex peripheral artery disease: a prospective European registry.

BACKGROUND: This study aimed to investigate performance, effectiveness, and safety of excimer laser atherectomy for the treatment of complex lower limb artery disease in a real-world setting. METHODS: In our prospective, multicenter registry, consecutive patients with complex lower limb lesions underwent excimer laser atherectomy with optional standard balloon angioplasty, paclitaxel-coated balloon angioplasty, and bailout stenting. Primary outcome was technical success. Secondary outcomes were device performance of the excimer laser system, freedom from target lesion revascularization (TLR), peri-procedural complications, and amputation-free survival in patients with critical limb ischemia (CLI). RESULTS: A total of 294 patients were enrolled at 14 European centers (mean lesion length 109±103 mm, total occlusions 56.8% [167 of 294 lesions], CLI 47.3% [132 of 279 patients]. Adjuvant balloon angioplasty was conducted in 283 (96.3%), and complementary stent implantation in 98 patients (33.3%). Technical success was achieved in 95.3% of patients. Increasing lesion length was associated with decreased laser atherectomy performance (odds ratio [OR] per 10 mm: 0.94 [95% confidence interval [CI] 0.90 to 0.99], P=0.01). A total of 66 patients (22.4%) completed the 12-month follow-up. Freedom from TLR was 83.5% (95% CI: 74.9 to 92.1) at 12 months. Chronic total occlusions were associated with more TLR (OR 5.03 [95% CI: 1.01 to 25.1], P=0.049). Amputation -free survival in patients with CLI was 93.1% (95% CI: 83.9 to 100). CONCLUSIONS: Excimer laser atherectomy substantially contributed to technical success of endovascular treatment of complex infra-inguinal lesions. Freedom from 12-month TLR was reasonable.

Response rate and safety in patients with hepatocellular carcinoma treated with transarterial chemoembolization using 40-µm doxorubicin-eluting microspheres.

PURPOSE: To evaluate the response rate and safety of superselective drug-eluting beats transarterial chemoembolization (DEB-TACE) with doxorubicin-loaded 40-µm microspheres in patients with hepatocellular carcinoma (HCC). METHODS: One hundred and forty-one treatments with doxorubicin-loaded 40-µm microspheres in 83 patients between 2012 and 2017 were retrospectively evaluated. Images of the treated lesions were analyzed before and after each treatment according to mRECIST (modified Response Evaluation Criteria in Solid Tumors). Therapy response (complete response [CR] + partial response [PR]) and disease control (CR + PR + stable disease [SD]) rates were determined, and the correlation between the longitudinal axis (longest diameter of the tumor) and volume was investigated using a newly developed software for systematic tumor response assessment. Additional endpoints were progression-free survival (PFS) and time to progression (TTP). RESULTS: In the target tumors, a therapy response rate of 63.1% and a disease control rate of 95.7% were achieved. There was a good correlation between the measurement of the longitudinal axis and volume of the measured lesion (r value, 0.954). The median PFS was 2.23 months, and the median TTP was 5.91 months. The serious adverse event rate (SAE) was 10.64%. CONCLUSION: Superselective DEB-TACE with 40-µm sized Embozene Tandem™ can be considered an effective and safe treatment, given the number of procedure-related complications.

Primary Intrapulmonary Thymoma Appearing as a Solitary Pulmonary Nodule: The "Master of Disguise" of Lung Tumors?: Case Report.

Primary intrapulmonary thymomas (PITs) are defined as thymomas arising in intrapulmonary locations, without an associated mediastinal component. They are rare lesions, the diagnosis of which can be very difficult. We present a case of PIT in an asymptomatic 74-year-old woman in whom pulmonary nodules were found on pulmonary angiography performed for an episode of pulmonary embolism. She underwent wedge resection and the pathology report revealed a PIT. We also summarize this patient's clinicopathological features and discuss the diagnosis, pathogenesis, and treatment of PIT.

Deep Learning CT Image Reconstruction in Clinical Practice.

BACKGROUND: Computed tomography (CT) is a central modality in modern radiology contributing to diagnostic medicine in almost every medical subspecialty, but particularly in emergency services. To solve the inverse problem of reconstructing anatomical slice images from the raw output the scanner measures, several methods have been developed, with filtered back projection (FBP) and iterative reconstruction (IR) subsequently providing criterion standards. Currently there are new approaches to reconstruction in the field of artificial intelligence utilizing the upcoming possibilities of machine learning (ML), or more specifically, deep learning (DL). METHOD: This review covers the principles of present CT image reconstruction as well as the basic concepts of DL and its implementation in reconstruction. Subsequently commercially available algorithms and current limitations are being discussed. RESULTS AND CONCLUSION: DL is an ML method that utilizes a trained artificial neural network to solve specific problems. Currently two vendors are providing DL image reconstruction algorithms for the clinical routine. For these algorithms, a decrease in image noise and an increase in overall image quality that could potentially facilitate the diagnostic confidence in lesion conspicuity or may translate to dose reduction for given clinical tasks have been shown. One study showed equal diagnostic accuracy in the detection of coronary artery stenosis for DL reconstructed images compared to IR at higher image quality levels. Consequently, a lot more research is necessary and should aim at diagnostic superiority in the clinical context covering a broadness of pathologies to demonstrate the reliability of such DL approaches. KEY POINTS: · Following iterative reconstruction, there is a new approach to CT image reconstruction in the clinical routine using deep learning (DL) as a method of artificial intelligence.. · DL image reconstruction algorithms decrease image noise, improve image quality, and have potential to reduce radiation dose.. · Diagnostic superiority in the clinical context should be demonstrated in future trials.. CITATION FORMAT: · Arndt C, Güttler F, Heinrich A et al. Deep Learning CT Image Reconstruction in Clinical Practice. Fortschr Röntgenstr 2021; 193: 252 - 261.

Alpha-Cyclodextrin Attenuates the Glycemic and Insulinemic Impact of White Bread in Healthy Male Volunteers.

The demonstration of a physiological benefit has recently become an indispensible element of the definition of dietary fibers. In the here-reported pilot study, the effect of alpha-cyclodextrin (alpha-CD) on the postprandial glycemic and insulinemic effect of starch was examined. Twelve fasted, healthy male volunteers received, on three subsequent days, a test breakfast consisting of (A) 100 g fresh white bread (providing 50 g starch) and 250 mL drinking water, (B) the same bread with a supplement of 10 g alpha-CD dissolved in the drinking water, and (C) 25 g alpha-CD dissolved in drinking water. Capillary and venous blood was sampled before the breakfast and in regular intervals for a three-hour period thereafter. Glucose was determined in capillary blood and insulin in the plasma of venous blood samples. Breakfast (A) led to a rapid rise in blood glucose and insulin. In breakfast (B), alpha-CD reduced the areas under the curve of blood glucose and insulin significantly by 59% and 57%, respectively, demonstrating that alpha-CD inhibits and thereby delays starch digestion. Treatment (C) was not associated with a rise of blood glucose. Hence, alpha-CD complies with the current definition of dietary fiber in every respect.

Influence of Interventionists' Experience on Radiation Exposure of Patients Who Underwent Prostate Artery Embolization: 4-Year Results from a Retrospective, Single-Center Study.

PURPOSE: To assess radiation exposure in men undergoing prostate artery embolization (PAE) for the treatment for symptomatic, benign prostatic hyperplasia depending on growing experience of interventional radiologists over a 4-year period. METHODS: A total of 250 consecutive patients underwent PAE at a single center. Data on radiation exposure [dose area product (DAP), effective dose (ED), entrance skin dose (ESD), and fluoroscopy time (FT)] were retrospectively evaluated. Primary outcomes of interest were patient radiation exposure in five consecutive groups of 50 patients each and Pearson correlation with the number of patients treated. RESULTS: Median DAP, ED, and ESD during prostate artery embolization were significantly higher in the first compared to the second 50 patients (56 298 µGym2 vs. 24 709 µGym2, p < 0.001, 146.4 mSv vs. 64.2 mSv, p < 0.001, and 5.1 Gy vs. 2.4 Gy, p < 0.001, respectively). The following consecutive groups did not differ significantly from the respective preceding group in terms of DAP, ED, and ESD. Number of digital subtraction angiography series, FT, and procedure time decreased with increasing operator experience (Pearson's r = - 0.240, p < 0.001, r = - 0.269, p < 0.001, and r = - 0.504, p < 0.001, respectively). Bilateral prostate artery embolization was associated with less ESD and shorter FT than unilateral embolization (median 2.5 vs. 3.5 Gy, p = 0.02, and 26 min vs. 42 min, p < 0.001, respectively). CONCLUSION: Exposure to radiation in men who underwent PAE decreased with growing operator experience and decreasing complexity of procedures.

Impact of Fractional Flow Reserve Derived From Coronary Computed Tomography Angiography on Heart Team Treatment Decision-Making in Patients With Multivessel Coronary Artery Disease: Insights From the SYNTAX III REVOLUTION Trial.

BACKGROUND: Fractional flow reserve (FFR) is a reliable tool for the functional assessment of coronary stenoses. FFR computed tomography (CT) derived (FFRCT) has shown to be accurate, but its clinical usefulness in patients with complex coronary artery disease remains to be investigated. The present study sought to determine the impact of FFRCT on heart team's treatment decision-making and selection of vessels for revascularization in patients with 3-vessel coronary artery disease. METHODS: The trial was an international, multicenter study randomizing 2 heart teams to make a treatment decision between percutaneous coronary interventions and coronary artery bypass grafting using either coronary computed tomography angiography or conventional angiography. The heart teams received the FFRCT and had to make a treatment decision and planning integrating the functional component of the stenoses. Each heart team calculated the anatomic SYNTAX score, the noninvasive functional SYNTAX score and subsequently integrated the clinical information to compute the SYNTAX score III providing a treatment recommendation, that is, coronary artery bypass grafting, percutaneous coronary intervention, or equipoise coronary artery bypass grafting-percutaneous coronary intervention. The primary objective was to determine the proportion of patients in whom FFRCT changed the treatment decision and planning. RESULTS: Overall, 223 patients were included. Coronary computed tomography angiography assessment was feasible in 99% of the patients and FFRCT analysis in 88%. FFRCT was available for 1030 lesions (mean FFRCT value 0.64±13). A treatment recommendation of coronary artery bypass grafting was made in 24% of the patients with coronary computed tomography angiography with FFRCT. The addition of FFRCT changed the treatment decision in 7% of the patients and modified selection of vessels for revascularization in 12%. With conventional angiography as reference, FFRCT assessment resulted in reclassification of 14% of patients from intermediate and high to low SYNTAX score tertile. CONCLUSIONS: In patients with 3-vessel coronary artery disease, a noninvasive physiology assessment using FFRCT changed heart team's treatment decision-making and procedural planning in one-fifth of the patients. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02813473.

Prostate Artery Embolization: Indication, Technique and Clinical Results. / Prostataarterienembolisation: Indikation, Technik und klinische Ergebnisse.

BACKGROUND: Prostate artery embolization (PAE) is a new embolization therapy to treat benign prostate syndrome (BPS). MATERIALS AND METHODS: This review article presents the rationale and impact mechanism of PAE, criteria for patient selection, and discusses the anatomy of prostate arteries. The study results are seen in the context of complications and clinical partners. RESULTS: Important preconditions for successful prostate artery embolization are a strict indication, precise knowledge of the anatomy of the pelvic arteries and advanced interventional-radiological skills. Several studies showed that urological parameters after prostate artery embolization improve at a similar level as for established post-surgical treatments. At the same time, it could be proven that prostate artery embolization has no impact on erectile function and is associated with a relatively low complication rate. CONCLUSION: PAE is increasingly developing to an alternative for the established surgical treatments in BPS patients. KEY POINTS: · PAE is a new embolization method for treating BPS and represents an alternative to classic urological surgical procedure such as TURP.. · Due to the low caliber of the prostate artery (0.5 - 2 mm), the presence of anatomical variations, and the arteriosclerosis seen in most older men, PAE is a technically challenging embolization method.. · In patients with a high postoperative bleeding risk in classic urological surgical treatment concepts, PAE is a very gentle alternative method.. CITATION FORMAT: · Teichgräber U, Aschenbach R, Diamantis I et al. Prostate Artery Embolization: Indication, Technique and Clinical Results. Fortschr Röntgenstr 2018; 190: 847 - 855.

A case of eosinophilic gastroenteritis with severe peripheral eosinophilia.

Eosinophilic gastroenteritis is a rare heterogeneous disorder of undetermined etiology that is characterized by eosinophilic infiltration of the gastrointestinal tissues and various clinical manifestations. We report an uncommon case of eosinophilic gastroenteritis involving a patient with a short history of mild upper abdominal pain, severe peripheral eosinophilia (absolute eosinophil count of > 5,000 cells per microL), and ascites. The patient was treated successfully with a course of methylprednisolone.

Macroscopy predicts tumor progression in gastric cancer: A retrospective patho-historical analysis based on Napoleon Bonaparte's autopsy report.

BACKGROUND: The cause of Napoleon Bonaparte's death remains controversial. Originally suggested to be gastric cancer, whether this was truly neoplastic or a benign lesion has been recently debated. AIMS: To interpret findings of original autopsy reports in light of the current knowledge of gastric cancer and to highlight the significance of accurate macroscopy in modern-day medicine. METHODS: Using original autopsy documents, endoscopic images and data from current literature, Napoleon's gastric situation was reconstructed. In a multicenter collection of 2071 gastric cancer specimens, the relationship between tumor size and features of tumor progression was assessed. RESULTS: Greater tumor size was associated with advanced pT, nodal metastases and Borrmann types 3-4 (p<0.001). The best cut-off for predicting pT3-4 tumors was 6.5cm (AUC 0.8; OR 1.397, 95% CI 1.35-1.446), and 6cm for lymph node metastases (AUC 0.775; OR 1.389, 95% CI 1.338-1.442). The 6cm cut-off of had a positive predictive value of 0.820 for nodal metastases and a negative predictive value of 0.880 for distant metastases. CONCLUSION: This analysis combines Napoleon's autopsy with present-day knowledge to support gastric cancer as his terminal illness and emphasizes the role of macroscopy, which may provide valuable information on gastric cancer progression and aid patient management.

Autoimmune hepatitis: evolving concepts.

The liver is continuously exposed to a large antigenic load that includes pathogens, toxins, tumor cells and dietary antigens. A loss of tolerance against its own antigens may result in autoimmune hepatitis (AIH). The current paradigm holds that the disease is the result of self-perpetuating autoimmune process triggered by yet unknown factors (infections, chemicals, drugs) in a genetically susceptible host. To date, several putative hepatocellular surface antigens have been identified: P450-IID6 (recognized by the anti-LKM-1 autoantibodies) a membrane bound asialoglycoprotein receptor (a liver-specific membrane protein), a cytosolic UGA-suppressor tRNA associated protein (recognized by anti-SMA and anti-LP antibodies) and argininosuccinate lysate and formiminotransferase cyclodeaminase (recognized by ant-LC1 antibodies). In contrast to other chronic hepatitides patients with AIH display significant T cell hypereactivity to autologous liver antigens. Tissue injury seems to be mediated by CD4+ or CD8+ T cells and/or by antibody-dependent cell mediated cytotoxicity.

Octreotide regulates CC but not CXC LPS-induced chemokine secretion in rat Kupffer cells.

Kupffer cells (KC) and lipopolysaccharide (LPS) interaction is the initial event leading to hepatic inflammation and fibrosis in many types of liver injury. We studied chemokine secretion by KC activated with LPS and the possible effect of the somatostatin analogue octreotide, in the regulation of this process. KC isolated from Sprague-Dawley rats were cultured in the presence of LPS added alone or with different concentrations of octreotide for 24 and 48 h, and chemokine production was assessed in culture supernatants by ELISA. CC chemokine mRNA expression was assessed by semiquantitative RT-PCR. Vehicle-stimulated KC produced a basal amount of CC and CXC chemokines. LPS-stimulated KC secreted significantly increased amounts of IL-8 (GRO/CINC-1) (P<0.001), MIP-2 (P<0.001), MCP-1 (P<0.001), and RANTES (P<0.01). Octreotide inhibited LPS-induced secretion of the CC chemokines MCP-1 (P<0.05) and RANTES (P<0.05), but not the CXC chemokines IL-8 (GRO/CINC-1) and MIP-2, in a concentration-dependent manner. Downregulation of basal and LPS-induced mRNA expression of the CC chemokines was also observed in the presence of octreotide. Pretreatment with phosphatidylinositol 3 (PI3)-kinase inhibitors reduced chemokine production by LPS-treated KC in both the mRNA and protein level. Furthermore, it prevented the octreotide inhibitory effect on LPS-induced chemokine secretion, indicating a possible involvement of the PI3-kinase pathway. In conclusion, these data demonstrate that chemokine secretion by KC can be differentially regulated by octreotide, and suggest that this somatostatin analogue may have immunoregulatory effects on resident liver macrophages. British Journal of Pharmacology (2004) 141, 477-487. doi:10.1038/sj.bjp.0705633

Intestinal ischemia as the first manifestation of vasculitis.

OBJECTIVE: To summarize current knowledge regarding the diagnosis and management of gastrointestinal vasculitis. METHODS: Three cases of gastrointestinal vasculitis with acute abdominal ischemia as their first manifestation are presented. Underlying diseases were microscopic polyangiitis, systemic lupus erythematosus (SLE), and polyarteritis nodosa (PAN). Relevant English-language articles collected from the PubMed database were reviewed. RESULTS: Among the angiitides, PAN, SLE, and Henoch-Schönlein are those most commonly accompanied by gastrointestinal complications. Intestinal vasculitis usually occurs when there is evidence of generalized disease activity. Abdominal computerized tomography is a valuable tool for diagnosing intestinal ischemia and suspected vasculitis. CONCLUSIONS: In young patients presenting with intestinal ischemia, it is essential to assess the possibility of an underlying systemic disease. With prompt initiation of immunosuppressive treatment, surgery may be avoided. Prognosis is improved when there is minimal delay in surgical intervention.

Differential expression of matrix metalloproteinases in viral and non-viral chronic liver diseases.

BACKGROUND: Fibrosis is a common consequence of chronic liver diseases irrespective of aetiology. Metalloproteinases play an important role in the fibrotic process participating in the balance between collagen synthesis and degradation. We examined whether matrix gelatinases and stromelysins are similarly involved in the development of viral (HCV, HBV) and non-viral (NASH) liver diseases. METHODS: Hepatic mRNA levels of matrix metalloproteinase MMP-2, MMP-9, MMP-10 and MMP-11 isolated from liver biopsies were measured by semi-quantitative RT-PCR. Seventy-three patients were examined in this study: non-diseased controls (10), patients with chronic hepatitis B (14), chronic hepatitis C (33) and non-alcoholic steatohepatitis (16). RESULTS: A significant increase of MMP-9 and MMP-10 expression was found in patients with non-viral (non-alcoholic steatohepatitis) liver disease. Patients with chronic hepatitis B and hepatitis C showed an increase in MMP-2 mRNA expression compared to controls. Moreover, chronic hepatitis B and hepatitis C patients had significantly different mRNA expression patterns. CONCLUSIONS: These findings indicate that matrix metalloproteinases are differentially involved in the fibrotic process of viral and non-viral chronic liver diseases. Differences exist between HBV and HCV chronic hepatitis. Differences between early and late fibrosis indicate that in future studies, careful staging of patients is mandatory for interpretation of results.

Anticardiolipin antibodies in chronic hepatitis B and chronic hepatitis D infection, and hepatitis B-related hepatocellular carcinoma. Relationship with portal vein thrombosis.

OBJECTIVE: To assess the presence of anticardiolipin antibodies (ACAs) in patients with chronic hepatitis B virus (HBV) infection, chronic hepatitis D virus (HDV) infection and HBV-related hepatocellular carcinoma (HCC) and to associate this with the incidence of portal vein thrombosis (PVT) in HCC patients. PATIENTS AND METHODS: Sixty-five cirrhotic patients with HBV-related HCC, 28 naive patients with chronic HBV infection and 14 naive patients with chronic HDV infection were enrolled prospectively in the study. Thirty-two healthy blood donors were used as controls. The ACAs (immunoglobulin G and immunoglobulin M) were measured using an enzyme-linked immunosorbent assay system. Statistical analysis used non-parametric methodology (chi-squared test, Student t-test and Fisher exact test, P value<0.05). RESULTS: Eleven of the 65 patients with HCC (16.9%) showed a positive ACA titre and 22 of the patients (34%) had PVT. Of these patients, eight (36%) had a positive ACA titre. In contrast, from the 43 patients without PVT, only three (11%) showed a positive titre. From the 28 HBV patients, six (21.5%) had a positive ACA titre, and six out of 14 (42.8%) HDV patients also showed a positive ACA titre. Three of the six ACA positive HBV patients presented an extrahepatic manifestation of the disease. One out of 32 control patients (3%) had positive ACAs. CONCLUSION: Both chronic HBV and chronic HDV infections are potent stimulants for the production of ACAs. The presence of ACAs in a great proportion of HBV-cirrhosis-related HCC patients with PVT suggests their possible participation in thrombotic mechanisms and in the hypercoagulable state that occurs in advanced liver disease and HCC.

Differential cell cycle and proliferation marker expression in ductal pancreatic adenocarcinoma and pancreatic intraepithelial neoplasia (PanIN).

AIMS: Pancreatic cancer is an aggressive tumour following a multistep progression model through precursors called pancreatic intraepithelial neoplasia (PanIN). Identification of reliable prognostic markers would help in improving survival. The aim of this study was to investigate the role as well as the prognostic significance of different cell cycle and proliferation markers, namely p21, p27, p53 and Ki-67, in pancreatic carcinogenesis. METHODS: We analysed the expression of p21, p27, p53 and Ki-67, in 210 ductal pancreatic adenocarcinomas, 40 PanIN-3 cases and 40 normal controls combined in a tissue microarray. The results were correlated with clinicopathological and follow-up data. RESULTS: Our study revealed a differential p27, p21, p53, and Ki-67 expression between ductal adenocarcinoma, PanIN-3 and normal pancreas. p27 expression progressively decreased from normal pancreas to PanIN and to pancreatic cancer. Decreased p27 and increased p53 expression showed a significant association with the T stage. A Ki-67 >5% correlated with reduced survival. CONCLUSIONS: In pancreatic cancer, loss of p27 and increased p53 expression is associated with a more aggressive phenotype. p27 may play an important role in pancreatic carcinogenesis. A Ki-67 >5% independently predicted poor outcome.

Loss of the CBX7 protein expression correlates with a more aggressive phenotype in pancreatic cancer.

Polycomb group (PcG) proteins function as multiprotein complexes and are part of a gene regulatory mechanism that determines cell fate during normal and pathogenic development. Several studies have implicated the deregulation of different PcG proteins in neoplastic progression. Pancreatic ductal adenocarcinoma is an aggressive neoplasm that follows a multistep model of progression through precursor lesions called pancreatic intraepithelial neoplasia (PanIN). Aim of this study was to investigate the role of PcG protein CBX7 in pancreatic carcinogenesis and to evaluate its possible diagnostic and prognostic significance. We analysed by immunohistochemistry the expression of CBX7 in 210 ductal pancreatic adenocarcinomas from resection specimens, combined on a tissue microarray (TMA) including additional 40 PanIN cases and 40 normal controls. The results were evaluated by using receiver operating characteristic (ROC) curve analysis for the selection of cut-off scores and correlated to the clinicopathological parameters of the tumours and the outcome of the patients. Expression of E-cadherin, a protein positively regulated by CBX7, was also assessed. A significantly differential, and progressively decreasing CBX7 protein expression was found between normal pancreatic tissue, PanINs and invasive ductal adenocarcinoma. Loss of CBX7 expression was associated with increasing malignancy grade in pancreatic adenocarcinoma, whereas the maintenance of CBX7 expression showed a trend toward a longer survival. Moreover, loss of E-cadherin expression was associated with loss of CBX7 and with a trend towards worse patient survival. These results suggest that CBX7 plays a role in pancreatic carcinogenesis and that its loss of expression correlates to a more aggressive phenotype.

Clinical significance of cell cycle- and apoptosis-related markers in biliary tract cancer: a tissue microarray-based approach revealing a distinctive immunophenotype for intrahepatic and extrahepatic cholangiocarcinomas.

Cholangiocarcinoma is the second most common malignant tumor of the liver. We analyzed, immunohistochemically, the significance of cell cycle- and apoptosis-related markers in 128 cholangiocarcinomas (42 intrahepatic, 70 extrahepatic, and 16 gallbladder carcinomas) combined in a tissue microarray. Follow-up was available for 57 patients (44.5%). In comparison with normal tissue (29 specimens), cholangiocarcinomas expressed significantly more frequently p53, bcl-2, bax, and COX-2 (P.05 <). Intrahepatic tumors were significantly more frequently bcl-2+ and p16+, whereas extrahepatic tumors were more often p53+ (P < .05). Loss of p16 expression was associated with reduced survival of patients. Our data show that p53, bcl-2, bax, and COX-2 have an important role in the pathogenesis of cholangiocarcinomas. The differential expression of p16, bcl-2, and p53 between intrahepatic and extrahepatic tumors demonstrates that there are location-related differences in the phenotype and the genetic profiles of these tumors. Moreover, p16 was identified as an important prognostic marker in cholangiocarcinomas.