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Copyright of Der Chirurg is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Chirurg is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Anastomotic leakage represents a major complication following resections in colorectal surgery. Among others, intestinal inflammation such as in inflammatory bowel disease is a significant risk factor for disturbed anastomotic healing. Despite technical advancements and several decades of focused research, the underlying mechanisms remain incompletely understood. Animal experiments will remain the backbone of this research in the near future. Here, instructions on a standardized and reproducible murine model of preoperative colitis and colorectal anastomosis formation are provided to amplify research on anastomotic healing during inflammatory disease. Methods: We demonstrate the combination of experimental colitis and colorectal anastomosis formation in a mouse model. The model allows for monitoring of anastomotic healing during inflammatory disease through functional outcomes, clinical scores, and endoscopy and histopathological examination, as well as molecular analysis. Discussion: Postoperative weight loss is used as a parameter to monitor general recovery. Functional stability can be measured by recording bursting pressure and location. Anastomotic healing can be evaluated macroscopically from the luminal side by endoscopic scoring and from the extraluminal side by assessing adhesion and abscess formation or presence of dehiscence. Histologic examination allows for detailed evaluation of the healing process. Conclusion: The murine model presented in this paper combines adjustable levels of experimental colitis with a standardized method for colorectal anastomosis formation. Extensive options for sample analysis and evaluation of clinical outcomes allow for detailed research of the mechanisms behind defective anastomotic healing. [ABSTRACT FROM AUTHOR]

Due to the increasing prevalence pancreatic cancer represents a severe tumor burden to the population and will be ranked second for cancer-related mortality by the year 2030. If a curative approach is pursued a radical R0 resection of the tumor with sufficient cancer-free resection margins (≥1 mm) should be performed. This has been shown to be associated with a clear benefit for survival. For treatment planning of pancreatic cancer the tumor stage plays a pivotal role. In cases of distant metastases a palliative concept is normally initiated. If no distant metastases are detected neoadjuvant treatment can be performed in cases of borderline resectability or locally advanced stages in order to downsize these tumors. In this situation a neoadjuvant treatment has been shown to significantly increase resectability rates and to improve the tumor stage (downstaging). The most recent randomized trials were able to show a significant survival advantage of neoadjuvant treatment for borderline resectable pancreatic cancer. In cases of primarily resectable pancreatic cancer the current standard of care is an upfront resection followed by adjuvant chemotherapy. Initial data are also available indicating a survival benefit even for resectable pancreatic cancer after neoadjuvant treatment; however, reliable randomized controlled trials showing a survival advantage of neoadjuvant treatment compared to the current standard treatment of adjuvant chemotherapy following resection are missing. Numerous randomized controlled trials investigating the efficacy of neoadjuvant chemotherapy for resectable pancreatic cancer are currently underway. [ABSTRACT FROM AUTHOR]

Copyright of Der Chirurg is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Chirurg is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Colo-Proctology is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Chirurg is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Th17 cells have been shown to play an important role in the pathogenesis of a variety of autoimmune diseases. The aim of this study was to investigate the potential role of Th17 cells in autoimmune pancreatitis (AIP). Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine gene expression of the signature cytokines of Th17 cells IL-17A and IL-21 and of the Th17 lineage-specific transcription factor retinoic acid receptor-related orphan receptor C (RORC) in human tissue specimens of AIP, classical chronic pancreatitis (CP), and normal pancreas (NP). Infiltrating immune cells were characterized by immunohistochemistry (IHC). Gene expression of IL-17A, IL-21, and RORC were found to be significantly increased in AIP. Accordingly, the number of Th17 cells was significantly increased in AIP compared to NP or CP. Both gene expression analysis and IHC revealed a clear difference between type 1 and 2 AIP. In the periductal compartment of type 2 AIP, which is characterized by granulocytic epithelial lesions (GELs), the number of infiltrating Th17 cells and neutrophilic granulocytes was significantly increased compared to type 1 AIP. Our data suggest that Th17 cells play a role in the pathogenesis of AIP, in particular of type 2 AIP. Cross-talk between Th17 cells and neutrophilic granulocytes mediated via IL-17A may be a potential mechanism by which neutrophils are recruited to the duct and acinar cells with subsequent destruction, a process that is pathognomonic for type 2 AIP. [ABSTRACT FROM AUTHOR]

In the last years, the impact of weight loss in patients with malignant tumors has come more and more into the focus of clinical research, as the occurrence of weight loss is often associated with a reduced survival. Weight loss can be a hint for metastases in patients suffering from malignant tumors; furthermore, these patients are usually not able to be treated with chemotherapy. The aim of the study was to show the influence of weight loss and an elevated nutrition risk score on survival following tumor resection in patients suffering from gastric cancer. In 99 patients in whom a gastrectomy due to gastric cancer was performed, the nutrition risk score was calculated and its influence on mortality, morbidity and survival was analyzed. Of the included patients, 45 % of the patients gave a history of weight loss; they had significantly more often a NRS ≥ 3. In UICC stage 1a/b, a NRS ≥ 3 was associated with a significantly reduced survival compared to patients with a NRS < 3. In early tumor stages (UICC 1a/b), a NRS ≥ 3 was associated with a significantly reduced survival, while in progressed tumor stage, the influence of a poor NRS was not significant. This seems to show that in progressed stages in patients with gastric cancer, the influence of a reduced NRS is negligible. [ABSTRACT FROM AUTHOR]

Copyright of Der Chirurg is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Antibodies of various immunoglobulin classes to different cow's milk proteins were studied with the fluorescent immunosorbent test in 601 newborns, infants, children and adults (A). The antibody levels, expressed as the geometric mean (gm) of four antibody titres to casein, β-lactoglobulin, α-lactalbumin and bovine serum albumin, showed a clear dependence on age. They were compared with the antibody levels in children with cow's milk protein intolerance (C), other gastrointestinal disorders (B) and coeliac disease (D). The 20 children with cow's milk protein intolerance clearly differed (significance level 2×10) from those of the two control groups (A, B) insofar as the criterion adopted was not the titre against a single protein but the gm of the four antibody titres, and insofar as allowance was made for the age of the patients. All patients with cow's milk protein intolerance also showed elevated gm titres of IgE, IgA and IgM antibodies. However, since a number of children in the control groups also showed higher values, particularly with regard to IgE antibodies, the determination of the IgE, IgA and IgM antibodies adds little to the diagnosis and at best provides a further discriminatory aid. Although antibody titres fall immediately after placing the child on a milk-free diet, it is a matter of months before they become negative (titre <1∶20). After challenge titres rise again. In a longitudinal study of 25 children with acute gastroenteritis (E) it was shown that the antibody titres remained unchanged during and after the attack. This contradicts the often expressed opinion that the cow's milk antibodies frequently observed in healthy infants are induced as a consequence of gastroenteritis. In contrast to the other groups, all 26 children with proven coeliac disease (D) had antibodies to gliadin, irrespective of whether their gm cow's milk antibody titre was high or low. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to define the significance of hyponatremia as a marker of anastomotic leakage after colorectal surgery. Methods: All anastomoses in colorectal surgery performed at a single institution between July 2007 and July 2012 ( n = 1,106) were retrospectively identified. Serum sodium levels and leukocyte values measured when an anastomotic leak was diagnosed by CT scan and/or surgical reintervention ( n = 81) were compared to the values preferably on postoperative day 5 in the absence of an anastomotic leak ( n = 1,025). Results: The leak rate in anastomoses of the rectum was 9.0 %, while the leak rate of the other anastomoses was 5.4 %. Mean serum sodium level was 138.8 mmol/l in the group with an anastomotic leak and 140.5 mmol/l in the group without. Hyponatremia (<136 mmol/l) was present in 23 % of patients in the group with an anastomotic leak and in 15 % in the group without ( p < 0.001). In multivariate analysis, leukocytes and serum sodium level remained as significant markers of an anastomotic leak. As a marker of an anastomotic leak, hyponatremia had a specificity of 93 % and a sensitivity of 23 %, while the presence of either leukocytosis or hyponatremia had a sensitivity of 68 %, a specificity of 75 %, a positive predictive value of 18 %, and a negative predictive value of 97 %. Conclusions: Hyponatremia could be a specific and relevant marker of anastomotic leakage after colorectal surgery. If hyponatremia and leukocytosis are present after colorectal surgery, anastomotic leakage should be suspected and a CT scan with rectal contrast dye is recommended. [ABSTRACT FROM AUTHOR]

Background:The aims of our study were to identify serum biomarkers that distinguish pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) patients from benign pancreatic disease patients and healthy subjects, and to assess the effects of jaundice on biomarker performance.Methods:Isobaric tags for relative and absolute quantification were used to compare pooled serum and pancreatic juice samples from a test set of 59 and 25 subjects, respectively. Validation was undertaken in 113 independent subjects.Results:Candidate proteins Complement C5, inter-α-trypsin inhibitor heavy chain H3, α1-β glycoprotein and polymeric immunoglobulin receptor were elevated in cancer, as were the reference markers CA19-9 and Reg3A. Biliary obstruction had a significant effect on the performance of the markers, in particular within the PDAC group where the presence of jaundice was associated with a significant increase in the levels of all six proteins (P<0.01). Consequently, in the absence of jaundice, proteins showed reduced sensitivity for PDAC patients over benign subjects and healthy controls (HCs). Similarly, in the presence of jaundice, markers showed reduced specificity for PDAC patients over benign subjects with jaundice. Combining markers enabled improved sensitivity for non-jaundiced PDAC patients over HCs and improved specificity for jaundiced PDAC patients over jaundiced benign disease subjects.Conclusions:The presence-absence of jaundice in the clinical scenario severely impacts the performance of biomarkers for PDAC diagnosis and has implications for their clinical translation. [ABSTRACT FROM AUTHOR]

Background: Natural orifice translumenal endoscopic surgery (NOTES) is a new surgical concept that requires training before it is introduced into clinical practice. The endoscopic–laparoscopic interdisciplinary training entity (ELITE) is a training model for NOTES interventions. The latest research has concentrated on new materials for organs with realistic optical and haptic characteristics and the possibility of high-frequency dissection. This study aimed to assess both the ELITE model in a surgical training course and the construct validity of a newly developed NOTES appendectomy scenario.Methods: The 70 attendees of the 2010 Practical Course for Visceral Surgery (Warnemuende, Germany) took part in the study and performed a NOTES appendectomy via a transsigmoidal access. The primary end point was the total time required for the appendectomy, including retrieval of the appendix. Subjective evaluation of the model was performed using a questionnaire. Subgroups were analyzed according to laparoscopic and endoscopic experience.Results: The participants with endoscopic or laparoscopic experience completed the task significantly faster than the inexperienced participants (p = 0.009 and 0.019, respectively). Endoscopic experience was the strongest influencing factor, whereas laparoscopic experience had limited impact on the participants with previous endoscopic experience. As shown by the findings, 87.3% of the participants stated that the ELITE model was suitable for the NOTES training scenario, and 88.7% found the newly developed model anatomically realistic.Conclusions: This study was able to establish face and construct validity for the ELITE model with a large group of surgeons. The ELITE model seems to be well suited for the training of NOTES as a new surgical technique in an established gastrointestinal surgery skills course. [ABSTRACT FROM AUTHOR]

BACKGROUND: Rat liver transplantation is a common method in liver transplantation research. There are lots of different methods described until today. Although liver transplantation with retrograde reperfusion is established in the clinical routine there is no rat liver model described. METHODS: Arterialized rat liver transplantation with initial retrograde reperfusion was performed on n = 7 male LEWIS-(RT)-rats. 1, 24 and 48 hours after the operation, serum parameters were determined. Furthermore, after 48 hours the liver was taken for histological assessment. RESULTS: The AST and the ALT levels showed a linear decrease during the first 48 hours after transplantation. GLDH levels showed an increase during the first 24 hours before they decreased strongly. In histology, the livers showed a good quality with only less necrosis. The highest amount of necrosis could be seen in the Rappaport zone 3. CONCLUSIONS: We were able to show that arterialized rat liver transplantation with initial retrograde reperfusion is feasible and shows a good outcome. Especially in centers where retrograde reperfusion of the liver is performed in clinical transplantation this method should be used for transplantation research to reach the closest possible relation between science and clinic. [ABSTRACT FROM AUTHOR]

Purpose: Despite recent advances in clinical imaging modalities, differentiation of pancreatic masses remains difficult. Here, we tested the diagnostic accuracy of molecular-based imaging including 3′-deoxy-3′-[F]fluorothymidine (FLT) positron emission tomography (PET) and [F]fluorodeoxyglucose (FDG) PET/CT in patients with suspected pancreatic masses scheduled to undergo surgery. Methods: A total of 46 patients with pancreatic tumours suspicious for malignancy and scheduled for resective surgery were recruited prospectively. In 41 patients, FLT PET and FDG PET/CT scans were performed. A diagnostic CT performed on a routine basis was available in 31 patients. FLT PET and FDG PET/CT emission images were acquired according to standard protocols. Tracer uptake in the tumour [FDG and FLT standardized uptake value (SUV)] was quantified by the region of interest (ROI) technique. For FDG PET/CT analysis, correct ROI placement was ensured via side-by-side reading of corresponding CT images. Results: Of 41 patients, 33 had malignancy, whereas 8 patients had benign disease. Visual analysis of FDG and FLT PET resulted in sensitivity values of 91% (30/33) and 70% (23/33), respectively. Corresponding specificities were 50% (4/8) for FDG PET and 75% (6/8) for FLT PET. In the subgroup of patients with contrast-enhanced CT ( n = 31), sensitivities were 96% (PET/CT), 88% (CT alone), 92% (FDG PET) and 72% (FLT PET), respectively. Mean FLT uptake in all malignant tumours was 3.0 (range SUV 1.1-6.5; mean FDG SUV 7.9, range 3.3-17.8; p < 0.001). Conclusion: For differentiation of pancreatic tumours, FDG PET and FDG PET/CT showed a higher sensitivity but lower specificity than FLT PET. Interestingly, visual analysis of FLT PET led to two false-positive findings by misinterpreting physiological bowel uptake as pathological FLT uptake in the pancreas. Due to the limited number of patients, the clinical value of adding FLT PET to the diagnostic workup of pancreatic tumours remains to be determined. [ABSTRACT FROM AUTHOR]

BACKGROUND: The aim of the study was to evaluate prognostic factors and survival improvements in stage IV colorectal cancer patients who had all undergone resection of their primary tumor. METHODS: Between 1982 and 2006, 639 consecutive patients with UICC stage IV colorectal cancer underwent tumor resection followed by chemotherapy. Clinical, surgical, histopathological, and follow-up data were investigated and correlated with survival. RESULTS: Total R0 status was achieved in 101 patients (16%), and 128 patients (20%) underwent multivisceral resection. Median cause-specific survival for total R0 resected patients was 41 (95% CI: 32-50) months. The median cause-specific survival increased continuously from 10 (95% CI: 8-12) months for patients treated in the first years to 23 (95% CI: 19-27) months for those treated in the last 5 years of the study period. Multivariable analysis identified patients' age, pN, cM1a/b, R status, and the date of resection of the primary tumor as independent prognostic factors. CONCLUSIONS: Prognosis of stage IV colorectal cancer improved continuously in the last decades. Despite the ongoing discussion if the primary tumors should be resected in stage IV disease, prognostic factors can help to select M1 patients with potential long-term survival, who should undergo resection of the primary tumors and metastases followed by chemotherapy. [ABSTRACT FROM AUTHOR]

Background:There are no established biomarkers to identify tumour recurrence in stage II colon cancer. As shown previously, the enzymatic activity of the cyclin-dependent kinases 1 and 2 (CDK1 and CDK2) predicts outcome in breast cancer. Therefore, we investigated whether CDK activity identifies tumour recurrence in colon cancer.Methods:In all, 254 patients with completely resected (R0) UICC stage II colon cancer were analysed retrospectively from two independent cohorts from Munich (Germany) and Leiden (Netherlands). None of the patients received adjuvant treatment. Development of distant metastasis was observed in 27 patients (median follow-up: 86 months). Protein expression and activity of CDKs were measured on fresh-frozen tumour samples.Results:Specific activity (SA) of CDK1 (CDK1SA), but not CDK2, significantly predicted distant metastasis (concordance index=0.69, 95% confidence interval (CI): 0.55-0.79, P=0.036). Cutoff derivation by maximum log-rank statistics yielded a threshold of CDK1SA at 11 (SA units, P=0.029). Accordingly, 59% of patients were classified as high-risk (CDK1SA 11). Cox proportional hazard analysis revealed CDK1SA as independent prognostic variable (hazard ratio=6.2, 95% CI: 1.44-26.9, P=0.012). Moreover, CKD1SA was significantly elevated in microsatellite-stable tumours.Conclusion:Specific activity of CDK1 is a promising biomarker for metastasis risk in stage II colon cancer. [ABSTRACT FROM AUTHOR]

Copyright of Der Chirurg is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Chirurg is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The transcription factor HOXC8 regulates many genes involved in tumour progression. This study was to investigate the role of HOXC8 in pancreatic ductal adenocarcinoma (PDAC) growth and metastasis.Methods: The Hoxc8 expression was determined in 15 PDAC cell lines and human specimens by RT-polymerase chain reaction and/or immunohistochemistry. The effects of HOXC8 silencing by RNA interference were investigated by functional tests.Results: The Hoxc8 mRNA expression in PDAC cell lines was negatively related to their growth in vivo. Except for Suit2-007 cells, only those with low Hoxc8 mRNA expression grew in nude rats. Successful down-regulation of HOXC8 expression caused increased proliferation, migration (P ≤ 0.05) and colony formation (P ≤ 0.05) in Suit2-007, Panc-1 and MIA PaCa-2 PDAC cells, respectively. The Hoxc8 mRNA levels in diseased human pancreas tissues were significantly increased over normal in PDAC and autoimmune chronic pancreatitis specimens (P<0.01, respectively), but negatively related to tumour stage (P=0.09). In primary and metastatic tumour samples, immunohistochemical staining for HOXC8 was stronger in surrounding than in neoplastic tissues. Furthermore, grading of primary carcinomas was negatively associated with HOXC8 staining (P=0.03). Liver metastases showed the lowest HOXC8 expression of all neoplastic lesions.Conclusion: These data indicate that HOXC8 expression is inversely related to PDAC progression and metastasis. [ABSTRACT FROM AUTHOR]

Aim: The aim of this trial was to evaluate the impact of conversion from a calcineurin-inhibitor (CNI)-based immunosuppressive regimen to mycophenolate mofetil (MMF) and reduced-dose CNI on long-term renal function and survival in a series of 63 liver transplant patients with CNI-induced renal dysfunction.Methods: CNI dosage was significantly tapered after introduction of 2,000 mg MMF per day. Renal function was assessed by determination of serum creatinine levels and calculated creatinine clearance (CCl). The impact of relevant clinical parameters on renal function and survival post-conversion was analyzed by univariate and multivariate analysis.Results: At 60 months post-conversion, mean creatinine level had significantly declined from 197.2±58.3 μmol/l at baseline to 160.0±76.5 μmol/l, and mean CCl has significantly increased from 38.4±13.4 ml/min at baseline to 47.9±21.1 ml/min (p<0.001), respectively. Forty-six patients (73.1%) demonstrated sustained renal response to modified immunosuppression. Full-dose MMF medication (p=0.006) and the early conversion (p=0.02) were identified as independent predictors of persistent renal function improvement. Sustained renal response to MMF plus reduced-dose CNI was identified as the most relevant independent promoter of long-term survival (hazard ratio 6.9). Five-year survival rate post-conversion was 93.9% in renal responders and 64.3% in renal non-responders (log rank<0.001).Conclusions: Sustained renal response to MMF and CNI dose reduction promotes long-term survival in liver transplant patients with CNI-induced renal dysfunction. [ABSTRACT FROM AUTHOR]

Purpose: Tumour hypoxia activates hypoxia-inducible factor-1 (HIF-1) and indluences angiogenesis, cell survival and invasion. Prolyl hydroxylase-3 (PHD3) regulates degradation of HIF-1α. The effects of PHD3 in tumour growth are largely unknown.Experimental Design: PHD3 expression was analysed in human pancreatic cancer tissues and cancer cell lines by real-time quantitative PCR and immunohistochemistry. PHD3 overexpression was established by stable transfection and downregulation by short interfering RNA technology. VEGF was quantified by enzyme-linked immunosorbent assay. Matrigel invasion assays were performed to examine tumour cell invasion. Apoptosis was measured by annexin-V staining and caspase-3 assays. The effect of PHD3 on tumour growth in vivo was evaluated in an established orthotopic murine model.Results: PHD3 was upregulated in well-differentiated human tumours and cell lines, and regulated hypoxic VEGF secretion. PHD3 overexpression mediated tumour cell growth and invasion by induction of apoptosis in a nerve growth factor-dependent manner by the activation of caspase-3 and phosphorylation of focal adhesion kinase HIF-1 independently. In vivo, PHD3 inhibited tumour growth by abrogation of tumour angiogenesis.Conclusion: Our results indicate essential functions of PHD3 in tumour growth, apoptosis and angiogenesis and through HIF-1-dependent and HIF-1-independent pathways. [ABSTRACT FROM AUTHOR]

Epithelial-to-mesenchymal transdifferentiation (EMT) mediated by transforming growth factor-β (TGF-β) signaling leads to aggressive cancer progression. In this study, we identified zinc-α2-glycoprotein (AZGP1, ZAG) as a tumor suppressor in pancreatic ductal adenocarcinoma whose expression is lost due to histone deacetylation. In vitro, ZAG silencing strikingly increased invasiveness of pancreatic cancer cells accompanied by the induction of a mesenchymal phenotype. Expression analysis of a set of EMT markers showed an increase in the expression of mesenchymal markers (vimentin (VIM) and integrin-α5) and a concomitant reduction in the expression of epithelial markers (cadherin 1 (CDH1), desmoplakin and keratin-19). Blockade of endogenous TGF-β signaling inhibited these morphological changes and the downregulation of CDH1, as elicited by ZAG silencing. In a ZAG-negative cell line, human recombinant ZAG (rZAG) specifically inhibited exogenous TGF-β-mediated tumor cell invasion and VIM expression. Furthermore, rZAG blocked TGF-β-mediated ERK2 phosphorylation. PCR array analysis revealed that ZAG-induced epithelial transdifferentiation was accompanied by a series of concerted cellular events including a shift in the energy metabolism and prosurvival signals. Thus, epigenetically regulated ZAG is a novel tumor suppressor essential for maintaining an epithelial phenotype. [ABSTRACT FROM AUTHOR]

Copyright of European Surgery: ACA Acta Chirurgica Austriaca is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Der Chirurg is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of European Surgery: ACA Acta Chirurgica Austriaca is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of European Surgery: ACA Acta Chirurgica Austriaca is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The informed consent is a legal requirement prior to surgery and should be based on an extensive preoperative interview. Multimedia productions can therefore be utilised as supporting tool. In a prospective randomised trial, we evaluated the impact of an extended education on patients undergoing cholecystectomy. For extended patient information, a professionally built DVD was used. After randomisation to either the DVD or the control group, patients were informed with or without additional presentation of the DVD. The quality of education was evaluated using a purpose-built questionnaire. One hundred fourteen patients were included in the DVD and 98 in the control group. Patient characteristics did not differ significantly despite a higher educational level in the DVD group. The score of correctly answered questions was higher in the DVD group (19.88 vs. 17.58 points, p < 0.001). As subgroup analysis revealed, particular patient characteristics additionally impacted on results. Patients should be informed the most extensively prior to any surgical procedure. Multimedia productions therefore offer a suitable instrument. In the presented study, we could prove the positive impact of an information DVD on patients knowledge. Nevertheless, multimedia tools cannot replace personal interaction and should only be used to support daily work. [ABSTRACT FROM AUTHOR]

Background: Large, colorectal polyps or those that are difficult to access may be unamenable to conventional snare polypectomy and may require surgical resection. This study was designed to evaluate the resection of such lesions by the use of combined laparoscopic-endoscopic resections (CLER).Methods: Patients who had received CLER for colorectal polyps between January 1997 and December 2006 were identified from a prospectively maintained database. Patients with biopsies consistent with invasive cancer were excluded from the combined approach. Baseline characteristics, surgical, pathological, postoperative, and follow-up data of patients and lesions were reviewed.Results: A total of 146 consecutive patients underwent CLER for 154 lesions, and 120 (82%) patients underwent local excision (i.e., laparoscopy-assisted endoscopic resection, endoscopy-assisted wedge resection, and endoscopy-assisted transluminal resection). Twenty-six (18%) patients received endoscopy-assisted segmental colon resection. Conversion rate was 5% and intraoperative complications occurred in two patients (1%). Major postoperative complications occurred in five patients (3%), necessitating surgical reintervention in four of them. Follow-up colonoscopy revealed metachronous adenomas in 33 patients, of which 8 patients showed macroscopic or microscopic characteristics of advanced lesions. One patient, who had been converted to open resection because of incomplete laparoscopic resection of an adenoma, developed relapse of the initial adenoma and was successfully treated with repeat CLER accounting for a local recurrence rate of 0.9%.Conclusions: Combined laparoscopic-endoscopic resection is an efficient, safe, and minimally invasive alternative to open resection for selected patients with difficult polyps, but it should be restricted to benign disease. [ABSTRACT FROM AUTHOR]

Copyright of Der Radiologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Pancreatic cancer has an abysmal prognosis. Targets for early detection, prevention and therapy are desperately needed. Inflammatory pathways have an important impact on tumour growth and progression. Expression of BLT2 (the second leukotriene B(4) receptor) was investigated by real-time RT-PCR and immunohistochemistry. Cell proliferation was studied after stable transfection with BLT2, after treatment with siRNA and Compound A as an agonist. BLT2 is expressed in all pancreatic cancer cell lines. Results from real-time RT-PCR revealed significant overexpression of BLT2 in malignant intraductal papillary mucinous neoplasias (IPMNs) and pancreatic adenocarcinoma. Intense staining was evident in IPMNs, infiltrating tumour cells and advanced pancreatic intraepithelial neoplasias (PanINs) but not in normal ductal cells. Overexpression of BLT2 as well as stimulation of Colo357, Panc-1 and AsPC1 cells with Compound A caused a significant increase in tumour cell proliferation, an effect reversed after siRNA treatment. This study demonstrates for the first time the expression of BLT2 in the pancreas and overexpression in pancreatic cancers and malignant IPMNs in particular. Upregulation of BLT2 is already evident in precursor lesions (PanINs, IPMNs). Overexpression of this receptor leads to significant growth stimulation. Therefore, we suggest BLT2 as a new target for chemoprevention and therapy for pancreatic cancer. [ABSTRACT FROM AUTHOR]

Efficacy of chemotherapy for pancreatic cancer may be improved by tailoring it to individual chemosensitivity profiles. Identification of nonresponders before initiation of treatment may help to avoid side effects. In this study, primary pancreatic cancer cells were isolated from 18 patients undergoing pancreaticoduodenectomy for pancreatic cancer. Eight commonly used pancreatic cancer cell lines were used as controls. Ex vivo chemosensitivity for gemcitabine, 5-fluorouracil, mitomycin-C, cisplatinum, oxaliplatinum, paclitaxel and a combination of gemcitabine with oxaliplatinum or mitomycin-C was determined using a cellular ATP-based tumour chemosensitivity assay (ATP-TCA). Quantitative real-time-polymerase chain reaction was performed to determine RNA expression levels of genes implicated in chemoresistance. Chemosensitivity towards cytotoxic agents was highly variable in primary pancreatic cancer cells and pancreatic cancer cell lines. ATP-TCA results for gemcitabine correlated to the tissue expression of human equilibrative nucleoside transporter-1 (hENT1). Time to relapse in patients with gemcitabine-sensitive tumours was significantly higher than in patients with chemoresistant pancreatic cancers (P=0.01; 71 vs 269 days). Furthermore, time to relapse in gemcitabine-treated patients was related to hENT1 expression (P=0.0067). Thus, chemosensitivity testing using ATP-TCA in pancreatic cancer is feasible and correlated with time to relapse in gemcitabine-treated patients. This suggests that ATP-TCA testing could be used as a decision-making tool in the adjuvant treatment of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Little is known about the factors that enable the mobilisation of human mesenchymal stem cells (MSC) from the bone marrow into the blood stream and their recruitment to and retention in the tumour. We found specific migration of MSC towards growth factors present in pancreatic tumours, such as PDGF, EGF, VEGF and specific inhibitors Glivec, Erbitux and Avastin interfered with migration. Within a few hours, MSC migrated into spheroids consisting of pancreatic cancer cells, fibroblasts and endothelial cells as measured by time-lapse microscopy. Supernatant from subconfluent MSC increased sprouting of HUVEC due to VEGF production by MSC itself as demonstrated by RT-PCR and ELISA. Only few MSCs were differentiated into endothelial cells in vitro, whereas in vivo differentiation was not observed. Lentiviral GFP-marked MSCs, injected in nude mice xenografted with orthotopic pancreatic tumours, preferentially migrated into the tumours as observed by FACS analysis of green fluorescent cells. By immunofluorescence and intravital microscopic studies, we found the interaction of MSC with the endothelium of blood vessels. Mesenchymal stem cells supported tumour angiogenesis in vivo, that is CD31(+) vessel density was increased after the transfer of MSC compared with siVEGF-MSC. Our data demonstrate the migration of MSC toward tumour vessels and suggest a supportive role in angiogenesis. [ABSTRACT FROM AUTHOR]

Genetic modification of human bone marrow mesenchymal stem cells (MSC) is highly valuable for their exploitation in basic science and therapeutic applications, for example in cancer. We present here a new, fast and easy-to-use method to enrich a functional population of lentiviral (LV)-transduced MSC expressing enhanced green fluorescent protein (eGFP). We replaced the eGFP gene by a fusion gene of puromycin acetyltransferase and eGFP. Upon LV gene transfer and puromycin selection, we quickly obtained a pure transduced MSC population, in which growth, differentiation capacity and migration preferences were not compromised. Furthermore, we are the first to report the migration velocity of MSC among which 30% were moving and velocity of about 15 μm h−1 was not altered by LV transduction. Manipulated MSC underwent senescence one passage earlier than non-transduced cells, suggesting the use for therapeutic intervention in early passage numbers. Upon tail vein application in nude mice, the majority of LV-transduced MSC could be detected in human orthotopic pancreatic tumor xenografts and to a minor extent in mouse liver, kidney and lung. Together, LV transduction of genes to MSC followed by puromycin selection is a powerful tool for basic research and improves the therapeutic prospects of MSC as vehicles in gene therapy.Cancer Gene Therapy (2008) 15, 231–240; doi:10.1038/sj.cgt.7701097; published online 18 January 2008 [ABSTRACT FROM AUTHOR]

Recent evidence suggests that Runt-related transcription factors play a role in different human tumours. In the present study, the localisation of the Runt-related transcription factor-2 (Runx2), its transcriptional activity, as well as its regulation of expression was analysed in human pancreatic ductal adenocarcinoma (PDAC). Quantitative real-time PCR and immunohistochemistry were used for Runx2 expression and localisation analysis. Runt-related transcription factor-2 expression was silenced using specific siRNA oligonucleotides in pancreatic cancer cells (Panc-1) and immortalised pancreatic stellate cells (IPSCs). Overexpression of Runx2 was achieved using a full-length expression vector. TGF-β1, BMP2, and other cytokines were assessed for their potential to regulate Runx2 expression. There was a 6.1-fold increase in median Runx2 mRNA levels in PDAC tissues compared to normal pancreatic tissues (P<0.0001). Runt-related transcription factor-2 was localised in pancreatic cancer cells, tubular complexes, and PanIN lesions of PDAC tissues as well as in tumour-associated fibroblasts/stellate cells. Coculture of IPSCs and Panc-1 cells, as well as treatment with TGF-β1 and BMP2, led to increased Runx2 expression in Panc-1 cells. Runt-related transcription factor-2 overexpression was associated with decreased MMP1 release as well as decreased growth and invasion of Panc-1 cells. These effects were reversed by Runx2 silencing. In conclusion, Runx2 is overexpressed in PDAC, where it is regulated by certain cytokines such as TGF-β1 and BMP2 in an auto- and paracrine manner. In addition, Runx2 has the potential to regulate the transcription of extracellular matrix modulators such as SPARC and MMP1, thereby influencing the tumour microenvironment.British Journal of Cancer (2007) 97, 1106–1115. doi:10.1038/sj.bjc.6603984 www.bjcancer.com Published online 18 September 2007 [ABSTRACT FROM AUTHOR]

Background: With the increasing use of the surgical robotic system in the clinical arena, appropriate training programs and assessment systems need to be established for mastery of this new technology. The authors aimed to design and evaluate a clinic-like training program for the clinical introduction of the da Vinci robotic system in visceral and vascular surgery.Methods: Four trainees with different surgical levels of experience participated in this study using the da Vinci telemanipulator. Each participant started with an initial evaluation stage composed of standardized visceral and vascular operations (cholecystectomy, gastrotomy, anastomosis of the small intestine, and anastomosis of the aorta) in a porcine model. Then the participants went on to the training stage with the rat model, performing standardized visceral and vascular operations (gastrotomy, anastomosis of the large and small intestines, and anastomosis of the aorta) four times in four rats. The final evaluation stage was again identical to the initial stage. The operative times, the number of complications, and the performance quality of the participants were compared between the two evaluation stages to assess the impact of the training stage on the results.Results: The operative times in the final evaluation stage were considerably shorter than in the initial evaluation stage and, except for cholecystectomies, all the differences reached statistical significance. Also, significantly fewer complications and improved quality for each operation in the final evaluation stage were documented, as compared with their counterparts in the initial evaluation stage. These improvements were recorded at each level of experience.Conclusions: The presented experimental small and large animal model is a standardized and reproducible training method for robotic surgery that allows evaluation of the surgical performance while shortening and optimizing the learning-curve. [ABSTRACT FROM AUTHOR]

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Copyright of Der Onkologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and aim. Due to increased capillary permeability and the early appearance of vasoactive and toxic agents, patients suffering from necrotizing pancreatitis frequently develop a systemic inflammatory response syndrome (SIRS). Endothelin, a potent vasoconstrictor, is thought to play a major role in these changes via the regulation of microcirculation. An improved outcome of acute experimental necrotizing pancreatitis by blocking the endothelin receptors ETA and ETB, either selectively (only ETA) or unselectively (ETA and ETB), has been suggested. The aim of this study was to investigate further the beneficial effects of new, highly potent endothelin-receptor (ET-R) antagonists in acute experimental pancreatitis. Methods. The influence of the selective ET-RA antagonist BSF208075 (1 mg/kg) on mortality was studied in three severity groups of acute necrotizing pancreatitis (retrograde injection of 4%, 5% and 6% of sodium taurocholate into the main pancreatic duct). The effects of the selective ET-RA antagonists LU135252 (LU13) and BSF208075 (BSF20) and of the unselective endothelin receptor (ET-RA/B) antagonist BSF420627 (BSF42) were additionally analyzed in 4% taurocholate-induced necrotizing pancreatitis. Furthermore, the significance of variable doses of the endothelin receptor antagonist LU13 (1 mg/kg, 3 mg/kg and 100 mg/kg) was determined in a 4% sodium taurocholate model and in a cerulein pancreatitis model. Results. Prophylactic ET-R antagonism increased the mortality rate in the 4% sodium taurocholate-induced pancreatitis. No reduction in pancreatic damage after induction of taurocholate pancreatitis was found by ET-R blockage. Application of ET-R antagonists had no beneficial influence in ascites development. However, administration of LU13 (100 mg/kg) resulted in a non-significant increase in pancreatic oedema, whereas peritoneal necrosis was not affected. Conclusion. The selective and unselective ET-R antagonists BSF20, BSF42 and LU13 failed to improve survival and pancreatic damage during acute experimental pancreatitis. Therefore, previously reported beneficial effects of ET-R antagonists in experimental acute pancreatitis have to be critically evaluated before conclusions for further clinical development are made. [ABSTRACT FROM AUTHOR]

Up to now, in most surgical departments there has been no central patient management coordinating the admission, the diagnostic work-up, and the surgical procedures of patients with the resources available in the hospital. In future, however, it will be essential for surgical departments to establish such a central patient management, not only in view of the importance of patient-oriented medicine but also considering the planned introduction of diagnosis related groups. A central patient management will reduce preoperative and overall length of stay through adequate organisation and communication structures. In addition, a central patient management will make optimal use of the available resources in terms of operation rooms and hospital beds. In this article, we will present our basic concept of a central patient management in a surgical university department. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. To improve diagnosis and treatment, key mechanisms of deregulated molecular functions have to be identified. Using microarray analysis, the expression patterns of 5600 human genes were assessed in PDAC by comparison with the normal pancreas and chronic pancreatitis (CP). The expression of 467 of 5600 genes was increased in PDAC in comparison to the normal pancreas, and the expression of 120 of these genes was not increased in CP. In addition, 341 of 5600 genes were expressed at decreased levels in PDAC tissues, of which 96 were decreased in comparison to both normal and CP tissues. Thus, a total of 808 of 5600 human genes were differentially expressed in pancreatic cancer. The identification of a large panel of altered genes in PDAC will stimulate additional studies that will lead to improved understanding of the molecular mechanisms underlying pancreatic malignant growth. [ABSTRACT FROM AUTHOR]

Copyright of Der Chirurg is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

PTEN is a candidate tumour suppressor gene and frequently mutated in multiple cancers, however, not in pancreatic cancer. Recently, it has been demonstrated that PTEN expression is regulated by TGF-beta1. Using TGF-beta1 transgenic mice (n=7) and wildtype littermates (n=6), as well as pancreatic tissues obtained from organ donors (n=10) and patients with pancreatic cancer (n=10), we assessed the expression of PTEN by means of immunohistochemistry and semiquantitative PCR analysis. In addition, PANC-1 cells were treated with TGF-beta1 in vitro and the levels of PTEN mRNA were determined in these cells. In human pancreatic cancers PTEN mRNA levels were significantly decreased (P<0.05). In addition, in the pancreas of TGF-beta1 transgenic mice the expression of PTEN was significantly reduced (P<0.01), as compared to wildtype littermates and incubation of PANC-1 cells with TGF-beta1 decreased PTEN mRNA levels after 24 h. Inasmuch as TGF-beta1 decreases PTEN expression in human pancreatic cancer cells and human pancreatic cancers overexpress TGF-beta1, the reduced expression of PTEN in pancreatic cancer may be mediated by TGF-beta1 overexpression. Thus, although PTEN is not mutated in pancreatic cancers, the reduction of its expression may give pancreatic cancer cells an additional growth advantage. [ABSTRACT FROM AUTHOR]

Our purpose was to investigate brain-derived neurotrophic factor (BDNF) in chronic pancreatitis (CP) in comparison with the normal pancreas and to evaluate its association with pain. By immunohistochemistry, in the normal pancreas BDNF immunoreactivity was moderately present in the cytoplasm of most ductal cells and weakly present in most acinar cells, islet cells, nerve fibers (including perineurium), and ganglia cells. In contrast, in CP intense immunostaining of BDNF was present in most cells of ductular complexes and in the perineurium of enlarged nerves. Moderate immunostaining of BDNF was found in degenerating acinar cells and islet cells. In addition, moderate immunoreactivity of BDNF was also detected in most enlarged nerve fibers and intrinsic pancreatic ganglia cells in CP samples. Western blot analysis also revealed 5.6-fold higher BDNF levels in CP samples (P < 0.01) compared with normal pancreas samples. The expression level of BDNF was positively correlated with pain intensity (P < 0.01) and pain frequency (P < 0.01) of CP patients. Furthermore, there was a significant relationship (r = 0.68, P < 0.01) between the BDNF immunostaining and the global pain scores. BDNF is increased in CP. Its association with pain suggests that it functions as a peripheral and central pain modulator, as reported previously in other inflammatory disorders. [ABSTRACT FROM AUTHOR]

Smad2 belongs to a family of cytoplasmic molecules that are critical components in the transforming growth factor beta (TGF-beta) signaling pathway. Upon ligand binding, the type II TGF-beta receptor (TbetaRII) heterodimerizes with and activates TGF-beta receptor type I (TbetaRI). Activated TbetaRI phosphorylates Smad2, which then heterodimerizes with Smad4, translocates into the nucleus, and subsequently effects gene transcription. Previously we have shown that pancreatic cancers overexpress TGF-betas and TbetaRII. Here, we show by northern blot analysis that Smad2 mRNA levels are significantly increased in pancreatic cancer samples in comparison with normal pancreatic tissues. By immunohistochemistry, Smad2 is present in the cancer cells of 67% of the pancreatic cancer samples. Analysis of serial sections reveals coexpression of Smad2 and TGF-beta1 in the cancer cells. Furthermore, TGF-beta1 increases steady-state levels of Smad2 mRNA in the TGF-beta1-sensitive pancreatic cancer cell line COLO-357. It is suggested that pancreatic cancer cells have the capacity to up-regulate Smad2 expression, which may lead to excessive activation of specific components of the TGF-beta-signaling pathway. [ABSTRACT FROM AUTHOR]