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Purpose The effectiveness of modern perioperative treatment concepts has been demonstrated in several studies and meta-analyses. Despite good evidence, limited implementation of the fast track (FT) concept is still a widespread concern. To assess the status quo in Austrian and German hospitals, a survey on the implementation of FT measures was conducted among members of the German Society of General and Visceralsurgery (DGAV), the German Society of Coloproctology (DGK) and the Austrian Society of Surgery (OEGCH) to analyze where there is potential for improvement. Methods Twenty questions on perioperative care of colorectal surgery patients were sent to the members of the DGAV, DGK and OEGCH using the online survey tool SurveyMonkey®. Descriptive data analysis was performed using Microsoft Excel. Results While some of the FT measures have already been routinely adopted in clinical practice (e.g. minimally invasive surgical approach, early mobilization and diet buildup), for other components there are discrepancies between current recommendations and present implementation (e.g. the use of local nerve blocks to provide opioid-sparing analgesia or the use of abdominal drains). Conclusion The implementation of the FT concept in Austria and Germany is still in need of improvement. Particularly regarding the use of abdominal drains and postoperative analgesia, there is a tendency to stick to traditional structures. To overcome the issues with FT implementation, the development of an evidence-based S3 guideline for perioperative care, followed by the founding of a surgical working group to conduct a structured education and certification process, may lead to significant improvements in perioperative patient care.

Zusammenfassung Hintergrund Im Rahmen der Qualitätsinitiative der Deutschen Gesellschaft für Allgemein- und Viszeralchirurgie (DGAV) wurde eine Übersichtsarbeit auf der Grundlage einer systematischen Literatursuche verfasst und Empfehlungen für die aktuelle Diagnostik und Therapie des Ösophaguskarzinoms erarbeitet. Methoden Die systematische Literatursuche erfolgte gemäß den PRISMA-Kriterien unter Verwendung der MEDLINE-Datenbank und wurde im März 2019 durchgeführt. Die Empfehlungen wurden auf der Grundlage von Abstimmungen in der DGAV formuliert. Ergebnisse und Schlussfolgerung Operationen unterhalb der derzeit gültigen Mindestmenge sollten nicht mehr durchgeführt werden. Es spricht vieles dafür, die Mindestmenge in Deutschland auf ≥20 Resektionen/Jahr/Krankenhaus anzuheben, um die Qualität flächendeckend zu verbessern. Prähabilitationsprogramme mit Ausdauer‑, Kraft- und intensivem Atemtraining und Ernährungstherapie verbessern das Patientenoutcome. Die aktuelle Therapie des Ösophaguskarzinoms erfolgt stadienabhängig und umfasst die endoskopische Resektion bei (sub‑)mukosalen Low-risk-Tumoren (T1m1–3 bzw. T1sm1 „low risk“), die primäre Ösophagektomie bei submukosalen High-risk-Tumoren (T1a), Submukosakarzinomen (T1sm2–3) und T2N0-Tumoren, die multimodale Therapie mittels neoadjuvanter Radiochemotherapie bzw. perioperativer Chemotherapie und Operation bei fortgeschrittenen Befunden. Die Ösophagektomie wird gegenwärtig einzeitig als sog. Hybridverfahren (Laparoskopie und muskelschonende Thorakotomie) oder als total minimal-invasive Operation (Laparoskopie und Thorakoskopie) durchgeführt.

Ein positiver Zusammenhang zwischen Operationszahl und postoperativer Krankenhausletalitat, die sog. Fallzahl-Behandlungsergebnis-Beziehung, ist in der Literatur fur die Osophaguschirurgie vielfach belegt. Die Definition der zugrunde gelegten Volumina ist allerdings nicht einheitlich. Die Zahl von 26 Resektionen/Jahr/Institution, die jetzt vom Gemeinsamen Bundesausschuss als kunftige Mindestmenge festgelegt wurde, wird in dieser Stellungnahme der Chirurgischen Arbeitsgemeinschaft oberer Gastrointestinaltrakt (CAOGI) sowie der Qualitatskommission der Deutschen Gesellschaft fur Allgemein- und Viszeralchirurgie (DGAV) unter Berucksichtigung der Versorgungssituation in Deutschland und der aktuellen Datenlage diskutiert.

Background: Surgical treatment of Graves&rsquo, disease (GD) has a potentially increased incidence of postoperative hypoparathyroidism, recurrent laryngeal nerve palsy (RLNP) and bleeding. The aim of this study was to evaluate the current extent of surgery for the treatment of GD and its safety as a short-term outcome. Methods: Patients who underwent thyroid resection for GD were identified from the prospective StuDoQ/Thyroid registry. Patient data were retrospectively analyzed regarding demographics, surgical procedures and perioperative outcomes. Statistics were performed with Student&rsquo, s t-test or Fisher&rsquo, s exact test and multivariate Cox regression analysis. The level of statistical significance was set at p &lt, 0.05. Results: A total of 1808 patients with GD with a median age of 44 (range 14&ndash, 85) years were enrolled in a 25-month period by 78 departments, of which 35.7% (n = 645) had an endocrine orbitopathy and 0.1% (n = 6) had thyrotoxic crisis. Conventional open surgery was used in 98.6% of cases and minimally invasive or remote-access approaches were used in 1.4%. Total thyroidectomy was performed in 93.4% of cases (n = 1688). Intraoperative neuromonitoring (IONM) was used in 98.9% (n = 1789) of procedures. In 98.3% (n = 1777) at least one parathyroid gland was visualized and in 20.7% (n = 375) parathyroids were autografted. The rates of unilateral and bilateral transient RLNP were 3.9% (n = 134/3429 nerves at risk) and 0.1% (n = 4/3429 NAR). The rates of transient RLNP tended to be higher when intermittent IONM was used compared to continuous IONM (4.1% vs. 3.4%, p &lt, 0.059). The rate of transient postoperative hypoparathyroidism was overall 29% (n = 525/1808). Multivariate analysis revealed fewer than 300 thyroid resections and fewer than 15 thyroid resections for GD per year, male sex, BMI &gt, 30, autotransplantation of parathyroid glands and previous bilateral thyroid surgery as independent risk factors for postoperative temporary hypoparathyroidism. Reoperations for bleeding (1.3%) were rare. Conclusion: Total thyroidectomy with IONM is safe and currently the most common surgical therapy for GD in Germany. Postoperative hypoparathyroidism is the major complication which should be focused on.

BACKGROUND: A number of studies have revealed higher postoperative mortality after operations that were performed toward the end of the week. It is not yet known whether a day-of-the-week effect exists after visceral surgical procedures for cancer in Germany. METHODS: Data on resections of carcinomas of the colon, rectum (2010–2017), and head of the pancreas (2014–2017) (n = 19 703) that had been prospectively acquired by the Study, Documentation, and Quality Center of the German Society for General and Visceral Surgery were analyzed in relation to the day of the week on which the operation was performed. The primary endpoint was postoperative 30-day mortality; the secondary endpoints were complications, length of hospital stay, and MTL30 (a combined outcome criterion that is positive if the patient has died, is still in the hospital, or has been transferred to another acute care hospital 30 days after the index procedure). RESULTS: Resections of colon carcinomas that were performed on Mondays were associated with more advanced tumor stages (T4: 18.4% vs. 15.7%, p

Background: To evaluate the current indications, resection strategies and short-term outcomes of surgery for benign goitre in a country with endemic goitre. Methods: Data of patients who underwent surgery for benign goitre were retrieved from the prospective StuDoQ/Thyroid registry and retrospectively analysed regarding the patient’s demographics, indications for surgery, surgical procedures, histology, and perioperative outcomes. Results: In a 15-month period, 12,888 patients from 83 departments underwent thyroid resections for benign conditions. Main indications for surgery were exclusion of malignancy (68%), compression symptoms (20.7%) and hyperthyroidism (9.7%). Preoperative fine needle aspiration cytology was performed in only 12.2% of patients with the indication “exclusion of malignancy”. Thyroidectomy (49.8%) or hemithyroidectomy (36.9%) were performed in 86.7% of patients. Minimally invasive or alternative surgical techniques were applied in only 2.2%. Intraoperative neuromonitoring was used in 98.4% of procedures, in 97.5% of patients at least one parathyroid gland was visualized, and in 15.3% of patients parathyroid tissue was autografted, respectively. The rates of unilateral and bilateral transient recurrent nerve palsy were 3.6% and 0.07% of nerves at risk, the rate of transitory hypoparathyroidism was 15.3%. The rates of postoperative bleeding and wound infections requiring reoperation were 1.4% and 0.07%, respectively. Conclusions: The indication “exclusion of malignancy” is made too liberally, and there is a strong attitude to perform complete thyroid resections. Postoperative hypoparathyroidism is the major complication after surgery for benign thyroid disease, thus requiring more awareness.

Transmembrane tyrosine-kinase Ephrin receptors promote tumor progression and/or metastasis of several malignancies including leukemia, follicular lymphoma, glioma, malignant pleural mesothelioma, papillary thyroid carcinoma, sarcomas and ovarian, breast, bladder and non-small cell lung cancers. They also drive intestinal stem cell proliferation and positioning, control intestinal tissue boundaries and are involved in liver, pancreatic and colorectal cancers, indicating involvement in additional digestive system malignancies. We investigated the role of Ephrin-B4 receptor (EPHB4), and its ligand EFNB2, in gastric and gastroesophageal junction cancers in patient cohorts through computational, mathematical, molecular and immunohistochemical analyses. We show that EPHB4 is upregulated in preneoplastic gastroesophageal lesions and its expression further increased in gastroesophageal cancers in several independent cohorts. The closely related EPHB6 receptor, which also binds EFNB2, was downregulated in all tested cohorts, consistent with its tumor-suppressive properties in other cancers. EFNB2 expression is induced in esophageal cells by acidity, suggesting that gastroesophageal reflux disease (GERD) may constitute an early triggering event in activating EFNB2-EPHB4 signaling. Association of EPHB4 to both Barrett's esophagus and to advanced tumor stages, and its overexpression at the tumor invasion front and vascular endothelial cells intimate the notion that EPHB4 may be associated with multiple steps of gastroesophageal tumorigenesis. Analysis of oncogenomic signatures uncovered the first EPHB4-associated gene network (false discovery rate: 7 × 10(-90) ) composed of a five-transcription factor interconnected gene network that drives proliferation, angiogenesis and invasiveness. The EPHB4 oncogenomic network provides a molecular basis for its role in tumor progression and points to EPHB4 as a potential tumor aggressiveness biomarker and drug target in gastroesophageal cancers.

Background Thyroidectomy is still three to six times more common in Germany than in the USA, Great Britain, and the Scandinavian countries. Thus, the question is often asked whether thyroidectomy in Germany is being performed for the correct indications. Methods This review is based on studies and guidelines containing information on the indications for surgery in benign goiter and Graves' disease; these publications were retrieved by a systematic literature search in the Medline and Cochrane Library databases (1990-2016). The indications recommended here were determined by vote by the German Society for General and Visceral Surgery (Deutsche Gesellschaft fur Allgemein- und Viszeralchirurgie, DGAV). Results On the basis of the available evidence (levels 2-4), and in the absence of prospective studies, the indications for surgery in goiter include a well-founded suspicion of malignancy, local compressive symptoms, and, rarely, cosmesis. In hyperthyroid goiter and Graves' disease, surgery is a potential alternative to radio - iodine therapy, particularly if the volume of the thyroid gland exceeds 80 mL, in patients with advanced or active orbitopathy, and in female patients who are, or plan to be, pregnant. Large, asymptomatic, euthyroid nodular goiter without any suspicion of malignancy and scintigraphically "cold" nodules without any other evidence of malignancy are not indications for surgery. Thyroid operations of higher levels of difficulty (e.g., recurrent goiter, retrosternal extension, Graves' disease) should be carried out in institutions with special expertise in thyroid surgery. Conclusion The decision to operate should be made on an interdisciplinary basis and in conformity with the relevant guidelines after all of the appropriate diagnostic studies have been performed. The radicality of any proposed surgical procedure should be weighed against its potential complications.

Background Pancreatic resections are among the most complex procedures in visceral surgery. While mortality has decreased substantially over the past decades, morbidity remains high. The volume-outcome correlation in pancreatic surgery is among the strongest in the field of surgery. The German Society for General and Visceral Surgery (DGAV) established a national registry for quality control, risk assessment and outcomes research in pancreatic surgery in Germany (DGAV SuDoQ|Pancreas). Methods Here, we present the aims and scope of the DGAV StuDoQ|Pancreas Registry. A systematic assessment of registry quality is performed based on the recommendations of the German network for outcomes research (DNVF). Results The registry quality was assessed by consensus criteria of the DNVF in regard to the domains Systematics and Appropriateness, Standardization, Validity of the sampling procedure, Validity of data collection, Validity of statistical analysis and reports, and General demands for registry quality. In summary, DGAV StuDoQ|Pancreas meets most of the criteria of a high-quality clinical registry. Conclusion The DGAV StuDoQ|Pancreas provides a valuable platform for quality assessment, outcomes research as well as randomized registry trials in pancreatic surgery. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-1911-x) contains supplementary material, which is available to authorized users.

The taurine derivative taurolidine (TRD) exerts anti-neoplastic effects in a variety of tumor models. On the other hand, TRD at low doses was shown to reduce cell-cell adhesion, a prerequisite for metastasis. The aim of this study was to elucidate the effects of low-dose TRD on pancreatic cancer. Human pancreatic cancer cell lines representing diverse states of differentiation were exposed to TRD for 24 h. Cell viability was assessed by MTT assay and trypan blue staining, apoptosis by caspase-3/7 activity, and flow-cytometric cell cycle analysis. Expression of Snail and E-cadherin was analyzed by polymerase chain reaction and Western blotting. MTT-tested viability of all pancreatic cancer cell lines decreased dose-dependently up to 50 % of the untreated control. In contrast to staurosporine TRD (100 and 250 μM) did not induce apoptosis but increased the percentage of cells in G1/G0 arrest. Correlation of MTT test and trypan blue staining revealed a decreased adherence of vital tumor cells at 250 μM TRD. This was associated with reduced expression of the adhesion molecule E-cadherin and an increased expression of the transcription factor Snail, a regulator of epithelial-mesenchymal transition (EMT). Low-dose TRD reduces not only viability but also cell-cell adherence and E-cadherin expression of pancreatic cancer cells, whereas the expression of the EMT inducer Snail was increased. By induction of these EMT hallmarks, low-dose TRD may promote metastasis in pancreatic cancer.

Background Currently, early changes of tumor vasculature after angiogenesis inhibition can only be evaluated by histopathology, a method not suitable in a clinical setting. Purpose To quantify effects of different angiogenesis inhibitors on the microvasculature of orthotopically implanted pancreatic cancers by contrast-enhanced magnetic resonance imaging (MRI) in order to establish a non-invasive technique for monitoring antiangiogenic cancer treatment. Material and Methods DSL-6A/C1 pancreatic cancers were implanted in the pancreas of 109 Lewis rats. Three weeks later, antiangiogenic treatment was initiated by administration of Bevacizumab ( n = 38) or Suramin ( n = 27) while the control group ( n = 44) remained untreated. Dynamic MRI was performed 24 h, 1 week, and 4 weeks after treatment initiation. Fractional tumor plasma volume (fPV, %) and vascular permeability (KPS, mL/min/100 cc) were calculated based on the MRI data by using a pharmacokinetic model. Results Twenty-four hours after the initial dose, a significant decline in KPS was observed in the Bevacizumab group compared to the control and Suramin group (0.002 ± 0.008; 0.057 ± 0.046 and 0.064 ± 0.062 (mean ± SD); P 3; P Conclusion Dynamic MRI can quantify antiangiogenic effects on tumor microvasculature before changes in tumor volumes are detectable. Thus, this technique is a reasonable addition to morphological MRI and may be applied as an alternative to histopathology.

Histopathological regression grading has been shown to predict outcome in chemoradiated rectal cancer. Lymph node spread is still considered the most important single prognostic parameter. Therefore, we investigated the association of regression grading with tumor spread in a single center retrospective cohort. 102 consecutive patients who had undergone neoadjuvant therapy for rectal adenocarcinoma were included. Surgery was performed, including total mesorectal excision. Pathological examination included UICC staging and Dworak's five-tier tumor regression grading. Histological complete response was achieved in 16.7% of cases. Dworak's regression grading and a simplified two tier scheme both correlated excellently with ypT, ypN and UICC stage. However, cases with poor histological response were strongly represented in ypN0. Tumor regression grading is a reliable method for assessment of response to neoadjuvant therapy, but the optimal cut-off for separating good and poor response remains to be established based on clinical outcome.

Bipolar radio-frequency-induced thermofusion (BiRTh) of intestinal tissue might replace conventional stapling devices which are associated with technical and functional complications. Previous results of our study group confirmed the feasibility to fuse intestinal tissue using BiRTh-induced thermofusion ex vivo. The aim of this study was now to evaluate the efficacy of fusing intestinal tissue in vivo by BiRTh-induced thermofusion.In male Wistar rats a blind bowel originating from the caecum was closed either by BiRTh (n = 24) or conventional suture (n = 16). At 6 h, 48 h, 4 days, and 2 weeks after the procedure caecum bursting pressure was measured to compare both groups.In total 18 of 21 (85.7%) thermofused and 15 of 16 (93.7%) sutured cecal stumps were primarily tight and leakage-proof (p0.05). The operative time was comparable in both groups without significant differences. Both groups showed increases in bursting pressure over the post-operative period. The mean bursting pressure for thermofusion was 47.8, 48.3, 55.2, and 68.0 mmHg, compared to 69.8, 51.5, 70.0 and 71.0 mmHg in the hand-sutured group (p 0.05) after 6 h, 48 h, 4 days, and 2 weeks, respectively.These results suggest that BiRTh-induced thermofusion is a safe and feasible method for fusing intestinal tissue in this experimental in vivo model and could be an innovative approach for achieving gastrointestinal anastomoses.

Coloproctomucosectomy (CPM) with ileopouchanal anastomosis (IPAA), as the procedure of choice for surgical management of ulcerative colitis (UC), is commonly performed either as a 2- or 3-staged procedure. For patients with considerable immunosuppression, reduced nutritional or general health status, and as part of emergency treatment, a 3-staged (3S) procedure is recommended by guidelines to minimize perioperative complication rates compared to 2-staged (2S) procedure. However, the necessity of additional hospitalization and surgery is suspect to affect quality of life (QoL). In this prospective, observational study, we evaluate the long-term QoL after 2- and 3-staged interventions of CPM with IPAA for patients with UC.Between 1997 and 2011, a total of 233 patients underwent CPM and had a 2- or 3-staged procedure. In 108 patients, surgical procedure was completed, and evaluation of QoL was performed by specific questionnaires (IBDQ, FIQoL, SF-12, CCS) up to 20 years after ileostomy closure. Data were collected within the framework of a prospective study.Observing a total of 84 patients (2S: n = 59; 3S: n = 25), QoL measured by IBDQ was higher after CPM, compared to preoperative (2S: 15 → 31; 3S: 17 → 28; p 0.01), with no differences between 2S or 3S procedures (p 0.05). Specific QoL assessment concerning incontinence and stool frequency (CCS, FIQoL) did not differ either (CCS: 2S:3S = 12:15; p 0.05). General health-related QoL, determined by SF-12 score, did not differ between 2S or 3S procedures.The indication for a 2-staged or 3-staged procedure should be adjusted to the severity of the underlying disease, nutritional status of the patient, and the extent of immunosuppression at the time of surgery. It should not be affected by the fear of complications or a reduced quality of life by additional surgery in 3-staged versus 2-staged procedures.

Recurrent Crohn's disease activity at the site of anastomosis after ileocecal resection is of great surgical importance. This prospective randomized multi-center trial with an estimated case number of 224 patients was initially planned to investigate whether stapled side-to-side anastomosis, compared to hand-sewn end-to-end anastomosis, results in a decreased recurrence of Crohn's disease following ileocolic resection (primary endpoint). The secondary endpoint was to focus on the early postoperative results comparing both surgical methods. The study was terminated early due to insufficient patient recruitment and because another large study investigated the same question, while our trial was ongoing.Patients with stenosing ileitis terminalis in Crohn's disease who underwent an ileocolic resection were randomized to side-to-side or end-to-end anastomosis. Due to its early discontinuation, our study only investigated the secondary endpoints, the early postoperative results (complications: bleeding, wound infection, anastomotic leakage, first postoperative stool, duration of hospital stay).From February 2006 until June 2010, 67 patients were enrolled in nine participating centers. The two treatment groups were comparable to their demographic and pre-operative data. BMI and Crohn's Disease Activity Index were 22.2 (± 4.47) and 200.5 (± 73.66), respectively, in the side-to-side group compared with 23.3 (± 4.99) and 219.6 (± 89.03) in the end-to-end group. The duration of surgery was 126.7 (± 42.8) min in the side-to-side anastomosis group and 137.4 (± 51.9) min in the end-to-end anastomosis group. Two patients in the end-to-end anastomosis group developed an anastomotic leakage (6.5%). Impaired wound healing was found in 13.9% of the side-to-side anastomosis group, while 6.5% of the end-to-end anastomosis group developed this complication. The duration of hospital stay was comparable in both groups with 9.9 (± 3.93) and 10.4 (± 3.26) days, respectively.Because of the early discontinuation of the study, it is not possible to provide a statement about the perianastomotic recurrence rates regarding the primary endpoint. With regard to the early postoperative outcome, we observed no difference between the two types of anastomosis.

Die Kolondivertikulose gehort zu den haufigsten Erkrankungen des Gastrointestinaltrakts weltweit mit einer ansteigenden Inzidenz. Wahrend der weit uberwiegende Teil der Divertikulosetrager asymptomati

Background The prevalence of thyroid nodules ranges between 2% and 60% depending on the population studied. However, minimally invasive procedures like radiofrequency ablation (rfA) are increasingly used to treat tumors of parenchymatous organs, and seem to be suitable for singular thyroid nodules as well. Their successful clinical application depends on the induction of sufficiently large lesions and a knowledge of the energy parameters required for complete thermal ablation. The aim of this study was to establish a dose-response relationship for rfA of thyroid nodules. Material and Methods Thermal lesions were induced in healthy porcine thyroid glands ex vivo ( n = 110) and in vivo ( n = 10) using a bipolar radiofrequency system; rf was applied in a power range of 10–20 watts. During the ablation, continuous temperature measurement at a distance of 5 and 10 mm from the applicator was performed. The transversal and axial lesion diameters were measured, and the volume was calculated. Furthermore, enzyme histochemical analysis of the thyroid tissue was performed. Results The inducible lesion volumes were between 0.91 ± 0.71cm 3 at 20W and 2.80 ± 0.85cm 3 at 14W. The maximum temperatures after rf ablation were between 44.0 ± 9.7°C and 61.6 ± 13.9°C at a distance of 5mm and between 30.0 ± 8.6°C and 53.5 ± 8.6°C at a distance of 10mm from the applicator. The histochemical analysis demonstrates a complete loss of nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) dehydrogenase activity in thermal lesions as a sign of irreversible cell damage. Conclusion This study is the first to demonstrate a dose-response relationship for rfA of thyroid tissue. rfA is suitable for singular thyroid nodules and induces reproducible, clinically relevant lesions with irreversible cell damage in an appropriate application time.

Correct diagnosis, surgical treatment, and perioperative management of patients with esophageal carcinoma remain crucial for prognosis within multimodal treatment procedures. This study aims to achieve a consensus regarding current management strategies in esophageal cancer by questioning a panel of experts from the German Advanced Surgical Treatment Study (GAST) group, comprised of 9 centers specialized in esophageal surgery, with a combined total of >220 esophagectomies per year. The Delphi method, a systematic and interactive, evidence-based approach, was used to obtain consensus statements from the GAST group regarding ambiguities and disparities in diagnosis, patient selection, surgical technique, and perioperative management of patients with esophageal carcinoma. After four rounds of surveys, agreement was measured by Likert scales and defined as full (100% agreement), near (≥66.6% agreement), or no consensus (

Background Sigmoid diverticulitis (SD) is common in the West; its incidence is increasing as the average age of the population increases. The aim of this study was to assess the clinical outcomes of patients with acute SD and to determine whether emergency operation was associated more often with previous episodes of acute diverticulitis. Methods All consecutive patients admitted for acute SD were recruited prospectively over an 11-year period from January 1998 to December 2008. Multiple logistic regression was used to identify risk factors for free perforation. Results We included 934 patients (490 men and 444 women; median age, 59.2 years): 450 (48.2%) presented for their first SD episode and 484 (51.8%) had a prior history of SD. Free perforation occurred in 152 patients: during the first episode of SD in 114 patients (25.3%), during the second in 29 (12.7%), during the third in 8 (5.9%), and during the fifth in 1 patient (0.9%; P 5 previous episodes of SD had free perforation. All 152 patients with free perforation required emergent operative intervention. After initial conservative therapy in 782 patients, 82 required early elective operative intervention owing to exacerbation of infection under antibiotic treatment. Late elective colectomy was performed in 299 patients during the inflammation-free interval, and operative intervention was recommended in 345 patients owing to complicated diverticulitis. Uncomplicated SD in 56 patients was managed conservatively. Comorbidity (>1 disorder) and the first episode of SD were identified as risk factors for free perforation on multiple logistic regression. Conclusion The risk of free perforation in acute SD decreases with the number of previous episodes of SD. The first episode thus is the most dangerous for a free perforation. The indication for colectomy should not be made based on the potential risk of free perforation.

Alternative minimally invasive treatment options such as radiofrequency ablation (RFA) or laser-induced thermotherapy (LITT) are at present under investigation for achieving a nonsurgical targeted cytoreduction in benign and malignant thyroid lesions. So far, studies have not been able to show a secure advantage for neither LITT nor RFA. The aim of this study was to compare the two ablation procedures in terms of their effectiveness. Thermal lesions were induced in porcine thyroid glands either by LITT or bipolar RFA ex vivo (n = 110 each) and in vivo (n = 10 each) using power settings between 10 and 20 W. Temperature spread during application was documented in 5- and 10-mm distance of the applicator. Postinterventional lesion diameters were measured and lesion size was calculated. Furthermore, enzyme histochemical analysis of the thyroid tissue was performed in vivo. Lesion volumes induced by LITT ranged between 0.74 ± 0.18 cm(3) (10 W) and 3.80 ± 0.41 cm(3) (20 W) with a maximum of 5.13 ± 0.16 cm(3) at 18 W. The inducible lesion volumes by RFA were between 2.43 ± 0.68 cm(3) (10 W) and 0.91 ± 0.71 cm(3) (20 W) with a maximum of 2.80 ± 0.85 cm(3) at 14 W. The maximum temperatures were 112.9 ± 9.2°C (LITT) and 61.6 ± 13.9°C (RFA) at a distance of 5 mm and 73.2 ± 6.7°C (LITT) and 53.5 ± 8.6°C (RFA) at a distance of 10 mm. The histochemical analysis demonstrates a complete loss of NADPH dehydrogenase activity in thermal lesions as a sign of irreversible cell damage both for LITT and RFA. This study is the first to compare the effectiveness of laser-induced thermotherapy and radiofrequency ablation of thyroid tissue. LITT as well as RFA are suitable for singular thyroid nodules and induces reproducible clinically relevant lesions in an appropriate application time. The maximum inducible lesion volumes by LITT are significantly larger than by RFA with the devices used herein.

In situ ablation is increasingly being used for the treatment of liver malignancies. The application of these techniques is limited by the lack of a precise prediction of the destruction volume. This holds especially true in anatomically difficult situations, such as metastases in the vicinity of larger liver vessels. We developed a three-dimensional (3D) planning system for laser-induced thermotherapy (LITT) of liver tumors. The aim of the study was to validate the system for calculation of the destruction volume.LITT (28 W, 20 min) was performed in close contact to major hepatic vessels in six pigs. After explantation of the liver, the coagulation area was documented. The liver and its vascular structures were segmented from a pre-interventional CT scan. Therapy planning was carried out including the cooling effect of adjacent liver vessels. The lesions in vivo and the simulated lesions were compared with a morphometric analysis.The volume of lesions in vivo was 6,568.3 ± 3,245.9 mm(3), which was not different to the simulation result of 6,935.2 ± 2,538.5 mm(3) (P = 0.937). The morphometric analysis showed a sensitivity of the system of 0.896 ± 0.093 (correct prediction of destructed tissue). The specificity was 0.858 ± 0.090 (correct prediction of vital tissue).A 3D computer planning system for the prediction of thermal lesions in LITT was developed. The calculation of the directional cooling effect of intrahepatic vessels is possible for the first time. The morphometric analysis showed a good correlation under clinical conditions. The pre-therapeutic calculation of the ablation zone might be a valuable tool for procedure planning.

Surgical therapy remains the only curative option for pancreatic ductal adenocarcinoma. But even after complete resection, almost all patients suffer from local tumor recurrence. Current standard adjuvant therapy with gemcitabine does not impressively affect the recurrence rate. The aim of this study was to evaluate a novel anti-angiogenic adjuvant treatment strategy by targeting the vascular endothelial growth factor receptor (VEGFR). We assayed the effects of a novel VEGFR inhibitor (ZK261991) on pancreatic carcinoma. ZK261991 is a highly selective and potent VEGFR-kinase inhibitor, which is orally available. We used a previously established nude mouse orthotopic pancreatic cancer resection model. Subcutaneous donor tumor fragments (1 mm3) derived from human pancreatic cancer cell lines HPAF-2 and AsPC-1 were implanted in the pancreatic tail of 48 nude mice. Fourteen days afterwards, all mice underwent a histologically confirmed curative tumor resection followed by daily adjuvant oral therapy with ZK261991 (50 mg/kg; n = 24) vs. placebo (n = 24). The mice were sacrificed after 12 weeks of therapy or in case of defined endpoints. All sacrificed mice underwent autopsy. A dissemination score (local and systemic tumor spread), size of recurrent tumor mass, survival, and weight loss/gain were surveyed. Kaplan–Meier analysis of survival showed a significant benefit for mice treated with ZK261991 after HPAF-2 tumor resection: 83.8 days (95% CI 73.9–93.6) vs. 60.9 days (95% CI 48.9–73.0), p = 0.006. Adjuvant treatment with ZK261991 of AsPC-1-derived tumors showed a tendency towards a benefit compared to control but no significant difference: 75.8 days (95% CI 59.7–91.9) vs. 65.7 days (95% CI 51.6–79.7). There were no significant differences in dissemination score and size of recurrent tumor mass between the treatment groups. Adjuvant anti-angiogenic therapy with the novel VEGFR-inhibitor ZK261991 resulted in a significant survival benefit after curative tumor resection in a clinically relevant orthotopic animal model of pancreatic cancer. Combination of anti-angiogenic treatment with cytotoxic agents may further improve the results of adjuvant therapy.

Purpose To investigate the cytostatic effect of 5-fluorouracil (5-FU) encapsulated in polyethylene glycol (PEG) liposomes with or without degradable starch microspheres (DSM) in a long-term trial using a rat liver tumor model. Materials and Methods The cytostatics were applied once either as a hepatic arterial infusion (HAI) or were systemically infused via the tail vein. Seven groups were compared with respect to tumor growth and survival times: 5-FU HAI (group I), 5-FU + DSM HAI (group II), PEG-5-FU HAI (group III), PEG-5-FU + DSM HAI (group IV), NaCl HAI (group V), 5-FU i.v. (group VI), and PEG-5-FU i.v. (group VII). Results Seven and 14 days after treatment in groups III and IV, only group IV had significantly inhibited tumor growth on day 21 compared to the groups treated intravenously. On day 28, none of the animals from the intravenously treated groups were still alive compared to a significantly longer survival time of 6 and 8 weeks in groups III and IV. Conclusion Locoregional therapy with 5-fluorouracil encapsulated in PEGylated liposomes may further improve the treatment success with longer-lasting tumor regression and prolonged survival times.

The prognostic value of p53 and p21 expression in colorectal cancer is still under debate. We hypothesize that the prognostic impact of p53 expression is dependent on p21 status. The expression of p53 and p21 was immunohistochemically investigated in a prospective cohort of 116 patients with UICC stage II and III sporadic colorectal cancer. The results were correlated with overall and recurrence-free survival. The mean observation period was 51.8 ± 2.5 months. Expression of p53 was observed in 72 tumors (63%). Overall survival was significantly better in patients with p53-positive carcinomas than in those without p53 expression (p = 0.048). No differences were found in recurrence-free survival (p = 0.161). The p53+/p21− combination was seen in 68% (n = 49), the p53+/p21+ combination in 32% (n = 23). Patients with p53+/p21− carcinomas had significantly better overall and recurrence-free survival than those with p53+/p21+ (p < 0.0001 resp. p = 0.003). Our data suggest that the prognostic impact of p53 expression on sporadic colorectal cancer is dependent on p21 status.

There is controversy over whether sigmoid diverticulitis (SD) is more aggressive with a higher risk of perforation in younger than in older patients. The aim of this study was to assess the clinical presentation and outcome of patients ≤40 and >40 years old with acute diverticulitis. Consecutive admissions of all patients with acute SD were prospectively recruited from January 1998 to June 2010. A total of 1,019 patients were included: 513 (69 ≤40 years and 444 >40 years) presented with their first episode, while 506 (20 ≤40 years, 486 >40 years) had a prior history of SD. The percentage of patients with severe SD did not differ between the two age groups either for the first (covered perforation, 30.4% vs. 29.5%, p = 0.875; free perforation, 26.1% vs. 23.9%, p = 0.69) or for the recurrent episode (covered perforation, 15% vs. 8.2%, p = 0.287; free perforation, 5% vs. 4.1%, p = 0.846). Furthermore, the rate of emergency surgery did not differ between both age groups either for the first (26.1% vs. 23.9%, p = 0.690) or the recurrent episode (5% vs. 4.1%, p = 0.846). No differences in the rate of Hartmann’s procedure (52.6% vs. 68.3%, p = 0.180) and failure of conservative treatment (3.4% vs. 4.9%, p = 0.607) were observed between younger and older patients. Acute SD in younger patients is not more aggressive and has no higher risk of perforation or need for emergency surgery compared to older patients.

Incisional hernias are one of the most often complications in abdominal surgery and therefore present a significant surgical and socioeconomic problem. To date, incisional hernias are always an indication for surgery, regardless of the patient’s symptoms. However, it remains unclear to what extent the surgery actually results in symptomatic improvement and whether a relevant risk of incarceration exists. The purpose of this study was to investigate the motivation that led to incisional hernia repairs and whether patients benefit from surgery with regard to pain and subjective criteria. This prospective study included patients who underwent open abdominal incisional hernia repair using mesh implantation. Data collection was done preoperatively and 6 months postoperatively. The intensity of pain was evaluated using the Numeric Analog Scale (NAS). Patients were divided according to their preoperative level of pain into oligosymptomatic (NAS 0–3) and symptomatic (NAS 4–10) groups, and the postoperative outcome of both groups was compared. Ninety patients were prospectively enrolled: 45 males (50.0%) and 45 females (50.0%); 43 patients (47.8%) were oligosymptomatic preoperatively, while 47 patients (52.2%) reported relevant pain. The most frequent motivation for surgery named by the oligosymptomatic patients was fear of incarceration (79.1%), while the symptomatic patients mostly mentioned pain (76.6%). At 6 months postoperatively, significantly more oligosymptomatic patients complained of relevant pain (p

Surgical simulation modules for "open" surgery are limited in contrast to well-studied and validated laparoscopic trainers. In this study, face, content and construct validity of a devised simulation module (Berlin Operation Trainer, BOPT) for handsewn anastomoses in digestive surgery were analysed.Participants of a skills course for digestive surgery (novices: 1-3 years of training; experts: more than 5 years of training) were timed on performing four defined handsewn digestive anastomoses on formalin fixed porcine intestine in the BOPT. Questionnaires were answered regarding impression with the simulation module concerning appearance and realism using a five-point Likert and a three-point forced choice scale. Face and content validities were evaluated based on the responses of participants and construct validity by comparing novices to experts. Data collected were analysed with Fisher's exact test and two-sample t test.Twenty-two novices (median: second postgraduate year) and 26 experts (median: seventh postgraduate year) were enrolled in the study. The BOPT showed strong face and content validities with average scores for satisfaction parameters above 4.2 +/- 0.41 and 4.1 +/- 0.22, respectively. Construct validity was adequate for anastomosis simulation in the BOPT based on different percentages of anastomosis complete during set time between novices and experts as shown for simple (68.2% vs. 92.3%, p = 0.038) and for difficult anastomosis (18.2% vs. 50.0%, p = 0.021).The BOPT is a suitable instrument for advanced surgical training for novices and experienced colleagues creating a realistic and demanding situation. Further studies have to evaluate if a more realistic preoperative training will support an effective transfer of learned techniques to the operating room.

Paneth cells are part of the innate mucosal immunity of the gut with possible regulatory function. This study intends to identify the gene expression pattern of the orthotopic and metaplastic Paneth cells, searching for differences between metaplastic occurrence between Crohn's disease and ulcerative colitis.Paneth cells were collected in RNAse-free conditions via micro dissection. RNA isolation and super amplification was followed by microarray analysis of whole genome expression activity of the orthotopic and metaplastic Paneth cells. Immunohistology of beta-catenin and Frizzled-5 receptor was performed.Histological analysis showed no morphological or secretory change (Frizzled-5 receptor and beta-catenin) in orthotopic and metaplastic Paneth cells. Microarray analysis indicated an increased, but not mutant activation of Wnt/beta-catenin signaling and firstly showed expression of NALP 1, 7, 8 and 11 in metaplastic Paneth cells.Paneth cells might play a NALP-mediated role in the pathogenesis of IBD.

The indications for prophylactic surgery for phlegmonous and covered perforated type of acute sigmoid diverticulitis (SD) are currently matters of debate, and a more conservative approach has been advocated. However, it has not yet been clarified to what extent CT findings indicative of acute SD correlate with histological findings, and it is still uncertain how these findings change in the time interval between initial antibiotic treatment and late elective surgery. The aim of this study was to record time-course changes of inflammation in phlegmonous and abscess-forming diverticulitis after conservative treatment in order to check the indication for surgery. This study included all patients who underwent surgery for CT morphologically phlegmonous and covered perforated SD from January 2002 to June 2007. Two groups were formed to record time-course changes: early elective surgery (7–10 days after antibiotic treatment) and late elective surgery (4–6 weeks after conservative treatment). Exclusion criteria were emergency interventions, free perforations (Hinchey III and IV), recurrent inflammations, and contrast allergy. The extent of the inflammation recorded preoperatively by CT scan was compared with histological findings. A total of 257 patients (142 male and 115 female; mean age, 56.6 years) underwent surgery (116 early elective and 141 late elective) for phlegmonous and covered perforated SD. Phlegmonous SD was seen in 127 cases and covered perforated SD in 130 cases. In the phlegmonous type of SD, early surgery led to conformity with the preoperative stage in 56%, to more extensive findings in 11%, and to subsided inflammation in 33%. Late surgery led to conformity in 0% and to signs of subsided inflammation in 100%. In the covered perforated type of SD, early surgery led to conformity in 90%, to subsided inflammation in 10%, and to milder manifestation in 0%. In contrast, late surgery here led to conformity in 26% of the cases and to subsided inflammation in 74%. Considerable histological changes can be detected under conservative therapy. The acute inflammation subsides under antibiotic therapy as awaited. It must be clarified whether the phlegmonous form of SD should, in principal, be regarded as an indication for surgery, since it shows early and nearly complete regression of the inflammation. Otherwise, the covered perforated type of SD still shows marked inflammatory changes after conservative therapy in a high percentage of patients and should thus preferably be treated by surgery. However, the clinical appearance of the patient with sigmoid diverticulitis still remains the most important part of decision making.

Sacral nerve stimulation (SNS) can improve fecal incontinence, though the exact mechanism is not known. This study examines the following hypotheses: SNS leads to contraction of the pelvic floor, influences rectal perception, and improves continence and quality of life.Fourteen patients with sacral nerve stimulators implanted for fecal incontinence were examined prospectively. Morphological and functional assessment was done by endosonography, manometry, and volumetry with the stimulator turned on and off in direct succession. Questionnaires were used to determine incontinence and quality of life.With the stimulator turned on, rectal filling conditions were perceived only at higher volumes; in particular, the defecation urge was sensed only at higher volumes. There was also a reduction in the diameters of the external and internal anal sphincters and a decrease in the distance between the anal mucosa and the symphysis as a sign of pelvic floor elevation. Six months after surgery, continence and quality of life were markedly better than before the operation.We were able to confirm the hypotheses given above. The improvements of pelvic floor contraction and rectal perception are rapid adjustment processes in response to stimulation of sacral nerves S3/S4 when turning on the stimulator.

Knowledge about the changes in the electric conductivity during the coagulation process of radiofrequency ablation of the liver is a prerequisite for the predictability of produceable thermonecrosis in the liver.Continuous measurements of the electric conductivity sigma in ex vivo porcine liver (n = 25) were done during the coagulation and cooling process at the temperature range of the radiofrequency ablation at a frequency of 470 kHz relevant for the radiofrequency ablation. Measurements of the electric conductivity were performed in both perfused porcine liver (n = 3) and a human surgical specimen from a colorectal liver metastasis.At a body temperature of 37 degrees C, conductance sigma was 0.41 siemens per metre (0.32 S/m; 0.52 S/m). Conductance sigma increased continuously and uniformly at a temperature of 77 degrees C. Maximum conductance sigma with 0.79 S/m (0.7 S/m; 0.87 S/m) was reached at 80 degrees C. A continuous reduction of conductance was observed during the cooling phase. At 37 degrees C, the specific conductance sigma in the healthy perfused porcine liver was 0.52 S/m, 0.55 S/m and 0.57 S/m (mean 0.55 S/m). The electric conductivity of the human colorectal liver metastasis was clearly higher.Changes in the specific conductivity during the coagulation and the cooling phase play an important role for the produceable size of a coagulation necrosis and necessitates an adaptation of the therapy parameters during radiofrequency ablation.

Surgical skills courses are becoming increasingly popular. This study focuses on their long-term effects. Participants in a 1-week general and visceral surgery course were included. Exercises in conventional and laparoscopic surgery were conducted under tutor guidance. Eighteen months after the course at the earliest (18–90), all participants (n = 756) from 1999 to 2005 received a standardized questionnaire on the surgical training situation, the learning success, the implementation of acquired skills in routine clinical practice, and the value of skills courses. We evaluated 459 of 756 participants (60.7%). The percentage of participants fully confident in their ability to suture a simple and a difficult anastomosis increased from 56.9% and 21.6% before to 93.5% and 59.3% after the course (p

Background About one quarter of all medullary thyroid cancers (MTC) are determined genetically due to a mutation in the RET proto-oncogene. The most common site of mutation is in codon 634. Therapeutic approaches toward patients at risk for the development of MTC identified by family screening programs range from total thyroidectomy to total thyroidectomy with lymphadenectomy of all 4 compartments. Methods We report 17 patients (median age, 13 years; range, 4–36) carrying a mutation in codon 634 of the RET proto-oncogene who were operated on prophylactically at our department. All patients underwent thyroidectomy with bilateral cervicocentral lymphadenectomy. Current calcitonin level, overall survival, and disease-free survival were analyzed by contacting general practitioners and patients. Results Tumor classification was as follows: C-cell hyperplasia, 18% (n = 3); T1 ( 1 cm), 12% (n = 2). Only 2 patients had lymph node metastases (12%). These patients developed recurrent disease (median observation time, 147 months; range, 90–181). In 1 patient, the calcitonin level normalized after unilateral cervicolateral lymphadenectomy. The other patient (9 years old at primary operation) still has a persistently increased serum calcitonin level after 140 months of follow-up despite several operations for MTC. Conclusion Total thyroidectomy with bilateral cervicocentral lymphadenectomy is sufficient as routine “prophylactic therapy” for patients with mutations in codon 634 of the RET proto-oncogene. Cervicolateral lymphadenectomy is indicated if calcitonin remains elevated after primary surgery. Prophylactic thyroidectomy should be performed before the development of lymph node metastases.

Background and aims The etiology of pouchitis after coloproctomucosectomy with ileal pouch-anal anastomosis in patients with ulcerative colitis is still unknown. Beside changes in luminal antigens, the immunological predisposition is assumed to be responsible. In previous electrophysiological studies, we showed that mucosal barrier and transport function in pouchitis is markedly reduced. Thus, the aim of the present study was to analyze barrier function on the molecular level. Material and methods Pouch biopsies of 36 ulcerative colitis patients were analyzed. Time points were (1) intraoperative immediately prior to ileal pouch-anal anastomosis (n = 13), (2) >1 year after ileostomy closure (pouch, n = 12), and (3) during pouchitis (n = 11). Control terminal ileum biopsies were obtained from eight patients undergoing hemicolectomy due to carcinoma. Expression of tight junction proteins was analyzed by Western blotting and confocal laser-scanning microscopy. To elucidate effects on epithelial barrier properties, impedance spectroscopy was performed in miniaturized Ussing chambers. Results In pouchitis, epithelial resistance was markedly reduced compared to non-inflamed pouch and control ileum. Expression of tight junction proteins claudin-1, 3, 4, 5, and 7 and occludin revealed differential expression regulation with the tightening tight junction protein claudin-1 being decreased and an increase of the pore-forming claudin-2, whereas other claudins remained constant. Morphometry indicated the mucosal surface to be unchanged. Conclusion Pouchitis is characterized by a selective change of tight junction proteins in favor of opening the epithelial tight junction and, thus, the paracellular pathway, which contributes to the inflammatory process. This resembles changes in inflammatory bowel disease (IBD) and indicates IBD recurrence in pouchitis.

Background: Bevacizumab is increasingly used in combination with chemotherapy for treatment of unresectable non-small cell lung cancer. The aim of this report is to underline possible risks associated with this otherwise well-tolerated drug. Patient: A 69-year-old patient with metastatic non-small cell lung cancer was started on a palliative chemotherapy regimen containing carboplatin, paclitaxel, and bevacizumab. Results: After the second cycle of chemotherapy, the patient developed abdominal pain. On emergency laparotomy, there was diffuse perforation of the colonic wall, so the patient underwent a Hartmann's procedure with subtotal colectomy. Histopathological examination confirmed the diagnosis of ischemic colitis. Conclusion: Gastrointestinal perforation is a known adverse event of bevacizumab therapy which so far has occurred only in patients with predisposing risk factors. Our patient illustrates that there must always remain a high index of suspicion regarding bowel perforation in patients developing acute abdominal pain under bevacizumab therapy, even if they have no apparent risk factors.

We investigated the effect of suramin on tumor growth and spread in an immunocompetent, orthotopic rat model of pancreatic cancer and analyzed the tumor vasculature by intravital microscopy.In vitro, rat ductal pancreatic cancer cells (DSL-6A) were incubated with suramin (10-800 microg/ml), and cell proliferation was assessed. In vivo, DSL-6A tumors were induced in the pancreas of Lewis rats. Animals received suramin (60 mg/kg, weekly i.p.) or the vehicle (controls). Treatment started after 3 days. Intravital microscopy after 1, 4, and 8 weeks quantified diameter, density, and permeability of tumor vessels. Primary tumor volume, local infiltration, and metastatic spread were determined at autopsy. Microvessel density was analyzed by immunohistochemistry.In vitro, proliferation was inhibited by suramin up to 95%. In vivo, all controls developed extensive tumor growth and spread. No tumor was detectable in half of the suramin-treated animals after 8 weeks; tumor dissemination was almost completely depressed. Suramin therapy resulted in a complete regression of tumor macrovessels and a significant reduction of microvessel density.Suramin significantly reduces primary tumor growth and dissemination in a clinically relevant rat model of pancreatic cancer and seems to play an important role for the inhibition of tumor angiogenesis.

Backwash ileitis (BI) has not been identified as a risk factor for pouchitis. The aim of this study was to investigate the barrier function of the ileoanal pouch depending on the presence of BI. The incidence of pouchitis in a population of ulcerative colitis patients with BI is also reported.Biopsies were taken from 80 patients with ulcerative colitis: a) terminal ileum prior to pouch creation (pre-IAP); b) 16 months after ileostomy closure (intact pouch); and c) during pouchitis. Patients were stratified into the BI group and the non-BI (ØBI) group. Barrier function was determined in Ussing-chambers as epithelial resistance by impedance analysis and as mannitol permeability from (3)H-mannitol fluxes. Na(+)-glucose co-transport was measured as a change in short-circuit current (I(SC)) after addition of glucose. Relative risk of developing pouchitis was calculated by corrected chi(2) test.In 13/21 (BI/ØBI) pre-IAP patients, 23/37 (BI/ØBI) with an intact pouch, and 35/7 (BI/ØBI) with pouchitis, epithelial resistance in BI/ØBI was 13.5+/-1.6/14.3+/-0.9 Omega.cm(2) for pre-IAP, 12.7+/-1.3/16.8+/-1.2 Omega x cm(2) (p0.05 BI versus ØBI) for the intact pouch, and 10.1+/-1.1/9.9+/-1.8 Omega x cm(2) for pouchitis (p0.05 BI versus ØBI with an intact pouch). No differences were found for electrogenic chloride secretion and active Na(+)-glucose co-transport between BI/ØBI in the three groups. In patients with BI, pouchitis was more common (35 versus 7 patients, odds ratio 33.0 (95% CI 8.3-143.9; p0.0001)).Ulcerative colitis patients with BI show impaired barrier function in the further course of the ileoanal pouch. Thus, BI has a long-term impact on epithelial barrier function.

Purpose: Epithelial to mesenchymal transitions are vital for tumor growth and metastasis. Several inducers of epithelial to mesenchymal transition are transcription factors that repress E-cadherin expression, such as Snail, Slug, and Twist. In this study, we aimed to examine the expression of these transcription factors in pancreatic cancer. Experimental Design: The expression of Snail, Slug, and Twist was detected by immunohistochemistry in tissue samples from patients with pancreatic ductal adenocarcinoma. Five human pancreatic cancer cell lines (AsPC-1, Capan-1, HPAF-2, MiaPaCa-2, and Panc-1) were analyzed by reverse transcription-PCR, real-time PCR, and Western blotting. An orthotopic nude mouse model of pancreatic cancer was applied for in vivo experiments. Results: Seventy-eight percent of human pancreatic cancer tissues showed an expression of Snail, and 50% of the patients displayed positive expression of Slug. Twist showed no or only weak expression. Snail expression was higher in undifferentiated cancer cell lines (MiaPaCa-2 and Panc-1) than in more differentiated cell lines (Capan-1, HPAF-2, AsPC-1). Expression of Slug was detected in all cell lines with different intensities. Twist was not expressed. After exposure to hypoxia, the Twist gene was activated in all five pancreatic cancer cell lines. Conclusions: The transcription factors Snail and Slug are expressed in pancreatic cancer but not in normal tissue, suggesting a role in the progression of human pancreatic tumors. Twist, activated by hypoxia, may play an important role in the invasive behavior of pancreatic tumors.

Wnt signaling plays a fundamental role in the control of cell proliferation and differentiation and is frequently deregulated in colorectal carcinoma leading to an enhanced expression of Wnt target genes. Pontin, a member of the AAA(+) superfamily, has previously been shown to interact with beta-catenin and to enhance TCF/beta-catenin-mediated transcription of Wnt target genes and thus may contribute to carcinogenesis. Here, we studied the expression of pontin in 34 patients with histologically proven colorectal cancer by immunohistochemistry on paraffin-embedded colorectal cancer samples using the monoclonal mouse anti-pontin (5G3-11) antibody. Cytoplasmic pontin staining of tumor cells was present in all cases and was stronger in 84.6% and equal in 15.4% of the cases compared with normal mucosa. In 50% of tumor specimens, an additional nuclear pontin staining pattern was noted with positivity ranging from 10% to 60% of the nuclei. Interestingly, all cases with nuclear pontin expression also revealed nuclear beta-catenin localization. Furthermore, pontin staining was stronger at the invasive margin and in tumor buds than in the tumor center in 41.2% and 37.9% of the cases, respectively. In this context, 66.7% and 64.7% of the cases with enhanced beta-catenin staining at the invasive margin and in tumor buds, respectively, also revealed stronger pontin expression. Analysis of pontin expression in 8 patients by Western blotting confirmed the histologic results. These data suggest that upregulation and nuclear localization of pontin together with beta-catenin may contribute to progression of colorectal carcinoma.

Thermal ablation techniques like radiofrequency or laser-induced thermotherapy (LITT) are increasingly used to treat tumors of parenchymatous organs. Minimal access, parenchymal preservation, and a low complication rate render them suitable for pulmonary tumors as well. Their successful clinical application depends on the induction of sufficiently large lesions and a knowledge of the energy parameters required for complete thermal ablation. The aim of this study was to establish a dose-response relationship for a percutaneous and an intraoperative system for LITT of lung tissue. Thermal lesions were induced in healthy porcine lungs using an Nd:YAG laser (1,064 nm). LITT was performed with a percutaneous application system in group I (n = 18) and an intraoperative application system in group II (n = 90). Laser energy was applied for 600-1,200 s in a power range of 20-32 W (12,000-38,400 J). The lesions were longitudinally and transversally measured, and the volume was calculated after the intervention. Furthermore, an open application system was used to perform LITT under in vivo conditions during lung perfusion and ventilation in domestic pigs. Lesion volumes in both groups showed a plateau-like curve when the laser power increased from an initial level of 25 W. With the percutaneous puncture system (group I), the application of 28 W (16,800 J) for 10 min generated the largest lesions with a volume of 12.54 +/- 1.33 cm(3), an axial diameter of 39.33 +/- 2.52 mm, and a diametrical diameter of 24.67 +/- 1.15 mm. A longer application time was not possible due to thermal instability of the applicator. Moreover, group I started developing extensive carbonizations at a laser power of 22 W (13,200 J). The intraoperative application system (group II) achieved the largest lesion volumes of 11.03 +/- 2.54 cm(3) with diameters of 34.6 +/- 4.22 mm (axial) and 25.6 +/- 2.51 mm (diametrical) by an exposure time of 20 min and a power of 32 W (38,400 J). Here extensive carbonizations only started to occur at 28 W (33,600 J). Under in vivo conditions, all pigs tolerated the LITT procedure well without complications. Besides a typical cooling effect in the vicinity of blood vessels, the thermal lesions were about three times smaller than the ex vivo lesions. Both the percutaneous and the open LITT application system induced reproducible, clinically relevant lung lesions. The percutaneous puncture set generated large relevant lesions, although its usability is limited by its restricted capacity and high carbonization risk. It is suitable for powers up to 22 W. The intraoperative application system allows higher energy exposure to induce larger lesion volumes. This study elucidates the dose-effect relation of two clinically relevant puncture sets.

Total mesorectal excision (TME) has become the recommended method for treatment of cancer in the middle or lower third of the rectum. Thus very low anastomoses are necessary to preserve continence, and pouch reconstruction is favored. It is unclear whether the level of anastomosis is important for continence and quality of life in colonic J-pouch reconstruction. In this investigation all patients were included who underwent curative elective anterior continuity resection with colorectal or coloanal J-pouch reconstruction for primary rectal cancer between January 2001 and December 2004. Exclusion criteria were distant metastases and any signs of recurrence at the time of investigation. Evaluation of continence performance by Wexner and Holschneider questionnaire and quality of life using the QLQ-C30 and QLQ-CR38 (EORTC) questionnaires was done 220 +/- 38 days after closure of the protective Ileostomy, which was performed 106 +/- 48 days after primary intervention. Fifty-two patients (79%) were analyzed. Colopouch rectal anastomosis was performed in eighteen cases and colopouch anal anastomosis in thirty-four cases. Fifty percent of the patients in both groups were continent for solid stool. Patients with a colopouch anal anastomosis had a significantly higher rate of incontinence for liquid stool, however. They took stool-regulating medicine more frequently and complained of fecal soiling and a restricted quality of life. Patients with a colopouch anal anastomosis had a significantly lower score on the most important points of the QLQ-C30 (emotional functioning, social functioning, pain, and quality of life). The same applied to the QLQ-CR38 for body image and problems with defecation. The quality of life of patients with a colopouch anal anastomosis was still considered acceptable compared with reference data for the normal healthy population, however. Both continence and quality of life are substantially affected by the level of the anastomosis after colonic pouch reconstruction. This suggests preservation of a small part of the rectum when oncologically feasible and performing a colopouch rectal anastomosis.

Background and Objectives Proliferation and synthesis of hepatocellular tissue after tissue damage are promoted by specific growth factors such as hepatic tissue growth factor (HGF) and connective growth factor (CTGF). Laser-induced thermotherapy (LITT) for the treatment of liver metastases is deemed to be a parenchyma-saving procedure compared to hepatic resection. The aim of this study was to compare the impact of LITT and hepatic resection on intrahepatic residual tumor tissue and expression levels of mRNA HGF/CTGF within liver and tumor tissue. Study Design/Materials and Methods Two independent adenocarcinomas (CC531) were implanted into 75 WAG rats, one in the right (untreated tumor) and one in the left liver lobe (treated tumor). The left lobe tumor was treated either by LITT or partial hepatectomy. The control tumor was submitted to in-situ hybridization of HGF and CTGF 24–96 hours and 14 days after intervention. Results Volumes of the untreated tumors prior to intervention were 38±8 mm3 in group I (laser), 39 ± 7 mm3 in group II (resection), and 42 ± 12 mm3 in group III (control) and did not differ significantly (P > 0.05). Fourteen days after the intervention the mean tumor±SEM volume of untreated tumor in group I (laser) [223 ± 36] was smaller than in group II (resection) [1233.28 ± 181.52; P

In situ ablation of colorectal liver metastases is frequently assessed for palliative treatment only. The establishment of clinically relevant lesion size and a lack of long-term survival data were regarded as main limitations to using them with curative intention. In contrast to surgical liver resection, whose oncological findings seem to have remained unchanged over the years, the in situ ablation methods have considerably changed technically and clinically in the last few years.The aim of the paper was to point out experimental and clinical data underlining the impact of in situ ablation for potentially curative treatment of colorectal liver metastases.On the basis of experimental data, the aim of complete local tumor control (R0 ablation) can only be obtained if additional energy is applied after reaching the tumor-adapted maximal coagulation volume. Analogous to the oncological safety margin in surgical resection, we defined this decisive energy difference as the "energy safety margin" for in situ ablation. The energy safety margin is the energy that must be additionally applied after reaching the plateau in the energy/volume curve to achieve complete tumor coagulation. In addition to that, in situ ablation should be combined with temporary interruption of hepatic perfusion whenever possible to prevent intralesional recurrences. In this way, the thermoprotective mechanism of hepatic perfusion can be effectively eliminated. With restrictions, the survival data after ablation in specialized centers is comparable to surgical resection with concomitantly lower morbidity and mortality. Based on recent findings and with the corresponding expertise in the field of ablation and state-of-the-art equipment, ablation is, thus, an alternative to surgical resection. The combined application of surgical resection and ablation is also a suitable method for increasing the R0 rate and thus helps improve the prognosis of treated patients. In summary, it can be said that in situ ablation is a useful expansion of the therapeutic spectrum of liver metastases and can be applied as an alternative to or in combination with surgical resection.

Background Only monopolar systems have thus far been available for radiofrequency ablation of liver tumors, whose application is restricted because of the incalculable energy flow, reduction of electrical tissue conduction, and limited lesion size. The aim of this study was to evaluate a novel internally cooled bipolar radiofrequency application device under in vivo conditions and to compare the effect of this system on lesion size when combined with hepatic arterial microembolization or complete hepatic blood flow occlusion. Materials and methods In a porcine liver model, RFA (60 W, 12 min) was performed with either normal (n = 12), partially interrupted (arterial microembolization via a hepatic artery catheter n = 12) or completely interrupted hepatic perfusion (Pringle’s maneuver, n = 12). RFA parameters (impedance, power output, temperature, applied energy) were determined continuously during therapy. RFA lesions were macroscopically assessed after liver dissection. Results Bipolar RFA induced clinical relevant ellipsoid thermal lesions without complications. Hepatic inflow occlusion led to a 4.3-fold increase in lesion volume after arterial microembolization and a 5.8-fold increase after complete interruption (7.4 cm3versus 31.9 cm3versus 42.6 cm3, P < 0.01). Conclusions The novel bipolar RFA device is a safe and effective alternative to monopolar RFA-systems. Interrupting hepatic perfusion significantly increases lesion volumes in bipolar RFA. This beneficial effect can also be achieved in the percutaneous application mode by RFA combined with arterial microembolization via a hepatic artery catheter.