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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent, which selectively induces apoptosis in many transformed cells without apparent toxic side effects in normal tissue. We recently described the construction and characterization of a lentiviral vector for expression of TRAIL. In this report, we evaluate its suitability for therapeutic application. In vitro, we observed specific induction of apoptosis upon transduction in human lung cancer cells. Cell death was partially dependent on successful integration and TRAIL expression by the vectors, but was to some extent mediated by protein carryover, as we found TRAIL protein associated with virus particles. Transduction of subcutaneously growing lung tumors on nude mice with lentiviral TRAIL mediated a transient suppression of tumor growth. Analysis of tumor sections revealed that transduction efficiency of lentiviral control vector but not of lentiviral TRAIL vector was high. This was because of the direct cytotoxic activity of recombinant TRAIL present in viral particles, which prevented efficient tumor transduction. These data therefore suggest that enveloped viral vectors constitutively expressing TRAIL are well suited for ex vivo applications, such as the transduction of tumor-homing cells, but may have a lower effect when used directly for the transduction of tumor cells in vivo.

Pancreatic adenocarcinoma is one of the most aggressive human solid tumors with a 5-year survival rate of less than 5%. The only chance for cure is complete resection of the tumor. This can be achieved in approximately 8-15% of all cases since solely localized tumors and a small part of locally advanced carcinomas may be resected. However, many patients suffer from a local relapse after surgical therapy. In order to improve the long-term survival of surgically treated patients, extended lymphadenectomy after partial duodenopancreatectomy was introduced. Some retrospective studies from the 80 s showed improved survival rates for those patients in whom extended lymphadenectomy was performed. However, these results were not confirmed in following randomised controlled prospective studies. Extended lymphadenectomy can be performed with slightly increased morbidity and equal mortality but survival is not improved. Therefore, standard lymphadenectomy is recommended in patients undergoing duodenopancreatectomy for pancreatic cancer. Extended lymphadenectomy (with retroperitoneal clearance) should only be accomplished within controlled clinical studies.

Patients with malignant diseases are increasingly being treated with multimodal therapeutical concepts based on the three major modalities surgery, radiotherapy and chemotherapy. The perioperative period is crucial within this multimodal concept as the prognosis of patients may be directly influenced by perioperative measures. In addition, it is of major importance to avoid complications in the perioperative phase, as these might worsen the prognosis of the patient and in order to prevent a delay in the beginning of planned adjuvant therapies. These aspects demonstrate the important role of anesthesia in the treatment of patients with cancer. Further studies defining the relevance of anesthesiologic measures in oncologic patients are needed.

Simultaneous pancreas–kidney transplantation is an established procedure for patients with type I diabetes and end-stage renal disease. Continuous advances in the operation techniques with consequent reduction of perioperative morbidity and mortality and the introduction of modern immunosuppressive agents improved not only patients but also graft survival and significantly decreased rejection episodes of both kidney and pancreas grafts. Availability of a variety of new immunosuppressants in the clinical routine and increasing experience of the transplant specialists allowed further developments of therapeutic schemes with application of induction and maintenance immunosuppressive protocols. In this article, we summarize the current status of immunosuppressive regimens in simultaneous pancreas and kidney transplantation.

Liver transplantation (LTx) has become the treatment of choice for selected cases of benign and malignant liver disease. Despite becoming increasingly safer in recent years this procedure still incurs several serious postoperative complications. The most significant surgical complications are related to surgical technique, particularly the reconstruction and/or anastomosis of the hepatic artery. Arterial hypoperfusion may lead to graft failure, sepsis, or ischemic biliary lesions. In this review we focus on the Achilles' heel of LTx: the hepatic artery. We provide transplant surgeons with an overview of the technical options that are available to increase arterial inflow and subsequently improve patient outcome. We exemplify some of the discussed techniques using a liver transplant case with an eventful postoperative course because of arterial complications.

Infection of pancreatic necrosis (IPN) is strongly associated with sepsis and multiple organ dysfunction and is an absolute indication for surgery. Patients with IPN are critically ill at the time of surgery and may benefit from a minimally invasive approach with reduced surgical trauma. Recently, several minimally invasive necrosectomy techniques have been reported. However, the effects and potential dangers of a pneumoperitoneum in IPN cases are unknown. This study aimed to determine the effects of a pneumoperitoneum on systemic cytokine levels, bacterial translocation, and systemic organ complications in a rat model of IPN.For this study, IPN was induced in Wistar rats using retrograde intraductal infusion of 3% taurocholate. After 8 h, the animals were subjected to either laparoscopy (pneumoperitoneum at 8 mmHg) or laparotomy for 1 h and killed after 1 or 3 h. Severe acute pancreatitis with IPN was proved by serum amylase and lipase, histology, tissue activity of myeloperoxidase (MPO), and bacteriology. Systemic levels for interleukin-10 (IL-10), IL-6, tumor necrosis factor-alpha (TNF-alpha), and lipopolysaccarides were determined by enzyme-linked immunoassay (ELISA). Systemic organ damage and dysfunction were evaluated using MPO activity (lung), serum creatinine (kidney), and serum aminotransferases (liver).Necrotizing pancreatitis developed in all the animals. Most of the animals (85%) had proven infected necrosis. Elevated cytokine levels and deteriorated organ parameters demonstrated systemic inflammation and organ failure. Although there was a tendency toward a higher level of proinflammatory cytokines after laparotomy, there were no significant differences between laparotomy and laparoscopy. Furthermore, these alterations were not accompanied by any differences in bacterial translocation (lipopolysaccharides), systemic organ damage, or mortality between laparoscopy and laparotomy.In the current model of infected pancreatic necrosis, a pneumoperitoneum did not result in increased cytokine release or bacterial translocation. However, the putative advantage of less surgical trauma with the laparoscopic approach did not play a significant role in the setting of severe acute pancreatitis with IPN.

Kontinuierliche Verbesserungen chirurgischer und auch anasthesiologischer Techniken haben zu einer wesentlichen Reduktion perioperativer Komplikationen gefuhrt. Der postoperative Verlauf viszeralchirurgischer Patienten, deren individuelle postoperative Rekonvaleszenz und letztendlich auch die Dauer des stationaren Aufenthaltes werden mehr und mehr durch das klinische Bild des postoperativen Ileus bestimmt. In der vorliegenden Arbeit werden die moglichen Einflussgrosen diskutiert. Daruber hinaus werden die Moglichkeiten der Pravention und Therapie des postoperativen Ileus kurz dargestellt.

Traditionally open surgical resection has been recommended for colorectal tumours, but recently, laparoscopic surgery has gained popularity. This review summarizes the published data on laparoscopic colorectal cancer surgery with emphasis on recently published trials. For colon cancer laparoscopic resection appears to be associated with the same outcome as open surgery. However, whilst short-term outcome was better in the laparoscopic group in most of the randomized trials, when comparing laparoscopic with fast-track open surgery, no differences could be demonstrated in a randomized control trial. For rectal cancer the data are less clear. It seems that it may be feasible to resect at least small rectal cancers laparoscopically. Clearly the role of the laparoscopic technique needs to be better defined in rectal cancer. It has been well documented that short- and long-term outcome of colorectal cancer surgery depends on the quality and experience of the team treating the patient. Therefore, the major future challenge in laparoscopic colorectal cancer surgery will be to provide and structure adequate training and introduce quality control measures.

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.

Background Postoperative local water-filtered infrared A (wIRA) irradiation improves tissue oxygen partial pressure, tissue perfusion and tissue temperature, which are important in wound healing. Methods The effect of wIRA irradiation on abdominal wound healing following elective gastrointestinal surgery was evaluated. Some 111 patients undergoing moderate to major abdominal surgery were randomized into one of two groups: wIRA and visible light irradiation (wIRA group) or visible light irradiation alone (control group). Uncovered wounds were irradiated twice a day for 20 min from days 2–10 after operation. Results Irradiation with wIRA improved postoperative wound healing in comparison to visible light irradiation alone. Main variables of interest were: wound healing assessed on a visual analogue scale (VAS) by the surgeon (median 88·6 versus 78·5 respectively; P < 0·001) or patient (median 85·8 versus 81·0; P = 0·040), postoperative pain (median decrease in VAS score during irradiation 13·4 versus 0; P < 0·001), subcutaneous oxygen tension after irradiation (median 41·6 versus 30·2 mmHg; P < 0·001) and subcutaneous temperature after irradiation (median 38·9 versus 36·4 °C; P < 0·001). The overall result, in terms of wound healing, pain and cosmesis, measured on a VAS by the surgeon (median 79·0 versus 46·8; P < 0·001) or patient (79·0 versus 50·2; P < 0·001) was better after wIRA irradiation. Conclusion Postoperative irradiation with wIRA can improve normal postoperative wound healing and may reduce costs in gastrointestinal surgery.

Full right hepatic grafts are most frequently used for adult-to-adult living donor liver transplantation (LDLT). One of the major problems is venous drainage of segments 5 and 8. Thus, this study was designed to provide information on venous drainage of right liver lobes for operation-planning. Fifty-six CT data sets from routine clinical imaging were evaluated retrospectively using a liver operation-planning system. We defined and analyzed venous drainage segments and the impact of anatomic variations of the middle hepatic vein (MHV) on venous outflow from segments 5 and 8. MHV variations led to significant shifts of segment 5 drainage between the middle and right hepatic vein. In cases with the most frequent MHV branching pattern (n = 33), a virtual hepatectomy closely right to the MHV intersected drainage vessels that provided drainage for 30% of the potential graft, not taking into account potential veno-venous shunts. In individuals with inferior MHV branches that extend far into segments 5 and 6 (n = 10), the overall graft volume at risk of impaired venous drainage increased by 5% (p < 0.001). If this is confirmed in clinical trials and correlated with intraoperative findings, the use of liver operation-planning systems would be beneficial to improve overall outcome after right lobe LDLT.

Background Organ function after liver transplantation is determined by ischemia-reperfusion injury. Destruction of Kupffer cells with gadolinium chloride (GdCl 3 ) has been shown to have a possible preventive effect on the extent of this injury, which can be extrapolated by analyzing the distribution of hepatic microperfusion. The aim of this study was to evaluate the protective effect of GdCl 3 on disturbances of microperfusion in the transplanted liver. Methods Landrace pigs were randomly divided into three groups. In the control group (CG; n = 6) a mapping of the native liver was conducted. For mapping, the four hepatic liver lobes were named from right to left with A to D and every lobe was divided into three vertical segments (cranial, medial, and caudal). In each of these 12 areas, microperfusion was quantified using a thermodiffusion probe (TD [mL/100 g/min]). The other two groups were considered as transplanted treated group (TTG; n = 10) and transplanted nontreated group (TnTG; n = 10). The TTG received an infusion of 20 mg/kg GdCl 3 intravenously 24 hours before organ harvesting. Then standardized orthotopic liver transplantation was performed. In TnTG, standardized orthotopic liver transplantation was carried out without prior GdCl 3 injection. In the recipients, the microperfusion of transplanted livers were mapped in both TnTG and TTG, in two different time points (1 hour [ n = 5] and 24 hours ( n = 5]) after reperfusion. Results A significant reduction of macrophages in the TTG livers in comparison to the CG and TnTG livers was observed ( P P > .05). Regarding liver microperfusion, in TnTG, a marked heterogeneity was detected in the livers after reperfusion. Significant differences between liver lobes (horizontal planes; P = .032) and vertical layers of intralobar liver parenchyma ( P = .029) were observed. The same pattern was seen in TTG livers after reperfusion and a significant difference between horizontal ( P = .024) and vertical layers ( P = .018) of liver tissue were observed. Comparing intralobar regional flow data between vertical planes 24 hours after reperfusion still showed a prominent variation of hepatic tissue perfusion in TnTG livers ( P = .028). Within the same horizontal layers, no significant differences between lobes were measured anymore ( P = .16). Contrary to TnTG, in TTG, a homogenous pattern of regional liver tissue perfusion was recorded 24 hours after reperfusion. Comparison of TD data on the liver regions showed no significant microperfusion differences in either horizontal ( P = .888) or vertical ( P = .841) layers. Conclusions Application of GdCl 3 resulted in a significant reduction of Kupffer cells. Twenty four hours after transplantation microperfusion showed a homogeneous pattern, which constituted an earlier and better recovery of the transplanted liver. Therefore, destruction of Kupffer cells reduced ischemia-reperfusion injury and seemed to be responsible for the early recovery of microperfusion disturbances and thus for an improvement of graft function.

The prognosis of patients with rectal cancer has been improved significantly after introduction of the total mesorectal excision (TME). Just by performing TME, the local recurrence rates could be decreased to less than 10 %, independent of multi-modal therapeutic concepts. In contrast, the local recurrence rate reached 4 to 55 % (median 20 %) in a German multicenter study in 1995 prior to the nationwide introduction of TME. The goal of this overview is to compare the different concepts in the multi-modal therapy of rectal cancer with their advantages and disadvantages based on the current literature. Mentioned will be local recurrence rates and survival, but also toxicity, costs and acceptance of patients. Furthermore, a preview is given about future developments.

Hintergrund Die Medizinische Fakultat der Universitat Heidelberg implementierte 2001 ein problemorientiertes klinisches Kurrikulum (Heicumed, Heidelberger Curriculum medicinale). Die vorliegende Studie analysiert Evaluationsergebnisse zweier Studierendenkohorten vor Einfuhrung von Heicumed mit dem Ziel, Defizite der Ausbildung aufzudecken und Folgerungen fur die Implementierung von Heicumed zu ziehen.

Fur die Beurteilung der Nierenarterien, der Nierenvenen und auch der ableitenden Harnwege stehen heute hochwertige nichtinvasive bildgebende Verfahren zur Verfugung. Die Mehrschicht-Computertomographie (MS-CT) erlaubt eine verbesserte zeitliche und ortliche Auflosung durch isotrope Voxel mit einer Kantenlange von weniger als einem Millimeter. Mit dieser Technik konnen heute verlasslich Polgefase mit einem Durchmesser von 2 mm und Nierenarterienstenosen dargestellt werden. Die praoperative Diagnostik von arteriellen und venosen Gefasen in der MS-CT stimmt zu fast 100% mit dem intraoperativen/interventionellen Befund uberein. Bei der Darstellung des Nierenbeckens und der ableitenden Harnwege erlaubt die CT eine sichere Darstellung und Kontrastierung. Die kontrastmittelverstarkte Magnetresonanzangiographie (MRA) hat sich als verlassliche Methode bei der Darstellung von Nierengefasen und des ableitenden Systems etabliert und erlaubt, wie die CT-Untersuchung, auch die Darstellung von Parenchymveranderungen. Durch das sehr hohe Signal-zu-Rausch-Verhaltnis der MRT in der kontrastmittelverstarkten Darstellung konnte gezeigt werden, dass die MRT der digitalen Subtraktionsangiographie bei der Beurteilung von vaskularen und parenchymatoser Strukturen uberlegen ist. Vorteile der MRT sind das Fehlen einer Rontgenexposition und die sehr gute Vertraglichkeit des Kontrastmittels, vor allem fur Patienten mit eingeschrankter Nierenfunktion. Zusatzlich kann die Funktion der Niere beurteilt werden. Verbesserte 3D-Nachverarbeitungsprogramme in Verbindung mit leistungsstarken 3D-Rechnern erlauben heute unterschiedliche Nachverarbeitungsmodalitaten. 3D-Nachverarbeitungsmethoden wie Volume-rendering und Maximum-Intensity-Projektion erlauben die artefaktfreie Rekonstruktion und Darstellung des Situs zur Beurteilung der Nierengefase.

The term autoimmune pancreatitis (AIP) describes a nonalcoholic, chronic lymphoplasmocytic pancreatitis. The lymphoplasmocytic infiltration is characterized by periductal localization of predominantly CD4-positive T cells, fibrosis, and acinar atrophy, frequently resulting in stenosis of the main pancreatic and distal common bile ducts. Imaging studies often reveal a diffuse narrowing of the pancreatic main duct and swelling of the pancreatic head wrongly suggesting the presence of a malignant tumor. Clinical signs include mild abdominal pain, jaundice, recurrent episodes of acute pancreatitis, and even new-onset diabetes mellitus. Additionally, AIP can be associated with other autoimmune diseases such as Sjogren's syndrome, primary sclerosing cholangitis, chronic inflammatory bowel diseases, and retroperitoneal fibrosis. Serological markers include autoantibodies and increased levels of gamma globulin and especially IgG4. Steroids seem to be effective in improving clinical symptoms as well as in the resolution of pancreatic and bile duct narrowing. This distinguishes AIP from other forms of pancreatitis and from pancreatic neoplasms. Further studies of the underlying pathophysiologic mechanisms, prognosis, and new diagnostic tools are needed to provide adequate and effective treatment in the future. In this article, we summarize the current knowledge about AIP and present 17 cases that underwent surgical resection at our institution from 2003 to 2004.

Background Postoperative pancreatic fistula (POPF) is still regarded as a major complication. The incidence of POPF varies greatly in different reports, depending on the definition applied at each surgical center. Our aim was to agree upon an objective and internationally accepted definition to allow comparison of different surgical experiences. Methods An international panel of pancreatic surgeons, working in well-known, high-volume centers, reviewed the literature on the topic and worked together to develop a simple, objective, reliable, and easy-to-apply definition of POPF, graded primarily on clinical impact. Results A POPF represents a failure of healing/sealing of a pancreatic-enteric anastomosis or a parenchymal leak not directly related to an anastomosis. An all-inclusive definition is a drain output of any measurable volume of fluid on or after postoperative day 3 with an amylase content greater than 3 times the serum amylase activity. Three different grades of POPF (grades A, B, C) are defined according to the clinical impact on the patient's hospital course. Conclusions The present definition and clinical grading of POPF should allow realistic comparisons of surgical experiences in the future when new techniques, new operations, or new pharmacologic agents that may impact surgical treatment of pancreatic disorders are addressed.

Background and aims: Conflicting results exist about the presence of Mycobacterium avium subspecies paratuberculosis (MAP) specific IS 900 DNA in Crohn’s disease (CD) tissues. Therefore, we examined IS 900 in a large number of gut samples from patients with CD (n = 100) and ulcerative colitis (UC, n = 100), and in non-inflamed control tissues (nIBD, n = 100). We hypothesised that IS 900 DNA detection might be associated with distinct clinical phenotypic characteristics in CD. Methods: The prevalence of MAP DNA in surgically resected tissues was examined using a mechanical-enzymatic disruption technique and nested IS 900 specific polymerase chain reaction (PCR). CD patients were stratified according to the criteria of the Vienna classification and other clinical characteristics. Results: IS 900 PCR detection rate was significantly higher in CD tissue samples (52%) than in UC (2%) or nIBD (5%) specimens (p 900 DNA was detected in samples from both diseased small bowel (47%) as well as from the colon (61%). No firm association between MAP specific IS 900 detection rates and clinical phenotypic characteristics in CD could be established. However, corticosteroid medication constituted a factor which tended to have a negative influence on IS 900 DNA detection rates in CD (p Conclusions: The presence of MAP specific IS 900 DNA is a predominant feature of CD. Therapeutic intervention against MAP might represent a potential target for disease mitigation in Crohn’s disease.

Das Ziel der Studie war eine Erfassung der Lebens-, Arbeits- und Karrierebedingungen von Arztinnen an den chirurgischen Universitatskliniken. An 261 operativ tatige Arztinnen der Fachrichtungen Viszeral-, Unfall- und Gefaschirurgie an 36 deutschen Universitatskliniken wurde ein Fragebogen verschickt. Die Antworten von 134 Chirurginnen (51,3%) wurden ausgewertet. Das Durchschnittsalter der befragten Chirurginnen lag bei 35,1 Jahren (27–54 Jahre). 78% der Chirurginnen waren in der Fachrichtung Viszeralchirurgie, 17% in der Unfallchirurgie und 5% in der Gefaschirurgie tatig. 72% waren promoviert und 9% habilitiert, 45% waren als Facharztinnen und 19% als Oberarztinnen beschaftigt. 80% gaben an, meistens oder immer mit ihrer beruflichen Situation zufrieden zu sein. 79% berichteten uber berufliche Hindernisse. Als haufigste Grunde fur eine Behinderung der Karriere wurden Dominanz der mannlichen Strukturen (80%), fehlendes Mentoring (70%), zu geringe operative Tatigkeit (67%) und eine geringere Chancengleichheit im Vergleich zu mannlichen Kollegen (60%) genannt. Zum Abbau der beschriebenen Karrierehemmnisse und zur Vermeidung einer Abwanderung an nichtuniversitare Einrichtungen ist eine Verbesserung der Kooperation zwischen den Chirurginnen, den Klinikleitungen und auch den staatlichen Institutionen erforderlich.

Management of acute necrotizing pancreatitis has changed significantly over the past years. Early management is non-surgically and solely supportive. Today, more patients survive the early phase of severe pancreatitis due to improvements of intensive-care-medicine. Pancreatic infection is the major risk factor with regard to morbidity and mortality in the late phase of severe acute pancreatitis. Whereas early surgery and surgery for sterile necrosis can only be recommended in selected cases, pancreatic infection is a well accepted indication for surgical treatment. Surgery should ideally be postponed until four weeks after the onset of symptoms as necrosis is well demarcated at that time. Four surgical techniques can be performed with comparable results regarding mortality: necrosectomy combined with (1) open packing, (2) planned staged relaparotomies with repeated lavage, (3) closed continuous lavage of the retroperitoneum, and (4) closed packing. However, closed continuous lavage of the retroperitoneum, and closed packing seem to be associated with a lower morbidity compared to the other two approaches. Advances in radiologic imaging, new developments of interventional radiology and other minimal access interventions have revolutionized the management of many surgical conditions over the past decades. However, minimal invasive surgery and interventional therapy for infected necrosis should be limited to specific indications in patients who are critically ill and otherwise unfit for conventional surgery. Open surgical debridement is the “gold standard” for treatment of infected pancreatic and peripancreatic necrosis.

Kidney transplantation in rats is a useful model for microsurgery, transplantation, and immunology studies. Our aim was to analyze various techniques of kidney transplantation in rats with emphasis on guidelines for the prevention and management of complications. Complications were categorized into general, vascular, and urological types and respectively attributed to long transplantation time, core body temperature drop, nonreplaced intraoperative blood loss, anastomosis failure, and ureteral anastomoses with stents or cannulas, which increase the risk of calculus formation. In conclusion, to decrease the complication rates the animal should be placed on a heating pad. For hemodynamic stability NaCl should be administered subcutaneously. To reduce the risk of thrombosis, ice-cold saline containing heparin should be administered. Vascular complications, which mainly depend on the microsurgeon's expertise, can be prevented by meticulous surgical technique (preferably an end-in-end anastomosis). The main urinary complications can be minimized by avoiding stents and cannulas and focusing on using techniques like the bladder-patch technique.

Background Ischaemia–reperfusion (IR)-associated microcirculatory changes play a major role in acute post-transplantation pancreatitis. The pathophysiological role of platelets in these events is unknown. The aim of this study was to examine platelet adhesion and function during early reperfusion after pancreatic ischaemia. Methods Rats were subjected to warm pancreatic ischaemia by cross-clamping of the pancreatic vessels for 1 h. After 1 h of reperfusion, platelet–endothelium interaction was evaluated after platelet separation and staining by fluorescence microscopy. Amylase levels and pancreatic histology were evaluated 24 h after reperfusion. Animals treated according to an identical protocol, but without ischaemia, served as controls. Results Mild pancreatitis had developed by 24 h after IR; serum amylase levels were significantly higher than those in control animals. The numbers of adherent platelets in capillaries and venules were significantly increased, and platelet velocity in capillaries was significantly decreased, in the IR group compared with controls. There was significantly more oedema and inflammation in pancreatic tissue after IR. Conclusion Warm ischaemia for 1 h followed by reperfusion for 24 h caused mild pancreatitis in this experimental model. The pancreatic microcirculation was characterized by pronounced platelet–endothelium interaction in capillaries and venules. These results suggest that platelet activation may play an important role in acute post-transplantation pancreatitis.

Background It is not known whether pylorus-preserving duodenopancreatectomy is as effective as the classical Whipple procedure in the resection of pancreatic and periampullary tumours. A prospective randomized trial was undertaken to compare the results of the two procedures. Methods Clinical data, histological findings, short-term results, survival and quality of life of all patients having surgery for suspected pancreatic or periampullary cancer between June 1996 and September 2001 were analysed. Results Two hundred and fourteen patients were randomized to undergo either a standard or a pylorus-preserving Whipple resection. After exclusion of 84 patients on the basis of intraoperative findings, 130 patients (66 standard Whipple operation and 64 pylorus-preserving resection) were entered into the trial. Of these, 110 patients with proven adenocarcinoma (57 standard Whipple and 53 pylorus-preserving resection) were analysed for long-term survival and quality of life. There was no difference in perioperative morbidity. Long-term survival, quality of life and weight gain were identical after a median follow-up of 63·1 (range 4–93) months. At 6 months, capacity to work was better after the pylorus-preserving procedure (77 versus 56 per cent; P = 0·019). Conclusion Both procedures were equally effective for the treatment of pancreatic and periampullary cancer. Pylorus-preserving Whipple resection offers some minor advantages in the early postoperative period, but not in the long term.

Over many decades the surgical treatment of gastrointestinal tumours was limited to cases of manifest malignancy and was performed with curative or palliative intent. Molecular diagnostics have now led to an optimised characterisation of different sporadic and hereditary tumour entities. Furthermore, a number of diseases which are an obligatory precancerosis or which carry a very high risk of cancer in their long courses have now been identified. Parallel to these developments, a dramatic reduction of morbidity has been achieved in major abdominal surgery due to more subtle and blood-sparing surgical techniques and mortality has been reduced to a minimum even in the most major procedures. This combination nowadays safely allows preventive or preventive extended surgical measures in cases where interventional therapy cannot be adequately employed.

Even in pancreatic surgery, as in other organs, there is a tendency towards subtle organ-preserving techniques. Benign duodenal tumors which cannot be resected transduodenally or multiple dysplastic duodenal adenomas in patients with familial adenomatous polyposis (FAP) usually require partial pancreaticoduodenectomy. However, pancreas-preserving duodenectomy may represent a viable alternative. This technique allows for the resection of the entire duodenum without resection of the pancreatic head. Large duodenal adenomas, multiple adenomas with dysplasia in patients with FAP, and based on the literature extended duodenal injury after trauma may represent indications for this surgical technique. Compared with duodenopancreatectomy, this intervention can be performed with a comparably low morbidity and leads to good functional results. Beside the preservation of pancreatic parenchyma and the reduction of the number of anastomoses, this technique offers the advantage of uncomplicated endoscopic follow-up. In this article we describe the surgical technique of pancreas-preserving duodenectomy and our experience with this intervention.

Uber den Zeitraum 2001 bis 2003 wurden alle in der allgemein-chirurgischen Hochschulambulanz der Universitatsklinik Heidelberg anfallenden Behandlungsfalle, Diagnosen und Prozeduren, sowie Daten zu Patientenherkunft und Zuweisercharakteristik, differenziert nach viszeral-, gefaschirurgischen und traumatologischen Bereichen prospektiv aufgezeichnet. Weiterer Fokus wurde auf die Quantifizierung von zeitphasenabhangigen Variabilitaten der Leistungsvolumina und der resultierenden Belastungsschwankungen gesetzt. Zusatzlich wurde retrospektiv eine Aufwandsabschatzung in den Bereichen Forschung, Lehre und Krankenversorgung mittels strukturierten Fragebogen und Interviews durchgefuhrt. Die Daten verdeutlichen die dominierend medizinische Versorgungsfunktion einer allgemein-chirurgischen Hochschulambulanz mit Uberlauffunktion fur den ambulanten Sektor. Forschung und Lehre treten in der Bedeutung zuruck und werden uberwiegend in nachgeschalteten Spezialambulanzen realisiert. Allgemein-chirurgische Ambulanzen, konnen damit fur integrierte medizinische Versorgungsmodelle eine gute Basis darstellen. Die Leistungsvergutung muss allerdings wegen der hohen Versorgungsvolumina und hohen Leistungsvorhaltungserfordernis durch immense Belastungsschwankungen zukunftig kostendeckender gestaltet werden.

Orthotopic liver transplantation (OLT) in rat is a demanding procedure, which has become a popular model to investigate various problems. Our aim was to review and analyze the various techniques of experimental OLT in the rat. A review of the literature revealed 30 techniques or technical modifications. Each modification represented a change or a simplification of the reconstruction method of five anatomical structures, which are cornerstones of a successful OLT: the suprahepatic inferior vena cava (SHVC), portal vein (PV), infrahepatic inferior vena cava (IHVC), hepatic artery (HA), and bile duct (BD). SHVC is anastomosed via microsuture or cuff. The PV anastomosis is performed by microsuture, cuff, or a microsuture-temporary splint technique. IHVC is reconstructed by a microsuture, cuff, or microsuture-temporary splint technique. Arterialization has been accomplished via microsuture (aortic segment, celiac segment, or aortic patch), cuff, splint, sleeve, or telescopic method. Nonarterialization of the graft has also been described. Methods for BD reconstruction include pull-through, telescopic, splint, and T-tube. Although a high level of microsurgical skill is the basic requirement in the microsuture technique which provides the most physiological situation and concomitantly reduces thrombosis, it increases anhepatic time compared to the cuff procedure. The learning curve of microsuture techniques is flat; beginners need much practice to become expert. The most physiologic techniques for anastomoses are preferred for long-term survival studies, while the faster techniques are options for short-term survival studies. Each research group must choose techniques according to study defined aims.

Background/Aims: The influence of type of surgery and occurrence of post-operative complications on survival following adjuvant therapy for pancreatic cancer are uncertain. Methods: Cox proportional hazard modelling was used to investigate the influence of type of surgery and the presence of complications on survival in conjunction with clinico-pathological variables in the 550 patients of the ESPAC-1 adjuvant randomized controlled trial. Results: Standard Kausch-Whipple (KW) was performed in 282 (54%) patients, 186 (35%) had a pylorus-preserving (PP) KW, 39 (7%) had a distal pancreatectomy and 21 (4%) had a total pancreatectomy. Post-operative complications were reported in 140 (27%) patients. PP-KW patients survived longer with a median (95% CI) survival of 19.9 (17.3, 23.1) months compared to 14.8 (13.0, 16.7) for KW patients (χ2LR = 15.1, p < 0.001). KW patients were more likely however to have R1 margins (67 (24%) vs. 29 (16%), χ2 = 4.59, p = 0.032), poorly differentiated tumours (70 (26%) vs. 19 (10%), χ2 = 18.65, p < 0.001) and positive lymph nodes (165 (60%) vs. 81 (44%), χ2 = 11.32, p < 0.001). Post-operative complications did not significantly affect survival. Independent prognostic factors were tumour grade, nodal status and tumour size but not type of surgery or post-operative complications. There was a survival benefit for chemotherapy irrespective of the type of surgery or post-operative complications. Conclusions: The KW and PP-KW procedures did not significantly influence the hazard of death in the presence of tumour staging, demonstrating that ESPAC-1 surgeons showed good judgement in their choice of operation. Post-operative complications did not adversely affect the survival benefit from adjuvant chemotherapy.

Background Restorative proctocolectomy is increasingly being performed using minimally invasive surgery. In published series laparoscopically assisted techniques have usually included a suprapubic incision to enable major parts of the operation to be done openly. Methods Fifty consecutive patients with familial adenomatous polyposis or ulcerative colitis underwent laparoscopic restorative proctocolectomy using only a small perumbilical incision of 4 cm or less for vascular dissection and pouch formation; all other steps were performed entirely laparoscopically. Logistic regression was used for statistical analysis. Results In four patients (8 per cent) the operation was converted to an open procedure. The diagnosis of ulcerative colitis was associated with a higher overall rate of complications (P = 0·011), and an increased body mass index (BMI) with a higher rate of major complications (P = 0·050). The occurrence of wound infection was related to the diagnosis of ulcerative colitis (P = 0·049). Conversion resulted in greater blood loss (P = 0·004), but not in a higher complication rate. No patient required a blood transfusion. Patients with an increased BMI and those taking immunosuppressive therapy had a longer hospital stay (P = 0·043). Conclusion Laparoscopic restorative proctocolectomy is technically feasible. Patients with ulcerative colitis and increased BMI have a higher risk of complications. This minimally invasive technique may reduce the need for perioperative blood transfusion.

In den westlichen Industrienationen sterben jahrlich ca.150.000 Patienten an einem Pankreaskarzinom, davon allein ca. 40.000 in Europa. Damit ist das Pankreaskarzinom die viert- bis funfthaufigste Todesursache bei Krebserkrankungen in der westlichen Welt. Mit einer insgesamt beschriebenen Funfjahresuberlebensrate von weniger als 1% stellt das Pankreaskarzinom somit eine der aggressivsten Tumorerkrankungen uberhaupt dar. Die Tumorresektion ist nach wie vor die einzige Moglichkeit, das Pankreaskarzinom zu heilen. Trotz groser klinischer Anstrengungen hat sich die Langzeitprognose von Pankreaskarzinompatienten nur unwesentlich verandert. Die Chirurgie des Pankreaskarzinoms hat in den vergangenen 10 Jahren allerdings wesentliche Fortschritte gemacht, und heute konnen mehr Patienten reseziert und die Operation sicher und mit geringer Morbiditat und Mortalitat ausgefuhrt werden. Ein groses Problem stellt die fruhzeitige Diagnose dar. Nur 10–15% aller Patienten mit der Diagnose eines Pankreaskarzinoms werden in einem resektablen Stadium diagnostiziert. Die dabei erzielten Funfjahresuberlebensraten konnten in der Vergangenheit auf ungefahr 25% gesteigert werden, sind aber weiterhin nicht befriedigend. Auf der anderen Seite tragen die niedrige Ansprechrate auf Chemotherapeutika, Radiotherapie, Immuntherapie und antihormonale Therapien zur schlechten Prognose von diesen Patienten bei.

Organ transplant recipients display a high cardiovascular mortality rate. The type of immunosuppression has a major impact on cardiovascular risk factors (e.g., hypertension [HTN]). We assessed 24-hour blood pressure (BP) and metabolic profiles in a cohort of 106 long-term liver allograft recipients treated with either tacrolimus (Tac) or cyclosporine (CyA). The median age of patients was 50.8 years (range, 11 to 77) and the median time of follow-up was 65.4 months (ranges 12 to 168). Immunosuppression included low-dose steroids and either Tac (n = 46) or CyA (n = 60). Twenty-four-hour BP measurements revealed a significant difference in systolic BP (127.1 mmHg [94 to 163] Tac versus 132.7 mmHg [103 to 177] CyA; P

Laparoscopic surgery has potential theoretical advantages over open surgery in reducing the rate of adhesion formation, but very few comparative studies are available to prove this. A literature search was performed within Medline and Cochrane databases using the key words: adhesion*, adhesiolysis, laparoscop*, laparotomy, open surgery. Further articles were identified from the reference lists of retrieved literature. Both clinical and experimental studies comparing laparoscopy and laparotomy with regard to adhesion formation were retained. In each article, the rates of adhesion formation were identified or deduced for the operative site, access wound site, and distant sites. Fifteen studies from 1987 to 2001 were identified. Most studies assessed the operative site. Thus, three clinical studies and six experimental ones found fewer adhesions following laparoscopy than laparotomy, while other five experimental studies found similar adhesion rates for the two surgical methods. There were fewer adhesions to trocar wounds than to the laparotomy wounds in seven studies and equal rates of adhesion in one study. The problem of distant adhesions is poorly represented in literature; three studies favored laparoscopy as being followed by fewer adhesions. Because of the important differences between studies with regard to the design, end points, and statistical calculations, a metaanalysis could not be achieved. The conclusion is based on the prevalence of evidence. All clinical studies and most of the experimental studies found a reduction of adhesion formation after laparoscopic surgery compared to open surgery.

Aim: Runx transcription factors are important regulators of lineage specific gene expression, cell proliferation, and differentiation. Runx3 expression is lost in a high proportion of gastric cancers, suggesting a tumour suppressive role in this malignancy. This study investigates the expression and localisation of Runx3 in pancreatic tissues. Methods: Quantitative polymerase chain reaction was used to measure Runx3 mRNA. Immunohistochemistry was carried out to localise Runx3 in normal pancreatic tissues, and in primary and metastatic pancreatic ductal adenocarcinoma (PDAC). Basal and transforming growth factor β1 (TGFβ1) induced Runx3 expression was analysed in cultured pancreatic cancer cell lines. Results: Runx3 expression was low to absent in normal pancreatic tissues, but increased in a third of cancer tissues. Runx3 was present only in islets in normal pancreas, whereas in pancreatic cancers, Runx3 was detected in the cancer cells of seven of 24 samples analysed. In addition, it was expressed by lymphocytes in six of the 16 cases with lymphocyte infiltration. In pancreatic cancer cell lines, Runx3 mRNA was present in Colo-357 and T3M4 cells, but was low to absent in the other cell lines tested. TGFβ1 repressed Runx3 mRNA expressed in Colo-357 cells, and had no effect on Runx3 expression in the other pancreatic cancer cell lines. Conclusion: Runx3 expression is restricted to islets in the normal pancreas. In contrast, a considerable proportion of pancreatic tumours express Runx3, and its expression is localised in the tumour cells and in the infiltrating lymphocytes. Thus, Runx3 might play a role in the pathogenesis of PDAC.

The treatment of malignancies of the gallbladder and the extrahepatic biliary tract by surgical resection is still the only curative treatment option of this rare and problematic tumor entity today. Due to the rare early diagnosis and the close site to complex adjoining structures, only a minority of patients is resectable in a curative manner. In selected patients an adequate surgical therapy can improve prognostic survival chances combined with an acceptable perioperative morbidity. In surgical strategies, obtaining tumor-free resection margins is most relevant. The basic surgical policy with curative intention in gallbladder carcinomas is the conventional en-bloc resection of the gallbladder and the cystic duct enclosing liver tissue adjoining the gallbladder bed and the lymph nodes at the cystic duct, the hepatoduodenal ligament, and the suprapancreatic tissue. In carcinomas of the extrahepatic bile duct, the complete resection of extrahepatic bile ducts with closure in its suprapancreatic segment plus en-bloc removal of all adjacent lymphatic tissues of the hepatoduodenal ligament is the basis of all surgical strategies with curative objective. In individual cases supplementary multivisceral resection or ultra-radical procedures provide a chance for prognostic improvements.

Surgical Treatment of Chronic Pancreatitis Chronic pancreatitis is characterized by recurrent episodes of pancreatitis and a chronic pain syndrome. The pancreatic structure becomes more and more fibrotic, and the patients suffer from exocrine and endocrine pancreatic insufficiency. The pathogenesis of the pain is based on the release of inflammatory cytokines, changes of the sensory nerves, and an increase of the intraductal and parenchymal pressures in the pancreas. The surgical therapy consists of drainage operations and/or pancreatic resections. In the last decade organpreserving operations such as the duodenum-preserving pancreatic head resection has evolved. Prospective studies demonstrated better results for duodenum-preserving pancreatic head resection in terms of quality of life and endocrine function. After modern pancreatic surgery, up to 90% of the patients are free of pain, and over 70% sustain a normal quality of life index.

Background: Although providing excellent outcome results, laparoscopy also induces particular pathophysiological changes in response to pneumoperitoneum. Knowledge of the pathophysiology of a CO2 pneumoperitoneum can help minimize complications while profiting from the benefits of laparoscopic surgery without concerns about its safety. Methods: A review of articles on the pathophysiological changes and complications of carbon dioxide pneumoperitoneum as well as prevention and treatment of these complications was performed using the Medline database. Results: The main pathophysiological changes during CO2 pneumoperitoneum refer to the cardiovascular system and are mainly correlated with the amount of intra-abdominal pressure in combination with the patient’s position on the operating table. These changes are well tolerated even in older and more debilitated patients, and except for a slight increase in the incidence of cardiac arrhythmias, no other significant cardiovascular complications occur. Although there are important pulmonary pathophysiological changes, hypercarbia, hypoxemia and barotraumas, they would develop rarely since effective ventilation monitoring and techniques are applied. The alteration in splanchnic perfusion is proportional with the increase in intra-abdominal pressure and duration of pneumoperitoneum. Conclusion: A moderate-to-low intra-abdominal pressure (