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Aktuelle Ergebnisse auf der Basis molekularer Ansatze weisen auf einen Einfluss des intestinalen Mikrobioms auf die Pathogenese, Diagnostik und das Therapieansprechen des Kolorektalkarzinoms (KRK) und seiner Vorstufen hin. Unzahlige Assoziationen zwischen mukosalen und fakalen mikrobiellen Signaturen und phanotypischen Veranderungen der kolorektalen Mukosa unterstreichen eine Rolle kommensaler Bakterien auch in der Pathogenese der KRK. Neue, nicht-invasive Mikrobiomanalysen weisen eine hohe diagnostische Reliabilitat fur das Vorliegen (pra)kanzeroser Lasionen und fur die Beurteilung der Lokalisation des Primartumors im Gastrointestinaltrakt auf. Eine ungunstige Zusammensetzung des Mikrobioms wirkt sich auf die Wirkung klassischer Chemotherapeutika aus und beeinflusst das Ausmas medikamenteninduzierter Nebenwirkungen. Definierte bakterielle Gemeinschaften scheinen das Ansprechen auf eine Checkpointinhibitortherapie zu verbessern. Die Rolle des Mikrobioms in der Pathogenese, Diagnostik und Therapie von KRK wird auf Basis einer selektiven Literatursuche dargestellt. Assoziationsstudien und Ergebnisse aus Tiermodellen bieten Hinweise fur einen Einfluss kommensaler Bakterien auf die Genese des KRK. Vorlaufige Daten aus Studien zum Einsatz von Mikrobiomsignaturen in der nichtinvasiven Diagnostik von (pra)malignen Lasionen deuten auf eine mogliche zukunftige Bedeutung dieser Diagnostik hin. Anhaltspunkte fur einen positiven Einfluss des Mikrobioms auf die Wirkung und Nebenwirkungen von Checkpointinhibitoren aus anderen Tumorentitaten mussen fur KRK noch uberpruft werden.

The universal access to treatment and care for people living with HIV (PLWHIV) is still a major problem, especially in sub-Saharan Africa, where 70% of HIV-infected people live. Equally important is the fact that HIV/AIDS-related stigma is recognized to be a major obstacle to successfully control the spread of this disease. We devised a pilot project (titled “My friend with HIV remains a friend”) to fight the HIV/AIDS stigmatization through educating secondary school students by openly HIV-positive teachers. In a first step, we have measured the amount and type of stigma felt by the PLWHIV in Buea/Cameroon using the “The people living with HIV Stigma Index” from Joint United Nations Programme on HIV/AIDS. Gossiping and verbal insults were experienced by 90% of the interviewees, while 9% have experienced physical assaults. Using these data and material from the “Toolkit for action” from the “International Centre for the Research on Women,” the teachers educated the students on multiple aspects of HIV/AIDS and stigma. The teaching curriculum included role-plays, picture visualizations, drawing, and other forms of interactions like visits to HIV and AIDS treatment units. Before and after this intervention, the students undertook “True/False” examinations on HIV/AIDS and stigma. We compared these results with results from students from another school, who did not participate in this intervention. We were able to show that the students taking part in the intervention improved by almost 20% points in comparison to the other students. Their results did not change.

Introduction: Fundoplication techniques for treatment of gastroesophageal reflux are discussed concerning impairments and success. This randomized trial was conducted to compare Nissen’s wrap and the anterior partial technique (Dor) concerning patients’ quality of life (QoL) and functional data after a mid-term follow-up. Methods: In a 24-month period, 64 patients were equally randomized into group A (Nissen’s fundoplication) and group B (180° anterior partial fundoplication). After a mean follow-up of 18 months, all patients were examined and interviewed using standardized QoL questionnaires (Gastrointestinal Quality of Life Index), Visick score, 24-hour pH-metry and esophageal manometry. Data of 57 patients (group A: 27, group B: 30) could be analyzed. Results: After partial fundoplication, 9 patients (30%) stated the operative results were worse than perfect. Only 2 patients (7%) evaluated the outcome after Nissen’s fundoplication as unsuccessful (p = 0.04). However, postoperative Gastrointestinal Quality of Life Index showed no differences between groups (p = 0.5). Additionally, functional data were not different (DeMeester 10 vs. 12, p = 0.17, and lower esophageal sphincter pressure 13 vs. 12 mm Hg, p = 0.5). Conclusion: The anterior partial fundoplication technique did not lead to disadvantages in postoperative QoL, physiological function and reflux control when compared to Nissen’s approach in a mid-term follow-up.

Probiotic bacteria are live microorganisms which contribute health benefits to their host. The numerous mechanisms of the probiotic-acting microorganisms include the induction of expression of certain cytokines and increasing the secretion of IgA and mucin. They activate lymphocytes and macrophages and inhibit the adhesion and invasion of epithelial cells. Escherichia coli Nissle 1917 (Mutaflor) is one of the most investigated probiotic bacteria. While the number of reports discussing the underlying mechanisms of Mutaflor has increased rapidly in recent years, novel clinical studies are missing. Here we provide an overview of the mechanisms of action and clinical studies related to Mutaflor. While most of the studies had positive outcomes, there are also a few in which Mutaflor did not perform to its expectations.

We used a solid tumor model to evaluate the influence of laparotomy versus laparoscopy on tumor growth after curative resection for rectal cancer in rats.Colon tumor cells (DHD/K12/TRb) were administered intraperitoneally in 15 rats, which were used as solid tumor donors. Twenty-one days later, a 20-mg piece was then implanted in the rectal submucosa of the study rats (n=45). Animals were randomized into 3 groups for rectal resection either open or laparoscopic using either carbon dioxide (CO2) or helium for pneumoperitoneum. Autopsy took place 21 days after resection and tumor recurrence was evaluated.Port-site metastasis was observed after laparoscopy with CO2 (1 animal) and helium (1), whereas intraperitoneal tumor growth was detected in 2 and 3 animals of these groups. No tumor recurrence was observed after open surgery.Our solid tumor model is a novel neoplastic model that might simulate the clinical situation of an upper rectal carcinoma. It might be helpful to develop new protocols in studying solid tumor biology and different surgical procedures for cancer to address problematic issues in oncologic research.

We set up a pilot study to evaluate the efficacy of telerobotic surgery using the da Vinci system for several procedures for which traditional laparoscopy (or thoracoscopy) is a standard approach in a single institution.We performed fundoplications (hiatal hernia repair and antireflux surgery, n=112), upside-down stomach (14), cholecystectomy (16), gastric banding (3), colectomy (5), esophagectomy (4), sub/total gastrectomy (2), gastrojejunostomy (2), along with thymectomy (100), thoracic symatectomy (11), lobectomy (5), mediastinal parathyroidectomy (5), and left pancreatic resection (1).The median set up time for all procedures was reduced from 25.0 to 10.4 minutes. Conversion to traditional laparoscopy or thoracoscopy occurred in 12 cases and in open surgery in 11 cases. There was no morbidity related to the telerobotic system.Robotically assisted laparoscopic and thoracoscopic surgery is feasible and safe for a variety of procedures in general, visceral, and thoracic surgery.

Preclinical studies revealed that curcumin, the yellow curry pigment, emodin, a compound derived from grapes, and taurolidine, derived from a biogenic amino acid, and some of their structural homologs possess anti-angiogenic and cancer chemopreventive properties. Whereas curcumin and emodin can act via inhibition of COP9 signalosome-associated kinases, taurolidine blocks protein biosynthesis.

Surgical therapy of peritoneal surface malignancy from colorectal origin in combination with Hyperthermic Intraoperative Peritoneal Chemotherapy (HIPEC) has now become an established treatment approach in very few specialised centres. A peritonectomy procedure is possible to perform with additional HIPEC in patients. An experimental model to simulate peritonectomy procedure and HIPEC does not exist so far in rats. Nevertheless, animal models seem to be very important for evaluation of new therapeutic opportunities and toxicity of different multimodal therapies. In a first step we analysed the surgical tumour debulking of peritoneal surface malignancy in rats. A peritoneal surface malignancy from colonic origin was induced in 75 male BD IX rats. Twenty one days after induction of peritoneal surface malignancy rats were randomised and animals intend to create an operation with surgical tumour debulking. There was no tumour growth in two animals. The aim of the peritonectomy procedure was the complete tumour reduction. In this study the results of the surgical approach will be described. A complete tumour reduction (R0) was achieved in 34 animals. In 39 rats a macroscopic tumour deposit was left behind (R2). The intraoperative experimental Peritoneal Cancer Index (ePCI) was used to describe tumour weight and number of tumour inoculations. Both parameters were found to be dependent factors of complete tumour reduction. Six animals died due to therapeutical interventions. Surgical tumour debulking in rats with peritoneal surface malignancy is possible with high reliability and a low mortality rate. This animal model could be an important step for investigation of multimodal treatment options and toxicity in treatment regimens of peritoneal surface malignancy.

Intestinal dendritic cells (DCs) are believed to sample and present commensal bacteria to the gut-associated immune system to maintain immune homeostasis. How antigen sampling pathways handle intestinal pathogens remains elusive. We present a murine colitogenic Salmonella infection model that is highly dependent on DCs. Conditional DC depletion experiments revealed that intestinal virulence of S. Typhimurium SL1344 ΔinvG mutant lacking a functional type 3 secretion system-1 (ΔinvG)critically required DCs for invasion across the epithelium. The DC-dependency was limited to the early phase of infection when bacteria colocalized with CD11c+CX3CR1+ mucosal DCs. At later stages, the bacteria became associated with other (CD11c−CX3CR1−) lamina propria cells, DC depletion no longer attenuated the pathology, and a MyD88-dependent mucosal inflammation was initiated. Using bone marrow chimeric mice, we showed that the MyD88 signaling within hematopoietic cells, which are distinct from DCs, was required and sufficient for induction of the colitis. Moreover, MyD88-deficient DCs supported transepithelial uptake of the bacteria and the induction of MyD88-dependent colitis. These results establish that pathogen sampling by DCs is a discrete, and MyD88-independent, step during the initiation of a mucosal innate immune response to bacterial infection in vivo.

Hintergrund: Die gastroosophageale Refluxkrankheit stellt mit einer Inzidenz von 10% der Gesamtbevolkerung ein bedeutendes medizinisches wie auch zunehmend okonomisches Problem in d

Background/Aim: Chemotherapy can induce serious leukopenia. The aim of our study was to investigate the effects on leukopoiesis when the antineoplastic agent taurolidine (TRD) is administered by a bolus injection or during repetitive treatment (21 cycles) over 7 days in rats. Methods: Rats were intravenously treated with a single injection (A) or by a 7-day treatment (B) with increasing doses of TRD versus control (isotone sodium) in a standardized animal model. Hematological adverse effects on leukopoiesis were analyzed in peripheral blood. Results: (A) Neither the highest TRD concentration (3%) nor 1 or 2% caused a significant difference between the control and TRD groups (p > 0.085) in the perioperative course after bolus administration. (B) The administration of TRD 3% led to a slight change of granulocyte and monocyte counts compared to the control group particularly on postoperative day 7, but this difference was not significant. In both protocols a slight postoperative increase in leukocytes was observed. Conclusion: We report that TRD administered intravenously in an antitumor dose does not affect leukopoiesis in rats. Thus, the agent offers a promising and safe means in cancer treatment. The effects are currently investigated in incurable cancer patients.

So far, the impact of telematic surgical approach in Gastroesophageal Reflux Disease (GERD) is still obscure. In this prospective study, we analyzed the Da Vinci® Intuitive Surgical robotic system for antireflux surgery. In April 2003, we set up a pilot study to evaluate the efficacy of laparoscopic telerobotic surgery using the three-arm Da Vinci® system. Optimal trocar positions, operating and setup times, conversion rate, intraoperative complications, and perioperative morbidity, as well as mortality rate, were analyzed. The median age was 53 years (range 25–74) in 118 patients (52 female/66 male). In 17 patients, an upside-down stomach- and in 101 GERD was surgical indication. The median operating time has been reduced from 105 min to 91 min after 40 procedures and setup time from 24.5 min to 10.4 min after 10 procedures. The system is safe and it seems to be superior to traditional laparoscopy during dissection in the esophageal hiatus region. This compensates long setup- and operating times. Disadvantages are the high costs, the time to master the setup/system and the necessity of exact trocar positioning.

We studied the putative significance of angiotensin I-converting enzyme (ACE) in colorectal cancer (CRC) biology. Local expression of ACE was investigated by quantitative reverse transcription- polymerase chain reaction and by immunohistochemistry in CRCs and adenomas. ACE insertion (I)/deletion (D) polymorphism was studied in 141 CRC patients and 189 controls. ACE mRNA was upregulated in CRCs compared to corresponding nonlesional tissues (2.5-fold; P = .009). ACE protein was more commonly expressed in adenomas [17 (81 %)] and cancer epithelial cells [22 (100%)] than in corresponding non-neoplastic crypt and surface epithelium [2 (10%) and 2 (9%), respectively]. Thirty-seven CRC patients (26%) carried II genotype, 69 (49%) carried ID genotype, 35 (25%) carried DD genotype. The distribution of the genotypes did not differ from that of controls. Female CRC patients more commonly carried the ID genotype and less frequently the II and DD genotypes compared with male patients (P = .033). Men heterozygous or homozygous for the D-allele had larger tumors compared to carriers of the II genotype (P < .01). Women homozygous for the D-allele lived longer than carriers of the ID and II genotypes. Our study shows that ACE is differentially expressed in CRCs and that gene polymorphism is associated with gender-specific differences in primary tumor size and patient survival.

Yersinia enterocolitica is a common cause of food-borne gastrointestinal disease leading to self-limiting diarrhea and mesenteric lymphadenitis. Occasionally, focal abscess formation in the livers and spleens of certain predisposed patients (those with iron overload states such as hemochromatosis) is observed. In the mouse oral infection model, yersiniae produce a similar disease involving the replication of yersiniae in the small intestine, the invasion of Peyer's patches, and dissemination to the liver and spleen. In these tissues and organs, yersiniae are known to replicate predominately extracellularly and to form microcolonies. By infecting mice orally with a mixture of equal amounts of green- and red-fluorescing yersiniae (yersiniae expressing green or red fluorescent protein), we were able to show for the first time that yersiniae produce exclusively monoclonal microcolonies in Peyer's patches, the liver, and the spleen, indicating that a single bacterium is sufficient to induce microcolony and microabscess formation in vivo. Furthermore, we present evidence for the clonal invasion of Peyer's patches from the small intestine. The finding that only very few yersiniae are required to establish microcolonies in Peyer's patches is due to both Yersinia -specific and host-specific factors. We demonstrate that yersiniae growing in the small intestinal lumen show strongly reduced levels of invasin, the most important factor for the early invasion of Peyer's patches. Furthermore, we show that the host severely restricts sequential microcolony formation in previously infected Peyer's patches.

Background Matrix metalloproteinases (MMP) are proteolytic enzymes which degrade the extracellular matrix and therefore play an important role in metastasis. However, the impact of MMP inhibitors (MMPI) on pancreatic cancer is still unclear. Thus we evaluated the influence of selective MMPI Ro 28-2653 on the incidence of liver metastases and the concentration of MMP-2 and MMP-9 in ductal pancreatic adenocarcinoma in Syrian hamster. Material and methods One hundred and thirty male Syrian hamsters were randomised into 8 groups (Gr.1–3: n = 15 , Gr.4–8: n = 17 ). Pancreatic cancer was induced by weekly subcutaneous injection of 10 mg N-nitrosobis-2-oxopropylamin (BOP)/kg body weight (Gr.4–8) while healthy control Gr. 1–3 received 0.5 ml sodium chloride 0.9%. Gr.1 and 4 had free access to a standard diet, Gr. 2, 3 and 5–8 received a diet rich in polyunsaturated fatty acids, which increases liver metastasis in this model. In week 17 oral therapy started: Gr.3 and 6: 60 mg Eudragit/kg body weight/d (vehicle of MMPI), Gr.7 and 8: 40 mg, respectively, 120 mg RO 28-2653/kg body weight/d; Gr.1, 2, 4, 5: no therapy. After 30 weeks all hamsters were sacrificed and histopathologically examined. Additionally concentrations of MMP-2 and MMP-9 were measured in non-metastatic liver and liver metastases. Results Concentrations of MMP-2 and MMP-9 in liver metastases were decreased by high- and low-dose therapy with MMPI. Furthermore, the incidence of liver metastases was significantly reduced by low-dose therapy with Ro 28-2653. Conclusion Low-dose therapy with Ro 28-2653 decreased liver metastasis due to an inhibition of MMP-2 and MMP-9 concentration in ductal pancreatic cancer.

Background The antitumor agent taurolidine (TRD) affects tumor growth in animals. Thus far, no animal studies have been published concerning the systemic or local toxicity and the effectiveness of long-term intraperitoneal (i.p.) and intravenous (i.v.) administration on advanced tumor growths. Materials and methods In a first experiment (A) the systemic toxicity of the liver and kidneys was examined only after i.v. treatment in 40 rats (BD IX). For local toxicity the superior vena cava (SVC) was histologically analyzed. In a second study (B) 20,000 colon adenocarcinoma cells (DHD/K12/TRb) were initially applied i.p. after laparotomy in 80 rats (BD IX). After 28 days a port catheter system was placed in the SVC and left for 1 week. The animals were randomized into eight groups (n = 10) and received a 7-day treatment (eight hourly, 1 ml): 1, 2, 3% TRD or Ringer’s solution (control group) either i.p. or i.v. Total i.p. tumor weight was measured 4 weeks after the end of the therapy. Side effects on differential blood counts and animal weight changes were examined. Results No organ lesions were detected in liver, kidneys, and SVC in experiment A. The i.v. administration of 2% TRD (P = 0.034) and 3% TRD (P = 0.05) as well the i.p. application of 2% TRD (P = 0.05) decreased the development of advanced i.p. tumor lesions. No changes of differential blood count nor relevant animal weight changes resulted. Three port catheter-related infections were examined. Conclusions TRD does not impair the liver tissue, kidneys, SVC, and leucopoiesis. The intravenous therapy of 2% TRD is safe and anti-tumorigenic in advanced local tumor growth in rats.

Recently introduced telerobotic surgical systems attempt to elude the inherent limitations of traditional laparoscopic surgery. Four patients (3 male, 1 female) with mixed hiatal and paraesophageal hernias with fixed intrathoracic partial or complete displacement of the stomach were operatively treated using the Da Vinci robotic system. Tissue dissection, hiatoplasty, and anterior hemifundoplication (Dor) were performed with the telerobotic system. There were no surgical complications. The system broke down in the fourth patient due to a software defect. Advantages were seen in terms of the intrathoracic dissection of displaced stomach through a narrow hiatus, intracorporeal suturing due to 6 degrees of freedom plus grasping. At the moment, lack of the appropriate robotic instruments for abdominal surgery as well as the enormous functional cost of the robotic system are considered to be the most significant current impediment to the adoption of robotic abdominal surgery. The continuous evolution and upgrade of the system is quite promising so far. Telerobotic-assisted hiatal hernia operation is feasible with many advantages compared with the traditional laparoscopic approach, especially during the dissection in the mediastinum in patients with intrathoracic stomach. A prospective, randomized trial will be performed later to evaluate the advantages and limitations of robotic compared with traditional laparoscopy. Technological evolution will perhaps diminish the current problems and the cost associated with robotic surgery.

Background experimental studies have shown that taurolidine suppresses intraperitoneal tumor growth following local application in rats. In opposite, a single intravenous therapy affected neither intraperitoneal nor subcutaneous growth of malignancies. Thus, an intravenous long-term therapy with taurolidine was investigated in rats after administration of a subcutaneous tumor load. VEGF and TNFα production and their effects on tumor growth have not been elucidated so far. Methods VEGF and TNFα levels of rat colon adenocarcinoma cells (DHD/K12/TRb) were analyzed in the supernatant undergoing treatment of increasing taurolidine doses in vitro. Besides the cell experiments rats were treated intravenously. At the beginning of the operation, 10 000 colon adenocarcinoma cells were applied subcutaneously at the back of the rats. Then the animals (n = 80, BD IX rats) were randomized into eight groups and underwent a standardized midline laparotomy for 30 min. At the end of the operation the animals were given either a bolus (1 ml Ringer’s solution) or a long-term intravenous therapy (7 days, eight-hourly 1 ml 1%, 2%, or 3% taurolidine) were performed. For long-term therapy, a jugularis vein port catheter system was placed and left for 1 week. The influence on subcutaneous tumor growth, animal growth, general side effects and leukocyte/granulocyte levels were analyzed. Total tumor weights were determined 4 weeks after cell application. Results The VEGF and TNFα levels decreased rapidly after taurolidine therapy with low doses in vitro. The subcutaneous tumor growth showed a downtrend of tumor weight (P = 0.075) with a statistical significance in solid tumor counts (P = 0.04) at the back of the animals. A slight and temporary depression in animal growth was observed only in long-term therapy groups. Independent of the therapeutic agents and the application forms, the operation itself caused a slight leukopenia shortly after the operation compensated by a moderate leukocytosis in the following course. Fast injections of taurolidine led to a reduction of breathing rate. Conclusions Only the intravenous long-term therapy of 3% taurolidine led to a slight downregulation in subcutaneous tumor growth. The changes of leukocyte counts were not affected by taurolidine. Fast injections have to be avoided. The findings prompted us to start new experiments to determine the influence of increasing doses of taurolidine on progressive tumor growth in rats.

Pneumatosis intestinalis (PI) is characterized by multiple gas cysts in the wall of the gastrointestinal tract. Primary PI is extremely rare. In most of the cases PI is due to an underlying disease (traumatic and mechanical, inflammatory and autoimmune diseases, infectious and pulmonary diseases, drug induced, immunosuppression, transplantation, or neoplasm). A 69-year-old woman was treated with mixed connective tissue disease and PI twice operatively and once conservatively in our department. Review of the english literature showed 13 more cases of PI with underlying mixed connective tissue disease. Most published cases of pneumatosis intestinalis with radiological finding of pneumoperitoneum were treated conservatively and should have not been considered as a reason for surgery. Therefore, the treatment of PI can present as a major dilemma for the surgeon.

Hintergrund: Iatrogene Lasionen der Trachea oder der Hauptbronchien sind sehr selten. Der Verlauf wird masgeblich durch fruhzeitige Erkennung, Verletzungsausmas und adaquate Versorgung bestimmt. Bei grosen Defekten konnte der kombinierte Einsatz neuer Materialien die Sicherheit primarer Nahte erhohen. Patienten und Methoden: Es wurden drei konsekutive iatrogene Tracheal- oder Bronchialverletzungen nach primarer Naht (Polydioxanon) zusatzlich mit resorbierbarem Soft PGA Mesh® (resorbierbares Polyglykol- Vlies) und Fibrin versorgt. Eine Patientin hatte bei einer notfallmasigen, orotrachealen Intubation eine langstreckige tracheale Verletzung der Pars membranacea erlitten. Bei einer weiteren Patientin (Ileus bei fortgeschrittenem Kolonkarzinom) war es durch mehrfache perkutane Tracheotomie bei Verlagerung der Trachea durch eine Arteria lusoria zu mehreren Defekten sowie einer grosen osophagotrachealen Fistel gekommen. Diese wurde erst am Folgetag identifiziert. Bei der dritten Patientin war bei stumpfer Dissektion eines fortgeschrittenen Osophaguskarzinoms ein erheblicher Defekt im Bereich der Bifurkation und des linken Hauptbronchus entstanden. Die therapeutischen Verlaufe wurden prospektiv erfasst und ausgewertet. Ergebnisse: Die jeweilige tracheale Versorgung blieb auch unter langwierigen Beatmungssituationen suffizient. Die erste Patientin blieb tetraparetisch und wurde nach 48 Tagen zur Rehabilitation verlegt. Die zweite Patientin verstarb am 15. postoperativen Tag unter dem Bild einer Urosepsis. Die dritte Patientin wurde 10 Tage lang intensivtherapeutisch behandelt und am 23. Tag von der Normalstation entlassen. Bronchoskopische und computertomographische Verlaufskontrollen sicherten adaquate lokale Ergebnisse. Schlussfolgerung: Nach suffizienter primarer Naht kann die zusatzliche Versorgung groser Verletzungen der Trachea und der Hauptbronchien mit resorbierbarem Material im Sinne eines Patches zu einer zusatzlichen Sicherung des Operationsergebnisses durch Ableitung auftretender Krafte (Cuff-Druck des Tubus, Beatmungsdruck) fuhren.

Obwohl die laparoskopische Resektion eines malignen Tumors impliziert, dass durch den Einsatz des minimal invasiven Verfahrens die immunologische Abwehr und das Tumorwachstum weniger beeinflusst werden als bei der konventionellen Chirurgie, ist der Stellenwert dieser Operationstechnik im Hinblick auf die Prognose der Tumorpatienten immer noch unvollstandig geklart. Ob die durch die Operation verursachte intra- und postoperative Immunsuppression nach laparoskopischen Operationen im Gegensatz zur konventionellen Technik wirklich reduziert ist und hierdurch moglicherweise die Prognose der Patienten gunstig beeinflusst werden kann, kann derzeit nicht eindeutig beantwortet werden. Zudem zeigen experimentelle Studien eher einen negativen Effekt von CO2 auf die Abwehrreaktion von Immunzellen und eine Stimulation des Wachstums von Tumorzellen. Hingegen konnten die meisten Tiermodelle einheitlich einen immunologischen Vorteil und eine geringere Stimulation des Tumorwachstums im Vergleich zur konventionellen Chirurgie nachweisen. Die klinischen Studien zeigen zwar bei kleineren chirurgischen Eingriffen eine deutlich geringere postoperative systemische Inflammation, allerdings konnte dieser Vorteil bei der Resektion von malignen Tumoren, wie dem kolorektalen Karzinom, nur bedingt bestatigt werden. Bislang konnte in allen prospektiv randomisierten Studien weder eine geringere Morbiditat noch eine Korrelation zwischen perioperativen immunologischen Veranderungen und postoperativen Komplikationen noch eine Verbesserung der Langzeitprognose nachgewiesen werden.

Experimental studies in the therapy of malignant abdominal tumors have shown that different cytotoxic agents suppress the intraperitoneal tumor growth. Nevertheless, a general accepted approach to prevent tumor recurrences does not exist. Following subcutaneous and intraperitoneal injection of 10(4) colon adenocarcinoma cells (DHD/K12/TRb), the influences of both taurolidine or taurolidine/heparin on intraperitoneal and subcutaneous tumor growth was investigated in 105 rats undergoing midline laparotomy. The animals were randomized into 7 groups and operated on during 30 min. To investigate the intraperitoneal (local) influence of either taurolidine or heparin on tumor growth, the substances were applied intraperitoneally. Systemic and intraperitoneal effects were evaluated after intravenous injection of the substances. Both application forms were also combined to analyze synergistic effects. Tumor weights, as well as the incidence of abdominal wound metastases, were determined four weeks after the intervention. In order to evaluate the effects of the agents, blood was taken to determine the peripheral leukocytes counts. Intraperitoneal tumor growth in rats receiving intraperitoneal application of taurolidine (median 7.0 mg, P = 0.05) and of taurolidine/heparin (median 0 mg, P = 0.02) was significantly reduced when compared to the control group (median 185 mg). The simultaneous instillation of both agents also reduced the intraperitoneal tumor growth (median 4 mg, P = 0.04), while the intravenous injection of the substances caused no local effect. In contrast, the subcutaneous tumor growth did not differ among all groups. In all groups, abdominal wound recurrences were rare and did not differ. Independent of the agents and the application form, the operation itself caused a slight leukopenia shortly after the operation and a leukocytosis in the following course. Intraperitoneal therapy of either taurolidine or in combination with heparin inhibits local tumor growth and abdominal wound recurrences in rats undergoing midline laparotomy. Neither the intraperitoneal nor the intravenous application or the combination of the two agents influenced the subcutaneous tumor growth. The substances did not alter the changes of peripheral leukocytes.

The cytokines involved in the systemic inflammatory response in acute pancreatitis (AP) comprise lipid mediators (eg, prostanoids, thromboxanes, leukotrienes) generated from arachidonic acid (AA) and eicosapentaenoic acid (EPA). The AA-derived mediators are generated from omega-6-fatty acid (FA) and have strong proinflammatory effects and the EPA-derived mediators generated from omega-3-fatty acid are less active or even exhibit anti-inflammatory effects. Basic parenteral nutrition delivers omega-6-FA and omega-3-FA at a ratio of approximately 7:1.To investigate whether altering the FA composition by fish oil supplementation (omega-3-FA) affects cytokine production and the parameters reflecting systemic disease severity in experimental AP.Severe AP was induced in 30 rats by standardized intraductal infusion of bile salt and IV cerulein. Six hours after AP induction, rats were randomized to TPN using commercial solutions with identical amounts of glucose, amino acids, and fat but different FA compositions: group 1 received a soybean-based fat solution without additional fish oil and group 2 was supplemented with 0.2 g/kg per day fish oil. TPN was continued for 2 days. Serum concentrations of IL-6 and IL-10 were measured before and after AP induction and at 24 and 48 hours after starting TPN. Routine cardiorespiratory and renal parameters were monitored to assess the systemic response at the organ level.Animals treated with fish oil had significantly higher IL-10 values (at 24 hours, 63 +/- 7 versus 46 +/- 3 pg/mL), produced more urine (28 +/- 0.9 versus 21 +/- 1.6 mL), and had significantly fewer episodes of respiratory dysfunction (defined as a pO280 mm Hg or pCO250 mm Hg for15 minutes; 29% versus 67%) during the observation period.Altering eicosanoid mediator precursor availability by infusion of (omega-3 fatty acid increases anti-inflammatory cytokines in this model of AP. This together with improved renal and respiratory function suggests that the systemic response to pancreatic injury is attenuated.

YopQ in Yersinia enterocolitica (YopK in Yersinia pseudotuberculosis) is a type III secreted protein required for virulence of yersiniae. In this study YopQ expression, secretion and nucleotide sequences of the corresponding yopQ gene from different yersinia strains were analysed. The cytosolic accumulation differed significantly among serotypes of Y. enterocolitica. These differences might be attributable to variations in the nucleotide sequence and their consequences on mRNA secondary structure. An mRNA signal hypothesis has been proposed for YopQ, predicting the coupling of translation and secretion via an mRNA signal. This hypothesis claims a strictly co-translational secretion of YopQ without its intracellular accumulation. The presence of YopQ in the cytosol, even with a closed secretion apparatus, is demonstrated. Moreover, post-translational secretion of YopQ could be demonstrated. These findings do not support the mRNA signal hypothesis for co-translational secretion.

The enteropathogenic Yersinia enterocolitica strains have several systems for scavenging iron from their environment. We have studied the expression of the fyuA gene, which encodes the outer membrane receptor for the siderophore yersiniabactin (Ybt), and the hemR gene, which encodes the receptor for heme, using the reporter genes gfp (encoding green fluorescent protein) and luc (encoding firefly luciferase). To study gene expression in vitro as well as in vivo, we have constructed several translational reporter gene fusions to monitor simultaneously expression of fyuA and hemR or expression of one gene by a gfp - luc tandem reporter. Results of the in vitro expression analysis (liquid media) indicated that fyuA and hemR are strongly derepressed under iron starvation conditions, resulting in strong fluorescence and/or luminescence at 27°C. In the in vivo BALB/C mouse infection model, tissue-specific expression of fyuA and hemR reporter fusions was observed. Surprisingly, fyuA and hemR reporter constructs were weakly expressed by yersiniae located in the liver and intestinal lumen, whereas strong expression was found for yersiniae in the peritoneal cavity and moderate expression was found in the spleen. Strikingly, yersiniae carrying fyuA or hemR reporter fusions exhibited threefold-stronger signals when grown in the peritoneal cavity of mice than those growing under iron derepression in vitro. This hyperexpression suggests that besides Fur derepression, additional activators may be involved in the enhanced expression of fyuA and hemR under peritoneal growth conditions. Differential expression of the fyuA and hemR reporter fusions could not be observed, suggesting similar regulation of fyuA and hemR in the mouse infection model.

Wiskott-Aldrich Syndrome protein (WASp) and related proteins stimulate actin filament nucleation by Arp2/3 complex. The isolated C-terminal VCA domain of WASp (containing Verprolin-like, Central and Acidic regions) is constitutively active but autoinhibited in the full-length protein. This study compared the ability of parts of VCA fused to the C terminus of glutathione S-transferase (GST) to bind actin and Arp2/3 complex in vitro and to activate actin polymerization in vitro and in cells. Fluorescence anisotropy measurements showed that GST-CA and GST-A bound Arp2/3 complex with K(d) values of 0.11 microm and 1.0 microm, respectively, whereas GST-VC displayed almost undetectable binding (K(d) > 1 mm). However, GST-VC activated actin nucleation through Arp2/3 complex in vitro, though requiring 70-fold higher concentration than GST-VCA while neither GST-CA nor GST-A activated Arp2/3 complex in vitro, though both GST-CA and GST-A inhibited Arp2/3 complex activation by WASp VCA. None of these constructs bound WASp from macrophage lysates. Both GST-VC and GST-CA induced actin accumulations when microinjected into primary human macrophages or human endothelial vein cells. However, only microinjection of GST-VC led to a significant increase of cellular polymerized actin. Additionally, endogenous Arp2/3 complex, but not WASp, colocalized with these GST-VC-induced actin accumulations. These data suggest that WASp constructs lacking the A region, previously thought to be indispensable for actin nucleation, are able to bind and activate Arp2/3 complex in vitro and in vivo.

Persistent oxidative stress is thought to play an important role in carcinogenesis. Vitamins may influence oxygen radical metabolism and thus inhibit tumor growth. In the present trial the effects of Vitamins (Vit.) A, C and E on neoplastic growth and lipid peroxidation in pancreatic tissue were evaluated on chemically-induced pancreatic adenocarcinoma in the Syrian hamster. The incidence of pancreatic cancer was decreased by Vit. A (64.3%) and Vit. C (71.4%) as compared to the control group (100%, P

Although the problem of port-site metastases is mainly related to the surgeon, the technique, manipulation of the tumor-bearing organ, and some other factors related to laparoscopy itself have been shown to influence tumor growth. The different experimental studies about basic research and possible new therapeutic strategies, including instillation of cytotoxic and immune modulating agents in combination with laparoscopy, are presented and discussed.

The gene encoding periplasmic 2',3'-cyclic phosphodiesterase in Yersinia enterocolitica O:8 (designated cpdB), was cloned and expressed in Escherichia coli. This enzyme enables Y. enterocolitica to grow on 2',3'-cAMP as a sole source of carbon and energy. Sequencing and analysis of a 3 kb ECO:RI fragment containing the cpdB gene revealed an open reading frame of 1179 bp, corresponding to a protein with a molecular mass of 71 kDa. The first 25 amino acid residues show features of a typical prokaryotic signal sequence. The predicted molecular mass of the mature peptide is therefore in agreement with the molecular mass estimated by SDS gel electrophoresis (68 kDa). The putative cpdB promoter region contains two possible -10 and -35 regions. Furthermore, the 5' untranslated region contains sequences with significant homology to the cyclic AMP-cyclic AMP receptor protein binding site and the sigma(28) consensus. This region is interrupted by an enterobacterial repetitive intergenic consensus (ERIC) sequence. Deletion of the ERIC element from the cpdB promoter region had no effect on cpdB expression. In the 3' untranslated region, a possible rho-independent transcriptional terminator was identified. The deduced amino acid sequence of the Y. enterocolitica CpdB protein shows 76% identity with CpdB of Salmonella typhimurium and E. coli. CpdB of Y. enterocolitica is exported to the periplasmic space. An isogenic Y. enterocolitica cpdB mutant strain, constructed by allelic exchange, was no longer able to grow on 2',3'-cAMP as sole source of carbon and energy. The CpdB mutant showed no significant change in virulence in an oral and intravenous mouse infection model.

Enteropathogenic Yersinia bacteria trigger the production of the proinflammatory chemokine IL-8, an important chemokine for the recruitment of polymorphonuclear leukocytes (PMN). Yersinia is resistant to phagocytosis by PMN, and the recruitment of these cells is thought to be part of a pathogenic strategy of Yersinia to establish infection by allowing the pathogen to gain access to, and disseminate within, host tissue. We report here that Yersinia expressing the outer membrane protein invasin triggers IL-8 production in epithelial cells. The 195 carboxyl-terminal amino acids of invasin when linked to latex beads are sufficient to trigger IL-8 production. By means of IL-8 promoter reporter gene assays and electrophoretic mobility shift assay experiments, the minimal optimal region of the IL-8 promoter responsive to invasin was identified and invasin-responsive control elements were characterized. Invasin-induced activation of the IL-8 promoter was found to be mediated through a previously identified NF-kappaB element. This NF-kappaB binding site preferentially binds Rel p65-p65 homodimers as well as some p50-p65 heterodimers in response to stimulation by invasin. Invasin-induced NF-kappaB activation correlated with degradation of IkappaBalpha and the inhibition of NF-kappaB by specific inhibitors of IkappaB activation blocked invasin-induced IL-8 secretion. Invasin-triggered IL-8 production does not depend on invasin-triggered uptake of bacteria, and is independent of a functional PI3-kinase. This report is the first to demonstrate the molecular basis of IL-8 production triggered by enteropathogenic bacteria. Together, these data elucidate the possible early pathomechanisms operating in Yersinia infection and may have implications for the design of novel therapeutics directed against this enteropathogen.

Background: Recent clinical and experimental studies investigated the problem and possible pathomechanisms of port-site metastases after laparoscopic resection of malignant tumours. A generally accepted approach to prevent these tumour implantations does not exist so far. Methods: After subcutaneous and intraperitoneal injection of 104 cells of colon adenocarcinoma (DHD/K12/TRb) the influences of either taurolidine or taurolidine/heparin on intraperitoneal and subcutaneous tumour growth were investigated in 105 rats undergoing laparoscopy with carbon dioxide. The animals were then randomised into seven groups. A pneumoperitoneum was established using carbon dioxide for 30 min (8 mmHg). Three incisions were used: median for the insufflation needle, and a right and left approach in the lower abdomen for trocars. To investigate the intraperitoneal (local) influence of either taurolidine and heparin on tumour growth the substances were instilled intraperitoneally. Systemic effects were expected when the substances were applied intravenously (iv). Synergistic influences were tested when both application forms were combined. The number and the weight of tumours as well as the incidence of abdominal wall and port-site metastases were determined four weeks after intervention. Blood was taken to evaluate the influences of taurolidine and heparin on systemic immunologic reactions: seven days before laparoscopy, two hours, two days, seven days, and four weeks after operation, and the peripheral lymphocytes were determined. Results: Intraperitoneal (ip) tumour weight in rats receiving taurolidine (median 7 mg) and taurolidine/heparin (0 mg) intraperitoneally was significantly reduced when compared to the control group (52 mg) (P=0.001). There was no difference of subcutaneus tumour growth among the groups (P=0.4). Trocar recurrences were decreased when taurolidine was applied ip (3/15), ipiv (4/15), and ip in combination with heparin (4/15) in comparison to the control group (10/15). Immediately after intervention treated and untreated groups showed a peripheral lymphopenia. Conclusions: The intraperitoneal therapy with taurolidine and the combination with heparin inhibits the intraperitoneal tumour growth and trocar recurrences. Neither the intraperitoneal nor the systemic application or the combination of taurolidine and heparin did reduce the subcutaneous tumour growth. The intervention caused a lymphopenia which was compensated on day two.

BACKGROUND The Whipple operation (PD) is the standard operation in patients with cancer of the head of the pancreas and the periampullary region. However, the pylorus-preserving duodenopancreatectomy (PPPD) is supposed to be superior in gastrointestinal function. METHODS In a prospective randomized trial (October 1994-October 1998) PD and PPPD were compared in terms of global and gastrointestinal quality of life, operation time, duration of hospital stay, transfusions and perioperative morbidity. Quality of life was analyzed under standardized conditions (EORTC-QLQ-30) pre- and postoperatively (weeks 2, 6, 12, 24, 36, 48, and 60). RESULTS A duodenopancreatectomy was performed in 48 patients because of cancer of the head of the pancreas (n = 38) and the periampullary region (n = 10) (PD, n = 24; PPPD, n = 24). The PD and PPPD groups did not differ according to age, gender or UICC stage. Operation time was shorter in the PPPD group (206 +/- 48 vs 306 +/- 54 min) (P 0.05). While there was no difference in global quality of life, gastrointestinal quality of life was postoperatively increased in the PPPD group regarding appetite, nausea and diarrhea (P < 0.05). While the preoperative body weight was reached after 6 months in 85% of the PPPD group (n = 20), this was true in only 60% of the PD-group (n = 14) (P < 0.05). CONCLUSION PPPD seems to be associated with a better postoperative gastrointestinal quality of life than PD.

Background and aims: It has not been clarified whether there is a correlation between the tumor size and the preoperative immune function in pancreatic carcinoma. Patients/methods: In a prospective trial, the influence of tumor size and lymph-node status on different immune system factors [interleukins (IL)-6 and -10, tumor necrosis factor (TNF)-α, CD3-, CD4-, and CD8-lymphocytes, and human leukocyte antigen (HLA)-DR-monocytes] was analyzed in 28 patients with pancreatic carcinoma and compared with a control group (n=20). There were 3 pancreatic carcinomas of the T1-tumor type, 20 T2- and 5 T3-tumors; 14 patients were in stage N1. Results: In comparison with the control group, tumor patients preoperatively showed a significant increase of leukocytes (P=0.02), monocytes (P=0.04), and granulocytes (P=0.03). The total count of lymphocytes, the number of CD3-, CD4- and CD8-lymphocytes, and the expression of HLA-DR on monocytes were significantly decreased as a sign of immunosuppression in tumor patients. A multivariate analysis proved that only tumor size (T-stage) but not lymph-node status correlates with the deficiency of immune competence. Progressive tumor size correlated with decreasing expression of HLA-DR on monocytes, CD3- (P=0.04) and CD8- (P=0.02) lymphocytes. In contrast IL-6, IL-10 (P=0.04) and TNF-α (P=0.02) increased with progressive tumor size. Conclusion: Regarding the negative prognosis after resection, the preoperative immune status could be an additional help for decision between a resection or a preoperative immune stimulation in pancreatic carcinoma.

Pathogenic Yersinia enterocolitica produces two virulence plasmid-encoded cytotoxins, YopE and YopT, that are translocated into target cells where they disrupt the actin cytoskeleton. Here we show that infection of cells with wild type Y. enterocolitica and a yopE mutant, but not with a yopT mutant, induces an increase in the electrophoretic mobility of the small GTPase RhoA. As tested by isoelectric focusing, YopT-dependent modification resulted in an acidic shift of RhoA. Furthermore, RhoA modification induced by YopT was accompanied by redistribution of membrane-bound RhoA toward the cytosol. Finally, a yopE mutant of Y. enterocolitica expressing the cytotoxic activity of YopT specifically disrupted RhoA-controlled actin stress fibers. These findings provide evidence for inactivation of RhoA by the translocated Y. enterocolitica cytotoxin YopT and suggest a novel inhibitory modification of RhoA by a bacterial virulence factor.

Neither experimental nor clinical data confirm the repeatedly published opinion that video-endoscopic surgery promotes tumor growth or the occurrence of implantation metastases in cancer patients. On the contrary, alterations due to pneumoperitoneum by the application of different gases, pressures, and temperatures might provide the basis for a new therapeutic approach to cancer surgery. Oncologically adequate resections defined by such terms as "no touch isolation" and "monobloc resection" can be performed video-endoscopically in a variety of intraabdominally or intrathoracically located cancers if a standardized technique is used. The benefit of video-endoscopic surgery is limited in large tumors, especially if they have reached the organ surface. There is still a major deficit in the clinical evaluation of video-endoscopic interventions in most oncologic diseases. Randomized studies comparing video-endoscopic and conventional surgery have been reported only for the resection of colorectal carcinoma. They show that laparoscopic resections can be performed with a minimum of postoperative complications to the same extent as conventional resections and offer several advantages during the early postoperative period. No reliable data from comparative trials are as yet available on the long-term results.

Increased intraperitoneal pressure and insufflation of carbon dioxide during laparoscopy may cause sepsis by promoting systemic inflammation in patients with intra-abdominal inflammatory diseases. The influence of carbon dioxide and helium during laparoscopy on bacteremia, endotoxemia, the plasma concentration of tumor necrosis factor-alpha (TNF-alpha), TNF-alpha secretion ex vivo by peripheral blood mononuclear cells (PBMCs), and intraperitoneal abscess formation was investigated in an animal model. A standardized fecal inoculum was injected intraperitoneally, and rats underwent laparoscopy with either carbon dioxide (N = 20) or helium (N = 20) or no further manipulation (control group; N = 20). Bacteremia was significantly more common 1 hour after laparoscopy with CO2 than in animals receiving helium or the control group. Furthermore, helium use led to a significant decrease of bacteremia 1 week after intervention. Fecal inoculation caused significant leukocytopenia in all groups within 1 hour after intervention, with complete recovery only in the helium-treated group (p0.05). The TNF-alpha plasma concentration was significantly lower in the helium-treated group, and suppression of ex vivo production recovered only in the animals undergoing laparoscopy with helium (p0.05). The number of intraperitoneal abscesses was significantly lower after laparoscopy with helium (2+/-1.5) than after CO2 laparoscopy (6.3+/-5.1) or in the control group (5.2+/-4.8). Laparoscopy with CO2 increased systemic inflammation only slightly, while helium use was associated with a significant lower incidence of bacteremia and local and systemic inflammation compared with the control group.

BACKGROUND In a prospective trial (October 1996-April 1998) the effect of octreotide and tamoxifen on the recurrence of pancreatic carcinoma after R0 resection was evaluated. METHODS Patients with a local recurrence after curative resection of ductal adenocarcinoma of the pancreas were treated with 100 micrograms of octreotide three times a day and tamoxifen 20 mg once daily. The median survival time, quality of life (EO-RTC-QLQ-30) and side effects of the octreotide-tamoxifen group were compared with a historic cohort (n = 14) of patients treated in our department (9/95-9/96) according to the "best supportive care" concept. RESULTS Recurrences were diagnosed after R0 resection in a mean time of 13 +/- 6.8 months. Patients treated with octreotide and tamoxifen had a significantly (P < 0.05) longer median survival time (7 months; range: 3-12) vs 3.5 months; range: 1.5-5). The octreotide-tamoxifen group suffered less from lack of appetite, nausea, fatigue, and pain and needed fewer analgesics. The only side effect of the octreotide-tamoxifen therapy was moderate diarrhea in 2 patients at the beginning of the therapy. CONCLUSION Since combined therapy with octreotide and tamoxifen can be administered comfortably for outpatient treatment, this seems to represent progress in the palliative therapy of pancreatic cancer.

Background: Abdominal hernia repair with implantation of synthetic meshes using the sublay technique has resulted in low recurrence rates and high patient satisfaction. Aim: The purpose of this experimental animal study was to investigate whether mesh fixation is necessary in abdominal hernia repair using a polypropylene mesh in the sublay technique. Methods: Forty-five rats were divided into three groups after creating an abdominal wall defect (CG control group, no mesh implantation; NoFixG mesh implantation without fixation group; SG mesh with suture fixation group) with 15 animals in each group. Endpoints were clinical herniation pressure, hydroxyproline (HP) concentration, mesh shape and number of fibroblasts/collagen fibres of the anchor zone 7, 14 and 90 days after implantation. Results: Herniation pressure, HP content and number of fibroblasts were similar between NoFixG and SG, although significantly higher in these groups than in the CG (P

The Yersinia outer protein YopE belongs to the translocated effector proteins of pathogenic yersiniae. We constructed various truncated yopE genes fused to gfp (encoding the green fluorescent protein) to study yopE gene expression and YopE–GFP translocation of Y. enterocolitica in cell culture and mouse infection models. The hybrid gene fusions were co-expressed in Y. enterocolitica (i) on a low-copy plasmid in the presence of the virulence plasmid pYV08 (in trans configuration) and (ii) after co-integration by homologous recombination of a yopE–gfp-carrying suicide plasmid into pYV08 (co-integrate configuration). After 30 min of infection of HEp-2 cell monolayers, extracellularly located yersiniae began to emit green fluorescence after excitation. In contrast, internalized bacteria were weakly fluorescent. Translocation of YopE–GFP into HEp-2 cells by attached yersiniae was visualized by optical sectioning of fluorescent HEp-2 cells using confocal laser scanning microscopy and was confirmed by immunoprecipitation of cytosolic YopE–GFP from selectively solubilized HEp-2 cells. The co-translocation of other Yops was not significantly impaired by YopE–GFP as shown by YopH/YopE-mediated suppression of the oxidative burst of infected neutrophils. The time course of yopE–gfp expression (in trans as well as in the co-integrate configuration) in the HEp-2 cell infection model as well as after in vitro induction was studied using a highly sensitive CCD camera and a flow cytometer. Similar results were obtained with a YopE–LUC (firefly luciferase) protein fusion as reporter. After intraperitoneal, intravenous and orogastrical infection of Balb/c mice with the recombinant yersiniae strains, green fluorescing bacteria could be visualized microscopically in the peritoneum, the spleen, the liver and in the Peyer's patches. However, only weakly fluorescent yersiniae were observed in the intestinal lumen. These results were quantified by flow cytometric measurements. The application of gfp as a reporter gene turned out to be promising for the study of protein translocation by protein type III secretion systems and differential virulence gene expression in vivo.

Background: Although tension-free techniques of hernia repair using synthetic meshes revealed encouraging results, the best method of inguinal hernia repair is still unclear. Methods: In a prospective randomized phase-II-B study, early postoperative results of laparoscopic transabdominal preperitoneal repair (n = 80), open plug and patch repair (n = 80), and Shouldice’s operation (n = 80) were compared. Postoperative pain and patient’s comfort were defined as main endpoints. Results: The laparoscopic approach had significantly longer operation time and was more expensive (61 ± 12 minutes; $1,211) than plug and patch repair (36 ± 14 minutes; $124) and Shouldice’s operation (47 ± 17 minutes; $69). Main postoperative complications were wound hematomas, seromas, and superficial wound infection, without significant difference between the groups. Postoperative pain, analgesia requirements, limitation of daily activities, and return to work did not differ between laparoscopic and open tension-free repair but were significantly lower in both groups compared with Shouldice’s operation. So far, no recurrence was observed after a mean follow-up of 25 months. Conclusion: Open plug and patch repair is a promising technique of hernia repair in adults, because it offers the same excellent patient comfort as the laparoscopic repair but is less expensive and can be performed under local anesthesia.

Purpose: The genesis of anastomotic leakage and late stenosis of esophagogastrostomy is still unknown, although minimal blood flow and tissue hypoxia of the gastric tube are discussed as main reasons. However, the changes in tissue oxygen tension (PtO 2 ) on esophagogastric anastomoses have not yet been evaluated in the perioperative course. Methods: Submucosal tissue oxygen tension (PtO 2 ) was measured in 33 patients with cervical esophagogastrostomy during resection of esophageal carcinoma and reconstruction by a gastric tube. Measurements were taken close to the projected resection line and latter anastomosis using a Clark-type oxygen electrode. Results: Mean baseline PtO 2 was 55.1 ± 10.4 mmHg. Following the ligature of the vasa gastricae brevis and the left gastroepiploic artery (46.1 ± 9.7 mmHg), the left gastric artery (34.8 ± 9.8 mmHg), and the pull up of the gastric tube, PtO 2 decreased to 25.8 ± 9.4 mmHg. Anastomotic leakage occurred in 6 patients and late stenosis in 10 patients. During the operation there was no significant evidence of decreased PtO 2 levels in these two groups. Postoperative PtO 2 levels showed a significant increase in patients with anastomotic leakage. Conclusion: A disorder in oxygen consumption may cause a significant increase of PtO 2 in anastomotic tissue, which is associated with anastomotic leakage.

The ability to synthesize and uptake the Yersinia siderophore yersiniabactin is a hallmark of the highly pathogenic, mouse-lethal species Yersinia pestis , Y. pseudotuberculosis , and Y. enterocolitica 1B. We have identified four genes, irp1 , irp3 , irp4 , and irp5 , on a 13-kb chromosomal DNA fragment of Y. enterocolitica O8, WA-314. These genes constitute the yersiniabactin biosynthetic gene cluster together with the previously defined irp2 . The irp1 gene consists of 9,486 bp capable of encoding a 3,161-amino-acid high-molecular-weight protein 1 (HMWP1) polypeptide with a predicted mass of 384.6 kDa. The first 3,000 bp of irp1 show similarity to the corresponding regions of the polyketide synthase genes of Bacillus subtilis and Streptomyces antibioticus . The remaining part of irp1 is most similar to irp2 , encoding HMWP2, which might be the reason for immunological cross-reactivity of the two polypeptides. Irp4 was found to have 41.7% similarity to thioesterase-like protein of the anguibactin biosynthetic genes of Vibrio anguillarum . Irp5 shows 41% similarity to EntE, the 2,3-dihydroxybenzoic acid-activating enzyme utilized in enterobactin synthesis of Escherichia coli . Irp4 and Irp5 are nearly identical to YbtT and YbtE, recently identified in Y. pestis. irp3 has no similarity to any known gene. Inactivation of either irp1 or irp2 abrogates yersiniabactin synthesis. Mutations in irp1 or fyuA (encoding yersiniabactin/pesticin receptor) result in downregulation of irp2 that can be upregulated by the addition of yersiniabactin. A FyuA-green fluorescent protein translational fusion was downregulated in an irp1 mutant. Upregulation was achieved by addition of yersiniabactin but not desferal, pesticin, or pyochelin, which indicates high specificity of the FyuA receptor and autoregulation of genes involved in synthesis and uptake of yersiniabactin.

Hintergrund: Zur Zeit existiert keine einheitlich akzeptierte Therapie zur Verhinderung von Trokarmetastasen bei laparoskopischen Operationen von malignen Tumoren. Methode: Um ein intraperitoneales Tumorwachstum und Trokarmetastasen bei laparoskopischen Operationen zu verhindern, wurden die Effekte von Taurolidin und Heparin auf das Wachstum von Kolonkarzinomzellen (DHD/K12/TRb) in vitro sowie im Rattenmodell untersucht. In vitro erfolgte zunachst nach Inkubation der Zellen mit Heparin, Taurolidin oder beiden Substanzen die Bestimmung der Wachstumskinetiken der Zellen. In einem 2. Experiment erfolgte dann bei Ratten (n = 60) die intraperitoneale Applikation der Tumorzellen und anschliesend der Aufbau eines Pneumoperitoneums fur 30 min. Die Ratten wurden in 4 Gruppen randomisiert (I: Tumorzellen; II: Tumorzellen und Heparin; III: Tumorzellen und Taurolidin; IV: Tumorzellen und Taurolidin + Heparin). Ergebnisse: Wahrend das Tumorzellwachstum in vitro durch Heparin nicht beeinflust wurde, konnte durch Taurolidin und Taurolidin/Heparin eine signifikante Supprimierung des Wachstums erreicht werden. In vivo hingegen war das intraperitoneale Tumorgewicht gegenuber der Kontrollgruppe (596 ± 278 mg) sowohl bei der Instillation von Heparin (298 ± 155 mg) als auch von Taurolidin (149 ± 247 mg) vermindert. Die Kombination beider Substanzen verursachte eine weitere Verminderung des Tumorgewichts auf durchschnittlich (21,5 ± 36 mg). Die Entwicklung von Trokarmetastasen konnte hingegen nur durch die Instillation von Taurolidin oder die Kombination von Taurolidin und Heparin signifikant supprimiert werden. Schlusfolgerung: Wahrend durch Heparin das intraperitoneale Tumorwachstum nur geringgradig beeinflust wurde, konnten durch die Instillation von Taurolidin und Taurolidin/Heparin sowohl das intraperitoneale Tumorwachstum als auch die Entwicklung von Trokarmetastasen fast vollstandig verhindert werden.

Hintergrund: Laparoskopische Operationen werden auch in zunehmendem Mas bei Patienten mit einer Peritonitis oder anderen intraabdominalen entzundlichen Prozessen durchgefuhrt, obwohl der erhohte intraabdominale Druck eine Sepsis durch eine gesteigerte Bakteriamie und systemische Inflammation begunstigen konnte. Methode: In einer experimentellen Studie wurde deshalb der Einflus einer Laparotomie und einer Laparoskopie auf die bakterielle Translokation sowie auf die Plasmaspiegel von TNFα und Endotoxin analysiert. Hierzu wurde zunachst bei Ratten eine standardisierte humane Stuhlprobe intraperitoneal appliziert und anschliesend eine Laparotomie (n = 20), eine Laparoskopie (n =20) oder keine weitere Manipulation in der Kontrollgruppe (n = 20) durchgefuhrt. Ergebnisse: Eine Stunde nach der Intervention kam es in allen Gruppen zu einer Bakteriamie, welche nach Laparotomie und Laparoskopie signifikant gegenuber der Kontrollgruppe gesteigert war (p = 0,01). Die Stuhlapplikation verursachte weiterhin in allen Gruppen eine signifikante Erhohung der TNFα- und Endotoxinplasmaspiegel. Bereits 1 h postoperativ stiegen die TNFα- und Endotoxinplasmaspiegel an, mit signifikant hoheren Werten nach Laparotomie (p < 0,05). Die durchschnittliche Zahl der intraperitonealen Abszesse war ebenfalls nach Laparotomie (n = 10) signifikant hoher (p < 0,05) als nach Laparoskopie (n = 8) und in der Kontrollgruppe (n = 5). Schlusfolgerung: Die Laparotomie und die Laparoskopie fuhren im Vergleich zur Kontrollgruppe zu einer transienten Steigerung der Bakteriamie und systemischen Inflammation. Die systemische Inflammation sowie die Entwicklung von intraperitonealen Abszessen war allerdings in diesem Modell nur nach einer Laparatomie signifikant gegenuber einer Laparoskopie und der Kontrollgruppe gesteigert.

The effects of laparotomy and laparoscopy with different gases on subcutaneous and intraperitoneal tumor growth have not been evaluated yet.Tumor growth of colon adenocarcinoma DHD/K12/TRb was measured in rats after laparotomy, laparoscopy with CO2 or air, and in control group. Cell kinetics were determined after incubation with carbon dioxide or air in vitro and tumor growth was measured subcutaneously and intraperitoneally after surgery in vivo.In vitro, tumor cell growth increased significantly after incubation with air and CO2. In vivo, intraperitoneal tumor weight was increased after laparotomy (1,203 +/- 780 mg) and after laparoscopy with air (1,085 +/- 891 mg) and with CO2 (718 +/- 690 mg) compared to control group (521 +/- 221 mg) (p0.05). Subcutaneous tumor growth was promoted after laparotomy (71 +/- 35 mg) and even more after laparoscopy with air (82 +/- 45 mg) and CO2 (99 +/- 55 mg) compared to control group (36 +/- 33 mg).Insufflation of air and CO2 promote tumor growth in vitro. In vivo, intraperitoneal tumor growth seems to be promoted primarily by intraperitoneal air and subcutaneous tumor growth by CO2.