HPV-associated anal lesions in HIV+ patients: long-term results regarding quality of life.

PURPOSE: HIV infection and concomitant HPV-associated anal lesions may significantly impact on patients' quality of life (QoL), as they are predicted to have negative effects on health, psyche, and sexuality. MATERIAL AND METHODS: Fifty-two HIV+ patients with HPV-associated anal lesions were enrolled in a survey approach after undergoing routine proctologic assessment and therapy for HPV-associated anal lesions if indicated over a time span of 11 years (11/2004-11/2015). Therapy consisted of surgical ablation and topic treatment. QoL was analyzed using the SF-36 and the CECA questionnaires. RESULTS: Fifty-two of 67 patients (77.6%) were successfully contacted and 29/52 provided full information. The mean age was 43.8 ± 12.8 years. The median follow-up from treatment to answering of the questionnaire was 34 months. Twenty-one percent (6/29) of the patients reported suffering from recurrence of condyloma acuminata, three patients from anal dysplasia (10.3%). In the SF-36, HIV+ patients did not rate their QoL as significantly different over all items after successful treatment of HPV-associated anal lesions. In the CECA questionnaire, patients with persisting HPV-associated anal lesions reported significantly higher emotional stress levels and disturbance of everyday life compared to patients who had successful treatment (71.9/100 ± 18.7 vs. 40.00/100 ± 27.4, p = 0.004). Importantly, the sexuality of patients with anal lesions was significantly impaired (59.8/100 ± 30.8 vs. 27.5/100 ± 12.2, p = 0.032). CONCLUSION: HPV-associated anal lesions impact significantly negative on QoL in HIV+ patients. Successful treatment of HPV-associated anal lesions in HIV+ patients improved QoL. Specific questionnaires, such as CECA, seem to be more adequate than the SF-36 in this setting.

Pancreatogastrostomy Versus Pancreatojejunostomy for RECOnstruction After PANCreatoduodenectomy (RECOPANC, DRKS 00000767): Perioperative and Long-term Results of a Multicenter Randomized Controlled Trial.

OBJECTIVES: To assess pancreatic fistula rate and secondary endpoints after pancreatogastrostomy (PG) versus pancreatojejunostomy (PJ) for reconstruction in pancreatoduodenectomy in the setting of a multicenter randomized controlled trial. BACKGROUND: PJ and PG are established methods for reconstruction in pancreatoduodenectomy. Recent prospective trials suggest superiority of the PG regarding perioperative complications. METHODS: A multicenter prospective randomized controlled trial comparing PG with PJ was conducted involving 14 German high-volume academic centers for pancreatic surgery. The primary endpoint was clinically relevant postoperative pancreatic fistula. Secondary endpoints comprised perioperative outcome and pancreatic function and quality of life measured at 6 and 12 months of follow-up. RESULTS: From May 2011 to December 2012, 440 patients were randomized, and 320 were included in the intention-to-treat analysis. There was no significant difference in the rate of grade B/C fistula after PG versus PJ (20% vs 22%, P = 0.617). The overall incidence of grade B/C fistula was 21%, and the in-hospital mortality was 6%. Multivariate analysis of the primary endpoint disclosed soft pancreatic texture (odds ratio: 2.1, P = 0.016) as the only independent risk factor. Compared with PJ, PG was associated with an increased rate of grade A/B bleeding events, perioperative stroke, less enzyme supplementation at 6 months, and improved results in some quality of life parameters. CONCLUSIONS: The rate of grade B/C fistula after PG versus PJ was not different. There were more postoperative bleeding events with PG. Perioperative morbidity and mortality of pancreatoduodenectomy seem to be underestimated, even in the high-volume center setting.

[Ruptured Abdominal Aortic Aneurysm - Results and Prognostic Factors at a Certified Centre of Vascular Surgery]. / Das rupturierte abdominale Aortenaneurysma ­ Ergebnisse und prognostische Faktoren an einem gefäßchirurgischen Zentrum.

Introduction: Although the perioperative management has been optimised over the past few decades, there has not been a remarkable improvement in the mortality rates of patients with a ruptured abdominal aortic aneurysm (rAAA). The aim of this retrospective trial was to define pre-, intra- and postoperative parameters which influence the perioperative and long-term outcome of patients and which can be modified by the operating team. Methods: A retrospective database analysis was performed in 49 patients who had undergone an operation of rAAA in our certified centre of vascular surgery between the beginning of 2006 and the end of 2012. The minimal follow-up period was 30 months. The statistical analysis was done univariately using the Kaplan-Meier method and a log-rank-test, and multivariately with the Cox model. Results: Intrahospital mortality was 40.8 %, perioperative mortality (30 postoperative days) was 28.9 %. The survival rate for 1 year was 52.4 %; the survival rate for 5 years was 45.3 %. In the univariate analysis, significant differences in the early postoperative survival rates were found depending on preoperative systolic blood pressure, preoperative haemoglobin (< 10 vs. ≥ 10 g/dl), the intraoperative need of blood and frozen plasma transfusions, type of perforation, type of AAA, the need for further surgical interventions, postoperative MOF, acute kidney failure and postoperative septicaemia. The late survival rates were significantly influenced by the type of perforation and AAA, pre-existing coronary disease and diabetes mellitus in fully identified patients discharged from hospital (n = 27). In the multivariate analysis pursuant to the Cox model, patients with pre-existing coronary disease had a 3.9-fold higher relative risk to die after the operation of rAAA, while patients with a free perforation of the rAA had a 10-fold higher relative risk. Conclusion: The high mortality of rAAA is caused by haemorrhagic shock and its complications, which are mostly non-surgical. Therapeutic efforts should focus on those perioperative parameters which can be modified by the treating teams. Alongside the centralisation of rAAA in high-volume-departments of vascular surgery, the systematic sonographic screening for asymptomatic AAA in the population older than 65 years should be enforced. A possible advantage of EVAR in rAAA has yet to be shown by trials in progress such as IMPROVE, AJAX and RCAR.

[Complications after Percutaneous Endoscopic Gastrostomy Tube Placement - A Retrospective Analysis]. / Komplikationen nach Anlage einer perkutanen endoskopischen Gastrostomie - eine retrospektive Analyse.

BACKGROUND: Enteral nutrition is vital for patients with inadequate or absent oral food intake, as it can help to avoid catabolic metabolism. Enteral feeding can be secured by placing a percutaneous endoscopic gastrostomy tube (PEG-tube) which is an approved method. Several clinical studies could verify the superiority of this procedure compared to other options. Even though PEG-tube placement is regarded as less invasive surgery, a considerable rate of complications is reported in literature. MATERIAL/METHODS: Here, we report a retrospective analysis of PEG-tube placements in the Bonn University Hospital from January 2005 to December 2012. RESULTS: Overall, 641 PEG-tubes were placed with a complication rate of 9.4 %, which can be further divided in 5.5 % minor complications (mic) and 3.9 % major complications (mac). Two cases of death occurred in the context of PEG-tube placement. Endoscopically inserted PEG-tubes showed a complication rate of 8.6 % (4.8 % mic, 3.8 % mac). 63.2 % of mac consisted of perforations, 15.8 % of intra-abdominal abscesses and 15.8 % of buried bumper syndromes. The complication rate of CT-guided placement of PEG-tubes was 38.9 % (27.8 % mic, 11.1 % mac). In this group, all mac were perforations. Surgical PEG-tube placement was accompanied by no mac and 7.7 % mic. CONCLUSION: The amount of complications during PEG-tube placement is remarkable, therefore the indication of this procedure must be contemplated critically and careful follow-up is crucial.

[Implementation of the Perioperative WHO Safety Checklist at a Maximum Care Hospital - A Retrospective Analysis]. / Implementierung der perioperativen WHO-Sicherheitscheckliste an einem Klinikum der Maximalversorgung - eine retrospektive Analyse.

BACKGROUND: In recent years there has been a significant increase of surgical procedures worldwide. Perioperative complication occurred in approximately 10 %, mortality was about 0.5 %. Half of these adverse events were considered to have been preventable. With the introduction of a perioperative checklist by the WHO in 2008, a significant reduction of morbidity and mortality could be achieved. The aim of this study was to investigate the success of the implementation process of the checklist at a maximum care hospital over a three-year period and to expose and analyse any occurring issues. PATIENTS AND METHODS: At various time points (introduction phase, five months, one year and three years after implementation) a total of 358 operations was investigated. First the presence and the handling of the checklist were investigated followed by an analysis of possible influencing factors on the processing. To examine a potential perioperative malpractice, three typical perioperative errors known from the literature on patient safety were analysed. RESULTS: The presence of the checklist improved significantly during the study. With the exception of the first column (signed by ward nurse) the checklist was processed more often among the participants (anaesthesia nurse, anaesthesia physician, surgeon) over the time. However the "sign out" column edited by the surgeon at the end of the operation fell below expectations. In addition to the duration after implementation the level of experience of the surgeon was a relevant factor for a properly completed checklist. During the study a malpractice was found in two cases, a checklist could not be detected. CONCLUSION: Within the study we could demonstrate the difficulties of introducing a surgical checklist at a maximum care hospital. Therefore involved nursing or medical staff must be aware of the usefulness of the checklist and should be motivated to use it. In addition, periodical lectures, training courses and role modelling of nursing and medical staff are required. The objective must be to establish the checklist into daily routine as it is a simple and efficient tool to reduce perioperative morbidity and mortality.

[Surgical Therapy and Prognostic Factors for Carcinoma of Vater's Papilla]. / Chirurgische Therapie und prognostische Faktoren des Papillenkarzinoms.

BACKGROUND: Carcinoma of ampulla of Vater are rare tumours of the GI-tract with an improved prognosis compared to other periampullary tumours. Analysis of survival and prognostic factors are limited due to the low incidence of the carcinoma. The intention of this study in patients with papillary carcinoma was to evaluate short- and long-term survival and to identify prognostic factors for pancreatectomy and reconstruction using pancreatogastrostomy as treatment of carcinoma of Vater's ampulla. PATIENTS AND METHODS: Between 1989 and 2008 76 patients with a carcinoma of the ampulla of Vater were treated by oncological resection followed by pancreatogastrostomy. Various factors such as demographics, perioperative factors, histopathological findings as well as short- and long-term survival were evaluated retrospectively. Data were analysed statistically using Kaplan-Meier estimates of survival with log-rank test and uni- and multivariate analysis with Cox regression. RESULTS: The overall 5-year survival was 46 %, the 10-year survival 26 % for resected patients. By univariate analysis we could demonstrate that lymph node metastasis is the only predictor for outcome. In the multivariate analysis, age, sex, grading and especially lymph node status were a significant predictor for the survival of patients. CONCLUSION: In the current patient cohort lymph node status was the most important independent predictor of outcome after resection of carcinoma of Vater's papilla.

[Posthepatectomy Liver Failure in Extended Liver Resections: An Overview Based on a Retrospective Single-Centre Analysis]. / Postoperatives Leberversagen nach erweiterten Leberresektionen - eine Übersicht, gestützt durch eine retrospektive Single-Center-Analyse.

BACKGROUND: Posthepatectomy liver failure (PHLF) is one of the most serious complications after major liver resections and an important factor in terms of perioperative morbidity and mortality. Despite many advances in the understanding and grading of PHLF, the definitions found in literature are very heterogeneous, which complicates the identification of high-risk patients. In this study we analysed the results of extended liver resections and potential risk factors for PHLF based on patient data derived from our tertiary referral centre. The aim of the study was to gain an overview of the essential aspects in the prevention of PHLF combined with key intraoperative issues and postoperative treatment strategies. METHODS: We analysed data from 202 patients who underwent extended elective liver resections at our centre between April 1989 and September 2009 (135 right hemihepatectomies, 39 left hemihepatectomies, 28 right trisectionectomies). According to Balzan's "50/50 criteria", PHLF was defined as prothrombin time (PT) < 50 % combined with serum bilirubin (SB) > 50 micromol/L on postoperative day (POD) 5 or as death due to primary or secondary liver failure. RESULTS: Thirty-day mortality and overall in-hospital mortality were 4.95 and 8.91 %, respectively. Twenty-eight (14 %) patients developed PHLF and 16 (57 %) patients died. Compared to patients with normal postoperative liver function, several significant pre- and intraoperative factors for PHLF were identified, e.g. primary malignant liver tumour (p < 0.001), extended liver resection (p < 0.001), time of surgery (p < 0.001) and intraoperative transfusion of packed RBC (p < 0.02) or FFP (p < 0.001). CONCLUSION: Although progress has been made in hepatobiliary surgery, PHLF remains a serious complication, especially after extended liver resections. Careful, optimised preoperative risk stratification is required to identify patients at risk for PHLF.

Effects of macrophage-dependent peroxisome proliferator-activated receptor γ signalling on adhesion formation after abdominal surgery in an experimental model.

BACKGROUND: The pathophysiology of adhesion formation after abdominal and pelvic surgery is still largely unknown. The aim of the study was to investigate the role of macrophage polarization and the effect of peroxisome proliferator-activated receptor (PPAR) γ stimulation on adhesion formation in an animal model. METHODS: Peritoneal adhesion formation was induced by the creation of ischaemic buttons within the peritoneal wall and the formation of a colonic anastomosis in wild-type, interleukin (IL) 10-deficient (IL-10(-/-) ), IL-4-deficient (IL-4(-/-) ) and CD11b-Cre/PPARγ(fl) (/fl) mice. Adhesions were assessed at regular intervals, and cell preparations were isolated from ischaemic buttons and normal peritoneum. These samples were analysed for macrophage differentiation and its markers, and expression of cytokines by quantitative PCR, fluorescence microscopy, arginase activity and pathological examination. Some animals underwent pioglitazone (PPAR-γ agonist) or vehicle treatment to inhibit adhesion formation. Anastomotic healing was evaluated by bursting pressure measurement and collagen gene expression. RESULTS: Macrophage M2 marker expression and arginase activity were raised in buttons without adhesions compared with buttons with adhesions. IL-4(-/-) and IL-10(-/-) mice were not affected, whereas CD11b-Cre/PPARγ(fl) (/fl) mice showed decreased arginase activity and increased adhesion formation. Perioperative pioglitazone treatment increased arginase activity and decreased adhesion formation in wild-type but not CD11b-Cre/PPARγ(fl) (/fl) mice. Pioglitazone had no effect on anastomotic healing. CONCLUSION: Endogenous macrophage-specific PPAR-γ signalling affected arginase activity and macrophage polarization, and counter-regulated peritoneal adhesion manifestation. Pharmacological PPAR-γ agonism induced a shift towards macrophage M2 polarization and ameliorated adhesion formation in a macrophage-dependent manner. Surgical relevance Postoperative adhesion formation is frequently seen after abdominal surgery and occurs in response to peritoneal trauma. The pathogenesis is still unknown but includes an imbalance in fibrinolysis, collagen production and inflammatory mechanisms. Little is known about the role of macrophages during adhesion formation. In an experimental model, macrophage M2 marker expression was associated with reduced peritoneal adhesion formation and involved PPAR-γ-mediated arginase activity. Macrophage-specific PPAR-γ deficiency resulted in reduced arginase activity and aggravated adhesion formation. Pioglitazone, a PPAR-γ agonist, induced M2 polarization and reduced postoperative adhesion formation without compromising anastomotic healing in mice. Pioglitazone ameliorated postoperative adhesion formation without compromising intestinal wound healing. Therefore, perioperative PPAR-γ agonism might be a promising strategy for prevention of adhesion formation after abdominal surgery.

[Hospital disinfection challenges due to multiresistant pathogens in surgery]. / Krankenhaushygienische Herausforderungen durch multiresistente Erreger in der Chirurgie.

The number of antibiotic-resistant pathogens is increasing continuously while the development of new, effective antibiotics cannot be expected in the near future. Postoperative infections represent most of the nosocomial infections by now. Based on this, hygienic strategies regain importance, since a sustainable control of nosocomial infections will not succeed without the implementation of such strategies. In this article, the most important preventive strategies for prevention of infections with MRSA and 3- and 4-fold resistant gram-negative bacteria on the basis of current recommendations of the Commission for Hospital Hygiene and Infection Prevention (KRINKO) are presented.

[Immunomodulatory aspects in the development, prophylaxis and therapy for postoperative ileus]. / Immunmodulatorische Aspekte bei der Entstehung, Prophylaxe und Therapie des postoperativen Ileus.

Postoperative ileus (POI) is defined as a transient episode of impaired gastrointestinal motility after abdominal surgery, which prevents effective transit of intestinal contents or tolerance of oral intake. This frequent postoperative complication is accompanied by a considerable increase in morbidity and hospitalisation costs. The aetiology of POI is multifactorial. Besides a suppression of peristalsis by inhibitory neuronal signalling and administration of opioids, particularly in the prolonged form, immunological processes play an important role. After surgical trauma, resident macrophages of the muscularis externa (ME) are activated leading to the liberation of proinflammatory mediators and a spreading of the inflammation along the entire gastrointestinal tract. To date, no prophylaxis or evidence-based single approach exists to treat POI. Since none of the current treatment approaches (i.e., prokinetic drug treatment) has provided a benefit in randomised trials, immunoregulatory interventions appear to be more promising in POI prevention or treatment. The present contribution gives an overview of immunological mechanisms leading to POI focusing on current and future therapeutic and prophylactic approaches.

The role of lymphoid tissue in the attenuation of the postoperative ileus.

Standardized intestinal manipulation (IM) leads to local bowel wall inflammation subsequently spreading over the entire gastrointestinal tract. Previously, we demonstrated that this so-called gastrointestinal field effect (FE) is immune-mediated. The aim of this study was to investigate the role of secondary lymphoid organs [mesenteric lymph nodes (MLN), gut-associated lymphoid tissue (GALT)] in IM-mediated FE by employing mice with deficient secondary lymphoid organs (aly/aly, MLN ex) or by administration of 2-amino-2-[2-(4-octylphenyl)ethyl]-1,3-propanediol (FTY720), an immunomodulating agent that inhibits emigration of lymphocytes out of lymphoid organs. Small bowel muscularis, and colonic muscularis from wild-type mice as control, from aly/aly mice, FTY720-treated mice (daily dose of 1.0 mg/kg mouse ip starting 3 days before surgical procedure), and wild-type mice that had undergone removal of mesenteric lymph nodes before IM (MLN ex mice) were obtained after selective IM of the jejunum or sham operation. FE was analyzed by measuring transit time of orally administered fluorescent dextran in the gastrointestinal tract [geometric center (GC) of fluorescent dextran], colonic transit time, infiltration of myeloperoxidase-positive cells, and circular smooth muscle contractility. Furthermore, mRNA levels of inflammatory cytokines [interleukin (IL)-6, tumor necrosis factor (TNF)-α, macrophage inflammatory protein (MIP)-1α] were determined by Taqman-PCR. We observed a significantly reduced upregulation of proinflammatory cytokines (IL-6, TNF-α, MIP-1α) in colonic muscularis of MLN ex mice, aly/aly mice, and FTY720-treated mice compared with wild-type mice. Contractility of circular muscularis strips of the colon but not the jejunum was significantly improved in aly/aly mice and FTY720-treated wild-type mice. Additionally, inflammation of the colon determined by the number of myeloperoxidase-positive cells and colonic transit time were significantly improved in aly/aly mice, FTY720-treated wild-type mice, and in MLN ex mice. In summary, lack of secondary lymphoid organs (MLN + GALT) in aly/aly mice or administration of FTY720 abrogated FE after IM as opposed to wild-type mice. These data demonstrate that secondary lymphoid organs are involved in the propagation of FE and postoperative ileus. FTY720 indirectly affects FE by inhibiting migration of activated T cells from the jejunum and adjacent secondary lymphoid organs to the colon. These findings support the crucial role of the adaptive immune system in FE, most likely by a sphyngosine 1-phosphate-dependent mechanism.

Primary perivascular epitheloid cell tumour (PEComa) of the liver: case report and review of the literature.

PURPOSE: Perivascular epitheloid cell tumour [PEComa] is a rare neoplasm entity, characterized by perivascular epitheloid cells with a coexpression of smooth muscle and melanocytic markers. PEComas are found in a variety of localizations, though lesions within the liver are still scarcely found. Although the majority of these tumours are recognized as benign, there are some reports about advanced and aggressive tumours even with fatal outcome. By means of this case report and literary review including other 21 published cases, potential treatment modalities concerning clinical diagnostics, therapy and the follow-up care should be discussed. METHODS: The following report presents the case of a 53-year old woman with a known liver lesion, since four years under regularly sonographic controls. Finally, after a haemorrhage episode, the lesion was resected and the diagnosis found. For the literary review a systematic search for case reports published between January 1, 1999 and May 1, 2012 was performed on Pubmed. RESULTS: The only way, till now, of confirming the diagnosis is through immunohistochemical examinations. The already published Malignancy criteria by Folpe et al. must be taken carefully in question, as there are cases of malignant behaviour, that do not exactly coincide with these. CONCLUSION: Primary PEComa of the liver must be treated as potential malignant and therefore a close follow-up is demanded.

[How does the surgical society (DGAV) support the continuing medical training in general and visceral surgery?] / Wie unterstützt die Fachgesellschaft (DGAV) die ärztliche Weiterbildung in der Allgemein- und Viszeralchirurgie?

The medical councils (Ärztekammern) develop the contents of the further training regulations with the support of the specialist society. The hospitals with the training supervisors have to implement these contents for the trainees in continuing education and confirm the acquisition of competence for the individual tasks. Surveys of young surgeons in recent years have shown that many participants do not receive structured continuing education, so that there is general dissatisfaction. Therefore, the German Society for General and Visceral Surgery (DGAV) is required to provide assistance to its members to improve continuing education in the departments. For example, the DGAV organizes more than 100 surgical courses annually on all topics of visceral surgery, anatomy, skills courses and revision courses with the Further Education and Advanced Training Quality Center (WeiFoQ). This year a continuing education curriculum was developed over the 6­year continuing education period, so that a structured continuing education is achievable. The contents of the continuing education regulations are included in this continuing education curriculum with explanations, video clips, and graphics, thus providing quick information on each individual surgical clinical picture. A digital surgical catalog provides a quick overview of the status of personal continuing education. It is planned to set up an interface to the eLogbook of the medical councils.

Intestinal regeneration, residual function and immunological priming following rescue therapy after rat small bowel transplantation.

Clinical evidence suggests that recurrent acute cellular rejection (ACR) may trigger chronic rejection and impair outcome after intestinal transplantation. To test this hypothesis and clarify underlying molecular mechanisms, orthotopic/allogenic intestinal transplantation was performed in rats. ACR was allowed to occur in a MHC-disparate combination (BN-LEW) and two rescue strategies (FK506monotherapy vs. FK506+infliximab) were tested against continuous immunosuppression without ACR, with observation for 7/14 and 21 days after transplantation. Both, FK506 and FK506+infliximab rescue therapy reversed ACR and resulted in improved histology and less cellular infiltration. Proinflammatory cytokines and chemotactic mediators in the muscle layer were significantly reduced in FK506 treated groups. Increased levels of CD4, FOXP3 and IL-17 (mRNA) were observed with infliximab. Contractile function improved significantly after FK506 rescue therapy, with a slight benefit from additional infliximab, but did not reach nontransplanted controls. Fibrosis onset was detected in both rescue groups by Sirius-Red staining with concomitant increase of the fibrogenic mediator VEGF. Recovery from ACR could be attained by both rescue therapy regimens, progressing steadily after initiation of immunosuppression. Reversal of ACR, however, resulted in early stage graft fibrosis. Additional infliximab treatment may enhance physiological recovery of the muscle layer and enteric nervous system independent of inflammatory reactions.

The novel orally active guanylhydrazone CPSI-2364 prevents postoperative ileus in mice independently of anti-inflammatory vagus nerve signaling.

PURPOSE: Postoperative ileus (POI) is an iatrogenic complication of abdominal surgery, mediated by a severe inflammation of the muscularis externa (ME). Previously, we demonstrated that intravenous application of the tetravalent guanylhydrazone semapimod (CNI-1493) prevents POI, but the underlying mode of action could not definitively be confirmed. Herein, we investigated the effect of a novel orally active salt of semapimod (CPSI-2364) on POI in rodents and distinguished between its inhibitory peripheral and stimulatory central nervous effects on anti-inflammatory vagus nerve signaling. METHODS: Distribution of radiolabeled orally administered CPSI-2364 was analyzed by whole body autoradiography and liquid scintillation counting. POI was induced by intestinal manipulation with or without preoperative vagotomy. CPSI-2364 was administered preoperatively via gavage in a dose- and time-dependent manner. ME specimens were assessed for p38-MAP kinase activity by immunoblotting, neutrophil extravasation, and nitric oxide production. Furthermore, in vivo gastrointestinal (GIT) and colonic transit were measured. RESULTS: Autoradiography demonstrated a near-exclusive detection of CPSI-2364 within the gastrointestinal wall and contents. Preoperative CPSI-2364 application significantly reduced postoperative neutrophil counts, nitric oxide release, GIT deceleration, and delay of colonic transit time, while intraoperatively administered CPSI-2364 failed to improve POI. CPSI-2364 also prevents postoperative neutrophil increase and GIT deceleration in vagotomized mice. CONCLUSIONS: Orally administered CPSI-2364 shows a near-exclusive dispersal in the gastrointestinal tract and effectively reduces POI independently of central vagus nerve stimulation. Its efficacy after single oral dosage affirms CPSI-2364 treatment as a promising strategy for prophylaxis of POI.

Perioperative infliximab application has marginal effects on ischemia-reperfusion injury in experimental small bowel transplantation in rats.

PURPOSE: Ischemia-reperfusion injury leads to impaired smooth muscle function and inflammatory reactions after intestinal transplantation. In previous studies, infliximab has been shown to effectively protect allogenic intestinal grafts in the early phase after transplantation with resulting improved contractility. This study was designed to reveal protective effects of infliximab on ischemia-reperfusion injury in isogenic transplantation. METHODS: Isogenic, orthotopic small bowel transplantation was performed in Lewis rats (3 h cold ischemia). Five groups were defined: non-transplanted animals with no treatment (group 1), isogenic transplanted animals with vehicle treatment (groups 2/3) or with infliximab treatment (5 mg/kg body weight intravenously, directly after reperfusion; groups 4/5). The treated animals were sacrificed after 3 (group 2/4) or 24 h (group 3/5). Histological and immunohistochemical analysis, TUNEL staining, real-time RT-PCR, and contractility measurements in a standard organ bath were used for determination of ischemia-reperfusion injury. RESULTS: All transplanted animals showed reduced smooth muscle function, while no significant advantage of infliximab treatment was observed. Reduced infiltration of neutrophils was noted in the early phase in animals treated with infliximab. The structural integrity of the bowel and infiltration of ED1-positive monocytes and macrophages did not improve with infliximab treatment. At 3 h after reperfusion, mRNA expression of interleukin (IL)-6, TNF-α, IL-10, and iNOS and MCP-1 displayed increased activation in the infliximab group. CONCLUSION: The protective effects of infliximab in the early phase after experimental small bowel transplantation seem to be unrelated to ischemia-reperfusion injury. The promising effects in allogenic transplantation indicate the need for further experiments with infliximab as complementary treatment under standard immunosuppressive therapy. Further experiments should focus on additional infliximab treatment in the setting of acute rejection.

[Implementation of fast-track measures in colorectal resections : A survey among members of the DGAI]. / Umsetzung anästhesiologischer Fast-Track-Maßnahmen bei kolorektalen Resektionen : Eine Umfrage unter Mitgliedern der DGAI.

PURPOSE: The fast-track (FT) concept is a multimodal, interdisciplinary approach to perioperative patient care intended to reduce postoperative complications. Despite good evidence implementation seems to need improvement, whereby almost all studies focused on the implementation of surgical modules regardless of the interdisciplinary aspect. Adherence to the anesthesiological measures (prehabilitation, premedication, volume and temperature management, pain therapy), on the other hand, has been insufficiently studied. To assess the status quo a survey on the implementation of anesthesiological FT measures was conducted among members of the German Society of Anesthesiology and Intensive Care Medicine (DGAI) to analyze where potential for improvement exists. METHODS: Using the SurveyMonkey® online survey tool, 28 questions regarding perioperative anesthesiological care of colorectal surgery patients were sent to DGAI members in order to analyze adherence to FT measures. RESULTS: While some of the FT measures (temperature management, PONV prophylaxis) are already routinely used, there is a divergence between current recommendations and clinical implementation for other components. In addition to premedication, interdisciplinary measures (prehabilitation) and measures that affect multiple interfaces (operating theatre, recovery room, ward), such as volume management or perioperative pain management, are particularly affected. CONCLUSION: The anesthesiological recommendations of the FT concept are only partially implemented in Germany. This particularly affects the interdisciplinary components as well as measures at the operating theatre, recovery room and ward interfaces. The establishment of an interdisciplinary FT team and interdisciplinary development of SOPs can optimize adherence, which in turn improves the short-term and long-term outcome of patients.

Impact of CCR7 on the gastrointestinal field effect.

Standardized intestinal manipulation (IM) leads to local bowel wall inflammation subsequently spreading over the entire gastrointestinal tract. Previously, we demonstrated that this so-called gastrointestinal field effect (FE) is immune mediated. This study aimed to investigate the role of CCR7 in IM-induced FE. Since CCR7 is expressed on activated dendritic cells and T cells and is well known to control their migration, we hypothesized that lack of CCR7 reduces or abolishes FE. Small bowel muscularis and colonic muscularis from CCR7(-/-) and wild-type (WT) mice were obtained after IM of the jejunum or sham operation. FE was analyzed by measuring gastrointestinal transit time of orally given fluorescent dextran (geometric center), colonic transit time, infiltration of MPO-positive cells, and circular smooth muscle contractility. Furthermore, mRNA levels of the inflammatory cytokine IL-6 were determined by RT-PCR. The number of dendritic cells and CD3+CD25+ T cells separately isolated from jejunum and colon was determined in mice after IM and sham operation. There was no significant difference in IL-6 mRNA upregulation in colonic muscularis between sham-operated WT and CCR7(-/-) mice after IM. Contractility of circular muscularis strips of the colon was significantly improved in CCR7(-/-) animals following IM and did not vary significantly from sham-operated animals. Additionally, inflammation of the colon determined by the number of MPO-positive cells and colonic transit time was significantly reduced in CCR7(-/-) mice. In contrast, jejunal contractility and jejunal inflammation of transgenic mice did not differ significantly from WT mice after IM. These data are supported by a significant increase of CD3+CD25+ T cells in the colonic muscularis of WT mice after IM, which could not be observed in CCR7(-/-) mice. These data demonstrate that CCR7 is required for FE and postoperative ileus. CCR7 indirectly affects FE by inhibiting migration of activated dendritic cells and of T cells from the jejunum to the colon. These findings support the critical role of the adaptive immune system in FE.

Meloxicam, a COX-2 inhibitor, ameliorates ischemia/reperfusion injury in non-heart-beating donor livers.

BACKGROUND/AIMS: Chronic organ donor shortage has led to the consideration to expand the donor pool with livers from non-heart-beating donors (NHBD), although a higher risk of graft dys- or nonfunction is associated with these livers. We examined the effects of selective cyclooxygenase-2 (COX-2) inhibition on hepatic warm ischemia (WI) reperfusion (I/R) injury of NHBD. METHODS: Male Wistar rats were used as donors and meloxicam (5 mg/kg body weight) was administered into the preservation solution. Livers were excised after 60 min of WI in situ, flushed and preserved for 24 h at 4°C. Reperfusion was carried out in vitro at a constant flow for 45 min. During reperfusion (5, 15, 30 and 45 min), enzyme release of alanine aminotransferase and glutamate lactate dehydrogenase were measured as well as portal venous pressure, bile production and oxygen consumption. The production of malondialdehyde was quantified and TUNEL staining was performed. Quantitative PCR analyzed COX-2 mRNA. COX-2 immunohistochemistry and TxB(2) detection completed the measurements. RESULTS: Meloxicam treatment led to better functional recovery concerning liver enzyme release, vascular resistance and metabolic activity over time in all animals. Oxidative stress and apoptosis were considerably reduced. CONCLUSION: Cold storage using meloxicam resulted in significantly better integrity and function of livers retrieved from NHBD. Selective COX-2 inhibition is a new therapeutic approach achieving improved preservation of grafts from NHBD.