Prevention of anastomotic leak in rectal cancer surgery with local antibiotic decontamination: a prospective, randomized, double-blind, placebo-controlled single center trial.

PURPOSE: Anastomotic leak and other infectious complications are septic complications of rectal cancer surgery caused by bacteria. Data from registry analysis show a beneficial effect of local antimicrobial administration on anastomotic leaks, but data are inconsistent in recent clinical trials. Therefore, our aim was to study the efficacy of topical antibiotic treatment on the incidence of anastomotic leaks in rectal cancer surgery. METHODS: A prospective, randomized, double-blind and placebo-controlled, single center trial was conducted. Patients received either placebo and amphotericin B or decontamination with polymyxin B, tobramycin, vancomycin, and amphotericin B four times per day starting the day before surgery until postoperative day 7. If a protective ileostomy was created, a catheter was placed transanally and the medication was administered locally to the anastomotic site. All patients received an intravenous perioperative antibiotic prophylaxis. RESULTS: The trial had to be stopped for ethical reasons after first interim analysis with 80 patients instead of the initially planned 280 patients. Of the 40 patients randomized to receive placebo, eight (20%) developed anastomotic leak compared to only 2 (5%) in the treatment group of 40 patients (decontamination) with significant difference in the χ2 test (p = 0.0425). Twenty percent of the placebo group and 12.5% in the treatment group developed infectious complications not associated with anastomotic leak (p = 0.5312). One patient (2.5%) in the placebo group died (p = 0.3141). CONCLUSION: Local decontamination with polymyxin, tobramycin, vancomycin, and amphotericin B is safe and effective in the prevention of anastomotic leak in rectal cancer surgery.

Moon phases and moon signs do not influence morbidity, mortality and long-term survival, after living donor kidney transplantation.

BACKGROUND: Approximately 11% of the German population are convinced that certain moon phases and moon signs may impact their health and the onset and clinical course of diseases. Before elective surgery, a considerable number of patients look to optimize the timing of the procedure based on the lunar cycle. Especially patients awaiting living donor kidney transplantation (LDKT) commonly look for an adjustment of the date of transplantation according to the moon calendar. This study therefore investigated the perioperative and long-term outcome of LDKT dependent on moon phases and zodiac signs. METHODS: Patient data were prospectively collected in a continuously updated kidney transplant database. Two hundred and seventy-eight consecutive patients who underwent LDKT between 1994 and December 2009 were selected for the study and retrospectively assigned to the four moon phases (new-moon, waxing-moon, full-moon, and waning-moon) and the corresponding zodiac sign (moon sign Libra), based on the date of transplantation. Preexisting comorbidities, perioperative mortality, surgical outcome, and long-term survival data were analyzed. RESULTS: Of all LDKT procedures, 11.9, 39.9, 11.5, and 36.5% were performed during the new, waxing, full, and waning moon, respectively, and 6.2% during the moon sign Libra, which is believed to interfere with renal surgery. Survival rates at 1, 5, and 10 years after transplantation were 98.9, 92, and 88.7% (patient survival) and 97.4, 91.6, and 80.6% (graft survival) without any differences between all groups of lunar phases and moon signs. Overall perioperative complications and early graft loss occurred in 21.2 and 1.4%, without statistical difference (p > 0.05) between groups. CONCLUSION: Moon phases and the moon sign Libra had no impact on early and long-term outcome measures following LDKT in our study. Thus, concerns of patients awaiting LDKT regarding the ideal time of surgery can be allayed, and surgery may be scheduled independently of the lunar phases.

The CR-POSSUM Risk Calculator Predicts Failure of Enhanced Recovery after Colorectal Surgery.

AIMS: To determine predictors of failed enhanced recovery after surgery (ERAS) in patients after elective colorectal surgery. METHODS: A cohort of 55 patients undergoing elective colorectal surgery was monitored prospectively. Perioperative care was based on a previously established protocol for ERAS. Pre-, intra-, and postoperative parameters were analyzed to elicit predictors of ERAS failure. ERAS failure was defined as prolonged hospital stay (> 7 days). The risk calculator CR-POSSUM was evaluated for its clinical utility. RESULTS: Body mass index (BMI) or the American Society of Anesthesiologists score (ASA) was not associated with ERAS failure on univariate analysis, but patients that failed ERAS were significantly older (64 y vs 54 y ; p = 0.023). Prolonged length of stay (> 7 days) was also associated with an open approach (p = 0.009), intraoperative nasogastric tube placement (p = 0.005), blood loss > 500 ml (p = 0.008), stoma formation (p = 0.006) and insertion of more than one intraabdominal drain during surgery (p = 0.005). Postoperative continuation of intravenous fluids (p = 0.027), reinsertion of urinary catheter (p = 0.045) and postoperative ileus (p = 0.020) were also strongly associated with delayed discharge on univariate analysis. After multivariate analysis the preoperative parameters CR-POSSUM score (p = 0.022), increasing BMI (p = 0.014) and preoperative albumin level (p = 0.031) were all independently associated with failure of ERAS. CONCLUSIONS: A variety of perioperative factors contribute to failure of ERAS in routine practice. CR-POSSUM can help to identify patients at risk for possible failure of ERAS. This may help to optimize avoidable factors, or accommodate those patients likely to require a longer post-operative stay.

The CR-POSSUM Risk Calculator Predicts Failure of Enhanced Recovery after Colorectal Surgery.

AIMS: To determine predictors of failed enhanced recovery after surgery (ERAS) in patients after elective colorectal surgery. METHODS: A cohort of 55 patients undergoing elective colorectal surgery was monitored prospectively. Perioperative care was based on a previously established protocol for ERAS. Pre-, intra-, and postoperative parameters were analyzed to elicit predictors of ERAS failure. ERAS failure was defined as prolonged hospital stay (> 7 days). The risk calculator CR-POSSUM was evaluated for its clinical utility. RESULTS: Body mass index (BMI) or the American Society of Anesthesiologists score (ASA) was not associated with ERAS failure on univariate analysis, but patients that failed ERAS were significantly older (64 y vs 54 y; p = 0.023). Prolonged length of stay (>7 days) was also associated with an open approach (p = 0.009), intraoperative nasogastric tube placement (p = 0.005), blood loss > 500 ml (p = 0.008), stoma formation (p = 0.006) and insertion of more than one intraabdominal drain during surgery (p = 0.005). Postoperative continuation of intravenous fluids (p = 0.027), reinsertion of urinary catheter (p = 0.045) and postoperative ileus (p = 0.020) were also strongly associated with delayed discharge on univariate analysis. After multivariate analysis the preoperative parameters CR-POSSUM score (p = 0.022), increasing BMI (p = 0.014) and preoperative albumin level (p = 0.031) were all independently associated with failure of ERAS. CONCLUSIONS: A variety of perioperative factors contribute to failure of ERAS in routine practice. CR-POSSUM can help to identify patients at risk for possible failure of ERAS. This may help to optimize avoidable factors, or accommodate those patients likely to require a longer post-operative stay.

[Significance of Mesenchymal Stem Cells in Gastrointestinal Disorders]. / Bedeutung mesenchymaler Stammzellen in der Viszeralmedizin.

In this review we summarise the recent developments regarding the experimental and clinical use of mesenchymal stem cells (MSCs), focusing mainly on the treatment of gastrointestinal disorders. Next to their relevance in the field of regenerative medicine and immunology, this population of cells has also raised great expectations for possible applications in cancer therapy. While clinical trials were able to demonstrate the efficacy of MSCs in cases of inflammatory bowel disease and degenerative conditions of the liver, controversial results have been presented regarding their antineoplastic potential in gastrointestinal tumours. MSCs can differentiate into a large variety of specialised cells. They are capable of regulating both wound healing and immune responses through paracrine and endocrine signalling. Moreover, MSCs can be transfected with a great number of different therapeutic genes - considering their ability to selectively migrate towards neoplastic tissues, this feature allows for targeted therapy of solid tumours. Transfected genes can be designed so that they are expressed exclusively in the vicinity of the tumour, eventually triggering apoptosis in cancer cells. In this review, we demonstrate the natural distribution of exogenously applied MSCs in the host. Furthermore, we mention various methods of tracking MSCs in vivo and different parameters of administration that tend to influence therapeutic outcome (e.g., origin of MSCs, mode of application, or the potency of transfected genes). Finally, this review points out the hazards of MSC therapy, emphasising the risks related to their widespread clinical use.

Simvastatin reduces leucocyte- and platelet-endothelial cell interaction in murine antigen-induced arthritis in vivo.

OBJECTIVES: The use of statins in the prevention and treatment of cardiovascular diseases is well established. Their use as anti-inflammatory and immunomodulatory agents in the treatment of rheumatoid arthritis (RA) has also been investigated, with several clinical and experimental studies indicating an anti-inflammatory effect of statins for RA, but other studies showing no effect or even the opposite. The current study was designed to examine the effect of simvastatin in an in vivo murine model of arthritis using intravital microscopy. METHOD: We assigned four groups (n = 7, female C57Bl6 mice), two with and two without antigen-induced arthritis (AiA), from which one of the non-AiA groups and one of the AiA groups were treated with simvastatin 40 mg/kg i.p. daily for 14 consecutive days after induction of arthritis. Platelet- and leucocyte-endothelial cell interaction was assessed by measurement of rolling and adherent fluorescence-labelled platelets and leucocytes, functional capillary density (FCD) was evaluated, and knee joint diameter was determined as a clinical parameter. RESULTS: In arthritic mice treated with simvastatin, a significant reduction in platelet- and leucocyte-endothelial cell interaction was observed in comparison to arthritic mice treated with vehicle. In addition, a significant reduction in FCD was seen in arthritic mice treated with simvastatin, along with a reduction in knee joint swelling of the AiA mice. CONCLUSIONS: Treatment of AiA mice with simvastatin showed significant reductions in platelet- and leucocyte-endothelial cell interactions, in FCD, and in the swelling of the knee joint. These results support the hypothesis of the anti-inflammatory effects of statins in the treatment of RA.

[Transplantation and hepatic, pancreatic, and biliary (HPB) surgery fellowship--a pilot project for a structured training in Germany]. / Fellowship für Transplantation und hepato-pankreatiko-biliäre (HPB) Chirurgie - Pilotprojekt für eine strukturierte Weiterbildung in Deutschland.

Currently, there is no structured training plan to become a transplant surgeon in Germany. Similar to the Anglo-Saxonian educational system we have implemented a 3-year fellowship in transplant and hepatic-, pancreatic-, biliary (HPB) surgery. The educational curriculum is based on the guidelines of the European Board of Surgery (EBS) for transplant and HPB surgery. Here, we describe the underlying thoughts, the selection process, structure and curriculum for this fellowship. Furthermore, we critically compare our programme to the established international training standards. So far, our programme has proven valuable. We believe a fellowship for transplant and HPB surgery is a reasonable approach to ensure a high quality training of the following generations of surgeons in this field.

[Structured teaching of surgery the LMU model in Munich]. / Strukturierte Lehre in der Chirurgie am Beispiel des Humanmedizinstudiums an der Ludwig-Maximilians-Universität München.

The medical curriculum (MeCuM) of the Ludwig Maximilian University (LMU) in Munich is a dynamic curriculum aimed to support the learning process of all students with their different learning styles. It is based on interactive, activating teaching methods in order to increase students' interest, and on repetitive evaluation of teaching units to modify the teaching in order to meet students' needs and wishes. In this context the teaching of surgery at our faculty takes place. Besides interdisciplinary lessons where diseases are taught in cooperation with our colleagues from internal medicine, indications for surgery, complications and consequences of surgery for the patients are analysed in PBL tutorials, online cases, bedside teachings and practical teaching on the ward. Surgical skills like suturing are demonstrated in videos, practiced on models or during practical teaching on the ward and they are tested in OSCEs. During the "praktisches Jahr", the students in the last year of their medical studies are supposed to apply their practical skills besides repeating theoretical knowledge in order to pass the final examination. For this purpose they are taught in a revision course called "LMU-StaR" (revision course for the Staatsexamen). In this paper we describe in detail the teaching of surgery at our faculty.

[Evidence for the digital rectal examination in the emergency assessment of acute abdominal pain]. / Sinnhaftigkeit der digital-rektalen Untersuchung bei akutem Abdomen in der Notfallaufnahme.

BACKGROUND: Physical examination of patients with undifferentiated abdominal pain (UAP) in the emergency room traditionally calls for digital rectal examination (DRE). Without a DRE, many textbooks deem a clinical examination incomplete. On the other hand, patients as well as physicians often feel uncomfortable with this breach of privacy involving a DRE. Especially emergency rooms do not offer an atmosphere where a relationship with the necessary mutual trust can be built up. In this light, the objective of this analysis is to assess the evidence for DRE via a systematic search of the relevant literature. METHODS AND RESULTS: A systematic search in Pubmed, Medline coupled with manual research laid the basis for the evaluation of relevant publications from January 1990 to March 2010. Keywords for the search were: "digital rectal examination" in combination with "acute abdominal pain", "acute abdomen" or "appendicitis". From the raw data of relevant publications, we extracted results into contingency tables and completed missing data. Above all parameters, we determined the likelihood ratios (LR) with corresponding 95 % confidence intervals to assess test quality. Opinions in the evaluated literature and many national and international textbooks diverge significantly on the necessity of DRE. Six studies question the significance of DRE when evaluating patients with undifferentiated abdominal pain and appendicitis, respectively. Out of these studies, five are prospective and one is retrospective. Overall, the diagnostic test quality of DRE was low in all studies with LR + in the range from 0.78 to 1.61 and LR -  from 0.91 to 1.29, respectively. No diagnostic relevance for DRE in combination with acute abdominal pain was found in these studies. Furthermore, in none of the reviewed cases did DRE have a relevant impact on management. CONCLUSION: The recommendation of generally applying DRE in the emergency room needs to be questioned critically. No evidence for the necessity and significance was found in the reviewed literature. Independently, these findings do not touch on the unequivocal indication of the DRE as a tool for assessing other specific conditions as well as screening for prostate or rectal cancer.

[Emergencies in vascular surgery--a major challenge for the local infrastructure]. / Gefäßchirurgische Notfälle--eine große Herausforderung an die lokale Infrastruktur.

INTRODUCTION: Emergencies in vascular surgery are often life-threatening and require a timely and prompt treatment. Little information is available in the literature about which demands must be made for this on the personnel and infrastructural resources of a hospital. METHODS: All vascular surgical emergency operations of the Surgical University Hospital of Munich - Grosshadern over a period of 2 years were evaluated concerning the emergency category, the leading clinical symptomatology, the genesis, the affected stream area, the intervention time, as well as the need for postoperative intensive medical care. RESULTS: The prevailing procedures were arterial operations (76 %). Ischaemia with 37 % and bleeding with 29 % were the leading clinical symptomatology. Thrombotic events (34 %) showed the most frequent genesis followed by embolism (13 %), stenosis (11 %), aneurysms (10 %) and iatrogenic impairments (10 %). 68 % of the emergencies were treated outside of the daytime working hours. A total of 77 % of the patients needed intensive care treatment or observation after surgery. CONCLUSION: The spectrum and the frequency of emergencies in vascular surgery make high demands on local infrastructure of the hospital and require a fair number of intensive care beds and an adequate and highly trained staff. Only under these conditions can a high quality of treatment be guaranteed for the sometimes life-threatened patients.

Nutritional screening for risk prediction in patients scheduled for abdominal operations.

BACKGROUND: Increased risks related to surgery might reflect the nutritional status of some patients. Such a group might benefit from perioperative nutritional support. The purpose of this study was to identify the relative importance of nutritional risk screening along with established medical, anaesthetic and surgical predictors of postoperative morbidity and mortality. METHODS: This prospective observational study enrolled consecutive eligible patients scheduled for elective abdominal operations. Data were collected on nutritional variables (body mass index, weight loss, food intake), age, sex, type and extent of operation, underlying disease, American Society of Anesthesiologists grade and co-morbidities. A modified composite nutritional screening tool (Nutritional Risk Screening, NRS 2002) currently recommended by European guidelines was used. Relative complication rates were calculated with multiple logistic regression and cumulative proportional odds models. RESULTS: Some 653 patients were enrolled of whom 132 (20.2 per cent) sustained one or more postoperative complications. The frequency of this event increased significantly with a lower food intake before hospital admission. No other individual or composite nutritional variable provided comparable or better risk prediction (including NRS 2002). Other factors significantly associated with severe postoperative complications were ASA grade, male sex, underlying disease, extent of surgical procedure and volume of transfused red cell concentrates. CONCLUSION: In abdominal surgery, preoperative investigation of feeding habits may be sufficient to identify patients at increased risk of complications. Nutritional risk alone, however, is not sufficient to predict individual risk of complications reliably.

Targeting the vasculature of visceral tumors: novel insights and treatment perspectives.

BACKGROUND: Angiogenesis, the formation of new blood vessels from the endothelium of the existing vasculature, describes a crucial process in tumor growth, disease progression, and metastasis. Therefore, the upcoming strategy of inhibiting tumor angiogenesis has generated different treatment modalities, which have been transferred into clinical practice in recent years. Currently, this concept is applied to target the vasculature of different visceral tumors and intensive clinical research has just started. MATERIALS AND METHODS: This review summarizes the modifications of systemic treatment of visceral tumors by targeting the vasculature in the past years. Moreover, novel targets and treatment strategies will be discussed to evaluate future directions. RESULTS: Leading antiangiogenic drugs combined with systemic chemotherapy have been applied with increasing success during the last years. Therefore, the concept of combining vascular targeting agents with established chemotherapeutic regimens has been increasingly adopted into the therapies of different visceral tumors. CONCLUSION: Targeting the vasculature of visceral tumors in combination with established standard tumor therapies includes major clinical potential for future therapy concepts.

Clinical implication of targeting of cancer stem cells.

The existence of cancer stem cells (CSCs) is receiving increasing interest particularly due to its potential ability to enter clinical routine. Rapid advances in the CSC field have provided evidence for the development of more reliable anticancer therapies in the future. CSCs typically only constitute a small fraction of the total tumor burden; however, they harbor self-renewal capacity and appear to be relatively resistant to conventional therapies. Recent therapeutic approaches aim to eliminate or differentiate CSCs or to disrupt the niches in which they reside. Better understanding of the biological characteristics of CSCs as well as improved preclinical and clinical trials targeting CSCs may revolutionize the treatment of many cancers.

[Improving continuing medical education: a valuable investment for the future of surgery]. / Verbesserung der Weiterbildung: Eine wertvolle Investition in die Zukunft der Chirurgie.

At present, surgery in Germany is suffering from the problem of poor attractivity jeopardizing nationwide availability of competent and high quality surgical care in the future. The causes for this have been repeatedly attributed to structural problems, above all in medical training and continuing medical education. In this article, we present the results of questionnaires of the National Society of German Surgeons and the German National Chamber of Physicians, identify the specific problem, and finally analyse them in an attempt to show how surgical training can be optimised and the attractivity of this specialty can be improved. In this context, the "Grosshadern Concept" for continuing surgical education is introduced as an example for an established and good functioning training curriculum.

[Learning from aviation - how to increase patient safety in surgery]. / Kann die Chirurgie wirklich von der Luftfahrt lernen?

During the last years attempts have been made to draw lessons from aviation to increase patient safety in medicine. In particular similar conditions are present in surgery as pilots and surgeons may have to support high physical and mental pressure. The use of a few safety instruments from aviation is feasible in an attempt to increase safety in surgery. First a "root caused" accident research may be established. This is achievable by morbidity and mortality conferences and critical incident reporting systems (CIRS). Second, standard operating procedures may assure a uniform mental model of team members. Furthermore, crew resource management illustrates a strategy and attitude concept, which is applicable in all situations. Safety instruments from aviation, therefore, seem to have a high potential to increase safety in surgery when properly employed.

Individual development and uPA-receptor expression of disseminated tumour cells in bone marrow: a reference to early systemic disease in solid cancer.

It is unclear whether disseminated tumour cells detected in bone marrow in early stages of solid cancers indicate a subclinical systemic disease component determining the patient's fate or simply represent mainly irrelevant shed cells. Moreover, characteristics differentiating high and low metastatic potential of disseminated tumour cells are not defined. We performed repeated serial bone marrow biopsies during follow-up in operated gastric cancer patients. Most patients with later tumour relapse revealed either an increase or a constantly high number of tumour cells. In contrast, in patients without recurrence, either clearance of tumour cells or negative or low cell counts were seen. Urokinase plasminogen activator (uPA)-receptor expression on disseminated tumour cells was significantly correlated with increasing tumour cell counts and clinical prognosis. These results demonstrate a systemic component in early solid cancer, indicated by early systemically disseminated tumour cells, which may predict individual disease development.

[Current developments in liver transplantation in Germany: MELD-based organ allocation and incentives for transplant centres]. / Aktuelle Entwicklungen der Lebertransplantation in Deutschland: MELD-basierte Organallokation und "incentives" für Transplantationszentren.

Liver transplantation represents a successful and well-established therapeutic concept for patients with advanced liver diseases. Organ donor shortage continues to pose a significant problem. To ensure fair and transparent allocation of too few post-mortem grafts, the model of end-stage liver disease (MELD)-based allocation was implemented in December 2006. This has decreased waiting list mortality from 20 to 10 % but at the same time has reduced post OLT survival (1-year survival from almost 90% to below 80%), which is largely due to patients with a labMELD score > 30. Following MELD introduction the regular allocation threshold has increased from a matchMELD of initially 25 to meanwhile 34. At the same time the quality of donor organs has seen a continuous deterioration over the last 10 - 15 years: 63% of organs are "suboptimal" with a donor risk index of > 1.5. Moreover, the numbers of living-related liver transplantations have decreased. In Germany incentives for transplant centres are inappropriate: patients with decompensated cirrhosis, high MELD scores and high post-transplant mortality as well as marginal liver grafts are accepted for transplantation without the necessary consideration of outcomes, and against a background of the still absent publication and transparency of outcome results. The outlined development calls for measures for improvement: (i) the increase of donor grafts (e. g., living donation, opt-out solutions, non-heart beating donors), (ii) the elimination of inappropriate incentives for transplant centres, (iii) changes of allocation guidelines, that take the current situation and suboptimal donor grafts into account, and (iv) the systematic and complete collection of transplant-related data in order to allow for the development of improved prognostic scores.

[Bariatric surgery and associated complications: radiological imaging]. / Adipositaschirurgie und ihre Komplikationen : Radiologische Bildgebung.

Obesity is an increasing problem faced by the healthcare system. In managing obesity, bariatric surgery is becoming more important with evidence showing a reduction in long-term morbidity and mortality. There are special challenges faced by the radiology department in providing an imaging service for this population of patients, from technical requirements through to the interpretation of post-surgical images. This article provides an overview of the most frequently performed procedures, normal postoperative imaging findings and the appearance of common complications.

[Acute abdominal pain in the emergency department - a clinical algorithm for adult patients]. / Der akute Abdominalschmerz in der Notfallambulanz - ein klinischer Algorithmus für den erwachsenen Patienten.

Acute abdominal pain represents the cardinal symptom behind a vast number of possible under-lying causes including several ones that re-quire surgical treatment. It is the most common sur-gical emergency, the most common cause for a surgical consultation in the emergency department and the most common cause for non-trauma related hospital admissions. The golden mis-sion statement is to rapidly identify whether the underlying cause requires an urgent or even immediate surgical intervention. However, behind the same cardinal symptom one may encounter harmless or non-urgent problems. By employing diagnostic means cost effectively and with the aim to avoid unnecessary exposure of the patient to X-rays in mind, the challenge remains to identify patients with an indication for emergency surgery from those who suffer from a less serious condition and thus can be treated conservatively and without any pressure of time. Dealing with such a highly complex decision-making process calls for a clinical algorithm. Many publications are available that have scrutinised the different aspects of the initial assessment and the emergency management of acute abdominal pain. How-ever, the large body of evidence seems to miss articles that describe a formally correct priority- and problem-based approach. Clinical algorithms apply to complex disease states such as acute abdominal pain and translate them into one clearly laid out, logically coordinated and systematic overall process. Our intention is to devel-op such an algorithm to approach acute abdominal pain from the surgeon's point of view. Based on daily practice and with reference to available literature, it is the aim of this study to define a work flow that simply summarises all steps in-volved and defines the required decision process in order to form the intellectual basis for an evidence-based clinical algorithm. The result is illustrated as a first draft of such an evidence-based algorithm to allow emergency evaluation of adult patients with acute abdominal pain.