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.

Right-sided diaphragmatic rupture after repair of a large Morgagni hernia.

We present a case of a combination of primary and secondary diaphragmatic hernia in a 63-year male patient. For progressive dyspnea and palpitations caused by a large and symptomatic Morgagni hernia resulting in a right-sided enterothorax, an open tension-free mesh repair was performed. The postoperative course was complicated by a secondary hepatothorax through a spontaneous rupture of the right diaphragm. Primary mesh repair of the Morgagni hernia, however, proved to be sufficient. This recurrent herniation might be a consequence of (1) preexisting atrophy of the right diaphragm caused by disposition and/or long-term diaphragmatic dysfunction due to the large hernia, combined with (2) further thinning out of the diaphragm by intraoperative hernia sac resection, and (3) postoperative increase of intra-abdominal pressure.

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.

Recombinant TIMP-1-GPI inhibits growth of fibrosarcoma and enhances tumor sensitivity to doxorubicin.

Fibrosarcomas show a high incidence of recurrence and general resistance to apoptosis. Limiting tumor regrowth and increasing their sensitivity to chemotherapy and apoptosis represent key issues in developing more effective treatments of these tumors. Tissue inhibitor of metalloproteinase 1 (TIMP-1) broadly blocks matrix metalloproteinase (MMP) activity and can moderate tumor growth and metastasis. We previously described generation of a recombinant fusion protein linking TIMP-1 to glycosylphophatidylinositol (GPI) anchor (TIMP-1-GPI) that efficiently directs the inhibitor to cell surfaces. In the present report, we examined the effect of TIMP-1-GPI treatment on fibrosarcoma biology. Exogenously applied TIMP-1-GPI efficiently incorporated into surface membranes of human HT1080 fibrosarcoma cells. It inhibited their proliferation, migration, suppressed cancer cell clone formation, and enhanced apoptosis. Doxorubicin, the standard chemotherapeutic drug for fibrosarcoma, was tested alone or in combination with TIMP-1-GPI. In parallel, the influence of treatment on HT1080 side population cells (exhibiting tumor stem cell-like characteristics) was investigated using Hoechst 33342 staining. The sequential combination of TIMP-1-GPI and doxorubicin showed more than additive effects on apoptosis, while TIMP-1-GPI treatment alone effectively decreased "stem-cell like" side population cells of HT1080. TIMP-1-GPI treatment was validated using HT1080 fibrosarcoma murine xenografts. Growing tumors treated with repeated local injections of TIMP-1-GPI showed dramatically inhibited fibrosarcoma growth and reduced angiogenesis. Intraoperative peritumoral application of GPI-anchored TIMP-1 as an adjuvant to surgery may help maintain tumor control by targeting microscopic residual fibrosarcoma cells and increasing their sensitivity to chemotherapy.

[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.

Right-sided diaphragmatic rupture after repair of a large Morgagni hernia.

We present a case of a combination of primary and secondary diaphragmatic hernia in a 63-year male patient. For progressive dyspnea and palpitations caused by a large and symptomatic Morgagni hernia resulting in a right-sided enterothorax, an open tension-free mesh repair was performed. The postoperative course was complicated by a secondary hepatothorax through a spontaneous rupture of the right diaphragm. Primary mesh repair of the Morgagni hernia, however, proved to be sufficient. This recurrent herniation might be a consequence of (1) preexisting atrophy of the right diaphragm caused by disposition and/or long-term diaphragmatic dysfunction due to the large hernia, combined with (2) further thinning out of the diaphragm by intraoperative hernia sac resection, and (3) postoperative increase of intra-abdominal pressure.

[Pancreatic cancer in the elderly: guidelines and individualized therapy]. / Pankreaskarzinom im hohen Alter: Leitlinien und individualisierte Therapie.

The considerable increase of the aged population in western civilisation within the next years will result in a rising incidence of pancreatic cancer. Until the year 2020 an increment of 20  % of patients beyond 65 years old can be anticipated. Therefore, the focus will be on management of old and geriatric surgical patients leading to strategical re-evaluation of surgical indications under critical consideration of feasibility and purpose. Even under modern interdisciplinary therapy concepts the prognosis of ductal adenocarcinoma of the pancreas remains poor with an overall 5-year survival rate of less than 5  %. The surgical resection is still considered as the only potential curative treatment option with extended life expectancy; however, it is technically demanding and furthermore associated with significant morbidity. In particular, the quality of surgery of the now interdisciplinary therapy of pancreatic cancer is markedly improved when performed at a high-volume centres. Until now only a few retrospective data analyses evaluating the perioperative and long-term outcome after pancreatic tumor resections in geriatric patients exist. The available results, however, support radical surgical procedures even beyond the age of 75 years.

[Therapy of hepatocellular carcinoma before liver transplantation]. / Therapie des hepatozellulären Karzinoms vor Lebertransplantation.

Liver transplantation is the optimal therapy for patients with non-resectable early stage hepatocellular carcinoma (HCC) which is limited to the liver. During the sometimes long waiting period patients usually receive neoadjuvant bridging therapy to avoid tumor progression. The armamentarium of bridging therapies includes local ablative and systemic therapies as well as liver resection. The oncological benefit of neoadjuvant therapy for patients who receive a liver transplantation is unclear; however, bridging therapy keeps patients eligible for transplantation in the formal framework of current allocation rules. Moreover, response to therapy may serve as a surrogate marker for favorable tumor biology and may therefore help to guide the selection process for patients undergoing liver transplantation for HCC.

[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.

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.