München Klinik Neuperlach

BACKGROUND: Recent studies indicate that MRI, after administration of gadolinium-diethylenetriamine pentaacetic acid, can identify nonviable areas in dysfunctional myocardium. We compared MRI hyperenhancement with PET as a gold standard for detection and quantification of myocardial scar tissue. METHODS AND RESULTS: Thirty-one patients with ischemic heart failure (ejection fraction, 28+/-9%) were imaged with PET and MRI. Scar was defined as regionally increased MRI signal intensity 20 minutes after injection of 0.2 mmol/kg gadolinium-diethylenetriamine pentaacetic acid and as concordantly reduced perfusion and glucose metabolism as defined by PET. Sensitivity and specificity of MRI in identifying patients and segments (n=1023) with matched flow/metabolism defects was 0.96 of 1.0 and 0.86 of 0.94, respectively. Eleven percent of segments defined as viable by PET showed some degree of MRI hyperenhancement. Defect severity score based on visual analysis was 44.3+/-9.1 for PET and 47.6+/-11.1 for MRI (r=0.91, P<0.0001). Quantitatively assessed relative MRI infarct mass correlated well with PET infarct size (r=0.81, P<0.0001). Furthermore, MRI hyperenhancement was a better predictor of scar tissue than end-diastolic and end-systolic wall thickness or thickening. CONCLUSIONS: In severe ischemic heart failure, MRI hyperenhancement as a marker of myocardial scar closely agrees with PET data. Although hyperenhancement correlated with areas of decreased flow and metabolism, it seems to identify scar tissue more frequently than PET, reflecting the higher spatial resolution. Additional functional studies after revascularization are required to define the significance of small islands of scar detected by MRI.

PURPOSE: To evaluate panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated wild-type (WT) KRAS exon 2 (codons 12 and 13) metastatic colorectal cancer (mCRC). A prespecified secondary objective was to assess treatment effects in an extended RAS analysis that included exons 2, 3, and 4 of KRAS and NRAS. PATIENTS AND METHODS: Patients with WT KRAS exon 2 tumors were randomly assigned at a one-to-one ratio to panitumumab plus mFOLFOX6 or bevacizumab plus mFOLFOX6. The primary end point was progression-free survival (PFS); secondary end points included overall survival (OS) and safety. RESULTS: Of 285 randomly assigned patients, 278 received treatment. In the WT KRAS exon 2 intent-to-treat group, PFS was similar between arms (hazard ratio [HR], 0.87; 95% CI, 0.65 to 1.17; P = .353). Median OS was 34.2 and 24.3 months in the panitumumab and bevacizumab arms, respectively (HR, 0.62; 95% CI, 0.44 to 0.89; P = .009). In the WT RAS subgroup (WT exons 2, 3, and 4 of KRAS and NRAS), PFS favored the panitumumab arm (HR, 0.65; 95% CI, 0.44 to 0.96; P = .029). Median OS was 41.3 and 28.9 months (HR, 0.63; 95% CI, 0.39 to 1.02; P = .058) in the panitumumab and bevacizumab arms, respectively. Treatment discontinuation rates because of adverse events were similar between arms. CONCLUSION: PFS was similar and OS was improved with panitumumab relative to bevacizumab when combined with mFOLFOX6 in patients with WT KRAS exon 2 tumors. Patients with WT RAS tumors seemed to experience more clinical benefit with anti-epidermal growth factor receptor therapy.

OBJECTIVE: Sepsis is associated with an increase in reactive oxygen species and low endogenous antioxidative capacity. We postulated that high-dose supplementation of sodium-selenite would improve the outcome of patients with severe sepsis and septic shock. DESIGN: Prospective randomized, placebo-controlled, multiple-center trial. SETTING: Eleven intensive care units in Germany. PATIENTS: Patients were 249 patients with severe systemic inflammatory response syndrome, sepsis, and septic shock and an Acute Physiology and Chronic Health Evaluation (APACHE) III score >70. INTERVENTIONS: Patients received 1000 microg of sodium-selenite as a 30-min bolus injection, followed by 14 daily continuous infusions of 1000 microg intravenously, or placebo. MEASUREMENTS AND MAIN RESULTS: The primary end point was 28-day mortality; secondary end points were survival time and clinical course of APACHE III and logistic organ dysfunction system scores. In addition, selenium levels in serum, whole blood, and urine as well as serum glutathione-peroxidase-3 activity were measured. From 249 patients included, 11 patients had to be excluded. The intention-to-treat analysis of the remaining 238 patients revealed a mortality rate of 50.0% in the placebo group and 39.7% in the selenium-treated group (p = .109; odds ratio, 0.66; confidence interval, 0.39-1.1). A further 49 patients had to be excluded before the final analysis because of severe violations of the study protocol. In the remaining 92 patients of the study group, the 28-day mortality rate was significantly reduced to 42.4% compared with 56.7% in 97 patients of the placebo group (p = .049, odds ratio, 0.56; confidence interval, 0.32-1.00). In predefined subgroup analyses, the mortality rate was significantly reduced in patients with septic shock with disseminated intravascular coagulation (n = 82, p = .018) as well as in the most critically ill patients with an APACHE III score > or =102 (>75% quartile, n = 54, p = .040) or in patients with more than three organ dysfunctions (n = 83, p = .039). Whole blood selenium concentrations and glutathione peroxidase-3 activity were within the upper normal range during selenium treatment, whereas they remained significantly low in the placebo group. There were no side effects observed due to high-dose sodium-selenite treatment. CONCLUSIONS: The adjuvant treatment of patients with high-dose sodium-selenite reduces mortality rate in patients with severe sepsis or septic shock.

BACKGROUND: As with endoscopic transmural drainage of peripancreatic fluid collections, the same transluminal access can be expanded to introduce an endoscope through the gastrointestinal wall into the retroperitoneum and remove infected pancreatic necroses under direct visual control. This study reports the first large series with long-term follow-up. METHODS: Data for all patients undergoing transluminal endoscopic removal of (peri)pancreatic necroses between 1999 and 2005 in six different centres were collected retrospectively, and the patients were followed up prospectively until 2008. The initial patient and treatment outcome data were recorded, as were long-term results. RESULTS: Ninety-three patients (63 men, 30 women; mean age 57 years) underwent a mean of six interventions starting at a mean of 43 days after an attack of severe acute pancreatitis. After establishment of transluminal access to the necrotic cavity and subsequent endoscopic necrosectomy, initial clinical success was obtained in 80% of the patients, with a 26% complication and a 7.5% mortality rate at 30 days. After a mean follow-up period of 43 months, 84% of the initially successfully treated patients had sustained clinical improvement, with 10% receiving further endoscopic and 4% receiving surgical treatment for recurrent cavities; 16% suffered recurrent pancreatitis. CONCLUSIONS: Direct transluminal endoscopic removal of pancreatic necroses is associated with good long-term maintenance of the high initial efficacy; complications can occur, with an associated mortality of around 7.5%. Further studies are necessary in order to optimise endotherapy and define its role in relation to surgery in the clinical management of such patients.

BACKGROUND: In patients receiving aspirin, the optimal duration of clopidogrel therapy after drug-eluting stent (DES) implantation remains unclear. METHODS: This multicentre, randomized, double-blind, placebo-controlled trial tested the hypothesis that in patients undergoing DES implantation, 6 months of clopidogrel is non-inferior to 12 months in terms of clinical outcomes. At 6 months after DES implantation, patients on clopidogrel were randomly assigned to either a 6-month period of placebo or an additional 6-month period of clopidogrel. The primary endpoint was the composite of death, myocardial infarction, stent thrombosis, stroke, and thrombolysis in myocardial infarction major bleeding at 9 months after randomization. RESULTS: Owing to slow recruitment and low event rates, the trial was stopped prematurely after enrolment of 4005 of 6000 planned patients. Of 4000 patients included in the final analysis, 1997 received 6 months of clopidogrel and 2003 received 12 months. The primary endpoint occurred in 29 patients (1.5%) assigned to 6 months of clopidogrel and 32 patients (1.6%) assigned to 12 months, observed difference -0.1%, upper limit of one-sided 95% confidence interval (CI) 0.5%, limit of non-inferiority 2%, Pfor noninferiority <0.001. Stent thrombosis was observed in five patients (0.3%) assigned to 6 months of clopidogrel and three patients (0.2%) assigned to 12 months; hazard ratio (HR) 1.66, 95% CI: 0.40-6.96, P = 0.49. Thrombolysis in myocardial infarction major bleeding was observed in 4 patients (0.2%) assigned to 6 months clopidogrel and 5 patients (0.3%) assigned to 12 months; HR 0.80, 95% CI: 0.21-2.98, P = 0.74. CONCLUSIONS: In the present trial, characterized by low event rates, we did not observe a significant difference in net clinical outcome between 6 and 12 months of clopidogrel therapy after DES implantation. However, the results of the trial must be considered in view of its premature termination and lower than expected event rates. The trial is registered with ClinicalTrials.gov, Identifier: NCT00661206.

Aims: The aim of this study was to investigate the effect of contact-to-balloon time on mortality in ST-segment elevation myocardial infarction (STEMI) patients with and without haemodynamic instability. Methods and results: Using data from the prospective, multicentre Feedback Intervention and Treatment Times in ST-Elevation Myocardial Infarction (FITT-STEMI) trial, we assessed the prognostic relevance of first medical contact-to-balloon time in n = 12 675 STEMI patients who used emergency medical service transportation and were treated with primary percutaneous coronary intervention (PCI). Patients were stratified by cardiogenic shock (CS) and out-of-hospital cardiac arrest (OHCA). For patients treated within 60 to 180 min from the first medical contact, we found a nearly linear relationship between contact-to-balloon times and mortality in all four STEMI groups. In CS patients with no OHCA, every 10-min treatment delay resulted in 3.31 additional deaths in 100 PCI-treated patients. This treatment delay-related increase in mortality was significantly higher as compared to the two groups of OHCA patients with shock (2.09) and without shock (1.34), as well as to haemodynamically stable patients (0.34, P < 0.0001). Conclusions: In patients with CS, the time elapsing from the first medical contact to primary PCI is a strong predictor of an adverse outcome. This patient group benefitted most from immediate PCI treatment, hence special efforts to shorten contact-to-balloon time should be applied in particular to these high-risk STEMI patients. Clinical Trial Registration: NCT00794001.

BACKGROUND AND STUDY AIMS: Screening colonoscopy with polypectomy has been shown to reduce the morbidity and mortality associated with colorectal cancer. However, there is a lack of large and systematic prospective studies of the complications of polypectomy. PATIENTS AND METHODS: Data on all snare polypectomies performed in 13 institutions (six hospitals and seven gastroenterology offices) were recorded prospectively during a 20-month period, including data on a 30-day follow-up period. The primary end points of the study were polypectomy complications, which were classed as "major" or "minor". Risk factors for complications were analyzed for both patient characteristics and polyp parameters. RESULTS: A total of 3976 snare polypectomies in 2257 patients (mean age 64.5 years) were included in the study. The mean polyp size was 1.1 cm, and 72% were sessile. Complications occurred in 9.7% of patients (6.1% of polyps); 75% of these complications were minor; and the mortality rate was zero. Multivariate regression analysis revealed polyp size as the main risk factor, both for complications overall (odds ratio 6.56, 95%CI 4.45-9.67) and for major complications (odds ratio 31.01, 95%CI 7.53-128.1). Right-sided polyp location was a significant risk factor for major complications (odds ratio 2.40, 95%CI 1.34-4.28). Setting a cut-off value of 3% as an acceptable rate for major complications, polyps larger than 1 cm in the right colon or 2 cm in the left colon, and multiple polyps carried an increased risk. CONCLUSIONS: Colonoscopic polypectomy is associated with a 10% rate of complications, but three-quarters of these are of minor clinical significance. More than 90% of the complications can be managed conservatively if adequate endoscopic expertise is available. Guidelines for intensified follow-up after polypectomy should be based on the size, location, and number of a patient's polyps.

INTRODUCTION: Colonic pouches have been used for 20 years to provide reservoir function after reconstructive proctectomy for rectal cancer. More recently coloplasty has been advocated as an alternative to a colonic pouch. However there have been no long-term randomized, controlled trials to compare functional outcomes of coloplasty, colonic J-Pouch (JP), or a straight anastomosis (SA) after the treatment of low rectal cancer. AIM: : To compare the complications, long-term functional outcome, and quality of life (QOL) of patients undergoing a coloplasty, JP, or an SA in reconstruction of the lower gastrointestinal tract after proctectomy for low rectal cancer. METHODS: A multicenter study enrolled patients with low rectal cancer, who were randomized intraoperatively to coloplasty (CP-1) or SA if JP was not feasible, or JP or coloplasty (CP-2) if a JP was feasible. Patients were followed for 24 months with SF-36 surveys to evaluate the QOL. Bowel function was measured quantitatively and using Fecal Incontinence Severity Index (FISI). Urinary function and sexual function were also assessed. RESULTS: Three hundred sixty-four patients were randomized. All patients were evaluated for complications and recurrence. Mean age was 60 +/-12 years, 71% were male. Twenty-three (7.4%) died within 24 months of surgery. No significant difference was observed in the complications among the 4 groups. Two hundred ninety-seven of 364 were evaluated for functional outcome at 24 months. There was no difference in bowel function between the CP-1 and SA groups. JP patients had fewer bowel movements, less clustering, used fewer pads and had a lower FISI than the CP-2 group. Other parameters were not statistically different. QOL scores at 24 months were similar for each of the 4 groups. CONCLUSIONS: In patients undergoing a restorative resection for low rectal cancer, a colonic JP offers significant advantages in function over an SA or a coloplasty. In patients who cannot have a pouch, coloplasty seems not to improve the bowel function of patients over that with an SA.

IMPORTANCE: Enteral administration of immune-modulating nutrients (eg, glutamine, omega-3 fatty acids, selenium, and antioxidants) has been suggested to reduce infections and improve recovery from critical illness. However, controversy exists on the use of immune-modulating enteral nutrition, reflected by lack of consensus in guidelines. OBJECTIVE: To determine whether high-protein enteral nutrition enriched with immune-modulating nutrients (IMHP) reduces the incidence of infections compared with standard high-protein enteral nutrition (HP) in mechanically ventilated critically ill patients. DESIGN, SETTING, AND PARTICIPANTS: The MetaPlus study, a randomized, double-blind, multicenter trial, was conducted from February 2010 through April 2012 including a 6-month follow-up period in 14 intensive care units (ICUs) in the Netherlands, Germany, France, and Belgium. A total of 301 adult patients who were expected to be ventilated for more than 72 hours and to require enteral nutrition for more than 72 hours were randomized to the IMHP (n = 152) or HP (n = 149) group and included in an intention-to-treat analysis, performed for the total population as well as predefined medical, surgical, and trauma subpopulations. INTERVENTIONS: High-protein enteral nutrition enriched with immune-modulating nutrients vs standard high-protein enteral nutrition, initiated within 48 hours of ICU admission and continued during the ICU stay for a maximum of 28 days. MAIN OUTCOMES AND MEASURES: The primary outcome measure was incidence of new infections according to the Centers for Disease Control and Prevention (CDC) definitions. Secondary end points included mortality, Sequential Organ Failure Assessment (SOFA) scores, mechanical ventilation duration, ICU and hospital lengths of stay, and subtypes of infections according CDC definitions. RESULTS: There were no statistically significant differences in incidence of new infections between the groups: 53% (95% CI, 44%-61%) in the IMHP group vs 52% (95% CI, 44%-61%) in the HP group (P = .96). No statistically significant differences were observed in other end points, except for a higher 6-month mortality rate in the medical subgroup: 54% (95% CI, 40%-67%) in the IMHP group vs 35% (95% CI, 22%-49%) in the HP group (P = .04), with a hazard ratio of 1.57 (95% CI, 1.03-2.39; P = .04) for 6-month mortality adjusted for age and Acute Physiology and Chronic Health Evaluation II score comparing the groups. CONCLUSIONS AND RELEVANCE: Among adult patients breathing with the aid of mechanical ventilation in the ICU, IMHP compared with HP did not improve infectious complications or other clinical end points and may be harmful as suggested by increased adjusted mortality at 6 months. These findings do not support the use of IMHP nutrients in these patients. TRIAL REGISTRATION: trialregister.nl Identifier: NTR2181.

Leitlinienprogramm Onkologie der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e. V. (AWMF), Deutschen Krebsgesellschaft e. V. und Deutschen Krebshilfe

BACKGROUND: Surrogate measures for cardiovascular disease events have the potential to increase greatly the efficiency of clinical trials. A leading candidate for such a surrogate is the progression of intima-media thickness (IMT) of the carotid artery; much experience has been gained with this endpoint in trials of HMG-CoA reductase inhibitors (statins). METHODS AND RESULTS: We examine two separate systems of criteria that have been proposed to define surrogate endpoints, based on clinical and statistical arguments. We use published results and a formal meta-analysis to evaluate whether progression of carotid IMT meets these criteria for HMG-CoA reductase inhibitors (statins).IMT meets clinical-based criteria to serve as a surrogate endpoint for cardiovascular events in statin trials, based on relative efficiency, linkage to endpoints, and congruency of effects. Results from a meta-analysis and post-trial follow-up from a single published study suggest that IMT meets established statistical criteria by accounting for intervention effects in regression models. CONCLUSION: Carotid IMT progression meets accepted definitions of a surrogate for cardiovascular disease endpoints in statin trials. This does not, however, establish that it may serve universally as a surrogate marker in trials of other agents.

Patienten mit kolorektalen Adenomen 769 5.1.2. Primrprvention 769 5.1.3. Vorsorgeuntersuchungen 769 5.1.3.1. Verwandte ersten Grades von Patienten mit kolorektalem Karzinom 769 5.1.3.2. Verwandte von Patienten mit kolorektalen Adenomen 770 5.2. Hereditre kolorektale Karzinome 770 5.2.1. Risikogruppen 771 5.2.1.1. HNPCC (hereditres kolorektales Karzinom ohne Polyposis)/Lynch-Syndrom 771 5.2.1.2. Adenomatse Polyposis-Syndrome 772 5.2.1.2.1. Patienten mit klassischer familirer adenomatser Polyposis (FAP) 772 5.2.1.2.2. Patienten mit attenuierter familirer adenomatser Polyposis (AFAP) 772 5.2.1.2.3. Patienten mit MUTYH-assoziierter Polyposis (MAP)

There is no widely accepted standard for antifungal prophylaxis in patients with hematologic malignancies. The Infectious Diseases Working Party of the German Society for Haematology and Oncology assigned a committee of hematologists and infectious disease specialists to develop recommendations. Literature data bases were systematically searched for clinical trials on antifungal prophylaxis. The studies identified were shared within the committee. Data were extracted by two of the authors (OAC and MSi). The consensus process was conducted by email communication. Finally, a review committee discussed the proposed recommendations. After consensus was established the recommendations were finalized. A total of 86 trials were identified including 16,922 patients. Only a few trials yielded significant differences in efficacy. Fluconazole 400 mg/d improved the incidence rates of invasive fungal infections and attributable mortality in allogeneic stem cell recipients. Posaconazole 600 mg/d reduced the incidence of IFI and attributable mortality in allogeneic stem cell recipients with severe graft versus host disease, and in patients with acute myelogenous leukemia or myelodysplastic syndrome additionally reduced overall mortality. Aerosolized liposomal amphotericin B reduced the incidence rate of invasive pulmonary aspergillosis. Posaconazole 600 mg/d is recommended in patients with acute myelogenous leukemia/myelodysplastic syndrome or undergoing allogeneic stem cell recipients with graft versus host disease for the prevention of invasive fungal infections and attributable mortality (Level A I). Fluconazole 400 mg/d is recommended in allogeneic stem cell recipients until development of graft versus host disease only (Level A I). Aerosolized liposomal amphotericin B is recommended during prolonged neutropenia (Level B II).

Early enteral nutrition (EN) is consistently recommended as first-line nutrition therapy in critically ill patients since it favorably alters outcome, providing both nutrition and nonnutrition benefits. However, critically ill patients receiving mechanical ventilation are at risk for regurgitation, pulmonary aspiration, and eventually ventilator-associated pneumonia (VAP). EN may increase these risks when gastrointestinal (GI) dysfunction is present. Gastric residual volume (GRV) is considered a surrogate parameter of GI dysfunction during the progression of enteral feeding in the early phase of critical illness and beyond. By monitoring GRV, clinicians may detect patients with delayed gastric emptying earlier and intervene with strategies that minimize or prevent VAP as one of the major risks of EN. The value of periodic GRV measurements with regard to risk reduction of VAP incidence has frequently been questioned in the past years. Increasing the GRV threshold before interrupting gastric feeding results in marginal increases in EN delivery. More recently, a large randomized clinical trial revealed that abandoning GRV monitoring did not negatively affect clinical outcomes (including VAP) in mechanically ventilated patients. The results have revived the discussion on the role of GRV monitoring in critically ill, mechanically ventilated patients receiving early EN. This review summarizes the most recent clinical evidence on the use of GRV monitoring in critically ill patients. Based on the clinical evidence, it discusses the pros and cons and further addresses whether GRV is a dead marker or still alive for the nutrition management of critically ill patients.

OBJECTIVE: Unexplained hepatic iron overload with increased serum ferritin (SF) values has been associated with the insulin resistance syndrome (IRS), defined by the presence of one or more of the following criteria: increased body mass index (BMI), diabetes, hyperlipidemia or hypertension. However, as yet the association between IRS and SF in a representative population has not been investigated. METHODS: The study subjects participated in a nationwide epidemiological survey on metabolic disorders in the adult German population. The 1200 probands included in this study are representative of the German population. To eliminate major causes of secondary iron overload, 114 (9.5%) subjects with excessive alcohol consumption and 16 (1.5%) subjects with serological evidence for hepatitis B or C were excluded. For all remaining 1070 probands, complete clinical data of SF, HbA1c, known diabetes, BMI, cholesterol, high-density lipoprotein-cholesterol and blood pressure were available. RESULTS: SF values were significantly increased in men and women with high BMI (> 25 kg/m2), increased cholesterol (> 200 mg/dl), and increased systolic (> 160 mmHg) blood pressure, in women with diabetes, and in men with increased diastolic (> 95 mmHg) blood pressure. Furthermore, there was a significant correlation between the number of IRS criteria and SF. CONCLUSIONS: This study shows a significant correlation between SF and the presence of IRS criteria in a large representative population. Interestingly, the severity of the IRS seems to be associated with increased SF levels suggesting a causal connection. Further studies are required to investigate the pathophysiological mechanism and consequences of increased SF levels in patients with IRS.

Cancer patients frequently require central venous catheters for therapy and parenteral nutrition and are at high risk of central venous catheter-related infections (CRIs). Moreover, CRIs prolong hospitalization, cause an excess in resource utilization and treatment cost, often delay anti-cancer treatment, and are associated with a significant increase in mortality in cancer patients. We therefore summoned a panel of experts by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) and updated our previous guideline on CRIs in cancer patients. After conducting systematic literature searches on PubMed, Medline, and Cochrane databases, video- and meeting-based consensus discussions were held. In the presented guideline, we summarize recommendations on definition, diagnosis, management, and prevention of CRIs in cancer patients including the grading of strength of recommendations and the respective levels of evidence. This guideline supports clinicians and researchers alike in the evidence-based decision-making in the management of CRIs in cancer patients.

PURPOSE: To report planned final overall (OS) and progression-free survival (PFS) analyses from the phase II PEAK trial (NCT00819780). METHODS: Patients with previously untreated, KRAS exon 2 wild-type (WT) metastatic colorectal cancer (mCRC) were randomised to mFOLFOX6 plus panitumumab or bevacizumab. The primary endpoint was PFS; secondary endpoints included OS, objective response rate, duration of response (DoR), time to response, resection and safety. Treatment effect by tumour RAS status was a prespecified objective. Exploratory analyses included early tumour shrinkage (ETS) and depth of response (DpR). RESULTS: One hundred seventy patients had RAS WT and 156 had RAS WT/BRAF WT mCRC. Median PFS was longer for panitumumab versus bevacizumab in the RAS WT (12.8 vs 10.1 months; hazard ratio (HR) = 0.68 [95% confidence intervals (CI) = 0.48-0.96]; p = 0.029) and RAS WT/BRAF WT (13.1 vs 10.1 months; HR = 0.61 [95% CI = 0.42-0.88]; p = 0.0075) populations. Median OS (68% OS events) for panitumumab versus bevacizumab was 36.9 versus 28.9 months (HR = 0.76 [95% CI = 0.53-1.11]; p = 0.15) and 41.3 versus 28.9 months (HR = 0.70 [95% CI = 0.48-1.04]; p = 0.08), in the RAS WT and RAS WT/BRAF WT populations, respectively. Median DoR (11.4 vs 9.0 months; HR = 0.59 [95% CI = 0.39-0.88]; p = 0.011) and DpR (65.0 vs 46.3%; p = 0.0018) were improved in the panitumumab group. More panitumumab patients experienced ≥30% ETS at week 8 (64 vs 45%; p = 0.052); ETS was associated with improved PFS/OS. No new safety signals occurred. CONCLUSIONS: First-line panitumumab + mFOLFOX6 increases PFS versus bevacizumab + mFOLFOX6 in patients with RAS WT mCRC.

In Brief Objective: We analyzed 3 previously identified cut-off values of lymph node ratios (0.17, 0.41, and 0.69) in a large population-based collective of patients with colorectal cancer for their prognostic value. Summary Background Data: The lymph node ratio (LNR) (relation of tumor-infiltrated to total examined lymph nodes) has a high prognostic impact, but the relevant cut-off values are not determined. Methods: Patients (N = 27,803) with a primary colorectal cancer diagnosed and operated in the Munich region between 1991 and 2006 were registered in the Munich Cancer Registry. Lymph node numbers and survival data were available for 17,309 patients with a mean follow-up of 5.9 years. Results: The mean number (±SD) of resected lymph nodes was 16.8 ± 8.4. Twelve or more lymph nodes were resected in 76.8%. Estimated 5-year overall survival decreased significantly with increasing LNR: LNR = 0 in 71.4%, LNR 0.01 to 0.17 in 52.4%, LNR 0.18 to 0.41 in 33.3%, LNR 0.42 to 0.69 in 19.8%, and LNR ≥0.70 in 8.3% (P < 0.001). Multivariable survival analyses identified separately both LNR and pN- category, as well as number of resected lymph nodes, patient's age, tumor location, pT-category, pM-status, R-status, tumor grade, and year of operation as independent prognostic factors. Conclusion: The 3 cut-off values of LNRs had strong independent prognostic value in a population-based collective of patients with colorectal cancer. The LNR should be routinely reported and included in the American Joint Committee on Cancer staging system. Nevertheless, the benefit of lymphadenectomy on survival is still unclear. Three previously identified cut-off values of lymph node ratios were analyzed in a population-based collective of patients with colorectal cancer (N = 17,309). The study confirmed the strong independent prognostic value of the examined lymph node ratios. We recommend routinely reporting and including the lymph node ratio in the American Joint Committee on Cancer staging system.

OBJECTIVES: Sedation has been established for GI endoscopic procedures in most countries, but it is also associated with an added risk of complications. Reported complication rates are variable due to different study methodologies and often limited sample size. DESIGNS: Acute sedation-associated complications were prospectively recorded in an electronic endoscopy documentation in 39 study centres between December 2011 and August 2014 (median inclusion period 24 months). The sedation regimen was decided by each study centre. RESULTS: A total of 368 206 endoscopies was recorded; 11% without sedation. Propofol was the dominant drug used (62% only, 22.5% in combination with midazolam). Of the sedated patients, 38 (0.01%) suffered a major complication, and overall mortality was 0.005% (n=15); minor complications occurred in 0.3%. Multivariate analysis showed the following independent risk factors for all complications: American Society of Anesthesiologists class >2 (OR 2.29) and type and duration of endoscopy. Of the sedation regimens, propofol monosedation had the lowest rate (OR 0.75) compared with midazolam (reference) and combinations (OR 1.0-1.5). Compared with primary care hospitals, tertiary referral centres had higher complication rates (OR 1.61). Notably, compared with sedation by a two-person endoscopy team (endoscopist/assistant; 53.5% of all procedures), adding another person for sedation (nurse, physician) was associated with higher complication rates (ORs 1.40-4.46), probably due to higher complexity of procedures not evident in the multivariate analysis. CONCLUSIONS: This large multicentre registry study confirmed that severe acute sedation-related complications are rare during GI endoscopy with a very low mortality. The data are useful for planning risk factor-adapted sedation management to further prevent sedation-associated complications in selected patients. TRIAL REGISTRATION NUMBER: DRKS00007768; Pre-results.

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