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Background Matrixmetalloproteinases (MMPs) comprise a family of zinc-dependent endopeptidases which are involved in angiogenesis, tumor invasion and metastatic formation. Up to date, the prognostic relevance of MMPs in serum of patients with colon cancer remains unknown. Thus, we wanted to assess an expression pattern of MMPs in a homogenous cohort of colon cancer patients to assess their potential as prognostic biomarkers. Methods Differences in the expression pattern of MMP7, MMP10 and MMP12 in 78 serum specimens of patients with an adenocarcinoma of the colon and serum specimens of a healthy control group were assessed using Luminex-100 technologies. Subsequently, we correlated these results with histopathological and clinical data of the patients. Results Luminex based expression analysis revealed a significant overexpression of MMP7 and an overexpression of MMP10 and MMP12 in the sera of colon cancer patients compared to the healthy control group. Patients with vascular invasion showed a significantly higher MMP12 expression than V0-staged patients. Moreover overexpression of MMP7, MMP10 and MMP12 in colon cancer patients´ sera displayed a significantly impaired overall survival. Multivariate analysis revealed high MMP10 serum levels to be an independent adverse prognostic marker in colon cancer patients. Conclusions Expression patterns of MMP7, MMP10 and MMP12 in colon cancer patients´ sera are different compared to serum specimens of healthy individuals. Furthermore, overexpression of MMP7, MMP10 and MMP12 in colon cancer patients´ sera correlates with a dismal prognosis and may help to stratify patients into different risk groups. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2515-7) contains supplementary material, which is available to authorized users.

For patients with locally advanced and unresectable pancreatic cancer (PDAC), neodadjuvant treatment and consecutive surgical exploration have been studied during the last decade with various neoadjuvant therapies including chemotherapy and combinations with radiation. Aim of the study was the evaluation of neoadjuvant therapy with a focus on Folfirinox.All consecutive patients undergoing surgery for PDAC after neoadjuvant treatment were analyzed (clinico-pathological characteristics, secondary resection rates, outcome). Patients receiving Folfirinox were compared with other treatment regimens.Between December 2001 and June 2015, 575 patients received neoadjuvant treatment and were scheduled for resection after re-staging. A successful resection was achieved in 292 patients (50.8%). Resection rates following Folfirinox were 61% (76/125 patients) compared with 46% (150/322 patients) after gemcitabine and radiation, and 52% (66/128 patients) after other treatments (P = 0.026). Median overall survival was 15.3 months after resection vs 8.5 months after exploration alone (P0.0001). Subgroup median survival was 16.0 months (Folfirinox) vs 16.5 months (gemcitabine) and 14.5 months (others) with 3-year survival of 28.1%, 23.2%, and 19.7%, respectively (P = 0.8582). By multivariable analysis, Folfirinox was confirmed to be independently associated with a favorable prognosis.Folfirinox is a valuable treatment option in the neoadjuvant therapy of PDAC. From the present data, which represent the largest available study population to date, Folfirinox seems to be the most effective protocol resulting in a significantly better secondary resection rate and overall survival than other treatments. It should be considered in all patients fit for this regimen and consecutive surgical exploration.

Patient-derived cancer xenografts (PDX) are widely used to identify and evaluate novel therapeutic targets, and to test therapeutic approaches in preclinical mouse avatar trials. Despite their widespread use, potential caveats of PDX models remain considerably underappreciated. Here, we demonstrate that EBV-associated B-lymphoproliferations frequently develop following xenotransplantation of human colorectal and pancreatic carcinomas in highly immunodeficient NOD.Cg-Prkdc

Background Postoperative pancreatic fistula represents the most important complication after distal pancreatectomy. The aim of this study was to evaluate the use of a preoperative endoscopic injection of botulinum toxin into the sphincter of Oddi to prevent postoperative pancreatic fistula (German Clinical Trials Register number: DRKS00007885). Methods This was an investigator-initiated, prospective clinical phase I/II trial with an exploratory study design. We included patients who underwent preoperative endoscopic sphincter botulinum toxin injection (100 units of Botox). End points were the feasibility, safety, and postoperative outcomes, including postoperative pancreatic fistula within 30 days after distal pancreatectomy. Botulinum toxin patients were compared with a control collective of patients undergoing distal pancreatectomy without botulinum toxin injection by case-control matching in a 1:1 ratio. Results Between February 2015 and February 2016, 29 patients were included. All patients underwent successful sphincter of Oddi botulinum toxin injection within a median of 6 (range 0–10) days before operation. One patient had an asymptomatic, self-limiting (48 hours) increase in serum amylase and lipase after injection. Distal pancreatectomy was performed in 24/29 patients; 5 patients were not resectable. Of the patients receiving botulinum toxin, 7 (29%) had increased amylase levels in drainage fluid on postoperative day 3 (the International Study Group of Pancreatic Surgery definition of postoperative pancreatic fistula grade A) without symptoms or need for reintervention. Importantly, no clinically relevant fistulas (International Study Group of Pancreatic Surgery grades B/C) were observed in botulinum toxin patients compared to 33% postoperative pancreatic fistula grade B/C in case-control patients (P Conclusion Preoperative sphincter of Oddi botulinum toxin injection is a novel and safe approach to decrease the incidence of clinically relevant postoperative pancreatic fistula after distal pancreatectomy. The results of the present trial suggest its efficacy in the prevention of clinically relevant postoperative pancreatic fistula and are validated currently in the German Federal Government–sponsored, multicenter, randomized controlled PREBOT trial.

Minimally invasive surgery (MIS) of colorectal cancer (CRC) was first introduced over 20 years ago and recently has gained increasing acceptance and usage beyond clinical trials. However, data on dissemination of the method across countries and on long-term outcomes are still sparse. In the context of a European collaborative study, a total of 112,023 CRC cases from 3 population-based (N=109,695) and 4 institute-based clinical cancer registries (N=2328) were studied and compared on the utilization of MIS versus open surgery. Cox regression models were applied to study associations between surgery type and survival of patients from the population-based registries. The study considered adjustment for potential confounders. The percentage of CRC patients undergoing MIS differed substantially between centers and generally increased over time. MIS was significantly less often used in stage II to IV colon cancer compared with stage I in most centers. MIS tended to be less often used in older (70+) than in younger colon cancer patients. MIS tended to be more often used in women than in men with rectal cancer. MIS was associated with significantly reduced mortality among colon cancer patients in the Netherlands (hazard ratio [HR] 0.66, 95% confidence interval [CI] (0.63-0.69), Sweden (HR 0.68, 95% CI 0.60-0.76), and Norway (HR 0.73, 95% CI 0.67-0.79). Likewise, MIS was associated with reduced mortality of rectal cancer patients in the Netherlands (HR 0.74, 95% CI 0.68-0.80) and Sweden (HR 0.77, 95% CI 0.66-0.90). Utilization of MIS in CRC resection is increasing, but large variation between European countries and clinical centers prevails. Our results support association of MIS with substantially enhanced survival among colon cancer patients. Further studies controlling for selection bias and residual confounding are needed to establish role of MIS in survival of patients., SCOPUS: ar.j, info:eu-repo/semantics/published

This systematic review was performed to investigate the ethical justification, methodological quality, validity and safety of placebo controls in randomized placebo-controlled surgical trials. Central, MEDLINE, and EMBASE were systematically searched to identify randomized controlled trials comparing a surgical procedure to a placebo. “Surgical procedure” was defined as a medical procedure involving an incision with instruments. Placebo was defined as a blinded sham operation involving no change to the structural anatomy and without an expectable physiological response in the target body compartment. Ten randomized placebo-controlled controlled surgical trials were included, all of them published in high-ranking medical journals (mean impact factor: 20.1). Eight of 10 failed to show statistical superiority of the experimental intervention. Serious adverse events did not differ between the groups (rate ratio [RR] 1.38, 95% confidence interval [CI]: 0.92–2.06, P = 0.46). None of the trials had a high risk of bias in any domain. The ethical justification for the use of a placebo control remained unclear in 2 trials. Placebo-controlled surgical trials are feasible and provide high-quality data on efficacy of surgical treatments. The surgical placebo entails a considerable risk for study participants. Consequently, a placebo should be used only if justified by the clinical question and by methodological necessity. Based on the current evidence, a pragmatic proposal for the use of placebo controls in future randomized controlled surgical trials is made.

After esophageal surgery, many centers conduct a routine diagnostic test before reintroducing oral intake. However, the clinical value in asymptomatic patients has been questioned. Therefore, we left this decision to the discretion of the operating surgeon and documented the data prospectively. Between 2007 and 2013, 185 consecutive patients underwent elective esophageal resection in our institution. The decision as to whether an endoscopy was to be performed as a routine-check or when a leak was clinically suspected was at the discretion of the operating surgeon. An immediate endoscopy was performed on emerging clinical signs of a leak. If a routine check was planned, it was performed between postoperative days 5–7. Of the 185 patients, 84 % had an endoscopy of the anastomosis during the hospital stay. Of the patients who underwent an endoscopy, 61 % were on a routine-check. In this group, one patient showed a leak at the time of endoscopy, 11 patients had pathological findings, 3 of these patients developed a leak later. Eighty-three patients had no pathological findings; nevertheless, 7 developed a leak later. In the on-demand-group, 10 patients showed a leak at the time of endoscopy. In a minority of patients, a routine-check of the anastomosis between days 5–7 revealed pathological findings that later led to an anastomotic leak (3/11). In contrast, a routine-check without pathological findings could not rule out the development of a future leak (7/83). Therefore, we conclude that routine postoperative studies to identify leaks after esophageal resection are not justified.

Bleeding and vascular infections are serious potential complications during abdominal general surgery. The management of bleeding depends on the extent and localization and can range from the application of hemostatics to vascular sutures, interpositioning and ligatures. The use of prosthetic biomaterials implanted endoluminally or during open reconstruction permits palliation of potentially fatal conditions. The overall incidence of infections involving vascular prostheses is relatively low because of routine antibiotic prophylaxis prior to surgery, refinements in sterilization and packaging of devices and careful adherence to aseptic procedural and surgical techniques. When infections occur detection and definitive therapy of the vascular prosthesis are often delayed and the management is complex and tedious. Infections involving vascular prostheses are difficult to eradicate and in general, surgical therapy is required often coupled with excision of the prosthesis. Keys to success include accurate diagnostics to identify the organism and extent of graft infections, specific long-term antibiotic therapy and well-planned surgical interventions to excise and replace the infected graft and sterilize the local tissue. Regardless of the technique used to eradicate graft infections, success is measured by patient survival, freedom from recurrent infection and patency of revascularization. Even when treatment is successful, the morbidity associated with vascular graft infections is considerable. Aortoenteric fistulas (AEF) are a rare (incidence

New techniques using vascular clips or ultrasonically activated shears have been suggested to shorten operation time without compromising safety. The objective of the CLIVIT Trial was to compare ligatures with vascular clips for hemostasis in elective benign thyroid surgery. This multicenter, randomized, controlled, parallel group superiority trial was conducted in 13 German surgical centers. Patients scheduled for at least subtotal resection bilaterally were intraoperatively randomized. The primary endpoint was resection time. Secondary endpoints were the amount of postoperative bleeding, reoperation due to bleeding, wound infection, temporary (reversal within 12 months) and permanent (over 1 year) recurrent laryngeal nerve (RLN) paralysis, length of hospital stay, and safety. Registration: ISRCTN 96901396. Two hundred fifty patients were treated with ligatures and 241 with vascular clips. No differences in patients' baseline and surgical characteristics were observed. No difference was detected for mean resection time (clip 63.5 min ± 29.6, ligature 66.1 min ± 29.3, P = 0.258). Postoperative bleeding (mean 86 ml ± 93), reoperation due to bleeding (clips 4, ligature 2), wound infections (clips 4, ligature 4), postoperative hospital stay (mean 3.0 ± 1.9), and safety data also did not vary significantly. The rates of temporary and permanent RLN paralysis were 6.9 % (34/491) and 2.9 % (14/491), respectively. Not using a surgical drain (123 patients) was not associated with a higher rate of complications. Vascular clips did not reduce the resection time. However, a 2.9 % rate of permanent RLN paralysis is of concern. Drains in elective surgery may be of no benefit.

SUMMARY Advanced rectal cancer is defined by local tumor invasion into adjacent structures and organs in the pelvis. A curative multimodal therapy approach for patients with advanced rectal cancer includes neoadjuvant treatment with subsequent pelvic exenteration. Pelvic exenteration is associated with high perioperative morbidity as this surgical procedure includes an extensive resection of pelvic anatomical planes with en bloc removal of the tumor and surrounding organs and structures. Safe reconstruction of the large pelvic floor defect is very important. Quality of life and oncological outcome after pelvic exenteration for advanced rectal cancer are good. In this article, we highlight important clinical and surgical aspects of pelvic exenteration for advanced rectal cancer and review the recent literature.

Summary Human lamina propria T lymphocytes (LPT) possess functional properties profoundly different from those of peripheral blood T lymphocytes (PBT). While they are characterized by a low proliferative response to T cell receptor (TCR)/CD3 stimulation in vitro their responsiveness to activation through the ‘co-stimulatory’ CD2-receptor is enhanced when compared to PBT. In this study, we demonstrate that engagement of another co-stimulatory receptor on both LPT and PBT, namely CD28, by a single monoclonal antibody (mAb), respectively, strongly activates the former but not the latter through a PI3-kinase dependent signalling pathway leading to the production of inflammatory cytokines such as interleukin (IL)-2, tumour necrosis factor (TNF)-α, interferon (IFN)-γ and granulocyte–macrophage colony-stimulating factor (GM-CSF). In addition to the high sensitivity of LPT to CD2 stimulation, this finding supports the notion that ‘non-specific/innate’ mechanisms to activate T lymphocytes play a predominant role vis-à-vis ‘TCR driven/adaptive’ responses in the intestinal mucosa. Furthermore, it suggests that results from preclinical tests for therapeutic antibodies performed with human blood derived T cells are probably insufficient to predict reactivities of tissue-resident immune cells, which – given their quantitative predominance – may critically determine the in-vivo response to such compounds.

It is well known that some patients with resectable rectal cancer benefit from preoperative radiotherapy in combination with or without chemotherapy. In order to reduce local recurrence and improve long-term survival, current guidelines advocate such neoadjuvant treatment in UICC (Union for International Cancer Control) stage II and III patients. However, the vast majority of patients may be adequately treated by rectal resection with total mesorectal excision (TME) alone. Recent evidence suggests an overtreatment of patients leading to unnecessary exposure to acute and long-term toxicity of radiation therapy. The question which consequently arises is which patient does not need preoperative radiotherapy. Improvements in MRI combined with better understanding of prognostic indicators suggest that patients with UICC stage I tumors, with tumors more than 12 cm proximal the anal verge can and patients with a circumferential resection margin 6 > 2 mm as assessed by preoperative MRI might be managed by radical surgery with adequate TME alone. Copyright © 2012 S. Karger AG, Basel

The aim of the study was to assess whether preoperative carcinoembryonic antigen (CEA) level is an independent predictor of overall- and cancer-specific survival in stage I rectal cancer.Stage I rectal cancer patients were identified in the Surveillance, Epidemiology, and End Results database between 2004 and 2011. The impact of an elevated preoperative CEA level (C1-stage) compared with a normal CEA level (C0-stage) on overall and cancer-specific survival was assessed using risk-adjusted Cox proportional hazard regression models and propensity score methods.Overall, 1932 stage I rectal cancer patients were included, of which 328 (17 %) patients had C1-stage. The 5-year overall and cancer-specific survival for patients with C0-stage were 85.7 % (95 % CI 83.2-88.2 %) and 94.7 % (95 % CI 93.1-96.3 %), versus 76.8 % (95 % CI 70.9-83.1 %) and 88.1 % (95 % CI 83.3-93.2 %) for patients with C1-stage (P 0.001 and P = 0.001). The negative impact of C1-stage on overall and cancer-specific survival was confirmed by risk-adjusted Cox proportional hazard regression analysis (hazard ratio [HR] = 1.57, 95 % CI = 1.15-2.16, P = 0.007 and 2.04, 95 % CI = 1.25-3.33, P = 0.006), and after propensity score matching (overall survival [OS]: HR = 1.46, 95 % CI = 1.02-2.08, P = 0.044 and cancer-specific survival [CSS]: HR = 3.28, 95 % CI = 1.78-6.03, P 0.001).This is the first population-based investigation of a large cohort of exclusively stage I rectal cancer patients providing compelling evidence that elevated preoperative CEA level is a strong predictor of worse overall and cancer-specific survival.

Background Studies on the association between alcohol consumption and colorectal cancer (CRC) prognosis have yielded inconsistent results. Objective The associations of lifetime and 1-y prediagnostic alcohol consumption with relevant prognostic outcomes were evaluated in a large population-based cohort of CRC patients. Design In 2003-2010, 3121 patients diagnosed with CRC were interviewed on sociodemographic and lifestyle factors, medication, and comorbidities. Cancer recurrence, vital status, and cause of death were documented for a median follow-up time of 4.8 y. With the use of Cox proportional hazard regression, associations between lifetime and recent alcohol consumption and overall, CRC-specific, recurrence-free, and disease-free survival were analyzed. Results In this patient cohort with a median age of 69 y at diagnosis, lifetime abstainers showed poorer overall [adjusted HR (aHR): 1.25; 95% CI: 1.03, 1.52] and CRC-specific (aHR: 1.37; 95% CI: 1.10, 1.70) survival than lifetime light drinkers (women: >0-12 g/d; men: >0-24 g/d). Lifetime heavy drinkers showed poorer overall (aHR: 1.37; 95% CI: 1.06, 1.78) and disease-free (aHR: 1.38; 95% CI: 1.09, 1.74) survival. Alcohol abstaining in the year before diagnosis was associated with poorer overall (aHR: 1.42; 95% CI: 1.20, 1.68), CRC-specific (aHR: 1.38; 95% CI: 1.13, 1.68), and disease-free (aHR: 1.23; 95% CI: 1.05, 1.44) survival. Lifetime abstainers with nonmetastatic disease showed poorer CRC-specific (aHR: 1.48; 95% CI: 1.10, 2.00) and recurrence-free (aHR: 1.32; 95% CI: 1.02, 1.70) survival. Wine abstaining but not beer or liquor abstaining was associated with poorer survival. Associations between alcohol consumption and prognosis varied according to presence of diabetes and age. Conclusions Prediagnostic alcohol abstaining and heavy drinking were associated with poorer survival after a CRC diagnosis than light drinking. The protective effects of light consumption might be restricted to wine, and associations might differ according to age and presence of diabetes mellitus.

Background Resections of the pancreatic body and tail reaching to the left of the superior mesenteric vein are defined as distal pancreatectomy. Most distal pancreatectomies are elective treatments for chronic pancreatitis, benign or malignant diseases, and they have high morbidity rates of up to 40%. Pancreatic fistula formation is the main source of postoperative morbidity, associated with numerous further complications. Researchers have proposed several surgical resection and closure techniques of the pancreatic remnant in an attempt to reduce these complications. The two most common techniques are scalpel resection followed by hand-sewn closure of the pancreatic remnant and stapler resection and closure. Objectives To compare the rates of pancreatic fistula in people undergoing distal pancreatectomy using scalpel resection followed by hand-sewn closure of the pancreatic remnant versus stapler resection and closure. Search methods We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Biosis and Science Citation Index from database inception to October 2015. Selection criteria We included randomised controlled trials (RCTs) comparing stapler versus scalpel resection followed by hand-sewn closure of the pancreatic remnant for distal pancreatectomy (irrespective of language or publication status). Data collection and analysis Two authors independently assessed trials for inclusion and extracted the data. Taking into consideration the clinical heterogeneity between the trials (e.g. different endpoint definitions), we analysed data using a random-effects model with Review Manager (RevMan), calculating risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). Main results In two eligible trials, a total of 381 participants underwent distal pancreatic resection and were randomised to closure of the pancreatic remnant either with stapler (n = 191) or scalpel resection followed by hand-sewn closure (n = 190). One was a single centre pilot RCT and the other was a multicentre blinded RCT. The single centre pilot RCT evaluated 69 participants in five intervention arms (stapler, hand-sewn, fibrin glue, mesh and pancreaticojejunostomy), although we only assessed the stapler and hand-sewn closure groups (14 and 15 participants, respectively). The multicentre RCT had two interventional arms: stapler (n = 177) and hand-sewn closure (n = 175). The rate of postoperative pancreatic fistula was the main outcome, and it occurred in 79 of 190 participants in the hand-sewn group compared to 65 of 191 participants in the stapler group. Neither the individual trials nor the meta-analysis showed a significant difference between resection techniques (RR 0.90; 95% CI 0.55 to 1.45; P = 0.66). In the same way, postoperative mortality and operation time did not differ significantly. The single centre RCT had an unclear risk of bias in the randomisation, allocation and both blinding domains. However, the much larger multicentre RCT had a low risk of bias in all domains. Due to the small number of events and the wide confidence intervals that cannot exclude clinically important benefit or harm with stapler versus hand-sewn closure, there is a serious possibility of imprecision, making the overall quality of evidence moderate. Authors' conclusions The quality of evidence is moderate and mainly based on the high weight of the results of one multicentre RCT. Unfortunately, there are no other completed RCTs on this topic except for one relevant ongoing trial. Neither stapler nor scalpel resection followed by hand-sewn closure of the pancreatic remnant for distal pancreatectomy showed any benefit compared to the other method in terms of postoperative pancreatic fistula, overall postoperative mortality or operation time. Currently, the choice of closure is left up to the preference of the individual surgeon and the anatomical characteristics of the patient. Another (non-European) multicentre trial (e.g. with an equality or non-inferiority design) would help to corroborate the findings of this meta-analysis. Future trials assessing novel methods of stump closure should compare them either with stapler or hand-sewn closure as a control group to ensure comparability of results.

Purpose: To investigate the influence of the introduction of total mesorectal excision (TME) on local recurrence rate and survival in patients with rectal cancer. Methods: A total of 171 consecutive patients underwent anterior or abdominoperineal resection for primary rectal cancer. When the TME technique was introduced, the clinical setting, including the surgeons, remained the same. Group 1 (1993-95, n=53) underwent conventional surgery and group 2 (1995-2001, n=118) underwent TME. All patients were followed for 7years or until death. Results: Between the two groups, no statistically significant differences were present with regards to patient-, treatment-, or tumor-related characteristics apart from the time point of radiotherapy. The total local recurrence rates were 11 of 53 (20.8%) in group 1 and 7 of 118 (5.9%) in group 2, and the rates of isolated local recurrences were 6 of 53 (11.3%) in group 1 and 2 of 118 (1.7%) in group 2. Both differences were highly statistically significant. The disease-free survival in groups 1 and 2 was 60.4 and 65.3% at 5years, and 58.5 and 65.3% at 7years, respectively. Excluding patients with synchronous or metachronous distant metastasis from the analysis, both the disease-free survival and the cancer-specific survival were statistically significantly better in group 2 than in group 1. No statistically significant difference between the two groups was detected regarding the overall survival. Conclusions: The introduction of TME led to an impressive reduction of the local recurrence rate. Survival is mainly determined by the occurrence of distant metastasis, but TME seems to improve survival in patients without systemic disease

Leukocyte-depleted packed red blood cells (PRBC) were introduced to reduce potential immunomodulatory effects and transfusion-associated morbidity. It has, however, remained unclear, if leucocyte depletion prevents negative side effects of blood transfusion. The aim of this analysis was to examine the effects of leukocyte-depleted PRBC on surgical morbidity after elective colon cancer surgery. Data were prospectively collected from 531 consecutive patients undergoing elective colon cancer surgery at a single high-volume center (University Hospital) from 2002 to 2008. Potentially predictive factors for surgical morbidity were tested on univariate and multivariate analysis. A total of 531 patients with colon cancer were included. A curative (R0) resection was performed in 497 patients (94%). The mortality rate, overall morbidity rate, and surgical morbidity rate were 1.1, 33, and 21%, respectively. Some 135 patients (25%) received perioperative transfusion of PRBCs. On multivariate analysis age (odds ratio [OR] 1.04, 95% confidence interval [95% CI] 1.02–1.06; P = 0.001), BMI (OR 1.08, 95% CI 1.03–1.13; P = 0.003), and PRBC transfusion (2.4, 1.41–4.11; P = 0.001) were revealed as independent predictors of surgical morbidity. The risk of surgical complications increased continuously with the amount of transfused PRBCs. The adverse impact of PRBC transfusion was neither restricted to the timepoint of transfusion (intraoperative or postoperative), nor to the kind of complication (infectious vs noninfectious complication). Perioperative transfusion of leukocyte-depleted PRBCs has a significantly negative effect on surgical morbidity of patients undergoing elective colon cancer surgery. The use of perioperative blood transfusions in these patients should be avoided, whenever possible.

There is still controversy about the necessity of a diverting stoma after deep anterior resection with total mesorectal excision for rectal cancer. Recent results of randomized controlled trials and from systematic reviews have improved the currently available data. A significant benefit was shown for patients with diverting stoma in terms of clinically relevant anastomotic leakage and re-operation rates. The influence on mortality is not as clear. However, analysis of the data of 19 prospective studies within a systematic review including more than 9,000 patients, revealed a significant benefit for stoma creation. Furthermore, the rate of patients with stoma 5 years after primary resection was lower in the group of patients with diverting stoma. The purpose of this manuscript is to show the necessity of a diverting stoma based on the currently available data.

Adipose tissue has recently emerged as a driver of tumorigenesis, as adipose-associated factors enhance tumor growth and development. Here we investigated for the first time direct crosstalk between visceral adipose tissue (VAT) and tumor tissues in colorectal cancer (CRC) patients. We analyzed paired transcriptomic profiles of tissues and systemic inflammatory biomarkers among CRC patients to elucidate potential mechanisms and molecular signals driving the host-tumor interaction. Paired presurgery blood and tumor adjacent VAT, colorectal tumor and mucosa tissue samples collected during surgery were obtained from 47 Caucasian patients diagnosed with microsatellite-stable primary CRC enrolled in the ColoCare Study. Clinical/demographic information, and lifestyle-related risk factors, were reported. VAT was quantified by computed tomography. RNA was extracted from VAT, colorectal tumor and mucosa tissues, analyzed using HumanHT-12 Expression BeadChips, processed, and validated. Serum-based assays were conducted in 46 of 47 patients for systemic inflammatory markers with the Mesoscale Discovery Platform. High PTGS2 tumor expression was associated with 131 significantly altered VAT genes, of which 85.5% were upregulated. A significant upstream regulator of dysregulated VAT genes was SAA1. Investigation of circulating inflammatory biomarkers corroborated these transcriptomic findings, as patients with high PTGS2 tumor expression were also significantly more likely to have higher serum-based SAA levels. The differential expression of PPAR-γ in VAT identified 284 significantly altered tumor genes. 71.8% of tumor genes were upregulated in association with higher PPAR-γ VAT expression. Differentially expressed tumor genes were enriched in functional cellular movement. Inflammatory biomarkers in patient sera showed marginally significant differences for soluble ICAM-1 in association with differential PPAR-γ VAT expression. Overlap of the 131 altered VAT genes associated with differential PTGS2 tumor expression with the 284 dysregulated tumor genes associated with differential PPAR-γ VAT expression identified 15 common genes. Gene set enrichment analysis demonstrated that phenotypes associated with these genes in humans included cancer invasiveness signatures from tumor microenvironment interactions. Our multi-omics profiling of paired tissue transcriptomics and systemic inflammatory biomarkers from CRC patients established a bidirectional link between VAT and colorectal tumor tissue. We have demonstrated that this direct crosstalk activates signaling cascades to promote proinflammatory interactions and metabolic reprogramming. Future efforts to develop mechanism-based interventions that disrupt these molecular signals at the nexus of VAT-tumor crosstalk may improve obesity-driven CRC prevention and control. Citation Format: Andreana N. Holowatyj, Mariam Haffa, Tengda Lin, Biljana Gigic, Jennifer Ose, Christy Warby, Caroline Himbert, Clare Abbenhardt, Juergen Boehm, Magnus von Knebel Doeberitz, Nina Habermann, Esther Herpel, Hans-Ulrich Kauczor, Matthias Kloor, Johanna Nattenmüller, Peter Schirmacher, Martin Schneider, Petra Schrotz-King, Thomas Simon, Alexis Ulrich, Laura Bowers, Stephen D. Hursting, Cornelia M. Ulrich. Crosstalk between visceral adipose and tumor tissue in colorectal cancer patients: Molecular signals driving host-tumor interaction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5249.

Current knowledge on the role of retinol in the prognosis of patients with colorectal cancer (CRC) is very limited. We investigated the association of serum retinol levels with survival outcomes in a large cohort of 2908 CRC patients from Germany. Retinol concentrations were determined in serum collected shortly after diagnosis by mass spectrometry. Associations between serum retinol levels and survival outcomes were assessed using multivariable Cox regression and dose-response analyses. The joint association of serum retinol and serum 25-hydroxyvitamin D3 (25(OH)D3) with survival outcomes was also examined. During a median follow-up of 4.8 years, 787 deaths occurred, 573 of which were due to CRC. Dose-response curves showed an inverse relationship between serum retinol levels and survival endpoints in the range of

This study evaluated the role of the acute phase C-reactive protein (CRP) in the postoperative course of a large series of rectal resections on the basis of a prospective database. Main focus of this study was the early identification of complications.Three hundred eighty-three rectal resections with primary anastomosis for rectal cancer were screened for infectious postoperative complications. Forty-eight complicated cases were identified and matched with 48 patients with an uneventful postoperative course.In the postoperative setting, CRP peaked on postoperative day (POD) 2 with a median serum CRP of 140 mg/l and gradually declined thereafter in uncomplicated cases. In complicated cases, CRP elevation generally persisted after POD 2, whereas white blood cells and body temperature were within normal range in the early postoperative period. A cutoff CRP value of 140 mg/dl on PODs 3 and 4 resulted in predictive values of 85.7 and 90.5% (adjusted to the prevalence: 37.6 and 50.3%), sensitivities of 80.0 and 54.3%, and specificities of 81.0 and 92.3% for a complicated postoperative course (P0.001), respectively.Persistent CRP elevation and elevation of serum CRP above 140 mg/dl on PODs 3-4 are predictive of infectious postoperative complications and should prompt intense clinical search for an inflammatory process, especially for an anastomotic leak if pneumonia and wound infection are unlikely or excluded.

Since introduction of total mesorectal excision (TME) the prognosis of rectal cancer patients has improved significantly. Debate exists regarding the optimal mode of multimodal treatment. The aim of this survey was to determine the preferred multimodal treatment and the significance and acceptance of short-term radiotherapy (5 x 5 Gy) in Germany.In August 2003, a questionnaire was sent to the heads of all 1,275 surgical and 157 radiotherapy departments in Germany.Four hundred ninety-three of 1,275 surgical (39%) and 89 of 157 radiotherapeutic questionnaires (56%) were returned. The majority of the answering surgeons and radiotherapists performed adjuvant (89 and 100%), followed by neoadjuvant (61 and 94%) and short-term radiotherapy (5 x 5 Gy) (16 and 17%). Other questions of the survey dealt with indications for each treatment modality, the initiation of treatment, and reasons for objection to short term radiotherapy.Short-tem radiotherapy played a minor role in the treatment of rectal cancer patients in 2003 and was mainly initiated by surgeons (approximately 70%). However, 74% of the answering surgeons and 42% of the answering radiotherapists not performing short-term radiotherapy in 2003 were open minded towards the introduction of this treatment modality.

BACKGROUND Industry sponsorship has been identified as a source of bias in several fields of medical science. To date, the influence of industry sponsorship in the field of general and abdominal surgery has not been evaluated. METHODS A systematic literature search (1985-2014) was performed in the Cochrane Library, MEDLINE, and EMBASE to identify randomized controlled trials in general and abdominal surgery. Information on funding source, outcome, and methodological quality was extracted. Association of industry sponsorship and positive outcome was expressed as odds ratio (OR) with 95% confidence interval (CI). A χ test and a multivariate logistic regression analysis with study characteristics and known sources of bias were performed. RESULTS A total of 7934 articles were screened and 165 randomized controlled trials were included. No difference in methodological quality was found. Industry-funded trials more often presented statistically significant results for the primary endpoint (OR, 2.44; CI, 1.04-5.71; P = 0.04). Eighty-eight of 115 (76.5%) industry-funded trials and 19 of 50 (38.0%) non-industry-funded trials reported a positive outcome (OR, 5.32; CI, 2.60-10.88; P

Oxaliplatin is frequently used as part of a chemotherapeutic regimen with 5-fluorouracil in the treatment of colorectal cancer (CRC). The cellular availability of oxaliplatin is dependent on metabolic and transporter enzymes. Variants in genes encoding these enzymes may cause variation in response to oxaliplatin and could be potential predictive markers. Therefore, we used a two-step procedure to comprehensively investigate 1,444 single nucleotide polymorphisms (SNPs) from these pathways for their potential as predictive markers for oxaliplatin treatment, using 623 stage II-IV CRC patients (of whom 201 patients received oxaliplatin) from a German prospective patient cohort treated with adjuvant or palliative chemotherapy. First, all genes were screened using the global test that evaluated SNP*oxaliplatin interaction terms per gene. Second, one model was created by backward elimination on all SNP*oxaliplatin interactions of the selected genes. The statistical procedure was evaluated using bootstrap analyses. Nine genes differentially associated with overall survival according to oxaliplatin treatment (unadjusted p values0.05) were selected. Model selection resulted in the inclusion of 14 SNPs from eight genes (six transporter genes, ABCA9, ABCB11, ABCC10, ATP1A1, ATP1B2, ATP8B3, and two metabolism genes GSTM5, GRHPR), which significantly improved model fit. Using bootstrap analysis we show an improvement of the prediction error of 3.7% in patients treated with oxaliplatin. Several variants in genes involved in metabolism and transport could thus be potential predictive markers for oxaliplatin treatment in CRC patients. If confirmed, inclusion of these variants in a predictive test could identify patients who are more likely to benefit from treatment with oxaliplatin.

Ulcerative colitis (UC) patients have an increased risk of developing colorectal carcinoma (CRC). In contrast to clinical and pathogenetic differences, little is known about how prognosis compares between these patients and those with sporadic CRC. The aim of this study was to compare their characteristics and prognosis and identify independent risk factors for patients with UC-associated CRC. A total of 126 patients who underwent surgery in our department (1984–2010) for UC-associated (n = 63) or sporadic (n = 63) CRC were included in this analysis. Patients were matched according to sex, tumor location, and disease stage. Clinical parameters and overall, recurrence-free, and disease-specific survival were compared. In subgroup analyses, clinical parameters of UC patients were correlated with survival. Median follow-up was 129 months in the UC group and 99 months in the sporadic CRC group. UC patients were significantly younger and had more multifocal, high-grade, and mucinous carcinomas. Five-year overall survival rate for UC-associated and sporadic CRC was similar (65.7 vs. 63.2 %, p = 0.98). Recurrence-free survival for International Union Against Cancer (UICC) stage II disease was superior in the sporadic CRC group (p = 0.039). In a subgroup analysis of UC patients, a shorter duration of UC (p = 0.045) and male sex (p = 0.005) were associated with a worse prognosis. Despite multiple clinical and histopathologic differences between UC-associated and sporadic CRC patients, overall survival and disease-specific survival are similar. In a subgroup analysis of UC patients with CRC, female sex was associated with a significantly better prognosis. This finding implies that estrogens may play a protective role in UC-associated CRC carcinogenesis.

There is an ongoing debate on whether palliative removal of the primary tumor may result in a survival benefit for patients with incurable stage IV pancreatic neuroendocrine tumors (P-NET). The objective of this study was to assess whether palliative resection of the primary tumor in patients with incurable stage IV P-NET has an impact on survival. Patients with stage IV P-NET registered in the Surveillance, Epidemiology, and End Results database between 2004 and 2011 were identified. Those undergoing resection of metastases were excluded. Overall and cancer-specific survival of patients who did and did not undergo resection of their primary tumor were compared by means of risk-adjusted Cox proportional hazard regression analysis and propensity score-matched analysis. A total of 442 stage IV P-NET patients were identified, of whom 75 (17.0 %) underwent palliative primary tumor resection. The latter showed a significant benefit in both overall survival (hazard ratio [HR] of death = 0.41, 95 % confidence interval [CI] 0.25–0.66, p

Hypoxia is a common feature of solid tumors. Prolyl hydroxylase enzymes (PHD1–3) are molecular oxygen sensors that regulate hypoxia-inducible factor activity, but their functions in metastatic disease remain unclear. Here, we assessed the significance of PHD enzymes during the metastatic spread of colorectal cancer. PHD expression analysis in 124 colorectal cancer patients revealed that reduced tumoral expression of PHD3 correlated with increased frequency of distant metastases and poor outcome. Tumorigenicity and metastatic potential of colorectal tumor cells over and underexpressing PHD3 were investigated in orthotopic and heterotopic tumor models. PHD3 overexpression in a syngeneic tumor model resulted in fewer liver metastases, whereas PHD3 knockdown induced tumor spread. The migration of PHD3-overexpressing tumor cells was also attenuated in vitro. Conversely, migratory potential and colony formation were enhanced in PHD3-deficient cells, and this phenotype was associated with enhanced mitochondrial ATP production. Furthermore, the effects of PHD3 deficiency were accompanied by increased mitochondrial expression of the BCL-2 family member, member myeloid cell leukemia sequence 1 (MCL-1), and could be reversed by simultaneous inhibition of MCL-1. MCL-1 protein expression was likewise enhanced in human colorectal tumors expressing low levels of PHD3. Therefore, we demonstrate that downregulation of PHD3 augments metastatic spread in human colorectal cancer and identify MCL-1 as a novel downstream effector of oxygen sensing. Importantly, these findings offer new insight into the possible, context-specific deleterious effects of pharmacologic PHD inhibition. Cancer Res; 76(8); 2219–30. ©2016 AACR.

Current guidelines advocate that all rectal cancer patients with American Joint Committee on Cancer (AJCC) stages II and III disease should be subjected to neoadjuvant therapy. However, improvements in surgical technique have resulted in single-digit local recurrence rates with surgery only. Operative, postoperative, and oncological outcomes of patients with and without neoadjuvant therapy were compared between January 2002 and December 2013. For this purpose, all patients resected with low anterior rectal resection (LAR) and total mesorectal excision (TME) who had or had not been irradiated were identified from the authors’ prospectively maintained database. Patients who were excluded were those with high rectal cancer or AJCC stage IV disease; in the surgery-only group, patients with AJCC stage I disease or with pT4Nx rectal cancer; and in the irradiated patients, patients with ypT4Nx or cT4Nx rectal cancer. Overall, 454 consecutive patients were included. A total of 342 (75 %) patients were irradiated and 112 (25 %) were not irradiated. Median follow-up for all patients was 48 months. Among patients with and without irradiation, pathological circumferential resection margin positivity rates (2.9 vs. 1.8 %, p = 0.5) were not different. At 5 years, in irradiated patients compared with surgery-only patients, the incidence of local recurrence was decreased (4.5 vs. 3.8 %, p = 0.5); however, systemic recurrences occurred more frequently (10 vs. 17.8 %, p = 0.2). Irradiation did not affect overall or disease-free survival (neoadjuvant treatment vs. surgery-only: 84.9 vs. 88.2 %, p = 0.9; 76 vs. 79.1 %, p = 0.8). The current study adds to the growing evidence that suggests a selective rather than generalized indication for neoadjuvant treatment in stages II and III rectal cancer.

In the past, elderly patients with upper GI cancers were excluded from surgery or multimodal treatment only due to their advanced age. In an aging society this way of patient selection seems to be questionable. The aim of this retrospective exploratory study was to investigate how patients with upper GI cancer over the age of 70 years differ from younger patients in the postoperative course and which parameters influence overall survival in older patient populations.From 2002 to 2012 1,005 patients underwent resection of esophageal or gastric cancer at the University of Heidelberg. 272 patients were older than 70 years and analyzed in subgroups (70-74 years: n = 146; 75-79 years: n = 82; 80 years or older: n = 44). Patients older than 70 years were compared to patients under 70 years (n = 733) with focus on differences in patients characteristics and outcome. Statistical analyses were made retrospectively on a prospective database.Fewer older patients were treated neoadjuvantly ( 70 years: 41.5%; 70 years: 24.7%, P 0.001) and extended resection (abdominothoracic approach) was applied less frequently compared to patients under 70 years ( 70 years: 38.9%; 70 years: 19.9%, P 0.001). The pNM-category (HR 1.41/2.56) and R-status (HR 1.78) remain the most important predictive factor for survival (all 0.001). Female patients had a longer survival than men over the age of 70 (84.9 vs. 23.5 months, P 0.01). Patients over 80 years had a significant shortened overall survival ( 80 years: 16.7 vs. 70 years: 37.4 months) compared to the other subgroups (P 0.001) and a significant increased in-hospital mortality ( 80 years: 20.5% vs. 70 years: 6.0%, P = 0.002).An exclusion from surgical therapy due to advanced age in general seems not to be justified. However, the decision for a surgical resection in patients over 80 years should be made with caution. pNM-categories and R0-resection remain the most important predictive factors for overall survival in all subgroups. No survival benefit for neoadjuvant treatment in patients over 70 years was found, while women survived longer than men. However, the decision concerning a (radio) chemotherapy should be made individually in each patient.

Oxaliplatin-based chemotherapy exerts its effects through generating DNA damage. Hence, genetic variants in DNA repair pathways could modulate treatment response. We used a prospective cohort of 623 colorectal cancer patients with stage II-IV disease treated with adjuvant/palliative chemotherapy to comprehensively investigate 1727 genetic variants in the DNA repair pathways as potential predictive markers for oxaliplatin treatment. Single nucleotide polymorphisms (SNP) associations with overall survival and recurrence-free survival were assessed using a Cox regression model. Pathway analysis was performed using the gamma method. Patients carrying variant alleles of rs3783819 (MNAT1) and rs1043953 (XPC) experienced a longer overall survival after treatment with oxaliplatin than patients who did not carry the variant allele, while the opposite association was found in patients who were not treated with oxaliplatin (false discovery rate-adjusted P-values for heterogeneity 0.0047 and 0.0237, respectively). The nucleotide excision repair (NER) pathway was found to be most likely associated with overall survival in patients who received oxaliplatin (P-value=0.002). Our data show that genetic variants in the NER pathway are potentially predictive of treatment response to oxaliplatin.

VEGFR-2 is expressed on tumor vasculature and a target for anti-angiogenic intervention. VXM01 is a first in kind orally applied tumor vaccine based on live, attenuated Salmonella bacteria carrying an expression plasmid, encoding VEGFR-2. We here studied the safety, tolerability, T effector (Teff), T regulatory (Treg) and humoral responses to VEGFR2 and anti-angiogenic effects in advanced pancreatic cancer patients in a randomized, dose escalation phase I clinical trial. Results of the first 3 mo observation period are reported. Locally advanced or metastatic, pancreatic cancer patients were enrolled. In five escalating dose groups, 30 patients received VXM01 and 15 placebo on days 1, 3, 5, and 7. Treatment was well tolerated at all dose levels. No dose-limiting toxicities were observed. Salmonella excretion and salmonella-specific humoral immune responses occurred in the two highest dose groups. VEGFR2 specific Teff, but not Treg responses were overall increased in vaccinated patients. We furthermore observed a significant reduction of tumor perfusion after 38 d in vaccinated patients together with increased levels of serum biomarkers indicative of anti-angiogenic activity, VEGF-A, and collagen IV. Vaccine specific Teff responses significantly correlated with reductions of tumor perfusion and high levels of preexisting VEGFR2-specific Teff while those showing no antiangiogenic activity had low levels of preexisting VEGFR2 specific Teff, showed a transient early increase of VEGFR2-specific Treg and reduced levels of VEGFR2-specific Teff at later time points - pointing to the possibility that early anti-angiogenic activity might be based at least in part on specific reactivation of preexisting memory T cells.

Local recurrence of rectal cancer after curative surgery predicts patients’ prognosis. The correlation between the exact anatomic location of tumour recurrence and patients’ survival is still under debate. Thus, this study aimed to investigate the impact of the exact location of recurrent rectal cancer on post-operative morbidity and survival. This is a retrospective study including 90 patients with locally recurrent rectal cancer. The location of tumour recurrence was classified into intraluminal and extraluminal recurrence. Univariate and multivariable Cox regression analyses were used to determine the impact on post-operative morbidity and survival. Patients’ survival with intraluminal recurrence was significantly longer compared to patients with extraluminal recurrence (p = 0.027). Curative resection was associated with prolonged survival in univariate and multivariable analyses (p = 0.0001) and was more often achieved in patients with intraluminal recurrence (p = 0.024). Survival of curative resected patients with intraluminal recurrence was significantly longer compared to curatively resected patients with extraluminal recurrence (p = 0.0001). The rate of post-operative morbidity between intraluminal and extraluminal recurrence was not statistically different (p = 0.59). Based on the present investigation, intraluminal recurrence is associated with superior outcome. Post-operative morbidity did not differ significantly between both groups.

OBJECTIVE To assess whether palliative primary tumor resection in colorectal cancer patients with incurable stage IV disease is associated with improved survival. BACKGROUND There is a heated debate regarding whether or not an asymptomatic primary tumor should be removed in patients with incurable stage IV colorectal disease. METHODS Stage IV colorectal cancer patients were identified in the Surveillance, Epidemiology, and End Results database between 1998 and 2009. Patients undergoing surgery to metastatic sites were excluded. Overall survival and cancer-specific survival were compared between patients with and without palliative primary tumor resection using risk-adjusted Cox proportional hazard regression models and stratified propensity score methods. RESULTS Overall, 37,793 stage IV colorectal cancer patients were identified. Of those, 23,004 (60.9%) underwent palliative primary tumor resection. The rate of patients undergoing palliative primary cancer resection decreased from 68.4% in 1998 to 50.7% in 2009 (P < 0.001). In Cox regression analysis after propensity score matching primary cancer resection was associated with a significantly improved overall survival [hazard ratio (HR) of death = 0.40, 95% confidence interval (CI) = 0.39-0.42, P < 0.001] and cancer-specific survival (HR of death = 0.39, 95% CI = 0.38-0.40, P < 0.001). The benefit of palliative primary cancer resection persisted during the time period 1998 to 2009 with HRs equal to or less than 0.47 for both overall and cancer-specific survival. CONCLUSIONS On the basis of this population-based cohort of stage IV colorectal cancer patients, palliative primary tumor resection was associated with improved overall and cancer-specific survival. Therefore, the dogma that an asymptomatic primary tumor never should be resected in patients with unresectable colorectal cancer metastases must be questioned.

The prognosis of patients with rectal cancer has been improved significantly after introduction of the total mesorectal excision (TME). Just by performing TME, the local recurrence rates could be decreased to less than 10 %, independent of multi-modal therapeutic concepts. In contrast, the local recurrence rate reached 4 to 55 % (median 20 %) in a German multicenter study in 1995 prior to the nationwide introduction of TME. The goal of this overview is to compare the different concepts in the multi-modal therapy of rectal cancer with their advantages and disadvantages based on the current literature. Mentioned will be local recurrence rates and survival, but also toxicity, costs and acceptance of patients. Furthermore, a preview is given about future developments.

Current evidence on the association between smoking and colorectal cancer (CRC) prognosis after diagnosis is heterogeneous and few have investigated dose-response effects or outcomes other than overall survival. Therefore, the association of smoking status and intensity with several prognostic outcomes was evaluated in a large population-based cohort of CRC patients; 3,130 patients with incident CRC, diagnosed between 2003 and 2010, were interviewed on sociodemographic factors, smoking behavior, medication and comorbidities. Tumor characteristics were collected from medical records. Vital status, recurrence and cause of death were documented for a median follow-up time of 4.9 years. Using Cox proportional hazards regression, associations between smoking characteristics and overall, CRC-specific, non-CRC related, recurrence-free and disease-free survival were evaluated. Among stage I-III patients, being a smoker at diagnosis and smoking ≥15 cigarettes/day were associated with lower recurrence-free (adjusted hazard ratios (aHR): 1.29; 95% confidence interval (CI): 0.93-1.79 and aHR: 1.31; 95%-CI: 0.92-1.87) and disease-free survival (aHR: 1.26; 95%-CI: 0.95-1.67 and aHR: 1.29; 95%-CI: 0.94-1.77). Smoking was associated with decreased survival in stage I-III smokers with pack years ≥20 (Overall survival: aHR: 1.40; 95%-CI: 1.01-1.95), in colon cancer cases (Overall survival: aHR: 1.51; 95%-CI: 1.05-2.17) and men (Recurrence-free survival: aHR: 1.51; 95%-CI: 1.09-2.10; disease-free survival: aHR: 1.49; 95%-CI: 1.12-1.97), whereas no associations were seen among women, stage IV or rectal cancer patients. The observed patterns support the existence of adverse effects of smoking on CRC prognosis among nonmetastatic CRC patients. The potential to enhance prognosis of CRC patients by promotion of smoking cessation, embedded in tertiary prevention programs warrants careful evaluation in future investigations.

The role of reactive carbonyl species, such as methylglyoxal (MG), has been overlooked within the context of the sepsis syndrome. The aims of this study were to assess the impact of MG formation in different inflammatory settings and to evaluate its use for early diagnosis as well as prognosis of the sepsis syndrome. In total, 120 patients in three groups were enrolled in this observational clinical pilot study. The three groups included patients with septic shock (n = 60), postoperative controls (n = 30), and healthy volunteers (n = 30). Plasma samples from patients with septic shock were collected at sepsis onset and after 24 hours and 4, 7, 14, and 28 days. Plasma samples from postoperative controls were collected prior to surgery, immediately following the end of the surgical procedure as well as 24 hours later and from healthy volunteers once. Plasma levels of MG were determined by high-performance liquid chromatography. Additionally, plasma levels of procalcitonin, C-reactive protein, soluble CD14 subtype, and interleukin-6 were determined. Patients with septic shock showed significantly higher plasma levels of MG at all measured times, compared with postoperative controls. MG was found to identify patients with septic shock more effectively—area under the curve (AUC): 0.993—than procalcitonin (AUC: 0.844), C-reactive protein (AUC: 0.791), soluble CD14 subtype (AUC: 0.832), and interleukin-6 (AUC: 0.898) as assessed by receiver operating characteristic (ROC) analysis. Moreover, plasma levels of MG in non-survivors were significantly higher than in survivors (sepsis onset: *P = 0.018 for 90-day survival; **P = 0.008 for 28-day survival). Plasma levels of MG proved to be an early predictor for survival in patients with septic shock (sepsis onset: ROC-AUC 0.710 for 28-day survival; ROC-AUC 0.686 for 90-day survival). MG was identified as a marker for monitoring the onset, development, and remission of sepsis and was found to be more useful than routine diagnostic markers. Further studies are required to determine the extent of MG modification in sepsis and whether targeting this pathway could be therapeutically beneficial to the patient. German Clinical Trials Register DRKS00000505 . Registered 8 November 2010.

Only limited data exist investigating the outcome of patients older than 75 years after resection of colorectal liver metastases (CLM). Therefore, the present study aims to evaluate clinical and oncological outcome of elderly patients.A cohort of 405 patients was divided into three age-groups: (1)65 years; (2) 65-75 years; and (3)75 years of age. Patients' data were prospectively collected and retrospectively analyzed. We performed survival analysis and added age-correction. Univariate and multivariate analysis was performed to determine independent prognostic risk factors.The 5-year survival rate of the75 years age-group was distinctly decreased, compared to the other age-groups. After age-correction, the 5-year survival rates and the survival curves increased to the greatest extent in patients older than 75 years. The MSKCC score proved to be a sufficient independent prognostic factor in the total patient cohort, patients65 years and patients 65-75 years. In patients older than 75 years, only localization of the primary tumors was a significant prognostic factor for overall survival.Patients' age is no reason to deny surgical treatment of CLM. Prognostic factors, such as MSKCC score, are not sufficient predictors of survival in patients older than 75 years.

Trotz optimierter chirurgischer Technik und multimodalen Therapiekonzepten mit einer deutlichen Senkung der Lokalrezidivrate stellen Lokalrezidive des Rektumkarzinoms weiterhin eine therapeutische Herausforderung dar. Eine Kuration ist nur durch eine vollstandige Resektion moglich, wobei der Eingriff mit einer signifikanten Morbiditat assoziiert ist. Ob durch die Anwendung multimodaler Therapiekonzepte die Prognose dieser Patienten verbessert werden kann, ist formal nicht belegt, aber wahrscheinlich. Auch die palliative Resektion von Lokalrezidiven ist moglicherweise sinnvoll. Eine Alternative hierzu stellt die perkutane Bestrahlung dar. Der Stellenwert alternativer Therapieverfahren, z.B. Hyperthermie oder isolierte Beckenperfusion, in dieser Situation muss in weiteren Studien definiert werden. Das Hauptaugenmerk sollte aber auf der Vermeidung von Lokalrezidiven durch eine adaquate Primartherapie von Rektumkarzinomen liegen.

The overexpression of ErbB2 in pancreatic cancer has been reported with a varying incidence ranging between 1 and 80%. Our routine examination, however, revealed a consistently strong immunoreactivity of three anti-ErbB2 growth factor receptor antibodies in pancreatic islets and intrapancreatic ganglia. To validate our findings and to understand the reasons for the reported differences in the frequency of ErbB2 overexpression in pancreatic cancer, the following studies were performed.Tissue samples from 12 normal pancreata, 7 surgical chronic pancreatitis cases, 21 primary pancreatic adenocarcinomas, 9 metastatic pancreatic adenocarcinomas, and 4 islet cell tumors were subjected to immunohistochemical examination using antibodies from three manufacturers. Cultured human islet cells and pancreatic cancer cell lines, as well as samples from the gastrointestinal tract, the CNS, and the adrenal gland were included in the study. For comparison, mammary cancer tissue and mammary cancer cells, as well as selected tissues from Syrian golden hamsters, were used. To verify the results, Western blot and Northern slot-blot analyses were performed.Pancreatic cancer cells, in vitro and in vivo, showed a remarkable heterogeneity in the immunostaining of ErbB2, ranging from very faintly to strongly stained. On the other hand, in both humans and hamsters, a consistently strong immunostaining was found in the Langerhans' islets, in the ganglia of intrapancreatic and extrapancreatic nerves, as well as in the CNS, spinal cord and adrenal gland.ErbB2 appears to play an important role in neuroendocrine tissues and is probably involved in the development and functional regulation of these cells. The concomitant expression of these factors and islet cell hormones very likely results in the activation of multiple growth-promoting pathways in pancreatic cancer and its aggressive behavior.