Abstracts DGCH

s – DGCH Annual Congress 2019 – Munich, March 26–29 • DOI 10.1515/iss-2019-2002 s206 Innov Surg Sci 2019; 4, (Suppl 1): s206–s307

Subgroup composition had no effect on completion time improvement. There were significant differences in the training results among subgroups divided by the number of errors, men (p=0,001), women (p= 0,001) and number of changes between hands, men (p<0,001), women (p=0,002). Moreover, the execution of cognitive exhausting tasks prior to training was significantly beneficial, men (p=0,019), women (p=0,043). Female participants who watched their team partner complete the task, advanced significantly more than females who had no interest in their teammate's work. (p=0,017). Male participants with a strong subjective spatial sense had a significantly better completion time improvement (p=0,013). Supporting the team member in the all-male teams or mixed gender teams also proved to be of significance (p=0,014).

Conclusion:
A clear impact of team composition could not be found. However, there are influences that need to be considered when constructing a MIS-training. It is a valuable addition to surgical curricula and should be incorporated in already existing surgical programs. It seems reasonable to give a short lecture of instructions on technique and teamwork before starting the training. In addition, giving participants a clear framework as well as encouraging mutual support during sessions will improve the trainees' performance. Abstracts -DGCH Annual Congress 2019-Munich, March 26-29 • DOI 10.1515/iss-2019-2002 s209 Innov Surg Sci 2019; 4, (Suppl 1): s206-s307 Serious Games enable the simulation of daily working practices and constitute a potential tool for teaching both declarative and procedural knowledge. The availability of educational Serious Games offering a high-fidelity, three-dimensional environment in combination with profound medical background is limited, and most published studies have assessed student satisfaction rather than learning outcome as a function of game use.

Serious Games in surgical medical education: A virtual Emergency department as a Tool for Teaching Clinical Reasoning in Surgery
It was our aim to test the effect of a Serious Game simulating an accident & emergency department ("EMERGE") on students' declarative and procedural knowledge as well as their satisfaction with the serious game.

Materials and methods:
140 medical students in the clinical part of their training (5th Semester to PJ (practical year)) selfselected to participate in an experimental study. Declarative knowledge (measured with 20 multiple choice questions) and procedural knowledge (measured with written questions derived from an OSCE station) were assessed before and after working with EMERGE. Students' impression of the effectiveness and applicability of EMERGE were measured on a 6-point Likert scale.

Results:
A pre-post comparison yielded a significant increase in declarative and procedural knowledge. The effect on declarative knowledge was larger in students in earlier years of education than in students of higher semesters. Additionally, students' overall impression of EMERGE was positive.

Conclusion:
The current study reveals that working with a Serious Game, such as EMERGE, has a positive effect on declarative and procedural gain and can may be used as an additional tool for teaching medical students. Future studies should investigate what specific aspects of playing EMERGE lead to the reported effects. Research is increasingly being conducted towards the potential of Virtual Reality (VR) technology as a tool in education at schools and universities. In this context, we developed a prototype of a virtual anatomy atlas for surgical anatomical training and further education. The aim of this study was to evaluate the difference in learning outcome between this digital teaching medium and a conventional "open book" method (OB) in randomized students of the 11th grade of two German high schools under exam conditions.

Materials and methods:
A total of 28 students divided into two Groups were asked nine anatomy questions. One group used conventional anatomy books and charts to answer the questions below. The other group used the VR Anatomy Atlas.
How many lobes does the right lung have? What is the structure between stomach and lungs? Name the annular muscle that surrounds the eye Name the Latin term of the kneecap Name the nerve structure connecting the brain to the spinal cord How many muscles are in direct contact with the femur? How many parts does the calf muscle consist of? Where is the thyroid gland? In front of or behind the windpipe? What is the right temporal muscle (in German: "Schläfenmuskel") called in Latin? Sketch the Achilles tendon in proportion to the leg To measure the success for each learning method, the error rate, the processing speed for the individual questions (stratified for school affiliation), the satisfaction with the teaching unit and the existence of a medical career wish were evaluated.

Results:
The error rate was the same for both schools and between both teaching aids (VR: 34.2%; OB: 34.1%). The answering speed for correctly answered questions in the OB group was approx. twice as high as for the VR group (mean value OB: 98sec, range: 2-410sec; VR: 50sec, 1-290sec). There was also a significant difference between the students of the two schools based on a longer processing time in the OB condition in School B (mean OB in School A: 158sec; OB in School B: 77sec). The subjective survey on the learning methods showed a significantly better school grade for VR (p = .012). Medical career aspirations have been strengthened with VR, while interest in the OB group has tended to decline.

Conclusion:
We conclude that the immersive anatomy atlas helped the subjects to actively and intuitively perform targeted actions that led to correct answers even without prior knowledge of VR and anatomy. With the OB method, orientation difficulties and/or the technical effort in the handling of the topographical anatomy atlas generally seem to lead to a significantly longer response time, especially if the students are not specially trained in literature research in books or texts. This seems to indicate that the VR environment in the sense of constructivist learning might be a more intuitive and easier to use learning environment than the more traditional acquisition of knowledge from books. During the clinical internships of medical students, students are regularly placed in the operating theatre. A structured curriculum for intraoperative clinical training is not available at most hospitals and university clinics. Clinical skills are taught either situatively or in clinical training centres outside the operating theatre. Nevertheless, the students spend a substantial part of their internship in the operating theatre and are part of the surgical team. Here they can gain insights into surgical procedures and techniques and refresh their anatomical knowledge, but curricular training by the surgeon usually does not take place or takes place very individually. We are not aware of any studies on the additional stress situation of the surgeon due to structured intraoperative training. This study is intended to compare the workload of surgeons with and without structured intraoperative teaching. In addition, quality and success of intraoperative clinical teaching are evaluated from the students' point of view.

Materials and methods:
The prospective randomized study was initiated after a positive ethics vote. Over a period of 9 months, either thyroid gland resection, laparoscopic cholecystectomy (CHE) or inguinal hernia surgery (TEP) was performed on n=90 patients, where a medical student was present in the operating theatre. Group A (n=43) received an intraoperatively structured teaching and group B (n=37) operated only the instruments required for situs control. Biometric data of the patients, the surgeons, type and extent as well as intraoperative peculiarities of the performed operation were recorded and documented by a study nurse. For the surgeons, there was no obligation intraoperatively to carry out the teaching units and they were also able to end the teaching unit in stress situations. After the operation, the subjective workload of the surgeons in the operating room was evaluated by the NASA-TLX Score as well as the teaching quality from the student's point of view.

Results:
For the operations recorded, the average duration of the teaching-related OP conversations in group A was 7.5 minutes. (range: 0 -26min). In group B, the duration of intraoperative communication was 3.3 minutes (range: 0 -23min). In group A there was a significantly longer operation time for the lap. CHE and TEP (CHE= 49 min group B vs. 78 min group A; TEP: 40 min vs. 54 min). For thyroid gland resections, no influence on the cut/suture time could be found (82 vs. 81 min). The workplace exposure measured with the NASA-TLX was higher in the dimensions "mental, physical and temporal demands", as well as in the estimated "effort" and "frustration" in group A than in group B. (Fig. 1).

Conclusion:
Structured intraoperative teaching increases the workload of the surgeon and also prolongs the operation time. This effect of intraoperative teaching seems to be particularly important in minimally invasive surgery. Larger studies should validate these observations and, if necessary, develop preand postoperative training concepts to reduce the intraoperative burden on the surgeons. The influence of intraoperative teaching on patient safety is unclear. Physicians not only need medical knowledge but also scientific competences to be able to find the best treatments for their patients at all times. However, curricula for medical studies in Germany often focus very little on the training of scientific skills with the doctoral thesis usually being the only scientific project during the course of medical studies. We are aiming to improve the scientific expertise of medical students with a structured program for obtaining a medical doctoral degree in the Department of Surgery at the University Hospital Heidelberg.

Materials and methods:
The doctoral program supports students of medicine and dental medicine during their doctoral thesis work in the Department of Surgery with a structured curriculum. All participants regularly take part in Journal Clubs and workgroup meetings to promote scientific exchange among students and their supervisors. Furthermore, participation in a seminar of good scientific practice and in a scientific conference is compulsory for all students. Further courses (experimental techniques, statistical analysis, animal handling, scientific writing, etc.) must be chosen according to interests and specific needs of the doctoral thesis project. To help with successful planning of the project, to give additional scientific advice, and to encourage critical discussions about the project, a thesis advisory committee, consisting of the project supervisor and two additional researchers, accompanies every student during the work on his doctoral thesis. Students register for participation in the doctoral program at the beginning of their research work. During the registration process, students are asked about the general frameworks of their doctoral thesis, such as planned total duration, amount of time dedicated to full-time research work or motivation for joining the doctoral program, and the answers are analyzed.

Results:
Between October 2016 and September 2018 85 students registered for participation in the structured doctoral program. The participants expect an average duration of research work of 17 ± 6 months (mean ± SD) until completion of their doctoral thesis. Most participants choose experimental research projects (61%), followed by clinical research projects (21%). Research projects in the field of medical education were chosen by 11% of students, followed by projects in the field of minimally invasive surgery (7%). 39% of registered students plan to make use of the possibility to interrupt their medical studies for one semester to be able to work on their research project for 6 months full-time. 56% are willing to work more than 6 months full-time, therefore pausing their studies for more than one semester. Only 5% of participants enrolled in the doctoral program exclusively work part-time or less than one semester full-time for their doctoral degree. Students name "Access to training workshops" and "Scientific exchange" as the main reasons for registering to the doctoral program.

Conclusion:
A structured doctoral program attracts mostly enthusiastic students with ambitious research plans. Further follow-up is needed to determine if participating students benefit from a better performance during their doctoral thesis, e.g. determined by publication success or results from doctoral thesis evaluations.

Background:
Evidence should define and guide modern clinical care, yet many relevant questions in surgical practice remain unconfirmed by data. Meaningful clinical research however is challenging to conduct and its overall infrastructure in Germany was -until recently -considered poor as compared to other leading countries. While this has been significantly improved following the establishment of the Studienzentrum der Deutschen Gesellschaft für Chirurgie (SDGC) and the surgical clinical trial network CHIR-Net, limited focus has been put on training and recruitment of medical students to become competent clinician scientists.

Materials and methods:
To address these challenges, the CHIR-Net has established a student-initiated clinical trial network (SIMGA; Student-Initiated German Medical Audit) in 2017. Inspired by initiatives from the United Kingdom, this network enables students to participate in academic research projects and serves as exchange platform between students and physicians. As part of the SIGMA network, students contribute to national multi-center trials while improving clinical and research skills and gaining an insight into clinical academia. PATRONUS (Multicenter prospective cohort study of PATient-Reported Outcomes and complications following major abdominal Neoplastic Surgery) is the first SIGMAinitiated project and the first-ever student-lead clinical trial in Germany.

Results:
SIGMA achieved the following objectives: -Creation of a national multicenter network of medical students and associated clinician scientists (n=15 established centers) -Training of medical students in methodology, regulatory affairs and ethical conduct (SIGMA Prüfstudierendenkurs, n=32 trained participants).
-Design, initiation, conduction, analysis and publication of prospective multicenter clinical trials initiated by medical students (PATRONUS, n=351 recruited patients)

Conclusion:
SIGMA is a product of strong collaboration between clinical scientists and medical trainees, enabling students to contribute to high-quality clinical trials. Additionally, participants are offered extensive training to support the next generation of research-active clinicians. PATRONUS is the first-ever student-lead clinical trial in Germany and successfully recruited 351 patients. Preliminary data of patient follow-up will be available by early 2019. The arrival of robotic assisted surgery in the treatment of morbidly obese patients has enlarged the armamentarium for surgeons involved in bariatric surgery.
While the implementation of the technique has faced many hospitals with increasing costs and training the advantages of the technical development have been demonstrated in several recent studies. Three dimensional optical view and the endowrist technique are two main features of the system facilitating the surgeons capability in intraabdominal dissection and suturing and increasing the exposition of the operational field due to the instrument holding arms and a third hand for the console surgeon.
This in particular is of great advantage not only in primary cases but also in patients undergoing revisional procedures following preceeding upper GI surgery.
Aim: In the following the experience with revisional surgery using the Da Vinci robotic system will be reported and compared to conventional laparoscopic treatment and the literature.

Materials and methods:
Patients and methods: In a 12 months period a total of 59 minimally invasive bariatric procedures (20 robotic assisted, 39 laparoscopic) were performed. 14 patients received a gastric bypass, 31 a gastric sleeve and in 14 patients a band was removed or adhesions were resected without an alternative procedure. Out of the 14 GBP procedures 8 (58%) were performed robotic. Out of these 4 (50%) had previous operations 1 hiatal mesh repair, 1 open Mason operation, 1 gastric band, 1 gastric sleeve. The Da Vinci Xi was used for the surgery.

Results:
Results: All these patients resumed oral nutrition on day 2 post OP and were discharged from the hospital 4,4,4, and 7 (pneumonia) days post OP. No patient had to be reoperated. The average operating time was 194,5 min (142-228) vs 290,2 min (154-480) of the remaining.

Conclusion:
Conclusion: This preliminary experience suggests that robotic revisional surgery can be performed safely even in complicated cases and with a short learning curve. Abstracts -DGCH Annual Congress 2019-Munich, March 26-29 • DOI 10.1515/iss-2019-2002 s219 Innov Surg Sci 2019; 4, (Suppl 1): s206-s307 Telephone call management systems: Is an intelligent operating room system able to reduce unnecessary stress factors during an operation? (Abstract ID: 511)

Klinikum Rechts der Isar der TU München
Background: Mobile phones increase reachability of a surgeon and improve patient's care. But interruptions of the surgical workflow in the OR due to incoming calls influence the surgeon's concentration and therefore have a negative impact on patient safety.We evaluated if a cognitive OR system could be used for a situation-adapted preselection of incoming calls for the surgical team.

Materials and methods:
46 volunteers were confronted with three call type scenarios of different urgency in combination with different OR situations and time lines. Tree different types of caller scenarios with a graded importance for patient care were given. For each call type scenario the callers were informed about the approximate remaining operating time (60, 30 or 15 minutes) and the current situation in the OR (normal, irregular, critical).

Results:
For minor inquiries only 1% of all participants confirmed to forward the call, for major inquiries, 7% of all calls were routed to the surgeon. For vital inquiries 78% of all test persons opted for a forwarding. With a remaining operating time of 15 minutes, only 37% of the participants decided to be forwarded in case of a vital inquiry. Results did not show a correlation between increasing message severity for different OR situations (normal, irregular, critical) and the percentage of calls being forwarded.

Conclusion:
Results indicate a statistically significant correlation between the importance of the call and the number of calls being forwarded. Emergency calls are largely transmitted by the system while less important calls are blocked. The different OR situations had no clear influence on the percentage of forwarded calls.

Universitätsspital Bern
Background: Specialized surgical teams have been shown to improve outcomes in multiple elective patient populations. Starting in the USA ten years ago, Acute Care Surgery (ACS) is currently evolving worldwide. ACS focusses on patients with acute surgical disease, including traumatic and nontraumatic emergencies. At an academic, tertiary referral center, an ACS service has been established in 2016. Here we report our experience two years after the implementation of the ACS service.

Materials and methods:
Retrospective descriptive analysis of a prospectively collected database including all patients that underwent emergency abdominal surgery 01/2016-12/2017.

Results:
During the 2-year study period, a total of 1106 patients underwent emergency abdominal surgery. Of these, 79.3% were admissions to the Emergency Department (ED) and 20.7% were already hospitalized for other diseases. Overall, 65.7% of the patients were admitted from home and 27.1% from other hospitals. Median age was 57.0 years (IQR 31). Most frequent indications for surgery were appendicitis (17.0%), diseases of the colon (14.0%), diseases of the gallbladder (12.6%), hollowviscus perforations (10.7%), small bowel obstruction (7.0%), bleeding (4.4%), and mesenteric ischemia (3.6%). Admission to the Intensive Care Unit (ICU) was required in 28.4% and 33.5% were admitted to the Intermediate Care Unit. In-hospital mortality was 6.7% and median length of stay 7.0 days (IQR 14).

Conclusion:
During the first two years after the establishment of an ACS service, surgery has been performed for multiple abdominal emergencies, both in patients admitted from home and patients that were already hospitalized. The ICU admission rate of 28.4% reflects the high grade of physiologic derangement in ACS patients. In times of increasing subspecialization, dedicated ACS services with broad knowledge and skills in the management of patients with acute surgical disease may provide high-quality of care in this patient population with extensive treatment needs. Aim of the study is to assess the views, knowledge, and experience of Dutch physicians with regard to the general objectives and values of the pay-for-performance (P4P) system, as the Dutch healthcare industry might find it useful, in terms of governance and health economy, to explore this approach further, compared to the standard DRG system.

Materials and methods:
A quantitative cross-sectional survey study was conducted among 48 physicians in surgical specialties in the Netherlands between May 2014 and July 2014. The survey questionnaire was designed to gather information regarding the intensity of feelings, on a 7-point Likert scale, toward statements that address the P4P system. Confidence intervals were calculated using the bootstrap technique with 1000 iterations.

Results:
Physicians see a positive value in P4P for their organizations rather than for personal attainment (mean = 5.00; 95% CI = 4.62-5.39), even though they feared that P4P might put financial pressure on them (mean = 5.03; 95% CI = 4.50-5.54). They strongly share the view that other colleagues will resist adopting P4P as a business model (mean = 5.74; 95% CI = 5.43-6.04). Respondents stated that they would not leave their current jobs if P4P were to be incorporated in their organization.

Conclusion:
Physicians see value in P4P for their organizations, and consider that P4P could provide an incentive for improving medical outcomes compared to the standard DRG system. There seems to be potential for the P4P system as participants expressed positive support for its values. There is an intersection of interests between the value of P4P and the physicians' aim of achieving quality outcomes; however, further studies would be needed to investigate perceptions about specific design features in a larger sample. In addition, prior to implementing P4P, broad education about the system should be provided in order to counteract pre-conceptions and prevent resistance.

Background:
Remote Ischemic Conditioning (RIC) is a non-invasive method of tissue conditioning. Over the last years it has been demonstrated as a promising technique to render tissues and organs resilient against prolonged ischemic events and the ischemia/reperfusion injury in a variety of surgical fields. Furthermore, RIC has been shown to improve cutaneous microcirculation of e.g. free or pedicle fasciocutaneous and myo-cutaneous flaps. Through its remote mode of action there are no anatomical barriers or limitations between the conditioning site (e.g. upper limb) and the target organ (e.g. free flap transplanted to the lower limb).
The aim of our prospective clinical study was further optimization of the RIC technique with regard to its effect on cutaneous microcirculation. We focused on the impact of a different number of applied conditioning cycles as well as the duration of changes.

Materials and methods:
In a prospective randomized clinical study perfusion changes as a result of the RIC treatment were investigated in 80 young, healthy subjects. The RIC stimulus as applied at the upper limb through inflation/deflation of a surgical tourniquet. One RIC cycle consisted of 10 minutes of ischemia followed by 10 minutes of reperfusion. The applicated number of cycles was 1, 3, 5 or 7, respectively. Cutaneous microcirculation was assessed continuously at the antero-lateral thigh. Combined laserdoppler flowmetry and white-light spectroscopy was used to analyze cutaneous blood flow, tissue oxygen saturation and relative hemoglobin content during the conditioning. Measurements were continued for 4h after the last applied cycle to assess the duration of microcirculatory changes.

Results:
RIC caused significant (p<0.05) changes of superficial and deep cutaneous microcirculation. Tissue oxygen saturation increased due to an improved blood flow. Group II with application of 3 cycles showed most pronounced changes whereas a higher number of cycles did not lead to a further increase of measured parameters. Overall, changes were more pronounced in superficial layers than in the deep subdermal level. Sustainable (p<0.05) microcirculatory improvement was present for at least two to four hours after the RIC stimulus.

Conclusion:
RIC is a simple non-invasive technique to enhance cutaneous microcirculation. Due to its remote character application is safe, because tissues at risk are not directly subjected to certain ischemic events. A conditioning protocol of 3 cycles, each consisting of an interval of 10 minutes of ischemia followed by 10 minutes of reperfusion, appears most reasonable with regard to its beneficial effect on cutaneous microcirculation.

Background:
A colorectal anastomotic leakage (CAL) is a major complication after colorectal surgery and leads to high rates of morbidity and prolonged hospital stay. The study aims to evaluate the benefit of using bilirubin, urobilinogen, pancreas elastase and bile acid in the drain fluid (DF) as a predictive marker for the CAL.

Materials and methods:
From June 2015 to October 2017 100 patients, who underwent left hemicolectomy (LH), sigma resection (SR), high anterior resection (HAR), low anterior resection (LAR) or reversal of Hartmann´s Procedure (ROHP) were included in this monocentric non-randomized prospective clinical trial. During the first four postoperative days (POD) the concentration of bilirubin, urobilinogen, pancreas elastase and bile acid in the DF was measured.

Results:
In total 100 patients were recruited. 17 were excluded due to intraoperative decisions to conduct a protective stoma. 6 patients had a CAL. The patients of the control group (n=77) and the patients who suffered from a CAL (n=6) had no increased concentration of urobilinogen and pancreas elastase in the DF. The concentration of bile acid in the DF of the patients who suffered from a CAL differed from those of the control group on the 4th POD (p=0.055).The concentration of bilirubin in the DF of the patients who suffered from a CAL significantly differed from those of the control group on the 1st POD (p=0.031) and on the 3rd POD (p=0.041).

Conclusion:
Bilirubin and bile acid in the DF may function as a predictive marker for a CAL. Hair has been accused as the causative agent of pilonidal sinus disease (PSD). A great amount of hair can be found in pilonidal sinus cavities. Astonishingly, macroscopic and microscopic examinations of hair found inside pilonidal sinus cavities have been scarce. The purpose of this study was to examine the morphological aspects of the hair found in PSD in order to determine the origin of the hair.

Materials and methods:
Occipital, lumbar and intergluteal hair was harvested from 20 PSD-Patients and 20 volunteer matched pair patients. Hair from inside pilonidal sinus cavities was collected intraoperatively from the 20 Pilonidal sinus patients, differentiating between the hair sticking inside the pores and the hair found deeply inside the cavities. Numbers and lengths were recorded and intra and intergroup variations of hair length were characterized using analysis of variance. The hair was examined macroscopically and microscopically using light and scanning electron microscopy with gold an carbon dust coating techniques, thus reaching an enlargement of 1000 times.

Results:
The analysis of 624 pilonidal sinus nest hairs found in the 20 sinus cavities reveales rootlessness in 74%. Body hair shows roots on one end. The hair found inside the cavities was significantly shorter than the hair from the other examined body regions (length 0,9±0,7 cm p < 0,0001). Furthermore the hair found inside the cavities was significantly shorter than the hair protruding from pores (p < 0,0001). Microscopic examination shows razor sharp hair ends inside the sinus cavitites. Comparing electron microscopy, these spikey hair end resemble cur hair ends. Overall, the pilonidal hair nest contains between 1 and over 400 hair fragments.

Conclusion:
Short hair fragments were found within pilonidal sinus cavities. Moprhologically, these fragments resemble short cut hair rather than intact body hair. These fragments seem so be more capable of entering a pilonidal sinus cavity than longer body hair. The source of these hair fragments has to be eliminated when aiming to prevent pilonidal sinus disease.

Klinikum der LMU München
Background: Distant metastases frequently occur in gastroenteropancreatic neuroendocrine tumors. If hepatic surgery is not feasible, patients are treated with somatostatin analogs. However, the underlying mechanisms of action of this treatment remain to be defined. The aim of the present study was to analyze the micro-RNA expression profile intra-individually before and after the treatment with somatostatin analogs.

Materials and methods:
Tumor specimens of all included patients (n=8) before and after the onset of a therapy with somatostatin analogs were analyzed and a micro-RNA expression profile (754 micro-RNAs) of each probe was generated. This analysis in an intra-individual setting was selected to avoid bias from interindividual differences. The micro-RNA expression profiles were validated by qPCR. Patients with any other systemic treatment were excluded from the present study.

Results:
Eight patients were included in the present study of which all had neuroendocrine tumors of the small intestine with diffuse hepatic metastases. Grouped analyses revealed that 15 micro-RNAs were differentially expressed (3 up-and 12 downregulated) after the exposure to somatostatin analogs. Additionally, let-7c-5p and mir-3137 are concordantly regulated in the intra-individual analysis.

Conclusion:
This is the first study analyzing the individual micro-RNA expression profile before and after a therapy with somatostatin analogs. Data from this study reveal that somatostatin analogs may in part exert their beneficial effects through an alteration in the micro-RNA expression profile. Resistance to drug and radiation treatment limits current therapies for oesophageal adenocarcinoma (EAC). The TP53 gene is mutated in 80% of EACs, and given the central role of p53 in controling cellular response to therapy, we study the impact of mutant p53 on EAC response to cytotoxic agents. We previously demonstrated that knockout of mutant p53 can result in increased radiation and drug resistance in EAC cells. In another study we reported that the expression of SLC7A11, a component of the redox maintenance system xC-, is suppressed by mutant p53 and this increases susceptibility to oxidative damage. In this current study we sought to investigate the role of SLC7A11 in mediating the increased radiation resistance seen in mutant p53 knockout vs mutant p53 carrying EAC cells.

Materials and methods:
We used the JH-EsoAd1 cell line, which has a missense c797G>A mutation in TP53 resulting in an amino acid change of G266E. The IARC transactivation classification for this mutation is "nonfunctional". Three CRISPR-mediated TP53 knockout (KO) JH-EsoAd1 clones, and three control parental lines retaining endogenous mut-p53 (parental polyclonal, parental clonal and Cas9 only) were treated. Radiation sensitivity (2Gy) was determined by a clonogenic survival assay. Baseline SLC7A11 expression in parental lines as well as the clones was determined by Western Blot. For transfection experiments, cells were transfected with SLC7A11 siRNA and knockdown of SLC7A11 was confirmed by Western Blot.

Conclusion:
The current data show that inhibition of SLC7A11 can restore radiosensitivity in p53 null cells, most likely via enhanced sensitivity to oxidative stress. Further studies are required to identify the exact mechanisms underlying the increased sensitivity to ionising radiation following SLC7A11 knockdown in order to develop new therapeutic opportunities to target this amino acid transporter for cancer treatment. Furthermore, the results provide promising starting points for a better understanding of the important role of SLC7A11 in cancer metabolism and redox balance and the influence of p53 on these processes.

Background:
The mechanistic target of rapamycin (mTOR) is known as a key modulator of ageing and age-related disease. The aim of the present study was to discover a potential new regulatory mechanism involved in mTOR related ageing. As microRNAs (miRNAs) are naturally occurring non-coding regulatory molecules and key control elements of crucial regulatory pathways, we aimed to identify a specific miRNA regulating mTOR in an age-dependant mode.

Materials and methods:
MTOR and miRNA expression were studied in young (average age 22, n = 40) and old blood donors (average age 78, n = 40) applying qRT PCR and ELISA. Various computer software programmes were employed to identify a specific miRNA that potentially interacts with mTOR. Functional implications of miRNAs with the 3'UTR of mTOR were analyzed by a Luciferase assay system. Accordingly, cell line HELA K was transfected with miRNA mimics and gene and protein expression of mTOR was monitored using qRT PCR and Western blot analysis.

Results:
MTOR protein expression was significantly down-regulated in an old cohorte of blood donors with respect to a young cohorte (P < 0.05). Hence, a specific miRNA, miR-496, was identified by target prediction programmes to potentially interact with mTOR and subsequently shown to be significantly up-regulated in the old cohorte with respect to the young cohorte (P < 0.05). Accordingly, miR-496 was demonstrated to functionally interact with mTOR. Thus, addition of miR-496 led to significant down-regulation of luciferase activity (P < 0.05) and mTOR expression after transfection of HELA K cells with the respective miRNA mimics (P < 0.05). Further, functional effects on mTOR downstream activity related to miR-496 were demonstrated.

Conclusion:
We have demonstrated an age-related aberrant and inverse expression pattern of mTOR and miR-496 in an old cohorte of blood donors with respect to a young cohort. Moreover, this miRNA was shown to regulate mTOR expression in vitro and to affect mTOR downstream activity. Together, these results strongly indicate that regulation of mTOR expression by miR-496 is a new regulatory mechanism involved in ageing.

Background:
Mechanistic target of rapamycin (mTOR) regulates lipid and glucose metabolism thus playing a key role in metabolic diseases like type 2 diabetes mellitus (T2DM). Recently, we demonstrated a functional interaction of miRNA-496 (miR-496) with mTOR and its impact on the regulation of human ageing. As T2DM is most prevalent in older adults, we hypothesized that miR-496 may also have an impact on mTOR regulation in T2DM.

Materials and methods:
Based on real time PCR and enzyme-linked immunosorbent assay (ELISA) mTOR gene and protein expression as well as miR-496 expression was monitored in Peripheral Blood Mononuclear Cells (PBMC) from T2DM patients (median age: 71) and healthy age-and BMI matched controls (median age: 69). Further the mTOR protein-and miR-496 expression was determined in T2DM patients with different degrees of obesity.

Results:
Our data indicate miR-496 involvement in the regulation of T2DM through the control of mTOR. We further demonstrate that this interaction may be dependent on the patient's body mass index with significantly elevated mTOR activity reflecting the progression of the underlying obesity disorder.

Conclusion:
Monitoring mTOR expression may be considered as a marker for T2DM development and the progression of obesity. As mTOR up-regulation caused by obesity maintains circulating fatty acids within the physiological range, the BMI-dependent mTOR up-regulation may be considered as a compensatory mechanism to protect the body from metabolic harm.
Origin: Rubie C. et al.: mTOR and microRNA 496 are associated with type 2 diabetes mellitus and obesity in eldery people. ANM 2019.

Lungenklinik Löwenstein
Background: The surgical resection of pulmonary metastases (PM) is associated with a survival benefit in selected patients. The use of laser-assisted surgery (LAS) for PM has been shown in a variety of retrospective studies to facilitate the complete resection, especially for higher number of metastases, while preserving a maximum of healthy parenchyma. This is the first prospective study to evaluate perioperative surgical, oncologic and clinical parameters including the changes of lung function after LAS.

Materials and methods:
This is an interim-analysis of a prospective, bicentric, single-arm trial. So far we analyzed 78 operations in which PM was carried out in curative intent. A 1.320 nm diode-pumped Nd: YAG-Laser was used for resection of the metastases. Surgical and clinical data were collected using a standardized form and postoperative lung function changes after 3 and 6 months were assessed using whole body plethysmography and diffusion capacity for carbon monoxide (DLCO).

Results:
Median operative time was 129 minutes (range, 55-334 minutes) and a median of 3 metastases were resected per operation (range 1-23). The median duration of postoperative air leak was 1 day (range 0-11 days), and median length of hospital stay was 8 days (range, 4-15 days). LAS associated, postoperative minor complications were observed in 7 (9%) cases and there were no mortalities. The analysis of perioperative lung function showed that mean FEV1 3 months after surgery was reduced by 13% (p<0.0001) and DLCO by 14% (p=0.001) respectively. There was no relevant regeneration of lung function at 6 months. Decline of DLCO correlated with the number of resected metastases (r=0.48, p=0.01). All metastases were radiologically measured for distance to pleural surface and size. Adding up diameter and distance to pleural surface there was a positive correlation to the changes of the residual volume at 3 months (r=0.52, p=0.04).

Conclusion:
We present excellent results after LAS even in high numbers of metastases with short duration of postoperative air leak and little morbidity. Number, size and depth of the metastases affect lung function changes after resection, particularly diffusion capacity and residual volume.

Background:
Introduction. Molecular and biological differences in primary tumors of metastasized colorectal cancer (CRC) have been shown to be associated with metastatic route. In this respect, increased expression of tumor stem cell markers and differences in miRNA expression profiles (i.e. miRNA 31 affecting EMT via c-Met) are present in CRC with hepatic vs. peritoneal metastases. Aim of the present study was to further elucidate the underlying mechanisms for the above observations by investigating gene expression patterns of primary CRC with liver vs. peritoneal metastases.

Materials and methods:
Material and Methods. CRC with (A) hepatic metastases (n=10), (B) peritoneal metastases (n=10) and (C) locally advanced CRC without metastases for 5 years (n=10) was analyzed. RNA of the primary tumors was isolated by microdissection from the pathological specimens. A NanoString analysis (nCounter® PanCancer Progression Panel) of 770 genes was performed. Gene expression was analyzed by conducting univariate analysis using the Chi-square test; p-values less than 0.05 were considered significant.

Results:
Results. Genes are significantly differentially expressed depending on the metastatic pattern. Patients of group A had 26 differentially expressed genes, mainly associated with epithelial-mesenchymal transition (EMT) and angiogenesis, compared to group C. Patients of group B had 18 differentially expressed genes compared to group C. In contrast to group A, EMT associated genes were downregulated in group B. Moreover, angiogenesis associated genes did not play a pivotal role in group B.

Conclusion:
Discussion. For the first time it was shown that CRC leading to hepatic or peritoneal metastases exerts a difference in gene expression. An upregulation of genes associated with EMT or angiogenesis was found in CRC with hematogenous spread to the liver. However, a downregulation of EMT associated genes was seen in CRC with peritoneal carcinomatosis. These findings suggest that differences in the gene signature of the primary tumor trigger and direct the metastatic route of CRC.

Background:
The prevalence of age-related diseases like osteoporosis and sarcopenia is increasing. While bone loss is commonly treated, sarcopenia is often neglected. However targeting sarcopenia is especially important after an osteoporotic fracture as bone healing causes further muscle atrophy through inactivity.
Low sex hormone concentrations are among the key reasons for sarcopenia and muscle weakness. Hormone replacement therapy (HRT) with estrogen or testosterone has been shown to increase muscle mass and function. HRT however can lead to side effects especially on the cardiovascular function. Selective estrogen and androgen receptor modulators (SERMs and SARMs) target similar hormone receptors and are thought to have fewer side effects than endogenous hormone substitution.
This study is focused on the effects of the SARM ostarine (OS) and/or the SERM raloxifene (RL) on skeletal muscle in an osteopenic rat model undergoing bone healing period.
OVX rats were divided into 4 groups, of 15 rats. Group 1 was left untreated (OVX). Group 2 received OS (OVX+OS). Group 3 was treated with RL (OVX+RL). Group 4 underwent combined treatment with OS and RL (OVX+OS+RL). The average daily doses were 0.6 mg/kg body weight (BW) for OS and 11 mg/kg BW for RL. Eight weeks following OVX, all rats underwent osteotomy of both tibia metaphysis with plate osteosynthesis. Treatments lasted up to 13 weeks after OVX and ended on extraction and weighing of the M. gastrocnemius, M. soleus, M. longissimus, and the uterus. The cross-sectional areas of glycolytic, intermediate, and oxidative fibers in muscles were measured. Cell-nuclei and capillary density were quantified. In serum creatine kinase activity was assessed.

Results:
At experiment onset, BW did not differ between groups, but had increased significantly at the end in the OVX+OS and OVX groups compared to all other groups. BW of OS rats was higher than that of OVX rats. The changes in muscle weight (MW) were similar to those in BW. MW was the highest in OS group. Compared to the OVX and OVX+RL groups, the NON-OVX, OVX+OS, and OVX+OS+RL groups had a significantly higher uterus weight.
Fiber size (FS) was larger in OVX and OVX+OS groups than in any other. The FS in OVX+RL and OVX+OS+RL groups was similar to that in the NON-OVX group.
Nucleus density was higher in the OVX+OS+RL group than in the NON-OVX group in the M. gastrocnemius. No differences between the groups were observed in other muscles. Capillary density increased in OVX+OS group in M. soleus and M. longissimus. In M. gastrocnemius, the NON-OVX group had the lowest capillary density.

Conclusion:
Abstracts The OS treatment alone increased BW, MW and capillarization, whereas FS remained at the level of OVX rats. Enhanced uterus weight after OS treatment alone and combined with RL suggests an androgen-like activity of OS in the uterus. This may be considered as unfavorable side effect. Rats under RL and OS+RL treatments demonstrated muscle structures similar to NON-OVX rats. RL treatment alone did not change uterus weight. Thus, RL treatment appears to be more favorable than OS or OS+RL for treating muscle tissue in estrogen-deficient individuals. Considering its current application in osteoporosis therapy, RL could be an alternative treatment for other musculoskeletal diseases, including post-fracture muscle loss.

Background:
High Resolution Respiratory has been shown as an effective tool to measure the mitochondrial respiration in striated muscle, as well as the measurement of citrate synthase activity (CSA) has been shown to give information of the amount of mitochondria in a tissue.
In patients with peripheral arterial disease it has been shown that the function and the amount of mitochondria depends on the blood supply measured by the HRR.
So far, there is no knowledge about the High Resolution Respiratory in the smooth muscle of the intestine.The investigation of the mitochondria in the smooth muscle of the intestine could be of great interest e.g. because the occurrence of anastomotic leakage is still a relevant complication in the colorectal surgery with poorly understood mechanism.

Materials and methods:
10 patients were included. The HRR and measurement of the CSA was performed with all samples. Some of them have been analysed with the TEM.

Results:
Through High Resolution Respirometry performed by using an Oxygraph-2k we were able to evaluate the mitochondrial respiration of the smooth muscle in the intestine. According to our findings of striated muscle in patients with peripheral arterial disease we observed similar results on a lower level, as expected due to the lower content of mitochondria in the smooth muscle. After correction for the CSA we could see similar ratios and proved that the HRR is transferable to smooth muscle tissue. Further evidence for the portability of smooth muscle we examine the Tunica muscularis of the intestine by transmission electron microscopy (TEM) and compared it with the results of straited muscle with similar results.

Conclusion:
By High Resolution Respirometry using an Oxygraph-2k we were able to measure the activity and amount of mitochondria of the smooth muscle in the intestine.
Thereby we established a new tool for further questions such as the function of mitochondria in reduced blood circulations in the intestine associated with anastomotic leakage.

Universitätsklinikum Hamburg Eppendorf
Background: Current modalities to predict tumor recurrence and survival in esophageal cancer are insufficient. Locoregional and distant relapse is even common in lymph node-negative patients and more precise staging methods are therefore needed. So far, only the CellSearch system was used to detect circulating tumor cells (CTC) in esophageal cancer patients. Studies analyzing different CTC detection assays using combined enrichment techniques to potentially increase the sensitivity are missing.

Materials and methods:
In this single-centre, prospective study, peripheral blood samples from 100 esophageal cancer patients were obtained preoperatively and analyzed for the presence of CTC by two distinct methods. A total of 90 cases have been evaluated for the presence of CTCs by MACS enrichment (anticytokeratin/ anti-Ep-Cam) with subsequent immunocytochemical staining and in parallel by the CellSearch method. Data were correlated with clinicopathological parameters and patient outcomes.

Results:
CTCs were detected in 25.6% (23/90) of patients by MACS enrichment/Ariol (0-150 CTCs/7.5ml) and in 17.8% (16/90)of patients (0-56 CTCs/7.5ml) using the CellSearch system. CTCdetection with the CellSearch system correlated significantly with the pT stage and M stage. However, no significant correlation has been found with histopathological parameters and CTC detection with the combined cytokeratin/EpCAM enrichment. The mean follow-up time was 38 months. Within this time, 65/100patients relapsed and died, respectively. End points were progression-free (PFS) and overall survival (OS). Presence of CTCs correlated with significantly shorter OS and PFS in univariate and multivariate analysis using MACS enrichment or the CellSearch method.

Conclusion:
CTC detection by MACS enrichment/ Ariol correlates with a shorter progression-free and overall survival, using a cut of value of >= 2 CTCs, whereas patients with >1 CTC or <= 1CTC did notshow significant differences in PFS and OS. However, the CellSearch system is a strong independent prognosticator for overall and progression-free survival, regardless of the cut offvalue and thus remains the gold standard for CTC detection. The human microbiota has recently become subject of multiple investigations because of its role in development or maintenance of different physiological and pathological states of the human body. Due to its interaction with tissues, cells and the immune system on external and internal body surfaces, it has important influence on prevention as well as development of inflammatory, benign and malignant tumorous diseases. With the development of biobanking of human tissue samples, such as biopsies or tissue samples of surgical specimens, a multitude of normal and pathological tissue samples has been stored and is available for up-to-date research, especially in the fields of personalized medicine and pathogenesis of human diseases.
The aim of our work was to establish and validate a microbiome analysis pipeline for different kinds of snap frozen biobank samples including feces, mucosa scrapings (containing the intestinal mucin layer) and mucosa samples.

Materials and methods:
Samples (feces, mucosal scrapings and mucosa) from normal tissues of transverse colon from surgical specimens were collected during surgery. The samples were stored snap-frozen in the biobank at our surgical department. Microbiome analysis of the fecal samples was performed according to protocols normally used for human and mouse intestinal samples: after DNA extraction and amplification using specific primers targeting the V3-4 variable regions of the bacterial 16S rRNA gene, amplicons were sequenced on the Illumina MiSeq v.3 platform. Additionally, the routine protocol for microbiome analysis in stool was expanded for the analysis of mucosa scrapings and mucosa samples. For validation of microbiome analysis, number of taxa, α-and ß-diversity metrics and differential abundance analysis were performed.

Results:
Microbiome analysis from fecal samples and scrapings were successfully established according to the already existing protocols. DNA extraction from mucosa samples was optimized to yield enough highquality DNA and amplicons for successful sequencing. Validation of this pipeline was performed based on different population measures like absolute number of taxa, α -and ß-diversity and differential abundance analysis.

Conclusion:
After successful establishment and validation of microbiome analysis from snap frozen mucosa samples, it seems feasible to perform microbiome analysis on samples already stored in a biobank. The entire biobank collection of tissues obtained from surgical specimens resected during inflammatory (like inflammatory bowel disease) and mostly malignant diseases (all kind of gastrointestinal and other cancers), is therefore potentially available for microbiome analysis. Together with the clinical documentation, this data will be valuable to correlate disease states with microbiota profiles. The interaction between human microbiota and the pathogenesis and progression of different diseases, as well as the microbiota's impact on development of perioperative infectious complications

Charité -Universitätsmedizin Berlin CVK
Background: Prolonged perioperative fasting periods are associated with delayed recovery after surgery. Clinical guidelines (e.g. ESPEN, 2017) emphasize the benefits and feasibility of preoperative fasting of solid food for only six hours and clear fluids for two hours before induction of anaesthesia. Furthermore, oral feeding should not be interrupted by surgery and has been shown to be safe even in patients undergoing surgery for gastrointestinal (GI) tract malignancies. The aim of our study was to assess, whether these fasting recommendations are achieved in clinical practice in patients undergoing GI tract surgery. In addition, this study seeks to identify potential nutritional support improvement strategies during the clinical care process.

Materials and methods:
Patients scheduled for elective surgery of the upper (n=23) or lower (n=27) GI tract participated in a prospective observational study. Patients' charateristics and nutritional status (assessed by Mini Nutritional Assessment, MNA and Nutritional Risk Screening, NRS) were recorded and blood samples were drawn on the day of admission and on postoperative day (POD) four. Nutrient intake and timing was assessed by nutrition diaries during hospitalization. Intensified nutritional support included preoperative nutrition counseling and daily nutrition support during hospitalization by a dietitian.

Results:
Within our patient cohort, the prevalence of "risk for malnutrition" was 61.2% or 38% when assessed with the NRS or MNA score, respectively. The MNA also graded 6.3% of the patients as "malnourished" at the time of admission.
Preoperative fasting periods of solid food ranged between 9. . By the intensified nutritional support, the total energy deficit accumulating between the day of admission till POD4 was reduced by 27%.
Prolonged preoperative fasting was reflected in disturbed amino acid plasma profiles with significantly elevated branched-chain amino acid levels and reduced non-essential amino acids, like glutamic acid. Postoperatively, the fasting periods correlated significantly positive with C-reactive protein and 3methylhistidine plasma levels, the latter being a marker of muscle protein degradation.

Conclusion:
Significant reductions of perioperative fasting periods and an improve daily energy intake were achieved by the intensified nutritional support of surgical patients. Despite the high levels of awareness of the medical staff for the importance of sufficient feeding of the patients, there is a discrepancy between guideline-adhering short perioperative fasting periods and the actual achieved times in the individuals' clinical treatment process. One strategy for preoperative risk assessemnt in liver surgery includes the combined assessment of the dynamic liver function by the 13C-methacetin maximal liver function capacity (LiMAx) test, the volumetric analysis of the liver and calculation of future liver remnant function. However, this so-called volume-function analysis assumes that the remaining CYP1A2 activity (the enzyme system specifically addressed by the LiMAx test) in any tumor lesion is zero. This study aims to assess the remaining CYP1A2 activities in different hepatic tumor lesions and its consequences for the volume-function analysis.

Materials and methods:
The activity of CYP1A2 was determined in human liver tissue samples collected after surgical resection of hepatocellular adenomas (HCA, n=9), hepatocellular carcinomas (HCC, n=25) or colorectal liver metastases (CRLM, n=5). Paired tissue samples were collected, one from the lesion and one from adjacent non-tumor liver tissue. CYP1A2 abundance was assessed by immunofluorecence staining of paraffine-embedded tissue sections. In all patients a LiMAx test was performed prior to surgery and representative volume-funtcion analysis were conducted.

Conclusion:
In conclusion, CYP1A2 activity is virtually absent in HCCs but considerable activity detectable in HCAs. These findings are important for an accurate surgical risk assessment and an improved preoperative volume-function analysis in HCA cases with low LiMAx values.

Background:
Human exposure to infrasound is increasing due to different factors, raising questions regarding its public safety. The aim of this work is to evaluate whether this exposure interferes directly with human cardiac function and hence attributes to any kind of pathological process.

Materials and methods:
Human myocardial tissues, obtained from patients undergoing cardiac surgery, were prepared in small muscle samples and then stimulated electrically with a frequency of 75 bpm for a period of almost 120 minutes under sustained perfusion with an oxygenated physiological solution. Two samples were obtained from each patient: one was subjected to infrasound and the other served as a control. The exhibited isometric contraction force (CF) and contraction duration (CD) were measured before and after the treatment. The changes in these values were compared to the control samples in each trial. Three groups of trials were conducted with three different levels of infrasound: 120, 110 and 100 dB SPL. Each group contained 6 trials.

Results:
Using linear regression, we found a correlation between increasing infrasound level above 100 dB SPL und decreasing CF (r²=0.26; one-sided p= 0.014). The 120 dB SPL group showed a decrease in its CF of almost 20.6% in comparison to its control. The 110 dB SPL showed a decrease of 11.7%. There was no significant change in CF in the 100 dB SPL group. The CD remained unchanged in all groups.

Conclusion:
Exposure to high levels of infrasound (120 dB SPL) resulted in a relevant (18%) and statistically significant decrease in CF. These results should be considered when looking at environmental regulations.

Klinikum Rechts der Isar der TU München
Background: Annexin A1 (AnxA1) is a potent anti-inflammatory protein that has been described as one of the main effector molecules of glucocorticoids. It suppresses leukocyte activation and transmigration and exhibits anti-inflammatory properties in inflammation models such as endotoxemia, peritonitis and arthritis. Furthermore AnxA1 has been shown to be centrally involved in intestinal wound healing and inflammation. Thus it shows high potential as an immune regulator for inhibition of inflammation and stimulation of wound closure in the gut. Little is known about the endogenous role of AnxA1 in inflammatory bowel disease. Thus we aimed to further characterize the expression of AnxA1 in Crohn´s disease.

Materials and methods:
To analyze the endogenous role of AnxA1 in Crohn´s disease, surgical specimen of patients who have had intestinal resections for Crohn´s disease have been analyzed (n=60 patients): For protein analysis and evaluation of AnxA1 expression-patterns immunohistochemistry was performed and corroborated with analysis of AnxA1 RNA expression using realtime PCR (n=20 patients). Furthermore serial immunofluorescence co-stainings of cell markers and AnxA1 were used to determine the main cell source of AnxA1 expression within the tissue. Ultimately AnxA1 expression was correlated to histologic scoring of the specimen and the clinical course of disease of the patients.

Results:
Immunohistochemistry (IHC) revealed correlation of AnxA1 expression with increase of intestinal inflammation. Using co-staining of AnxA1 with different cell markers, we identified CD4 positive T cells to highly positive for AnxA1. Corresponding to the results of IHC, RT-PCR showed elevated expression of AnxA1 RNA in samples of inflamed areas compared to non-inflamed tissue which correlated well with the histologic scoring of the tissue.

Conclusion:
Within our analysis, the expression pattern of the anti-inflammatory protein AnxA1 correlated well with intestinal inflammation in patients with Crohn´s disease. We will now further characterize the expression of AnxA1 with clinicopathological features of the disease to determine whether the protein might serve to be a valid biomarker for the disease. Due to its anti-inflammatory character and role in regulation of intestinal inflammation AnxA1 might be a promising therapeutic in inflammatory bowel disease. Aim of the present restrospective study is to compare the long-term clinical outcomes of surgical (venous thrombectomy and anticoagulation) vs. conservative therapy (anticoagulation) for acute inferior vena cava thrombosis.

Materials and methods:
All patients with thrombosis of the inferior vena cava treated conservatively or surgically from January 2005 to December 2017 at University Hospital Frankfurt were included in the study. Long-term outcomes in terms of venous patency and development of post-thrombotic syndrome (PTS) were analyzed.

Results:
A total of 48 patients with acute inferior vena cava thrombosis were treated in this period in our hospital. Twenty-three patients (8 female, 15 male; mean age, 40 years; range, 14-72 years) underwent transfemoral venous thrombectomy combined with a temporary arterio-venous fistula and anticoagulation. Four patients underwent additionally balloon angioplasty and stenting of an iliac vein stenosis due to May-Thurner Syndrome. 25 patients (15 female, 10 male; mean age, 48 years; range, 12-75 years) were treated conservatively with oral anticoagulation (coumarine derivatives). In the 6-and 24 months follow-up, venous patency was controlled using duplex ultrasonography. Development of PTS was assessed using the Villalta score. In the 24 months follow-up, the patency rate of the inferior vena cava and iliofemoral veins was 85,7 % in the surgical group, and 72 % in the conservative treatment group (P=0.231). 21,5% of patients in the surgical group developed moderate to severe PTS compared to 33,0% in the conservative group (P=0.715). In the surgical group 5 patients (22%) developed re-thrombosis in the first postoperative week and underwent new surgical procedure. One patient developed pulmonaly embolism. Two patients died because of multi organ insufficiency (mortality rate during first hospital stay: 8%).

Conclusion:
Surgical therapy for acute vena cava thrombosis seems to offer better long-term results in terms of venous patency and PTS development compared to anticoagulation alone. Nevertheless, open surgery has a higher incidence of perioperative complications. Furthermore, there is a need for more studies with larger patient populations.

Background:
The systemic inflammatory response (SIR) is a complex system comprising humoral and cellular components and gained growing evidence in the development and progression of cancer. The neutrophil-to-lymphocyte ratio (NLR) is one of the most common hematologic parameters reflecting the systemic inflammation and predict survival in varied type of cancers. Soluble ICAM-1 (sICAM-1) is also an inflammatory associated marker, elevated in different type of cancers. Therefore, in the present study we set out to evaluate the effect and the prognostic relevance of combination NLR and sICAM in a large cohort of patients with colon cancer at the time of initial diagnosis to predict outcome in these patients.

Materials and methods:
In this retrospective analysis of prospectively collected blood samples (collected by peripheral venous punction before surgery) 225 patients with previously untreated colon cancer (stage I-IV) were enrolled. Clinical data were obtained from the Erlangen Registry for Colorectal Carcinomas. NLR was measured via the routine blood analysis and receiver operating characteristic (ROC) analysis was used to identify the best cutoff value of NLR. On the basis of our previously published data, sICAM levels were analyzed by commercial available ELISA kit and a cut-off level of 250 ng/ml was identified. Survival curves were determined by the Kaplan-Meier method.

Conclusion:
The combination of NLR and sICAM, both simple and easily obtained markers, is a useful prognostic indicator for OS in patients with colon cancer. Postoperative pancreatic fistulas (POPF) occur in up to 30% of patients after partial resection of the pancreas. The mechanical properties of the adjacent non-malignant tissue is significantly associated with the development of. Consequences thereof are a prolonged stay in the hospital, which doubles the cost of care after pancreatic surgery, and an increased postoperative morbidity and mortality.

Materials and methods:
The aim of this interdisciplinary project was to (i) develop novel techniques to quantify pancreas mechanical properties in an objective manner and (ii) to better understand the tissue composition and structural factors causing alterations in the tissue mechanical properties. Postoperative ex-vivo mechanical testing (bulk unconfined compression testing) was flanked by structural tissue and cell characterization (histology, polarized light microscopy and immunofluorescent staining) and correlated to clinical data and tumor characteristics.

Results:
In total, 91 samples of 59 patients were analyzed, including 48 tumor samples and 43 samples of adjacent non malignant tissue. We could clearly show a correlation of the preoperative presence of cholestasis and a reduced rate of POPF. Furthermore, patients who developed POPF after pancreatic surgery showed a more viscoelastic tissue composition of the adjacent non-malignant tissue represented by a shorter stress relaxation half time measurement. A trend was observed for lower fibrous tissue content as well as reduced content of collagen I in adjacent non-malignant tissue in patients developing POPF. We could not detect a difference between the content of fibronectine, hyaluronic acid, collagen III and IV, and patients developing POPF or not.

Conclusion:
The risk of POPF seems to be lower in patients presenting with preoperative cholestasis and a more viscoelastic tissue composition of the pancreas remnant. Methods to quantify mechanical properties of the pancreas in an objective manner are needed to establish risk stratification algorithms to identify patients at high risk for POPF.

Materials and methods:
Priority Setting Partnerships (PSPs) aim to involve patients, caregivers, doctors and other relevant stakeholders as equal partners to find the most urgent unanswered research question for a certain disease. This is achieved by a transparent 7-step process including survey, literature reviews and prioritizations. The PSP Pancreatic cancer and the PSP Colorectal cancer were initiated in Heidelberg in cooperation with the UK-based James Lind Alliance, a non-profit-making initiative established in 2004. The aim is to separately identify and prioritize the top 10 open research questions / uncertainties on (diagnostics and) treatment of the two diseases. The intention of these projects is to stimulate and steer future research in the field of colorectal and pancreatic cancer, by identifying the most important research areas for patients and clinicians.

Results:
The first nation-wide survey of the PSP Pancreatic cancer was carried out from August to November 2017 and revealed 566 questions submitted by 140 participants. The gathered uncertainties included questions about medical and surgical therapy, palliative care, naturopathy, nutrition, the impact of psycho-oncology, and more. After removal of duplicates and out of scope questions, uncertainties were checked against current evidence. A second online survey for interim prioritization and the final face-to-face consensus conference will follow.
The PSP Colorectal cancer started in 03/2018 and is founded by the BMBF. Potential stakeholders and partner organization were identified and the online survey is planned for 11-12/2018.
At the congress, the TOP 10 List of the PSP Pancreas and first results of the nationwide online survey of the PSP Colorectal cancer can be presented. The consecutive steps of the ongoing PSPs will explained and discussed.

Conclusion:
The identified questions warrant realized patient involvement and initiate patient-relevant research and research funding, thus improving the care of those most affected by pancreatic and colorectal cancer. The presented PSPs establish the transparent, validated JLA method for the first time in Germany and they are the first PSPs on the subject of pancreatic cancer and colorectal cancer world-wide.

Background:
Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) and its technical modification by the additional use of an electrostatic aerosol precipitation device (ePIPAC) is a new technology to deliver intraperitoneal chemotherapy. It is reported that the ratio between peritoneal and systemic drug concentrations is superior compared to that of liquid hyperthermic intraperitoneal chemotherapy (HIPEC). So far, there is no direct comparative data available supporting such an assumption.

Materials and methods:
Three groups of four French landrace pigs each underwent either PIPAC with oxaliplatin 92mg in 150ml dextrose 5% (Group 1), electrostatic aerosol precipitation PIPAC (Group 2) or laparoscopic HIPEC (L-HIPEC) with oxaliplatin 400mg in 4 litres dextrose 5% at 42°C (Group 3). Blood as well as peritoneal tissue concentrations of platinum were determined by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). To obtain Oxaliplatin concentrations, the measured platinum concentrations must be multiplied with a factor 2.03.

Conclusion:
During PIPAC and ePIPAC, relevant platinum absorption, similar to that observed during L-HIPEC was found. Irrespective of the technique used, the overall platinum concentrations measured in the peritoneum showed also no significant differences among the three groups. No superiority was found for ePIPAC.  Impaired postoperative renal function increases morbidity and mortality after liver resection.

Renal Impairment is associated with reduced outcome after Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy: Data from the ALPPS Registry
Preoperative laboratory values such as elevated alanine transaminase and an increased MELD score and comorbidities (cardiovascular disease, diabetes, chronic renal failure and advanced age) have an impact on the incidence of postoperative renal function. However, intraoperative risk factors, such as major hepatectomy and prolonged operative time, are the most important components to have impact on postoperative renal function.
It is unknown whether the incidence and risk factors for impaired renal function after standard liver resections also apply to Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy. With two operation steps, a prolonged operation time and higher use of blood transfusions a much higher incidence can be assumed. However, the prognostic value of renal function on the outcome in ALPPS patients could be much more severe than after conventional liver resections.

Materials and methods:
All patients included in the ALPPS Registry were screened for preoperative serum-creatinine levels (sCr) and were excluded if the value was not available.Interstage Renal Impairment (IRI) was defined as an increaseof Serum-Creatinine by >=0,3mg/dl referring to preoperative value or an increase of Serum-Creatinine by >=1,5x of the preoperative value on the fifth postoperative day after stage-1. Primary endpoint was the occurrence of renal impairment after stage-1. Secondary endpoints were morbidity and mortality after each stage.

Results:
We identified 741 patients for analysis. Overall, 7,5% had an IRI on postoperative day 5 after stage-1. Patients developing an IRI were significantly older and comorbidities such as myocardial infarction, cerebral vascular disease and liver diseases were significantly associated with IRI.
During stage-1, they had a significant longer operation duration, a higher proportion of intraoperative transfusions and additional procedures. After stage-1, IRI patients had more major complications and higher interstage mortality (1% vs. 8%, p<0,001). No differences were seen in volumetric analysis.
There was no significant difference in the extension of the resection and operation duration of stage-2. Furthermore, patients with IRI are more likely to have more and severe complications after completion of stage-2.
The mortality in patients with an IRI is higher (38%) compared to non-IRI (8%, p<0,001), although the PHFL was not significant. However, in 41% of the patients with IRI the renal function recovered before stage-2, the mortality after stage-2 remained high (28%). The survival after completion of stage-2 was Risk factors for the development of an IRI were age over 67 years, a prolonged operation time over 5h and additional procedure during stage-1. However, IRI was no independent risk factor for mortality in this cohort.

Conclusion:
This study shows that interstage renal impairment is a prognostic factor for interstage and post-stage-2 morbidity and perioperative mortality and for the first time contributes risk factors for renal impairment after stage-1. However, if IRI causes the reduced outcome or serves a surrogate marker for major interstage complications remains unknown.

Universitätsklinikum Münster
Background: Annexin A1 (AnxA1) has been described as one of the main effector molecules of the antiinflammatory effects of glucocorticoids. It exerts anti-inflammatory effects by suppression of leukocyte activation and transmigration, and exhibits anti-inflammatory properties in inflammation models that include endotoxemia, peritonitis and arthritis. Furthermore it has been described to play a role in intestinal wound healing. The effects on intestinal anastomotic healing and the cellular expression patterns in anastomotic tissue have not been analyzed yet. Thus we aimed to characterize the functional role of AnxA1 in intestinal anastomotic healing and further examine the cellular expression patterns of AnxA1 in anastomotic tissue.

Materials and methods:
To characterize the role of AnxA1 in intestinal anastomotic healing a surgical model of anastomotic leakage in mice has been established. A colonic anastomosis was performed in AnxA1 knockout mice (n=30) and wildtype controls (n=30). Anastomotic tissue was harvested after 1, 3 and 5 days and grade of inflammation (mild, medium, severe) was scored by a pathologist in a blinded fashion. To further examine cell specific expression patterns of AnxA1, immunohistochemistry (IHC) in slides of anastomotic tissue of human patients suffering from anastomotic leakage was performed. Expression of AnxA1 in anastomotic and non-anastomotic tissue areas was quantified. Furthermore immunofluorescence co-stainings of AnxA1 and different cell markers (CD20, CD4, CD8 and CD68) were used to identify the main sources of expression within the anastomotic tissue.

Results:
Increased histologic inflammation scores in AnxA1 null mice compared to wild type controls were found. The difference was more pronounced in the very early inflammatory period. IHC showed pronounced presence of AnxA1 positive lymphocytes within anastomotic area, whereas fibroblasts and endothelial cells showed only mild expression and epithelial cells showed no expression. The immunofluorescence co-staining revealed T cells highly positive for AnxA1 but B cells showed no expression.

Conclusion:
AnxA1 seems to be essential for uncomplicated intestinal anastomotic healing in mice. The expression of the anti-inflammatory protein AnxA1 was elevated in tissue of patients with proven anastomotic leakage, interestingly AnxA1 is mainly expressed by CD4 positive T cells. We will next evaluate the therapeutic potential of AnxA1 for improving intestinal anastomotic healing.

Background:
Post-hepatectomy liver failure (PHLF) is one of the most challenging complications following extended hepatectomy. Up to now it is not known if there is an individualized risk for impaired liver regeneration and which are potential targets for regeneration preconditioning. Cytokines and growth factor play a important role in every phase of liver reganeration. Aim of the study was to predict the individualized regeneration capacity of the liver by cytokine -and growth factor profiling.

Materials and methods:
Longitudinal blood samples (day -1, 1,3,7 realted to surgery) and liver tissue samples of 30 patients undergoing major liver resection were analysed. Primary human hepatocytes (PHH) were prepared out of tissue specimens for each patient. Cytokine and growth factor expression was analysed by Luminex bead-based multiplex assay, tissue protein expression by mass spectometry and PHH by Sybr Green Assay. Spearman-Correlation, Wilcoxon-and Kruskal-Wallis Test, Lasso Regression and Cytoscape were used for data analysis.

Results:
Preoperative status (ASA, Age, Co-morbidities) and postoperative complications correlate significantly with PHLF and mortality after liver resection. Expression of IL6, IL8, HGF, VEGF, EGF, APO2, PLGF and TGFß changes individually between day -1 and 7 after surgery. Correlation plotting identifies clear patterns associated with PHLF, complications Clavien Dindo >3a and exitus. Prediction models based on preoperative cytokine and growth factor expression predict the individual risk for PHLF. Clustering according to growth factor expression allows prediction of risk for death postoperatively. Combination of clinical parameters and cytokine/growth factor profile are surrogates for postoperative prognosis. A multifactorial interaction network was identified. Mass spectometry identified 158 significantly regulated proteins for liver failure. PHLF was associated with overexpression of 102 proteins e.g. HCCS, DDX47 and ITIH4 which are responsible for apoptotic signalling pathway, impaired response to cytokines as well as Oxidation-reduction process. In contrast patients with good liver regeneration overexpressed PTPN1(regulation of HGF signalling pathway), NHLRC2 (cell redox homeostasis) and GAK (regulation of cytokine response). Primary hepatocyte analysis revealed individual growth pattern upon stimulation with HGF and/or IL6. PHH growth capacity was significantly associated with postoperative liver function and clinical course.

Conclusion:
Cytokine-and growth factor profiling and modelling is a reliable method for preoperative prediction of the postoperative clinical outcome. The individual expression patterns correlate with the risk for PHLF. Validation on tissue level by massspectometry and functional level by primary hepatocytes supports the hypothesis of individual targeted regeneration preconditioning in the future.

Background:
The loop ileostomy is commonly used for prevention of severe sepsis by fecal diversion due to anastomotic leakage after anterior rectal resection. It has been suggested that defunctioning ileostomy ameliorates the effects of a leak, which potentially leads to life-threatening pelvic sepsis. However, the presence of a stoma is connected to the risk of adverse effects related to the stoma itself as well as to the subsequent stoma closure.

Materials and methods:
We present a retrospective single-center analysis of 138 patients, who underwent a primary open anterior rectal resection with primary anastomosis and defunctioning loop ileostomy. It was divided into a group with an early stoma closure within 30 days after primary operation (group A, n=25) and into a group with the closure at a later date (group B, n=113). Primary endpoints were stenosis, bleeding, hernia, retraction, abscess and fistula of the stoma as well as paralysis, exsiccosis and colitis.

Results:
The most frequent adverse effect in both groups was the loss of fluid and electrolytes due to high stoma flow. Patients with a preoperative high morbidity of ASA III-IV showed a significant need for inpatient treatment of exsiccosis (p=0.037). Furthermore, patients with an early stoma closure (group A) showed a significant appearance of parastomal abscess (p=0.042), whereas parastomal hernia (p=0.038) and colitis (p= 0.012) were observed more frequently in patients with long-time stoma deviation (group B). Moreover, patients with late stoma closure showed significantly prolonged paralysis with the need for medical treatment (p=0.032).

Conclusion:
The construction of a defunctioning loop ileostomy during rectal resection is a safe and uncomplicated surgical procedure, but it can cause significant postoperative adverse effects. High fluid and electrolyte loss are well-known complications, but we herewith raise the evidence for parastomal hernia and colitis as well as for prolonged gut paralysis in patients with long-time defunctioning loop ileostomy. Therefore, the early stoma closure may avoid adverse effects that occur due to long-time deviation.

Universitätsklinikum Hamburg-Eppendorf
Background: CXCL10, a chemokine, has been attributed to several roles such as chemoattraction for monocytes/macrophages, promotion of T cell adhesion to endothelial cells, antitumor activity and angiogenesis. In our study, we aimed at assessing the prognostic relevance of the single-nucleotide polymorphism rs8878 in the CXCL10 gene in lung cancer patients.

Materials and methods:
Genomic DNA from blood and lymph node tissue samples from 186 lung cancer (squamous cell carcinoma and adenocarcinoma) patients was amplified and sequenced. The results were correlated with clinicopathological parameters and clinical outcome (disease free survival and overall survival).
Chi-square test, Kaplan-Meier estimator and cox regression hazard model were used to assess the prognostic value.

Conclusion:
To conclude, determination of CXCL 10 preoperatively might potentially allow allocation of lung cancer patients into different risk profiles which might influence individual therapeutic strategies.

Background:
Ductal adenocarcinoma of the pancreas (PDAC) as soon as metastasized cannot be cured by systemic therapy yet. Primary tumor and metastases exhibit a complex cancer pathology characterized by deposition of desmoplastic stroma, which contributes to cancer progression and chemoresistance. In this microenvironment, cancer cells engage in complex interactions with cancerassociated fibroblasts (CAFs). Concerning the role of CAFs it is heavily discussed if they support or fight the tumor. Even more the role of metastasis associated fibroblasts (MAFs) remains to be unclear and should be analyzed in this study.

Materials and methods:
In vitro we studied interaction of tumor cells of metastatic PDAC and fibroblasts in the context of tumor angiogenesis. We measured alterations of cell proteome via ELISA-proteome assay and proofed specific expression changes via qPCR. In angiogenesis assays we tried to block specifically expressed cytokine. In vivo we studied impact of antiangiogenic tyrosine kinase inhibitor Sunitinib on hepatic metastasis of PDAC and associated desmoplastic tumor microenvironment via immunohistochemistry.

Results:
Enhanced proangiogenic effect of co-cultured tumor cells and fibroblasts was seen. Additionally proliferation of fibroblasts was stimulated by tumor cells. Simultaneously cell proteome got augmented. Specifically up-regulation of cytokines interleukin 8 (Il-8/ CXCL8) and chemokine (C-C motif) ligand 2 (CCL2/ MCP-1) was seen in fibroblasts. Increased proangiogenic effects of co-cultures could be suppressed completely by blockage of IL-8-and CCL2-pathways. As anticipated in vivo Sunitinib led to reduction of metastasis. But beyond that it led to reduction of MAFs and simultaneously to increased proliferation of tumor cells in the field of micro-metastasis and cancer invasion front.

Conclusion:
Our results highlight that IL-8 and CCL2 from MAFs play a central role in tumor angiogenesis of metastasized PDAC which can be suppressed specifically. Nonspecific antiangiogenic therapy in fact reduces volume of metastases and number of MAFs yet it enhances aggressiveness of tumor cells.

Background:
Esophageal adenocarcinoma (EAC) is one of the most rapidly increasing tumor entities in the western world. Despite remarkable progress in the treatment of these patients, the overall outcome is still limited. More than 60 % of all patients who undergo an apparently curative, complete resection of a clinically non-metastatic primary tumor will eventually relapse or develop distant metastases, which might be caused by circulating tumor cells (CTC). However, there is little evidence about the significance of CTCs in patients with EAC.
Our study was designed as a pilot study of the ESOPEC-Trial. We evaluated the presence and morphology of CTCs during the treatment period and compared the well-established surface-antibody dependent CTC isolation technique (CellSearch®) with the isolation by size technique (ScreenCell®).
The experimental results will be correlated with patients' overall and relapse-free survival.

Materials and methods:
20 patients with non-metastatic EAC were consecutively enrolled into this trial prior to the beginning of the neoadjuvant treatment. The patients had no previous medical history of cancer. Blood specimen were sampled before the start of the neoadjuvant therapy (FLOT or CROSS protocol), after the neoadjuvant therapy, and finally after the surgery. CTC isolation was performed with CellSearch® isolation devices and by use of a cell size based filtration method (ScreenCell®). The cells isolated by size were subsequently stained with May-Grünwald Giemsa staining. We compared the results of the two CTC isolation techniques. Furthermore, the absolute number of CTCs per blood specimen was quantified and the morphology of both single and cluster CTCs during the time course of therapy was assessed.

Results:
75 % of the patient population was treated with neoadjuvant chemotherapy (FLOT protocol) while 25 % of the patient received radiochemotherapy (CROSS protocol). Using the ScreenCell® technique, single CTCs or cluster CTCs were found in 60 % of the patient population in at least one blood specimen. Interestingly, the number of CTC positive patients showed tendency to an increase after neoadjuvant therapy (before the neoadjuvant therapy: 30 %; after the neoadjuvant therapy 60%; after surgery: 62%). Additionally, we observed a tendency to an increase in the number of CTCs per/mL blood after the neoadjuvant therapy. However, due to the limited number of blood specimen no statistically significant differences could be observed during the time course of treatment. The CTCs showed a morphological diversity and could be grouped in four groups. However, CTC isolation by CellSearch® delivered unsatisfactory results since 40 % of the blood samples were non-analysable.

Conclusion:
In our study, we could observe a tendency to an increase of both the number of CTC positive patients and the absolute count of CTCs per ml after the neoadjuvant therapy. To our knowledge this is the first study to investigate the presence of CTCs during the time course of treatment in patients with EAC. The observed increase of CTCs after the therapy along with the role of the different morphological CTC subtypes will be further investigated in the patient population of the ESOPEC trial. Better isolation results were obtained using the cell size based filtration method (ScreenCell®). This supports the use

Background:
Despite modern concepts in diagnosis and treatment, colorectal cancer (CRC) remains the third most common cancer worldwide. Although multimodal treatment is standard of care, the 5 years survival rate is just about 50%, most deaths resulting from metastatic spread. The Liver is the main organ in which those metastases disseminate. Even patients diagnosed with local disease (UICCI+II) will eventually develop CLM in 50% of the cases. In those patients, surgical therapy offers better survival and, in some cases, a total remission; yet even after total R0-resection, 60% of these patients will still suffer recurrent CLM within 2 years of initial treatment. Even after long periods of clinical remission, CLM can arise. In 2% of patients who have had successful treatment of M0 CRC and no recurrence or CLM in the following 5 years, CLM developed up to 10 years after initial therapy. This observed latency until overt CLM arise points to a clinically relevant pool of metastasis initiating cells in a dormant stage, present in the liver from an early stage. Currently, no treatment of these dormant disseminated tumor cells exists, as research into this phenomenon is lacking.

Materials and methods:
Using RNeasy FFPE Kit we isolated mRNA from FFPE sections of synchronous and metachronous CLM, as well as primary tumors (PT) (n=28patients). After producing cDNA from the mRNA-samples, using qPCR (quantitative real time PCR), we looked for the expression of known dormancy factors NRF2F1, DEC2, p27 and TGFβ2. These factors have previously been implicated in dormancy, as well as cell-cycle arrest. The δδC(t) method was used to analyze the qPCR results, statistics were carried out using two-tailed t-test with the Prism software (Version 6).

Results:
While observing interindividual variation, NR2F1 and TGFβ2 were not detectable in the majority of samples. Low sample acquisition of PT of patients with metachronous CLM has, so far, resulted in an insufficient number of samples of this group. Further recruitment is ongoing. Surprisingly, metachronous metastases so far showed a significantly lower expression of DEC2 than the synchronous CLM. We observed no significant difference in p27 expression between these two groups in the samples analyzed this far. Between PT and their synchronous CLM, we could not detect a significant difference in p27 expression, yet a trend toward higher expression in the CLM was observed. The DEC2 expression in the synchronous CLM was significantly lower than in the concurrent PT.

Conclusion:
While metachronous metastases have developed at a later time, compared to synchronous CLM, and the metastasis initiating cells may thus have gone through a dormancy-phase, all of the hepatic lesions included here were, at the time of resection, viable and proliferating metastases. Thus, the observed lower expression of the putative dormancy factors in metachronous metastases could be caused by a subclone that has been able to effectively exit dormancy. Following this hypothesis, heterogenous populations within synchronous metastases could express dormancy factors, as well. The ongoing recruitment of new samples will hopefully enable us to further unravel the connection between the established dormancy factors and the chronology of CLM. Tumor dormancy, especially in CLM, has not been extensively researched. Understanding dormancy is critical in developing treatment options for metastatic CRC and to stop metastasis in the first place.

Universitätsklinikum Augsburg
Background: Treatment of locally advanced rectal cancer (stage II or III) consists of neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME). Complete pathologic remissions (pCR) are observed in 20-30% of patients (pts) undergoing nCRT. Several studies and case series comparing TME and "watch and wait" strategy after nCRT have reported similar excellent outcome for both patient groups (Kong et al. 2017). Thus, non-operative treatment for locally advanced rectal cancer might constitute a treatment option for selected pts. However, preoperative diagnostics including imaging, blood-derived protein biomarkers, histological and molecular markers have failed reliably predicting pCR. The detection of circulating tumor DNA (ctDNA) has proven to be sensitive for monitoring treatment response and detecting minimal residual disease (MRD). In a recent study, MRD assessment by ctDNA was successfully used for predicting relapse in stage II colon cancer demonstrating super predictive abilities compared to MRT and CT based follow-up. We hypothesized that monitoring ctDNA changes in pts with rectal cancer undergoing nCRT might facilitate identifying pts reaching pCR and thereby prospectively guide therapy.

Materials and methods:
We conducted a prospective single center study in pts with rectal cancer (stage II or III) planned for nCRT and curative resection. Serial peripheral blood samples were collected before, during and after nCRT and directly before TME. Circulating free DNA was extracted from 4 ml plasma. Informative somatic mutations were identified initially in rectal biopsies by next generation sequencing (Thermo Fisher Oncomine HotSpot Panel) and subsequently used for ctDNA quantification by digital PCR (dPCR; Thermo Fisher QuantStudio 3D Digital PCR System).

Results:
By the current interims analysis, 20 pts were included in the trial. Median age was 67 years (range 49-81), 60% were male. 7 pts who completed the trial protocol and reached surgery had ctDNA samples available for analysis. Of these, 4 pts had detectable ctDNA prior to therapy. Lower detection limit for dPCR assays on plasma from rectal cancer pts was established at a level of 0.1%. In 4 out of 4 pts, decrease of ctDNA was observable during nCRT. One out of 4 pts reached pCR, another patient achieved subtotal remission. One patient showed a continuous decline of mutant plasma DNA during nCRT (1.15%, 0.9% and 0.55%). Directly before TME, a 10-fold steep rise of mutant alleles (5.5%) was observed, which was consistent with new hepatic metastases. After resection of metastases, the mutant alleles decreased again. Taken together, our preliminary results indicate an interrelation between decrease of ctDNA and remission after nCRT.

Conclusion:
ctDNA is detectable in pts with stage II and III rectal cancer undergoing nCRT. ctDNA decrease can be observed upon nCRT and monitoring ctDNA dynamics during nCRT is a feasible approach to be further developed as predictive marker for achieving pCR.

Klinikum Leverkusen
Background: Postoperative ileus (POI) is a common complication after abdominal surgery. Invasive stimulation of the cervical vagus nerve is known to reduce inflammatory response and ameliorated POI after surgery in a mouse model. However, the transcutaneous vagus nerve stimulation (tVNS) is a possible noninvasive approach. Firsti we investigated to effect of tVNS in a mouse model, secondly, we aimed to investigate the effect of tVNS on the activation of the stomach muscle in humans in a clinical pilot trial.

Materials and methods:
Mice underwent abdominal surgery with intestinal manipulation. 24 hours after surgery, proinflammatory cytokines and leucocyte influx were investigated within the muscularis externa of the small bowel. To detect a functional effect of tVNS, gastrointestinal transit was assessed 24 hours after surgery. Secondly, we investigated the effect of tVNS in humans. Therefore, patients requiring open laparotomy were screened for a prospective proof of concept clinical study. After open laparotomy, muscle activity of the stomach was measured by a free running electromyography (EMG) before and during tVNS on the ear. Frequency and amplitude of compound gastric action potentials were the electrophysiological parameters we assessed to reveal the changes in electro motor gastric activity. Gastrin levels as a surrogate marker for vagus nerve activation was analyzed before, 1 and 3 hours after tVNS.

Results:
tVNS reduced significantly proinflammatory cytokine expression and leucocyte influx within the muscularis externa of the small bowel and improved gastrointestinal transit after abdominal surgery compared to sham-stimulation in mice. In humans, tVNS led to significant reduction of action potentials frequency and significant elevation of action potentials amplitude in the stomach compared to control. Gastrin levels were significantly elevated three hours after tVNS compared to levels before tVNS.

Conclusion:
Application of tVNS is a safe and feasible procedure during surgical intervention. Our results provide evidence that tVNS ameliorates postoperative ileus in mice and activates efferent visceral vagal fibers in humans. Therefore, this low risk and easy to perform method could be useful to prevent postoperative ileus.

Background:
The role and requirement of ventilation technology in the operating theatre with regards to the control of indoor climate (including management of thermal loads) and ensuring aspects of occupational safety (removal of toxic substances) is beyond dispute. In contrast, the impact on the prevention of surgical site infections has been subject of controversial discussions for many years. Internationally uniform standards are missing. The current recommendations of the WHO and the German KRINKO for the prevention of surgical site infections do not see a compelling proof for the use of a lowturbulence displacement flow (TAV). The studies underlying these recommendations show weaknesses. This raises the question what is the most effective and economical concept for ventilation and air conditioning systems in the operating room.

Materials and methods:
We reviewed data in the literature as well as conducted own studies (active air sampling according to SIS-TS 39:2015 and particle measurments according to DIN 1946DIN -4(2008) in order to compare lowturbulence displacement flow (TAV), turbulent dilution flow (TVS) and temperature-controlled airflow (TAF) systems with different advantages and disadvantages regarding their impact on minimizing airborne risk factors for surgical site infections.

Results:
The results of active airsampling according to SIS-TS 39:2015 show that TAV and TAF, but not TVS, result in less than 10 cfu/m3 at all measurement locations in the room during surgery. Peripherally in the room, the cfu concentration was lowest for TAF. The cfu concentration did not scale proportionally with airflow rates. Regarding particle Measurments only TAV and TAF are in compliance with the required protection degree levels according to DIN 1946DIN -4(2008. Compared with TAV, the power consumption of TAF is lower and there was significantly less disturbance from noise and draught.

Conclusion:
If you pay particular attention to the avoidance or minimization of potential risk factors for surgical site infections, you should select a technical solution that reduces the microbiological burden in the air of the operating theatre. Taking into account current publications and our data TAV and TAF are both suitable for this purpose. However, based on our findings and the current data in the literature ultimately, the operator, together with the responsible hospital hygienist, has to evaluate and define the ventilation system to be implemented. This is a risk management decision and has to consider the utilization concept and the planned clinical procedures for the respectiv operating theatre. Postoperative wound infection is a common complication after laparotomy causing increased morbidity and postoperative pain. Although many surgical departments conduct subcutaneous wound irrigation before skin closure in order to reduce wound infections, there is a lack of high-level evidence on the use of wound irrigation for the prevention of postoperative wound infection. Therefore, we conducted an investigator initiated randomized trial comparing antiseptic wound irrigation with Serasept® with saline.

Materials and methods:
The RECIPE trial is a single-centre, prospective, randomized-controlled trial with two parallel treatment groups, comparing subcutaneous wound irrigation with Serasept® (0.04 % Polihexanide) to irrigation with saline 0.9% after elective laparotomy. The primary endpoint is the rate of wound infection within 30 days postoperatively according to the criteria of the Centers for Disease Control (CDC). Secondary endpoints are colonisation of abdominal wall with bacteria, length of hospital stay, postoperative pain and cosmetic result.

Conclusion:
Subcutaneous wound irrigation with Serasept® reduces postoperative wound infections after elective laparotomy in visceral surgery. Furthermore, it reduces the colonisation of the abdominal wall with bacteria. Preoperative anaemia and intraoperative creation of an ostomy were also associated with postoperative wound infections.

Background:
Artificial intelligence, big data and machine learning algorithms are currently changing the way we look at medical data fundamentally. These technologies create new and fascinating possibilities for the interpretation and evaluation of a large number of clinical data. With their help doctors are able to discover patterns and complex relationships. However, a concrete implementation in clinical practice, especially in surgery, is still to find.

Materials and methods:
At the Department of Surgery, Charité -Universitätsmedizin Berlin, we are implementing machine learning algorithms for early detection of postoperative complication after major abdominal surgery. After abdominal surgery, signs of complication often occur delayed und indifferent, but once a patient shows signs of a severe complication, we are often behind the action, we are only able to react instead of act. The idea of this project is to collect all data from patients before and after pancreas, liver and colorectal surgery and analyse these data with machine learning algorithms. With the help of these algorithms, we hope to detect major postoperative complications at a much earlier stage. The heart of every machine learning algorithm is the quality of the underlying data. On an ICU these data can be easily obtained, because there is a continuous monitoring of the patient's vital signs, status etc. To achieve the required quality of the data on a normal surgical ward we needed to completely rethink and redesign the way we do our clinical documentation and develop our digital infrastructure.

Results:
We analyzed all our processes and mandatory documentation in our clinic and looked for synergies between the different documentation systems. Due to this analysis we came up with 50 patientrelated, 18-22 disease-related (depending on the disease) and 41-48 procedure-related factors (depending on the kind of surgery). For the postoperative course we identified 39-59 (depending whether blood samples were taken or not) parameters which were assessed every day. The next step was to find automated interfaces to document these factors and parameters in a standardized way. We identified 4 relevant forms for the documentation of the required data. These forms where specially designed for an easy standardized documentation for a desktop computer and tablet device layout. We the help of these specially designed forms we were able to generate a data set of approximately 300 data points until POD 4 per patients. All these previously described parameters were assessed one time a day, but the dynamic in a patient's postoperative course is missing. In cooperation with a berlin start up company we designed a wearable device for continuous measurement of patient's vital signs: Heart rate, blood pressure temperature, oxygen saturation. With this setup we are now able generate a sufficient standardized data set, which covers every aspect of the patient's course.

Conclusion:
The implementation of machine learning algorithms in daily surgical routine requires high effort in the planning and designing of the clinical documentation. In addition investments in the digital infrastructure are necessary. The effort for this is enormous, but the resulting advantages for patients and medical staff can be a game changer.

Background:
Intraoperative 3D-naviagtion is an innovative technique, that could help to perform parenchymasparing liver resection (3DNvL) in combination with microwave ablation (3DNvMWA) in case with multiple disseminated metastases. Many different technical details occurred to be important to guarantee an optimal use during the operation. Aim of this study is to analyze these aspects.

Materials and methods:
Prospective observational study during introduction of 3DNvL/3DNvMWA

Results:
After test runs 3DNvL was first performed in October 2017. Since then it was used in 10 cases. Data reconstruction was performed by MeViS. In one patient 3DNvL was not possible due to extensive alterations of the liver surface. The mean operation time was 294 ± 60min, the mean number of treated metastases was 7.1 ± 5.9. In 7 patients resection and microwave ablation was combined. In 3 patients 3DNvL was used to support parenchyma dissection in major anatomical resections (right hepatectomy, extended right hepatectomy, ALPPS). Registration of reference points was performed in apnoe. A combination of surface and intrahepatic ultrasound points was most precise (screenshot technique) compared to the sweep technique (dynamic registration of vessel via ultrasound). 3DNavL and 3DNvMWA was feasible in central located liver segments, which could be assessed without deforming the liver. 3DNvMWA should be well planned upfront, beginning at the caudal segments and be completed before resection. 3DNvMWA without ultrasound guidance was feasible also in lateral dorsal a parts of segments 7 and 8. Short ablation devices (14cm) could interfere with the navigation tools, so longer devices (up to 29 cm) should be available. Treated lesions should be marked on the navigation system to ease later orientation in the liver. Smaller surgical wound retractors with less steel ease the use of 3DNvL. Fixing the reference tool on a plastic covered ultrasound head did not compromise navigation. Actual software update allowed in-house local data reconstruction. The acceptance of 3DNavL by the scrub nurses during implementation increased with continuous use.

Conclusion:
3D-navigation could optimize surgical treatment of multiple hepatic lesions. Technical details are important in the daily use to reach precision.

Background:
Using a unique lightning model, cinematic rendering (CR), a new 3D rendering technique, converts conventional CT image datasets into photo-realistic 3D reconstructions. The aim of this study was to compare CR images of multifragmentary intraarticular lower extremity fractures with standard volume rendering technique (VRT) images to evaluate the potential of CR in fracture visualization.

Materials and methods:
In this retrospective, IRB-approved study, 41 patients (female: n=13; male: n=28; mean age: 52.3±17.9y) with multifragmentary intraarticular fractures of the lower extremity (calcaneus: n=16, tibial pilon: n=19, acetabulum: n=6) were included. All CT datasets were acquired on a 128-row dual source CT. Using a dedicated workstation VRT and CR images were reconstructed. Independently, two experienced board-certified traumatologists trained in special trauma surgery reviewed VRT and CR images. On a 6-point Likert scale (1=non-diagnostic to 6=excellent) image quality, anatomical accuracy and fracture visualization were rated. Axial CT images with MPR were used as reference standard. Additionally, the advantage of CR over VRT images for visualization of fracture morphology was assessed. Median values between both readers were calculated for each score. Wilcoxon-Ranksum test was performed to compare both reconstruction methods (p<0.05 indicating statistical significance).

Conclusion:
CR is superior to VRT due to higher image quality and higher anatomical accuracy. Because of improved visualization of lower extremity fractures, CR reconstructions should be used for fracture demonstration in interdisciplinary conferences.

Background:
In up to 19 % of colorectal resections an anastomotic leakage is clinically evident followed by a reintervention rate in up to 80 %. The consequence is a considerable increase in morbidity and mortality. Ischemia of the anastomosis is described as one of the main independent risk factors. Thus, routinely testing of the bowel perfusion with the near-infrared fluorescence technique using indocyanine-green (ICG) should minimize this risk factor potentially leading to a significant reduction of the anastomotic leakage rate.

Materials and methods:
Indocyanine-green (ICG) is an indicator dye with the ability to fluoresce after activation with infrared light. In medicine this technique is used after intravenous application routinely e.g. for the examination of the retina perfusion in ophthalmology. Newer indications are the examination of the perfusion of gastrointestinal anastomosis or e.g. to clarify intraoperatively the anatomy of the biliary duct or to show the location of the ureter. From February to September 2018 a standardized ICG-imaging of the bowel was performed in 67 patients with colorectal surgery before and after establishing an anastomosis.First, an imaging of the resection line of the bowel followed by an examination with an introduced head of a circular stapler (if applicable) was accomplished. Finally, the perfusion of the anastomosis was checked. In case a low quality of perfusion is detected, the plane of resection area was changed.

Results:
The median age of the patients was 67y. (35-96 y.; 32 male / 35 female). The risk stratification according to the ASA Score (American Society of Anaesthesiology) was ASA1 n=3, ASA2 n=46, and ASA 3 n=18 patients. 55 procedures were elective surgery, 18 procedures were emergency operations. The indication for operation was benign in n=30 cases, in n=37 cases malignant.Procedures: ileocoecal resection (n=7), right hemicolectomy (n=17), sigmoid-and rectosigmoid resections (n= 30), sigmoid resection with rectopexy (n=1), anterior rectum resection (n=5), transanal total mesorectal excision (TATME) (n=3) and reversal of Hartmann´s procedure (n=3). 18 procedures were operated openly, 49 procedures were performed laparoscopically.Intraoperatively a low perfusion was detected in n=3 patients and the resection plane was changed into an area of good perfusion. In these three cases there was no anastomotic leakage observed postoperatively.Overall 2 cases of anastomotic leakage were detected (2,99%). One Patient was clinically inapparent and the leakage was detected after 60 days in the context of diagnostic for a reversal procedure of a protective ileostomy (clavien dindo complication score grade 1). The second anastomotic leakage was apparent on the second postoperative day (clavien dindo complication score grade 3). After the retrospectively analysis of the video documentation of this case with a very early leakage we interpret this event as a technical malfunction of the used stapler which was not detected during the procedure.

Conclusion:
The standardized imaging of the bowel perfusion before and after performing gastrointestinal anastomosis might be a promising Our results have to be interpreted with caution due to the small sample size. But the ease of performing this procedure with tolerable costs for an additional valuable information for the surgeon can lead intraoperatively to a change of the intraoperative strategy finally leading to increase in patient safety.

Universitätsklinikum Erlangen
Background: Cinematic rendering, a novel 3D visualization technology for post-processing of computed tomography (CT) or magnetic resonance (MR), provides a natural and photorealistic representation of the patient anatomy. Research on potential advantages for the comprehension of the surgical anatomy is not available. We aimed to determine the value of cinematic rendering (CR) for the comprehension of the surgical anatomy in general surgery.

Materials and methods:
In a crossover fashion, eighteen surgeons with different expertise (9 residents, 9 attendants) evaluated CR and conventional images of 40 general surgery cases. The initial image modality of each case was assigned by random sequence. All surgeons had to answer questions addressing the patients' anatomy in regards to crucial aspects of pre-operative planning or intraoperative strategies. In addition, a multiple-item questionnaire was applied to rate participants' perceived advantage of using CR compared to conventional images.

Results:
Visualization with CR allowed a more correct and faster comprehension of the surgical anatomy. . Analysis of the self-assessment questionnaire showed that CR adds significant value for the comprehension of the surgical anatomy (Table 1). No carryover or period effects were observed.

Conclusion:
In this study, visualization with CR allowed a more correct and faster comprehension of the surgical anatomy compared to conventional CT imaging. In particular, less experienced residents benefitted from this visualization tool.

Universitätsklinikum Heidelberg
Background: The evaluation of tissue perfusion and integrity is a key component of successful surgery minimizing major complications such as tissue necrosis and anastomic insufficiency.
Despite great efforts from medical-tech companies and research groups, the simple visual aspect of the tissue still is the method of choice for most surgeons.

Materials and methods:
Hyperspectral Imaging (HSI) is a novel imaging technique that addresses this issue. It works by projecting white light of a wide spectrum from 500 to 995 nm wavelength onto tissue in a field of view measuring 25 x 30 cm. The integrated camera then receives signals that are reflected by the underlying tissue. This reflection is tissue-specific and depends on oxygen saturation, haemoglobin concentration, water content, tissue temperature and a variety of other influencing factors. The camera obtains the signal intensities for each individual pixel in 5 nm steps resulting in 100 measured values for each pixel. Certain substances have characteristic absorption spectra with maxima and minima at very specific wavelengths e.g. deoxyhaemoglobin with its maximum at 555 nm. Eventually, a computer calculates indices which are presented in artificially coloured images that are overlaid onto the original photograph of the recorded site.
For this experimental animal study in a porcine model, the TIVITA™ tissue system HSI Camera is used. Indices that are directly provided by this system are oxygen saturation, tissue haemoglobin, near-infrared and tisse water. In preliminary works, it could be shown that the sensitivity of these indices is sufficient for clinical evaluation. Neither contrast agent nor ionizing radiation has to be applied for this type of imaging technique.

Results:
Further development of this technology resulted in augmented hyperspectral imaging (AHSI). Dyes with characteristic absorption spectra such as methylene blue (MB), toluidine blue (TB) and indocyanine green (ICG) are combined with conventional hyperspectral imaging allowing for an improved evaluation of perfusion situation, anastomic leakage and stenosis.
The datacubes were imported into a Python script and own indices that were developed by preceding photometry of the dyes were applied resulting in pictures that were much more sensitive for the identification of dyes compared to the human eye.

Conclusion:
AHSI is a novel system for intraoperative real-time evaluation of tissue perfusion for specific organs. Its sensitivity for ischemic regions is greater than visual inspection and has the potential to be beneficial for surgical outcomes.

Background:
Clinical research in surgery, and surgical randomized controlled trials (RCTs) in particular, represent specific difficulties and have therefore suffered from limited quality for a long time. These challenges are even pronounced in complex surgical procedures such as pancreatic surgery. The aim of the current analysis was to systematically evaluate the quantity and quality of RCTs in pancreatic surgery.

Materials and methods:
A systematic literature search in the databases PubMed, Cochrane CENTRAL and Web of Science was performed to identify all RCTs considering pancreatic surgery. Quantity and quality was compared between three periods (P-I: before 1996; P-II: 1996-2007; P-III: after 2008). Extracted data, including basic trial data and quality measures, were organized in a relational database and evidence maps were created to identify lack of evidence for particular fields.

Results:
After thorough literature screening by two independent reviewers, a total of 246 RCTs comprising data on > 26,000 patients were included in the analysis. Quantity of RCTs in pancreatic surgery increased steadily over the study period. Methodological quality, excempted the domain 'blinding' of the Cochrane Collaboration's risk of bias tool, also improved significantly during the latter segments of the study period. Most trials were from Europe (46.3%), followed by Asia (35.0%) and North America (14.2%). Evidence mapping identified limited evidence from RCTs for pancreatic surgical procedures apart from pancreatoduodenectomy and for specific diseases such as intraductal papillary mucinous neoplasms and neuroendocrine neoplasms.

Conclusion:
RCTs considering pancreatic surgery demonstrated increasing quantity, but also improved quality in recent years. The evidence maps identified several evidence gaps, which could guide prioritization of future clinical research in pancreatic surgery. Over 230 million major surgical operations are performed each year worldwide and major morbidity complicates 3-16% of all inpatient surgical procedures in developed countries, in developing countries, studies suggest a death rate of 5-10% for major surgery. The knowledge of potential risk and known risk factors is essential for surgical decision making and obtaining consent of the patient.Calculating the perioperative risk in surgical patients often relied on expertise of the surgeon and complication factors known from the literature. Many are guided by the American society of Anaesthesiologists (ASA) classification. The American college of surgeons developed a preoperative surgical risk score (Surgeons National Surgical Quality Improvement Program, ACS-NSQIP) which calculates the perioperative risk for a patient for a specific procedure. This program has collected data from 393 hospitals. It allows the surgeon to calculate the perioperative risk for a specific procedure predicting 8 outcomes.

Materials and methods:
From May 2016 until May 2017 we collected risk data on all inpatient who received surgical treatment. Excluded were children under the age of 16 and patients with major burns. 1049 patients were included in the study. All patient data was collected retrospectively. Patients data was entered into the open access ACS-Risk calculator. The individual risk scores were calculated and entered into a database. Inpatient adverse events as well as 30 days outcome data was collected and compared with the estimated risk predicted by the risk calculator. Statistical analysis was performed using the SPSS performing descriptive and multi regression analysis.

Conclusion:
The use of surgical risk calculators has sparked recent discussions about its reliability. For years surgeons have relied on statistical outcome data and their own gut feeling. The introduction of prefabricated calculators should help guide patient selection and consent. However they are not universally usable and caution must be taken when interpreting their calculated data.

Background:
Current guidelines recommend neoadjuvant therapy in terms of short-course radiotherapy or chemoradiotherapy (CRT) for patients with stage II/III rectal cancer. Neoadjuvant therapy has been shown to reduce rates of local recurrence, while it has failed to improve overall survival. Intensified treatment regimens such as addition of platinum derivatives to fluoropyrimidine-based CRT have been frequently investigated but their role in patients with stage II/III rectal cancer remains controversial.

Materials and methods:
A systematic literature search of the databases MEDLINE (PubMed), Cochrane Library and Web of Science was performed to identify randomized controlled trials (RCTs) comparing fluoropyrimidinebased CRT with or without the addition of a platinum cytotoxic agent. Trial selection, data extraction and quality assessment were performed by two reviewers independently according to the recommendations of the Cochrane Collaboration. Main endpoints were overall and disease-free survival and further outcomes included pathologic complete response, local and distant recurrences, toxicity, perioperative morbidity and treatment compliance. Time-to-event data were pooled as hazard ratios by the inverse variance method and binary outcomes were aggregated as odds ratios by means of the Peto method.

Conclusion:
Intensified neoadjuvant CRT with addition of a platinum cytotoxic agent did not improve overall survival in patients with stage II/III rectal cancer. The improvement in disease-free survival, rates of distant recurrence and pathologic complete response is achieved at the cost of a substantially increased toxicity. Thus, neoadjuvant CRT with addition of a platinum derivative cannot be recommended comprehensively but may be considered as treatment option in patients with high-risk preoperative situations.