Roux-en-Y gastric bypass (RYGB) in patients with body mass index (BMI) ≥ 50 kg/m 2 is a challenging procedure and BMI ≥ 50 kg/m 2 has been identified as independent risk factor for postoperative complications and increased morbidity in previous studies. The objective of the present study was to assess whether a BMI ≥ 50 kg/m 2 and various established risk factors maintain their significance in patients undergoing fully robotic RYGB (rRYGB). A single-center analysis of prospectively collected data of 113 consecutive patients undergoing standardized rRYGB with robotic stapling technique and hand-sewn gastrojejunostomy using the daVinci Xi system. Surgical outcomes were analyzed considering a number of individual perioperative risk factors including BMI ≥ 50 kg/m 2 . The mean BMI of the total cohort was 50.6 ± 5.5 kg/m 2 and 63.7% of patients had a BMI ≥ 50 kg/m 2 . There were no major surgical and perioperative complications in patients with BMI ≥ 50 kg/m 2 as well as in those with BMI < 50 kg/m 2 after rRYGB. We identified female sex and surgeon experience but neither body weight, BMI, metabolic disorders, ASA nor EOSS scores as independent factors for shorter operation times (OT) in multivariate analyses. Complication rates and length of hospital stay (LOS) did not significantly differ between patients with potential risk factors and those without. rRYGB is a safe procedure in both, patients with BMI ≥ 50 kg/m 2 and with BMI < 50 kg/m 2 . Higher body weight and BMI did affect neither OT nor LOS. A fully robotic approach for RYGB might help to overcome “traditional” risk factors identified in conventional laparoscopic bariatric surgery. However, larger and prospective studies are necessary to confirm these results.

Supplementary Figure S1; Supplementary Table S1.

Long-term therapy for unresectable colorectal liver metastases remains challenging. Intraarterial treatments aim to avoid systemic adverse effects of chemotherapy. Nanoliposomal cytotoxic drugs manage to increase the drug concentration within the tumor while reducing toxicity in healthy tissue. In this study we analyzed the effect of hepatic arterial infusion (HAI) with nanoliposomal irinotecan with or without the combination of embolization particles in a rat model for colorectal liver metastases. For the study 32 WAG/Rij rats received subcapsular tumor implantation with CC531 rat colonic adenocarcinoma cells. After ten days tumor size was assessed via ultrasound and animals underwent HAI. One group served as control receiving NaCl 0.9

The use of robotic systems in bariatric surgery has constantly increased over the last years. However, beside its technical advantages in morbidly obese patients the conclusive role of robotics in bariatric and metabolic surgery is still under controversial debate. This is an analysis of prospectively collected data of consecutive patients undergoing fully robotic Roux-en-Y gastric bypasses (TR-RYGB) during the first year after implementation of a robotic bariatric program at a tertiary university hospital. All patients were operated by a previously untrained robotic but experienced laparoscopic bariatric surgeon using the daVinci Xi system (Intuitive Surgical, Sarl). Data recording included patient characteristics, operative and functional outcomes, complications and learning curves for surgeon and assistants. In total, 80 patients underwent primary or revisional robotic bariatric surgery. Seventy-two patients (90%) received a TR-RYGB. There were no major complications, re-interventions or readmissions. The overall complication rate was 2.5% (Clavien–Dindo grade I and II). The overall operation time was 140.7 ± 24.6 min and decreased significantly from the first to the last decade of procedures (procedure 1–10: 171.2 ± 26.3 min versus procedure 63–72: 116.0 ± 10.9 min, p < 0.0001). A stabilization of the learning curve was observed after 30 procedures for the surgeon and after five procedures for the bedside assistant. With immediate effect, TR-RYGB is a safe procedure with low complication rates for an experienced laparoscopic bariatric surgeon without prior robotic skills. Learning curves are steep and operation times can be effectively decreased by increasing the experience of the surgeon.

Background: The association of treatment volume and oncological outcome of rectal cancer patients undergoing multidisciplinary treatment is subject of an ongoing debate. Prospective data on long-term local control and overall survival (OS) are not available so far. This study investigated the long-term influence of hospital and surgeon volume on local recurrence (LR) and OS in patients with locally advanced rectal cancers. Methods: In a post-hoc analysis of the randomized phase III CAO/ARO/AIO-94 trial after a follow-up of more than 10 years, 799 patients with stage II/III rectal cancers were evaluated. LR-rates and OS were stratified by hospital recruitment volume (<20 vs. 21-90 vs. >90 patients) and by surgeon volume (<10 vs. 11-50 vs. >50 procedures) Results: Patients treated in high-volume hospitals had a longer OS than those treated in hospitals with medium or low treatment volume (p = 0.03). The surgeon volume was adversely associated with LR (p = 0.01) but had no influence on overall survival. The positive effect of neoadjuvant chemoradiation (CRT) on local control was the strongest in patients being operated by medium-volume surgeons, less in patients being operated by high-volume surgeons and missing in those being operated by low-volume surgeons. Conclusions: Patients with locally advanced rectal cancers might benefit from treatment in specialized high-volume hospitals. In particular, the surgeon volume had significant influence on long-term local tumour control. The effect of neoadjuvant CRT on local tumour control may likewise depend on the surgeon volume.

To assess the diagnostic potential of dynamic real-time MRI for fundoplication failure in patients with persistent or recurrent GERD-like (gastroesophageal reflux disease) complaints. Twenty-two consecutive patients (male n = 11; female n = 11; median age 59 years) with recurrent or persistent GERD-like symptom after fundoplication were enrolled between 2015 and 2017. Median duration of GERD-like symptoms was 21 months. Real-time MRI (3 Tesla) was performed at 40 ms temporal resolution using undersampled radial fast low-angle shot acquisitions with nonlinear inverse image reconstruction. MRI movies dynamically visualized bolus transit of pineapple juice through the gastroesophageal junction, position of the fundoplication wrap and recurring hernia or reflux during Valsalva maneuver. MRI results were compared to endoscopic findings. Real-time MRI was successfully completed in all patients without adverse events (average examination time 15 min). Morphological correlates for GERD-like symptoms were evident in 20 patients (90.1%) with gastric reflux in 19 cases. Nine patients (40.1%) had wrap disruption and recurrent gastric hernia. Wrap migration or telescoping hernia was detected in nine patients (40.1%). One patient presented with continued reflux despite intact fundoplication wrap. Esophageal dysmotility with delayed bolus passage was observed in one case. On endoscopy, gastric hernia or wrap disruption was diagnosed in seven cases, and esophagitis or Barret’s metaplasia in nine cases. Real-time MRI is a fast and safe modality for dynamic imaging after fundoplication, without radiation exposure or administration of gadolinium-based contrast media. In a relevant number of cases, real-time MRI reveals correlates for GERD-like symptoms. • Real-time MRI reliably visualizes the gastroesophageal junction after fundoplication surgery. • Patients with recurring GERD-like symptoms have a high rate of morphological failure patterns that can be identified by real-time MRI. • Dynamic assessment of gastroesophageal junction by real-time MRI is a perspective diagnostic tool for detection of fundoplication failure.

Intraarterial chemotherapy for colorectal liver metastases (CRLM) can be applied alone or together with embolization particles. It remains unclear whether different types of embolization particles lead to higher intratumoral drug concentration. Herein, we quantified the concentrations of CPT-11 and its active metabolite SN-38 in plasma, liver and tumor tissue after hepatic arterial infusion (HAI) of irinotecan, with or without further application of embolization particles, in a rat model of CRLM. Animals underwent either systemic application of irinotecan, or HAI with or without the embolization particles Embocept® S and Tandem™. Four hours after treatment concentrations of CPT-11 and SN-38 were analyzed in plasma, tumor and liver samples by high-performance liquid chromatography. Additionally, DNA-damage and apoptosis were analyzed immunohistochemically. Tumor tissue concentrations of SN-38 were significantly increased after HAI with irinotecan and EmboCept® S compared to the other groups. The number of apoptotic cells was significantly higher after both HAI with irinotecan and EmboCept® S or Tandem™ loaded with irinotecan compared to the control group. HAI with irinotecan and EmboCept® S resulted in an increased SN-38 tumor concentration. Both HAI with irinotecan and EmboCept® S or Tandem™ loaded with irinotecan were highly effective with regard to apoptosis.

To assess the diagnostic potential of real-time MRI for assessment of hiatal hernias in patients with GERD-like symptoms compared to endoscopy. One hundred eight patients with GERD-like symptoms were included in this observational cohort study between 2015 and 2017. Real-time MRI was performed at 3.0 Tesla with temporal resolution of 40 ms, dynamically visualizing the esophageal transport of a pineapple juice bolus, its passage through the gastroesophageal junction, and functional responses during Valsalva maneuver. Hernia detection on MRI and endoscopy was calculated using contingency tables with diagnosis of hernia on either modality as reference. Of 108 patients, 107 underwent successful MRI without adverse events; 1 examination was aborted to inability to swallow pineapple juice in supine position. No perforation or acute bleeding occurred during endoscopy. Median examination time was 15 min. Eighty-five patients (79.4%) were diagnosed with hiatal hernia on either real-time MRI or endoscopy. Forty-six hernias were visible on both modalities. Seventeen hernias were evident exclusively on MRI, and 22 exclusively on endoscopy. Sixteen of the 63 MRI-detected hernias (25.4%) were detectable only during Valsalva maneuver, which were smaller compared to hernias at rest (median − 13.5 vs − 33.0 mm, p < 0.001). Diagnostic accuracy for hernia detection was comparable for MRI and endoscopy (sensitivity 74% vs 80%, p = 0.4223; specificity 100% vs 100%, p > 0.99). Real-time MRI is a fast and safe modality for assessment of the gastroesophageal junction, without radiation exposure or administration of gadolinium-based contrast media. Although MRI and endoscopy yield comparable diagnostic accuracy, dynamic MRI sequences are able to visualize hiatal hernias that were occult on static MRI sequences or endoscopy in a relevant number of cases. • Real-time MRI is a safe and fast imaging modality for examination of the gastroesophageal junction, combining anatomical and functional information for enhanced detection of hiatal hernias. • Real-time MRI and endoscopy yield comparably high diagnostic accuracy: real-time MRI visualizes hiatal hernias that were occult on endoscopy in a relevant number of patients; however, several hiatal hernias detected on endoscopy were occult on real-time MRI. • There is clinical potential of real-time MR imaging in patients with GERD-like symptoms and equivocal findings on endoscopy or pH-metry, for anatomical visualization in patients planned for surgical intervention, or those with suspected fundoplication failures.

738 Background: The association of hospital and surgeon volume with the outcome of rectal cancer patients is under debate. In this study the long-term influence of the hospital as well as the surgeon volume on overall survival and local recurrence were investigated. Methods: In a post-hoc analysis of the randomized phase III CAO/ARO/AIO-94 trial after a follow-up of more than 10 years, 799 patients with locally advanced rectal cancers were evaluated. Survival and local recurrence rates were stratified by the hospital recruitment volume (≤20 vs. 21-90 vs. > 90 patients) and by the surgeon volume (≤10 vs. 11-50 vs. > 50 procedures). Results: Patients treated in „high-volume“ hospitals had a longer overall survival than those treated in hospitals with medium or low treatment volume (p = 0.03). The surgeon volume was significantly associated with decreased local recurrences (p = 0.01) but had no influence on overall survival. The effect of neoadjuvant chemoradiation on local control was the strongest in patients being operated by medium-volume surgeons. Conclusions: Patients with locally advanced rectal cancers might benefit from treatment in in specialized high-volume hospitals. In particular, the surgeon volume had significant influence on local control.

The influence of postoperative complications on survival in patients with locally advanced rectal cancer undergoing combined modality treatment is debatable. This study evaluated the impact of surgical complications on oncological outcomes in patients with locally advanced rectal cancer treated within the randomized CAO/ARO/AIO‐94 (Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society) trial.

The cellular sarcoma gene (SRC) is a proto-oncogene encoding for a tyrosine kinase.SRC expression was determined in locally advanced rectal adenocarcinoma tissue from pretreatment biopsies and resection specimens.The expression level was correlated with clinicopathological parameters to evaluate the predictive and prognostic capacity.For this monocentric analysis 186 patients with locally advanced rectal cancer (median: 63.7 years; 130 men (69.9%), 56 women (30.1%)) were included.Patients with a carcinoma of the upper third of the rectum were treated with primary tumor resection (n=27; 14.5%).All other patients received a preoperative chemoradiotherapy (CRT) with 50.4 Gy and concomitant 5-fluorouracil (5-FU) or 5-FU+oxaliplatin followed by postoperative chemotherapy with 5-FU or 5-FU+oxaliplatin.SRC expression was determined with immunohistochemical staining from pretreatment biopsies (n=152) and residual tumor tissue from the resection specimens (n=163).The results were correlated with clinicopathological parameters and long-term follow-up.The expression of SRC was determined in pretherapeutic biopsies (mean H-Score: 229) and resection specimens (mean H-Score: 254).High SRC expression in pretherapeutic tumor samples significantly correlated with a negative postoperative nodal status (p=0.005).Furthermore an increased protein expression in residual tumor tissue was associated with fewer distant metastases (p=0.04).The overexpression of SRC in pretreatment tumor biopsies showed also a trend for a longer cancer-specific survival (CSS; p=0.05) and fewer local relapses (p=0.06)during long-term follow-up.High SRC expression in rectal cancer seems to be associated with a better long-term outcome.This finding could help in the future to stratify patients for a recurrence risk adapted postoperative treatment.

Die Therapie von Tumorerkrankungen innerhalb spezialisierter Zentren mit entsprechend hohen Behandlungsvolumina wird zunehmend als vorteilhaft für den onkologischen Verlauf und das Überleben der Patienten angesehen.

670 Background: The influence of major surgical complications on survival in patients with locally advanced rectal cancer undergoing combined modality treatment is still debatable. The aim of this study was to evaluate the impact of surgical complications on oncological outcome in 823 patients with locally advanced rectal cancer treated within the phase III CAO/ARO/AIO-94 trial. Methods: Anastomotic leakages as well as wound healing disorders were prospectively evaluated and correlated with overall survival (OS) and the cumulative incidence of distant metastasis and local recurrence after a long-term follow-up of more than 10 years. Results: Anastomotic leakage after restorative rectal resection is significantly correlated with an impaired 10-year OS (51.0% vs. 65.2%, p = 0.02). Patients with abdominal or sacral wound healing disorders had a significantly reduced OS compared to those with sufficient wound healing (45.2% vs. 62.7%, p = 0.009). Patients developing any surgical complication (anastomotic leakage or/and wound healing disorder) had an impaired OS (50.6% vs 65.3%, p = 0.0002) as well as higher rates of distant metastases (65.3% vs. 72.7%, p = 0.03) and local recurrences (6.0% vs. 12.9%, p = 0.0007). In a multivariate cox regression model the only independent factors for restricted OS were lymph node metastases (p < 0.0001) and the occurrence of surgical complications (p = 0.008). Conclusions: Surgical complications are significantly associated with an adverse oncological outcome and reduced long-term OS in patients undergoing combined modality treatment for locally advanced rectal cancer.

For patients with rectal cancer and complete remission (ypT0) or with good response and residual tumor restricted only to the bowel wall (ypT1-2) after neoadjuvant chemoradiotherapy (CRT), local excision has been suggested as an alternative to avoid the significant morbidity and functional deficits associated with total mesorectal excision (TME). The aim of this investigation was to investigate the incidence, distribution and tumor-related localization of mesorectal lymph node (LN) metastases in TME specimens with complete remission (ypT0), intramural (ypT1-2) and extramural (ypT3-4) residual tumor tissue.Specimens of TME from 81 patients with locally advanced rectal cancer (UICC II-III) undergoing neoadjuvant CRT within the phase III German rectal cancer trial CAO/ARO/AIO-04 were prospectively evaluated. The entire mesorectal compartment was microscopically screened after complete paraffin embedding. The number and localization of all detectable LN metastases were documented in relation to the primary tumor.Whereas 50 patients (62 %) had ypT3-4 rectal cancer after neoadjuvant CRT, 20 patients (25 %) presented with residual tumor within the bowel wall (ypT1-2), 11 patients (14 %) had pathological complete remission (ypT0), an average of 28 +/- 13.7 LN were detected per specimen and 25 patients (31 %) had residual LN metastases after CRT. Although the incidence of LN metastases was higher in the ypT3-4 group (40 %), 25 % of patients in the ypT1-2 group with intramural residual tumor had a mean number of 2.2 residual LN metastases of which 55 % were located far from the primary lesion in the proximal mesorectum. None of the patients with ypT0 status (complete response) had residual LN metastases.Even in patients with good response and post-CRT tumor tissue restricted only to the bowel wall (ypT1-2), there is still a considerable risk for residual LN metastases. Local excision of residual rectal cancer was accompanied by a higher rate of local failure and radical surgery with TME should remain the standard treatment in these patients. To date, valid selection criteria for patients eligible for organ-sparing surgery are still lacking.

Für Patienten mit Rektumkarzinom und kompletter Remission (ypT0) oder guter Response mit intramuralem Residualtumor (ypT1–2) nach neoadjuvanter Radiochemotherapie (RCT) wurden – zur Reduktion postoperativer Funktionseinschränkungen – wiederholt lokale Operationsverfahren als Alternative zur totalen mesorektalen Exzision (TME) vorgeschlagen. Ziel dieser Untersuchung war eine vergleichende Analyse von Frequenz und tumorabhängiger Lokalisation mesorektaler Lymphknotenmetastasen bei Patienten mit kompletter Remission (ypT0), intramuralem (ypT1–2) und wandüberschreitendem Residualtumor (ypT3–4).

BACKGROUND: For patients with ycT1/2 rectal carcinomas after neoadjuvant chemoradiotherapy, local excision instead of radical surgery has increasingly been discussed as a way to avoid postoperative morbidity associated with radical surgery. OBJECTIVE: The purpose of this study was to determine the incidence of lymph node metastases in total mesorectal excision specimens with ypT0, ypT1/2, and ypT3/4 rectal cancers. DESIGN: This is a prospective and retrospective cohort study. SETTINGS: This study was conducted in tertiary referral hospitals that are part of the German Rectal Cancer Study Group. PATIENTS: A total of 479 patients with stage II and III rectal cancers treated within phase III trials of the German Rectal Cancer Study Group were evaluated. Specimens from 81 patients treated in the Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society (CAO/ARO/AIO-04) trial were prospectively studied with extensive microscopic screening of the entire mesorectum. The frequency and localization of nodal metastases were specified and compared with those of 398 patients having received neoadjuvant chemoradiation within the CAO/ARO/AIO-94 trial. MAIN OUTCOME MEASURES: Frequency and localization of mesorectal lymph node metastases in patients with ypT0, ypT1/2, or ypT3/4 cancer were measured. RESULTS: A mean number of 28.0 ± 13.7 nodes were detected per specimen within the prospective group. A total of 25% of patients in the ypT1/2 group had nodal metastases compared with 40% in the ypT3/4 group. Patients with node-positive ypT1/2 had a mean number of 2.2 metastases, and 55% of these metastases were located far from the primary lesion in the proximal mesorectum. Within the CAO/ARO/AIO-94 cohort (n = 398), 19% of patients with ypT1/2 (ypT1 = 22%; ypT2 = 18%) had ypN+ status compared with 43% with ypT3/4 cancers (ypT3 = 40%; ypT4 = 73%). LIMITATIONS: Low numbers of patients with ypT0 limited the evaluation of nodal metastases in pathologic complete responders. CONCLUSIONS: Even in good responders (ypT1/2), >20% of rectal carcinomas still harbored residual lymph node metastases. Local excision for patients with ycT1/2 rectal cancers would, thus, miss metastases in a considerable percentage and might involve the risk of significant undertreatment in a number of patients.

575 Background: The development of metachronous distant metastasis is – despite remarkable progress - still a challenging problem after multimodality treatment of rectal cancer. The host immune response has been identified as a valid prognostic marker in primary colon cancer but not in rectal cancer after neoadjuvant chemoradiotherpy so far. Methods: We analysed the mRNA and protein expression of the B- and T-cell chemokines CXCL13 and CXCL9 as well as the B-cell marker IGHM in 77 rectal cancer specimens undergoing preoperative chemoradiotherapy and investigated the role of the host immune response on the occurrence of distant metastasis and survival. Results: The intratumoral mRNA expression levels of the T-cell activator CXCL9 (p < 0.001) as well as the B-cell chemokine CXCL13 (p < 0.01) were inversely correlated with the development of distant metastasis. Patients with high CXCL9 (p < 0.0001) or CXCL13 expression (p < 0.01) had a significantly prolonged DFS. Moreover, patients with high mRNA levels of both CXCL9 and CXCL13 had an excellent DFS compared to patients without expression of any of the chemokines (p < 0.0001). Additionally, CXCL9 expression was correlated with an improved CSS (p < 0.05). There was no significant correlation between the B-cell marker IGHM and metastasis or survival. Conclusions: The host immune response represented by intratumoral expression levels of the lymphocyte-activating chemokines CXCL9 and 13 is associated with reduced rates of distant metastases and improved survival in rectal cancers after multimodality treatment. Further investigations are needed to prospectively validate these results and characterize the underlying cellular and molecular mechanisms.

585 Background: Members of the EGFR family are established targets for specific therapy approaches in a variety of malignancies. Especially HER-2 has been targeted for more than a decade in breast cancer and more recently in gastric cancer and adenocarcinomas of the gastroesophageal junction. Applying the HER-2 scoring algorithm established in gastric cancer we here investigated HER-2 expression in rectal cancer using FFPE tumor samples from both large trials of the German Rectal Cancer Study Group (GRCSG)-(CAO/ARO/AIO-94 and -04). Methods: Overall, FFPE samples from 839 patients from 63 sites were available. All patients received standardized multidisciplinary treatment according to protocols of the phase-III-trials. 104 patients were treated by primary tumor resection followed by adjuvant CRT, all other patients (n=547) had preoperative CRT either with concomitant 5-FU mono therapy (n=329, 60.1%) or a combination of 5-FU and oxaliplatin (n=218, 39.9%). The HER-2-status was determined in resection specimens using immunohistochemistry scoring and S-ISH-amplification detection. Tumors with IHC 3+ or S-ISH ratios of ≥2.2 were classified HER-2-positive; these results were correlated with clinicopathological parameters (e.g., resection status, nodal-status ((y)pN)), time to recurrence (TTR) and cancer specific survival (CSS). Results: Positive HER-2-status was found in 13.8% of resected specimens. Positivity rate in primary resection specimens was 11.5% (n=12), while after preoperative CRT 13.2% (n=78 ) patients showed a HER-2 positive tumor; 13.1% (n=43) after 5-FU mono and 13.3% (n=35) after combination of 5-FU and oxaliplatin. There was no prognostic difference according to the HER-2 status regarding TTR (p=0.90) and CSS (p=0.68) overall. However in the 5-FU mono subgroup the HER-2 expression was of prognostic relevance as measured by CSS (p=0.034). Conclusions: Analysis of 839 patients from the GRCSG validated a relevant HER-2 amplification of 13.8% in samples of rectal adenocarcinoma. Besides its potential as an independent predictor of survival HER-2 may represent a promising target for innovative therapies and should be further assessed.