Robotic-assisted rectosigmoid resection rectopexy with natural orifice specimen extraction (NOSE): technical notes, short-term results, and functional outcome.

PURPOSE: Rectosigmoid resection rectopexy has been established as an effective therapy for obstructive defecation syndrome. The addition of the NOSE-technique provides an even less invasive approach avoiding minilaparotomy, but can be technically challenging. Application of a robotic platform has been proposed to facilitate the specimen extraction and fashioning of the intracorporeal anastomosis and has been proven to be effective in left-sided colectomies. METHODS: After establishing laparoscopic rectosigmoid-resection-rectopexy with NOSE, we modified our technique by addition of the robotic platform. Whenever robotic capacity was available, elective patients scheduled for rectosigmoid resection rectopexy for obstructive defecation syndrome were operated robotically assisted. Demographic and intraoperative data were prospectively collected. Follow up was assessed using the Wexner constipation score, Wexner incontinence score, and Altomare ODS score. RESULTS: The NOSE-RRR technique was completed in all 31 patients. The mean operative time was 166 min (range 67-230). No conversion was required. The median hospital stay was 5 days (range 3-28). Four patients had minor complications (Clavien I). Two patients were reoperated (Clavien IIIb). Functional scores improved significantly postoperatively. Mean Wexner incontinence score was 7.1 preoperatively, 6.9 after 1 month, and decreased significantly to 3.93 after 3 months (p < 0.001). Mean Altomare ODS score was 17.47 preoperatively and 6.93/5.03 after 1/3 months (p < 0.001). Wexner constipation score (12.83) also showed a significant improvement after 1/3 months (6.97/6.67; p < 0.001). CONCLUSION: NOSE-RRR can be performed safely with a low rate of manageable complications. The technique provides a significant improvement for ODS-Symptoms.

Technical feasibility and perioperative outcome of laparoscopic resection rectopexy with natural orifice specimen extraction (NOSE) and intracorporeal anastomosis (ICA).

PURPOSE: Laparoscopic rectosigmoid resection rectopexy (LRR) is the most effective treatment of obstructive defecation syndrome but is associated with a higher postoperative morbidity compared to transanal approaches. Natural orifice specimen extraction (NOSE) has been described as a promising technique to lower morbidity in colorectal cancer surgery. In this study, we analyze the technical challenges of adapting this technique to LRR and compare the perioperative results to the conventional laparoscopic technique with specimen extraction via minilaparotomy and extracorporeal anastomosis. METHODS: We retrospectively analyzed 45 patients who underwent laparoscopic rectosigmoid resection rectopexy due to obstructive defecation syndrome at our institutions. From September 2020 to July 2021, we treated 17 consecutive patients with NOSE-LRR and compared the results to a historic cohort of 28 consecutive patients treated with conventional laparoscopic rectosigmoid resection rectopexy plus minilaparotomy (LAP-LRR) for specimen extraction between January 2019 and July 2020. Assessed were patient- and disease-specific parameters, operative time, hospital and postoperative complications and subjective patient satisfaction after 6 months of follow-up. RESULTS: Both groups were comparable in terms of gender distribution, age, and comorbidities. The median operating time was similar and the perioperative morbidity was comparable in both groups. The length of stay in hospital was significantly shorter in the NOSE-LRR group (median 6 vs 8 days). CONCLUSION: NOSE-LRR can be implemented safely, performed in a comparable operating time, and is associated with a comparable rate of postoperative complications. The technique offers the a potentially fast postoperative recovery compared to the conventional laparoscopic technique.

[Robotic Pancreatic Surgery - Learning Curve and Implementation]. / Robotische Pankreaschirurgie ­ Lernkurve und Etablierung.

Minimally invasive resection techniques for the treatment of various pathologies of the pancreas are potentially advantageous for the treated patients in terms of restitution time and postoperative morbidity, but are a technical challenge for the responsible surgeon. The introduction of robotic assistance in visceral surgery offers a possibility for further distribution of minimally invasive procedures in pancreatic surgery.The aim of this study was to examine the possibilities for developing robotic pancreatic surgery in Germany. The data are based on the quality reports of the hospitals for the years 2015-2019 combined with a selective literature search.The number of quality reports available decreased from 1635 to 1594 between 2015 and 2019. A median of 96 clinics performed 11-20, 56 clinics 21-50 and 15 clinics more than 50 pancreaticoduodenectomies. For distal resections, there were 35 clinics with 11-20, 14 clinics with 21-50 and two clinics with more than 50 procedures. In relation to all clinics with at least five distal resections per year, minimally invasive procedures were performed at only 29 clinics; a ratio to laparoscopic left resections of over 50% was reported in only seven clinics.According to the literature, the learning curves for robotic pancreatic distal resection and pancreaticoduodenectomy diverge. While the learning curve for robotic distal resection is completed after around 20 procedures, the learning curve for robotic pancreaticoduodenectomy has several plateaus, which are reached after around 30, 100 and 250 procedures.Due to the decentralised structure of pancreatic surgery in Germany, a nationwide introduction of robotic pancreatic surgery is unlikely. The routine use of robotic pancreaticoduodenectomy will probably be restricted to high volume centres in the foreseeable future.

Perioperative FLOT chemotherapy plus surgery for oligometastatic esophagogastric adenocarcinoma: surgical outcome and overall survival.

BACKGROUND: Guidelines do not recommend surgery for patients with oligometastatic disease from esophagogastric adenocarcinoma (EGAC), although some studies suggest a more favorable survival. We analyzed the outcome of oligometastatic EGAC receiving FLOT chemotherapy followed by surgery. METHODS: The data of patients with either pre-therapeutic, post-neoadjuvant or intraoperative clinical diagnosis of oligometastatic EGAC were extracted from a prospective database of the 2009-2018 treatment period. 48 consecutive patients were identified with oligometastatic disease, who underwent perioperative chemotherapy plus surgery. We retrospectively analyzed surgical outcome and overall survival. RESULTS: The overall 5-year survival was 18%. 12 patients (25%) with pre-therapeutic oligometastatic EGAC, who had no histologic vital tumor evidence of metastases after surgery had a survival rate of 48% compared to an 11% 5-year survival rate of 36 patients (75%), who had histologic vital tumor metastatic evidence after FLOT chemotherapy and surgical resection (p = 0.012). The survival rates after R0, R1 and R2 (non-resected metastases) resection were 21% (n = 33), 0% (n = 4) and 17% (n = 11), respectively (p = 0.273). CONCLUSION: Oligometastatic EGAC is associated with poor overall survival even after complete resection of all tumor manifestations. The subgroup of patients with a complete histologic response of metastatic lesions to neoadjuvant FLOT shows 5-year survival rates similar to non-metastatic EGAC. Trial registration Not applicable.

[Robot-assisted Living Donor Nephrectomy - Technical Aspects and Initial Evidence]. / Robotisch assistierte Nierenlebendspende ­ technische Aspekte und erste Evidenz.

Minimally invasive donor nephrectomy has become the standard procedure in most transplant centres over the past two decades and has contributed to a reduction in postoperative morbidity for the donor. Robot-assisted technology is an alternative to conventional (hand-assisted) laparoscopic technology and will find increasing use in the future. In this review article, we address technical aspects of robotic-assisted donor nephrectomy, in accordance with our own experience and will provide an overview of the currently available literature. Robot-assisted living kidney donation is a safe procedure with a very low postoperative complication rate. The procedure offers advantages over the open surgical technique with respect to the reduction in the postoperative need for analgesia and the duration of hospital stay, with longer operating times and warm ischemia times, but without a measurable effect on transplant function. The postoperative outcome parameters are comparable to those of the laparoscopic technique, indicating a further acceleration of postoperative convalescence. The advantages of robot-assisted technology, due to the better exposure options, are most relevant in patients with a high BMI and multiple renal arteries, as well as in right-sided nephrectomies in which a longer transplant artery can be obtained. Robot-assisted living kidney donation will play a major role in the future of transplant surgery and is a serious alternative to conventional laparoscopic technology.

Simultaneous ipsilateral nephrectomy during kidney transplantation in autosomal dominant polycystic kidney disease: a matched pair analysis of 193 consecutive cases.

BACKGROUND: In end-stage renal transplant recipients with autosomal-dominant polycystic kidney disease (ADPKD), the imperative, optimal timing, and technique of native nephrectomy remains under discussion. The Freiburg Transplant Center routinely performs a simultaneous ipsilateral nephrectomy. METHODS: From April 1998 to May 2017, we retrospectively analyzed 193 consecutive ADPKD recipients, receiving per protocol simultaneous ipsilateral nephrectomy and compared morbidity, mortality, and outcome with 193 non-ADPKD recipients of a matched pair control. RESULTS: The incidence of surgical complications was similar with respect to severe medical, surgical, urological, vascular, and wound-related complications as well as reoperation rates and 30-day mortality. Intraoperative blood transfusions were required more often in the ADPKD (22.8%) compared with the control group (6.7%; p < 0.0001). Early postoperative urinary tract infections occurred more frequent (ADPKD 40.4%/control 29.0%; p = 0.0246). Time of surgery was prolonged by 30 min (ADPKD 169 min; 95%CI 159.8-175.6 min/control 139 min; 95%CI 131.4-145.0 min; p < 0.0001). One-year patient (ADPKD 96.4%/control 95.8%; p = 0.6537) and death-censored graft survival (ADPKD 94.8%/control 93.7%; p = 0.5479) were comparable between both groups. CONCLUSIONS: With respect to morbidity and mortality, per protocol, simultaneous native nephrectomy is a safe procedure. Especially in asymptomatic ADPKD KTx recipients, the number of total operations can be reduced and residual diuresis preserved up until transplantation. In living donation, even preemptive transplantation is possible.

Recurring Anastomotic Leak-A Prospective Clinicopathological Investigation of a Distinct Disease Pattern.

BACKGROUND: Intestinal anastomotic insufficiency (AI) is a common problem in visceral surgery associated with overexpression of matrix metalloproteinases (MMPs). In some patients it occurs more than once. The etiology of recurring anastomotic insufficiency (RAI) is not understood yet and should be addressed as an independent disease entity. MATERIALS AND METHODS: Thirty nine consecutive patients with AI were treated at our university center and were included in this prospective study. Clinical data were evaluated by correlative statistical analysis to identify independent risk factors for RAI. Patients were divided in two groups: 18 patients had a single operative revision until restoration (group SAI), and 21 patients had two or more revisions (group RAI). Anastomotic tissue samples as well as untouched bowel wall were collected during reoperations for analysis of MMPs and tissue inhibitor of metalloproteinases (TIMP2). Clinical data were correlated with pathological observations. RESULTS: Significant differences of clinical and molecular pathological data were found between the two groups. Transfusion of red blood cells until the first reoperation and alcohol abuse led to RAI and were the only independent risk factors for RAI in multivariate analysis. Overexpression of MMP-8, -9, and -13 in anastomotic tissue correlated with the administration of red blood cells during initial operation. Reduced expression of TIMP2 was frequent in nearly all patients without differences throughout the subgroups. CONCLUSIONS: RAI seems to have an independent disease pattern. Transfusion of blood products is not only a known risk factor for AI but seems to significantly disturb the anastomotic healing process leading to RAI.

The effect of pasireotide on intestinal anastomotic healing with and without whole-body irradiation in a rat model.

OBJECTIVE: To examine pasireotide's effect on intestinal anastomotic healing under physiological conditions and following preoperative whole-body irradiation. MATERIAL AND METHODS: Forty-five male Wistar rats received an ileoileal end-to-end anastomosis. Group 1 (Co, n = 9) served as control. Group 2 (SOM, n = 10) received pasireotide (60 mg/kg) 6 days preoperatively. Group 3 (R-Co, n = 13) was subjected to 8 Gy whole-body irradiation 4 days preoperatively. Finally, group 4 (R-SOM, n = 13) received pasireotide 6 days preoperatively and whole-body irradiation 4 days preoperatively. On postoperative day 4, anastomotic bursting pressure, histology, IGF-1 staining, and collagen density were examined. RESULTS: Mortality was higher in irradiated animals (30.8% vs. 5.3%, p = 0.021), and anastomotic bursting pressure was significantly lower (median, R-Co = 83 mmHg; R-SOM = 101 mmHg; Co = 149.5 mmHg; SOM = 169 mmHg). Inflammation measured by leukocyte infiltration following irradiation was reduced (p = 0.023), and less collagen was observed, though this was not statistically significant. Bursting pressure did not significantly differ between Co and SOM and between R-Co and R-SOM animals respectively. Semi-quantitative scoring of IGF-1, fibroblast bridging, or collagen density did not reveal significant differences among the groups. CONCLUSION: Whole-body irradiation decreases the quality of intestinal anastomotic wound healing and increases mortality. Pasireotide does not significantly lessen this detrimental effect.

Single cohort study: ABO-incompatible kidney transplant recipients have a higher risk of lymphocele formation.

PURPOSE: Since 2004, ABO-incompatible kidney transplantation (ABOi KTx) became an established procedure to expand the living donor pool in Germany. Currently, ABOi KTx comprises > 20% of all living donor KTx. Up to September 2015, > 100 ABOi KTx were performed in Freiburg. Regarding lymphocele formation, only scarce data exist. METHODS: Between April 2004 and September 2015, 106 consecutive ABOi and 277 consecutive ABO-compatible kidney transplantations (ABOc KTx) were performed. Two ABOi and 117 ABOc recipients were excluded due to differences in immunosuppression. One hundred-four ABOi and 160 ABOc KTx patients were analyzed concerning lymphocele formation. RESULTS: The incidence of lymphoceles in ABOi KTx was 25.2% and 10.6% in ABOc KTx (p = 0.003). A major risk factor appeared the frequency of ≥ 8 preoperative immunoadsorption and/or plasmapheresis sessions (OR 5.61, 95% CI 2.31-13.61, p < 0.001). Particularly, these ABOi KTx recipients had a distinctly higher risk of developing lymphocele (40.0% vs. 19.2%, p = 0.044). IA/PE sessions on day of transplantation (no lymphocele 20.0% vs. lymphocele 28.6%, p = 0.362) or postoperative IA/PE sessions (no lymphocele 25.7% vs. lymphocele 24.1%, p = 1.0) showed no influence on formation of lymphoceles. CONCLUSION: In ABOi KTx, the incidence of lymphocele formation is significantly increased compared to ABOc KTx and leads to more frequent surgical reinterventions without having an impact on graft survival.

Epidural analgesia and avoidance of blood transfusion are associated with reduced mortality in patients with postoperative pulmonary complications following thoracotomic esophagectomy: a retrospective cohort study of 335 patients.

BACKGROUND: Postoperative pulmonary complications (PPCs) represent the most frequent complications after esophagectomy. The aim of this study was to identify modifiable risk factors for PPCs and 90-days mortality related to PPCs after esophagectomy in esophageal cancer patients. METHODS: This is a single center retrospective cohort study of 335 patients suffering from esophageal cancer who underwent esophagectomy between 1996 and 2014 at a university hospital center. Statistical processing was conducted using univariate and multivariate stepwise logistic regression analysis of patient-specific and procedural risk factors for PPCs and mortality. RESULTS: The incidence of PPCs was 52% (175/335) and the 90-days mortality rate of patients with PPCs was 8% (26/335) in this study cohort. The univariate and multivariate analysis revealed the following independent risk factors for PPCs and its associated mortality. ASA score ≥ 3 was the only independent patient-specific risk factor for the incidence of PPCs and 90-days mortality of patients with an odds ratio for PPCs being 1.7 (1.1-2.6 95% CI) and an odds ratio of 2.6 (1.1-6.2 95% CI) for 90-days mortality. The multivariate approach depicted two independent procedural risk factors including transfusion of packed red blood cells (PRBCs) odds ratio of 1.9 (1.2-3 95% CI) for PPCs and an odds ratio of 5.0 (2.0-12.6 95% CI) for 90-days mortality; absence of thoracic epidural anesthesia (TEA) revealed the highest odds ratio 2.0 (1.01-3.8 95% CI) for PPCs and an odds ratio of 3.9 (1.6-9.7 95% CI) for 90-days mortality. CONCLUSION: In esophageal cancer patients undergoing esophagectomy via thoracotomy, epidural analgesia and the avoidance of intraoperative blood transfusion are significantly associated with a reduced 90-days mortality related to PPCs.

Outcome after hepatic resection for isolated non-colorectal, non-neuroendocrine liver metastases in 100 patients - the role of the embryologic origin of the primary tumor.

BACKGROUND: The indication for hepatic resection (HR) in patients suffering from liver metastases (LM) other than colorectal and neuroendocrine tumors is one focus of current multidisciplinary, oncologic considerations. This study retrospectively analyzes outcome after HR for non-colorectal, non-neuroendocrine (NCNNE) LM in the absence of distant or extrahepatic metastases. METHODS: We included 100 consecutive patients undergoing HR for isolated NCNNE LM from a prospective database in our institution, including postoperative follow-up. Primary tumors were of mesodermal origin in 44%, of ectodermal origin in 29% and of entodermal origin in 27%. Survival analysis was performed by univariate and multivariable methods. Mean follow-up after hepatic surgery was 3.6 years (0.25-16). RESULTS: Median age at the time of HR was 59.5 years. Kaplan-Meier-estimated survival after liver resection was 56.8%, 34.3% and 24.5% after 5, 10 and 15 years, respectively. Univariate analysis after HR revealed residual disease (hepatic or primary; p = 0.02), female gender (p = 0.013), entodermal origin (p = 0.009) and early onset of metastatic disease (≤24 months, p = 0.002), as negative prognostic factors. Multivariable survival analysis confirmed residual disease, female gender, entodermal embryologic origin and early onset of metastatic disease (≤24 months) as independent negative prognostic factors. CONCLUSION: Overall outcome after HR of NCNNE LM results in acceptable long-term outcome. Although individual decision-making today mostly relies on clinical experience for this type of disease, risk factors derived from the embryologic origin of the tumor might help in patient selection.

[Prevention and Surgical Therapy of Chylothorax]. / Prävention und operative Therapie des Chylothorax.

BACKGROUND: Chylothorax is a rare complication after thoracic trauma or surgery, especially oesophagectomy, which, if left untreated, can be potentially life-threatening. METHODS: This article provides an overview of the existing literature on the prevention and surgical therapy of chylothorax. RESULTS: The risk of chyle leakage after oesophagectomy increases with the difficulty of mediastinal dissection and is reported to be around 3% for oesophagectomy. With this risk, there is the possibility of a prophylactic intraoperative ligature of the thoracic duct, either as a selective or mass ligation. Meta-analyses confirm the effectiveness of this measure, with a reduction in the risk to less than 1%. In the case of postoperative chylothorax, a conservative therapeutic trial may be undertaken with drainage of up to 1000 ml per day for up to one week. If there is any indication of persistent leakage, rapid surgical reintervention appears appropriate. This can be either transthoracic or transhiatal as a selective or mass ligation and has a probability of success of over 90%. CONCLUSION: The prophylactic primary or therapeutic secondary ligature of the thoracic duct is an effective surgical preventive measure and therapy of postoperative chyle leakage.

Internet-based perioperative exercise program in patients with Barrett's carcinoma scheduled for esophagectomy [iPEP - study] a prospective randomized-controlled trial.

BACKGROUND: Patients undergoing surgery for esophageal cancer have a high risk for postoperative deterioration of lung function and pulmonary complications. This is partly due to one-lung ventilation during thoracotomy. This often accounts for prolonged stay on intensive care units, delayed postoperative reconvalescence and reduced quality of life. Socioeconomic disadvantages can result from these problems. Physical preconditioning has become a crucial leverage to optimize fitness and lung function in patients scheduled for esophagectomy, in particular during the time period of neoadjuvant therapy. METHODS/STUDY DESIGN: We designed a prospective multicenter randomized-controlled trial. The objective is to evaluate the impact of an internet-based exercise program on postoperative respiratory parameters and pneumonia rates in patients with Barrett's carcinoma scheduled for esophagectomy. Patients are randomly assigned to either execute internet-based perioperative exercise program (iPEP), including daily endurance, resistance and ventilation training or treatment as usual (TAU). During neoadjuvant therapy and recovery, patients in the intervention group receive an individually designed intensive exercise program based on functional measurements at baseline. Personal feedback of the supervisor with customized training programs is provided in weekly intervals. DISCUSSION: This study will evaluate if an intensive individually adapted training program via online supervision during neoadjuvant therapy will improve cardiorespiratory fitness and reduce pulmonary complications following esophagectomy for Barrett's cancer. TRIAL REGISTRATION: NCT02478996 , registered 26 May 2015.

Hybrid minimally invasive esophagectomy vs. open esophagectomy: a matched case analysis in 120 patients.

PURPOSE: In esophageal surgery, total minimally invasive techniques compete with hybrid and robot-assisted procedures. The benefit of the individual techniques for the patient remains vague. At our institution, the hybrid minimally invasive laparoscopic-thoracotomic esophagectomy (HMIE) has been routinely applied since 2013. We conducted this retrospective study to analyze the perioperative outcome. METHODS: Since 2013, 60 patients were operated in HMIE technique for esophageal cancer. Each of these patients was paired according to the criteria of gender, BMI, age, tumor histology, pulmonary preexisting conditions, and a history of smoking with a patient treated by open esophagectomy (OE). Perioperative parameters were extracted from our prospectively maintained database and compared among the groups. RESULTS: The HMIE and OE groups were homogeneous in terms of patient- and tumor-related data. There was no difference in lymph nodes harvested (22 vs. 20, p = 0.459) and R0-resection rate (95 vs. 93%, p = 0.500). The operation time for the HMIE was significantly shorter (329 vs. 407 min, p < 0.001). There was no difference between the groups with respect to surgical complications (37 vs. 37%, p = 0.575), but the patients undergoing hybrid technique showed more delayed gastric emptying (23 vs. 10%, p = 0.042). Pulmonary morbidity was significantly reduced after HMIE (20 vs. 42%, p = 0.009). This affected both the occurrence of pneumonia and pleural effusions. The difference in the overall complication rate was not significant (50 vs. 60%, p = 0.179), but life-threatening complications (Clavien/Dindo 4/5) were less frequent (2 vs. 12%, p = 0.031). Overall, there was significantly less need for transfusion after HMIE (18 vs. 50%, p < 0.001), and hospital (and IMC) stay was significantly shorter (14 (6) vs. 18 (7) days, p = 0.002 (0.003)). The multivariate analysis confirms the surgical procedure as an independent risk factor for the development of pulmonary complications (OR 3.2, p = 0.011). Furthermore, preexisting pulmonary conditions were identified as a risk factor (OR 3.6, p = 0.006). CONCLUSION: Our retrospective analysis shows that reduction of postoperative pulmonary morbidity, perioperative blood loss, and shortening of hospital stay can be achieved by HMIE. The procedure is safe, and the rate of surgical complications and oncological radicality is comparable to the conventional procedure.

Management and outcome of esophageal stenting for spontaneous esophageal perforations.

Treatment of spontaneous esophageal perforation (SEP) consists of different conservative, surgical and endoscopic treatment modalities. In this study, we evaluated the clinical efficacy and the outcome of covered self-expanding stent (CSES) treatment of SEP. All patients with SEP treated by CSES at our institution between 2005 and 2014 were included in this prospective single-center study. The data were collected from a prospective database based on clinical, endoscopic and operative reports. Follow-up data were procured by contacting the patients or their family doctors. The patient data were analyzed concerning course of treatment, leakage sealing rate, complications, and mortality. Patients with iatrogenic or malignant perforations were excluded. In total, 16 patients underwent endoscopic CSES placement for SEP between 2005 and 2014. Sealing of the leakage was immediately successful in 50% (8 patients). A second stent was placed in 5 patients, but did not achieve sealing of the perforation in any case, requiring a switch in treatment to a surgical procedure (n=4) or drainage of the persisting leakage (n=4). In-hospital mortality was 13%. Only delayed treatment was identified as a risk factor for inferior outcome. Patients with successful CSES treatment had a shorter ICU- and hospital stay and had a reduced risk of developing esophageal stenosis (RR: 0.4) or persisting dysphagia despite treatment (RR: 0.33). Endoscopic treatment of SEP is beneficial to the patient if immediately successful, but in our experience, failure rates are higher than described in the literature. Secondary placement of CSES was not successful when initial stent treatment failed, while both surgical intervention and drainage of the perforation showed good results in sealing the leakage.

Postoperative fluid overload is a risk factor for adverse surgical outcome in patients undergoing esophagectomy for esophageal cancer: a retrospective study in 335 patients.

BACKGROUND: Restrictive intraoperative fluid management is increasingly recommended for patients undergoing esophagectomy. Controversy still exists about the impact of postoperative fluid management on perioperative outcome. METHODS: We retrospectively examined 335 patients who had undergone esophagectomy for esophageal cancer at the University Hospital Freiburg between 1996 and 2014 to investigate the relation between intra- and postoperative fluid management and postoperative morbidity after esophagectomy. RESULTS: Perioperative morbidity was 75%, the in-hospital mortality 8%. A fluid balance above average on the operation day was strongly associated with a higher rate of postoperative mortality (21% vs 3%, p < 0.001) and morbidity (83% vs 66%, p = 0.001). Univariate analysis for risk factors for adverse surgical outcome (Clavien ≥ III) identified ASA-score (p = 0.002), smoking (p = 0.036), reconstruction by colonic interposition (p = 0.036), cervical anastomosis (p = 0.017), blood transfusion (p = 0.038) and total fluid balance on the operation day and on POD 4 (p = 0.001) as risk factors. Multivariate analysis confirmed only ASA-score (p = 0.001) and total fluid balance (p = 0.001) as independent predictors of adverse surgical outcome. CONCLUSION: Intra- and postoperative fluid overload is strongly associated with increased postoperative morbidity. Our results suggest restrictive intra- and especially postoperative fluid management to optimize the outcome after esophagectomy.

KRAS mutations in pancreatic circulating tumor cells: a pilot study.

Pancreatic ductal adenocarcinoma (PDAC) is most often diagnosed in a metastatic stage. Circulating tumor cells (CTC) in the blood are hypothesized as the means of systemic dissemination. We aimed to isolate and characterize CTC to evaluate their significance as prognostic markers in PDAC. Blood obtained from healthy donors and patients with PDAC before therapy was filtered with ScreenCell® filtration devices for size-based CTC isolation. Captured cells were analyzed by immunofluorescence for an epithelial to mesenchymal transition (EMT) marker (zinc finger E-box binding homebox 1 (ZEB1)) and an epithelial antigen (cytokeratin (CK)). Molecular analysis of parallel specimens evaluated the KRAS mutation status of the CTC. The survival of each patient after study was recorded. As demonstrated by either cytology or finding of a KRAS mutation, CTC were detected in 18 of 21 patients (86 %) with proven PDAC: 8 out of 10 patients (80 %) with early stage (UICC IIA/IIB) and 10 out of 11 (91 %) with late stage (UICC III/IV) disease. CTC were not found in any of the 10 control patients (p < 0.001). The presence of CTC did not adversely affect median survival: 16 months in CTC-positive (n = 18) vs. 10 months in CTC-negative (n = 3) patients. Neither ZEB1 nor cytological characteristics correlated with overall survival, although ZEB1 was found almost exclusively in CTC of patients with established metastases. Patients with a CTC KRAS mutation (CTC-KRAS (mut)) had a substantially better survival, 19.4 vs. 7.4 months than patients with wild type KRAS (p = 0.015). With ScreenCell filtration, CTC are commonly found in PDAC (86 %). Molecular and genetic characterization, including mutations such as KRAS, may prove useful for prognosis.

ESOPEC: prospective randomized controlled multicenter phase III trial comparing perioperative chemotherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in patients with adenocarcinoma of the esophagus (NCT02509286).

BACKGROUND: Recent randomized controlled trials comparing neoadjuvant chemoradiation plus surgery or perioperative chemotherapy plus surgery with surgery alone showed significant survival benefits for combined modality treatment of patients with localized esophageal adenocarcinoma. However, head-to-head comparisons of neoadjuvant chemoradiation and perioperative chemotherapy applying contemporary treatment protocols are lacking. The present trial was initiated to obtain valid information whether neoadjuvant chemoradiation or perioperative chemotherapy yields better survival in the treatment of localized esophageal adenocarcinoma. METHODS/DESIGN: The ESOPEC trial is an investigator-initiated multicenter prospective randomized controlled two-arm trial, comparing the efficacy of neoadjuvant chemoradiation (CROSS protocol: 41.4Gy plus carboplatin/paclitaxel) followed by surgery versus perioperative chemotherapy and surgery (FLOT protocol: 5-FU/leucovorin/oxaliplatin/docetaxel) for the curative treatment of localized esophageal adenocarcinoma. Patients with cT1cN + cM0 and cT2-4acNxcM0 esophageal and junctional adenocarcinoma are eligible. The trial aims to include 438 participants who are centrally randomized to one of the two treatment groups in a 1:1 ratio stratified by N-stage and study site. The primary endpoint of the trial is overall survival assessed with a minimum follow-up of 36 months. Secondary objectives are progression-free survival, recurrence-free survival, site of failure, postoperative morbidity and mortality, duration of hospitalization as well as quality of life. DISCUSSION: The ESOPEC trial compares perioperative chemotherapy according to the FLOT protocol to neoadjuvant chemoradiation according to the CROSS protocol in multimodal treatment of non-metastasized recectable adenocarcinoma of the esophagus and the gastroesophageal junction. The goal of the trial is identify the superior protocol with regard to patient survival, treatment morbidity and quality of life. TRIAL REGISTRATION: NCT02509286 (July 22, 2015).

The degree of local inflammatory response after colonic resection depends on the surgical approach: an observational study in 61 patients.

BACKGROUND: Clinical data indicate that laparoscopic surgery reduces postoperative inflammatory response and benefits patient recovery. Little is known about the mechanisms involved in reduced systemic and local inflammation and the contribution of reduced trauma to the abdominal wall and the parietal peritoneum. METHODS: Included were 61 patients, who underwent elective colorectal resection without intraabdominal complications; 17 received a completely laparoscopic, 13 a laparoscopically- assisted procedure and 31 open surgery. Local inflammatory response was quantified by measurement of intraperitoneal leukocytes and IL-6 levels during the first 4 days after surgery. RESULTS: There was no statistical difference between the groups in systemic inflammatory parameters and intraperitoneal leukocytes. Intraperitoneal interleukin-6 was significantly lower in the laparoscopic group than in the laparoscopically-assisted and open group on postoperative day 1 (26.16 versus 43.25 versus 40.83 ng/ml; p = 0.001). No difference between the groups was recorded on POD 2-4. Intraperitoneal interleukin-6 showed a correlation with duration of hospital stay on POD 1 (0.233, p = 0.036), but not on POD 2-4. Patients who developed a surgical wound infection showed higher levels of intraperitoneal interleukin-6 on postoperative day 2-4 (POD 2: 42.56 versus 30.02 ng/ml, p = 0.03), POD 3: 36.52 versus 23.62 ng/ml, p = 0.06 and POD 4: 34.43 versus 19.99 ng/ml, p = 0.046). Extraabdominal infections had no impact. CONCLUSION: The analysis shows an attenuated intraperitoneal inflammatory response on POD 1 in completely laparoscopically-operated patients, associated with a quicker recovery. This effect cannot be observed in patients, who underwent a laparoscopically-assisted or open procedure. Factors inflicting additional trauma to the abdominal wall and parietal peritoneum promote the intraperitoneal inflammation process.

Impact of intraoperative temperature and humidity on healing of intestinal anastomoses.

PURPOSE: Clinical data indicate that laparoscopic surgery has a beneficial effect on intestinal wound healing and is associated with a lower incidence of anastomotic leakage. This observation is based on weak evidence, and little is known about the impact of intraoperative parameters during laparoscopic surgery, e.g., temperature and humidity. METHODS: A small-bowel anastomosis was formed in rats inside an incubator, in an environment of stable humidity and temperature. Three groups of ten Wistar rats were operated: a control group (G1) in an open surgical environment and two groups (G2 and G3) in the incubator at a humidity of 60 % and a temperature of 30 and 37 °C (G2 and G3, respectively). After 4 days, bursting pressure and hydroxyproline concentration of the anastomosis were analyzed. The tissue was histologically examined. Serum levels of C-reactive-protein (CRP) were measured. RESULTS: No significant changes were seen in the evaluation of anastomotic stability. Bursting pressure was very similar among the groups. Hydroxyproline concentration in G3 (36.3 µg/g) was lower by trend (p = 0.072) than in G1 (51.7 µg/g) and G2 (46.4 µg/g). The histological evaluation showed similar results regarding necrosis, inflammatory cells, edema, and epithelization for all groups. G3 (2.56) showed a distinctly worse score for submucosal bridging (p = 0.061) than G1 (1.68). A highly significant increase (p = 0.008) in CRP was detected in G3 (598.96 ng/ml) compared to G1 (439.49 ng/ml) and G2 (460 ng/ml). CONCLUSION: A combination of high temperature and humidity during surgery induces an increased systemic inflammatory response and seems to be attenuating the early regeneration process in the anastomotic tissue.