Information and counselling needs of patients with major low anterior resection syndrome: A qualitative study.

AIMS AND OBJECTIVES: The aim was to explore the information and counselling needs of rectal cancer survivors confronted with major low anterior resection syndrome. BACKGROUND: Rectal cancer survivors are often confronted with bowel problems after surgery. This is called low anterior resection syndrome. Patients are unsure what to expect after treatment and healthcare professionals often underestimate the impact of low anterior resection syndrome on patients' lives. DESIGN: A qualitative study with a grounded theory approach was conducted. METHODS: Patients were recruited between 2017 and 2019 in three hospitals, and a call was distributed in two patients' organisations. Semi-structured interviews with patients confronted with major low anterior resection syndrome were performed. An iterative process between data collection and data analysis was used. Data analysis was done using the constant comparative method, and investigators' triangulation was applied. Qualitative data were reported following COREQ guidelines. The study was registered at Clinicaltrials.gov NCT04896879. RESULTS: A total of 28 patients were interviewed until theoretical data saturation. Before surgery patients' need for information varied according to their individual coping mechanisms. Some patients required information before surgery, while others considered this too overwhelming. When confronted with LARS, patients desired that healthcare professionals recognised its impact and clarified its expected evolution. A proactive counselling with an easy accessible and approachable healthcare professional was beneficial. CONCLUSION: Patients expressed several needs regarding the information before rectal cancer surgery and counselling of low anterior resection syndrome after surgery. RELEVANCE TO CLINICAL PRACTICE: Better knowledge and understanding of major low anterior resection syndrome and its challenges by healthcare professionals are crucial. Especially the impact on quality of life is significant for patients and underestimated by healthcare professionals. Information before surgery and counselling when confronted with major low anterior resection syndrome should be optimised and tailored to patients' needs.

Patient-reported outcomes after pelvic exenteration for colorectal cancer: A systematic review.

AIM: Pelvic exenteration (PE) carries high morbidity. Our aim was to analyse the use of patient-reported outcome measures (PROMs) in PE patients. METHOD: Search strategies were protocolized and registered in PROSPERO. PubMed, Embase, Cochrane Library, Google Scholar, Web of Science and ClinicalTrials.gov were searched with the terms 'patient reported outcomes', 'pelvic exenteration' and 'colorectal cancer'. Studies published after 1980 reporting on PROMs for at least 10 PE patients were considered. Study selection, data extraction, rating of certainty of evidence (GRADE) and risk of bias (ROBINS-I) were performed independently by two reviewers. RESULTS: Nineteen of 173 studies were included (13 retrospective, six prospective). All studies were low to very low quality, with an overall moderate/serious risk of bias. Studies included data on 878 patients with locally advanced rectal cancer (n = 344), recurrent rectal cancer (n = 411) or cancer of unknown type (n = 123). Thirteen studies used validated questionnaires, four used non-validated measures and two used both. Questionnaires included the Functional Assessment of Cancer Therapy-Colorectal questionnaire (n = 6), Short Form Health Survey (n = 6), European Organization for Research and Treatment for Cancer (EORTC) Quality of Life Questionnaire C30 (n = 6), EORTC-CR38 (n = 4), EORTC-BLM30 (n = 1), Brief Pain Inventory (n = 2), Short Form 12 (n = 1), Assessment of Quality of Life (n = 1), Short Form Six-Dimension (n = 1), the Memorial Sloan Kettering Cancer Center Sphincter Function Scale (n = 1), the Cleveland Global Quality of Life (n = 1) or other (n = 4). Timing varied between studies. CONCLUSIONS: Whilst the use of validated questionnaires increased over time, this study shows that there is a need for uniform use and timing of PROMs to enable multicentre studies.

Clinical utility of near-infrared perfusion assessment of the gastric tube during Ivor Lewis esophagectomy.

BACKGROUND: Anastomotic leakage (AL) after Ivor Lewis esophagectomy with intrathoracic anastomosis carries a significant morbidity. Adequate perfusion of the gastric tube (GT) is an important predictor of anastomotic integrity. Recently, near infrared fluorescent (NIRF) imaging using indocyanine green (ICG) was introduced in clinical practice to evaluate tissue perfusion. We evaluated the feasibility and efficacy of GT indocyanine green angiography (ICGA) after Ivor Lewis esophagectomy. METHODS: This retrospective analysis used data from a prospectively kept database of consecutive patients who underwent Ivor Lewis (IL) esophagectomy with GT construction for cancer between January 2016 and December 2020. Relevant outcomes were feasibility, ICGA complications and the impact of ICGA on AL. RESULTS: 266 consecutive IL patients were identified who matched the inclusion criteria. The 115 patients operated with perioperative ICGA were compared to a control group in whom surgery was performed according to the standard of care. ICGA perfusion assessment was feasible and safe in all 115 procedures and suggested a poorly perfused tip in 56/115 (48.7%) cases, for which additional resection was performed. The overall AL rate was 16% (43/266), with 12% (33/266) needing an endoscopic our surgical intervention and 6% (17/266) needing ICU support. In univariable and multivariable analyses, ICGA was not correlated with the risk of AL (ICGA:14.8% vs non-ICGA:17.2%, p = 0.62). However, poor ICGA perfusion of the GT predicted a higher AL rate, despite additional resection of the tip (ICGA poorly perfused: 19.6% vs ICG well perfused: 10.2%, p = 0.19). CONCLUSIONS: ICGA is safe and feasible, but did not result in a reduction of AL. The interpretation and necessary action in case of perioperative presence of ischemia on ICGA have yet to be determined. Prospective randomized trials are warranted to analyze its benefit on AL in esophageal surgery. Trial registration Ethical approval for a prospective esophageal surgery database was granted by the Ethical committee of the Ghent University Hospital. Belgian registration number: B670201111232. Ethical approval for this retrospective data analysis was granted by our institutional EC. REGISTRATION NUMBER: BC-09216.

Quality of Life after Minimally Invasive Esophagectomy: A Cross-Sectional Study.

INTRODUCTION: Surgery remains essential in the curative treatment of esophageal cancer (EC), but it is known for its high morbidity and impaired health-related QoL. Minimally invasive esophagectomy (MIE) was introduced to reduce surgical trauma and improve QoL. METHODS: This cross-sectional study aimed to evaluate long-term HRQoL after MIE in comparison with the general population. HRQoL assessment was based on three questionnaires: the European Organisation for Research and Treatment of Cancer (EORTC) Core 30 (QLQ-C30, version 3), the EORTC QLQ Oesophago Gastric 25 (QLQ-OG25), and the Supportive Care Needs Survey-Short Form 34 (SCNS-SF34). Results were compared to a healthy reference population. RESULTS: One hundred and forty eligible MIE patients were identified, of whom met the inclusion criteria, and 49 completed all questionnaires. Patients reported a significantly better mean score on the global health status and QoL than the healthy reference population (71.5 ± 15.1 vs. 66.1 ± 21.7; p = 0.016). However, patients scored significantly worse about functioning (physical, role, and social) (p < 0.05), fatigue (p = 0.021), eating, dysphagia, pain and discomfort, reflux, appetite loss, weight loss, coughing, and taste (p < 0.001). DISCUSSION/CONCLUSION: EC survivors can reach a high global health status and QoL at least 1 year after MIE, despite long-term functional, nutritional, and gastrointestinal complaints. Patients provided written informed consent, and the study protocol was approved by the Ethics Committee of Ghent University Hospital (identifier: ID B670201940737).

The Effect of Postoperative Complications After Minimally Invasive Esophagectomy on Long-term Survival: An International Multicenter Cohort Study.

BACKGROUND: Esophagectomy is a technically challenging procedure, associated with significant morbidity. The introduction of minimally invasive esophagectomy (MIE) has reduced postoperative morbidity. OBJECTIVE: Although the short-term effect on complications is increasingly being recognized, the impact on long-term survival remains unclear. This study aims to investigate the association between postoperative complications following MIE and long-term survival. METHODS: Data were collected from the EsoBenchmark Collaborative composed by 13 high-volume, expert centers routinely performing MIE. Patients operated between June 1, 2011 and May 31, 2016 were included. Complications were graded using the Clavien-Dindo (CD) classification. To correct for short-term effects of postoperative complications on mortality, patients who died within 90 days postoperative were excluded. Primary endpoint was 5-year overall survival. RESULTS: A total of 915 patients were included with a mean follow-up time of 30.8 months (standard deviation 17.9). Complications occurred in 542 patients (59.2%) of which 50.2% had a CD grade ≥III complication [ie, (re)intervention, organ dysfunction, or death]. The incidence of anastomotic leakage (AL) was 135 of 915 patients (14.8%) of which 84 patients were classified as a CD grade ≥III. Multivariable analysis showed a significantly deteriorated long-term survival in all patients with AL [hazard ratio (HR) 1.68, 95% confidence interval (CI) 1.25-2.24]. This inverse relation was most distinct when AL was scored as a CD grade ≥III (HR 1.83, 95% CI 1.30-2.58). For all other complications, no significant association with long-term survival was found. CONCLUSION: The occurrence and severity of AL, but not overall complications, after MIE negatively affect long-term survival of esophageal cancer patients.

Technique of open and minimally invasive intrathoracic reconstruction following esophagectomy-an expert consensus based on a modified Delphi process.

BACKGROUND: In recent years, minimally invasive Ivor Lewis (IL) esophagectomy with high intrathoracic anastomosis has emerged as surgical standard of care for esophageal cancer in expert centers. Alongside this process, many divergent technical aspects of this procedure have been devised in different centers. This study aims at achieving international consensus on the surgical steps of IL reconstruction using Delphi methodology. METHODS: The expert panel consisted of specialized esophageal surgeons from 8 European countries. During a two-round Delphi process, a detailed analysis and consensus on key steps of intrathoracic gastric tube reconstruction (IL esophagectomy) was performed. RESULTS: Response rates in Delphi rounds 1 and 2 were 100% (22 of 22 experts) and 83.3% (20 of 24 experts), respectively. Three essential technical areas of intrathoracic gastric tube reconstruction were identified: first, vascularization of the gastric conduit, second, gastric mobilization, tube formation and pull-up, and third, anastomotic technique. In addition, 3 main techniques for minimally invasive intrathoracic anastomosis are currently practiced: (i) end-to-side circular stapled, (ii) end-to-side double stapling, and (iii) side-to-side linear stapled technique. The step-by-step procedural analysis unveiled common approaches but also different expert practice. CONCLUSION: This precise technical description may serve as a clinical guideline for intrathoracic reconstruction after esophagectomy. In addition, the results may aid to harmonize the technical evolution of this complex surgical procedure and thereby facilitate surgical training.

Primary care providers' knowledge about the therapeutic management of refractory pelvic floor dysfunctions in Flanders, Belgium: a cross-sectional study.

BACKGROUND: Pelvic floor dysfunctions (PFD) are prevalent conditions in primary care practice. Basic knowledge of second-line therapies among primary care providers (PCPs) is indispensable to well-inform refractory patients and improve their access to specialized care. OBJECTIVES: Getting insight into the extent of knowledge about second-line therapies for refractory PFD among PCPs in Flanders, Belgium. METHODS: From January to March 2019 Flemish PCPs participated in the OptiLUTS trial - Part A (EC/2018/0244), by the completion of a 22-item online Dutch questionnaire. Prevalence of PCPs having awareness about sacral neuromodulation (SNM), intradetrusor botulinum toxin injections (BTX) and percutaneous tibial nerve stimulation (PTNS) was explored. Descriptive statistics, univariate analyses, and multiple logistic regression analyses were performed. RESULTS: Sixty PCPs, 55% GPs, 45% GP trainees, median age 29 years, participated. Respectively, 90, 73 and 5% had ever heard about BTX, SNM and PTNS. The profession was an independent predictive factor for never having heard of SNM therapy, GPs being more likely to have a lack of knowledge than trainees (OR = 29, 95%CI [1.9-442.5]). Ninety-three percent want to learn more about these therapies. CONCLUSION: There is a margin for improvement in the knowledge of PCPs regarding therapies for refractory PFD. Awareness among PCPs should be increased for the optimization of patient care.

Development of a flowchart reflecting the current attitude and approach towards idiopathic overactive bladder treatment in Belgium: A Delphi study.

AIMS: Idiopathic overactive bladder syndrome (iOAB) is a prevalent condition in urological practice. The variability in management between specialists and between centers remains high. Even existing guidelines contain inconsistencies. We aimed to develop a treatment algorithm for iOAB for use in daily clinical practice. METHODS: From October 2018 till November 2019, a Delphi study was conducted to obtain expert consensus on the management of iOAB. Members from the Belgian Working Group of Functional Urology were asked to rate online statements, based on gaps and variabilities between the American Urology Association (AUA), European Association of Urology (EAU) and International Consultation on Incontinence (ICI) guidelines on iOAB. The consensus was reached if ≥75% of the panel agreed on the level of appropriateness. Two Delphi rounds and an open discussion session were held. RESULTS: Twenty out of 49 members completed the first round and 18 completed the second round. The consensus was reached on 44/143 statements and 15/56 statements in the first and second round, respectively. The consensus was reached on criteria by which to phenotype OAB patients, the terminology relating to the first-, second- and third-line treatment, the duration of therapies, the chronological order, and the choice between therapies. No consensus was reached on the role of percutaneous tibial nerve stimulation (PTNS) in the treatment algorithm. CONCLUSIONS: A flowchart reflecting the current attitude and approach of a Delphi expert panel towards the treatment of iOAB was developed. We propose its use in daily clinical practice to increase the standardization of OAB treatment.

Symptomatic gastric involvement in a parastomal hernia: uncommon presentation.

Introduction: A parastomal hernia (PSH) is the most common complication of a stoma creation. The PSH contents normally consist of mobile abdominal structures, i.e. omentum and small or large bowel loops. A herniated stomach is thereby very rare, given that only eight cases are reported in the literature.Patients and methods: Two female patients with clinical symptoms of gastric involvement in a PSH were admitted in our centre.Results: Computed tomography (CT) imaging, nasogastric decompression and an efficient operative intervention ensured a good clinical outcome in both patients, but with a long hospital stay and temporary gastroparesis in one patient. Regarding our two cases and the eight cases reported in the literature, mainly older females with colostomies are at risk and most of them need surgery. Conclusions: In patients presenting with obstructive symptoms, one should be aware of a possible gastric outlet obstruction because of its involvement in a PSH, although sporadic. Surgery might be considered as the treatment of choice because conservative treatment mostly fails. Earlier surgery might perhaps also reduce postoperative hospital stay and gastroparesis.

Anastomotic Techniques and Associated Morbidity in Total Minimally Invasive Transthoracic Esophagectomy: Results From the EsoBenchmark Database.

OBJECTIVE: The aim of this study was to describe anastomotic techniques used for total minimally invasive transthoracic esophagectomy (ttMIE) and to analyze the associated morbidity. BACKGROUND: ttMIE faces increasing application in surgical treatment of esophageal cancer. For esophagogastric reconstruction, different anastomotic techniques are currently used, but their effect on postoperative anastomotic leakage and morbidity has not been investigated. PATIENTS AND METHODS: Patients were selected from a basic dataset, collected during a 5-year period from 13 international surgical high-volume centers. Endpoints were anastomotic leakage rate and postoperative morbidity in correlation to anastomotic techniques, measured by the Clavien-Dindo classification and the Comprehensive Complication Index (CCI). RESULTS: Five anastomotic techniques were identified in 966 patients after ttMIE: intrathoracic end-to-side circular-stapled technique in 427 patients (double-stapling n = 90, purse-string n = 337), intrathoracic (n = 109) or cervical (n = 255) side-to-side linear-stapled, and cervical end-to-side hand-sewn (n = 175). Leakage rates were similar in intrathoracic and cervical anastomoses (15.9% vs 17.2%, P = 0.601), but overall complications (56.7%% vs 63.7%, P = 0.029) and median 90-day CCI {21 [interquartile range (IQR) 0-36] vs 29 [IQR 0-40], P = 0.019} favored intrathoracic reconstructions. Leakage rates after intrathoracic end-to-side double-stapling (23.3%) and cervical end-to-side hand-sewn (25.1%) techniques were significantly higher compared with intrathoracic side-to-side linear (15.6%), end-to-side purse-string (13.9%), and cervical side-to-side linear-stapled esophagogastrostomies (11.8%) (P < 0.001). Multivariable analysis confirmed anastomotic technique as independent predictor of leakage after ttMIE. CONCLUSION: Results of this analysis present the current status of the technical evolution of ttMIE with anastomotic leakage as predominant surgical complication. However, technique-related morbidity requires cautious interpretation considering the long learning curve of this complex surgical procedure.

Distribution of lymph node metastases in esophageal carcinoma [TIGER study]: study protocol of a multinational observational study.

BACKGROUND: An important parameter for survival in patients with esophageal carcinoma is lymph node status. The distribution of lymph node metastases depends on tumor characteristics such as tumor location, histology, invasion depth, and on neoadjuvant treatment. The exact distribution is unknown. Neoadjuvant treatment and surgical strategy depends on the distribution pattern of nodal metastases but consensus on the extent of lymphadenectomy has not been reached. The aim of this study is to determine the distribution of lymph node metastases in patients with resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed. This can be the foundation for a uniform worldwide staging system and establishment of the optimal surgical strategy for esophageal cancer patients. METHODS: The TIGER study is an international observational cohort study with 50 participating centers. Patients with a resectable esophageal or gastro-esophageal junction carcinoma in whom a transthoracic esophagectomy with a 2- or 3-field lymphadenectomy is performed in participating centers will be included. All lymph node stations will be excised and separately individually analyzed by pathological examination. The aim is to include 5000 patients. The primary endpoint is the distribution of lymph node metastases in esophageal and esophago-gastric junction carcinoma specimens following transthoracic esophagectomy with at least 2-field lymphadenectomy in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and (disease free) survival. DISCUSSION: The TIGER study will provide a roadmap of the location of lymph node metastases in relation to tumor histology, tumor location, invasion depth, number of lymph nodes and lymph node metastases, pre-operative diagnostics, neo-adjuvant therapy and survival. Patient-tailored treatment can be developed based on these results, such as the optimal radiation field and extent of lymphadenectomy based on the primary tumor characteristics. TRIAL REGISTRATION: NCT03222895 , date of registration: July 19th, 2017.

Is the Human Brain Capable of Controlling Seven Degrees of Freedom?

BACKGROUND: Conventional rigid laparoscopic instruments offer five degrees of freedom (DOF). Robotic instruments add two independent DOFs allowing unconstrained directional steering. Several nonrobotic instruments have been developed with the additional DOFs, but with these devices, surgeon's wrist movements are not intuitively transmitted into tip movements. In this study, a new articulated instrument has been evaluated. The aim of the study was to compare learning curves and performances of conventional laparoscopic instruments, the da Vinci system and Steerable devices in a crossover study. MATERIALS AND METHODS: A total of 16 medical students without any laparoscopic experience were trained for 27 h to operate all of a rigid, a robotic, and a new Steerable instrument in a random order. Learning curves and ultimate experience scores were determined for each instrument. Strain in wrist and shoulders was assessed with a visual analog score. RESULTS: Performing the suturing task with rigid and robot instruments required 4 h of training, compared with 6 h to master the Steerable instrument. After 9 h of training with each instrument, completing the complex suturing pattern required 662 ± 308 s with rigid instruments, 279 ± 90 s with the da Vinci system, and 279 ± 53 s with the Steerable instrument. Pain scores were significantly higher after using the rigid instruments compared with the Steerable instruments. CONCLUSIONS: Transmission of torque and the presence of additional two DOFs in combination with reduced crosstalk significantly improved the instrument dexterity where the Steerable platform is concerned. Although the learning curve is longer, once mastered, it provides enhanced surgical freedom.

Radiation dose and pathological response in oesophageal cancer patients treated with neoadjuvant chemoradiotherapy followed by surgery: a multi-institutional analysis.

Purpose: To explore whether a higher neoadjuvant radiation dose increases the probability of a pathological complete response (pCR) or pathological major response (pMR) response in oesophageal cancer patients. Material and methods: Between 2000 and 2017, 1048 patients from four institutions were stratified according to prescribed neoadjuvant radiation doses of 36.0 Gy (13.3%), 40.0 Gy (7.4%), 41.4 Gy (20.1%), 45.0 Gy (25.5%) or 50.4 Gy (33.7%) in 1.8-2.0 Gy fractions. Endpoints were pCR (tumour regression grade (TRG) 1) and pMR (TRG 1 + 2). Multivariable binary (TRG 1 + 2 vs. TRG > 2) and ordinal (TRG 1 vs. TRG 2 vs. TRG > 2) logistic regression analyses were performed, with subgroup analyses according to histology (squamous cell carcinoma (SCC) vs. adenocarcinoma (AC)). Variables entered in the regression model along with neoadjuvant radiation dose were clinical tumour stage (cT), histology, chemotherapy regimen, induction chemotherapy and time from neoadjuvant chemoradiation to surgery. Results: A pCR was observed in 312 patients (29.8%); in 22.7% patients with AC and in 49.6% patients with SCC. No radiation dose-response relation was observed for pCR (OR = 1.01, 95% CI: 0.98-1.05 for AC and OR = 1.03, 95% CI: 0.96-1.10 for SCC). A pMR was observed in 597 patients (57.0%); in 53.4% patients with AC and in 67.2% patients with SCC. A higher radiation dose increased the probability of achieving pMR (OR = 1.04, 95% CI: 1.02-1.05). Factors reducing this probability were advanced cT stage (reference = cT1-2; cT3: OR = 0.54, 95% CI: 0.37-0.80; cT4: OR = 0.45, 95% CI: 0.24-0.84), AC histology (reference = SCC; OR = 0.62, 95% CI: 0.44-0.88), the use of non-platinum based chemotherapy in SCC patients (OR = 0.30, 95% CI: 0.10-0.91) and platinum based chemotherapy without induction chemotherapy in patients with AC (OR = 0.56, 95% CI: 0.42-0.76). The radiation dose-response relation was confirmed in a subgroup analysis of histologic subtypes (OR = 1.02, 95% CI: 1.01-1.04 for AC and OR = 1.05, 95% CI: 1.02-1.08 for SCC). Conclusions: Neoadjuvant radiation dose impacts pathological response in terms of pMR in oesophageal cancer patients. No radiation dose-response effect was observed for pCR. Further prospective trials are needed to investigate the dose-response relation in terms of pCR.

Intraoperative radiation therapy for rectal cancer and recurrent intra-abdominal sarcomas.

PURPOSE: The aim of this study was to evaluate the effect of high-dose-rate intraoperative radiation therapy (HDR-IORT) in a multimodality treatment on the local control (LC) and the overall survival (OS) rate in locally advanced rectal cancer (LARC), locally recurrent rectal cancer (LRRC) and recurrent intra-abdominal sarcomas (RS). MATERIALS AND METHODS: A retrospective analysis was performed on 27 patients who were treated with radical resection and HDR-IORT between April 2007 and January 2017. Patient, tumor and surgical characteristics were analyzed and the perioperative (<30 days) and long-term complications (>30 days) were assessed and graded. RESULTS: None of the patients with LARC (n = 4) developed a local recurrence and all patients were still alive at the end of the follow-up. The LC rates of LRRC (n = 17) after one and three years were respectively 48% and 40% and the one, three and five years OS were respectively 93%, 62% and 44%. For RS (n = 6), the LC rates after one and three years were both 33% and the one and three years OS rate were respectively 83% and 46%. CONCLUSIONS: The results of our study show that HDR-IORT could be a valuable asset in the multimodality management of LARC, LRRC and RS.

FA01.02: THE EFFECT OF POSTOPERATIVE COMPLICATIONS AFTER MIE ON LONG-TERM SURVIVAL: A RETROSPECTIVE, MULTI-CENTER COHORT STUDY.

BACKGROUND: Esophagectomy has a high incidence of postoperative morbidity. Complications lead to a decreased short-term survival, however the influence of those complications on long-term survival is still unclear. Most of the performed studies are small, single center cohort series with inconclusive or conflicting results. Minimally invasive esophagectomy (MIE) has been shown to be associated with a reduced postoperative morbidity. In this study, the influence of complications on long-term survival for patients with esophageal cancer undergoing a MIE were investigated. METHODS: Data was collected from the EsoBenchmark database, a collaboration of 13 high-volume centers routinely performing MIE. Patients were included in this database from June 1, 2011 until May 31, 2016. Complications were scored according to the Clavien-Dindo (CD) classification for surgical complications. Major complications were defined as a CD grade ≥ 3. The data were corrected for 90-day mortality to correct for the short-term effect of postoperative complications on mortality. Overall survival was analyzed using the Kaplan Meier, log rank- and (uni- and multivariable) Cox-regression analyses. RESULTS: A total of 926 patients were eligible for analysis. Mean follow-up time was 30.8 months (SD 17.9). Complications occurred in 543 patients (59.2%) of which 39.3% had a major complication. Anastomotic leakage (AL) occurred in 135 patients (14.5%) of which 9.2% needed an intervention (CD grade ≥ 3). A significant worse long-term survival was observed in patients with any AL (HR 1.73, 95% CI 1.29-2.32, P < 0.001) and for patients with AL CD grade ≥3 (HR 1.86, 95% CI 1.32-2.63, P < 0.001). Major cardiac complications occurred in 18 patients (1.9%) and were related to a decreased long-term survival (HR 2.72, 95% CI 1.38-5.35, p 0.004). For all other complications, no significant influence on long-term survival was found. CONCLUSION: The occurrence and severity of anastomotic leakage and cardiac complications after MIE negatively affect long-term survival of esophageal cancer patients. DISCLOSURE: All authors have declared no conflicts of interest.

Systematic review of surgical training on reperfused human cadavers.

BACKGROUND: The role of reperfused human cadavers in surgical training has not been established. METHODS: Reports describing reperfused human cadaver models in terms of simulated surgeries, the use of tools to assess technical competency and skills transfer to patients, cadaver status and reperfusion techniques were included. RESULTS: Thirty-five reports were included. Most participants practised vascular (n = 27), flap (n = 6) and trauma (n = 4) procedures. Training progression was evaluated objectively in only two studies. In two publications, flap techniques were practised on cadavers and repeated successfully in patients. Eighteen studies employed whole bodies. Fresh and embalmed cadavers were both used in 17 publications. Most embalmed cadavers were formalin-fixed (n = 10), resulting in stiffness. Few trainings were offered on soft Thiel-embalmed cadavers (n = 5). Only arteries were reperfused in 20 studies, while in 13 publications, the arteries and veins were filled. Arteries and/or veins were mostly pressurized (n = 21) and arterial flow was generated in 14 studies. CONCLUSIONS: Various reperfused human cadaver models exist, enabling practise of mainly vascular procedures. Preservation method determines the level of simulation fidelity. Thorough evaluation of these models as surgical training tools and transfer effectiveness is still lacking.

Long-term survival after multimodality therapy including surgery for metastatic esophageal cancer.

BACKGROUND AND OBJECTIVES: Esophageal cancer (EC) remains an aggressive disease with a poor survival. Management of metastatic EC is limited to palliative chemotherapy (CT). Scientific contributions regarding the role of surgery are scarce and controversial. We analysed outcome of surgically treated metastatic EC patients. METHODS: We retrospectively identified surgically treated metastatic EC patients from our esophagectomy database. The aim of this study was to evaluate surgical complications, pathological response, oncological outcome and mean survival of these aggressively treated stage IV cancer patients. RESULTS: Twelve stage IV patients with disease presentation limited to outfield lymph node (LN) and/or liver metastasis were treated with an aggressive multimodality treatment including surgery. Mean age was 58 years (75% male, 75% Adenocarcinomas). Median postoperative hospital stay was 15 d. Radiological anastomotic leakage occurred in one patient. In hospital, mortality was nil. Complete resection was achieved in all but one. Metastatic recurrence occurred in 64% of R0 resected patients. At date of censoring, after a median follow-up of 22 months, 50% of the surgical resected patients are still alive and 33% are free of disease recurrence. Kaplan-Meier curves show a possibility to long-term survival after aggressive multimodality therapy including surgery. CONCLUSIONS: In selected metastatic EC patients, multimodality treatment including surgery has an acceptable surgical outcome with a potentially long-term survival.

Defining Benchmarks for Transthoracic Esophagectomy: A Multicenter Analysis of Total Minimally Invasive Esophagectomy in Low Risk Patients.

OBJECTIVE: To define "best possible" outcomes in total minimally invasive transthoracic esophagectomy (ttMIE). BACKGROUND: TtMIE, performed by experts in patients with low comorbidity, may serve as a benchmark procedure for esophagectomy. PATIENTS AND METHODS: From a cohort of 1057 ttMIE, performed over a 5-year period in 13 high-volume centers for esophageal surgery, we selected a study group of 334 patients (31.6%) that fulfilled criteria of low comorbidity (American Society of Anesthesiologists score ≤2, WHO/ECOG score ≤1, age ≤65 years, body mass index 19-29 kg/m). Endpoints included postoperative morbidity measured by the Clavien-Dindo classification and the comprehensive complication index. Benchmark values were defined as the 75th percentile of the median outcome parameters of the participating centers to represent best achievable results. RESULTS: Benchmark patients were predominantly male (82.9%) with a median age of 58 years (53-62). High intrathoracic (Ivor Lewis) and cervical esophagogastrostomy (McKeown) were performed in 188 (56.3%) and 146 (43.7%) patients, respectively. Median (IQR) ICU and hospital stay was 0 (0-2) and 12 (9-18) days, respectively. 56.0% of patients developed at least 1 complication, and 26.9% experienced major morbidity (≥grade III), mostly related to pulmonary complications (25.7%), anastomotic leakage (15.9%), and cardiac events (13.5%). Benchmark values at 30 days after hospital discharge were ≤55.7% and ≤30.8% for overall and major complications, ≤18.0% for readmission, ≤3.1% for positive resection margins, and ≥23 for lymph node yield. Benchmarks at 30 and 90 days were ≤1.0% and ≤4.6% for mortality, and ≤40.8 and ≤42.8 for the comprehensive complication index, respectively. CONCLUSION: This outcome analysis of patients with low comorbidity undergoing ttMIE may serve as a reference to evaluate surgical performance in major esophageal resection.

Effect of abdominopelvic sepsis on cancer outcome in patients undergoing sphincter saving surgery for rectal cancer.

BACKGROUND: In rectal cancer, the significance of abdominopelvic sepsis (APS) on metastatic tumor growth remains uncertain. We aimed to analyze the effect of abdominopelvic sepsis on long-term survival in patients undergoing restorative rectal cancer surgery. METHODS: Data were used from the Belgian PROCARE rectal cancer registry. The effect of abdominopelvic infection on survival was assessed in uni- and multivariable Cox regression models. The effect of clinical and pathological covariates was controlled by propensity score-based matching of cases with controls. The effect of abdominopelvic sepsis on the rate of local and metastatic recurrence was evaluated using crosstabulation and the Pearson χ2 test. RESULTS: In univariable analysis, the presence of APS was associated with significantly worse overall survival (HR 1.3, P = 0.025). After propensity score matching including age, BMI, tumor level, pTstage, pN stage, CRM, tumor grade, number of lymph nodes, and presence of lymphovascular invasion, the association of APS with OS was no longer significant (HR 1.26, 95%CI 0.92-1.74, P = 0.15). No differences were observed in the risk of local or metastatic recurrence (3.6% vs 2.9% and 13% vs 16.5%). CONCLUSIONS: In this analysis APS after rectal cancer resection was not significantly associated with OS, metastatic, or local recurrence.

The VEGFR Inhibitor Cediranib Improves the Efficacy of Fractionated Radiotherapy in a Colorectal Cancer Xenograft Model.

BACKGROUND/PURPOSE: Radiotherapy (RT) increases local tumor control in locally advanced rectal cancer, but complete histological response is seen in only a minority of cases. Antiangiogenic therapy has been proposed to improve RT efficacy by "normalizing" the tumor microvasculature. Here, we examined whether cediranib, a pan-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, improves microvascular function and tumor control in combination with RT in a mouse colorectal cancer (CRC) model. METHODS: CRC xenografts (HT29) were grown subcutaneously in mice. Animals were treated for 5 consecutive days with vehicle, RT (1.8 Gy daily), cediranib (6 mg/kg po), or combined therapy (cediranib 2 h prior to radiation). Tumor volume was measured with calipers. Vascular changes were analyzed by dynamic contrast-enhanced MRI, oxygenation and interstitial fluid pressure probes and histology. To investigate vascular changes more in detail, a second set of mice were fitted with titanium dorsal skinfold window chambers, wherein a HT29 tumor cell suspension was injected. In vivo fluorescence microscopy was performed before and after treatment (same treatment protocol). RESULTS: In vivo microscopy analyses showed that VEGFR inhibition with cediranib led to a "normalization" of the vessel wall, with decreased microvessel permeability (p < 0.0001) and tortuosity (p < 0.01), and a trend to decreased vessel diameters. This seemed to lead to lower tumor hypoxia rates in the cediranib and combination groups compared to the control and RT groups. This led to an increased tumor control in the combination group compared to controls or monotherapy (p < 0.0001). CONCLUSIONS: The combination of RT with cediranib enhances tumor control in a CRC xenograft mouse model. Microvascular analyses suggest that cediranib leads to vascular normalization and improved oxygenation.