Early postoperative systemic inflammatory response as predictor of anastomotic leakage after esophagectomy: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Postesophagectomy anastomotic leakage occurs in up to 16% of patients and is the main cause of morbidity and mortality. The leak severity is determined by the extent of contamination and the degree of sepsis, both of which are related to the time from onset to treatment. Early prediction based on inflammatory biomarkers such as C-reactive protein (CRP) levels, white blood cell counts, albumin levels, and combined Noble-Underwood (NUn) scores can guide early management. This review aimed to determine the diagnostic accuracy of these biomarkers. METHODS: This study was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the PROSPERO (International Prospective Register of Systematic Reviews) database. Two reviewers independently conducted searches across PubMed, MEDLINE, Web of Science, and Embase. Sources of bias were assessed, and a meta-analysis was performed. RESULTS: Data from 5348 patients were analyzed, and 13% experienced leakage. The diagnostic accuracy of the serum biomarkers was analyzed, and pooled cutoff values were identified. CRP levels were found to have good diagnostic accuracy on days 2 to 5. The best discrimination was identified on day 2 for a cutoff value < 222 mg/L (area under the curve = 0.824, sensitivity = 81%, specificity = 88%, positive predictive value = 38.6%, and negative predictive value = 98%). A NUn score of >10 on day 4 correlated with poor diagnostic accuracy. CONCLUSION: The NUn score failed to achieve adequate accuracy. CRP seems to be the only valuable biomarker and is a negative predictor of postesophagectomy leakage. Patients with a CRP concentration of <222 mg/L on day 2 are unlikely to develop a leak, and patients can safely proceed through their enhanced recovery after surgery protocol. Patients with a CRP concentration of <127 mg/L on day 5 can be safely discharged when clinically possible.

Outcomes after Surgical Treatment of Oesophagogastric Cancer with Synchronous Liver Metastases: A Multicentre Retrospective Cohort Study.

Approximately 10-12% of patients with oesophageal or gastric cancer (OGC) present with oligometastatic disease at diagnosis. It remains unclear if there is a role for radical surgery in these patients. We aimed to assess the outcomes of OGC patients who underwent simultaneous treatment for the primary tumour and synchronous liver metastases. Patients with OGC who underwent surgical treatment between 2008 and 2020 for the primary tumour and up to five synchronous liver metastases aiming for complete tumour removal or ablation (i.e., no residual tumour) were identified from four institutional databases. The primary outcome was overall survival (OS), calculated with the Kaplan-Meier method. Secondary outcomes were disease-free survival and postoperative outcomes. Thirty-one patients were included, with complete follow-up data for 30 patients. Twenty-six patients (84%) received neoadjuvant therapy followed by response evaluation. Median OS was 21 months [IQR 9-36] with 2- and 5-year survival rates of 43% and 30%, respectively. While disease recurred in 80% of patients (20 of 25 patients) after radical resection, patients with a solitary liver metastasis had a median OS of 34 months. The number of liver metastases was a prognostic factor for OS (solitary metastasis aHR 0.330; p-value = 0.025). Thirty-day mortality was zero and complications occurred in 55% of patients. Long-term survival can be achieved in well-selected patients who undergo surgical resection of the primary tumour and local treatment of synchronous liver metastases. In particular, patients with a solitary liver metastasis seem to have a favourable prognosis.

Systemic Inflammatory Response and the Noble and Underwood (NUn) Score as Early Predictors of Anastomotic Leakage after Esophageal Reconstructive Surgery.

Anastomotic leakage (AL) remains the main cause of post-esophagectomy morbidity and mortality. Early detection can avoid sepsis and reduce morbidity and mortality. This study evaluates the diagnostic accuracy of the Nun score and its components as early detectors of AL. This single-center observational cohort study included all esophagectomies from 2010 to 2020. C-reactive protein (CRP), albumin (Alb), and white cell count (WCC) were analyzed and NUn scores were calculated. The area under the curve statistic (AUC) was used to assess their predictive accuracy. A total of 74 of the 668 patients (11%) developed an AL. CRP and the NUn-score proved to be good diagnostic accuracy tests on postoperative day (POD) 2 (CRP AUC: 0.859; NUn score AUC: 0.869) and POD 4 (CRP AUC: 0.924; NUn score AUC: 0.948). A 182 mg/L CRP cut-off on POD 4 yielded a 87% sensitivity, 88% specificity, a negative predictive value (NPV) of 98%, and a positive predictive value (PPV) of 47.7%. A NUn score cut-off > 10 resulted in 92% sensitivity, 95% specificity, 99% NPV, and 68% PPV. Albumin and WCC have limited value in the detection of post-esophagectomy AL. Elevated CRP and a high NUn score on POD 4 provide high accuracy in predicting AL after esophageal cancer surgery. Their high negative predictive value allows to select patients who can safely proceed with enhanced recovery protocols.

A Video-Based Procedure-Specific Competency Assessment Tool for Minimally Invasive Esophagectomy.

Importance: Minimally invasive esophagectomy (MIE) is a complex procedure with substantial learning curves. In other complex minimally invasive procedures, suboptimal surgical performance has convincingly been associated with less favorable patient outcomes as assessed by peer review of the surgical procedure. Objective: To develop and validate a procedure-specific competency assessment tool (CAT) for MIE. Design, Setting, and Participants: In this international quality improvement study, a procedure-specific MIE-CAT was developed and validated. The MIE-CAT contains 8 procedural phases, and 4 quality components per phase are scored with a Likert scale ranging from 1 to 4. For evaluation of the MIE-CAT, intraoperative MIE videos performed by a single surgical team in the Esophageal Center East Netherlands were peer reviewed by 18 independent international MIE experts (with more than 120 MIEs performed). Each video was assessed by 2 or 3 blinded experts to evaluate feasibility, content validity, reliability, and construct validity. MIE-CAT version 2 was composed with refined content aimed at improving interrater reliability. A total of 32 full-length MIE videos from patients who underwent MIE between 2011 and 2020 were analyzed. Data were analyzed from January 2021 to January 2023. Exposure: Performance assessment of transthoracic MIE with an intrathoracic anastomosis. Main Outcomes and Measures: Feasibility, content validity, interrater and intrarater reliability, and construct validity, including correlations with both experience of the surgical team and clinical parameters, of the developed MIE-CAT. Results: Experts found the MIE-CAT easy to understand and easy to use to grade surgical performance. The MIE-CAT demonstrated good intrarater reliability (range of intraclass correlation coefficients [ICCs], 0.807 [95% CI, 0.656 to 0.892] for quality component score to 0.898 [95% CI, 0.846 to 0.932] for phase score). Interrater reliability was moderate (range of ICCs, 0.536 [95% CI, -0.220 to 0.994] for total MIE-CAT score to 0.705 [95% CI, 0.473 to 0.846] for quality component score), and most discrepancies originated in the lymphadenectomy phases. Hypothesis testing for construct validity showed more than 75% of hypotheses correct: MIE-CAT performance scores correlated with experience of the surgical team (r = 0.288 to 0.622), blood loss (r = -0.034 to -0.545), operative time (r = -0.309 to -0.611), intraoperative complications (r = -0.052 to -0.319), and severe postoperative complications (r = -0.207 to -0.395). MIE-CAT version 2 increased usability. Interrater reliability improved but remained moderate (range of ICCs, 0.666 to 0.743), and most discrepancies between raters remained in the lymphadenectomy phases. Conclusions and Relevance: The MIE-CAT was developed and its feasibility, content validity, reliability, and construct validity were demonstrated. By providing insight into surgical performance of MIE, the MIE-CAT might be used for clinical, training, and research purposes.

Global surgery education in Belgium: Student's knowledge, attitudes and exposure.

PURPOSE: Understanding how medical students perceive global surgery will be essential in strengthening the global surgery workforce by 2030. This study investigated the knowledge, attitudes and exposure of Belgian medical students towards global surgery and identified avenues for medical institutions to include meaningful educational opportunities. METHODS: An online survey was distributed to first to final year medical students across Belgian universities using social media. Data were collected on demographics, exposure, knowledge and attitudes towards global surgery. Odds ratios with 95% confidence intervals were calculated. RESULTS: A total of 304 medical students participated from four Belgian universities. A minority reported having exposure to global surgery (24.7%), and most wanted more exposure (75.3%). Almost all respondents agreed (94.4%) that it is a relevant topic for medical students, and most agreed (71%) more compulsory education on the topic is needed. Only 13 to 44% of students could correctly answer questions testing global surgery knowledge. Personal/family responsibilities were the most important barrier to pursuing global surgery careers. CONCLUSIONS: Global surgery knowledge and exposure is limited among Belgian medical students despite interest in the field. These results advocate for the inclusion of decolonised global surgery education alongside equitable international clinical internships in medical education worldwide.

Crowd-sourced and expert video assessment in minimally invasive esophagectomy.

BACKGROUND: Video-based assessment by experts may structurally measure surgical performance using procedure-specific competency assessment tools (CATs). A CAT for minimally invasive esophagectomy (MIE-CAT) was developed and validated previously. However, surgeon's time is scarce and video assessment is time-consuming and labor intensive. This study investigated non-procedure-specific assessment of MIE video clips by MIE experts and crowdsourcing, collective surgical performance evaluation by anonymous and untrained laypeople, to assist procedure-specific expert review. METHODS: Two surgical performance scoring frameworks were used to assess eight MIE videos. First, global performance was assessed with the non-procedure-specific Global Operative Assessment of Laparoscopic Skills (GOALS) of 64 procedural phase-based video clips < 10 min. Each clip was assessed by two MIE experts and > 30 crowd workers. Second, the same experts assessed procedure-specific performance with the MIE-CAT of the corresponding full-length video. Reliability and convergent validity of GOALS for MIE were investigated using hypothesis testing with correlations (experience, blood loss, operative time, and MIE-CAT). RESULTS: Less than 75% of hypothesized correlations between GOALS scores and experience of the surgical team (r < 0.3), blood loss (r = - 0.82 to 0.02), operative time (r = - 0.42 to 0.07), and the MIE-CAT scores (r = - 0.04 to 0.76) were met for both crowd workers and experts. Interestingly, experts' GOALS and MIE-CAT scores correlated strongly (r = 0.40 to 0.79), while crowd workers' GOALS and experts' MIE-CAT scores correlations were weak (r = - 0.04 to 0.49). Expert and crowd worker GOALS scores correlated poorly (ICC ≤ 0.42). CONCLUSION: GOALS assessments by crowd workers lacked convergent validity and showed poor reliability. It is likely that MIE is technically too difficult to assess for laypeople. Convergent validity of GOALS assessments by experts could also not be established. GOALS might not be comprehensive enough to assess detailed MIE performance. However, expert's GOALS and MIE-CAT scores strongly correlated indicating video clip (instead of full-length video) assessments could be useful to shorten assessment time.

A Population-Based Study Using Belgian Cancer Registry Data Supports Centralization of Esophageal Cancer Surgery in Belgium.

BACKGROUND: Esophageal cancer surgery outcomes benefit from higher hospital volumes. Despite the evidence, organization of national health care often is complex and depends on various factors. The volume-outcome results of this population-based study supported national health policy measures regarding concentration of esophageal resections in Belgium. METHODS: The Belgian Cancer Registry (BCR) database was linked to administrative data on cancer treatment. All Belgian patients with newly diagnosed esophageal cancer in 2008-2018 undergoing resection were allocated to the hospital at which surgery was performed. The study assessed hospital volume association with 90-day mortality and 5-year overall survival, classifying average annual hospital volume of resections as low (LV, <6), medium (MV, 6-19), or high (HV, ≥20) and as a continuous covariate in the regression models. RESULTS: The study included 4156 patients who had surgery in 79 hospitals (2 HV hospitals [37% of all surgeries], 12 MV hospitals [30% of all surgeries], and 65 LV hospitals [33% of all surgeries]). Adjusted 90-day mortality in HV hospitals was lower than in LV hospitals (odds ratio [OR], 0.37; 95% CI, 0.21-0.65; p = 0.001). Case-mix adjusted 5-year survival was superior in HV versus LV (hazard ratio [HR], 0.43; 95% CI, 0.31-0.60; p < 0.001). The continuous model demonstrated a lower 90-day mortality (OR, 0.40; 95% CI, 0.23-0.71; p = 0.002) and a superior 5-year survival (HR, 0.45; 95% CI, 0.33-0.63; p < 0.001) in hospitals with volumes of 40 or more resections annually. CONCLUSION: Population-based data from the BCR confirmed a strong volume-outcome association for esophageal resections. Improved 5-year survival in centers with annual volumes of 20 or more resections was driven mainly by the achievement of superior 90-day mortality. These findings supported centralization of esophageal resections in Belgium.

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).

Treatment of anastomotic leak after esophagectomy: insights of an international case vignette survey and expert discussions.

Anastomotic leak (AL) is a severe complication after esophagectomy. Clinical presentation of AL is diverse and there is large practice variation regarding treatment of AL. This study aimed to explore different AL treatment strategies and their underlying rationale. This mixed-methods study consisted of an international survey among upper gastro-intestinal (GI) surgeons and focus groups with expert upper GI surgeons. The survey included 10 case vignettes and data sources were integrated after separate analysis. The survey was completed by 188 respondents (completion rate 69%) and 6 focus groups were conducted with 20 international experts. Prevention of mortality was the most important goal of primary treatment. Goals of secondary treatment were to promote tissue healing, return to oral feeding and safe hospital discharge. There was substantial variation in the preferred treatment principles (e.g. drainage or defect closure) and modalities (e.g. stent or endoVAC) within different presentations of AL. Patients with local symptoms were treated by supportive means only or by non-surgical drainage and/or defect closure. Drainage was routinely performed in patients with intrathoracic collections and often combined with defect closure. Patients with conduit necrosis were predominantly treated by resection and reconstruction of the anastomosis or by esophageal diversion. This mixed-methods study shows that overall treatment strategies for AL are determined by vitality of the conduit and presence of intrathoracic collections. There is large variation in preferred treatment principles and modalities. Future research may investigate optimal treatment for specific AL presentations and aim to develop consensus-based treatment guidelines for AL after esophagectomy.

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.

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.

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.

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.

Near-infrared fluorescence guided esophageal reconstructive surgery: A systematic review.

BACKGROUND: After an esophagectomy, the stomach is most commonly used to restore continuity of the upper gastrointestinal tract. These esophago-gastric anastomoses are prone to serious complications such as leakage associated with high morbidity and mortality. Graft perfusion is considered to be an important predictor for anastomotic integrity. Based on the current literature we believe Indocyanine green fluorescence angiography (ICGA) is an easy assessment tool for gastric tube (GT) perfusion, and it might predict anastomotic leakage (AL). AIM: To evaluate feasibility and effectiveness of ICGA in GT perfusion assessment and as a predictor of AL. METHODS: This study was designed according to the PRISMA guidelines and registered in the PROSPERO database. PubMed and EMBASE were independently searched by 2 reviewers for studies presenting data on intraoperative ICGA GT perfusion assessment during esophago-gastric reconstruction after esophagectomy. Relevant outcomes such as feasibility, complications, intraoperative surgical changes based on ICGA findings, quantification attempts, anatomical data and the impact of ICGA on postoperative anastomotic complications, were collected by 2 independent researchers. The quality of the included articles was assessed based on the Methodological Index for Non-Randomized Studies. The 19 included studies presented data on 1192 esophagectomy patients, in 758 patients ICGA was used perioperative to guide esophageal reconstruction. RESULTS: The 19 included studies for qualitative analyses all described ICGA as a safe and easy method to evaluate gastric graft perfusion. AL occurred in 13.8% of the entire cohort, 10% in the ICG guided group and 20.6% in the control group (P < 0.001). When poorly perfused cases are excluded from the analyses, the difference in AL was even larger (AL well-perfused group 6.3% vs control group 20.5%, P < 0.001). The AL rate in the group with an altered surgical plan based on the ICG image was 6.5%, similar to the well perfused group (6.3%) and significantly less than the poorly perfused group (47.8%) (P < 0.001), suggesting that the technique is able to identify and alter a potential bad outcome. CONCLUSION: ICGA is a safe, feasible and promising method for perfusion assessment. The lower AL rate in the well perfused group suggest that a good fluorescent signal predicts a good outcome.

Articulated Instruments and 3D Visualization: A Synergy? Evaluation of Execution Time, Errors, and Visual Fatigue.

Objective. The introduction of advanced endoscopic systems, such as the Storz Image1S and the Olympus Endoeye, heralds a new era of 3-dimensional (3D) visualization. The aim of this report is to provide a comprehensive overview of the neurophysiology of 3D view, its relevance in videoscopy, and to quantify the benefit of the new 3D technologies for both rigid and articulated instruments. Method. Sixteen medical students without any laparoscopic experience were trained each for a total of 27 hours. Proficiency scores were determined for rigid and articulated instruments under 2D and 3D visualization conditions. Results. A reduction in execution time of 14%, 28%, and 36% was seen for the rigid instruments, the da Vinci, and Steerable instruments, respectively. A reduction in errors of 84%, 92%, and 87% was seen for the rigid instruments, the da Vinci, and Steerable instruments, respectively. Conclusion. 3D visualization greatly augments endoscopic procedures. The advanced endoscopic systems employed in the recent study caused no visual fatigue or discomfort. The benefit of 3D was most distinct with articulated instruments.

Quality of life of patients with a colonic interposition postoesophagectomy.

OBJECTIVES: After oesophagectomy, stomach grafts are most frequently used to restore intestinal continuity. Less frequently, a colonic graft is used. There is quite a large body of literature addressing the functional outcome after gastric pull-up, but little is known about the functional results of colonic interposition (CI). The aim of this study was to assess the short-term outcomes and the long-term quality of life and function of the CI postoesophagectomy. METHODS: Between 2002 and 2016, we retrospectively collected data on 80 patients with CI from personal health records at the Ghent University hospital. We prospectively compared the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-OG25 and Swallowing Quality of Life (SWAL-QOL) questionnaire scores to the healthy reference group and the gastric tube (GT) group. RESULTS: The 30-day mortality rate was 5%. Anastomotic leakage occurred in 37.5% and stenosis in 20% of the patients. The median overall survival of all patients was 33.9 months (95% confidence interval 8.3-59.4). The mean general health score of the CI patients was less than the healthy reference group but comparable to the GT group (CI = 62.1 vs healthy reference group = 71.2 vs GT = 60). Fifty percent of the patients reported their health as good and 15% as very good. The mean functional results with a CI were better than with a GT. Compared to GT patients, CI patients had less dyspnoea, reflux and dysphagia, but they reported more food selection, diarrhoea and weight loss. CONCLUSIONS: Despite the high complication rate, the severity of the disease and the demanding operation, patients perceived themselves as being in good health and reported very good long-term functionality after CI. CLINICAL TRIAL REGISTRATION NUMBER: B670201630635.

Assessment of graft perfusion and oxygenation for improved outcome in esophageal cancer surgery: Protocol for a single-center prospective observational study.

INTRODUCTION: The main cause of anastomotic leakage (AL) is tissue hypoxia, which results from impaired perfusion of the pedicle stomach graft after esophageal reconstruction. Clinical judgment is unreliable in determining graft perfusion. Therefore, an objective, validated, and reproducible method is urgently needed. Near infrared fluorescence perfusion imaging using indocyanine green (ICG) is an emerging and promising modality. This study's objectives are to evaluate the feasibility of quantification of ICG angiography (ICGA) to assess graft perfusion and to validate ICGA by comparison with hemodynamic parameters, blood and tissue expression of hypoxia-induced markers, and tissue mitochondrial respiration rates. And, second, to evaluate its ability to predict AL in patients after minimally invasive esophagectomy (MIE). METHODS: Patients (N = 70) with resectable esophageal cancer will be recruited for standard MIE. ICGA will be performed after graft creation and thoracic pull-up. Dynamic digital images will be obtained starting after intravenous bolus administration of ICG. The resulting images will be subjected to curve analysis and to compartmental analysis based on the adiabatic approximation to tissue homogeneity kinetic model. The calculated perfusion parameters will be compared to intraoperative hemodynamic data to evaluate the effects of patient hemodynamics. To verify whether graft perfusion represents tissue oxygenation, ICGA perfusion parameters will be compared with systemic and serosa lactate from the stomach graft. In addition, perfusion parameters will be compared to tissue expression of hypoxia-related markers and mitochondrial chain respiratory rate. Finally, the ability of functional, histological, and cellular perfusion and oxygenation parameters to predict AL and postoperative morbidity in general will be evaluated using the appropriate univariate and multivariate statistical analyses. DISCUSSION: The results of this project may lead to a novel, reproducible, and minimally invasive method to objectively assess perioperative anastomotic perfusion during MIE, potentially reducing the incidence of AL and its associated severe morbidity and mortality. TRIAL REGISTRATION: Clinicaltrials.gov registration number is NCT03587532. The study was approved by the ethical committee of the Ghent University, Belgium (B670201836427).

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.

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.

Adipose-Derived Mesenchymal Stromal Cells Improve the Healing of Colonic Anastomoses Following High Dose of Irradiation Through Anti-Inflammatory and Angiogenic Processes.

Cancer patients treated with radiotherapy (RT) could develop severe late side effects that affect their quality of life. Long-term bowel complications after RT are mainly characterized by a transmural fibrosis that could lead to intestinal obstruction. Today, surgical resection is the only effective treatment. However, preoperative RT increases the risk of anastomotic leakage. In this study, we attempted to use mesenchymal stromal cells from adipose tissue (Ad-MSCs) to improve colonic anastomosis after high-dose irradiation. MSCs were isolated from the subcutaneous fat of rats, amplified in vitro, and characterized by flow cytometry. An animal model of late radiation side effects was induced by local irradiation of the colon. Colonic anastomosis was performed 4 wk after irradiation. It was analyzed another 4 wk later (i.e., 8 wk after irradiation). The Ad-MSC-treated group received injections several times before and after the surgical procedure. The therapeutic benefit of the Ad-MSC treatment was determined by colonoscopy and histology. The inflammatory process was investigated using Fluorine-182-Fluoro-2-Deoxy-d-Glucose Positron Emission Tomography and Computed Tomography (18F-FDG-PET/CT) imaging and macrophage infiltrate analyses. Vascular density was assessed using immunohistochemistry. Results show that Ad-MSC treatment reduces ulcer size, increases mucosal vascular density, and limits hemorrhage. We also determined that 1 Ad-MSC injection limits the inflammatory process, as evaluated through 18F-FDG-PET-CT (at 4 wk), with a greater proportion of type 2 macrophages after iterative cell injections (8 wk). In conclusion, Ad-MSC injections promote anastomotic healing in an irradiated colon through enhanced vessel formation and reduced inflammation. This study also determined parameters that could be improved in further investigations.