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.

Clinical implications of dose to functional lung volumes in the trimodality treatment of esophageal cancer.

BACKGROUND: Trimodality treatment, i.e., neoadjuvant chemoradiotherapy (nCRT) followed by surgery, for locally advanced esophageal cancer (EC) improves overall survival but also increases the risk of postoperative pulmonary complications. Here, we tried to identify a relation between dose to functional lung volumes (FLV) as determined by 4D-CT scans in EC patients and treatment-related lung toxicity. MATERIALS AND METHODS: All patients with EC undergoing trimodality treatment between 2017 and 2022 in UZ Leuven and scanned with 4D-CT-simulation were selected. FLVs were determined based on Jacobian determinants of deformable image registration between maximum inspiration and expiration phases. Dose/volume parameters of the anatomical lung volume (ALV) and FLV were compared between patients with versus without postoperative pulmonary complications. Results of pre- and post-nCRT pulmonary function tests (PFTs) were collected and compared in relation to radiation dose. RESULTS: Twelve out of 51 EC patients developed postoperative pulmonary complications. ALV was smaller while FLV10Gy and FLV20Gy were larger in patients with complications (respectively 3141 ± 858mL vs 3601 ± 635mL, p = 0.025; 360 ± 216mL vs 264 ± 139mL, p = 0.038; 166 ± 106mL vs 118 ± 63mL, p = 0.030). No differences in ALV dose-volume parameters were detected. Baseline FEV1 and TLC were significantly lower in patients with complications (respectively 90 ± 17%pred vs 102 ± 20%pred, p = 0.033 and 93 ± 17%pred vs 110 ± 13%pred, p = 0.001), though no other PFTs were significantly different between both groups. DLCO was the only PFT that had a meaningful decrease after nCRT (85 ± 17%pred vs 68 ± 15%pred, p < 0.001) but was not related to dose to ALV/FLV. CONCLUSION: Small ALV and increasing FLV exposed to intermediate (10 to 20 Gy) dose are associated to postoperative pulmonary complications. Changes of DLCO occur during nCRT but do not seem to be related to radiation dose to ALV or FLV. This information could attribute towards toxicity risk prediction and reduction strategies for EC.

The Belsey Mark IV procedure in the era of minimally invasive antireflux surgery.

BACKGROUND: Different surgical techniques exist in the treatment of giant and complex hiatal hernia. The aim of this study was to identify the role of the Belsey Mark IV (BMIV) antireflux procedure in the era of minimally invasive techniques. METHODS: A single-center, retrospective cohort study was conducted. All patients who underwent an elective BMIV procedure aged 18 years or older, during a 15-year period (January 1, 2002 until December 31, 2016), were included. Demographics, pre-, per- and postoperative data were analyzed. Three groups were compared. Group A: BMIV as first procedure-group B: BMIV as a second procedure (first redo intervention)-group C: patients who had two or more previous antireflux interventions. RESULTS: A total of 216 patients were included for analysis (group A n = 127; group B n = 51; group C n = 38). Median follow-up in groups A, B and C was 28, 48 and 56 months, respectively. Patients in group A were older and had a higher American Society of Anesthesiologists score compared to groups B and C. There was zero mortality in all groups. The severe complication rate of 7.9% in group A was higher compared with the 2.9% in group B and 3.9% in group C. Long-term outcome showed true recurrence, defined as both radiographic recurrence as well as associated symptoms, in 9.5% of cases in group A, 24.5% in group B and 44.7% in group C. CONCLUSIONS: The BMIV procedure is a safe procedure with good results, moreover in the aging and comorbid patient with primary repair of a giant hiatal hernia.

Primary Surgery Not Inferior to Neoadjuvant Chemoradiotherapy for Esophageal Adenocarcinoma.

BACKGROUND: The current gold standard for treatment of locally advanced esophageal adenocarcinoma is neoadjuvant chemotherapy or chemoradiotherapy followed by surgery. The shift toward neoadjuvant chemoradiotherapy (nCRT) was driven by the Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) trial. This study reassessed, in daily practice, the presumed advantage of nCRT followed by surgery on long-term survival compared with primary surgery, in a group of all adenocarcinomas treated through a transthoracic approach with extensive 2-field lymphadenectomy. METHODS: This retrospective cohort study with propensity score-matched analysis included all surgically treated patients between 2000 and 2018 with locally advanced adenocarcinoma (cT1/2 N+ or cT3/4 N0/+). For appropriate comparison, exclusion criteria of the CROSS trial were applied. Patients were matched on age, Charlson comorbidity score, clinical tumor length, and lymph node status. The primary end point was 5-year overall survival. RESULTS: There were 473 eligible patients who underwent primary surgery (225 patients) or nCRT + surgery (248 patients). After propensity score-matched analysis, 149 matched cases were defined in each group for analysis. There was no significant difference after 5 years between the matched groups in median overall survival (32.5 and 35.0 months, P = .41) and median disease-free survival (14.3 and 13.5 months, P = .16). nCRT was associated with significantly more postoperative complications (mean Comprehensive Complication Index score: 21.0 vs 30.5, P < .0001) and longer mean stay in the hospital (14.0 vs 18.2 days, P = .05) and intensive care unit (11.7 vs 37.7 days, P = .05). CONCLUSIONS: Our propensity score-matched results indicate that primary surgery, performed through transthoracic approach with extensive 2-field lymphadenectomy, can offer a comparable overall and disease-free survival after 5 years, with potentially fewer postoperative complications and shorter hospital and intensive care unit stay compared with nCRT followed by surgery.

How to handle brain tumors after esophagectomy with curative intent: A single center 20-year experience.

BACKGROUND: Brain metastases after esophagectomy are rare. Moreover, a diagnostic uncertainty remains as pathology is rarely obtained and radiological features can show similarities to primary brain tumors. Our aim was to demonstrate the diagnostic uncertainty and identify risk factors associated with brain tumors (BT) after esophagectomy with curative intent. METHODS: All patients who underwent an esophagectomy with curative intent from 2000 to 2019 were reviewed. Diagnostics and characteristics of BT were analyzed. Multivariable logistic and cox regression were performed to determine factors associated with development of BT and survival, respectively. RESULTS: In total, 2131 patients underwent esophagectomy with curative intent, of which 72 patients (3.4%) developed BT. Pathological diagnosis was obtained in 26 patients (1.2%), of which 2 patients were diagnosed with glioblastoma. On multivariate analysis, radiotherapy (OR, 7.71; 95%CI: 2.66-22.34, p < 0.001) was associated with an increased risk of BT and early-stage tumors (OR, 0.29; 95%CI: 0.10-0.90, p = 0.004) with a decreased risk of BT. Median overall survival was 7.4 months (95%CI: 4.80-9.96). BT treated with curative intent (surgery or stereotactic radiation) had a significantly better median overall survival (16 months; 95%CI: 11.3-20.7) compared to those without (3.7 months; 95%CI: 0.9-6.6, p < 0.001) CONCLUSIONS: Advanced stage tumors and radiotherapy seem related to the development of brain tumors after esophagectomy with curative intent. However, an important diagnostic uncertainty remains in these patients as pathological diagnosis is only obtained in a minority of cases. Tissue confirmation can be useful to inform a patient-tailored multimodality treatment strategy in select patient.

A Risk Model to Predict the Delivery of Adjuvant Chemotherapy Following Lung Resection in Patients With Pathologically Positive Lymph Nodes.

To investigate factors associated with the ability to receive adjuvant chemotherapy in patients with pathological N1 and N2 stage after anatomic lung resections for non-small cell lung cancer (NSCLC). Multicenter retrospective analysis on 707 consecutive patients found pathologic N1 (pN1) or N2 (pN2) disease following anatomic lung resections for NSCLC (2014-2019). Multiple imputation logistic regression was used to identify factors associated with adjuvant chemotherapy and to develop a model to predict the probability of starting this treatment. The model was externally validated in a population of 253 patients. In the derivation set, 442 patients were pN1 and 265 pN2. 58% received at least 1 cycle of adjuvant chemotherapy. The variables significantly associated with the probability of starting chemotherapy after multivariable regression analysis were: younger age (p < 0.0001), Body Mass Index (BMI) (p = 0.031), Forced Expiratory Volume in 1 second (FEV1) (p = 0.037), better performance status (PS) (p < 0.0001), absence of chronic kidney disease (CKD) (p = 0.016), resection lesser than pneumonectomy (p = 0.010). The logit of the prediction model was: 6.58 -0.112 x age +0.039 x BMI +0.009 x FEV1 -0.650 x PS -1.388 x CKD -0.550 x pneumonectomy. The predicted rate of adjuvant chemotherapy in the validation set was 59.2 and similar to the observed 1 (59%, p = 0.87) confirming the model performance in external setting. This study identified several factors associated with the probability of initiating adjuvant chemotherapy after lung resection in node-positive patients. This information can be used during preoperative multidisciplinary meetings and patients counseling to support decision-making process regarding the timing of systemic treatment.

Real-life introduction of powered circular stapler for esophagogastric anastomosis: cohort and propensity matched score study.

Anastomotic leakage after esophagectomy is one of the most feared complications, which results in increased morbidity and mortality. Our aim was to evaluate the impact of a powered circular stapler on complications after esophagectomy with intrathoracic anastomosis for esophageal cancer. Between May 2019 and July 2021, all consecutive oesophagectomies for cancer with intrathoracic anastomosis in a high-volume center were included in this retrospective study. Surgeons were free to choose either a manual or a powered circular stapler. Preoperative characteristics and postoperative complications were recorded in a prospective database, according to EsoData. Propensity score matching (age, body mass index, Eastern cooperative oncology group (ECOG) performance and neoadjuvant therapy) was conducted to reduce potential confounding. We included 128 patients. Powered and manual circular staplers were used in 62 and 66 patients, respectively. Fewer anastomotic leakages were observed with the powered stapler group (OR = 7.3 (95%CI: 1.58-33.7); [3.2% (n = 2) vs 19.7% (n = 13), respectively; p = 0.004]). After propensity score matching, this remained statistically significant (OR = 8.5 (95%CI: 1.80-40.1); [4.1% (n = 2) vs 20.4% (n = 10), respectively; p = 0.013]). Additionally, anastomotic diameter was significantly higher with the powered stapler (median: 29 mm (63.3%) vs 25 mm (57.1%), respectively; p < 0.0001). There was no significant difference in comprehensive complication index (p = 0.146). A decreased mean length of stay was observed in the powered stapler group (11.1 vs 18.7 days respectively; p = 0.022). Postoperative anastomotic leakage after esophageal resection was significantly reduced after the introduction of the powered circular stapler, consequently resulting in a reduced length of stay. Further evaluation on long-term strictures and quality of life are warranted to support these results.

Is Re-introducing Major Open and Minimally Invasive Surgery during COVID-19 Safe for Patients and Healthcare Workers? An International, Multi-centre Cohort Study in the Field of Oesophago-gastric Surgery.

INTRODUCTION: The COVID-19 pandemic has resulted in unparalleled changes to patient care, including the suspension of cancer surgery. Concerns regarding COVID-19-related risks to patients and healthcare workers with the re-introduction of major complex minimally invasive and open surgery have been raised. This study examines the COVID-19 related risks to patients and healthcare workers following the re-introduction of major oesophago-gastric (EG) surgery. PATIENTS AND METHODS: This was an international, multi-centre, observational study of consecutive patients treated by open and minimally invasive oesophagectomy and gastrectomy for malignant or benign disease. Patients were recruited from nine European centres serving regions with a high population incidence of COVID-19 between 1 May and 1 July 2020. The primary endpoint was 30-day COVID-19-related mortality. All staff involved in the operative care of patients were invited to complete a health-related survey to assess the incidence of COVID-19 in this group. RESULTS: In total, 158 patients were included in the study (71 oesophagectomy, 82 gastrectomy). Overall, 87 patients (57%) underwent MIS (59 oesophagectomy, 28 gastrectomy). A total of 403 staff were eligible for inclusion, of whom 313 (78%) completed the health survey. Approaches to mitigate against the risks of COVID-19 for patients and staff varied amongst centres. No patients developed COVID-19 in the post-operative period. Two healthcare workers developed self-limiting COVID-19. CONCLUSIONS: Precautions to minimise the risk of COVID-19 infection have enabled the safe re-introduction of minimally invasive and open EG surgery for both patients and staff. Further studies are necessary to determine the minimum requirements for mitigations against COVID-19.

Safety of Esophageal Cancer Surgery During the First Wave of the COVID-19 Pandemic in Europe: A Multicenter Study.

BACKGROUND: Many hospitals postponed elective surgical care during the first wave of the coronavirus disease 2019 (COVID-19) pandemic. Some centers continued elective surgery, including esophageal cancer surgery, with the use of preoperative screening methods; however, there is no evidence supporting the safety of this strategy as postoperative outcomes after esophageal cancer surgery during the COVID-19 pandemic have not yet been investigated. METHODS: This multicenter study in four European tertiary esophageal cancer referral centers included consecutive adult patients undergoing elective esophageal cancer surgery from a prospectively maintained database in a COVID-19 pandemic cohort (1 March 2020-31 May 2020) and a control cohort (1 October 2019-29 February 2020). The primary outcome was the rate of respiratory failure requiring mechanical ventilation. RESULTS: The COVID-19 cohort consisted of 139 patients, versus 168 patients in the control cohort. There was no difference in the rate of respiratory failure requiring mechanical ventilation (13.7% vs. 8.3%, p = 0.127) and number of pulmonary complications (32.4% vs. 29.9%, p = 0.646) between the COVID-19 cohort and the control cohort. Overall, postoperative morbidity and mortality rates were comparable between both cohorts. History taking and reverse transcription polymerase chain reaction (RT-PCR) were used as preoperative screening methods to detect a possible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in all centers. No patients were diagnosed with COVID-19 pre- or postoperatively. CONCLUSION: Esophageal cancer surgery during the first wave of the COVID-19 pandemic was not associated with an increase in pulmonary complications as no patients were diagnosed with COVID-19. Esophageal cancer surgery can be performed safely with the use of adequate preoperative SARS-CoV-2 screening methods.

Surgery for mediastinal neurogenic tumours: a 25-year single-centre retrospective study.

OBJECTIVES: Mediastinal neurogenic tumours are uncommon and often benign neoplasms mostly located in the posterior mediastinum and usually diagnosed incidentally. We reviewed our results after surgical resection. We compared patient characteristics and tumour nature between children and adults. Differences between thoracoscopic and open approach were analysed. METHODS: Departmental thoracic surgical database was queried for primary mediastinal neurogenic tumours resected between 1992 and 2017. Data included demographics, pathology, tumour nature, symptoms, surgical approach and postoperative morbidity/mortality. RESULTS: Fifty-one patients (8 children and 43 adults) underwent tumour resection. Pathology revealed nerve sheath tumour in 1 child (12.5%) versus 36 adults (83.7%; P < 0.001) and ganglion cell tumour in 7 (87.5%) versus 5 (11.6%; P < 0.001). Two adults had a paraganglioma. Malignancy was present in 2 children (25%) versus 2 adults (4.6%; P = 0.049). All malignant tumours caused symptoms while most patients with benign tumours (38/47) were asymptomatic (P < 0.001). Surgical approach included thoracotomy, thoracoscopy and cervicotomy (n = 19/31/1) of which 2 were combined neurosurgical approach. All malignant tumours were approached via thoracotomy while the majority of patients with benign tumours (31/47) underwent thoracoscopy (P = 0.007). No significant difference was noted in overall morbidity between thoracoscopic versus open approach (45.2% vs 42.1%; P = 0.83). Hospital stay was significantly shorter following thoracoscopy (7.4 ± 3.3 vs 13.1 ± 9.8 days; P = 0.001). CONCLUSIONS: Children carry a higher incidence to present with a malignant tumour originating from ganglion cells while most tumours in adults are benign, originating from the nerve sheath. The majority of patients with mediastinal neurogenic tumours are asymptomatic. Most tumours are amenable for thoracoscopic resection.

Importance of Lymph Node Response After Neoadjuvant Chemoradiotherapy for Esophageal Adenocarcinoma.

BACKGROUND: Tumor response and lymph node involvement are the most important prognosticators in resected patients with esophageal adenocarcinoma after neoadjuvant chemoradiotherapy (nCRT). We hypothesize that lymph node response (LNR) is also a valuable prognosticator in these patients, potentially revealing the added effect of nCRT. METHODS: Hematoxylin and eosin slides of 193 esophageal adenocarcinoma patients with clinical suspicion of lymph node involvement (cN+) and treated with nCRT between 2008 and 2015 were assessed. Lymph nodes containing viable tumor cells were considered ypN+, and those negative for viable tumor were ypN0. LNR was also described according to an earlier defined method. Three groups were obtained: ypN0/LNR-, ypN0/LNR+, and ypN+. They were compared with 188 cN+ patients being pN0 (n = 45) or pN+ (n = 143) after upfront esophageal resection. RESULTS: Forty-four patients were ypN0/LNR-, 55 were ypN0/LNR+, and 94 were ypN+. Median overall survival was 96.4, 31.2, and 20.6 months, respectively, and was significantly different between ypN0/LNR- and ypN0/LNR+ groups (P = .020). Survival was comparable between ypN0/LNR- and pN0 (104.2 months) groups (P = .519) and between ypN+ and pN+ (21.6 months) groups (P = .966). In ypN0 patients, risk of death in LNR+ patients was tripled compared with LNR- patients. CONCLUSIONS: In cN+ esophageal adenocarcinoma patients treated with nCRT with postoperative final pathology being ypN0, median overall survival is tripled when no signs of LNR were found and comparable to cN+/pN0 upfront esophagectomy patients, suggesting that 23% of patients treated with nCRT were in fact true N0 and overtreated by nCRT. ypN+ patients have no survival benefit compared with pN+ patients.

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.

Perioperative fluid management in esophagectomy for cancer and its relation to postoperative respiratory complications.

The optimal perioperative fluid management during esophagectomy is still not clear. Liberal regimens have been associated with higher morbidity and respiratory complications. Restrictive regimens might raise concerns for kidney function and increase the need to associate vasopressors. The aim of this study was to investigate retrospectively the perioperative fluid administration during esophagectomy and to correlate this with postoperative respiratory outcome. All patients who underwent esophagectomy between January and December 2016 were retrospectively analyzed. Patient characteristics, type of surgery and postoperative course were reviewed. Fluid administration and vasopressor use were calculated intraoperatively and during the postoperative stay at the recovery unit. Fluid overload was defined as a positive fluid balance of more than 125 mL/m2/h during the first 24 hours. Patients were divided in 3 groups: GRP0 (no fluid overload/no vasopressors); GRP1 (no fluid overload/need for vasopressors); GRP2 (fluid overload with/without vasopressors). Postoperative complications were prospectively recorded according to Esophagectomy Complications Consensus Group criteria. A total of 103 patients were analyzed: 35 (34%) GRP0, 50 (49%) GRP1 and 18 (17%) GRP2. No significant differences were found for age, treatment (neoadjuvant vs. primary), type of surgery (open/minimally invasive), histology nor comorbidities. There were significant (P ≤ 0.001) differences in fluid balance/m2/h (75 ± 21 mL; 86 ± 22 mL and 144 ± 20 mL) across GRP0, GRP1 and GRP2, respectively. We found differences in respiratory complications (GRP0 (20%) versus GRP1 (42%; P = 0.034) and GRP0 (20%) versus GRP2 (61%; P = 0.002)) and "Comprehensive Complications Index" (GRP0 (20.5) versus GRP1 (34.6; P = 0.015) and GRP0 (20.5) versus GRP2 (35.1; P = 0.009)). Multivariable analysis (binary logistic regression) for "any respiratory complication" was performed. Patients who received fluid overload (GRP2) had a 10.24 times higher risk to develop postoperative respiratory complications. When patients received vasopressors alone (GRP1), the chances of developing these complications were 3.57 times higher compared to GRP0. Among patients undergoing esophagectomy, there is a wide variety in the administration of fluid during the first 24 hours. There was a higher incidence of respiratory complications when patients received higher amounts of fluid or when vasopressors were used. We believe that a personalized and protocolized fluid administration algorithm should be implemented and that individual risk factors should be identified.

NTCP model for postoperative complications and one-year mortality after trimodality treatment in oesophageal cancer.

PURPOSE/OBJECTIVES: To develop normal tissue complication probability (NTCP) models for postoperative pulmonary and cardiac complications and one-year mortality after preoperative chemoradiotherapy and surgery in oesophageal cancer patients. METHODS: 691 patients from two institutions (2002-2017) were included; 134 treated with protons. Multivariable logistic regression analyses on 601 patients studied the predictive value of clinical/treatment-related (gender, age, body mass index (BMI), smoking, cardiac comorbidity, chronic obstructive pulmonary disease, histology, cT/N) and dosimetric variables (absolute/relative lung/heart volumes receiving or spared from xGy, mean doses, planning target volume) for the presence of pulmonary complications, cardiac complications and one-year mortality. Model validation was performed using a nonrandom split-sample of 90 patients. Model performance was assessed by AUC and calibration plots. RESULTS: Respectively 144/601 (24.0%) and 165/601 (27.5%) patients developed a pulmonary or cardiac complication. For pulmonary complications, an NTCP model with optimism-corrected AUC of 0.75 (95%CI = 0.73-0.76) was obtained. The model contained mean lung dose (OR = 1.15, 95%CI = 1.09-1.22, p < 0.001), increasing age (OR = 1.03, 95%CI = 1.01-1.06, p = 0.002), BMI (OR = 1.04, 95%CI = 0.99-1.08, p = 0.084) and squamous cell carcinoma (OR = 3.22, 95%CI = 1.97-5.24, p < 0.001) as predictors. In validation, AUC of 0.79 was obtained (calibration slope 1.26). For cardiac complications, only age (OR = 1.06, 95%CI = 1.04-1.09, p < 0.001) with optimism-corrected AUC of 0.67 (95%CI = 0.65-0.68) was selected. For one-year mortality, an NTCP model with optimism-corrected AUC of 0.63 (95%CI = 0.58-0.66) was obtained. Lung absolute V35 (OR = 1.0016, 95%CI = 1.0007-1.0026, p = 0.001), cN (OR = 2.45, 95%CI = 1.18-5.09, p = 0.017), cT4 (OR = 2.51, 95%CI = 1.10-5.74, p = 0.029) and cardiac comorbidity (OR = 2.91, 95%CI = 1.46-5.77, p = 0.002) were selected as predictors. At validation, AUC of 0.57 was obtained (calibration slope 0.75). CONCLUSION: We were able to build and validate NTCP models for the presence of a postoperative pulmonary complication and for one-year mortality after trimodality treatment in oesophageal cancer.

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.

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.

Analysis of patients scheduled for neoadjuvant therapy followed by surgery for esophageal cancer, who never made it to esophagectomy.

BACKGROUND: Neoadjuvant treatment followed by esophagectomy is standard practice in locally advanced esophageal cancer. However, not all patients who started neoadjuvant treatment will undergo esophageal resection. The purpose of our study was to investigate the group of patients, scheduled for neoadjuvant treatment followed by esophagectomy, who never made it to esophageal resection. METHODS: We retrospectively analyzed patients treated between 2002 and 2015 for locally advanced esophageal cancer, who did not undergo esophagectomy after neoadjuvant treatment. Subanalysis was performed according to time period (2002-2010 versus 2011-2015) and histology (adenocarcinoma versus squamous cell carcinoma). RESULTS: In 114 of 679 patients (16.8%), surgery was not performed after neoadjuvant treatment. Reasons for cancelation were disease progression (50 patients, 43.9%), poor general condition (26 patients, 22.8%), irresectability (14 patients, 12.3%), patients' own decision (15 patients, 13.2%), and death during neoadjuvant treatment (9 patients, 7.9%). In the second time period, there were less irresectable tumors (17.7% versus 5.8%; p = 0.044). Median overall survival was not different over time (9.2 versus 12.5 months; p = 0.937). Irresectability (p = 0.032), patients' refusal (p = 0.012), and poor general condition (p = 0.002) were more frequent as reasons for cancelation in squamous cell carcinoma patients. Median overall survival was, respectively, 12.5 and 9.9 months for adenocarcinoma and squamous cell carcinoma patients (p = 0.441). The majority of patients refusing surgery had a clinical complete response (73.3%). They had a median overall survival of 33.2 months. CONCLUSIONS: One in six patients starting neoadjuvant treatment for locally advanced esophageal cancer never made it to esophagectomy, more than half of them for oncological reasons, but also 1.3% because of death during treatment. Over time, irresectability as reason decreased. As a result, the relative weight of medical inoperability increased, indicating the importance of upfront testing of medical operability. Cancelation of surgery was significantly more common in patients with a squamous cell carcinoma, and this histology seems to represent a more complex oncological and functional entity. Refusal of esophagectomy based on clinical complete response showed a significant survival benefit compared to those who did not undergo esophagectomy because of other reasons.

Combined modality treatment for malignant pleural mesothelioma: a single-centre long-term survival analysis using extrapleural pneumonectomy.

OBJECTIVES: Combined modality treatment (CMT) for malignant pleural mesothelioma (MPM) remains a matter of debate regarding the choice of surgical procedure: extrapleural pneumonectomy (EPP) or pleurectomy/decortication. METHODS: We performed a prospective interventional cohort study between 2003 and 2014. All consecutive patients with any histological MPM subtype, ≤70 years old, World Health Organization performance status ≤1, medically fit for pneumonectomy and stage cT1-2cN0-2cM0 (TNM7) or lower were included. Eligibility for CMT was discussed by the multidisciplinary tumour board. Our local CMT protocol consisted of induction chemotherapy, followed by EPP and hemithoracic radiotherapy. Induction chemotherapy consisted of 3 cycles of cisplatin (75 mg/m2 day 1) and pemetrexed (500 mg/m2 day 1), each administered once every 3 weeks. If non-progressive, EPP was performed followed by hemithoracic radiotherapy (most frequently, intensity-modulated radiotherapy; dose 54 Gy/1.8 Gy ± boost). Feasibility and long-term survival analyses were performed. Overall survival and disease-free survival (DFS) were calculated from histological confirmation of a diagnosis of MPM. RESULTS: Out of 197 patients, 97 started with CMT (79 epithelioid, 15 mixed and 3 sarcomatoid tumours, based on histological analysis). Clinical TNM was IA (n = 9)/IB (n = 8)/II (n = 57)/III (n = 23). A total of 76 patients underwent surgery (EPP: n = 56; exploratory thoracotomy: n = 20). The in-hospital mortality rate was 3.6%. Out of 56 patients who underwent surgery, 47 completed the entire CMT protocol. The intent-to-treat median and 5-year OS were 22.4 [95% confidence interval (CI) = 15.5-27.9] months and 11.2% (95% CI = 6.9-23.4). In patients who completed the CMT protocol (n = 47), these values were 33.2 (95% CI = 23.0-45.0) months and 24.2% (95% CI = 13.4-43.8). The intent-to-treat median and 5-year DFS were 15.6 (95% CI = 14.0-17.3) months and 9.9% (95% CI = 5.1-19.2), 19.8 (95% CI = 16.8-27.7) months and 17.2% (95% CI = 8.6-34.1) in those who had the full CMT. The Cox proportional hazards model showed a significantly lower DFS in positive lymph nodes (HR 2.79, 95% CI=1.35-5.78; P=0.006). In 30 (64%) patients with epithelioid type MPM without positive lymph nodes (pN0) after EPP, the 5-year DFS was 27.0% (95% CI=14.1-51.7). CONCLUSIONS: CMT with EPP for MPM is feasible, with an acceptable surgical mortality rate, and results in a 5-year survival rate of 24%. Careful patient selection (staging and physical performance) is extremely important.

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.

Palliative esophagectomy in unexpected metastatic disease: sense or nonsense?

Background Despite integrated positron emission tomography and computed tomography screening before and after neoadjuvant treatment in patients with locally advanced esophageal cancer, unexpected metastatic disease is still found in some patients during surgery. Should then esophagectomy be aborted or is there a place for palliative resection? Methods Between 2002 and 2015, 681 patients with potentially resectable esophageal cancer were sheduled for neoadjuvant therapy and subsequent esophagectomy. In 552 patients, a potentially curative esophagectomy was performed. In 12 patients, unexpected disease was discovered during surgery but esophagectomy was performed with synchronous resection of metastases; 10 of them had oligometastatic disease (≤4 single-organ metastases). Esophagectomy was not performed in 117 patients (because of disease progression in 50); 14 were also single-organ oligometastatic. Data of 10 single-organ oligometastatic patients who underwent esophageal resection (group 1) were compared those of 10 non-resected but treated counterparts (group 2) and with 228 patients who underwent potentially curative esophagectomy with persistent pathological lymph nodes (group 3). Results Five oligometastatic esophagectomy patients had lung metastases: 1 peritoneal, 2 adrenal, 1 pleural, and 1 pancreatic. Two oligometastatic non-resected patients had lung, 5 liver, and 3 brain metastases. Median overall survival was 21.4, 12.1, and 20.2 months in the respective groups (group 1 vs. group 2 p = 0.042; group 2 vs. group 3 p = 0.002; group 1 vs. group 3 p = 0.88). Conclusions Survival is longer in patients undergoing palliative esophagectomy with unexpected single-organ oligometastatic disease and comparable to survival in patients with persistent pathological lymph nodes. Palliative resection in these patients seems to be justified.