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.

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.

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.

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.

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.

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.

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.