Implementation of an enhanced recovery protocol for lung volume reduction surgery: an observational cohort study.

OBJECTIVES: Lung volume reduction surgery (LVRS) is an established therapeutic option for advanced emphysema. To improve patients' safety and reduce complications, an enhanced recovery protocol (ERP) was implemented. This study aims to describe and evaluate the short-term outcome of this ERP. METHODS: This retrospective single-centre study included all consecutive LVRS patients (1 January 2017 until 15 September 2020). An ERP for LVRS was implemented and stepwise optimised from 1 August 2019, it consisted of changes in pre-, peri- and postoperative care pathways. Patients were compared before and after implementation of ERP. Primary outcome was incidence of postoperative complications (Clavien-Dindo), and secondary outcomes included chest tube duration, incidence of prolonged air leak (PAL), length of stay (LOS) and 90-day mortality. Lung function and exercise capacity were evaluated at 3 and 6 months post-LVRS. RESULTS: Seventy-six LVRS patients were included (pre-ERP: n=41, ERP: n=35). The ERP cohort presented with lower incidence of postoperative complications (42% vs 83%, P=0.0002), shorter chest tube duration (4 vs 12 days, P<0.0001) with a lower incidence of PAL (21% vs 61%, P=0.0005) and shorter LOS (6 vs 14 days, P<0.0001). No in-hospital mortality occurred in the ERP cohort versus 4 pre-ERP. Postoperative forced expiratory volume in 1 s was higher in the ERP cohort compared to pre-ERP at 3 months (1.35 vs 1.02 l) and at 6 months (1.31 vs 1.01 l). CONCLUSIONS: Implementation of ERP as part of a comprehensive reconceptualisation towards LVRS, demonstrated fewer postoperative complications, including PAL, resulting in reduced LOS. Improved short-term functional outcomes were observed at 3 and 6 months.

Complications related to extracorporeal life support in lung transplantation: single-center analysis.

Background: Extracorporeal life support (ECLS) is not routinely used at our center during sequential single-lung transplantation (LTx), but is restricted to anticipate and overcome hemodynamic and respiratory problems occurring peri-operatively. In this retrospective descriptive cohort study, we aim to describe our single-center experience with ECLS in LTx, analyzing ECLS-related complications. Methods: All transplantations with peri-operative ECLS use [2010-2020] were retrospectively analyzed. Multi-organ and heart-lung transplantation were excluded. Demographics, support type and indications are described. Complications are categorized according to the underlying nature and type. Data are presented as median [interquartile range (IQR)]. Kaplan-Meier was used for survival analysis. Results: The overall use of ECLS was 22% (156/703 patients) with a mean age of 52 years (IQR, 36-59 years). Transplant indications in ECLS cohort were interstitial lung disease (38%; n=60), chronic obstructive pulmonary disease (COPD) (19%; n=29), cystic fibrosis (17%; n=26) and others (26%; n=41). Per indication, 94% (15/16) of pulmonary arterial hypertension patients required ECLS, whereas only 8% (29/382) of COPD patients did. In 16% (25/156) of supported patients, veno-venous extracorporeal membrane oxygenation was initiated, while 77% (120/156) required veno-arterial support, and 7% (11/156) cardiopulmonary bypass. Thirty-day mortality was 6% (9/156). Sixteen percent (25/156) of patients were bridged to transplantation on ECLS and 24% (37/156) required post-operative support. Main reasons to use ECLS were intra-operative hemodynamic instability (53%; n=82), ventilation/oxygenation problems (22%; n=34) and reperfusion edema (17%; n=26). Overall incidence of patients with at least one ECLS-related complication was 67% (n=104). Most common complications were hemothorax (25%; n=39), need for continuous renal replacement therapy (19%; n=30), and thromboembolism (14%; n=22). Conclusions: ECLS was required in 22% of LTxs, with a reported ECLS-related complication rate of 67%, of which the most common was hemothorax. Larger databases are needed to further analyze complications and develop tailored deployment strategies for ECLS-use in LTx.

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.

Lung Transplant Outcome From Selected Older Donors (≥70 Years) Equals Younger Donors (<70 Years): A Propensity-matched Analysis.

OBJECTIVE: To describe our experience with lung transplantation (LTx) from donors ≥70 years and compare short and long-term outcomes to a propensity-matched cohort of donors <70 years. BACKGROUND: Although extended-criteria donors have been widely used to enlarge the donor pool, the experience with LTx from older donors (≥70 years) remains limited. METHODS: All single-center bilateral LTx between 2010 and 2020 were retrospectively analyzed. Matching (1:1) was performed for the donor (type, sex, smoking history, x-ray abnormalities, partial pressure of oxygen/fraction of inspired oxygen ratio, and time on ventilator) and recipient characteristics (age, sex, LTx indication, perioperative extracorporeal life support, and cytomegalovirus mismatch). Primary graft dysfunction grade-3, 5-year patient, and chronic lung allograft dysfunction-free survival were analyzed. RESULTS: Out of 647 bilateral LTx, 69 were performed from donors ≥70 years. The mean age in the older donor cohort was 74 years (range: 70-84 years) versus 49 years (range: 12-69 years) in the matched younger group. No significant differences were observed in the length of ventilatory support, intensive care unit, or hospital stay. Primary graft dysfunction-3 was 26% in the older group versus 29% in younger donor recipients ( P = 0.85). Reintervention rate was comparable (29% vs 16%; P = 0.10). Follow-up bronchoscopy revealed no difference in bronchial anastomotic complications ( P = 1.00). Five-year patient and chronic lung allograft dysfunction-free survivals were 73.6% versus 73.1% ( P = 0.72) and 51.5% versus 59.2% ( P = 0.41), respectively. CONCLUSIONS: LTx from selected donors ≥70 years is feasible and safe, yielding comparable short and long-term outcomes in a propensity-matched analysis with younger donors (<70 years).

Online Survey Evaluation of Three Years of European Society of Thoracic Surgeons Educational Webinars as Part of The E-learning Platform.

BACKGROUND: E-learning has become an important tool in surgical education in the last decade. The European Society of Thoracic Surgeons launched its e-learning platform in 2013 and started its educational webinars series in 2018. The aim of this paper is to discuss the introduction, evolution and impact of the educational webinars within this e-learning platform. METHODS: Twenty-four English spoken webinars discussing different subdomains in general thoracic surgery (21 expert talks, 2 pro-con debates and 1 multidisciplinary case discussion) were analyzed. An online questionnaire on timing, quality and technical aspects of the webinars was sent to 3012 registrants. RESULTS: The webinars reached 3128 unique registrants from 76 countries worldwide. The mean number of registrants was 355 with 171 live attendees (48%) and 155 replay watchers (36%). Hundred and twenty-six attendees (13.1% of people who registered for at least 4 webinars) completed the questionnaire. Timing and duration of the webinars were rated "very good" to "excellent" in 78%, and the quality of the webinar content and the expertise of the webinar presenters were rated "very good" to "excellent" in 88% and 90%, respectively. The impact on knowledge and clinical practice was scored with a weighted average of 7.27 out of 10 and 6.79 out of 10, respectively. CONCLUSIONS: The ESTS educational webinars were effective in delivering up-to-date knowledge to almost half of the countries around the globe. The impact of these events on knowledge and clinical practice were rated high. New e-learning tools should be added to the surgical educational curriculum.

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.

Impact of the first COVID-19 wave on surgical training in Flanders: are we losing competence?

BACKGROUND: The COVID-19 pandemic has tremendously impacted the healthcare system and residency programs worldwide. Surgical residents were redeployed to COVID-19 units, whereas education and scientific didactics were reduced. The aim of this study is to identify the impact of COVID-19 on Flemish surgical residents' education, personal life and volume of performed surgeries. METHODS: A cross-sectional retrospective survey on educational and personal impact during the first COVID-19 wave was administered anonymously to all surgical residents in Flanders. A quantitative comparison of performed surgeries during this period and the same period a year earlier was conducted. RESULTS: A total of 193 surgical residents (46%) completed the survey. 63% of residents were no longer admitted to multidisciplinary oncologic meetings and 107 (55%) residents had no longer any scientific theoretical meetings at all. Almost one in two residents (46%) indicated more than 50% reduction in time in the operating theater and one in three (31%) residents were involved in care for COVID-19 positive surgical patients. Seventy-eight percent of the residents experienced a negative impact on their surgical training and 41% experienced a negative influence on their private situation. Performed surgical cases during the COVID-19 period were on average 40% less for second, third- and fourth-year residents. CONCLUSION: Surgical residents perceived a high negative impact on personal and professional lives during the start of the COVID-19 pandemic in Flanders. Education and training programs were cancelled and volume of performed surgeries decreased tremendously. Policymakers and surgical program coordinators should ensure surgical education during further evolution of this and future pandemics.

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.

Risk Factors, Diagnosis and Management of Chyle Leak Following Esophagectomy for Cancers: An International Consensus Statement.

This Delphi exercise aimed to gather consensus surrounding risk factors, diagnosis, and management of chyle leaks after esophagectomy and to develop recommendations for clinical practice. Background: Chyle leaks following esophagectomy for malignancy are uncommon. Although they are associated with increased morbidity and mortality, diagnosis and management of these patients remain controversial and a challenge globally. Methods: This was a modified Delphi exercise was delivered to clinicians across the oesophagogastric anastomosis collaborative. A 5-staged iterative process was used to gather consensus on clinical practice, including a scoping systematic review (stage 1), 2 rounds of anonymous electronic voting (stages 2 and 3), data-based analysis (stage 4), and guideline and consensus development (stage 5). Stratified analyses were performed by surgeon specialty and surgeon volume. Results: In stage 1, the steering committee proposed areas of uncertainty across 5 domains: risk factors, intraoperative techniques, and postoperative management (ie, diagnosis, severity, and treatment). In stages 2 and 3, 275 and 250 respondents respectively participated in online voting. Consensus was achieved on intraoperative thoracic duct ligation, postoperative diagnosis by milky chest drain output and biochemical testing with triglycerides and chylomicrons, assessing severity with volume of chest drain over 24 hours and a step-up approach in the management of chyle leaks. Stratified analyses demonstrated consistent results. In stage 4, data from the Oesophagogastric Anastomosis Audit demonstrated that chyle leaks occurred in 5.4% (122/2247). Increasing chyle leak grades were associated with higher rates of pulmonary complications, return to theater, prolonged length of stay, and 90-day mortality. In stage 5, 41 surgeons developed a set of recommendations in the intraoperative techniques, diagnosis, and management of chyle leaks. Conclusions: Several areas of consensus were reached surrounding diagnosis and management of chyle leaks following esophagectomy for malignancy. Guidance in clinical practice through adaptation of recommendations from this consensus may help in the prevention of, timely diagnosis, and management of chyle leaks.

Neoadjuvant camrelizumab plus chemotherapy for resectable, locally advanced esophageal squamous cell carcinoma (NIC-ESCC2019): A multicenter, phase 2 study.

Optimal treatment for resectable esophageal squamous cell carcinoma (ESCC) is controversial, especially in the context of potential benefit of combining PD-1 blockade with neoadjuvant therapy. This phase 2 study aimed to assess neoadjuvant camrelizumab plus chemotherapy in this population. Patients (clinical stage II-IVA) received two cycles of neoadjuvant chemoimmunotherapy (NIC) with camrelizumab (200 mg on day 1) plus nab-paclitaxel (260 mg/m2 in total on day 1 and day 8) and cisplatin (75 mg/m2 in total on days 1-3) of each 21-day cycle. Surgery was performed approximately 6 weeks after completion of NIC. Primary endpoint was complete pathologic response (CPR) rate in primary tumor. Secondary endpoints were objective response rate (ORR) per RECIST v1.1, 2-year progression-free survival (PFS) rate after surgery, PFS, overall survival (OS) and safety during NIC and perioperative period. Between 17 January 2020 and 8 December 2020, 56 patients were enrolled, and 51 received esophagectomy. Data cutoff date was 25 August 2021. The CPR rate was 35.3% (95% CI, 21.7%-48.9%). NIC had an ORR of 66.7% (95% CI, 40.0%-70.4%) and treatment-related adverse events (TRAEs) of low severity (grade 1-2, 75.0%; grade 3, 10.7%; grade 4-5, no). No perioperative mortality occurred. Three (5.9%) patients had tumor recurrence and one (2.0%) patient died. The 2-year PFS rate, median PFS and median OS had not been reached yet. Camrelizumab plus neoadjuvant chemotherapy in resectable ESCC demonstrates promising efficacy with acceptable toxicity, providing a feasible and effective option. Study is ongoing for long-term survival analyses.

Subxiphoid Versus Unilateral Video-assisted Thoracoscopic Surgery Thymectomy for Thymomas: A Propensity Score Matching Analysis.

BACKGROUND: The appropriate approach for video-assisted thoracoscopic surgery for early stage thymoma remains unclear. The present study aimed to explore the safety and feasibility of subxiphoid and subcostal arch thoracoscopic thymectomy in comparison with unilateral thoracoscopic thymectomy for treatment of early stage thymoma. METHODS: The outcomes of 237 patients without myasthenia gravis who had undergone thoracoscopic thymectomy for Masaoka stage I and II thymoma from January 2015 to May 2019 at our center were retrospectively evaluated (subxiphoid and subcostal arch approach, 39; unilateral video-assisted thoracoscopic surgery approach, 198). A propensity score matching analysis was generated to control for selection bias due to nonrandom group assignment in a 1:1 manner. RESULTS: There was no surgery-related mortality in included patients. Matching of patients according to propensity score resulted in a cohort that consisted of 39 patients in both groups. Patients had similar clinical characteristics in both groups. Compared with patients in the unilateral group, patients in the subxiphoid group yielded lower pain scores at 24 and 72 hours after operation, respectively (P < .01). In addition, the operation time was longer in the subxiphoid group (147.5 ± 43.6 vs 93.2 ± 33.8 minutes, P < .01). There were no significant differences in blood loss, total volume and time of drainage, complications, or postoperative hospital stays between the two groups. CONCLUSIONS: Subxiphoid and subcostal arch thoracoscopic thymectomy for early stage thymoma appears to be a safe and feasible procedure. It is considered to be less invasive as it may cause minimal postoperative pain compared with the unilateral video-assisted thoracoscopic surgery approach.

Preserving the eponym: Klinkenbergh technique for bronchial stump suturing.

The technique for bronchial stump suturing following lung resection which is currently applied in the Department of Thoracic Surgery at the University Hospitals Leuven, Belgium owes its name to the Dutch surgeon Dr. Klinkenbergh (1891-1985). A true pioneer of cardiothoracic surgery in Europe, Dr. Klinkenbergh dedicated himself to the surgical treatment of pulmonary tuberculosis. His work was praised by his peers for his precision and the reasoning behind every gesture. The Klinkenbergh technique consists in performing two running sutures which cross each other 'in the same manner as the laces of a shoe' to close the bronchus, limiting the occurrence of broncho-pleural fistulas. In our experience with more than 100 patients in the last 5 years (2016-2020) who underwent open pneumonectomy for benign or malignant disease, less than 2% developed post-operative broncho-pleural fistulas.

Intranodal Lymphangiography With High-Dose Ethiodized Oil Shows Efficient Results in Patients With Refractory, High-Output Postsurgical Chylothorax: A Retrospective Study.

OBJECTIVE. The purpose of this study is to evaluate the safety and efficacy of intranodal lymphangiography (INL) with high-dose ethiodized oil in patients with postoperative refractory chylothorax. MATERIALS AND METHODS. A retrospective review of a cohort of 18 patients with refractory postoperative chylothorax seen between May 2015 and March 2019 was conducted. All patients underwent intranodal lymphangiography with high doses of ethiodized oil (mean, 75 mL; range, 40-140 mL). The following information was gathered from the institutional database: patient demographics, type of surgery, output volumes, interval between surgery and lymphangiography, imaging results, amount of ethiodized oil injected, clinical success, and time to resolution. RESULTS. Of the 18 patients, 11 (61%) had previously undergone thoracic duct ligation, and seven (39%) had not. A lymphatic leak was confirmed by lymphangiography in 12 of 18 patients (67%). A total of five patients underwent a second session of INL, which was successful in three of the patients (60%). Removal of all chest tubes was possible in 15 of 18 patients (83%) after a mean of 12 days (range, 1-25 days). Two patients had an anastomotic leak develop after esophagectomy and died with their chest tubes in situ. One patient underwent thoracic duct ligation after two failed INL procedures. No complications were recorded. CONCLUSION. INL with a high dose of injected ethiodized oil is a safe and effective procedure for the management of postsurgical refractory chylothorax, with chest tube removal in 83% of patients.

Evaluation of a marker independent isolation method for circulating tumor cells in esophageal adenocarcinoma.

OBJECTIVE: The enrichment of circulating tumor cells (CTCs) from blood provides a minimally invasive method for biomarker discovery in cancer. Longitudinal interrogation allows monitoring or prediction of therapy response, detection of minimal residual disease or progression, and determination of prognosis. Despite inherent phenotypic heterogeneity and differences in cell surface marker expression, most CTC isolation technologies typically use positive selection. This necessitates the optimization of marker-independent CTC methods, enabling the capture of heterogenous CTCs. The aim of this report is to compare a size-dependent and a marker-dependent CTC-isolation method, using spiked esophageal cells in healthy donor blood and blood from patients diagnosed with esophageal adenocarcinoma. METHODS: Using esophageal cancer cell lines (OE19 and OE33) spiked into blood of a healthy donor, we investigated tumor cell isolation by Parsortix post cell fixation, immunostaining and transfer to a glass slide, and benchmarked its performance against the CellSearch system. Additionally, we performed DEPArray cell sorting to infer the feasibility to select and isolate cells of interest, aiming towards downstream single-cell molecular characterization in future studies. Finally, we measured CTC prevalence by Parsortix in venous blood samples from patients with various esophageal adenocarcinoma tumor stages. RESULTS: OE19 and OE33 cells were spiked in healthy donor blood and subsequently processed using CellSearch (n = 16) or Parsortix (n = 16). Upon tumor cell enrichment and enumeration, the recovery rate ranged from 76.3 ± 23.2% to 21.3 ± 9.2% for CellSearch and Parsortix, respectively. Parsortix-enriched and stained cell fractions were successfully transferred to the DEPArray instrument with preservation of cell morphology, allowing isolation of cells of interest. Finally, despite low CTC prevalence and abundance, Parsortix detected traditional CTCs (i.e. cytokeratin+/CD45-) in 8/29 (27.6%) of patients with esophageal adenocarcinoma, of whom 50% had early stage (I-II) disease. CONCLUSIONS: We refined an epitope-independent isolation workflow to study CTCs in patients with esophageal adenocarcinoma. CTC recovery using Parsortix was substantially lower compared to CellSearch when focusing on the traditional CTC phenotype with CD45-negative and cytokeratin-positive staining characteristics. Future research could determine if this method allows downstream molecular interrogation of CTCs to infer new prognostic and predictive biomarkers on a single-cell level.

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.

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.