The aim of this study was to compare open esophagectomy (OE) with minimally invasive esophagectomy (MIE) in a population-based setting.
Randomized controlled trials and cohort studies have shown that ...MIE is associated with reduced pulmonary complications and shorter hospital stay as compared to OE.
Patients who underwent transthoracic esophagectomy for cancer between 2011 and 2015 were selected from the national Dutch Upper Gastrointestinal Cancer Audit. Hybrid, transhiatal, and emergency procedures were excluded. Patients who underwent OE were compared with those treated by MIE. Propensity score matching was used to correct for differences in baseline characteristics. The primary endpoint was postoperative pulmonary complications; secondary endpoints were morbidity, mortality, convalescence, and pathology.
Some 1727 patients were included. After propensity score matching the percentage of patients with 1 or more complications was 62.6% after OE (N = 433) and 60.2% after MIE (N = 433) (P = 0.468). Pulmonary complication rate did not differ between groups: 34.2% (OE) versus 35.6% (MIE) (P = 0.669). Anastomotic leak (15.5% vs 21.2%, P = 0.028) and reintervention rates (21.1% vs 28.2%, P = 0.017) were higher after MIE. Mortality was 3.0% in the OE group and 4.7% in the MIE group (P = 0.209). Median hospital stay was shorter after MIE (14 vs 13 days, P = 0.001). Percentages of R0 resections (93%) did not differ between groups. The median (range) lymph node count was 18 (2-53) (OE) versus 20 (2-52) (MIE) (P < 0.001).
This population-based study showed that mortality and pulmonary complications were similar for OE and MIE. Anastomotic leaks and reinterventions were more frequently observed after MIE. MIE was associated with a shorter hospital stay.
The aim of this study was to investigate 3-year survival following a randomized controlled trial comparing minimally invasive with open esophagectomy in patients with esophageal cancer.
Research on ...minimally invasive esophagectomy (MIE) has shown faster postoperative recovery and a marked decrease in pulmonary complications. Debate is ongoing as to whether the procedure is equivalent to open resection regarding oncologic outcomes. The study is a follow-up study of the TIME-trial (traditional invasive vs minimally invasive esophagectomy, a multicenter, randomized trial).
Between June 2009 and March 2011, patients with a resectable intrathoracic esophageal carcinoma, including the gastroesophageal junction tumors (Siewert I), were randomized between open and MI esophagectomy with curative intent. Primary outcome was 3-year disease-free survival. Secondary outcomes include overall survival, lymph node yield, short-term morbidity, mortality, complications, radicality, local recurrence, and metastasis. Analysis was by intention-to-treat. This trial is registered with the Netherlands Trial Register, NTR TC 2452. Both trial protocol and short-term results have been published previously.
One hundred fifteen patients were included from 5 European hospitals and randomly assigned to open (n = 56) or MI esophagectomy (n = 59). Combined overall 3-year survival was 40.4% (SD 7.7%) in the open group versus 50.5% (SD 8%) in the minimally invasive group (P = 0.207). The hazard ratio (HR) is 0.883 (0.540 to 1.441) for MIE compared with open surgery. Disease-free 3-year survival was 35.9% (SD 6.8%) in the open versus 40.2% (SD 6.9%) in the MI group HR 0.691 (0.389 to 1.239).
The study presented here depicted no differences in disease-free and overall 3-year survival for open and MI esophagectomy. These results, together with short-term results, further support the use of minimally invasive surgical techniques in the treatment of esophageal cancer.
Goal-directed therapy (GDT) can reduce postoperative complications in high-risk surgery patients. It is uncertain whether GDT has the same benefits in patients undergoing esophageal surgery. Goal of ...this Quality Improvement study was to evaluate the effects of a stroke volume guided GDT on post-operative outcome.
We compared the postoperative outcome of patients undergoing esophagectomy before (99 patients) and after (100 patients) implementation of GDT. There was no difference in the proportion of patients with a complication (56% vs. 54%, p = 0.82), hospital stay and mortality. The incidence of prolonged ICU stay (>48 hours) was reduced (28% vs. 12, p = .005) in patients treated with GDT. Secondary analysis of complication rate showed a decrease in pneumonia (29 vs. 15%, p = .02), mediastinal abscesses (12 vs. 3%, p = .02), and gastric tube necrosis (5% vs. 0%, p = .03) in patients treated with GDT. Patients in the GDT group received significantly less fluids but received more colloids.
The implementation of GDT during esophagectomy was not associated with reductions in overall morbidity, mortality and hospital length of stay. However, we observed a decrease in pneumonia, mediastinal abscesses, gastric tube necrosis, and ICU length of stay.
Utilizing a standardized dataset with specific definitions to prospectively collect international data to provide a benchmark for complications and outcomes associated with esophagectomy.
Outcome ...reporting in oncologic surgery has suffered from the lack of a standardized system for reporting operative results particularly complications. This is particularly the case for esophagectomy affecting the accuracy and relevance of international outcome assessments, clinical trial results, and quality improvement projects.
The Esophageal Complications Consensus Group (ECCG) involving 24 high-volume esophageal surgical centers in 14 countries developed a standardized platform for recording complications and quality measures associated with esophagectomy. Using a secure online database (ESODATA.org), ECCG centers prospectively recorded data on all resections according to the ECCG platform from these centers over a 2-year period.
Between January 2015 and December 2016, 2704 resections were entered into the database. All demographic and follow-up data fields were 100% complete. The majority of operations were for cancer (95.6%) and typically located in the distal esophagus (56.2%). Some 1192 patients received neoadjuvant chemoradiation (46.1%) and 763 neoadjuvant chemotherapy (29.5%). Surgical approach involved open procedures in 52.1% and minimally invasive operations in 47.9%. Chest anastomoses were done most commonly (60.7%) and R0 resections were accomplished in 93.4% of patients. The overall incidence of complications was 59% with the most common individual complications being pneumonia (14.6%) and atrial dysrhythmia (14.5%). Anastomotic leak, conduit necrosis, chyle leaks, recurrent nerve injury occurred in 11.4%, 1.3%, 4.7%, and 4.2% of cases, respectively. Clavien-Dindo complications ≥ IIIb occurred in 17.2% of patients. Readmissions occurred in 11.2% of cases and 30- and 90-day mortality was 2.4% and 4.5%, respectively.
Standardized methods provide contemporary international benchmarks for reporting outcomes after esophagectomy.
A high preoperative neutrophil-lymphocyte ratio (NLR) has been shown in several studies as a predictor of worse survival in many solid neoplasms, including esophageal cancer, but its impact remains ...unclear. The goal of this systematic review was to gain all the evidence about NLR in order to analyse its potential in predicting survival in esophageal cancer. Therefore, we conducted a systematic literature search of all relevant studies reporting data on NLR as prognostic marker in esophageal cancer patients. We considered overall survival (OS) as primary outcome, disease-free survival (DFS) and progression-free survival (PFS) as secondary outcomes. We included studies with a directly or indirectly available hazard ratio (HR), furthermore we used both fixed effect model and random effect model depending on heterogeneity. We included a total of 20 studies, published between 2011 and 2017, consisting of 6,457 patients. The NLR cut-off value ranges from 1.7 to 5. The HR for OS of all included studies was 1.60. The HR for DFS and PFS was 1.75 and 1.66 respectively. The survival sub-analysis about tumor characteristics, treatment modality, blood sample timing also confirmed NLR prognostic relevance with statistically significant results. The meta-analysis showed that high preoperative NLR is associated with worse survival in esophageal cancer, as shown in several solid tumors, but its use in the clinical practice is still underestimated. High-quality studies are needed to assess the most effective cut-off in survival prognostication and NLR relevance on postoperative complications.
Background
Sex differences in clinicopathological characteristics, treatment, and postoperative outcomes of gastric and esophageal cancer are largely undefined. This study aimed to compare tumor and ...treatment characteristics and outcomes of gastric and esophageal cancer surgery between male and female patients.
Methods
Patients after elective surgery for primary esophageal (EAC) or gastric adenocarcinoma (GAC) registered in the Dutch Upper GI Cancer Audit between 2011 and 2016 were included. The primary endpoint, 5-year relative survival with relative excess risk (RER), i.e., adjusted for the normal life expectancy, was compared between male and female patients with EAC and GAC.
Results
In total, 4937 patients were included (75% male) with a mean age of 66 years. cT and cN-stages showed a similar distribution in male and female patients. In females, antrum GAC was more frequent (47% vs. 38%,
p
< 0.001). Female patients with EAC less frequently received neo-adjuvant treatment (OR = 0.60, 95% CI 0.38–0.96,
p
= 0.033). For GAC, less postoperative morbidity (33% vs. 38%
p
= 0.017) and less re-interventions (12% vs. 16%,
p
= 0.008) were observed in females, although they had inferior 5-year relative survival (49% vs. 56%, RER = 1.31, 95% CI 1.09–1.58,
p
= 0.004). No differences in relative survival of EAC were observed.
Conclusions
In addition to significant sex differences in tumor location, female patients with esophageal adenocarcinoma less frequently received neo-adjuvant therapy, and female patients with gastric adenocarcinoma had inferior relative survival. Further consideration and exploration of sex differences in surgical treatment and outcomes are necessary to improve tailored treatment and outcomes.
Biological sex and gender have been reported to affect incidence and overall survival (OS) of curatively treated gastroesophageal cancer. The aim of this study was to compare palliative treatment ...allocation and OS between women and men with advanced gastroesophageal cancer.
Patients with an unresectable or metastatic esophageal (including cardia) adenocarcinoma (EAC) or squamous cell carcinoma (ESCC) or gastric adenocarcinoma (GAC) diagnosed in 2015-2018 were identified in the Netherlands Cancer Registry. Treatment allocation was compared using χ2 tests and multivariable logistic regression analyses, and OS using the Kaplan-Meier method with log-rank test and Cox proportional hazards analysis. All statistical tests were 2-sided.
Of patients with EAC (n = 3077), ESCC (n = 794), and GAC (n = 1836), 18.0%, 39.4%, and 39.1% were women, respectively. Women less often received systemic treatment compared with men for EAC (42.7% vs 47.4%, P = .045) and GAC (33.8% vs 38.8%, P = .03) but not for ESCC (33.2% vs 39.5%, P = .07). Women had a lower probability of receiving systemic treatment for GAC in multivariable analyses (odds ratio OR = 0.79, 95% confidence interval CI = 0.62 to 1.00) but not for EAC (OR = 0.86, 95% CI = 0.69 to 1.06) and ESCC (OR = 0.81, 95% CI = 0.57 to 1.14). Median OS was lower in women with EAC (4.4 vs 5.2 months, P = .04) but did not differ after adjustment for patient and tumor characteristics and systemic treatment administration.
We observed statistically significant and clinically relevant gender differences in systemic treatment administration and OS in advanced gastroesophageal cancer. Causes of these disparities may be sex based (ie, related to tumor biology) as well as gender based (eg, related to differences in treatment choices).
The aim of this study was to examine the external validity of the randomized TIME trial, when minimally invasive esophagectomy (MIE) was implemented nationally in the Netherlands, using data from the ...Dutch Upper GI Cancer Audit (DUCA) for transthoracic esophagectomy.
Original patient data from the TIME trial were extracted along with data from the DUCA dataset (2011-2017). Multivariate analysis, with adjustment for patient factors, tumor factors, and year of surgery, was performed for the effect of MIE versus open esophagectomy on clinical outcomes.
One hundred fifteen patients from the TIME trial (59 MIE
56 open) and 4,605 patients from the DUCA dataset (2,652 MIE
1,953 open) were included. In the TIME trial, univariate analysis showed that MIE reduced pulmonary complications and length of hospital stay. On the contrary, in the DUCA dataset, MIE was associated with increased total and pulmonary complications and reoperations; however, benefits included increased proportion of R0 margin and lymph nodes harvested, and reduced 30-day mortality. Multivariate analysis from the TIME trial showed that MIE reduced pulmonary complications (odds ratio OR, 0.19; 95% CI, 0.06 to 0.61). In the DUCA dataset, MIE was associated with increased total complications (OR, 1.36; 95% CI, 1.19 to 1.57), pulmonary complications (OR, 1.50; 95% CI, 1.29 to 1.74), reoperations (OR, 1.74; 95% CI, 1.42 to 2.14), and length of hospital stay. Multivariate analysis of the combined and MIE datasets showed that inclusion in the TIME trial was associated with a reduction in reoperations, Clavien-Dindo grade > 1 complications, and length of hospital stay.
When adopted nationally outside the TIME trial, MIE was associated with an increase in total and pulmonary complications and reoperation rate. This may reflect nonexpert surgeons outside of high-volume centers performing this minimally invasive technique in a nonstandardized fashion outside of a controlled environment.
The CROSS trial established neoadjuvant chemoradiotherapy (nCRT) for patients with resectable esophageal adenocarcinoma (rEAC). In the PERFECT trial, we investigated the feasibility and efficacy of ...nCRT combined with programmed-death ligand-1 (PD-L1) inhibition for rEAC.
Patients with rEAC received nCRT according to the CROSS regimen combined with five cycles of atezolizumab (1,200 mg). The primary endpoint was the feasibility of administering five cycles of atezolizumab in ≥75% patients. A propensity score-matched nCRT cohort was used to compare pathologic response, overall survival, and progression-free survival. Exploratory biomarker analysis was performed on repeated tumor biopsies.
We enrolled 40 patients of whom 85% received all cycles of atezolizumab. Immune-related adverse events of any grade were observed in 6 patients. In total, 83% proceeded to surgery. Reasons for not undergoing surgery were progression (
= 4), patient choice (
= 2), and death (
= 1). The pathologic complete response rate was 25% (10/40). No statistically significant difference in response or survival was found between the PERFECT and the nCRT cohort. Baseline expression of an established IFNγ signature was higher in responders compared with nonresponders (
= 0.043). On-treatment nonresponders showed either a high number of cytotoxic lymphocytes (CTL) with a transcriptional signature consistent with expression of immune checkpoints, or a low number of CTLs.
Combining nCRT with atezolizumab is feasible in patients with rEAC. On the basis of our exploratory biomarker study, future studies are necessary to elucidate the potential of neoadjuvant immunotherapy in patient subgroups.
.
Background
Selective lymphadenectomy using sentinel node-navigated surgery (SNNS) might offer a less invasive alternative to esophagectomy in patients with high-risk T1 esophageal adenocarcinoma ...(EAC). The aim of this study was to evaluate the feasibility and safety of a new treatment strategy, consisting of radical endoscopic resection of the tumor followed by SNNS.
Methods
In this multicenter pilot study, ten patients with a radically resected high-risk pT1cN0 EAC underwent SNNS. A hybrid tracer of technetium-99m nanocolloid and indocyanine green was injected endoscopically around the resection scar the day before surgery, followed by preoperative imaging. During surgery, sentinel nodes (SNs) were identified using a thoracolaparoscopic gammaprobe and fluorescence-based detection, and subsequently resected. Endpoints were surgical morbidity and number of detected and resected (tumor-positive) SNs.
Results
Localization and dissection of SNs was feasible in all ten patients (median 3 SNs per patient, range 1–6). The concordance between preoperative imaging and intraoperative detection was high. In one patient (10%), dissection was considered incomplete after two SNs were not identified intraoperatively. Additional peritumoral SNs were resected in four patients (40%) after fluorescence-based detection. In two patients (20%), a (micro)metastasis was found in one of the resected SNs. One patient experienced neuropathic thoracic pain related to surgery, while none of the patients developed functional gastroesophageal disorders.
Conclusions
SNNS appears to be a feasible and safe instrument to tailor lymphadenectomy in patients with high-risk T1 EAC. Future research with long-term follow-up is warranted to determine whether this esophageal preserving strategy is justified for high-risk T1 EAC.
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