Association of hospital volume and operative approach with clinical and financial outcomes of elective esophagectomy in the United States.

INTRODUCTION: Literature regarding the impact of esophagectomy approach on hospitalizations costs and short-term outcomes is limited. Moreover, few have examined how institutional MIS experience affects costs. We thus examined utilization trends, costs, and short-term outcomes of open and minimally invasive (MIS) esophagectomy as well as assessing the relationship between institutional MIS volume and hospitalization costs. METHODS: All adults undergoing elective esophagectomy were identified from the 2016-2020 Nationwide Readmissions Database. Multiple regression models were used to assess approach with costs, in-hospital mortality, and major complications. Additionally, annual hospital MIS esophagectomy volume was modeled as a restricted cubic spline against costs. Institutions performing > 16 cases/year corresponding with the inflection point were categorized as high-volume hospitals (HVH). We subsequently examined the association of HVH status with costs, in-hospital mortality, and major complications in patients undergoing minimally invasive esophagectomy. RESULTS: Of an estimated 29,116 patients meeting inclusion, 10,876 (37.4%) underwent MIS esophagectomy. MIS approaches were associated with $10,600 in increased incremental costs (95% CI 8,800-12,500), but lower odds of in-hospital mortality (AOR 0.76; 95% CI 0.61-0.96) or major complications (AOR 0.68; 95% CI 0.60, 0.77). Moreover, HVH status was associated with decreased adjusted costs, as well as lower odds of postoperative complications for patients undergoing MIS operations. CONCLUSION: In this nationwide study, MIS esophagectomy was associated with increased hospitalization costs, but improved short-term outcomes. In MIS operations, cost differences were mitigated by volume, as HVH status was linked with decreased costs in the setting of decreased odds of complications. Centralization of care to HVH centers should be considered as MIS approaches are increasingly utilized.

Surgical and Perioperative Treatments for Esophagogastric Junction Cancer.

Esophagogastric junction cancer (EGJC) is a rare malignant disease that occurs in the gastroesophageal transition zone. In recent years, its incidence has been rapidly increasing not only in Western countries but also in East Asia, and it has been attracting the attention of both clinicians and researchers. EGJC has a worse prognosis than gastric cancer (GC) and is characterized by complex lymphatic drainage pathways in the mediastinal and abdominal regions. EGJC was previously treated in the same way as GC or esophageal cancer, but, in recent years, it has been treated as an independent malignant disease, and treatment focusing only on EGJC has been developed. A recent multicenter prospective study revealed the frequency of lymph node metastasis by station and established the optimal extent of lymph node dissection. In perioperative treatment, the combination of multi-drug chemotherapy, radiation therapy, molecular targeted therapy, and immunotherapy is expected to improve the prognosis. In this review, we summarize previous clinical trials and their important evidence on surgical and perioperative treatments for EGJC.

Dynamic volume-outcome association for esophagectomies: Do current volume thresholds still apply?

BACKGROUND: It is unknown if the current minimum case volume recommendation of 20 cases per year per hospital is applicable to contemporary practice. METHODS: Patients undergoing esophageal resection between 2005 and 2015 were identified in the National Cancer Database. High, medium, and low-volume hospital strata were defined by quartiles. Adjusted odds ratios and adjusted 30-day mortality between low-, medium-, and high-volume hospitals were calculated using logistic regression analyses and trended over time. RESULTS: Only 1.1% of hospitals had ≥20 annual cases. The unadjusted 30-day mortality for esophagectomy was 3.8% overall. Unadjusted and adjusted 30-day mortality trended down for all three strata between 2005 and 2015, with disproportionate decreases for low-volume and medium-volume versus high-volume hospitals. By 2015, adjusted 30-day mortality was similar in medium- and high-volume hospitals (odds ratio 1.35, 95% confidence interval 0.96-1.91). For hospitals with 20 or more annual cases the adjusted 30-day mortality was 2.7% overall. To achieve this same 30-day mortality the minimum volume threshold had lowered to 7 annual cases by 2015. CONCLUSION: Only 1.1% of hospitals meet current volume recommendations for esophagectomy. Differential improvements in postoperative mortality at low- and medium- versus high-volume hospitals have led to 7 cases in 2015 achieving the same adjusted 30-day mortality as 20 cases in the overall cohort. Lowering volume thresholds for esophagectomy in contemporary practice would potentially increase the proportion of hospitals able to meet volume standards and increase access to quality care without sacrificing quality.

Textbook outcome after esophagectomy: A retrospective study from a high-volume center.

BACKGROUND: Textbook outcome is a composite quality measurement in esophageal cancer surgery. This study aimed to estimate the rate of textbook outcome esophagectomies at a high-volume center and investigate associations between textbook outcome and overall and recurrence-free survival. METHODS: A retrospective single-center study was conducted at Copenhagen University Hospital, Rigshospitalet, Denmark, analyzing esophagectomies performed from November 1, 2016, to December 31, 2021. Patients with primary carcinoma of the gastroesophageal junction who underwent elective and curative esophagectomy were included. The rate of textbook outcome esophagectomies was calculated, and the impact of textbook outcome on overall and recurrence-free survival was analyzed using Kaplan-Meier and Cox regression. RESULTS: A total of 433 patients were included in the study. Textbook outcome was achieved in 195 patients (45%). Achieving textbook outcome was independently associated with improved overall survival (HR 0.67; P = .011) and with a median overall survival of 57 months and 32 months for patients with or without textbook outcome, respectively. A trend for improved recurrence-free survival was observed for patients with textbook outcome (HR 0.74; P = .064). CONCLUSION: The present study found a consensus-based textbook outcome rate of 45%. Textbook outcome was found to be directly associated with improved overall survival. These results emphasize the association between improved short-term outcomes and long-term survival.

Premature mortality for patients after completely resected early adenocarcinoma of the esophagus or stomach.

OBJECTIVE: To establish the life expectancy burden of esophago-gastric cancer by analyzing years of life lost (YLL) for a Western patient population after treatment of early esophageal (EAC) or early gastric (GAC) adenocarcinoma. BACKGROUND: For patients with early EAC or GAC, the short-term prognosis after surgical resection is very good. Little data is available regarding long-term prognosis when compared to the general population. METHODS: Two hundred and fourteen patients with pT1 EAC (n = 112) or GAC (n = 102) were included in the study. Patients with EAC underwent transthoracic en-bloc esophagectomy; those with GAC had total or subtotal gastrectomy with D2-lymphadenectomy. Surviving patients had a median follow-up of approximately 14 years. YLL was calculated using average life expectancy data from Germany. RESULTS: Patients with EAC were younger (median age 61 years) than those with GAC (66 years) (p = 0.031). The male:female ratio was 10:1 for EAC and 3:2 for GAC (p < 0.001). Multivariate survival analysis showed the age of the patients ≥60 years and the existence of lymph node metastasis was associated with poor prognosis. The median YLL for all patients who died over follow-up was 8.0 years. For patients under 60 years, it was approximately 20 years, and for older patients, approximately 5 years (p < 0.001) without difference in tumor stage between these age cohorts. YLL did not differ for GAC vs. EAC. CONCLUSION: After surgical resection, the prognostic burden as measured by YLL is relevant for all patients with early esophageal and gastric adenocarcinomas and especially for younger patients. Reasons for YLL need further studies.

Utility of Initial Tumor Reduction as a Prognostic Factor in Esophageal Squamous Cell Cancer Patients Undergoing Neoadjuvant Chemotherapy Followed by Surgery : A Retrospective Cohort Study.

BACKGROUND: While a neoadjuvant chemotherapy regimen using docetaxel, cisplatin, and 5-fluorouracil (NAC-DCF) is considered the standard treatment for locally advanced esophageal cancer (EC) in Japan, a reliable marker for early prediction of treatment efficacy remains unclear. We investigated the utility of the tumor response after a first course of NAC-DCF as a post-surgery survival predictor in patients with EC. METHODS: We enrolled 150 consecutive patients who underwent NAC-DCF followed by surgery for EC between September 2009 and January 2019. The initial tumor reduction (ITR), defined as the percentage decrease in the shorter diameter of the tumor after the first course of NAC-DCF, was evaluated using computed tomography. We analyzed the relationship between ITR, clinicopathological parameters, and survival. RESULTS: The median ITR was 21.07% (range -11.45 to 50.13%). The optimal cut-off value for ITR for predicting prognosis was 10% (hazard ratio [HR] 3.30, 95% confidence interval [CI] 1.98-5.51), based on univariate logistic regression analyses for recurrence-free survival (RFS). Compared with patients with ITR <10%, patients with ITR ≥10% showed a significantly higher proportion of ypM0 (80.0% vs. 92.5%) and responders in terms of overall clinical response (50.0% vs. 80.8%). Multivariate analysis for RFS revealed that ypN2-3 (HR 2.78, 95% CI 1.67-4.62), non-response in terms of overall clinical response (HR 1.87, 95% CI 1.10-3.18), and ITR <10% (HR 2.48, 95% CI 1.42-4.32) were independent prognostic factors. CONCLUSIONS: Tumor response after the first course of NAC-DCF may be a good predictor of survival in patients with EC who underwent NAC-DCF plus surgery.

Root cause analysis of mortality after esophagectomy for cancer: a multicenter cohort study from the FREGAT database.

BACKGROUND: Esophagectomy is associated with significant mortality. A better understanding of the causes leading to death may help to reduce mortality. A root cause analysis of mortality after esophagectomy was performed. METHODS: Root cause analysis was retrospectively applied by an independent expert panel of 4 upper gastrointestinal surgeons and 1 anesthesiologist-intensivist to patients included in the French national multicenter prospective cohort FREGAT between August 2014 and September 2019 who underwent an esophagectomy for cancer and died within 90 days of surgery. A cause-and-effect diagram was used to determine the root causes related to death. Death was classified as potentially preventable or non-preventable. RESULTS: Among the 1,040 patients included in the FREGAT cohort, 70 (6.7%) patients (male: 81%, median age 68 [62-72] years) from 17 centers were included. Death was potentially preventable in 37 patients (53%). Root causes independently associated with preventable death were inappropriate indication (odds ratio 35.16 [2.50-494.39]; P = .008), patient characteristics (odds ratio 5.15 [1.19-22.35]; P = .029), unexpected intraoperative findings (odds ratio 18.99 [1.07-335.55]; P = .045), and delay in diagnosis of a complication (odds ratio 98.10 [6.24-1,541.04]; P = .001). Delay in treatment of a complication was found only in preventable deaths (28 [76%] vs 0; P < .001). National guidelines were less frequently followed (16 [43%] vs 22 [67%]; P = .050) in preventable deaths. The only independent risk factor of preventable death was center volume <26 esophagectomies per year (odds ratio 4.71 [1.55-14.33]; P = .006). CONCLUSIONS: More than one-half of deaths after esophagectomy were potentially preventable. Better patient selection, early diagnosis, and adequate management of complications through centralization could reduce mortality.

Siewert II esophagogastric junction adenocarcinoma: Still searching for the right treatment transabdominal or transthoracic surgical approaches?

INTRODUCTION: To date, the discussion is still ongoing whether the Siewert II adenocarcinoma of the esophagogastric junction (AEG) should be resected either by thoracoabdominal esophagectomy or gastrectomy with resection of the distal esophagus by transhiatal extension. The aim of our study was to compare the oncological and perioperative outcomes of the transthoracic approach (TTA) and the transabdominal approach (TAA). METHODS: Searches of electronic databases identifying studies from Cochrane, PubMed and Google Scholar were performed. Randomised and non-randomised studies comparing TTA and TAA approaches for surgical treatment of AEG Siewert type II were included. The Newcastle-Ottawa and Jada scales were used to evaluate methodological quality. The risk of bias was assessed using the Rob v2 and Robins-I tools. Meta-analyses were conducted for the outcomes. RESULTS: We included 17 trials (2 randomised controlled trials and 15 cohorts) involving 15297 patients. Longer three-year overall survival, five-year overall survival and R0 resection rates were observed in the TTA group. However, TTA had greater morbidity and pulmonary complications. CONCLUSION: Transthoracic approach appears to be preferable for selected Siewert II tumours. This may lead to higher survival rates and better R0 resection rate. Well-designed studies are needed to confirm the results of this systematic review.

Surgical outcomes and survival following esophagectomy for squamous cell carcinoma with or without liver cirrhosis: retrospective cohort study.

BACKGROUND AND AIMS: Esophageal squamous cell carcinoma (ESCC) shares common risk factors with liver cirrhosis (LC). The influence of LC in patients with ESCC has not been fully investigated. This study aimed to investigate the postoperative and long-term survival outcomes of esophagectomy for ESCC according to LC presence. METHODS: Among patients who underwent curative-intent surgery for ESCC between 1994 and 2018, 121 patients with Child-Pugh class A LC and 2810 patients without LC were compared. RESULTS: Among the LC patients, 73 (60.3%) were diagnosed with LC before surgery and 48 (39.7%) were diagnosed intraoperatively. There were no significant differences in baseline characteristics between patients with LC and those without LC. However, intraoperative blood loss was higher, and operation time, hospital stay, and ICU stay were longer in patients with LC than in those without LC. Moreover, the reoperation, 30-day morbidity (60.6 vs. 73.6%, P =0.006) and 90-day mortality (2.2 vs. 4.9%, P =0.049) were significantly higher in patients with LC. The 5-year overall survival (OS) rate was significantly higher in patients without LC than in those with LC. After adjusting the confounding variables, LC was an adverse risk factor of OS (hazard ratio 1.402, P =0.004). Among patients with LC, the Model of End-Stage Liver Disease score was related to the development of complications of grade more than III (odds ratio 1.459, P =0.013). CONCLUSION: ESCC patients with Child-Pugh class A LC have high incidences of postoperative morbidity and mortality, and poor OS. Thus, careful patient selection, meticulous operation, and careful postoperative care are needed.

Impact of Metastatic Lymph Nodes on Survival of Patients with pN1-Category Esophageal Squamous Cell Carcinoma: A Long-Term Survival Analysis.

BACKGROUND: The morbidity and mortality rates of esophageal squamous cell carcinoma (ESCC) are high in China. The overall survival (OS) of patients with ESCC is related to lymph node (LN) metastasis (LNM). This study aimed to discuss the impact of metastasis in LN stations on the OS of patients with pathologic N1 (pN1) ESCC. METHODS: Data were obtained from the Esophageal Cancer Case Management database of Sichuan Cancer Hospital and Institute (SCCH-ECCM). Additionally, data of patients with pN1-category ESCC collected between January 2010 and December 2017 were retrospectively analyzed. RESULTS: Data from 807 patients were analyzed. The median OS of the patients with one metastatic LN (group 1) was 49.8 months (95 % confidence interval [CI], 30.8-68.9 months), whereas the OS of those with two metastatic LNs (group 2) was only 33.3 months (P = 0.0001). Moreover, group 1 did not show a significantly longer OS than group 2.1 (patients with 2 metastatic LNs in 1 LNM station; P = 0.5736), but did show a significantly longer OS than group 2.2 (patients with 2 metastatic LNs in 2 LNM stations; P < 0.0001). After propensity score-matching, the 5-year survival rate for group 1 was 28 %, whereas that for group 2 was 14 % (P = 0.0027). CONCLUSIONS: The OS for the patients with one metastatic LN in one LNM was not significantly longer than for the patients with two metastatic LNs in one LNM station. Patients with one LNM station had a significantly longer OS than those with two LNM stations. Thus, the number of LNM stations is a significant determinant of OS in pN1 ESCC.

Hospital volume-mortality association after esophagectomy for cancer: a systematic review and meta-analysis.

BACKGROUND: Postoperative mortality plays an important role in evaluating the surgical safety of esophagectomy. Although postoperative mortality after esophagectomy is partly influenced by the yearly hospital surgical case volume (hospital volume), this association remains unclear. METHODS: Studies assessing the association between hospital volume and postoperative mortality in patients who underwent esophagectomy for esophageal cancer were searched for eligibility. Odds ratios were pooled for the highest versus lowest categories of hospital volume using a random effects model. The dose-response association between hospital volume and the risk of postoperative mortality was analyzed. The study protocol was registered with PROSPERO. RESULTS: Fifty-six studies including 385 469 participants were included. A higher-volume hospital significantly reduced the risk of postesophagectomy mortality by 53% compared with their lower-volume counterparts (odds ratio, 0.47; 95% CI: 0.42-0.53). Similar results were found in subgroup analyses. Volume-outcome analysis suggested that postesophagectomy mortality rates remained roughly stable after the hospital volume reached a plateau of 45 esophagectomies per year. CONCLUSIONS: Higher-volume hospitals had significantly lower postesophagectomy mortality rates in patients with esophageal cancer, with a threshold of 45 esophagectomies per year for a high-volume hospital. This remarkable negative correlation showed the benefit of a better safety in centralization of esophagectomy to a high-volume hospital.

Long-Term Survival and Recurrence Patterns in Locally Advanced Esophageal Squamous Cell Carcinoma Patients with Pathologic Complete Response After Neoadjuvant Chemotherapy Followed by Surgery.

BACKGROUND: The higher pathologic complete response (pCR) after neoadjuvant chemoradiotherapy compared with neoadjuvant chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC) has not translated into significant gains in overall survival. Data on the long-term survival of patients who obtained a pCR after neoadjuvant chemotherapy are scarce. Therefore, this study aimed to evaluate the long-term prognosis and recurrence patterns in these patients. METHODS: The study enrolled patients with locally advanced ESCC after neoadjuvant chemotherapy followed by surgery in the authors' hospital between January 2007 and December 2020. The factors predictive of pCR were analyzed. Furthermore, propensity score-matching was performed for those who did and those who did not have a pCR using 1:5 ratio for a long-term survival analysis. Finally, the survival and recurrence patterns of patients obtaining pCR after neoadjuvant chemotherapy were analyzed. RESULTS: A pCR was achieved for 61 (8.70%) of the 701 patients in the study. Univariate analysis showed that the patients without alcohol drinking had a higher possibility of obtaining a pCR, although multivariate analysis failed to confirm the difference as significant. After propensity score-matching, the 5-year overall survival was 84.50% for the patients who had a pCR and 52.90% for those who did not (p < 0.001). Among the 61 patients with a pCR, 9 patients (14.80%) experienced recurrence, including 6 patients with locoregional recurrence and 3 patients with distant metastasis. CONCLUSION: Advanced ESCC patients with pCR after neoadjuvant chemotherapy had a favorable prognosis, yet some still experienced recurrence, particularly locoregional recurrence. Therefore, for this group of patients, regular follow-up evaluation also is needed.

Adjuvant Therapy for Patients with a Tumor-Positive Resection Margin After Neoadjuvant Chemoradiotherapy and Esophagectomy.

BACKGROUND: Approximately 4-9% of patients have a tumor-positive resection margin after neoadjuvant chemoradiotherapy (nCRT) and esophagectomy. Although it is associated with decreased survival, Western guidelines do not recommend adjuvant treatment. OBJECTIVE: The aim of this study was to assess the proportion of patients who received adjuvant therapy, and to evaluate overall survival (OS) after esophagectomy in patients with a tumor-positive resection margin. METHODS: Patients diagnosed with resectable (cT2-4a/cTxN0-3/NxM0) esophageal cancer between 2015 and 2022, and treated with nCRT followed by irradical esophagectomy, were selected from the Netherlands Cancer Registry. The primary outcome was the proportion of patients with a tumor-positive resection margin who started adjuvant treatment ≤16 weeks after esophagectomy, including chemotherapy/radiotherapy, immunotherapy, or targeted therapy. OS was calculated from the date of surgery until the date of death or last day of follow-up. RESULTS: Overall, 376 patients were included in our study, of whom 357 were treated with nCRT. Of these 357 patients, 98.3% had a microscopically irradical resection and 1.7% had a macroscopically irradical resection. Approximately 72.3% of tumors showed a partial response (Mandard 2-3) and 11.8% showed little/no pathological response (Mandard 4-5) to nCRT. One of 357 patients underwent adjuvant chemoradiotherapy and 39 patients (61%) underwent adjuvant immunotherapy (nivolumab). The median and 5-year OS rate of all patients was 16.4 months (95% confidence interval 13.1-19.8) and 21%, respectively. CONCLUSION: Real-world population-level data showed that no patients with a tumor-positive resection margin underwent adjuvant therapy following nCRT and esophagectomy prior to 2021. Interestingly, 61% of patients were treated with adjuvant nivolumab in 2021-2022. OS after irradical esophagectomy is poor and long-term data will explore the added value of nivolumab.

Postoperative survival effect of the number of examined lymph nodes on esophageal squamous cell carcinoma with pathological stage T1-3N0M0.

BACKGROUND: The postoperative survival effect of the number of examined lymph nodes on patients of R0-resected esophageal squamous cell carcinoma with pathological stage T1-3N0M0 is still unclear. METHODS: Patients diagnosed with pathological stage T1-3N0M0 esophageal squamous cell carcinoma from two cancer databases-our cancer center (N = 707), and Surveillance Epidemiology and End Results (N = 151). The primary clinical endpoint was overall survival. The X-tile software was used to determine the optimal cutoff value of the number of examined lymph nodes, and propensity score matching was conducted to reduce selection bias according to the results of X-tile software. The cohort of 151 patients from another database was used for validation. RESULTS: X-tile software provided an optimal cutoff value of 15 examined lymph nodes based on 707 patients, and 231 pairs of matched patients were included. In the unmatched cohort, Cox proportional hazard regression analysis revealed better overall survival in patients with more than 15 examined lymph nodes (adjusted hazard ratio, 0.566, 95% confidence interval, 0.445-0.720; p < 0.001) compared with patients with 15 or fewer examined lymph nodes. In the validation cohort, patients with more than 15 examined lymph nodes also had better overall survival (adjusted hazard ratio 0.665, p = 0.047). CONCLUSIONS: The number of examined lymph nodes is a significant prognostic factor in esophageal squamous cell carcinoma patients with pathological stage T1-3N0M0, and more than 15 examined lymph nodes are associated with better overall survival. Although the difference is not significant, the survival curve of patients with examined lymph nodes > 30 is better than those with examined lymph nodes 15-30. We believe that the number of examined lymph nodes can provide prognostic guidance for those patients, and the more examined lymph nodes cause lesser occult lymph nodes metastasis and lead to a better prognosis. Therefore, surgeons and pathologists should try to examine as many lymph nodes as possible to evaluate the pathological stage precisely. However, we need more validation from other studies.

Comparison of Preoperative Nutritional Indexes for Outcomes after Primary Esophageal Surgery for Esophageal Squamous Cell Carcinoma.

BACKGROUND: This study aimed to compare the controlling nutritional status (CONUT) score, prognostic nutritional index (PNI), and geriatric nutritional risk index (GNRI) for predicting postoperative outcomes in patients with esophageal squamous cell carcinoma undergoing esophagectomy. METHODS: We retrospectively reviewed the data of 1265 consecutive patients who underwent elective esophageal surgery. The patients were classified into no risk, low-risk, moderate-risk, and high-risk groups based on nutritional scores. RESULTS: The moderate-risk (hazard ratio [HR]: 1.55, 95% confidence interval [CI]: 1.24-1.92, p < 0.001 in CONUT; HR: 1.61, 95% CI: 1.22-2.12, p = 0.001 in GNRI; HR: 1.65, 95% CI: 1.20-2.26, p = 0.002 in PNI) and high-risk groups (HR: 1.91, 95% CI: 1.47-2.48, p < 0.001 in CONUT; HR: 2.54, 95% CI: 1.64-3.93, p < 0.001 in GNRI; HR: 2.32, 95% CI: 1.77-3.06, p < 0.001 in PNI) exhibited significantly worse 5-year overall survival (OS) compared with the no-risk group. As the nutritional status worsened, the trend in the OS rates decreased (p for trend in all indexes < 0.05). CONCLUSIONS: Malnutrition, evaluated by any of three nutritional indexes, was an independent prognostic factor for postoperative survival.