Curative Resection For Esophageal Cancer Research Articles

382. NUMBER OF LYMPH NODES RESECTED IS ASSOCIATED WITH OVERALL SURVIVAL IN PATHOLOGICALLY NODE-NEGATIVE ESOPHAGEAL CANCER

Abstract Background Lymphadenectomy is a key part of curative resection of esophageal cancer, with multiple quality assurance systems suggesting a minimum of 15 lymph nodes should be resected and subjected to pathological examination. Nevertheless, whether the absolute number of nodes resected is a surrogate marker for quality in surgery and staging, or has therapeutic benefit is debated. The aim of this study was to determine the impact of lymphadenectomy on survival in patients with resected pathologically node-negative disease (both treated and untreated with neoadjuvant therapy). Methods A review of our institutional prospectively maintained database was conducted from 2010-2020 inclusive. Inclusion criteria were patients undergoing esophagectomy for esophageal cancer aged 18+ who consented to data inclusion. Exclusion criteria were patients undergoing resection for benign disease, patients with Siewert III tumours undergoing gastrectomy or extended total gastrectomy, patients undergoing re-operative surgery, or patients where final pathology was not available. Univariable and multivariable analyses were performed as appropriate. Results 195 patients (49%) had pathologically node negative disease, with median lymph node count of 25. 47% of patients were clinically node positive, but pathologically node negative following neoadjuvant therapy. On univariable survival analysis, number of nodes resected was a significant predictor of overall survival (HR 0.96, 0.93-0.98, p=0.001). On multivariable analysis, R status (HR 4.9, 1.2-21.1, p=0.03), number of nodes resected (HR 0.97, 0.94-0.99, p=0.02) and prior cN+ status (HR 2.28, 1.16-4.49, p=0.02) were predictors of overall survival. Patients with cN0, (y)pN0 disease had improved overall survival compared with cN+, (y)pN0 (median not reached vs 43.4 months, p=0.04). Conclusion Lymphadenectomy is a key part of resection of esophageal cancer. In pathologically node negative patients, the extent of lymphadenectomy remains a key predictor of overall survival. Conversion from clinically node positive to pathologically node negative disease is associated with worse outcomes compared to clinically and pathologically node negative disease. Even in early stage cancer, a thorough, multi-field lymphadenectomy should be encouraged.

Nature, severity, and impact of chronic oropharyngeal dysphagia following curative resection for esophageal cancer: a cross-sectional study.

Chronic oropharyngeal dysphagia (COD) and aspiration after esophageal cancer surgery may have clinical significance; however, it is a rarely studied topic. In a prospective cross-sectional observational study we comprehensively evaluated the nature, severity, and impact of COD, its predictors, and the impact of the surgical approach and site of anastomosis. Forty participants were recruited via purposive sampling from the (Irish) National Center between November 2021 and August 2022. Swallow evaluations included videofluoroscopy [Dynamic Imaging Grade of Swallowing Toxicity v2 (DIGESTv2), MBS Impairment Profile, Penetration-Aspiration Scale)]. Functional Oral Intake Scale (FOIS) identified oral intake status. The patient reported outcome measures of swallowing, and Quality of Life (QL) included EAT-10 and MD Anderson Dysphagia Inventory (MDADI). Fourteen (35%) participants presented with COD on DIGESTv2 and 10% had uncleared penetration/aspiration. Avoidance or modification of diet on FOIS was observed in 17 (42.5%). FOIS was associated with pharyngeal dysphagia (OR = 4.05, P = 0.046). Median (range) EAT-10 and MDADI Composite results were 3(0-30) and 77.9(60-92.6), respectively. Aspiration rates significantly differed across surgical groups (P = 0.029); only patients undergoing transhiatal surgery aspirated. Survivors of esophageal cancer surgery may have COD that is undiagnosed, potentially impacting swallow-related QL. Given the small number of aspirators, further research is required to determine whether aspiration risk is associated with surgical approach. A FOIS score below 7 may be a clinically useful prompt for the MDT to refer for evaluation of COD following curative intent surgery. These data present findings that may guide preventive and rehabilitative strategies toward optimizing survivorship.

546 INTENSIVE SURVEILLANCE AFTER CURATIVE INTENT SURGERY FOR ESOPHAGEAL CANCER: INITIAL RESULTS OF THE ENSURE STUDY

Abstract Emerging data demonstrate long-term survival after salvage interventions for local or oligometastatic recurrence after planned curative resection for esophageal cancer, providing rationale for postoperative surveillance. However, the impact of intensive surveillance on oncologic outcome is unknown. This multicenter collaborative study aimed to characterize oncologic surveillance protocols across esophageal cancer centers internationally and determine the independent effect of intensive surveillance on oncologic outcome. Methods The ENSURE international multicenter study included consecutive patients who underwent surgery with curative intent for cTxNxM0 esophageal cancer from June 2009 to June 2015. Intensive surveillance was defined as use of cross-sectional imaging, at least annually, during the first three postoperative years. The estimated sample size of 4425 provided 90% power to detect a 5% increase in 5-year overall survival (OS, primary outcome measure). Secondary outcome measures included disease-free (DFS) and disease-specific survival (DSS), surveillance strategies, incidence of oligometastatic recurrence, treatment strategies, and HRQOL. The study was registered on ClinicalTrials.gov (NCT03461341). Results 4597 patients were included. The participating 27 centres undertook mean(SD) 52.3(17.1) esophageal cancer resections annually between 3.5 ± 1.3 attending surgeons. 37%, 11% and 19% centers utilized postoperative surveillance CT, PET-CT and endoscopy, respectively. Among all patients, intensive surveillance was associated with improved OS (HR0.92 [0.85–0.99]) but not DSS (HR0.93 [0.85–1.01]) or DFS (HR0.97 [0.90–1.04]), and on multivariable analysis, intensive surveillance did not provide oncologic benefit (OS HR1.10 [0.99–1.22], DSS HR1.12 [1.00–1.25]), but reduced observed DFS (HR1.19 [1.08–1.31]). Evaluating surveillance modalities, neither surveillance endoscopy nor laboratory tests improved oncologic outcome, however flexible nasolaryngoscopy was associated with improved OS (HR0.84 [0.69–1.0]). Conclusion ENSURE, the first study powered to assess the impact of postoperative surveillance protocols on oncologic outcome in esophageal cancer, demonstrated no overall survival benefit following intensive imaging surveillance, with reduced observed disease-free survival time. However, routine assessment for secondary aerodigestive malignancies may be of oncologic benefit. The present data do not support the use of intensive imaging surveillance among all patients following esophageal cancer surgery. Further reports detailing subgroup analyses and HRQOL impact are anticipated.

Association between postoperative pneumonia and prognosis of patients with esophageal cancer.

370 Background: We examined the association between postoperative pneumonia and prognosis of patients with esophageal cancer after curative surgery. Methods: We enrolled 122 patients who underwent curative resection for esophageal cancer between 2008 and 2018. The patients who had postoperative pneumonia were categorized into the pneumonia group, while those without postoperative pneumonia were classified into the non-pneumonia group. We identified the risk factors for the recurrence-free survival (RFS) and the overall survival (OS). Postoperative pneumonia was defined using the revised Uniform Pneumonia Score. Results: Thirty-four of the 122 patients (27.9%) had postoperative pneumonia. The 5-year OS rate after surgery in the pneumonia group was significantly lower than that in the non-pneumonia group (28.2% versus 55.1%, p = 0.006). Although not significant, the 5-year RFS rate after surgery in the pneumonia group tended to be lower than that in the non-pneumonia group (18.9% versus 49.2%, p = 0.061). A multivariate analysis identified postoperative pneumonia as a significant independent risk factor for the OS (hazard ratio = 2.15; 95% confidence interval, 1.25 to 3.68; P = 0.006). Conclusions: Our analysis showed postoperative pneumonia was an independent risk factor for worse overall survival in patients who underwent curative resection for esophageal cancer. This finding suggests that we should plan the surgical procedure, perioperative care and surgical strategy to prevent postoperative pneumonia.

P66 ENSURE: EUROPEAN INVESTIGATION OF SURVEILLANCE AFTER RESECTION FOR ESOPHAGEAL CANCER

Abstract Aim To characterize oncologic surveillance protocols across European esophageal cancer centers and determine the independent impact of intensive surveillance on oncologic outcome. Background Emerging data demonstrate long-term survival after salvage interventions for local or oligometastatic recurrence after planned curative resection for esophageal cancer, providing rationale for postoperative surveillance. However, the impact of intensive surveillance on oncologic outcome and health-related quality of life (HRQOL) is unknown. Methods First, a survey of surveillance protocols across European esophageal cancer centres was undertaken (Phase 1). Then, an international multicentre study including consecutive patients who underwent surgery with curative intent for cTxNxM0 esophageal or junctional cancer from June 2009 to June 2015 was initiated (Phase 2). The estimated sample size of 4425, with 31% undergoing intensive surveillance, will provide 90% power to detect a 5% increase in 5-year overall survival (primary outcome measure). Secondary outcome measures include disease-free survival, incidence of oligometastatic recurrence, treatment strategies, and HRQOL. Subgroup analyses by age, histologic type and HER-2 status are planned. The study is registered on ClinicalTrials.gov (NCT03461341). Results For Phase 1, 27 centres across 13 European and North American countries participated. Centers undertook 52.3±17.1 esophageal cancer resections per year between 3.5±1.3 attending surgeons. The majority of centers utilized a standardized surveillance protocol for all patients (23, 85.2%). Routine laboratory investigations, nutritional profiling and tumor markers were assessed in 10 (37.0%), 9 (33.3%) and 4 (14.8%) of centers, respectively. 10 centers (37.0%) utilized routine postoperative surveillance computed tomography, of whom 3 (11.1%) also undertook routine postoperative PET-CT in follow-up. Surveillance endoscopy was performed in 7 centers (18.9%). Centers undertaking intensive imaging surveillance had fewer attending surgeons (P=0.036) but similar surgeon volume (P=0.832). Surveillance intensity was not associated with national health expenditure (P=0.733). For Phase 2, data for 4010 patients (31.1% intensive surveillance) from 18 centres across 9 European countries have been submitted to date, with results expected in September 2019. Conclusion The ENSURE study will provide the first appropriately powered evidence assessing the impact of postoperative surveillance strategies on oncologic outcome and HRQOL following potentially curative resection for esophageal cancer.

Postoperative Myocardial Injury in Middle-Aged and Elderly Patients Following Curative Resection of Esophageal Cancer With Aggressive or Standard Body Temperature Management: A Randomized Controlled Trial.

Risk of intraoperative hypothermia is relatively high in middle-aged and elderly patients undergoing curative resection of esophageal cancer, which may cause myocardial ischemia during the early postoperative period. The objective of this study was to compare aggressive or standard body temperature management for lowering the incidence of postoperative myocardial injury that was assessed by troponin levels collected at a priori defined set times in these patients. Seventy patients undergoing elective curative resection of esophageal cancer were randomly assigned to undergo aggressive body temperature management (nasopharyngeal temperature ≥36°C) or standard body temperature management (n = 35 in each arm). The primary outcome was myocardial injury, defined as the occurrence of elevated troponin I (>0.06 µg/L) or elevated high-sensitivity troponin T (≥0.065, or 0.02 µg/L≤ high-sensitivity troponin T <0.065 µg/L, but with an absolute change of at least 0.005 µg/L) or both during 2 days after surgery. Secondary outcomes included (1) severe arrhythmia, including atrial fibrillation, supraventricular tachycardia, frequent premature ventricular contractions intraoperatively or during 3 days postoperatively; (2) hypoxemia or metabolic acidosis during the first 12 h postoperatively; and (3) deep vein thrombosis or pulmonary embolism during 3 days postoperatively. Incidence of postoperative 2-day myocardial injury was 8.6% (3/35) among patients receiving aggressive body temperature management and 31.4% (11/35) among patients receiving standard body temperature management (P = .017, χ). Relative risk of myocardial injury in the aggressive body temperature management group was 0.27 (95% CI, 0.08-0.89). Incidence of intra- and postoperative 3-day severe cardiac arrhythmia was 2.9% (1/35) among patients receiving aggressive body temperature management and 28.6% (10/35) among patients receiving standard body temperature management. Incidence of postoperative 12-h hypoxia was 17.1% (6/35) with aggressive body temperature management and 40.0% (14/35) with standard body temperature management. Incidence of postoperative 12-h metabolic acidosis was 20% (7/35) among patients receiving aggressive body temperature management and 48.6% (17/35) among patients receiving standard body temperature management. Incidence of postoperative 3-day deep vein thrombosis or pulmonary embolism was 0% (0/35) with aggressive body temperature management and 2.9% (1/35) with standard body temperature management. Aggressive body temperature management may be associated with a lower incidence of postoperative myocardial injury.

Surveillance Implications of Recurrence Patterns in Early Node-Negative Esophageal Adenocarcinoma

There are limited data regarding optimal surveillance after curative resection for esophageal cancer. Once disease recurrence is diagnosed, the prognosis is poor. The purpose of this article was to characterize disease recurrence in patients with early esophageal adenocarcinoma. Two hundred sixty patients were identified from a prospective institutional database with pathologic T1 and T2 node-negative disease therapy treated with curative esophagectomy alone for esophageal adenocarcinoma between 1995 and 2017. Competing risk analysis was used to analyze factors associated with recurrence. The 5-year cumulative incidence of recurrence was 12%. Predictive factors for increased risk of recurrence included increasing tumor size, poor differentiation, and pathologic T2 disease (P < .05), whereas presence of Barrett's esophagus on pathology was protective. Recurrence within 2 years was 2.5%, 6.1%, and 12% for T1a, T1b, and T2 disease, respectively. At 5 years cumulative incidence of recurrence was 8.2%, 11.5% and 22.2%, respectively. Median overall survival after recurrence was 1.04 years (95% confidence interval, 0.7-2.4). There were 14 subclinical and 13 symptomatic recurrences; patients with symptomatic recurrence had a significantly shorter overall survival after recurrence occurred (0.31 vs 0.71 years, P= .018). Among early node-negative patients with esophageal cancer undergoing curative resection, 5-year recurrence was 12%. Survival after recurrence was poor, and only a few patients had isolated locoregional recurrence at time of diagnosis, suggesting that scheduled surveillance may have an important role.

Salvage Carbon-ion Radiotherapy for Isolated Lymph Node Recurrence Following Curative Resection of Esophageal Cancer.

Evaluation of the therapeutic efficacy of carbon-ion radiation therapy for isolated lymph node recurrence following curative resection of esophageal cancer. Ten cases with lymph node recurrence after esophageal cancer surgery were treated with carbon-ion radiation therapy. A total of 48.0 Gy [relative biologic effectiveness (RBE)] was delivered over 3 weeks with a daily dose of 4.0 Gy (RBE). The median follow-up duration was 27.1 months (range=3-92.0 months) after carbon-ion radiation therapy. The local control rates at 2, 3 and 5 years were 92.4%. The overall survival rates at 2, 3 and 5 years were 70.0%, 58.3% and 21.9%. The median survival period was 45.3 months after carbon-ion radiation therapy. There were no toxicities of grade 3 or higher. Carbon-ion radiation therapy may be a safe and effective treatment option for isolated lymph node recurrence after radical surgery for esophageal cancer.

The impact of obesity on esophagectomy: a meta-analysis.

The impact of body mass index (BMI) on postoperative outcomes after curative resection for esophageal cancer has been assessed in many studies worldwide with conflicting conclusions. The aim of this meta-analysis is to evaluate the influence of preoperative BMI on surgical and oncologic outcomes after radical surgery for esophageal cancer, in Western studies. A comprehensive electronic search was performed to identify Western publications reporting BMI and outcomes following surgery for esophageal cancer. Articles that did not report preoperative BMI, postoperative morbidity, and early mortality were excluded. Statistical analysis was performed using the OpenMetaAnalyst software (Version 10.10). One hundred and ninety records were examined and 8 studies were included with a total of 2838 patients. The study population was stratified into two groups: a nonobese group (BMI < 30 kg/m2), containing 2199 patients, and an obese group (BMI≥30 kg/m2), with 639 patients. In the obese group, there was an increased risk (up to 35%) of anastomotic leak (P=0.003; RR: 0.857, 95% CI: 0.497, 0.867). The obese group showed a significantly more favorable five-year overall survival (P=0.011). Although there was a significant association between anastomotic leak and obesity, patients with obesity also have a better overall 5-year survival. This meta-analysis demonstrates that patients with obesity should be counseled regarding the specific risks of surgery but they can be reassured that despite these risks overall outcome is satisfactory.

Prognostic significance of preoperative inflammatory response biomarkers in patients undergoing curative thoracoscopic esophagectomy for esophageal squamous cell carcinoma

BackgroundRecent studies have revealed significant relationships between the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) and survival in various cancers. The purpose of this study was to confirm whether the LMR, NLR, and PLR have prognostic values, independent of clinicopathological criteria, in patients undergoing curative resection for esophageal cancer. MethodsThe LMR, NLR and PLR were calculated in 147 consecutive patients who underwent curative esophagectomy between January 2006 and December 2014. Receiver operating characteristics (ROC) curve analysis was conducted to identify the optimal cutoff values of each biomarkers. ResultsIn multivariate analysis for cancer-specific survival (CSS), pTNM stage (p < 0.0001) and low LMR (p = 0.0081) were selected as independent prognostic factor. Similarly, pTNM stage(p < 0.0001) and low LMR (p = 0.0225) were found to be independent prognostic factor for overall survival (OS). There was no significant relationship between LMR, NLR and PLR and survival in patients with stage I or II, however, significant relationships between LMR and CSS or OS were observed in patients with stage III esophageal cancer. ConclusionsLMR can be used as a novel predictor of postoperative CSS and OS in patients with esophageal cancer and that it may be useful in identifying patients with a poor prognosis even after radical esophagectomy.

Isolated local recurrence or solitary solid organ metastasis after esophagectomy for cancer is not the end of the road.

Recurrent disease after esophagectomy bears an infaust prognosis, especially when multiple recurrences are present. But little is known about survival in patients with limited recurrence (solitary locoregional recurrence or solid organ metastasis). Herein, we report our experience with these subgroups. We analyzed 1754 consecutive patients surgically treated with curative resection for esophageal cancer and cancer of the gastroesophageal junction between 1990 and 2012. Seven subgroups were defined according to the recurrence type (locoregional vs. organ metastasis), the site of recurrence (abdominal, thoracic, cervical for lymph nodes and lung, liver, adrenals and others for organ metastasis) and also the number of lesions (one vs. multiple lymph node stations or organ metastasis) Of these groups; clinical isolated locoregional recurrence (ciLR) was defined as solitary lymph-node recurrence confined to one compartment (cervical, thoracic or abdominal, within or outside surgical dissection-field) at clinical staging. Clinical solitary solid organ metastasis (csSOM) was defined as metastasis in a resectable solid organ, i.e. liver, lung, brain or adrenal. Salvage therapies were grouped in five categories. Kaplan-Meier curves were used to calculate survival. Recurrent disease was observed in 766 patients (43.7%) with overall 5-year survival of 4.5% after diagnosis of recurrence. Fifty-seven patients (7.4%) showed ciLR and 110 (14.4%) csSOM. Median time-to-recurrence was 16.8months in ciLR and 9.9months in csSOM (P = 0.0074). Survival is significantly improved compared to supportive therapy when local therapy is possible (P < 0.0001). In 25 (15%) of ciLR or csSOM patients, surgical therapy with or without systemic therapy, yielded a 5-year survival of 49.9% (median 54.8months) after diagnosis of recurrence. When surgery was impossible or contraindicated, the combination of chemoradiotherapy appeared to be superior to chemotherapy alone (respectively 27.0% vs. 4.6% 5-year survival) or radiotherapy alone (no 5-year survival). Recurrent disease after esophagectomy is a common problem with poor overall survival. However prolonged survival could be obtained in selected patients if the recurrent disease is limited to ciLR or csSOM, if surgery (+/- systemic therapy) can be performed. If not a combination of chemoradiotherapy seems to offer the second best option. Patients presenting with a ciLR or csSOM should be discussed in a dedicated multidisciplinary team meeting as to evaluate and define the place of salvage treatment which in well selected cases could offer a perspective of prolonged survival.

Postoperative infectious complications-driven recurrence after radical resection for esophageal cancer

Few reports have reported the long-term outcome of esophageal cancer patients suffering from postoperative infectious complications. Here, we investigated the impact of postoperative infectious complications in patients who had undergone curative resection for esophageal cancer. The study population comprised 97 patients who underwent radical resection for esophageal cancer with curative intent between 2001 and 2008. Postoperative infectious complications were defined as surgical site infections and pneumonia. We compared clinical features, tumor histology, recurrence, and overall survival between patients with postoperative infections and those who did not. Of the 97 patients studied, 37 had postoperative infectious complications. The disease-free and overall survival rates of the entire cohort did not significantly differ between patients with and without postoperative infectious complications. Univariate analysis revealed that among patients with stage III esophageal cancer, those with postoperative infectious complications demonstrated significantly shorter disease-free survival than those without. Multivariate analysis demonstrated that postoperative infectious complications were independent prognostic indicators for disease-free survival of stage III esophageal cancer patients. Our findings suggest that postoperative infectious complications in stage III esophageal cancer patients have a negative impact on disease-free survival.

Prognostic significance of pre-treatment neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in locally advanced esophageal cancer.

172 Background: The prognosis for esophageal cancer remains poor despite advances in therapeutic modalities. Elevations of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been shown to be associated with poorer prognosis in several types of solid cancer. However, their prognostic value remains controversial in esophageal cancer. The aim of this study was to assess the prognostic value of NLR and PLR in esophageal and gastroesophageal junction (GEJ) cancer. Methods: We retrospectively reviewed the database of 77 patients who underwent neoadjuvant chemoradiation and potentially curative resection for esophageal cancer in our institute, between July 2006 and December 2011. NLR and PLR were calculated from laboratory data obtained prior to the start of chemoradiation. The predictive value of NLR and PLR was assessed using Kaplan-Meier curves and Cox regression models for an association with pathologic response to chemoradiation, relapse-free survival, and overall survival. Results: A total of 77 patients were identified with a median age at diagnosis of 62.5 years. In univariate analysis, neither NLR nor PLR were shown to be significantly associated with the pathologic response (p = 0.87, p = 0.89, respectively), relapse-free survival (p = 0.5, p = 0.4, respectively), or overall survival (p = 0.55, p = 0.44, respectively). Conclusions: The present study failed to confirm NLR and PLR as significant predictors of pathologic response to chemoradiation, relapse-free survival, and overall survival in patients with locally advanced esophageal and GEJ cancer undergoing neoadjuvant chemoradiation and surgical resection.

Prolonged postoperative length of stay is associated with poor overall survival after an esophagectomy for esophageal cancer.

To investigate the impact of prolonged length of stay (LoS) on long-term mortality in patients who have undergone curative resection for esophageal cancer (EC). Between January 2001 and December 2009, patients who underwent an esophagectomy for EC at Fudan University Shanghai Cancer Center were enrolled in this study. We retrospectively analyzed the medical charts of all of the enrolled patients. To determine the effect of postoperative LoS on long-term survival, we separated the patients into three groups based on the lengths of their postoperative LoS, including an LoS of less than 2 weeks (Group 1, ≤2 W), an LoS between 2 and 3 weeks (Group 2, ≤3 W) and an LoS of more than 3 weeks (Group 3, >3 W). Perioperative and long-term outcomes were compared between the groups. In total, 348 patients were included in this study. All of the patients underwent an esophagectomy with 3-field lymph node dissection (3FLND). The median postoperative hospital stay was 14 days (range: 8-153 days). Complications were observed in 123 patients (15.9% in Group 1 vs. 73.2% in Group 2 vs. 96.6% in Group 3, P<0.001). The median duration of follow-up was 39 months (range: 3-120 months). There were significant reductions in preventive adjuvant therapy (P=0.003) and postoperative salvage therapy (P<0.001) among the three groups. The 5-year survival rate was significantly different among the groups (43% vs. 36% vs. 29%, respectively, P=0.006). There was no difference in the 5-year disease-free survival rate among the three groups (23% vs. 21% vs. 19%, P=0.238). Prolonged LoS was significantly associated with reduced rates of overall survival (OS). The insufficient administration of adjuvant therapy may partly account for these findings.

Impact of inflammation-based prognostic score on survival after curative thoracoscopic esophagectomy for esophageal cancer

BackgroundDespite recent improvements in early detection, progress in surgical techniques, and development of chemoradiation therapies, prognosis of esophageal cancer remains poor. The aim of the present study was to assess whether Glasgow Prognostic Score (GPS), an inflammation-based prognostic score, has prognostic value independent of conventional clinicopathological criteria in patients undergoing curative resection for esophageal cancer, even in elderly patients. MethodsWe retrospectively reviewed the database of 141 consecutive patients with histologically verified esophageal squamous cell carcinoma who underwent potentially curative surgery in our institute, between January 2006 and December 2014. GPS and neutrophil lymphocyte ratio (NLR) were calculated. ResultsOn multivariate analysis, TNM stage (p < 0.0001) and GPS (p = 0.041) were independently associated with worse prognosis in overall patients with esophageal cancer.Multivariate analysis evaluated the prognostic factors in two different patient groups: patients younger than 70 years (non-elderly) and those aged 70 years or more (elderly).Multivariate analysis demonstrated that TNM stage (p = 0.0003) was an only independent risk factor for a worse prognosis among non-elderly group. Meanwhile, multivariate analysis demonstrated that TNM stage (p = 0.001) and GPS (p = 0.043) were the independent risk factor for a worse prognosis among elderly group. ConclusionThe present study demonstrated that GPS is associated with prognosis and can be considered as an independent prognostic marker in patients who underwent esophagectomy. Moreover, the GPS has the advantage of being simple to measure, routinely available and well standardized. But the present study failed to confirm the NLR as a significant predictor of survival following resection for esophageal cancer.

Definitive Therapy for Isolated Esophageal Metastases Prolongs Survival

Local and distant recurrences are frequent after curative resection for esophageal cancer and are considered uniformly fatal. However, some patients may present with isolated recurrences that appear amenable to definitive local therapy either by resection or chemoradiotherapy. We reviewed the clinical outcome of all patients with isolated nodal or distant metastases who were treated with curative intent. In this retrospective review, all patients (n=561) who underwent curative resection for esophageal cancer from 1988 to 2011 were identified from a prospectively assembled thoracic surgery database. Patients who had any type of recurrence were identified (n=205). In this group, 27 patients were identified with isolated disease defined as single station of nodal disease or isolated distant metastases. Survival was modeled using the Kaplan-Meier method, and subgroup survival estimates were compared by the log rank test. The impact of age, sex, histology, pathology stage, site of recurrence, and treatment modality on mortality were analyzed by logistic regression. Twenty-seven patients (22 male, median age 61 years) had an isolated esophageal cancer recurrence; of those, 15 patients underwent surgical resection and 12 underwent definitive chemoradiation therapy. The sites of isolated recurrence were most commonly nodal. Median overall survival from time of recurrence was 25.2 months; 3-year estimated survival was 33.0% (confidence interval: 13.7 to 52.5). In univariate analysis, no relationship was formed. In appropriately selected patients with isolated esophageal metastases, definitive therapy can prolong survival. A long disease-free interval and recurrence limited to single nodal stations may select patients likely to have longer survival after definitive local therapy.

Long-Term Results of Radiochemotherapy for Solitary Lymph Node Metastasis After Curative Resection of Esophageal Cancer

To evaluate the long-term efficacy and toxicity of definitive radiochemotherapy for solitary lymph node metastasis after curative surgery of esophageal cancer. We performed a retrospective review of 35 patients who underwent definitive radiochemotherapy at Tohoku University Hospital between 2000 and 2009 for solitary lymph node metastasis after curative esophagectomy with lymph node dissection for esophageal cancer. Radiotherapy doses ranged from 60 to 66 Gy (median, 60 Gy). Concurrent chemotherapy was platinum based in all patients. The endpoints of the present study were overall survival, cause-specific survival, progression-free survival, irradiated-field control, overall tumor response, and prognostic factors. The median observation period for survivors was 70.0 months. The 5-year overall survival was 39.2% (median survival, 39.0 months). The 5-year cause-specific survival, progression-free survival, and irradiated-field control were 43.3%, 31.0% and 59.9%, respectively. Metastatic lesion, size of the metastatic lymph node, and performance status before radiochemotherapy were significantly correlated with prognosis. Complete response and partial response were observed in 22.9% and 57.1% of the patients, respectively. There was no Grade 3 or higher adverse effect based on the Common Terminology Criteria for Adverse Events (CTCAE v3.0) in the late phase. Based on our study findings, approximately 40% of patients with solitary lymph node metastasis after curative resection for esophageal cancer have a chance of long-term survival with definitive radiochemotherapy.

Long-term Results of Chemoradiotherapy for Solitary Lymph Node Metastasis after Curative Resection of Esophageal Cancer

Long-term Results of Chemoradiotherapy for Solitary Lymph Node Metastasis after Curative Resection of Esophageal Cancer

Survival Factors in Patients with Recurrence After Curative Resection of Esophageal Squamous Cell Carcinomas

Approximately half of patients who undergo curative resection for esophageal cancers develop recurrence postoperatively. The factors affecting survival after such recurrence remain largely unknown. To investigate factors affecting survival after recurrence in patients who had undergone curative resection for esophageal cancer, we retrospectively reviewed data for 461 patients who underwent curative esophagectomy with or without preoperative therapy for esophageal squamous cell carcinoma from January 1996 to December 2007. The correlations between several clinicopathological factors and survival after recurrence were examined. Recurrence occurred in 196 of 461 patients (42.5%), with a median survival time after recurrence of 8.2months. Multivariate analysis identified advanced tumor stage, preoperative chemoradiotherapy (CRT), number of recurrent tumors, and the presence of recurrence at the local site and liver as associated with shortened survival after recurrence. The analysis also indicated that treatment of the recurrence prolonged survival regardless of the treatment type. Although the pattern of recurrence did not significantly differ according to type of preoperative therapy, patients who underwent preoperative CRT were less often treated with radiotherapy for recurrence. Patients with multiple recurrent tumors less often received radiotherapy or surgery than those with a solitary recurrence. Chemotherapy for recurrence was not associated with either preoperative therapy or the number of recurrences. Our retrospective study showed that multiple recurrent tumors and preoperative CRT limit the available treatment for recurrence and thereby are associated with poor prognosis. Vigorous treatment for recurrence can extend survival after recurrence in patients who undergo esophagectomy.

Detection of Lymph Node Involvement by Cytokeratin Immunohistochemistry is an Independent Prognostic Factor After Curative Resection of Esophageal Cancer

BackgroundInvolved lymph nodes (LN) are a negative prognostic factor in esophageal cancers. To assess the role of nodal micrometastases, we performed immunohistochemical analyses of LN after resection of node-negative esophageal cancers and correlated the results with survival. MethodsSeventy patients with esophageal cancer after curative resection and conventionally negative nodes were included. The LN were examined with six consecutive sections (three hematoxylin and eosin (HE) stained and three stained immunohistochemically with the cytokeratin (CK) antibodies AE1/AE3). Survival was evaluated uni- and multivariately. Median follow-up was 4.1 years. ResultsImmunohistochemical analysis showed CK-positive LN in 16 (23%) patients. Of those 16 cases with CK-positive LN, nine had aviable macrometastases, ten had CK-positive scars/fibrosis and five had viable micrometastases. All patients with aviable macrometastases or CK-positive scars/fibrosis had undergone neoadjuvant chemoradiation. Five-year survival was 48% in all patients. In univariate analysis, survival was worse in patients with CK-positive LN (5-year survival of 30% vs. 54% in CK-negative LN; p < 0.02) and in patients with squamous cell carcinoma (5-year survival of 38% vs. 75% in adenocarcinoma; p = 0.05). Multivariate analysis revealed CK-positive LN (p = 0.02) and (borderline) squamous cell carcinoma (p = 0.06) as negative prognostic factors. ConclusionsThe immunohistochemical analysis of LN may detect (viable or non-viable) tumor cells in lymph nodes after resection of conventionally node-negative esophageal cancers. Conventional pathological analysis by HE, therefore, understages esophageal cancer in these cases. The detection of CK-positive cells in resected LN is an independent prognostic factor in otherwise LN-negative esophageal cancer.