Prognostic value of Mandard score and nodal status for recurrence patterns and survival after multimodal treatment of oesophageal adenocarcinoma.

BACKGROUND: This study evaluated the association of pathological tumour response (tumour regression grade, TRG) and a novel scoring system, combining both TRG and nodal status (TRG-ypN score; TRG1-ypN0, TRG>1-ypN0, TRG1-ypN+ and TRG>1-ypN+), with recurrence patterns and survival after multimodal treatment of oesophageal adenocarcinoma. METHODS: This Dutch nationwide cohort study included patients treated with neoadjuvant chemoradiotherapy followed by oesophagectomy for distal oesophageal or gastro-oesophageal junctional adenocarcinoma between 2007 and 2016. The primary endpoint was the association of Mandard score and TRG-ypN score with recurrence patterns (rate, location, and time to recurrence). The secondary endpoint was overall survival. RESULTS: Among 2746 inclusions, recurrence rates increased with higher Mandard scores (TRG1 30.6%, TRG2 44.9%, TRG3 52.9%, TRG4 61.4%, TRG5 58.2%; P < 0.001). Among patients with recurrent disease, the distribution (locoregional versus distant) was the same for the different TRG groups. Patients with TRG1 developed more brain recurrences (17.7 versus 9.8%; P = 0.001) and had a longer mean overall survival (44 versus 35 months; P < 0.001) than those with TRG>1. The TRG>1-ypN+ group had the highest recurrence rate (64.9%) and worst overall survival (mean 27 months). Compared with the TRG>1-ypN0 group, patients with TRG1-ypN+ had a higher risk of recurrence (51.9 versus 39.6%; P < 0.001) and worse mean overall survival (33 versus 41 months; P < 0.001). CONCLUSION: Improved tumour response to neoadjuvant therapy was associated with lower recurrence rates and higher overall survival rates. Among patients with recurrent disease, TRG1 was associated with a higher incidence of brain recurrence than TRG>1. Residual nodal disease influenced prognosis more negatively than residual disease at the primary tumour site.

International Survey on the Management of Anastomotic Leakage After Esophageal Resection.

BACKGROUND: Anastomotic leakage is one of the most severe complications following esophageal surgery, leading to significant morbidity, prolonged hospital stay, considerable costs, decreased quality of life, and increased mortality. Management of anastomotic leakage is complicated and has currently not been standardized. The objective of this research is to gain insight into the different opinions on anastomotic leakage management among upper gastrointestinal surgeons and verify the need for diagnostic and treatment guidelines. METHODS: Surgeons with interest in esophageal surgery were invited to participate in an international online questionnaire. The survey consisted of questions pertaining to the surgeons' experience, operation techniques, management routine, and opinion on future international guidelines on the treatment of anastomotic leakage. RESULTS: Of the 331 invited surgeons, 40% participated in the survey. Among the 129 responders, 90.7% use laboratory diagnostics and 62.8% use imaging or endoscopy postoperatively on a routine basis to detect anastomotic leakage. In case of suspected anastomotic leakage, the most chosen diagnostic imaging modalities were computed tomography scan (35.7%) or dynamic swallow investigation (33.3%). Independent from the clinical manifestations, participants of this survey treat patients very differently. More than 70% of the responders agreed that there is a need for diagnostic and therapeutic international guidelines on anastomotic leakage management. CONCLUSIONS: This survey shows that there is no standardized guideline for diagnostic workup or management of anastomotic leakage and that there is a need for an international guideline regarding the optimal management of anastomotic leakage.

Capecitabine, 5-fluorouracil and S-1 based regimens for previously untreated advanced oesophagogastric cancer: A network meta-analysis.

As evidence is inconsistent and based on either isolated Asian or Western studies, we conducted a network meta-analysis (NMA) to examine efficacy and safety of 5-FU (5-fluorouracil), capecitabine and S-1-based first-line treatment of advanced esophagogastric cancer in Asian and Western patients. Medline, EMBASE, CENTRAL and conferences ASCO and ESMO were searched up to January 2016 for randomized-controlled-trials comparing 5-FU, capecitabine or S-1-based regimens with equal chemotherapy backbones. Direct and indirect data for overall survival (OS) and progression-free-survival (PFS) were combined on the Hazard Ratio (HR)-scale using random-effects NMA and calculated as combined HRs and 95%credible intervals (95%CrI). Grade 1-2 and grade 3-4 adverse events were compared with pair-wise meta-analysis. Fifteen studies were identified including capecitabine (n = 945), 5-FU (n = 2,132) or S-1 (n = 1,636). No differences were found in respectively OS and PFS for capecitabine-based versus 5-FU-based regimens (HR = 0.89, 95%CrI = 0.76-1.04 and HR = 0.98, 95%CrI = 0.75-1.32), S-1-based versus 5-FU-based regimens (HR = 0.92, 95%CrI = 0.82-1.04 and HR = 0.88, 95%CrI = 0.70-1.11) and S-1-based versus capecitabine-based regimens (HR = 1.03, 95%CrI = 0.87-1.22 and HR = 0.89, 95%CrI = 0.65-1.20). Effects were similar in Asian and Western subgroups. Toxicity profiles were different but a lower frequency of relevant adverse events was observed with S-1 In conclusion, as efficacy was similar, choosing fluoropyrimidines should be based on their individual toxicity profiles.

Effect of goal-directed therapy on outcome after esophageal surgery: A quality improvement study.

BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSIONS: 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.

Prognostic Significance of the Location of Lymph Node Metastases in Patients With Adenocarcinoma of the Distal Esophagus or Gastroesophageal Junction.

OBJECTIVE: To identify the prognostic significance of the location of lymph node metastases in patients with esophageal or gastroesophageal junction (GEJ) adenocarcinoma treated with neoadjuvant therapy followed by esophagectomy. BACKGROUND: Detection of lymph node metastases in the upper mediastinum and around the celiac trunk after neoadjuvant therapy and resection does not alter the TNM classification of esophageal carcinoma. The impact of these distant lymph node metastases on survival remains unclear. METHODS: Between March 2003 and September 2013, 479 consecutive patients with adenocarcinoma of the distal esophagus or GEJ who underwent transthoracic esophagectomy with en bloc 2-field lymphadenectomy after neoadjuvant therapy were included, and survival was analyzed according to the location of positive lymph nodes in the resection specimen. RESULTS: Two hundred fifty-three patients had nodal metastases in the resection specimen. Of these patients, 92 patients had metastases in locoregional nodes, 114 patients in truncal nodes, 21 patients in the proximal field of the chest, and 26 patients had both positive truncal and proximal field nodes. Median disease-free survival was 170 months in the absence of nodal metastases, 35 months for metastases limited to locoregional nodes, 16 months for positive truncal nodes, 15 months for positive nodes in the proximal field, and 8 months for nodal metastases in both truncal and the proximal field. On multivariate analysis, location of lymph node metastases was independently associated with survival. CONCLUSIONS: Location of lymph node metastases is an independent predictor for survival. Relatively distant lymph node metastases along the celiac axis and/or the proximal field have a negative impact on survival. Location of lymph node metastases should therefore be considered in future staging systems of esophageal and GEJ adenocarcinoma.

18F-FDG PET-CT after Neoadjuvant Chemoradiotherapy in Esophageal Cancer Patients to Optimize Surgical Decision Making.

BACKGROUND: Prognosis of esophageal cancer patients can be significantly improved by neoadjuvant chemoradiotherapy (nCRT). Given the aggressive nature of esophageal tumors, it is conceivable that in a significant portion of patients treated with nCRT, dissemination already becomes manifest during the period of nCRT. The aim of this retrospective study was to determine the value and diagnostic accuracy of PET-CT after neoadjuvant chemoradiotherapy to identify patients with metastases preoperatively in order to prevent non-curative surgery. METHODS: From January 2011 until February 2013 esophageal cancer patients deemed eligible for a curative approach with nCRT and surgical resection underwent a PET-CT after completion of nCRT. If abnormalities on PET-CT were suspected metastases, histological proof was acquired. A clinical decision model was designed to assess the cost-effectiveness of this diagnostic strategy. RESULTS: 156 patients underwent a PET-CT after nCRT. In 31 patients (19.9%) PET-CT showed abnormalities suspicious for dissemination, resulting in 17 cases of proven metastases (10.9%). Of the patients without proven metastases 133 patients were operated. In 6 of these 133 cases distant metastases were detected intraoperatively, corresponding to 4.5% false-negative results. The standard introduction of a post-neoadjuvant therapy PET-CT led to a reduction of overall health care costs per patient compared to a scenario without restaging with PET-CT ($34,088 vs. $36,490). CONCLUSION: In 10.9% of esophageal cancer patients distant metastases were detected by standard PET-CT after neoadjuvant chemoradiotherapy. To avoid non-curative resections we advocate post-neoadjuvant therapy PET-CT as a cost-effective step in the standard work-up of candidates for surgery.

Minimally invasive surgery for oesophageal cancer.

Worldwide an increasing part of oncologic oesophagectomies is performed in a minimally invasive way. Over the past decades multiple reports have addressed the perioperative outcomes and oncologic safety of minimally invasive oesophageal surgery. Although many of these (retrospective) case-control studies identified minimally invasive oesophagectomy as a safe alternative to open techniques, the clear benefit remained subject to debate. Recently, this controversy has partially resolved due to the results of the first randomized controlled trial that compared both techniques. In this trial short-term benefits of minimally invasive oesophagectomy were demonstrated in terms of lower incidence of pulmonary infections, shorter hospital stay and better postoperative quality of life. However, the current lack of long-term data on recurrence rate and overall survival precludes a comprehensive comparison of minimally invasive and open oesophagectomy. Proclaiming minimally invasive oesophagectomy as the standard of care for patients with resectable oesophageal cancer would therefore be a premature decision.