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Delayed gastric conduit emptying (DGCE) after esophagectomy for cancer is associated with adverse outcomes and troubling symptoms. Widely accepted diagnostic criteria and a symptom grading tool for DGCE are missing. This hampers the interpretation and comparison of studies. A modified Delphi process, using repeated web-based questionnaires, combined with live interim group discussions was conducted by 33 experts within the field, from Europe, North America, and Asia. DGCE was divided into early DGCE if present within 14 days of surgery and late if present later than 14 days after surgery. The final criteria for early DGCE, accepted by 25 of 27 (93%) experts, were as follows: >500 mL diurnal nasogastric tube output measured on the morning of postoperative day 5 or later or >100% increased gastric tube width on frontal chest x-ray projection together with the presence of an air–fluid level. The final criteria for late DGCE accepted by 89% of the experts were as follows: the patient should have 'quite a bit' or 'very much' of at least two of the following symptoms; early satiety/fullness, vomiting, nausea, regurgitation or inability to meet caloric need by oral intake and delayed contrast passage on upper gastrointestinal water-soluble contrast radiogram or on timed barium swallow. A symptom grading tool for late DGCE was constructed grading each symptom as: 'not at all', 'a little', 'quite a bit', or 'very much', generating 0, 1, 2, or 3 points, respectively. For the five symptoms retained in the diagnostic criteria for late DGCE, the minimum score would be 0, and the maximum score would be 15. The final symptom grading tool for late DGCE was accepted by 27 of 31 (87%) experts. For the first time, diagnostic criteria for early and late DGCE and a symptom grading tool for late DGCE are available, based on an international expert consensus process. [ABSTRACT FROM AUTHOR]

Background Neoadjuvant chemoradiotherapy (nCRT) induces a pathologically complete response in approximately 30% of patients with oesophageal cancer. To explore the possibility of safe postponement of surgery, accurate clinical response evaluations are needed to exclude residual disease. The present study aims to assess the value of F-18-FDG-PET/CT for the detection of residual tumour (> 10% tumour cells = TRG3–4 vs. no vital cells = TRG1) or metastases after nCRT. Methods FDG-PET/CT at baseline and 12 weeks after nCRT was performed according to the European Association of Nuclear Medicine guidelines 1.0 (2.3MBq/kg F-18-FDG; scanning 60 ± 5min.) and the protocol of the preSANO study. Qualitative analysis included sensitive reading of presence of residual tumour and/or metastases. A lesion was considered FDG-positive, when any uptake in the lesion itself was above the adjacent oesophageal background uptake. Quantitatively, SUV/lean body mass (SUL) measurements at tumour, lymph nodes, oesophagus, liver and bloodpool were recorded and compared with pathology (resection specimen: gold standard). Results Some 129 of 207 patients with FDG-avid tumours at baseline proceeded to FDG-PET/CT at around 12 weeks after nCRT just before surgery. Forty-one of 129 patients had TRG3–4, of whom 6 were missed on FDG-PET/CT (15% false negative) with SULmax 2.07 ± 0.25, SUL-ratio tumour/oesophagus (SULR) 1.35 ± 0.14. Sensitivity for TRG2–3-4 vs. TRG1 was 57/71 (80%). SULmax and SULR of FDG-positives were 3.76 ± 1.33 and 1.82 ± 0.69 respectively, compared to SULmax 2.21 ± 0.42 and SULR 1.31 ± 0.22 in FDG-negatives. Distant metastases were detected in 18 of 190 (10%) patients. Of all patients with postponed surgery, 12 had ≥ 1 additional FDG-PET/CT during follow-up (25–49.7 weeks after nCRT). Eventually, 4 patients underwent surgery. Three of 4 had increased FDG-signal and TRG3–4; 1 patient had decreased FDG-signal and no tumour left (TRG1). Conclusion FDG-PET/CT at around 12 weeks after nCRT misses TRG3–4 tumours in 15% and detects residual TRG2–3-4 in 80%. Furthermore, PET-CT detects distant metastases in 10% of patients after nCRT. These data indicate that serial FDG-PET may become valuable in an active surveillance approach. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background After curatively intended neoadjuvant chemoradiotherapy (nCRT) according to CROSS plus surgery for esophageal cancer, 29% of patients have a pathologic complete response. Active surveillance after nCRT, in which patients undergo frequent clinical examinations and where esophagectomy is only offered to those with a locoregional regrowth without distant metastases, has been proposed as novel treatment option. This study provides a systematic review and meta-analysis of the literature regarding the accuracy of endoscopic biopsies, endoscopic ultrasound (EUS) and 18F-FDG PET(-CT) for detecting residual disease after nCRT for esophageal cancer. Methods A systematic literature search in Embase, Medline, Cochrane and Web of Science was performed. Two reviewers independently collected studies on the diagnostic accuracy of endoscopic biopsies, EUS and 18F-FDG PET(-CT) for detecting residual disease after nCRT at the primary tumor site or in regional lymph nodes for potentially curable esophageal adenocarcinoma (AC) or squamous cell carcinoma (SCC). Histopathological examination of the resection specimen was the reference standard. Study quality was appraised with the QUADAS-2 tool. Sensitivity and specificity values were calculated and pooled using meta-analyses. Subgroup analyses were performed to investigate possible sources of heterogeneity. Results 60 studies were included for qualitative analysis and 40 for quantitative analysis. For detecting residual disease at the primary tumor site, 11 studies evaluated endoscopic biopsies, 11 described EUS qualitatively, 14 evaluated PET qualitatively, 12 evaluated PET quantitatively, 6 of them using SUVmax and 6 of them using DSUVmax. Summary sensitivity values were 0.36 (95%CI 0.27–0.45), 0.97 (95%CI 0.94–0.98), 0.74 (95%CI 0.66–0.81), 0.68 (95%CI 0.61–0.74) and 0.68 (95%CI 0.54–0.79), respectively. Summary specificity values were 0.93 (95%CI 0.85–0.97), 0.09 (95%CI 0.04–0.19), 0.52 (95%CI 0.40–0.63), 0.70 (95%CI 0.61–0.78), 0.70 (95%CI 0.60–0.78) and respectively. For detecting residual malignant lymph nodes, 11 studies evaluated EUS with a summary sensitivity of 0.68 (95%CI 0.54–0.80) and a summary specificity of 0.58 (95%CI 0.45–0.70). Subgroup analyses demonstrated that sensitivity of endoscopic biopsy, PET DSUVmax and EUS for nodal was higher in SCC than in AC. Conclusion Current literature suggests insufficient accuracy of endoscopic biopsies, EUS and 18F-FDG PET(-CT) as individual modalities for detecting residual disease after nCRT for potentially curable esophageal cancer. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background The presence of signet ring cells (SRC) is associated with poorer survival in multiple cancer types. Here we aimed to determine the predictive and prognostic value of SRC in oesophageal and junctional adenocarcinoma (OAC) for patients treated with neoadjuvant chemoradiotherapy (nCRT) or chemotherapy (nCT). Methods Patients who underwent nCRT and nCT followed by surgery for OAC between 2000 and 2016 were identified from two institutional prospective databases. Pre-treatment biopsy and surgical resection pathology reports were used to determine the presence of SRC morphology. The association between SRC histology and clinicopathological characteristics including pathological response was assessed. The prognostic impact of SRC on disease-free survival (DFS) and overall survival (OS) was determined. Survival was calculated with Kaplan Meier method and differences tested with log rank test. Results Of the 689 study patients, 129 had SRC (nCRT; n = 65, nCT; n = 64) and 560 patients had no evidence of SRC (nCRT; n = 326, nCT; n = 234). The SRC group had higher pT stage (P = 0.004) and median number of involved nodes (P = 0.004) following nCT compared with the non-SRC group. There were no significant differences between the two groups with respect to age, gender, tumour site, pN, R status or pathological complete response. For the 129 in the SRC group, nCT patients had significantly worse DFS (median [IQR]; 12 months [50–5]) compared with nCRT patients (median [IQR]; 26 months [111–9], P = 0.021). Moreover, nCT had a worse loco-regional recurrence-free survival (P  = 0.004), but not distant recurrence-free survival (P = 0.74), in the SRC group. In contrast, there were no differences in DFS (P = 0.245) or recurrence patterns between nCRT and nCT among the 560 non-SRC patients. However, there was no significant difference in OS according to SRC status following nCT (P = 0.076) or nCRT (P = 0.541). Conclusion For SRC OAC, nCRT is associated with better DFS and loco-regional control compared with nCT. However, the presence of SRC in OAC was not prognostic for OS following nCT or nCRT. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background An optimal model for predicting pathologic response after neoadjuvant chemoradiotherapy (nCRT) in oesophageal cancer has not been defined yet. FDG-PET/CT is frequently used in response assessments. The aim of this side study of the preSANO trial (NL41732.078.13) was to investigate if the FDG-PET parameters SUVmax, total lesion glycolysis (TLG) and metabolic tumour volume (MTV) were predictive for residual tumour in the resected specimen of oesophageal cancer patients treated with nCRT. Methods Patients underwent FDG-PET/CT at baseline according to the European Association of Nuclear Medicine guidelines 1.0 (2.3MBq/kg F-18-FDG; scanning 60 ± 5min.). All parameters were corrected for lean body mass. MTV was defined as the volume within a 41% of SULmax ( = SUV/lean body mass) isocontour threshold at tumour and lymph nodes. TLG was calculated as SULmean x MTV. Logarithmic transformation was performed because of non-normal distribution of TLG and MTV. Baseline PET parameters were compared to tumour regression grade in the resection specimen (TRG3–4 = > 10% residual tumour vs. TRG1 = complete response). Peroperatively irresectable tumours were recoded as TRG4. Analyses were performed using an independent-samples T-test. Results From a total of 207 patients who underwent FDG-PET/CT before nCRT, 197 were included for analysis (5 were non-FDG avid, 5 had incomplete data). Histological type of tumour: adenocarcinoma (AC) n = 154, squamous cell carcinoma (SCC) n = 42, and one adenosquamous carcinoma. Thirty-seven patients (19%) had TRG1 and 41 patients (21%) had TRG3–4. In complete responders (TRG1), SULmax, TLG and MTV (mean ± SD) were 9.6 ± 5.8, 85.3 ± 85.5 and 13.0 ± 9.9, respectively. In patients with TRG3–4, SULmax, TLG and MTV were 9.4 ± 5.4145.8 ± 164.6 and 21.9 ± 16.2, respectively. SULmax was not significantly different between both groups (P  = 0.8), but log(TLG) and log(MTV) (P  = 0.008 and P  = 0.001) were. In adenocarcinomas, log(TLG) did not differ between groups (P  = 0.1). Conclusion Initial FDG tumour mass, expressed as MTV, (rather than SULmax) is the most contributing factor in predicting residual disease after nCRT in both SCC and AC. The effect is stronger in SCC. Therefore, baseline FDG tumour mass should be included in a prediction model, besides other clinical and tumour parameters. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background An active surveillance approach has been proposed for patients with a clinically complete response (cCR) after neoadjuvant chemoradiotherapy (nCRT) in esophageal cancer (SANO trial). To justify renouncing surgical resection, patients with residual disease after nCRT should be accurately identified. However, substantial residual disease (TRG3–4) cannot be detected in 10% of patients with current diagnostic tests (preSANO trial). Circulating cell free tumor DNA (ctDNA) potentially improves detection of residual malignancy after nCRT and could be used for disease monitoring. The objective of this study was to investigate the feasibility of using ctDNA as biomarker for disease status after nCRT in esophageal cancer. Methods Twelve typical patients from the preSANO trial with variable pathological responses to nCRT were included. Blood was drawn and processed pretreatment. The feasibility of detecting TP53 mutations in baseline tumor biopsies was investigated using a next generation sequencing (NGS) panel. Subsequently, baseline blood samples of patients in whom specific TP53 mutations could be identified in baseline tumor biopsies or the surgical resection specimen were analyzed for ctDNA using cell free DNA NGS kits with single molecule barcoding (Oncomine Thermo Fisher). Results Baseline biopsy samples were available in 8 out of 12 patients. In 7 of these 8 patients (88%) specific TP53 mutations could be identified in their baseline biopsies. In 11 out of 12 patients (92%) specific TP53 mutations could be identified in baseline biopsies or the resection specimen. Eight of these 11 mutations were potentially detectable by the Oncomine panel. The panel detected TP53 mutational ctDNA in 4 of these 8 samples (50%). Conclusion Specific and clonal TP53 mutations can be identified in pretreatment biopsy samples and in surgical resection specimens of patients with esophageal cancer. These mutations can be matched to ctDNA identified in blood samples. Hence, ctDNA analyses in blood samples can potentially be used for disease monitoring during active surveillance and for disease monitoring in follow-up after surgical resection. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Background: After potentially curative resection of oesophageal cancer and prevertebral gastric tube reconstruction, approximately one-quarter of patients develop secondary dysphagia due to locoregional recurrence. In half of them dysphagia can be prevented by using an extra-anatomical reconstruction route. The present randomized study was conducted to compare the technical and functional results after prevertebral and retrosternal gastric tube reconstruction. Methods: Sixty patients underwent resection of a carcinoma of the oesophagus or gastro-oesophageal junction with curative intent. Subsequently, these patients were randomly allocated to either prevertebral (n=30) or retrosternal (n=30) gastric tube reconstruction. Early and late complications and functional results were carefully monitored. Results: Creation of the retrosternal tunnel was not accompanied by any perioperative complications. Postoperative recovery, anastomotic leakage and benign stricture formation were not significantly different between the two groups. Functional results, as measured by scintigraphic gastric emptying, quantitative and qualitative oral food intake, and changes in body-weight were similar in the two groups. Conclusion: After subtotal oesophagectomy retrosternal gastric tube reconstruction can be performed easily and safely, and gives functional results similar to those obtained with prevertebral reconstruction. In patients at high risk for developing secondary malignant dysphagia the extra-anatomical route is the reconstruction of first choice. [ABSTRACT FROM AUTHOR]

Background: Intrathoracic herniation of abdominal viscera is a potentially life-threatening condition, especially when diagnosis is delayed. The aim of this study was to estimate its incidence following oesophageal resection and to define contributing factors that might influence its occurrence. Methods: All radiographic studies of the chest that were made during follow-up in a series of 218 patients who underwent oesophagectomy between 1993 and 1997 were reviewed. Results: Herniation of bowel alongside the oesophageal substitute was detected in nine patients (4 per cent). Four hernias occurred within the first week after operation and five were detected at late follow-up. Surgical treatment was indicated in six patients. Analysis of predisposing factors revealed that extended incision and partial resection of the diaphragm were associated with an increased risk of postoperative hernia formation (four of 29 following extended enlargement versus five of 189 after routine opening of the oesophageal hiatus; P = 0·02). Conclusion: Diaphragmatic herniation was found in 4 per cent of patients after oesophagectomy. After extended iatrogenic disruption of the normal hiatal anatomy, narrowing of the diaphragmatic opening may be indicated to avoid postoperative herniation of bowel into the chest. Awareness of its possible occurrence may help prevent the development of intestinal obstruction and strangulation. [ABSTRACT FROM AUTHOR]