Accuracy of identification of tissue types in endoscopic esophageal mucosal biopsies used for molecular biology studies

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Chemotherapy followed by surgery versus surgery alone in patients with resectable oesophageal squamous cell carcinoma: Long-term results of a randomized controlled trial

Background: This is a randomized, controlled trial of preoperative chemotherapy in patients undergoing surgery for oesophageal squamous cell carcinoma (OSCC). Patients were allocated to chemotherapy, consisting of 2-4 cycles of cisplatin and etoposide, followed by surgery (CS group) or surgery alone (S group). Initial results reported only in abstract form in 1997, demonstrated an advantage for overall survival in the CS group. The results of this trial have been updated and discussed in the timeframe in which this study was performed.Methods: This trial recruited 169 patients with OSCC, 85 patients assigned to preoperative chemotherapy and 84 patients underwent immediate surgery. The primary study endpoint was overall survival (OS), secondary endpoints were disease free survival (DFS) and pattern of failure. Survival has been determined from Kaplan-Meier curves and treatment comparisons made with the log-rank test.Results: There were 148 deaths, 71 in the CS and 77 in the S group. Median OS time was 16 months in the CS group compared with 12 months in the S group; 2-year survival rates were 42% and 30%; and 5-year survival rates were 26% and 17%, respectively. Intention to treat analysis showed a significant overall survival benefit for patients in the CS group (P = 0.03, by the log-rank test; hazard ratio [HR] 0.71; 95%CI 0.51-0.98). DFS (from landmark time of 6 months after date of randomisation) was also better in the CS-group than in the S group (P = 0.02, by the log-rank test; HR 0.72; 95%CI 0.52-1.0). No difference in failure pattern was observed between both treatment arms.Conclusions: Preoperative chemotherapy with a combination of etoposide and cisplatin significantly improved overall survival in patients with OSCC

Surgical quality and prospective quality control of the D2-gastrectomy for gastric cancer in the multicenter randomized LOGICA-trial

Background: Quality of gastric cancer surgery is crucial for favorable prognosis. Generally, prospective trials lack quality control measures. This study assessed surgical quality and a novel D2-lymphadenectomy photo-scoring in the LOGICA-trial. Methods: The multicenter LOGICA-trial randomized laparoscopic versus open total/distal D2-gastrectomy for resectable gastric cancer (cT1-4aN0-3M0) in 10 Dutch hospitals. During the trial, two reviewers prospectively analyzed intraoperative photographs of dissected nodal stations for quality control, and provided centers weekly feedback on their D2-lymphadenectomy, as continuous quality-enhancing incentive. After the trial, these photographs were reanalyzed to develop a photo-scoring for future trials, rating the D2-lymphadenectomy dissection quality (optimal-good-suboptimal-unevaluable). Interobserver variability was calculated (weighted kappa). Regression analyses related the photo-scoring to nodal yield, recurrence and 5-years survival. Results: Between 2015 and 2018, 212 patients underwent total/distal D2-gastrectomy (n = 122/n = 90), and 158 (75%) received neoadjuvant chemotherapy. R0-resection rate was 95%. Rate of ≥15 retrieved lymph nodes was 95%. Moderate agreement was obtained in stations 8 + 9 (κ = 0.522), 11p/11d (κ = 0.446) and 12a (κ = 0.441). Consensus was reached for discordant cases (30%). Stations 8 + 9, 11p/11d and 12a were rated ‘optimal’ in 76%, 63% and 68%. Laparoscopic photographs could be rated better than open (2% versus 12% ‘unevaluable’; 73% versus 50% ‘optimal’; p = 0.042). The photo-scoring did not show associations with nodal yield (p = 0.214), recurrence (p = 0.406) and survival (p = 0.988). Conclusions: High radicality and nodal yield demonstrated good quality of D2-gastrectomy. The prospective quality control probably contributed to this. The photo-scoring did not show good performance, but can be refined. Laparoscopic D2-gastrectomy was better suited for standardized surgical photo-evaluation than open surgery.</p

Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus.

BACKGROUND & AIMS: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations. METHODS: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls. RESULTS: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)). CONCLUSIONS: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response

Submucosal invasion and risk of lymph node invasion in early Barrett's cancer : potential impact of different classification systems on patient management

BACKGROUND: Due to the high mortality and morbidity rates of esophagectomy, endoscopic mucosal resection (EMR) is increasingly used for the curative treatment of early low risk Barrett's adenocarcinoma. OBJECTIVE: This retrospective cohort study aimed to assess the prevalence of lymph node wmetastases (LNM) in submucosal (T1b) esophageal adenocarcinomas (EAC) in relation to the absolute depth of submucosal tumor invasion and demonstrate the efficacy of EMR for low risk (well and moderately differentiated without lymphovascular invasion) EAC with sm1 invasion (submucosal invasion ≤500 µm) according to the Paris classification. METHODS: The pathology reports of patients undergoing endoscopic resection and surgery from January 1994 until December 2013 at one center were reviewed and 54 patients with submucosal invasion were included. LNM were evaluated in surgical specimens and by follow up examinations in case of EMR. RESULTS: No LNM were observed in 10 patients with sm1 adenocarcinomas that underwent endoscopic resection. Three of them underwent supplementary endoscopic eradication therapy with a median follow up of 27 months for patients with sm1 tumors. In the surgical series two patients (29%) with sm1 invasion according to the pragmatic classification (subdivision of the submucosa into three equal thirds), staged as sm2-3 in the Paris classification, had LNM. The rate of LNM for surgical patients with low risk sm1 tumors was 10% according to the pragmatic classification and 0% according to Paris classification. CONCLUSION: Different classifications of the tumor invasion depth lead to different LNM risks and treatment strategies for sm1 adenocarcinomas. Patients with low risk sm1 adenocarcinomas appear to be suitable candidates for EMR

miR-200 family expression is downregulated upon neoplastic progression of Barrett’s esophagus

AIM: To investigate miR-200 family expression in Barrett’s epithelium, gastric and duodenal epithelia, and esophageal adenocarcinoma

The effectiveness of neoadjuvant chemoradiotherapy in oesophageal adenocarcinoma with presence of extracellular mucin, signet-ring cells, and/or poorly cohesive cells

Oesophageal adenocarcinomas may show different histopathological patterns, including excessive acellular mucin pools, signet-ring cells (SRCs), and poorly cohesive cells (PCCs). These components have been suggested to correlate with poor outcomes after neoadjuvant chemoradiotherapy (nCRT), which might influence patient management. However, these factors have not been studied independently of each other with adjustment for tumour differentiation grade (i.e. the presence of well-formed glands), which is a possible confounder. We studied the pre- and post-treatment presence of extracellular mucin, SRCs, and/or PCCs in relation to pathological response and prognosis after nCRT in patients with oesophageal or oesophagogastric junction adenocarcinoma. A total of 325 patients were retrospectively identified from institutional databases of two university hospitals. All patients were scheduled for ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) nCRT and oesophagectomy between 2001 and 2019. Percentages of well-formed glands, extracellular mucin, SRCs, and PCCs were scored in pre-treatment biopsies and post-treatment resection specimens. The association between histopathological factors (≥1 and >10%) and tumour regression grade 3-4 (i.e. >10% residual tumour), overall survival, and disease-free survival (DFS) was evaluated, adjusted for tumour differentiation grade amongst other clinicopathological variables. In pre-treatment biopsies, ≥1% extracellular mucin was present in 66 of 325 patients (20%); ≥1% SRCs in 43 of 325 (13%), and ≥1% PCCs in 126 of 325 (39%). We show that pre-treatment histopathological factors were unrelated to tumour regression grade. Pre-treatment presence of >10% PCCs was associated with lower DFS (hazard ratio [HR] 1.73, 95% CI 1.19-2.53). Patients with post-treatment presence of ≥1% SRCs had higher risk of death (HR 1.81, 95% CI 1.10-2.99). In conclusion, pre-treatment presence of extracellular mucin, SRCs, and/or PCCs is unrelated to pathological response. The presence of these factors should not be an argument to refrain from CROSS. At least 10% PCCs pre-treatment and any SRCs post-treatment, irrespective of the tumour differentiation grade, seem indicative of inferior prognosis, but require further validation in larger cohorts

FA01.02: THE EFFECT OF POSTOPERATIVE COMPLICATIONS AFTER MIE ON LONG-TERM SURVIVAL: A RETROSPECTIVE, MULTI-CENTER COHORT STUDY.

Background: Esophagectomy has a high incidence of postoperative morbidity. Complications lead to a decreased short-term survival, however the influence of those complications on long-term survival is still unclear. Most of the performed studies are small, single center cohort series with inconclusive or conflicting results. Minimally invasive esophagectomy (MIE) has been shown to be associated with a reduced postoperative morbidity. In this study, the influence of complications on long-term survival for patients with esophageal cancer undergoing a MIE were investigated. Methods: Data was collected from the EsoBenchmark database, a collaboration of 13 high-volume centers routinely performing MIE. Patients were included in this database from June 1, 2011 until May 31, 2016. Complications were scored according to the Clavien-Dindo (CD) classification for surgical complications. Major complications were defined as a CD grade ≥ 3. The data were corrected for 90-day mortality to correct for the short-term effect of postoperative complications on mortality. Overall survival was analyzed using the Kaplan Meier, log rank- and (uni- and multivariable) Cox-regression analyses. Results: A total of 926 patients were eligible for analysis. Mean follow-up time was 30.8 months (SD 17.9). Complications occurred in 543 patients (59.2%) of which 39.3% had a major complication. Anastomotic leakage (AL) occurred in 135 patients (14.5%) of which 9.2% needed an intervention (CD grade ≥ 3). A significant worse long-term survival was observed in patients with any AL (HR 1.73, 95% CI 1.29-2.32, P < 0.001) and for patients with AL CD grade ≥3 (HR 1.86, 95% CI 1.32-2.63, P < 0.001). Major cardiac complications occurred in 18 patients (1.9%) and were related to a decreased long-term survival (HR 2.72, 95% CI 1.38-5.35, p 0.004). For all other complications, no significant influence on long-term survival was found. Conclusion: The occurrence and severity of anastomotic leakage and cardiac complications after MIE negatively affect long-term survival of esophageal cancer patients. Disclosure: All authors have declared no conflicts of interest.status: publishe