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Contains fulltext : 291051.pdf (Publisher’s version ) (Open Access) Conventional esophagogastroduodenoscopy (cEGD) is currently the gold standard endoscopic procedure for diagnosis and surveillance of Barrett's esophagus (BE). This procedure is however less suitable for widespread screening because of its invasiveness and costs. An alternative endoscopic procedure is unsedated transnasal endoscopy (uTNE). We performed a systematic review and meta-analysis to evaluate the diagnostic accuracy, patient tolerability, technical success rate, and safety of uTNE compared with cEGD for detecting BE and related neoplasia. PubMed, EMBASE, and Cochrane Library were searched for studies that reported the diagnostic accuracy of uTNE compared with cEGD for detecting BE and related neoplasia. Eight prospective studies were included, in which 623 patients underwent both uTNE and cEGD. Pooled sensitivity and specificity of uTNE for detecting columnar epithelium were 98% (95% CI 83-100%) and 99% (95% CI 82-100%), respectively. Pooled sensitivity and specificity of uTNE for detecting intestinal metaplasia in biopsies were 89% (95% CI 78-95%) and 93% (95% CI 71-98%), respectively. In three of the six studies that reported patient tolerability, a higher patient tolerability of uTNE compared with cEGD was reported. The technical success rate of uTNE ranged from 89% to 100% and no (serious) adverse events were reported. This systematic review and meta-analysis provides evidence that uTNE is an accurate, safe, and well-tolerated procedure for the detection of columnar epithelium and can be considered as screening modality for BE.

Anastomotic leakage (AL) is a common and severe complication after esophagectomy. It is largely unknown which primary treatments are most effective for which type of leak. We aimed to investigate the effectiveness of different primary treatments of AL. Methods International retrospective cohort study, in which patients with AL after esophagectomy with gastric tube reconstruction were included in the period 2011-2019. Detailed data regarding case mix, resection, leakage characteristics (e.g. organ failure, leak circumference, contamination, drains present) and leakage treatment (e.g. hours from diagnosis to treatment, primary and secondary treatment modalities) were collected. Primary outcome was 90-day mortality and secondary outcomes included length of stay and leak healing time. Different clinically relevant leakage groups have been defined. Efficacy of different treatment strategies adjusted for leakage severity will be analyzed in these clinical groups. The study protocol is accessible at www.tentaclestudy.com. Results Detailed data of 1451 patients with AL was collected from 71 centers in 20 countries. Data accuracy was 96.5%. Preliminary results showed that the overall 90-day mortality was 11.6%. The analysis of TENTACLE—Esophagus data is currently being performed and efficacy of different leakage treatment strategies is being assessed. The efficacy of initial leakage treatment strategies will be ready to be presented at the ISDE meeting. Conclusion This is the largest study on effectiveness of AL treatments. The final results of initial leak treatments, which will be available for presentation at the ISDE meeting, could provide an evidence-based basis that can be used by clinicians to determine the preferred primary treatment strategy in patients with a given type of anastomotic leakage.

Anastomotic leakage (AL) is a common and potentially life-threatening complication after esophagectomy. In patients with AL it is largely unknown which patient parameters and leakage characteristics are associated with leak severity and mortality. We aimed to identify prognostic factors for mortality in patients with anastomotic leakage after esophagectomy. Methods The TENTACLE—Esophagus study is an international retrospective cohort study, in which 1451 patients with AL after esophagectomy between 2011 and 2019 were included in 71 centers from 20 countries. Potential prognostic factors were selected from literature and a hypothetical association with mortality. Confounders of (individual) prognostic factors were identified using a directed acyclic graph approach to minimize bias. Primary outcome was 90-day mortality. Logistic regression analysis was performed to estimate crude and adjusted odds ratios (AOR) and 95% confidence intervals (95%CI). The study protocol is accessible at www.tentaclestudy.com. Results Overall 90-day mortality rate was 11.6%. Leakage characteristics with the largest prognostic effect on mortality were gastric conduit ischemia/necrosis (AOR 2.23, 95%CI 1.43-3.49), defect circumference ≥ 25% (AOR 2.10, 95%CI 1.32-3.36) and intrathoracic fluid collections (drained AOR 1.98, 95%CI 1.05-3.75; undrained AOR 2.43, 95%CI 1.57-3.75). Patient parameters with the largest prognostic effect were ASA-score ≥ 3 (AOR 4.18, 95%CI 1.67-10.51), ECOG-score ≥ 2 (AOR 2.83, 95%CI 1.56-5.14) and respiratory failure (AOR 3.89, 95%CI 2.67-5.66), hemodynamic failure (AOR 3.09, 95%CI 1.96-4.88) or renal failure (AOR 4.08, 95%CI 2.20-7.59) at time of AL diagnosis. Conclusion Defect circumference, intrathoracic fluid collections, gastric conduit condition and several patient parameters were identified as prognostic factors for mortality in patients with AL. Adjusting for these prognostic factors may reduce confounding bias in future studies assessing efficacy of AL treatments. The identified prognostic factors contribute to the understanding of the severity of anastomotic leakage after esophagectomy and may be used to recognize the severity of an anastomotic leak in individual patients.

Geographical variation in cancer care has been observed between and within countries. Variation in treatment may occur at any point along the cancer care continuum attributing to potentially avoidable disparities in patient outcomes such as survival. Other studies have shown a large variation in the proportion of patients undergoing treatment with curative intent for esophageal(EC) and gastric cancer(GC). Due to these studies and thus an increased awareness, we hypothesize that variation has decreased over time. Methods Patients with potentially curable EC (n = 10,115) or GC (n = 3,983) diagnosed between 2012-2017 were selected from the Netherlands Cancer Registry. Multilevel multivariable logistic regression was used to examine the differences in the probability of treatment with curative intent between hospitals of diagnosis, comparing 2012-2014 with 2015-2017. We compared relative survival (RS) and relative excess risk of death (RER) between hospitals with different probabilities of treatment with curative intent. Results The range of proportions of patients undergoing treatment with curative intent per hospital of diagnosis was 45-95% in 2012-2014 and 54-89% in 2015-2017 for EC, and 52-100% and 45-100% for GC. The adjusted variation declined for EC with Odds Ratios (ORs) ranging from 0.50 to 1.72 between hospitals in the first period to 0.70–1.44 in the second period (p Conclusion Although substantial variation between hospitals of diagnosis in the probability in receiving treatment with curative intent still exists for both malignancies, it has decreased for EC, but did not change for GC. A low probability of receiving curative treatment was associated with a worse survival. Further research is needed to elucidate the factors associated with the observed variability.

Contains fulltext : 225282.pdf (Publisher’s version ) (Open Access) Barrett's esophagus (BE) is a metaplastic condition of the distal esophagus, resulting from longstanding gastroesophageal reflux disease (GERD). BE predisposes for the highly malignant esophageal adenocarcinoma (EAC). Both BE and EAC have the highest frequencies in white males. Only a subset of patients with GERD develop BE, while

Aim The aim of this study is to investigate which factors contribute to anastomotic leakage severity and to compose an evidence based anastomotic leakage severity score. Secondly, we aim to investigate which anastomotic leakage characteristics are associated with success of different anastomotic leakage treatments and to compare the effectiveness of different initial anastomotic leakage treatments for anastomotic leakage classified according to severity and leakage characteristics. Background Anastomotic leakage occurs in 0%-30% after esophagectomy for cancer. It is a severe complication with mortality rates approximately ranging from 2%-12%. In addition, it is associated with a prolonged ICU treatment and hospital stay. Anastomotic leakage severity is currently graded according to how it is treated (grade I: conservative treatment, grade II: endoscopic/radiologic intervention and grade III: surgical intervention). However, this scoring system cannot be used to guide decision making when anastomotic leakage is diagnosed in a clinical setting. Factors that may influence the severity of the anastomotic leakage are (amongst others) location of the anastomosis, estimated surface of the defect, estimated circumference of the defect, extent of contamination, degree of sepsis and time from diagnosis until therapy. However, little is known about to what extent these and other factors contribute to anastomotic leakage severity. In addition, there is a paucity of data on what leakage characteristics dictate the success of a specific treatment. Methods We will perform an international multicenter retrospective cohort study. All adult patients with anastomotic leakage according to the ECCG definition after esophagectomy and gastric conduit reconstruction for esophageal cancer are suitable for inclusion. We aim to include at least 1000 patients. The primary outcome parameter is 90-day mortality. Secondary outcome parameters are in-hospital mortality, 30-day mortality, 180-day mortality, comprehensive complications index, total number of reinterventions, hospital and ICU length of stay and hospital related costs. Results Data collection will take place from April 2019 until December 2019. Study results are expected in June 2020. Conclusion We hypothesize that we will be able to identify factors that influence the severity of the anastomotic leakage and to compose a leakage severity score. Furthermore, we expect to identify leakage characteristics dictating the success of a specific treatment.

Esophageal and gastric cancer is associated with a poor prognosis since many patients develop recurrent disease. Treatment requires specific expertise and a structured multidisciplinary approach. In the Netherlands, this type of expertise is mainly found at the University Medical Centers (UMCs) and a few specialized nonacademic centers. Aim of this study is to implement a national infrastructure for research to gain more insight in the etiology and prognosis of esophageal and gastric cancer and to evaluate and improve the response on (neoadjuvant) treatment. Clinical data are collected in a prospective database, which is linked to the patients' biomaterial. The collection and storage of biomaterial is performed according to standard operating procedures in all participating UMCs as established within the Parelsnoer Institute. The collected biomaterial consists of tumor biopsies, blood samples, samples of malignant and healthy tissue of the resected specimen and biopsies of recurrence. The collected material is stored in the local biobanks and is encoded to respect the privacy of the donors. After approval of the study was obtained from the Institutional Review Board, the first patient was included in October 2014. The target aim is to include 300 patients annually. In conclusion, the eight UMCs of the Netherlands collaborated to establish a nationwide database of clinical information and biomaterial of patients with esophageal and gastric cancer. Due to the national coverage, a high number of patients are expected to be included. This will provide opportunity for future studies to gain more insight in the etiology, treatment and prognosis of esophageal and gastric cancer.

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.

Barrett's esophagus (BE) is a metaplastic condition of the distal esophagus that occurs because of chronic gastroesophageal reflux. Previous studies have identified BE-specific microRNAs (miRNAs) in comparison with normal squamous epithelium (SQ). We hypothesized that BE-specific miRNAs could be induced in esophageal SQ cells by exposure to acid and/or bile salts. We aimed to determine whether BE-specific miRNAs are upregulated in an esophageal SQ cell line (Het-1A) in an environment with acid and/or bile salts and whether this is nuclear factor-κB (NF-κB) dependent. Acid and/or bile salt incubations were performed in Het-1A cells. Experiments were performed with or without inhibiting the NF-κB pathway. Quantitative reverse transcriptase polymerase chain reaction was performed to determine expression of miRNA-143, -145, -192, -194, cyclo-oxygenase-2 (COX2), mucin 2 (MUC2), and sex determining region Y-box 9. For validation, we determined levels of these miRNAs in biopsies from patients with reflux esophagitis and normal SQ. Significantly increased expression levels of miRNA-143 (2.7-fold), -145 (2.6-fold), -192 (2.0-fold), -194 (2.2-fold), COX2, MUC2, and sex determining region Y-box 9 were found upon acidic bile salt incubation, but not upon acid or bile salt alone. NF-κB pathway inhibition significantly decreased miRNA-143, -192, -194, COX2, and MUC2 expression. Additionally, miRNA-143, -145 and -194 expression was increased in reflux esophagitis biopsies compared with normal SQ, but no changes were found in miRNA-192 expression. Our findings suggest that upregulation of BE-specific miRNAs by acidic bile may be an early event in the transition of SQ to BE and that their expression is partly regulated by the NF-κB pathway.

Various treatments are available for the palliation of esophageal cancer, but the optimal therapeutic approach is unclear. This study aimed to assess the palliative treatment modalities used in patients with inoperable esophageal cancer and to identify factors associated with treatment decisions. A population-based, retrospective cohort study was conducted using data from the nationwide Netherlands Cancer Registry and medical records of seven participating hospitals. Patients diagnosed with stage III-IV inoperable esophageal or gastric cardia cancer in the central part of the Netherlands between 2001 and 2010 were included. Logistic regression analyses were performed to identify determinants of treatment choices. In total, 736 patients were initially treated with best supportive care (21%), stent placement (19%), chemotherapy (18%), external beam radiotherapy (EBRT) (16%), brachytherapy (6%), a combination of EBRT and brachytherapy (6%), a combination of chemotherapy and EBRT (5%) or another treatment (9%). The palliative approach varied for disease stage (P

SUMMARY Barrett's esophagus (BE) is a premalignant condition with an increased risk of developing esophageal adenocarcinoma (EAC). Risk factors for EAC overlap with those for esophageal squamous cell carcinoma (ESCC), but ESCC is surprisingly rare in BE. We report two cases of ESCC directly surrounded by BE. Both patients had a previous medical history of cancers, i.e., head and neck squamous cell carcinomas, and were using alcohol and smoking tobacco. Using immunohistochemistry for p63, CK5, CK7, and CDX2, it was confirmed that these carcinomas were pure squamous cell carcinomas, and not EACs or esophageal adenosquamous carcinomas arising from BE. Using TP53 mutation and loss of heterozygosity analysis, we established that the ESCCs in BE were not metastases of the previously diagnosed head and neck squamous cell carcinomas but de novo primary ESCCs. This study shows the strength of molecular analysis as an adjunct to the histopathologic diagnosis for distinguishing between metastases of prior cancers and primary cancers. Furthermore, these cases imply that presence of BE is not protective with regards to developing ESCC in the lower one third of the esophagus. We suggest that their ESCCs arose from islets of squamous epithelium in BE.

Background Anastomotic leakage affects up to 30% of patients after esophagectomy each year and leads to considerable morbidity and mortality. The aim of this study was to determine which treatment for anastomotic leakage after esophagectomy has the best clinical outcome, based on currently available literature. Methods A systematic literature search was performed in Medline, Embase and Web of Science until April 2017. All studies reporting on the treatment of anastomotic leakage following esophagectomy with gastric tube reconstruction for esophageal or cardia cancer were included. The primary outcome parameter was postoperative mortality. Methodological quality was assessed by the Newcastle-Ottawa Quality Assessment Scale. Results Nineteen retrospective cohort studies including 273 patients were identified. Methodological quality of all studies was poor to moderate. Regarding intrathoracic anastomotic leakages, mortality rates in the conservative, endoscopic stent, endoscopic drainage, endoscopic vacuum assisted closure system and surgery treatment group were 14%, 8%, 8%, 0%, and 50%, respectively. Regarding cervical anastomotic leakages, mortality rates in the conservative, endoscopic stent and endoscopic dilatation group were 8%, 29%, and 0%, respectively. Conclusion Due to small cohorts, heterogeneity between studies, and lack of data regarding leakage characteristics, no evidence supporting one treatment for anastomotic leakage after esophagectomy was found. A severity score based on leakage characteristics instead of treatment given is essential for determining the optimal treatment of anastomotic leakage. A prospective registration study could provide answers to issues as which leakage characteristics determine its severity and which treatment options have the best outcomes for a given anastomotic leakage severity. Disclosure All authors have declared no conflicts of interest.

Patients with longstanding achalasia have an increased risk of developing esophageal cancer. Surveillance is hampered by chronic stasis. We investigated whether aberrant expressions of tumor suppressor gene p53 and proliferation marker ki67 are early predictors for progression to malignancy. In 399 achalasia patients, 4% died of esophageal cancer despite surveillance. We performed a cohort study, using surveillance biopsies from 18 patients (11 carcinoma, one high-grade dysplasia [HGD], and six low-grade dysplasia [LGD]) and 10 controls (achalasia patients without cancer or dysplasia development). One hundred sixty-four biopsies were re-evaluated and studied for p53 and ki67 expression using immunohistochemistry. Eighty-two percent of patients with cancer/HGD showed p53 overexpression in surveillance biopsies at a mean of 6 (1-11) years prior to cancer development. In 67% of patients with LGD and only in 10% of the controls p53 overexpression was present. The proportion of samples with p53 overexpression increased with increasing grades of dysplasia. We found no difference for ki67 overexpression. p53 overexpression may identify achalasia patients at increased risk of developing esophageal carcinoma. Further study is needed to determine if patients with p53 overexpression would benefit from intensive surveillance to detect esophageal neoplasia at a potential curable stage.

We present two cases of Down syndrome with inoperable esophageal cancer at a relatively young age. The first patient had a locally advanced squamous cell carcinoma of the distal esophagus. The second had a short circular adenocarcinoma of the distal esophagus with peritoneal and liver metastases. The cases are discussed with regard to the current literature on Down syndrome and esophageal cancer. © 2007 The Authors. Journal compilation

In a retrospective study, the results after resection of carcinoma of the gastric cardia in the era without neoadjuvant therapy or extended lymph node dissection were evaluated. All 184 patients who underwent resection between January 1983 and December 1993 were included. Recurrence of disease, survival and prognostic factors were determined. The overall cumulative 5-year recurrence rate was 71% and the survival rate 23%. Multivariate analysis identified locoregional lymph node and distant metastases as the crucial prognosticators of recurrence of disease and survival. These results were similar to those from a previous study concerning our patients operated during the years 1983-88. The prognosis of a resected cardiacarcinoma has remained unchanged in our hands over the past 10 years. These results stress the importance of exploring new ways, such as the use of new diagnostic tools, to optimize preoperative patient selection and more aggressive treatment regimens to improve final outcome.