bluuebunny/crossref_metadata_2025 huggingface dataset:
562 THE EFFECT OF IONISING-RADIATION AND THE TUMOUR MICRO-ENVIRONMENT (TME) ON TREATMENT NAIVE ESOPHAGEAL ADENOCARCINOMA PATIENT T CELL FUNCTION AND ACTIVITY.
Authors: Donlon N , Sheppard A , Davern M , Donohoe C , Ravi N , Reynolds J , Lysaght J
Published: September 2020

There is extensive literature demonstrating CD8+ T cells are essential for initial tumour control following radiation, however, effects are reduced after time due to T cell exhaustion and a lack of release Damage Associated Molecular Patterns (DAMPS) which are essential for anti-tumour immune responses. In vivo, activated T-cells migrate to the tumour site within the field of irradiation, however translational studies on the effects of radiotherapy on T-cell activation, function and activity are lacking.

Methods

EAC patient (n = 6) PBMCs were isolated by density centrifugation in Ficoll Paque. T cells were activated and were irradiated at 1.8Gy, 3.6Gy bolus dosing and fractionation for 72 hrs. A panel of immune checkpoints, DAMPS, activation markers, and cytokines were assessed by flow cytometry. To determine the effect of the TME on T cells, PBMCs were cultured under conditions of nutrient deprivation (No Glucose & No Glutamine) under conditions of normoxia and hypoxia. We then ran the aforementioned panel by flow cytometry. We also activated PBMCs with immune checkpoint blockers to determine its effects on T cell expansion and survival.

Results

3.6Gy induced a significantly higher expression of DAPMS (Fig 1 p < 0.001); Calreticulin and HMGB1, most notably under conditions of nutrient deprivation (p < 0.001). Ionising radiation also resulted in an increase in the expression of cytokines and importantly in the context of targeted therapy, IR at both the conventional 1.8Gy and 3.6Gy induced a higher expression of checkpoints PD-1, PD-L1, TIGIT, and TIM-3 (p < 0.001). Interestingly, when T cells are activated in the presence of ICB (Atezolizumab, Pembrolizumab, Nivolumab), it increases the rate of T cell expansion, and enhances their survival compared to T cell activated only. (p < 0.001).

Conclusion

This work demonstrates the impact of clinically utilised fractions of radiation, and conditions of the TME on T cell function and activity, with improved T cell expansion and survival in the presence of ICB’s suggesting it may be a feasible combination therapy as an adjunct to radiotherapy.
82 POSSIBLE NOVEL BIOMARKER OF ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Saito R , Maruyama S , Shoda K , Kawaguchi Y , Akaike H , Yamamoto A , Takiguchi K , Furuya S , Hosomura N , Amemiya H , Sudo M , Kawaida H , Kono H , Ichikawa D
Published: September 2020

Recently, patients with esophageal squamous cell carcinoma (ESCC) have been treated with combination therapy, including surgical resection, chemotherapy, and/or radiation therapy. Therefore, the development of novel and useful biomarkers is expected because the malignant behavior of tumors and the treatment effect vary in each case. In this study, we examined the clinical significance of microRNA-X (miR-X) as a biomarker because it has been reported in studies that examined ESCC cell-lines in vitro.

Methods

In all, 81 consecutive patients who underwent radical esophagectomy without preoperative treatment for ESCC were examined. Total RNA was extracted from formalin-fixed paraffin-embedded samples and miR-X expression levels were evaluated. In this process, the miR-X levels were standardized against the RNU6B expression levels and were analyzed using the ΔΔCq method. Clinicopathological features between high and low expression groups of miR-X were compared using the median expression level as the cutoff value. Prognostic analyses were performed using several factors, including miR-X expression levels, to gage the cancer-specific (CSS) and recurrence-free survival (RFS) of these patients.

Results

High miR-X expression was found to be significantly related to deep invasion (p < 0.001) and high vascular invasion (p < 0.001). Prognostic analyses demonstrated the suitability of miR-X expression as a significant adverse prognostic factor both in cancer-specific and recurrence-free survival (p = 0.006 & p = 0.004, respectively) of patients. Multivariate analysis using factors such as T- and N-factors, tumor size and miR-X expression levels indicated that the miR-X level was an independent prognostic factor as well as T- factor (CSS, hazard ratio: 2.263, p = 0.034), and T- and N-factors (RFS, hazard ratio: 2.22, p = 0.033).

Conclusion

The present study revealed that high miR-X expression was related to deep invasion and high vascular invasion in ESCC. It was also independent adverse prognostic factor for patients with ESCC. Detailed examination including in vitro re-verification is required because these results were inconsistent with previous reports and miR-X might play different roles in clinical settings. In any case, further detailed studies might establish the significance of miR-X as a novel and useful biomarker of ESCC.
120 LYMPHADENECTOMY ALONG THE LEFT RECURRENT LARYNGEAL NERVE AFTER ESOPHAGEAL STRIPPING.
Authors: Makino H , Nomura S , Maruyama H , Yokoyama T , Hirakata A , Takata H , Kogo H , Iwai T , Yoshioka M , Yoshida H
Published: September 2020

The working space in the upper mediastinum is limited and lymphadenectomy along the left recurrent laryngeal nerve is difficult and anastomosis by a circular stapler in the narrow neck field is also difficult in VATS-E. We report our technique of the lymphadenectomy along the left recurrent laryngeal nerve.

Methods

(1) Patients.

One hundred forty seven patients with esophageal carcinomas underwent VATS-E.

(2) Methods.

i) VATS-E in prone position.

Esophagectomy is performed in prone position with 5 ports those are used at the intercostal space (ICS) and pneumothorax by maintaining CO2 insufflation.

ii) Lymphadenectomy around left recurrent laryngeal nerve.

Working space at the left upper mediastinal area for lymphadenectomy around the recurrent laryngeal nerve is limited in prone position. To obtain the space the residual esophagus is stripped in the reverse direction and retracted toward the neck after the stomach tube is removed through the nose.

Results

1. The rate of permanent and transient recurrent laryngeal nerve paralysis were 2.6% and 20%, respectively.

2. The rate of anastomotic leak and postoperative pneumonia was 3.9% and 2.9%.

Conclusion

Lymphadenectomy along the left recurrent laryngeal nerve after esophageal stripping is available in prone position of VATS-E.
135 ACCURACY OF ACHALSIA QUALITY OF LIFE AND ECKARDT SCORES FOR ASSESSMENT OF CLINICAL IMPROVEMENT POST TREATMENT FOR ACHALASIA
Authors: Slone S , Richter J , Kumar A , Velanovich V , Jacobs J
Published: September 2020

Achalasia Quality of Life (ASQ) and Eckardt scores are two patient-reported instruments used to assess symptom severity in achalasia patients. ASQ is validated and reliable. Although Eckardt is commonly used, it has not been assessed for validity or reliability. Our aims were to evaluate 1) the accuracy of both instruments for assessing improvement post-treatment (predictive validity) with pneumatic dilatation versus surgical myotomy and 2) convergent validity of both tools.

Methods

Patients with achalasia treated between 2011–2018 were eligible. Both instruments were administered by telephone. Treatment failure was determined by review of medical records by two clinicians. The predictive ability of ASQ and Eckardt instruments in identifying treatment successes and failures was determined using receiver operating characteristics analysis and summarized as Area Under the Curve (AUC).

Results

106 patients met inclusion criteria with 44 PD, 52 Heller Myotomy, and 10 per-oral endoscopic myotomy. A review of medical records and esophageal testing defined 13 failures (13%). AUC for Eckardt was 0.96 [95% CI 0.87–0.99] and ASQ 0.97 [95% CI 0.92–0.99]. The Eckardt cutoff 4, and ASQ, cutoff 15, were 94% and 87% accurate in identifying treatment successes versus failures. The correlation coefficient between the two tools was 0.84.

Conclusion

1) ASQ and Eckardt scores are valid and reliable tools to assess symptom severity in achalasia patients; 2) Both instruments accurately classify treatment successes versus failures. 3) The choice of tool should be informed by the physicians’ and patients’ values and preferences and repeat physiologic testing may be reserved for treatment failures with either instrument and patients classified as treatment successes may be spared routine physiologic testing in the long term.
147 EFFECTIVE UNDERWATER ENDOSCOPIC SUBMUCOSAL DISSECTION FOR A SUPERFICIAL CERVICAL ESOPHAGEAL CANCER
Authors: Sasaki S , Ishigaki N , Harada T , Hanada H
Published: September 2020

Underwater method is now mainly used in endoscopic mucosal resection of colorectal and duodenal lesions based on the fact that mucosa and submucosa float into the lumen moving away from the muscularis propria after filling with water without submucosal injection. We performed underwater endoscopic submucosal dissection (ESD) for a cervical esophageal lesion.

Methods

Case report.

Results

An 81-year-old man with a history of drinking and smoking underwent endoscopy, revealing a 1/3 round superficial cancer in the cervical esophagus. ESD was performed under general anesthesia and tracheal intubation. The lumen was so narrow from natural constriction that a good view could not be secured under CO2 insufflation. Therefore, we tried the underwater method. As the lumen was expanded by filling with 0.9% saline solution, it was possible to secure a visual field. Because the submucosal layer floated up underwater, a circumferential incision and submucosal dissection were completed easily and quickly.

Conclusion

Endoscopic resection for lesions within a physiologic narrow space is difficult. The underwater method is reported to be useful for treatment of rectal tumors near the dentate line and cecal tumors in the appendiceal orifice. We found that the underwater method made ESD for the cervical esophageal cancer even easier by securing a good view. To our knowledge, this is the first report of underwater ESD for a cervical esophageal cancer.
160 SURVIVAL ANALYSIS OF 18F-FDG PET/CT QUANTITATIVE PARAMETERS MEASURED IN PRIMARY TUMOR AND SUSPICIOUS LYMPH NODES IN PATIENTS WITH ESOPHAGEAL CARCINOMA
Authors: Tustumi F , Takeda F , Duarte P , Albenda D , Sallum R , Ribeiro Junior U , Buchpiguel C , Cecconello I
Published: September 2020

18F-FDG PET/CT quantitative techniques have been described as prognostic indicators in esophageal cancer. Objective: To evaluate the prognostic value of the maximal Standardized Uptake Value (SUVmax), the Metabolic Tumor Value (MTV) and the Total Lesion Glycolysis (TLG) measured in the primary tumor and in the suspicious lymph node.

Methods

A cohort study was performed to assess the association of SUVmax, MTV and TLG measured prior and post to neoadjuvant therapy, as well as the variation of these values between the two studies, with overall survival (OS) in patients with esophageal cancer submitted to trimodal therapy. The quantitative techniques were applied in the primary tumor (PT) and in the suspicious nodes (LN) by a nuclear medicine physician. The OS rates were analysed. Before neoadjuvant therapy, 106 patients had PET/CT, and 39 patients had post neoadjuvant PET/CT exams.

Results

Before neoadjuvant period all the variables related to LN were able to predict OS. MTV of primary (HR: 1.89; 95%CI: 1.01–3.52) tumor were also able to predict OS. On post neoadjuvant period and the variation pre-to-post neoadjuvant periods, none of the PET/CT variables related to LN were related to prognosis. All primary tumor volumetric variables were related to OS. MTV (HR: 4.66; 95%CI: 1.54–14.08) and TLG (HR: 4.86; 95%CI: 1.66–14.26) of PT of post neoadjuvant period; and the variation of MTV (HR: 2.95; 95%CI: 1.01–3.52) and TLG (HR: 3.49; 95%CI: 1.01–3.52) of the PT pre-to-post neoadjuvant periods were prognostic variables.

Conclusion

In patients with esophageal cancer, the burden of disease in the suspicious nodes and primary tumor prior to therapy and the residual burden of disease in PT in post therapy 18F-FDG PET/CT were associated with dismal prognosis.
163 TRANSHITAL ESOPHAGECTOMY IN THE TREATMENT OF ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Kruel C , Vieira F , Schramm R , Chedid M , Rosa A , Vieira A
Published: September 2020

In the state of Rio Grande do Sul, Brazil, it is encountered a very high incidence of. esophageal squamous cell carcinoma in the world.(1). Advances in surgical procedure techniques and. postoperative treatment have arisen in esophagectomy, which remains as with significant morbidity. and mortality. Compared to other esophagectomies. conducted with thoracotomy, such as Ivor-Lewis and McKeown techniques, the Transhiatal. esophagectomy has a shorter surgical time, a lower rate of mediastinitis and then lower morbidity.

Methods

Ninety-six patients undergoing transhiatal esophagectomy in the Hospital de Clínicas de Porto Alegre, between 2005 and 2017 were evaluated. Thirteen patients underwent neoadjuvant treatment with chemoradiotherapy. Ninety-day survival and 5-year survival were evaluated.

Results

Overall 90-day survival was 91.7%. The overall 5-year survival was 41.2%. Patients undergoing neoadjuvant therapy had a 90-day survival of 100% and a 5-year survival of 74.1%. Patients undergoing frontline esophagectomy had a 90-day survival of 90.3% and 5-year survival rate of 36%. Non-neoadjuvant patients with negative lymph nodes had a 5-year survival of 50.2%. The average surgical time was 253 minutes. Thirty-seven patients (38.5%) had positive lymph nodes in the surgical specimen. Multivariate analysis showed that surgical time and presence of positive lymph nodes are associated with a worse outcome.

Conclusion

Patients submitted to transhiatal esophagectomy present considerable long-term survival, which can be amplified in the absence of lymph node involvement. Operated patients who have undergone neoadjuvant therapy prior to surgery demonstrate increased survival times compared with those without treatment.

References

1) Corley DA, Buffler PA. Oesophageal and gastric cardia adenocarcinomas: analysis of regional variation using the Cancer Incidence in Five Continents database. Int J Epidemiol. 2001 Dec;30(6):1415–25.
179 FEASIBILITY AND ONCOLOGICAL OUTCOME OF CHEMORADIATION WITH INTENSIFIED IMRT IN LOCALLY ADVANCED ESOPHAGEAL CANCER
Authors: Innocente R , Navarria F , Petri R , Palazzari E , Gigante M , Vecchiato M , Ziccarelli A , Martino A , Foltran L , Buonadonna A , Lo Re G , Spina M , Ubiali P , Tonin D , Lauretta A , Polesel J , Franchin G , De Paoli A
Published: September 2020

To assess safety, feasibility and efficacy of an intensified preoperative IMRT and concomitant carboplatin and paclitaxel-based chemotherapy (Carbo/Tax CT) in patients (pts) with locally advanced esophageal cancer (LAEC) treated at our Institution.

Methods

a retrospective analysis of toxicity (CTCAE 4.03), progression free survival (PFS) and overall survival (OS) of pts affected by LAEC, treated with preoperative intensified radiotherapy (IMRT) and weekly concurrent carboplatin and paclitaxel-based chemotherapy (CT) according to the CROSS trial, between February 2016 and October 2019, at the Centro di Riferimento Oncologico, Aviano (CRO).

Results

Sixty-nine consecutive pts, 57(82.6%) males, were treated. The median age was 69 yrs (38–85), the ECOG PS 0–2. All pts underwent concurrent chemoradiotherapy, IMRT technique, 45 Gy/25 to PTV1 (primary tumor volume + regional nodes), a simultaneous boost from 52.5Gy to 54Gy to PTV2 (gross tumor volume) and weekly concurrent carboplatin (AUC2) and paclitaxel (50 mg/m2). Induction CT was administered to 17 pts. All pts completed RT with median 4 (1–5) CT cycles. Median follow-up was 8 months (4–17); 2-yr PFS and OS were 49.0% and 80.3%, respectively. At 2 yrs, local recurrence rate was 8.4% (CI 95%: 2.6%–18.8%).

Conclusion

Preoperative intensified IMRT with concomitant Carbo/Tax CT in pts with LAEC appears safe and feasible with promising oncological outcome and needs to be confirmed in a larger series of pts.
184 WHICH ROUTE FOR ESOPHAGEAL RECONSTRUCTION WHEN NONE IS FEASIBLE?
Authors: De Malleray H , Hubaud V , Bottet B , Brioude G , Trousse D , Thomas P , D'journo X
Published: September 2020

Which route for esophageal reconstruction when none is feasible?

Methods

What is in the video: this 3-minute video describes a challenging case of a complex esophageal reconstruction for a giant trachea-esophageal fistula in a patient with severe comorbidities and a radiation-induced mediastinal fibrosis. We depict the technical aspect of a presternal gastric by-pass covering with a pediculized myocutaneous latissimus dorsi flap.

Results

Why this video is important for the congress: this video exposes the surgical dilemma of the route of reconstruction for digestive continuity when none of traditional routes are allowed: 1) posterior mediastinum route forbidden because of post-radiation mediastinal fibrosis; 2) retrosternal route prohibited by a previous coronary artery by-pass; 3) subcutaneous route not feasible because of severe sternal radiodermatis.

Conclusion

In conclusion, our case shows that covering the presternal digestive interposition with a locoregional pediculized myocutaneous flap is a valid alternative when others routes have been eliminated.

Video

https://drive.google.com/open?id=1SXueOktZU15N8GgG324KJJb1SF-XqPym
203 RISK AND PROTECTIVE FACTORS OF GASTROESOPHAGEAL REFLUX DISEASE AFTER PERORAL ENDOSCOPIC MYOTOMY
Authors: Fukushima N , Masuda T , Yano F , Tsuboi K , Hoshino M , Yamamoto S , Akimoto S , Sakashita Y , Omura N , Mitsumori N , Kashiwagi H
Published: September 2020

Peroral endoscopic myotomy(POEM)has been reported as safe and effective treatment for achalasia. This procedure is proposed to be a less invasive alternative to conventional laparoscopic Heller-myotomy with Dor-fundoplicatin(LHD), previous studies have shown that POEM may result in a higher incidence of gastroesophageal reflux disease(GERD)compared with LHD. However, certain predictors of GERD after POEM remain unstudied limiting current treatment strategy of achalasia. The aim of this study is to clarify the protective factors of GERD post-POEM.

Methods

Fifty-one patients who underwent POEM at our institution between January 2016 and December 2019 were included. We performed esophagogram and high-resolution esophageal manometry (HRM) as a part of preoperative evaluation. Upper gastrointestinal endoscopy has been assessed 3 months, 1 year, and then yearly after POEM. Patients were divided into two groups based on post-POEM endoscopic findings: GERD group (patients who had esophagitis [n = 28; median age 53 years with 18 male]) and non-GERD group (patients who did not have GERD [n = 23; median age 50 years with 14 male]). We compared preoperative foregut tests between the two groups.

Results

Twenty-eight out of 51 patients (54.9%) developed esophagitis. There were no differences in age, sex, BMI, and findings of esophagogram between the groups. Based on HRM test, greater overall lower esophageal sphincter (LES) length was noted in the non-GERD group compared with the GERD group (3.0 vs. 2.6 cm, p = 0.034). Length of gastric myotomy was comparable between the GERD and non-GERD groups (2.0 vs. 3.0 cm, p = 0.477). Similar incidence of esophagitis was evident in patients who had a history of prior LHD and those who underwent POEM as a primary intervention (60% [9/15 patients] vs. 52.8% [19/36 patients], p = 0.437).

Conclusion

Shorter overall LES length appears to be associated with esophagitis post-POEM. Length of gastric myotomy did not correlate to GERD in the study cohort. Prior Dor fundoplication may not avert development of GERD after POEM. Further study is warranted.
257 CHEMORADIOTHERAPY FOLLOWED BY ACTIVE SURVEILLANCE VERSUS SURGERY FOR ESOPHAGEAL CANCER: A SYSTEMATIC REVIEW AND INDIVIDUAL PATIENT DATA META-ANALYSIS
Authors: Van Der Wilk B , Eyck B , Hofstetter W , Ajani J , Piessen G , Castoro C , Alfieri R , Kim J , Kim S , Furlong H , Walsh T , Nieboer D , Wijnhoven B , Lagarde S , Lanschot J
Published: September 2020

Up to 50% of patients with esophageal cancer have a pathologically complete response after neoadjuvant chemoradiotherapy (nCRT) plus surgery. An active surveillance strategy may be feasible in patients with a complete clinical response (cCR) after nCRT. The aim of this study was to perform a meta-analysis using data of individual patients that underwent active surveillance with surgery for recurrent disease versus standard surgery after nCRT.

Methods

A systematic search was performed in Embase, Medline, Web of Science, Scopus and Cochrane from inception to February 2020. Studies were sought that reported on overall survival and recurrence rates in patients with cCR after nCRT that underwent active surveillance versus standard surgery. Authors were contacted to supply individual patient data. Pooled hazard ratio (HR) comparing survival outcomes and distant dissemination rates (DDR) between patients with cCR undergoing active surveillance or standard surgery were estimated using a random-effect meta-analysis. Cumulative incidence of locoregional recurrences in active surveillance were assessed using a Cox Frailty model.

Results

Seven studies including 788 patients (256 active surveillance and 532 surgery) were identified. All authors provided anonymized patient data. Pooled two- and five-year overall-survival was 75% and 58% for active surveillance and 76% and 60% for standard surgery with a pooled HR of 1.04 (95%CI:0.73–1.49) (Figure 1). Two-years DDR was 18% and 19% for active surveillance and standard surgery, respectively (HR 1.10,95%CI:0.75–1.63). Locoregional recurrence rate necessitating esophagectomy in patients undergoing active surveillance was 24% at one year, 33% at two years and 38% at five years. Active surveillance patients undergoing postponed surgery had R0 in 91% of cases.

Conclusion

Overall survival is comparable in patients undergoing active surveillance with postponed surgery compared to standard surgery after neoadjuvant chemoradiation. Distant dissemination rate is also comparable between both groups. During active surveillance, local regrowths developing after two years are rare. Although these data support an active surveillance strategy, randomized trials have to be completed before an active surveillance strategy can be actively proposed to patients with esophageal cancer.
259 FEATURES PREDICTING WORSE POSTOPERATIVE HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH ESOPHAGEAL CANCER: RESULTS FROM THE CROSS-TRIAL
Authors: Van Der Wilk B , Eyck B , Timman R , Kranenburg L , Lagarde S , Wijnhoven B , Busschbach J , Lanschot J
Published: September 2020

Currently, trials are investigating active surveillance in esophageal cancer compared to standard esophagectomy after neoadjuvant chemoradiotherapy (nCRT). If non-inferiority is reported, on patients the choice will be imposed choice between active surveillance or immediate esophagectomy. The aim of this study was to identify clinical- and tumor characteristics that are predictive for a worse health-related quality of life (HR-QoL) after esophagectomy.

Methods

HR-QoL was measured using EORTC-QLQ-C30 and QLQ-OES24 questionnaires prior treatment and three, six, nine and twelve months postoperatively. Subgroups were predefined from patients with different clinical (global HR-QoL, WHO-status) and tumor characteristics (histology, disease stage and location of the tumor). High and low global HR-QoL were defined as global health scores ≥75 and < 75, respectively. Cohen’s d effect-sizes were determined, 0.5–0.8 was considered a medium and > 0.8 considered a large effect. The primary endpoints were physical functioning and eating problems. Secondary endpoints were global HRQOL, fatigue and emotional problems. Exploratory, the effect of age and gender on HR-QoL was assessed.

Results

In total, 363 patients received HR-QoL questionnaires. Patients who reported a high global HR-QoL prior treatment had a significantly worse deterioration in HR-QoL after esophagectomy than patients who reported a low HR-QoL prior treatment, on all endpoints except for physical functioning. Corresponding Cohen’s d scores were 0.85 for eating problems, −1.25 for global HR-QoL, 0.75 for fatigue and 0.65 for emotional problems. No additional differences between subgroups were identified. All predefined subgroups had impaired HR-QoL up to twelve months postoperatively for both physical functioning and fatigue with a medium to large Cohen’s d effect size.

Conclusion

Patients reporting high global HR-QoL prior treatent have worse deteriotation in HR-QoL than patients reporting low global HR-QoL prior treatment. No additional characteristics were identified that were predictive for worse HR-QoL after esophagectomy. This emphazises the need for shared-decision making in case active surveillance proves non-inferior compared to standard esophagectomy. All subgroups had deterioration in physical functioning and eating problems up to twelve months postoperatively.
273 PREDICTORS OF RESPONSE TO PPI THERAPY: REAL CLINICAL PRACTICE DATA FROM RUSSIAN FEDERATION
Authors: Bakulin I , Bordin D , Bakulina N , Zhuravleva M , Skazyvaeva E , Skalinskaya M , Ponomarenko E
Published: September 2020

The first-line medical therapy for GERD is commonly PPI. However, clinical practice data showed that about half of patients were refractory to PPI. In 20–50% of cases symptoms of GERD and/or endoscopic lesions of esophagus mucosa persisted during treatment with PPI for 8 weeks. The aim of the study was to identify predictors of the response to PPI therapy in patients with GERD according to the data of real clinical practice of Russian megalopolises.

Methods

The study included 1433 patients with GERD from Moscow, Moscow region and St. Petersburg. There were 595 (42%) men and 838 (58%) women with the average age 48 ± 16 years (from 7 to 91 years). The study design included 3 visits with an interval of 4 weeks, during which complaints and anamnestic data were gathered, anthropometry, upper endoscopy, tests for H. pylori infection and adherence evaluation were performed. For anti-secretory effect rabeprazole was prescribed for most of the patients (n = 1333, 96%). The obtained data were analyzed by SPSS.

Results

The proportion of patients with overweight and obesity dominated (904; 62.7%). In 614 (47.8%) patients EE was found, in 618 (48.1%)—NERD. In patients with EE infected with H. pylori, B-D grades were observed 1.3 times more often than in patients without H. pylori (p < 0.05, 95% CI = 1.02–1.54). The clinical symptoms were more pronounced in patients with obesity and current smokers (p < 0.05). The lowest percentage of mucous healing after 4 weeks of PPI therapy was observed in patients with EE grade D. In 95% patients with high adherence to PPI therapy clinical remission was achieved.

Conclusion

The prevalence of two main GERD phenotypes—EE and NERD—were approximately equal in the population of Russian megalopolises patients. The predictors of response to PPI therapy were normal BMI and WC, non-smoking, mild grade of EE, the choice of rabeprazole among PPI, 8-week duration of PPI treatment and high patients’ adherence to the PPI therapy.
276 SCRNA SEQUENCING OF SINGLE EAC ORGANOID REVEALS HETEROGENEITY OF STEM CELL LIKE POPULATIONS
Authors: Derouet M , Wilson G , Darling G , Yeung J
Published: September 2020

Tumor heterogeneity is one of the main contributor of poor response to treatment and metastasis. Esophageal adenocarcinoma (EAC) is known to be second only to melanoma in terms of heterogeneity. Robust in vitro models of EAC are lacking. In our patient derived organoid (PDO) culture, we identified different organoid morphologies from the same patient. We decided to investigate the transcriptional programs of the different organoid morphologies.

Methods

EAC organoids were established from endoscopic biopsies from 4 different patients. Based on their morphology, individual organoids were isolated and dissociated into single cell suspensions. The 10X Genomics platform was used for single cell RNA sequencing.

Results

The two morphologies identified by histology were cystic and intestinal. For the two intestinal populations the samples could be divided into stem-like (905/1646 and 1472/1926) and differentiated populations. Interestingly, we observed differences in the number of cycling cells in these Lgr5+ stem-like populations (905/905 and 337/1926). For the cystic samples the two populations could also be divided into stem-like populations (758/923 and 284/784) and differentiated populations. We also observed cell cycle differences in the Lgr5+ stem-like populations in these samples. RNA velocity analyses on each sample verified a differentiation trajectory from the stem-like to the differentiated cells.

Conclusion

Studying EAC organoids provides us with the ability to profile the transcriptional programs of progenitor-like cells, which are difficult to isolate from gross tumor. We demonstrate that we can isolate individual organoids and study them at single-cell resolution to evaluate the different types of organoid generating cells based on their morphology.
299 EXAMINATION OF ALBUMIN/GLOBULIN RATIO IN ESOPHAGEAL CANCER
Authors: Okubo T , Ogawa R , Hayakawa S , Sagawa H , Tanaka T , Takahashi H , Matsuo Y , Takiguchi S
Published: September 2020

Albumin and globulin make up the majority of serum proteins and are strongly involved in inflammation. In recent years, reports on cancer and inflammation have been scattered, and there are reports indicating that the albumin / globulin ratio (A/G ratio) may be a predictor of prognosis in patients with cancer. Here, we examined the A/G ratio and clinicopathological factors in curative cases of esophageal cancer.

Methods

A retrospective study was conducted on 122 patients who underwent radical surgery for esophageal cancer in our department from January 2013 to December 2017. We analyzed the correlation between A/G ratio and blood biochemical test values, and the relationship between postoperative complications and prognosis. With respect to prognosis, the cut-off value was set to 1.6 from the ROC curve, and divided into a high-value group and a low-value group, and comparatively examined.

Results

There were 106 males and 16 females. The median age at surgery was 69 years. Neoadjuvant chemotherapy was performed in 65 patients. A negative correlation was found between the A/G ratio and inflammatory markers. On the other hand, a positive correlation was observed between the A/G ratio and the value of a marker for nutritional indicators. In the prognostic study, the low-value group had a significantly worse prognosis than the high-value group. The group with an A/G ratio of less than 1.6 after chemotherapy had a poor prognosis. The A/G ratio was lower in the group with pneumonia after surgery.

Conclusion

The A/G ratio reflects the preoperative inflammatory response and nutritional status, suggesting that it is a useful factor for predicting postoperative complications and prognosis in patients with curative esophageal cancer.
301 IS IT WORTH USING MESH FOR THE TREATMENT OF GIANT HIATAL HERNIA? A SYSTEMATIC REVIEW AND META-ANALYSIS.
Authors: de Campos V , Palacio D , Glina F , Tustumi F , Bernardo W , de Sousa A
Published: September 2020

The use of mesh associated with cruroplasty is still controversial in giant hernias, due to possible complications of the prosthesis reported in the literature, such as infection, chest migration, shrinkage, esophageal and aortic erosion, stenosis and obstruction. This systematic review and meta-analysis aimed to compare the use or not of mesh as a reinforcement in the laparoscopic repair of giant hernias and to determine which technique has the best results in recurrence and complication rates.

Methods

A search was conducted using databases and included prospective and randomized studies. The studies should include patients with giant hernias who have undergone laparoscopic treatment comparatively analyzed between cruroplasty and suture associated with prosthetic reinforcement.

Results

Of the 768 articles analyzed, 8 were selected for systematic review, and 7 were included in the meta-analysis. The meta-analysis showed no statistically significant differences in favor of any of the intervention methods (mesh versus suture cruroplasty) for the different outcomes evaluated: recurrence (RD -0.06, CI [−0.13,0.01], I2 22%, p 0.27); postoperative complications (RD 0.04, CI [−0.01,0.9], I2 5%, p 0.30); deaths (RD -0.01, CI [−0.04, 0.02], I2 0%, p 74); intraoperative complications (RD -0.03, CI [−0.07, 0.1]); reoperation (RD -0.04, CI [− 0.10, 0.02], p 0.14).

Conclusion

There is no evidence supporting that routine mesh reinforcement in laparoscopic repair of giant hernias decreases recurrence and other complications. Systematic review registration number at PROSPERO: CRD42019147468.
327 IS LOCAL ENDOSCOPIC RESECTION A VIABLE THERAPEUTIC OPTION FOR EARLY CLINICAL STAGE T1A AND T1B OESOPHAGEAL ADENOCARCINOMA? A PROPENSITY-MATCHED ANALYSIS
Authors: Kamarajah S , Phillips A , Hanna G , Low D , Markar S
Published: September 2020

The role of endoscopic resection (ER) in the management of subsets of clinical T1N0 oesophageal adenocarcinoma is controversial. The aim of this study was to evaluate the outcome of ER versus oesophagectomy in node negative cT1a and cT1b oesophageal adenocarcinoma.

Methods

Data from the National Cancer Database (2010-2015), was used to identify patients with clinical T1aN0 (n = 2,545) and T1bN0 (n = 1,281) oesophageal adenocarcinoma that received either ER (cT1a, n = 1,581; cT1b, n = 335) or oesophagectomy (cT1a, n = 964; cT1b, n = 946). Propensity score matching (PSM) and Cox multivariable analyses were used to account for treatment selection bias.

Results

ER for cT1a and cT1b disease was performed more commonly over time. The rates of node-positive disease in patients with cT1a and cT1b oesophageal adenocarcinoma were 4% and 15%, respectively. In the matched cohort for cT1a cancers, ER had similar survival to oesophagectomy (HR: 0.85, 95% CI: 0.70-1.04, p = 0.1). The corresponding 5-year survival for ER and oesophagectomy were 70% and 74% (p = 0.1), respectively. For cT1b cancers, there was no statistically significant difference in overall survival between the treatment groups (HR: 0.87, 95% CI: 0.66-1.14, p = 0.3). The corresponding 5-year survival for ER and oesophagectomy were 53% vs. 61% (p = 0.3), respectively.

Conclusion

This study demonstrates ER has comparable long-term outcomes for clinical T1aN0 and T1bN0 oesophageal adenocarcinoma. However, 15% of patients with cT1b oesophageal cancer were found to have positive nodal disease. Future research should seek to identify the subset of T1b cancers at high risk of nodal metastasis and thus would benefit from oesophagectomy with lymphadenectomy.
340 EXPANDING THE ROLE OF POEM TO ESOPHAGEAL EPIPHRENIC DIVERTICULA—FEASIBLE, SAFE AND EFFECTIVE.
Authors: Sudarshan M , Sanaka M , Adhikari S , Murthy S , Thota P , Gabbard S , Ahmad U , Raja S
Published: September 2020

Epiphrenic diverticula (ED) is a rare disorder which can be associated with significant surgical morbidity. Presence of an esophageal motility disorder, often achalasia, is classically associated with ED with some arguing that symptoms are primarily attributed to the motility disorder rather than the diverticula itself. The role of peroral endoscopic myotomy (POEM) is expanding for palliation of achalasia. The objective of our study is to investigate the outcomes of POEM in patients with epiphrenic diverticula.

Methods

A retrospective analysis of a prospectively maintained database was conducted in a tertiary care institution between April 2014 and July 2019. A total of 217 patients receiving a POEM during the study time period were identified with 13 patients having ED. Video recordings of POEM with and without ED were compared for technical differences. Patient demographics, prior esophageal procedures and epiphrenic diverticula characteristics were collected. Primary outcome was post-operative Eckardt scores. We also explored integrated resting pressure (IRP) on manometry, barium column height and width, complications and patient reported outcomes. Standard statistical methods were applied using R.

Results

Among 13 patients with ED (median age 74.2, 69% male), 7 small and 6 large diverticula were identified. No post-operative complications were noted. The median Eckardt score significantly decreased from 8 [IQR 5–9] pre POEM to 0 [IQR 0–2] post POEM, with similar improvements in median IRPs (24.5 mmHg [IQR 16.9–31.3] vs. 4.3 mmHg [IQR 2.4–7.6], 1 min barium column height (9.2 cm [IQR 6.3–17.9] vs. 3.2 cm [IQR 0–7.1] and 1 min barium column width (3.3 cm [IQR 2.7–3.5] vs. 0.75 cm [IQR 0–3.7]. Post-operative pH studies were conducted in 7 (53.8%) patients demonstrating a DeMeester score of more than 14.72 in 5 (71.4%) patients.

Conclusion

We demonstrate that POEM is technically feasible, safe and associated with excellent outcomes in patients with small and large diverticula. In our study cohort no further surgical therapy was required to address the diverticula. Reflux was managed medically. Considering its low morbidity profile POEM should be considered for therapy in selected patients with epiphrenic diverticula.
350 EFFECTS OF EXERCISE TRAINING AFTER ESOPHAGECTOMY ON PHYSICAL FITNESS, QUALITY OF LIFE AND TREATMENT OUTCOMES
Authors: Simonsen C , Thorsen-Streit S , Sundberg A , Sigmundsdóttir Djurhuus S , Ehlers Mortensen C , Qvortrup C , Klarlund Pedersen B , Svendsen L , de Heer P , Frank Christensen J
Published: September 2020

Treatment for cancer of the gastro-esophageal junction (GEJ) can result in considerable and persistent decrements of physical fitness and health-related quality of life (HRQoL). Accordingly, a strong rationale exits to design interventions aiming at maintaining physical fitness and HRQoL during treatment. We aimed to investigate feasibility and safety of postoperative exercise training for patients with cancer of GEJ.

Methods

This follow-up of the PRESET pilot study (NCT02722785) included 49 patients with stage I-III GEJ cancer. The patients were allocated to postoperative exercise or usual care and followed for 1 year. The exercise group was prescribed 12 weeks of twice a week concurrent aerobic and resistance training. We evaluated the effects of exercise training on cardiorespiratory fitness, muscle strength and HRQoL. To assess safety, we recorded treatment outcomes including adherence to adjuvant chemotherapy, hospitalizations and 1-year overall survival.

Results

The exercise group improved muscle strength (+23.0 kg Leg press 1RM [95% CI, 12.4 to 33.5]) and cardiorespiratory fitness (+30.7 watt [95% CI, 16.3 to 45.1]). The exercise group had an improved HRQoL at 1-year follow-up (+14.9 points [95% CI, 4.5 to 25.3]). Exercise was safe with no differences in rate of patients receiving adjuvant therapy 87.5% vs. 84.2% (RR 1.04 [95% CI, 0.74 to 1.44]), rate of hospitalizations 36.8% vs. 26.1% (RR 1.41 [95% CI, 0.57 to 3.49]) or 1-year overall survival 80.0% vs. 79.3% (HR 0.87 [95% CI, 0.25 to 3.07]) for exercise and usual care, respectively.

Conclusion

Exercise in the postoperative period is safe and may improve HRQoL and physical fitness in patients with GEJ cancer. No differences in prognostic endpoints were observed.
374 VIDEO ESOPHAGOGRAM CORRELATES OF DYSPHAGIA IN PATIENTS WITH NORMAL LOWER ESOPHAGEAL SPHINCTER
Authors: Razia D , Giulini L , Bremner R , Mittal S
Published: September 2020

Dysphagia is a common foregut symptom. However, there is poor association between non-obstructive dysphagia and esophageal body peristaltic parameters in patients with normal lower esophageal sphincters (LES). The objective of this retrospective study was to study bolus transit patterns noted on barium esophagogram in patients experiencing dysphagia.

Methods

After IRB approval, we queried our esophageal database for patients with normal manometric LES. Jackhammer esophagus, esophageal spasm, previous foregut surgery, and unavailable foregut symptom questionnaires were exclusion criteria. Patients were grouped based on reported dysphagia: 0 = None; 1 = Mild; 2 = Moderate; 3 = Severe/very severe. All barium esophagograms were re-evaluated. Bolus esophageal transit time was studied with patients in both upright and prone positions, using live time stamps at bolus entry/exit. “Barium residue” was defined as persistent contrast on the esophageal wall after bolus exit. “Retrograde escape” referred to barium escaping proximally from the bolus into previously cleared esophagus. ANOVA and χ2 were used.

Results

In all, 150 patients met inclusion criteria. 76 (50.1%) were women. Mean age and body mass index were 58.4 ± 14.7 years and 22.9 ± 10.4 kg/m2, respectively. The number of patients in each dysphagia group (0, 1, 2, and 3) were 82(54.7%), 29(19.3%), 25(16.7%) and 14(9.3%), respectively. The difference in mean bolus transit time among dysphagia groups was statistically significant in prone-position swallows (39.3 ± 36.7, 75 ± 74.8, 98.8 ± 85 and 69.6 ± 43.7 seconds; p < 0.001) but not in upright-position swallows (14.6 ± 22, 12.4 ± 8.1, 14.3 ± 8.8 and 12.6 ± 8.2 seconds; p = 0.929; Fig. 1). The prevalence of residual contrast and retrograde escape in prone swallows were comparable among patients reporting dysphagia (p = 0.444, p = 0.173).

Conclusion

Bolus transit time in prone-position barium swallows is simple to assess, and correlates with dysphagia reported by patients with normal lower esophageal sphincters. However, further studies with comprehensive dysphagia score are needed.
Shipping the good agricultural products out: the differentiated impact of per-unit duties on developing countries
Authors: Emlinger Charlotte , Guimbard Houssein
Published: September 2020

We investigate the impact of per-unit duties (i.e. tariffs expressed in US dollars per unit of imported product) on world agricultural trade patterns. Using detailed data on trade and tariffs, we show first that they induce higher export unit values, confirming that the Alchian–Allen conjecture can be extended to per-unit duties. Second, we show that this effect is higher for developed countries, which can be explained by their specialization on high-priced products. Third, we find that the restrictive effect of per-unit duties on trade is higher for developing countries.
Longitudinal Associations Between Perceived Control and Health for American and Japanese Aging Adults
Authors: Toyama Masahiro , Fuller Heather R
Published: September 2020

Background and Objectives

Research suggests longitudinal and reciprocal relationships between perceived control over life circumstances and health for Western populations; yet, such associations have not been fully understood for non-Western populations. The present study addresses cultural differences in these associations for American and Japanese aging adults.

Research Design and Methods

For respondents aged 40 and older at 2 waves (Time 1 [T1] and Time 2 [T2]) of Midlife in the United States (N = 4,455) and Midlife in Japan (N = 827), cross-lagged path models were analyzed for T1 perceived control predicting change in each health measure (i.e., self-rated health, number of chronic health conditions, and functional limitations) from T1 to T2; and the matched T1 health measure predicting change in perceived control from T1 and T2. In these analyses, the effects of T1 age, T1 perceived control, and each T1 health measure were compared cross-nationally.

Results

A cross-national difference emerged in that T1 perceived control predicted change in chronic health conditions only for Americans. Similar tendencies were found between the 2 nationalities for T1 perceived control predicting changes in self-rated health and functional limitations. Reciprocal relationships between perceived control and health measures were found for Americans, but neither age nor any of the T1 health measures predicted change in perceived control for the Japanese respondents.

Discussion and Implications

The findings suggest cultural differences and similarities between the 2 nationalities, which have implications for potential health benefits of enhancing perceived control among American and Japanese aging adults. Building on these findings, the present study also indicates future directions of research.
Contribution of Staphylococcal Enterotoxin B toStaphylococcus aureusSystemic Infection
Authors: Bae Justin S , Da Fei , Liu Ryan , He Lei , Lv Huiying , Fisher Emilie L , Rajagopalan Govindarajan , Li Min , Cheung Gordon Y C , Otto Michael
Published: September 2020

Staphylococcal enterotoxin B (SEB), which is produced by the major human pathogen, Staphylococcus aureus, represents a powerful superantigenic toxin and is considered a bioweapon. However, the contribution of SEB to S. aureus pathogenesis has never been directly demonstrated with genetically defined mutants in clinically relevant strains. Many isolates of the predominant Asian community-associated methicillin-resistant S. aureus lineage sequence type (ST) 59 harbor seb, implying a significant role of SEB in the observed hypervirulence of this lineage. We created an isogenic seb mutant in a representative ST59 isolate and assessed its virulence potential in mouse infection models. We detected a significant contribution of seb to systemic ST59 infection that was associated with a cytokine storm. Our results directly demonstrate that seb contributes to S. aureus pathogenesis, suggesting the value of including SEB as a target in multipronged antistaphylococcal drug development strategies. Furthermore, they indicate that seb contributes to fatal exacerbation of community-associated methicillin-resistant S. aureus infection.
Association Between Functional Nucleotide Polymorphisms Up-regulating Transforming Growth Factor β1 Expression and Increased Tuberculosis Susceptibility
Authors: Zhang Su , Li Guobao , Bi Jing , Guo Qinglong , Fu Xiangdong , Wang Wenfei , Liu Shuyan , Xiao Guohui , Ou Min , Zhang Juanjuan , He Xing , Li Fang , Li Guanqiang , Feng Carl G , Chen Xinchun , Zhang Guoliang
Published: September 2020

Previous studies demonstrated that transforming growth factor (TGT) β1 plays an immunosuppressive role in clinical tuberculosis. However, the contribution of TGF-β1 gene polymorphisms to human tuberculosis susceptibility remains undetermined. In this study, we showed that single-nucleotide polymorphisms (SNPs) in TGF-β1 gene were associated with increased susceptibility to tuberculosis in the discovery cohort (1533 case patients and 1445 controls) and the validation cohort (832 case patients and 1084 controls), and 2 SNPs located in the promoter region (rs2317130 and rs4803457) are in strong linkage disequilibrium. The SNP rs2317130 was associated with the severity of tuberculosis. Further investigation demonstrated that rs2317130 CC genotype is associated with higher TGF-β1 and interleukin 17A production. The mechanistic study showed that rs2317130 C allele affected TGF-β1 promoter activity by regulating binding activity to nuclear extracts. These findings provide insights into the pathogenic role of TGF-β1 in human tuberculosis and reveal a function for the TGF-β1 promoter SNPs in regulating immune responses during Mycobacterium tuberculosis infection.