bluuebunny/crossref_metadata_2025 huggingface dataset:
Africa’s stalled structural transformation: the end of the flying geese?
Authors: Munyi Elijah N.
Published: September 2020

Is structural transformation happening in Africa, and can African states count on the neoliberal flying geese paradigm for industrialisation? Using recent data from World Bank and United Nations Conference of Trade and Development reports, this briefing suggests not. The post-2008 crisis ‘end of labour-cost arbitrage opportunities’ have nullified Africa’s attractiveness in global labour-intensive manufacturing. This is a position that negates the generally optimistic narrative recently espoused by the Journal of African Economies (vol. 27) on Africa’s industrialisation and China’s putative catalytic role in it.
SARS-CoV-2–triggered neutrophil extracellular traps mediate COVID-19 pathology
Authors: Veras Flavio Protasio , Pontelli Marjorie Cornejo , Silva Camila Meirelles , Toller-Kawahisa Juliana E. , de Lima Mikhael , Nascimento Daniele Carvalho , Schneider Ayda Henriques , Caetité Diego , Tavares Lucas Alves , Paiva Isadora M. , Rosales Roberta , Colón David , Martins Ronaldo , Castro Italo Araujo , Almeida Glaucia M. , Lopes Maria Isabel Fernandes , Benatti Maíra Nilson , Bonjorno Letícia Pastorelli , Giannini Marcela Cavichioli , Luppino-Assad Rodrigo , Almeida Sérgio Luna , Vilar Fernando , Santana Rodrigo , Bollela Valdes R. , Auxiliadora-Martins Maria , Borges Marcos , Miranda Carlos Henrique , Pazin-Filho Antônio , da Silva Luis Lamberti P. , Cunha Larissa Dias , Zamboni Dario S. , Dal-Pizzol Felipe , Leiria Luiz O. , Siyuan Li , Batah Sabrina , Fabro Alexandre , Mauad Thais , Dolhnikoff Marisa , Duarte-Neto Amaro , Saldiva Paulo , Cunha Thiago Mattar , Alves-Filho José Carlos , Arruda Eurico , Louzada-Junior Paulo , Oliveira Renê Donizeti , Cunha Fernando Queiroz
Published: September 2020

Severe COVID-19 patients develop acute respiratory distress syndrome that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that neutrophil extracellular traps (NETs) have been described as important mediators of tissue damage in inflammatory diseases, we investigated whether NETs would be involved in COVID-19 pathophysiology. A cohort of 32 hospitalized patients with a confirmed diagnosis of COVID-19 and healthy controls were enrolled. The concentration of NETs was augmented in plasma, tracheal aspirate, and lung autopsies tissues from COVID-19 patients, and their neutrophils released higher levels of NETs. Notably, we found that viable SARS-CoV-2 can directly induce the release of NETs by healthy neutrophils. Mechanistically, NETs triggered by SARS-CoV-2 depend on angiotensin-converting enzyme 2, serine protease, virus replication, and PAD-4. Finally, NETs released by SARS-CoV-2–activated neutrophils promote lung epithelial cell death in vitro. These results unravel a possible detrimental role of NETs in the pathophysiology of COVID-19. Therefore, the inhibition of NETs represents a potential therapeutic target for COVID-19.
Femtosecond PLD-grown YF3 nanoparticle thin films as improved filterless VUV photoconductive detectors
Authors: Yu Xi , Cadatal-Raduban Marilou , Kato Seiya , Kase Masahiko , Ono Shingo
Published: September 2020

A photoconductive detector (PCD) responding only to vacuum ultraviolet (VUV) radiations below 180 nm without any filter was fabricated using an yttrium fluoride (YF3) thin film grown by femtosecond (fs) laser pulsed laser deposition (PLD). The structural morphology (particle size and surface roughness) of the thin film was improved using a low laser fluence and a high substrate temperature during the fabrication. The smallest average particle size achieved was 159 nm with a roughness of 37 nm at a laser fluence of 13.5 J cm−2 and a substrate temperature of 400 °C. The resistances for the dark current of the PCD increased from 10 TΩ to 680 TΩ using YF3 thin films with a smaller average nanoparticle diameter of 159 nm rather than 330 nm. The time response of the PCD to a VUV flash lamp emitting at 170 nm showed that a small average nanoparticle diameter results to a fast response time. By covering the Al electrode pairs with another fs PLD-grown YF3 film, the influence of external photoelectric effect was suppressed and the response wavelength edge decreased from 280 nm to 180 nm without any filter. The filterless PCD is expected to enhance the use of fluoride thin films in conjunction with VUV light sources for various scientific and industrial applications.
Effects of initial electronic state on vortex patterns in counter-rotating circularly polarized attosecond pulses*
Authors: Zhen Qi , Chen Jia-He , Zhang Si-Qi , Yang Zhi-Jie , Liu Xue-Shen
Published: September 2020

We theoretically investigate the effects of different electronic states as the initial state on the vortex patterns in photoelectron momentum distributions (PMDs) from numerical solutions of the two-dimensional (2D) time-dependent Schrödinger equation (TDSE) of He+ with a pair of counter-rotating circularly polarized attosecond pulses. It is found that the number of spiral arms in vortex patterns is equal to the number of the absorbed photons when the initial state is the ground state. However, the number of spiral arms in vortex patterns is always two more than the number of the absorbed photons when the initial state is the excited state. This sensitivity is attributed to the initial electron density distribution. In addition, we have demonstrated the PMDs for different initial electronic states with the same wavelengths and analyzed their corresponding physical mechanisms. It is illustrated that the method presented can be employed to effectively control the distribution of the electron vortices.
Revealing stepping forces in sub-mg tiny insect walking*
Authors: Zheng Yelong , Yin Wei , Lu Hongyu , Tian Yu
Published: September 2020

Measuring walking forces of small or tiny insects can help the comprehension of their locomotion principles. However, as their size and force are generally too small, walking forces of small insects in sub-mg mass have never been actually measured. In this work, a convenient multi-lens and jelly surface based shadow method was developed for simultaneous multiple walking forces measuring, ranged from nN to mN with a sensitivity of sub-nN/pixel under ambient conditions. Walking force of six legs of a 0.3 mg water treader was demonstrated. The obtained results disclosed a rapid and extending middle leg strategy of water treader in walking forward above a jelly surface. This method is cost-effective and high-resolution, which could be easily used in measuring other tiny forces.
Artificial lateral line based relative state estimation between an upstream oscillating fin and a downstream robotic fish
Authors: Zheng Xingwen , Wang Wei , Li Liang , Xie Guangming
Published: September 2020

The lateral line enables fish to efficiently sense the surrounding environment, thus assisting flow-related fish behaviors. Inspired by this phenomenon, varieties of artificial lateral line systems (ALLSs) have been developed and applied to underwater robots. This article focuses on using the pressure sensor arrays based ALLS-measured hydrodynamic pressure variations (HPVs) for estimating the relative states between an upstream oscillating fin and a downstream robotic fish. The HPVs and relative states are measured in flume experiments in which the oscillating fin and the robotic fish have been locate with upstream-downstream formation in a flume. The relative states include the relative oscillating frequency, amplitude, and offset of the upstream oscillating fin to the downstream robotic fish, the relative vertical distance, the relative yaw angle, the relative pitch angle, and the relative roll angle between the upstream oscillating fin and the downstream robotic fish. Regression models between the ALLS-measured and the mentioned relative states are investigated, and regression models-based relative state estimations are conducted. Specifically, two criteria are proposed firstly to investigate not only the sensitivity of each pressure sensor to the variations of relative state but also the insufficiency and redundancy of the pressure sensors. And thus the pressure sensors used for regression analysis are determined. Then four typical regression methods, including random forest (RF) algorithm, support vector regression, back propagation neural network, and multiple linear regression method are used for establishing regression models between the ALLS-measured HPVs and the relative states. Then regression effects of the four methods are compared and discussed. Finally, the RF-based method, which has the best regression effect, is used to estimate the relative yaw angle and oscillating amplitude using the ALLS-measured HPVs and exhibits excellent estimation performance.
Tunabot Flex: a tuna-inspired robot with body flexibility improves high-performance swimming
Authors: White Carl H , Lauder George V , Bart-Smith Hilary
Published: September 2020

Tunas are flexible, high-performance open ocean swimmers that operate at high frequencies to achieve high swimming speeds. Most fish-like robotic systems operate at low frequencies (≤3 Hz) resulting in low swim speeds (≤1.5 body lengths per second), and the cost of transport (COT) is often one to four orders of magnitude higher than that of tunas. Furthermore, the impact of body flexibility on high-performance fish swimming remains unknown. Here we design and test a research platform based on yellowfin tuna (Thunnus albacares) to investigate the role of body flexibility and to close the performance gap between robotic and biological systems. This single-motor platform, termed Tunabot Flex, measures 25.5 cm in length. Flexibility is varied through joints in the tail to produce three tested configurations. We find that increasing body flexibility improves self-propelled swimming speeds on average by 0.5 body lengths per second while reducing the minimum COT by 53%. The most flexible configuration swims 4.60 body lengths per second with a tail beat frequency of 8.0 Hz and a COT measuring 18.4 J kg−1 m−1. We then compare these results in addition to the midline kinematics, stride length, and Strouhal number with yellowfin tuna data. The COT of Tunabot Flex’s most flexible configuration is less than a half-order of magnitude greater than that of yellowfin tuna across all tested speeds. Tunabot Flex provides a new baseline for the development of future bio-inspired underwater vehicles that aim to explore a fish-like, high-performance space and close the gap between engineered robotic systems and fish swimming ability.
Totally organic electrical skin patch powered by flexible biobattery
Authors: Yoshida Shotaro , Abe Hiroya , Abe Yuina , Kusama Shinya , Tsukada Kenichi , Komatsubara Ryo , Nishizawa Matsuhiko
Published: September 2020

An electrical skin patch that can be flexibly attached to the skin and activated in 30 s by adding water was developed by integrating a built-in flexible glucose/O2 biobattery. The latter consisted of a glucose dehydrogenase (GDH)-modified anode and an iron(II) phthalocyanine (FePc)-modified cathode. The quick activation of the patch components by water addition deep inside the patch was achieved by using a flexible water-absorbing sponge containing glucose and buffer electrolyte. A patch current of about 10 μA was maintained for more than 12 h by optimizing the amount of glucose and electrolyte contained in the sponge tank. The entire patch was soft and highly flexible to conform to curved skin surfaces, owing to its thinness (<2 mm) and the flexibility of all the patch components, including the enzyme electrodes based on the carbon fabric.
Strong solutions to a nonlocal-in-time semilinear heat equation
Authors: Walker Christoph
Published: September 2020

The existence of strong solutions to a nonlocal semilinear heat equation is shown. The main feature of the equation is that the nonlocal term depends on the unknown on the whole time interval of existence, the latter being given a priori. The proof relies on Schauder’s fixed point theorem and semigroup theory.
Compositional diversity and evolutionary pattern of coronavirus accessory proteins
Authors: Shang Jingzhe , Han Na , Chen Ziyi , Peng Yousong , Li Liang , Zhou Hangyu , Ji Chengyang , Meng Jing , Jiang Taijiao , Wu Aiping
Published: September 2020

Accessory proteins play important roles in the interaction between coronaviruses and their hosts. Accordingly, a comprehensive study of the compositional diversity and evolutionary patterns of accessory proteins is critical to understanding the host adaptation and epidemic variation of coronaviruses. Here, we developed a standardized genome annotation tool for coronavirus (CoroAnnoter) by combining open reading frame prediction, transcription regulatory sequence recognition and homologous alignment. Using CoroAnnoter, we annotated 39 representative coronavirus strains to form a compositional profile for all of the accessary proteins. Large variations were observed in the number of accessory proteins of 1–10 for different coronaviruses, with SARS-CoV-2 and SARS-CoV having the most (9 and 10, respectively). The variation between SARS-CoV and SARS-CoV-2 accessory proteins could be traced back to related coronaviruses in other hosts. The genomic distribution of accessory proteins had significant intra-genus conservation and inter-genus diversity and could be grouped into 1, 4, 2 and 1 types for alpha-, beta-, gamma-, and delta-coronaviruses, respectively. Evolutionary analysis suggested that accessory proteins are more conservative locating before the N-terminal of proteins E and M (E-M), while they are more diverse after these proteins. Furthermore, comparison of virus-host interaction networks of SARS-CoV-2 and SARS-CoV accessory proteins showed that they share multiple antiviral signaling pathways, those involved in the apoptotic process, viral life cycle and response to oxidative stress. In summary, our study provides a tool for coronavirus genome annotation and builds a comprehensive profile for coronavirus accessory proteins covering their composition, classification, evolutionary pattern and host interaction.
33 CRISCO-UGIS: COMPOSITE RISK SCORE TO PREDICT POST-OPERATIVE COMPLICATIONS FOR UPPER GASTROINTESTINAL CANCER SURGERY
Authors: Kammili A , Trépanier M , Naghawi H , Cools-Lartigue J , Mulder D , Ferri L , Mueller C
Published: September 2020

Gastroesophagectomy for cancer is associated with high risk of morbidity and mortality. Careful patient selection for surgery is essential for optimizing outcomes. The purpose of this study was to develop a reliable composite risk calculator to inform pre-operative decision-making using readily available patient and tumour characteristics.

Methods

Patients undergoing curative-intent resection for gastroesophageal cancer from January 2010 to December 2018 were identified from a prospectively collected database. Data were verified and collected from patients’ medical records. Multiple logistic regression modeling identified pre-operative variables associated with significantly elevated risk of moderate to severe post-operative complications (Clavien-Dindo score ≥ 2) within 30 days of surgery and a nomogram was developed to form the composite risk score (CRiSCo-UGIS). Internal model validation was performed.

Results

Among 520 patients, independent pre-operative risk factors for complications were: female sex, age-adjusted Charlson comorbidity index ≥5, albumin <35 g/L, proximal tumour location (esophagus and gastroesophageal junction) and reduced performance status (Eastern Cooperative Oncology Group performance status 2–3) (Table 1). CRiSCo-UGIS had a good model fit (Hosmer-Lemeshow p = 0.47, area under receiver operating characteristic curve = 0.69). The overall observed-to-expected ratio was 1.0 [95% confidence interval 0.9–1.1]. Patients were divided into low (0), moderate (1–2) and high (≥3 points) risk categories. The observed risk of complications was: 42% in low-risk, 53% in moderate-risk and 80% in high-risk.

Conclusion

CRiSCo-UGIS can reliably predict post-operative complications for gastroesophageal cancer resection based on readily available pre-operative characteristics. This composite score can be used to guide patient selection for surgery and enhance informed consent discussions.
52 SHORT-TERM OUTCOMES OF RAMIE VERSUS TLE FOR LOCALLY ADVANCED ESOPHAGEAL CANCER AFTER NEOADJUVANT CHEMORADIOTHERAPY: A PROPENSITY SCORE-MATCHED ANALYSIS
Authors: Guo X , Jiang H , Li B , Sun Y , Hua R , Li Z
Published: September 2020

This study aimed to compare the short-term outcomes of esophagectomy (RAMIE) versus thoracolaparoscopic esophagectomy (TLE) for patients undergoing neoadjuvant chemoradiotherapy (nCRT) for locally advanced esophageal cancer in a propensity matched cohort.

Methods

Data for consecutive patients receiving nCRT plus RAMIE or TLE were collected prospectively from February 2016 to December 2019. Baseline characteristics and perioperative outcomes of the RAMIE and TLE groups were retrospectively compared.

Results

After propensity matching, 48 pairs were identified. The conversion rate to open thoracotomy was comparable in RAMIE and TLE (4.2% vs 6.3%, P = 1). Median operative time in RAMIE was significantly shorter than TLE (237 vs 271 min, P < 0.001). Compared with TLE group, the median number of dissected lymph nodes was higher in RAMIE group at the left recurrent laryngeal nerve (RLN) area [2 (1–3) vs 1 (0–2), P = 0.014], total RLN area [4.5 (2.0–7.0) vs 2.5 (1.0–5.0), P = 0.008], and thoracic area [10.5(7.0–16.0) vs 8.5(5.0–14.5), P = 0.049]. There was no significant difference in pneumonia, leakage, and vocal cord paralysis.

Conclusion

Compared to traditional TLE, RAMIE can achieve more lymph nodes yield at the RLN region and shorter operative time for the patients undergoing nCRT with comparable postoperative outcomes.
62 THE STERNO-TRACHEAL DISTANCE IS AN IMPORTANT FACTOR OF ANASTOMOTIC LEAKAGE OF RETROSTERNAL GASTRIC TUBE RECONSTRUCTION AFTER ESOPHAGECTOMY
Authors: Inoue S
Published: September 2020

Background

Anastomotic leakage (AL) is a serious complication after esophagectomy. The retrosternal (RS) route has been selected majorly to reduce reflux and related pneumonia and considering mediastinal recurrences. AL has been developed more in RS than posterior mediastinal (PM) route reconstruction. Therefore, we suspected the sterno-tracheal distance (STD) might be related to AL and started the selection according to the STD from 2009.

Methods

A total of 221 patients who underwent a subtotal esophagectomy with gastric tube reconstruction during January 2004—April 2017 were investigated. The patients were classified into the 'after STD selection' (A; n = 144) group and the 'before STD selection' (B, n = 77) group. The incidences of and the risk factors for AL between the two groups were compared.

Results

The incidence of AL was high in the B group (18.2%), and 78.6% of the patients who developed AL were treated with RS route. The median STDs of the patients with AL and no AL were 10.3 mm and 14.5 mm, respectively (p = 0.001). These results demonstrated that the STD was a risk factor for AL in the RS route. Based on these results, 13 mm was set as the cutoff value. After STD selection, the median STD increased from 14.0 mm to 17.3 mm (p = 0.001), and the incidence of AL decreased significantly from 26.2% to 11.1% in the RS route (p = 0.037).

Conclusion

The STD was the independent risk factor for AL in the RS route. RS route reconstruction should be avoided for the patients with STD <13 mm.
64 STATISTICAL ANALYSIS OF PROGNOSTIC FACTORS AFFECTING LONG-TERM PROGNOSIS AFTER ENDOSCOPIC TREATMENT OF ESOPHAGEAL VARICES
Authors: Nishimura T
Published: September 2020

Gastroesophageal varices are present in approximately 50% of patients with cirrhosis, and their rupture is a life-threatening complication. However, mortality rates have declined due to the progress in the management of these patients. Especially advances in endoscopic treatment have contributed to the improved survival rates. In this study, we investigated the prognostic factors associated with long-term survival after endoscopic treatment for esophageal varices.

Methods

The subjects were 260 patients who underwent initial endoscopic treatment for esophageal varices in our hospital between January 1997 and June 2019. Among them, 160 successfully followed up. The patients’ characteristics were: mean age, 65.4 years (29–85); 109 men and 51 women; and median survival period, 53 months. For analysis, subjects were divided into long-term survival and non-long-term survival groups (n = 59 for each) with a 53-month survival period as a cut-off value.

Results

The long-term/non-long-term survival group had a preoperative Child-Pugh score of 6.2 ± 1.1/7.4 ± 2.0 (p < 0.01) and hepatocellular carcinoma (HCC) presence rate was 25.4%/55.9% (p < 0.01), significantly higher in the non-long-term group. Analysis of the factors affecting survival period using Cox proportional hazards model showed that Child-Pugh score B or C [hazard ratio(HR):2.0143, p < 0.05], total bilirubin value≧ 2 [HR:2.5573, p < 0.05], and presence of HCC [HR:2.2450, p < 0.01] were noted as significant factors. Only presence of HCC was found to be a significant factor affecting the long-term survival using multiple logistic regression analysis [odds ratio:0.3463, p < 0.05].

Conclusion

Our study revealed that liver function and the presence of HCC affect long-term prognosis after endoscopic treatment for esophageal varices.
406 REVIEWING THE DYSPLASIA DURING LONG FU OF BARRETT’S ESOPHAGUS. SHOULD WE RELY ON THE DIAGNOSIS OF DYSPLASIA?
Authors: Szachnowicz S , Duarte A , Mattos B , Iriya K , Bianchi E , Seguro F , da Rocha J , Sallum R , Cecconello I
Published: September 2020

Barrett’ s esophagus (BE) is a complication of severe gastroesophageal reflux disease (GERD). The major concern aspect is its association to dysplasia and esophageal adenocarcinoma. The endoscopic treatment of the epithelium, as well as the follow-up (FU) period, should be guided according to the diagnosis and the worst degree of dysplasia found in the last endoscopies. However, we are aware of the great difficulty and variation among pathologists in diagnosing and grading dysplasia in BE.

Methods

Aim: Review new diagnoses of low- and high-grade dysplasia (LGD and HGD) in BE with specialized pathologists during long-term FU in clinical or surgical treatment for GERD

From January 1980 to July 2019, 738 patients with BE were FU (average of 98 months), with routine endoscopic examination each 2 years with multiple biopsies, in patients with BE without dysplasia. 48 patients were diagnosed with any grade of dysplasia on FU endoscopic biopsies. The biopsies were reviewed by specialized pathologists and evaluated epidemiologic data, clinical or surgical treatment for the GERD and about the confirmation, downgrade or upgrade of dysplasia degree.

Results

48 patients were reviewed, 32 males. The medium age was 61,9 YO (29 -93). Only 18 patients were in follow-up after surgical treatment for GERD. 9 patients had first diagnosis of in situ Adenocarcinoma, after review 8 were confirmed and treated and 1 were downgrade to HGD. 8 patients had first HGD and after review, 2 were upgrade to Adenocarcinoma, 4 were confirmed as HGD (endoscopic treatment) and 2 downgraded to no dysplasia BE. 31 patients had first LGD. 2 had upgrade to HGD/Adeno, 8 are in FU annually and 21 were downgrade to non dysplastic BE.

Conclusion

The diagnosis of dysplasia in BE remains a challenge. 23 of 48 (47%) of our patients once marked with any grade of dysplasia, were downgrade after pathological review and FU to non dysplasic BE. These difficulty of appropriate dysplasia degree diagnosis could make some mistakes in BE treatment and surveilance.
40 INTRODUCING AN INTERACTIVE ONLINE-REPORT FROM THE SWEDISH NATIONAL QUALITY REGISTER FOR ESOPHAGEAL AND GASTRIC CANCER—OPEN NREV
Authors: Linder G , Lindblad M , Johansson J , Lindberg F , Smedh U , Moritz E , Hedberg J
Published: September 2020

The Swedish National Quality Register for Esophageal and Gastric Cancer (NREV) was introduced in 2007 and is the sole quality registry in Sweden for patients with esophageal and gastric cancer. Previously, selected variables from the registry was made available to both caregivers and the public through a downloadable annual report.

We aimed to make quality indicators readily available to all interested parties; caregivers, patient groups, hospital staff, researchers, administrators and health-political decision-makers.

Methods

A database was compiled with registry data presented for all years since 2007 and updated every six months. Several graphical and numeric presentations were implemented. Both medical expertise and a patient representative were involved in choosing relevant quality indicator variables as well as designing the web interface.

Results

Registry Coverage, Quality indicators/lead times, Treatment and Outcomes were the four main focus areas. All areas contained selectable sub-variables and the user was given the choice to present data on a national or regional level. Alterations in chosen variables or selection-base resulted in real time changes in the online report. Thus, a variable national or regional report could be tailored to the users’ needs. All data could be presented as comparative diagrams, crude tables or as time-trend analysis, as exemplified by figure 1.

Conclusion

An interactive online platform to display population based results and time-trends for important quality indicators in the diagnosis and treatment of esophageal and gastric cancer is now available for all. The main purpose, to make anonymized data available, was achieved by OPEN-NREV. We propose that presenting data in this manner is of interest to patients, caregivers, scientists and decision makers.
415 OCCUPATIONAL PHYSICAL ACTIVITY AND THE RISK OF GORD, BARRETT’S OESOPHAGUS AND OESOPHAGEAL ADENOCARCINOMA A PROSPECTIVE COHORT STUDY IN UK BIOBANK
Authors: Lam S , Savva G , Alexandre L , Kumar B , Hart A
Published: September 2020

Recreational physical activity has been shown to protect against the development of oesophageal adenocarcinoma as well as gastroesophageal reflux disease (GORD), but such effects have not been demonstrated for non-recreational activity. We examined whether high levels of occupational physical activity (heavy manual labour or physical work) were associated with the risk of oesophageal adenocarcinoma as well as its sequential precursor diseases; gastroesophageal reflux disease (GORD), reflux oesophagitis and Barrett’s oesophagus.

Methods

In this population-based prospective cohort study, participants aged between 37 to 73 years were recruited from 22 regions across the United Kingdom. Baseline occupational information of job type and levels of heavy manual activity was assessed using both questionnaires and verbal interviews. Incident cases were identified by linkage with routinely collected hospital inpatient and cancer registry data for England, Scotland and Wales. Primary clinical outcomes were GORD without oesophagitis, GORD with oesophagitis (reflux oesophagitis), Barrett’s oesophagus and oesophageal adenocarcinoma. The effects of heavy manual activity on disease risk were estimated using Cox proportional hazard regression.

Results

Between 2006 and 2010, 502 524 men and women were enrolled. Main analyses were limited to the working population with a full set of variables of interest (n = 266 453). Compared to jobs with low levels of heavy manual activity, high level jobs had increased hazard ratios (HRs) for GORD (1.20, 95% CI 1.11–1.30), reflux oesophagitis (1.17, 95% CI 1.04–1.31) and Barrett’s oesophagus (1.13, 95% CI 0.98–1.32), but not oesophageal adenocarcinoma (0.91 95% CI 0.54–1.56).

Conclusion

High levels of occupational heavy manual activity could be used as a risk factor for GORD and reflux oesophagitis, the precursor diseases of Barrett’s oesophagus and oesophageal adenocarcinoma.
442 HAS HOSPITAL VARIATION IN THE PROBABILITY OF RECEIVING TREATMENT WITH CURATIVE INTENT FOR ESOPHAGEAL AND GASTRIC CANCER DECREASED OVER TIME?
Authors: Luijten J , Vissers P , Lingsma H , van Leeuwen N , Rozema T , Siersema P , Rosman C , van Laarhoven H , Lemmens V , Nieuwenhuijzen G , Verhoeven R
Published: September 2020

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 < 0.001) and did not change for GC (ORs ranging from 0.78–1.23 to 0.82–1.23, p = 1.00). A higher probability of receiving treatment with curative intent was associated with better RS and reduced RER for both types of cancer.

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.
448 SYSTEMATIC IMPLEMENTATION OF A REGIONAL MULTIDISCIPLINARY TEAM MEETING IMPROVES PROGNOSIS FOR ESOPHAGEAL CANCER PATIENTS.
Authors: Luijten J , Haagsman V , Luyer M , Heesakkers F , Schrauwen R , Jürgens M , Buster E , Vincent J , Kneppelhout J , Verhoeven R , Nieuwenhuijzen G
Published: September 2020

Surgery for esophageal cancer (EC) has been centralized in the Netherlands. However, patients are still diagnosed in referral centers and not all patients are discussed with a resection center. The aim of this study was to examine the impact of the implementation of the regional Upper-GI video multidisciplinary team meeting (MDT) in the Eindhoven region in which all regional patients should be discussed, on the decision-making process, treatment, and survival of patients with EC.

Methods

All patients diagnosed between 2012 and 2018 with EC, in hospitals currently working together with the Catharina hospital, were selected from the Netherlands Cancer Registry (n = 1119). The regional MDT was implemented in 2 hospitals in May 2014 and the other hospitals gradually joined. The primary outcome of this study was the proportion of patients discussed in any MDT. Secondary outcomes were involvement of a resection center in MDT, treatment and survival. Outcomes were described prior to and after participation in the regional MDT and analyzed by chi-square tests. Kaplan–Meier curves and log-rank tests were used to compare overall survival.

Results

Since participation in the regional MDT more patients were discussed in any MDT (80%-89%, p < 0.0001) and involvement of a resection center during the MDT almost doubled (43%-82%, p < 0.0001). The proportion of patient who underwent treatment with a curative intent remained the same (75%). However, esophagectomy (41%-43%) and endoscopic resections (2%-6%) were performed more often and the use of definitive chemoradiation therapy decreased (31%-25%)(p = 0.049). The use of palliative systemic therapy increased (39%-52%, p < 0.001). Three-year overall survival for all EC patients increased significantly (24%-32%, p < 0.02)(Figure). A non-significant increase in 3-year survival in potentially curable patients (38%-48%, p = 0.09) and 1-year survival in palliative patients (18%-26%, p = 0.13) was observed.

Conclusion

After implementation of the regional MDT more EC patients were discussed during a MDT and also more often with the involvement of a resection center. This is the first study showing an association of the implementation of a regional MDT with an improved survival. Hypothetically, the implementation of the regional tumor specific video MDT could have had a positive effect on the quality and effectiveness of decision making in patients diagnosed with EC.
449 MANAGEMENT OF LATE PRESENTATION OF ESOPHAGEAL CANCER
Authors: Lim K
Published: September 2020

The incidence of esophageal carcinoma (EC) in Singapore is declining since 1970s. However, the age-incidence curve in 2010s shows a steep rise after age 40-50s. The majority of EC patients presented with locally advanced or metastatic disease. The 2 common risk factors are cigarette smoking and disease progression from acid reflux-related intestinal metaplasia.

Methods

Consecutive cases of esophageal malignancy (n = 62) including gastro-esophageal junction carcinoma were identified from the hospital electronic medical records between August 2015 to February 2020 for data analysis. True gastric cardia tumors not invading above squamo-columnar junction were excluded.

Results

The mean age was 65 years (range 40–90), predominantly male (n = 51) and 50% were smokers. The histological types were adenocarcinoma (n = 33), squamous cell carcinoma (n = 25), undifferentiated carcinoma (n = 3) and adenosquamous carcinoma (n = 1). Staging CT scan showed M1 disease in 42% of cases whilst 62% received palliative therapy including stent insertion (n = 4). Only a handful of cases received curative-intent treatment such as EMR (n = 2), ESD (n = 1), extended total gastrectomy (n = 2) and 2-staged esophagectomy (n = 2). From the time of EC diagnosis was made, the survival cases at Year 1, 2, 3, and 4 follow up were 30, 8, 5 and 1 respectively.

Conclusion

EC is a dismal disease to manage in this population group due to advanced disease at the time of presentation. The majority had Stage IV disease and was given palliative treatment. Primary and secondary preventative healthcare against development of EC should be targeted to reduce the risk factors such as cigarette smoking and chronic acid reflux.
504 THE USE OF ENDOSCOPIC VACUUM THERAPY (EVT) AS COMPARED TO ENDOSCOPIC STENTING (ES) FOR LEAKAGES AFTER FOREGUT SURGERY
Authors: Chan S , Yip H , Teoh A , Chiu P , Ng E
Published: September 2020

Anastomotic leakage after foregut surgeries are often difficult to manage. The conventional way of endoscopic treatment is ES. However, it carries a risk of stent migration and erosion. EVT is a novel way of treating these leaks.

Methods

This was a retrospective cohort study including all patients with anastomotic leak after foregut surgery and were treated with ES or EVT between July 2008 and July 2019. Patients’ demographics, type of surgery, size of anastomotic defect, success rate, complications, number of procedures were recorded and compared.

Results

There were 17 patients treated with ES and 7 patients treated with EVT. The success rate of both therapies are similar. (11/17(64.7%) in the ES group vs 5/7(71.4%) in the EVT group; p = 0.751). However, there was a trend to less complications in the EVT group (9/17 (52.9%) in ES group vs. 1/7(14.2%) in EVT group; p = 0.135). On the other hand, the EVT group has a trend to requiring more endoscopic procedures (median (range) 3 (7) procedures in the ES group vs 6(11) in the EVT group; p 0.435).

Conclusion

The use of EVT is feasible and safe in treating anastomotic leaks after foregut surgeries. Although more procedures are required, it achieved similar success rate while having a trend to less complications.
507 NEOADJUVANT AND ADJUVANT CHEMOTHERAPIES FOR PATIENTS WHO UNDERWENT RESECTION FOR SQUAMOUS CELL CARCINOMA CF THE THORACIC ESOPHAGUS
Authors: Liu J , Wang Y
Published: September 2020

The efficacy of neo-adjuvant chenmotherapy (NCT) and adjuvant chemotherapy (ACT) for squamous cell carcinoma (SCC) of the esophagus has not been fully expounded. This study analyzed the prognostic factors of patients who underwent esophagectomy for SCC of the thoracic esophagus, specially focused on NCT and ACT.

Methods

From January 2008 to January 2016, 1075 consecutive patients underwent esophgagectomy for stage T3-T4 SCC of the thoracic esophagus. Propensity-score matching (PSM) analyses were conducted in patients who underwent NCT, surgery alone (SA) and ACT. After PSM, there were 83 patients in NCT, 249 patients in SA and 249 patients in ACT group. Postoperative outcomes and prognostic factors of patients in the three groups were analyzed. Univariate analysis was performed using the Kaplan–Meier method and multivariate analysis using the Cox proportional hazard model. Differences were considered to be statistically significant when P < 0.05.

Results

The incidence of main postoperative complications was 9.6% (8/83) in NCT group compared to 6.8% (34/498) in SA and ACT groups (P = 0.834). In NCT group, 20 patients (24.1%) were downstaged by NCT and 63 patients (75.9%) remained stable. The 3-year survival rate of the entire group was 51.0%, and the 5-year survival rate was 33.4%. The 5-year survival rate was 32.2% in NCT group, 50.9% in ACT, and 19.5% in SA patients. In univariate analysis, both NCT and ACT were associated with long-term survival. In multivariate analysis, however, ACT rather than NCT was independent prognostic factor.

Conclusion

This study supports the use of postoperative ACT for patients with stage T3 or T4 SCC of the thoracic esophagus, but the effect of NCT needs further study.
510 IMPACT OF TUMOR REGRESSION ON PROGNOSIS AFTER NEOADJUVANT CHEMORADIOTHERAPY IN MINIMALLY INVASIVE ESOPHAGECTOMY TREATED ESOPHAGEAL ADENOCARCINOMA
Authors: Crull D , Hogenes M , van Det M , Kouwenhoven E
Published: September 2020

Multimodal therapy is the standard of care in curative esophageal cancer. However, tumor characteristics such as differentiation, subtype of adenocarcinoma and tumor regression grade (TRG) are not incorporated in the 8th AJCC-staging or used for prognosis. The aim of this study is to determine the impact of these tumor characteristics on overall survival (OS) and disease free survival (DFS) and explore the prognostic value when TRG is combined with the AJCC-staging.

Methods

Between 2011 and 2018, 316 patients underwent a minimally invasive esphagectomy (MIE) in a single, high volume center. 228 patients were selected based on having an adenocarcinoma treated with neoadjuvant chemo-radiotherapy, a radical resection and a pM0 stage. TRG was determined using Mandard Tumor Regression (MTR). Subtype of adenocarcinoma was confirmed using either the pre-operative biopsy or the residual tumor tissue after surgery. Differentiation grade was determined on resected tumor tissue. MTR was modified from a 5-tier to a 3-tier classification. MTR 1 and 2 were classified in one group of “major response”, MTR 4 and 5 as “minimal response”.

Results

Median follow up was 2.1 years. MTR was a strong predictor for OS and DFS in univariate analysis. MTR combined with AJCC-staging did not improve the prognostic value of the AJCC-staging for the prediction of OS. However, in DFS the prognostic value of AJCC-staging is improved by adding MTR (Hazard Ratio of 1.78 (CI 1.008–3.131)). DG or subtype neither correlated with OS or DFS and did not improve the prognostic value of the AJCC-staging.

Conclusion

The prognostic value of AJCC-staging on OS is not improved by either MTR, DG or subtype. However, the 8th AJCC-staging combined with a 3-tier MTR provides a better prognostic tool for DFS in esophageal adenocarcinoma treated with MIE after neoadjuvant chemo-radiotherapy.
514 CANCER CELLS PERSIST AFTER COMPLETE PATHOLOGICAL RESPONSE IN ESOPHAGEAL ADENOCARCINOMA
Authors: Walker R , Harrington J , Grace B , Sharpe B , Breininger S , Izadi F , Kelly J , Byrne J , Noble F , Rose-Zerilli M , Underwood T
Published: September 2020

In esophageal adenocarcinoma (EAC) with apparent pathological complete response (pCR) to neoadjuvant therapy (NAT) debate remains as to whether esophagectomy is required. Recurrence after pCR is not limited to distant metastases outside radiation or resection fields. It is unknown if cancer persists below the lower detection limit of current diagnostic technology. Trials randomising patients with apparent pCR to esophagectomy or active surveillance are currently recruiting in an attempt to spare patients the morbidity of esophagectomy.

Methods

Single cell (scRNAseq) was performed on fresh tissue taken at surgical resection to determine the transcriptomic profiles of cell populations in 24 EAC tumours and matched normal samples. Five tumour-normal pairs were also analysed using bulk RNA sequencing and high-precision mass spectrometry proteomics. Immunohistochemistry (IHC) was used to confirm pCR. Paired scRNAseq analysis of pre-and post-treatment specimens from three patients was used to compare transcriptomic profiles before and after NAT. Cancer cells were assigned a cancer stem cell module score curated from published gene sets.

Results

We analysed a total of 22,738 single cells forming 29 different cell states. In two samples with pCR, we repeated the pathological analysis and performed IHC using antibodies to known cancer proteins and identified no residual cancer cells (figure 1A). Bulk tissue RNA (figure 1B) and proteomic analysis did not detect cancer genes or proteins in the pCR samples. ScRNAseq, conversely, revealed small populations of persistent cancer cells in both complete responders (12/978 and 45/774) (figure 1C). Transcriptomic analysis of these residual cells identified upregulation of stem cell markers and high cancer stem cell scores in these remaining cells (figure 1D).

Conclusion

We have determined the cell states present across multiple different EAC and normal esophageal samples. We have shown cancer cells persisting after NAT, in patients with apparent pCR, beneath the lower detection limit of standard diagnostic approaches. These cells express gene programs consistent with cancer stem cells. Cancer stem cells are a critical subpopulation that drive tumour initiation, growth, and resistance to therapy. Esophagus sparing approaches in pCR may subject patients to risk of progression.
519 PERIOPERATIVE FLUID MANAGEMENT IN ESOPHAGECTOMY FOR CANCER AND ITS RELATION TO POSTOPERATIVE RESPIRATORY COMPLICATIONS
Authors: Van Dessel E , Moons J , Nafteux P , Van Veer H , Depypere L , Coosemans W , Coppens S , Neyrinck A
Published: September 2020

The optimal perioperative fluid management during esophagectomy is still not clear. Liberal regimens have been associated with higher morbidity and respiratory complications. Restrictive regimens might raise concerns for kidney function and increase the need to associate vasopressors. Recently, perioperative care is changing towards goal-directed fluid regimens as part of early recovery programs. The aim of this study was to investigate retrospectively the perioperative fluid administration during esophagectomy and to correlate this with postoperative respiratory outcome.

Methods

All patients who underwent esophagectomy between January–December 2016 were retrospectively analyzed. Patient characteristics, type of surgery and postoperative course were reviewed. Fluid administration and vasopressor use were calculated intra-operatively and during the postoperative stay at the recovery room. Fluid overload was defined as a positive fluid balance of more than 125 mL/m2/h during the first 24 hours. Patients were divided in 3 groups: GRP0 (no fluid overload/no vasopressors); GRP1 (need for vasopressors); GRP2 (fluid overload with/without vasopressors). Postoperative complications were prospectively recorded according to Esophagectomy Complications Consensus Group criteria. Multivariable analysis (binary logistic regression) for “any respiratory complication” was performed.

Results

103 patients were analyzed: 35 (34%) GRP0, 50 (49%) GRP1 and 18 (17%) GRP2. No significant differences were found for age, treatment (neoadjuvant vs. primary), type of surgery (Open/MIE), histology and comorbidities.

There were significant (p ≤ 0.001) differences in fluid balance/m2/h (75 ± 21 mL; 86 ± 22 mL and 144 ± 20 mL) across GRP0, GRP1 and GRP2 respectively.

We found differences in respiratory complications GRP0 (20%) versus GRP1 (42%;p = 0.034) and GRP0 (20%) versus GRP2 (61%;p = 0.002)) and “Comprehensive Complications Index” GRP0 (20.5) versus GRP1 (34.6;p = 0.015) and GRP0 (20.5) versus GRP2 (35.1;p = 0.009). Multivariable analysis for any respiratory complication is presented in FIGURE 1.

Conclusion

Among patients undergoing esophagectomy, there is a wide variety in the administration of fluid during the first 24 hours. There was a higher incidence of respiratory complications if patients received higher amounts of fluid or if vasopressors were used. Type of surgery (open versus MIE) did not impact respiratory outcome. We believe that a personalized and protocolized fluid administration algorithm should be implemented and that individual risk factors for patients at risk should be identified.
533 IMPACT OF LOCAL MICROBIOME ON THE ONSET OF ESOPHAGEAL ADENOCARCINOMA FOR THE DEVELOPMENT OF A STRATEGY FOR PREVENTION AND TREATMENT
Authors: Ricchitelli S
Published: September 2020

Esophageal adenocarcinoma (EAC) is one of the most aggressive gastrointestinal tumor. High mortality is due to difficulties in diagnosis at an early stage and to its biological aggressive features. Little is know about the association between esophageal microbiome dysbiosis and EAC pathogenesis. The aim of the study is the identification of a specific esophageal local microbiota that can be related to the pathogenesis and to the onset of EAC

Methods

We investigated the resident microbiome in 38 biopsies from Tumoral (T) and Non-Tumoral (NT) tissues obtained from 19 patients submitted to distal-EAC, cardiac-EAC, ESCC resection in Upper GI Surgery Division, Humanitas Research Hospital (Rozzano, Milano). We have analyzed the microbiota in biopsies obtained from EAC Tumoral tissues (T) and Non-Tumoral tissues (NT). After genomic DNA extraction the V3V4-hypervariable regions of the 16S-rRNA bacterial gene were amplified and sequenced on MiSeq Illumina sequencer. The Bioinformatic Data Analysis has been perfomed using the CLC Genomic Workbench.

Results

Alpha diversity analysis showed an increased microbial species richness in Esophageal Squamo-Cellular Carcinoma (ESCC) respect to distal/cardiac EAC and tissues without metaplasia. PERMANOVA statistical analysis was applied to estimate Beta Diversity significance. Bray-Curtis index showed a statistically significant different microbiome composition when comparing both cardiac and distal EAC versus ESCC (p-value 0.022 and 0.010 respectively) and when comparing samples with and without metaplasia. Relative abundances analysis obtained after the comparison of distal EAC, cardiac EAC and ESCC identified specific bacterial species in each group. Streptococcus genus is present only in cardiac EAC, Helicobacter pylori only in distal EAC.

Conclusion

Our study evidenced an increased microbial species richness in samples deriving from ESCC compared to EAC and samples without metaplasia. A significant difference was found comparing EAC with ESCC or with/without metaplasia tissues, mirroring a reduced biodiversity in EAC and metaplasia. We speculated a generalized alteration of the local microbiome from healthy to diseased tissue, characterized by certain bacterial strains that developed through the creation of a chronic inflammatory milieu that triggers the carcinogenic cascade.