bluuebunny/crossref_metadata_2025_split huggingface dataset:
804 THE PATTERN OF CT RECURRENCE FOLLOWING RESECTION OF ESOPHAGEAL CARCINOMA
Authors: Chowdhury Sheuli , Wong Lye-Yeng , DeSouza Melissa L , Dewey Elizabeth N , Hunter John G , Wood Stephanie G 
Published: September 2021

Abstract

While esophagectomy is the mainstay of multimodal treatment of esophageal cancer, the risk of recurrence is high. In spite of this, no formal recommendations exist on frequency or duration of computed tomography (CT) imaging for surveillance. The goal of this study was to determine the pattern of cancer recurrence following esophagectomy to develop an optimal surveillance program.

Methods
We performed a retrospective review of a single-institution esophageal disease registry, evaluating patients who underwent esophagectomy for esophageal cancer between 2000–2019. The surveillance protocol is CT in 3-month intervals for one year, 6-month intervals in year 2, then annually until the fifth year. Rates of recurrence were compared by stage, tumor factors, and chemoradiation status using chi-square tests. Monthly rates of recurrence and overall survival were assessed using Kaplan–Meier. Risk ratios for recurrence were evaluated with multivariate Cox regression accounting for age, gender, cancer type, stage, chemoradiation therapy, and tumor grade.

Results
Of the 368 included, 88% had Adenocarcinoma, 85% male, 96% Caucasian, 85% received chemotherapy, and 82% received radiation. 24% had pathologic complete response (pCR). The recurrence rate was 33%. 46% had clinical symptoms at time of recurrence, and 58% were diagnosed by routine surveillance CT. 21% of pCR had recurrence. 85% of recurrences occurred within 5 years, 72% within 3 years, and 56% within 2 years of surgery. Most frequent recurrence was lung (22%), followed by multi-site (21%), and regional lymph node (17%). There were notable differences in time to recurrence by site of recurrence (Figure 1) (p = 0.03).

Conclusion
In our population, 33% of patients had recurrence of esophageal cancer following surgical resection, with highest risk of recurrence within the first 3 postoperative years. These findings favor more frequent surveillance during this period, followed by annual surveillance until 5 years.
807 ASSOCIATION OF BOLUS TRANSIT TIME ON BARIUM ESOPHAGOGRAM WITH ESOPHAGEAL PERISTALSIS
Authors: Razia Deepika , Trahan Amy , Giulini Luca , Baboli Komeil M , Mittal Sumeet K 
Published: September 2021

Abstract

The threshold criteria for diagnosing ineffective esophageal motility (IEM) has changed over the years and is based on the proportion of failed and weak peristalses. Bolus transit time (BTT) on barium esophagogram (BE) can intuitively be the ‘gold standard' for assessing the effectiveness of esophageal peristalsis. The aim of this study was to associate upright and prone BTT with esophageal peristalsis and dysphagia in patients with normal lower esophageal sphincter (LES) parameters.

Methods
Patients with normal LES on high-resolution manometry (HRM) who also had a standard-protocol BE from 2017 to 2020 were included. Patients with previous foregut surgery, hiatal hernia, jackhammer esophagus, distal esophageal spasm, fragmented peristalsis, and those with &lt; or &gt; 10 single swallows on HRM were excluded. Based on the number of normal swallows (DCI &gt;450 mmHg.s.cm), the patients were divided into 11 groups (10 normal to 0 normal). Upright and prone BTT were measured on BE. Fractional polynomial and logistic regression analysis were used to study association (along with rate of change) between BTT, dysphagia, and peristalsis.

Results
In total, 146 patients met the inclusion criteria. Prone BTT increased in tandem with a decrease in the number of normal peristalses (p &lt; 0.001), but no difference was noted in upright BTT (p = 0.317). Two deflection points were noted on the association between peristalsis and prone BTT at 50%, 40 seconds and 30%, 80 seconds on the y and x-axes, respectively, after which declining peristaltic function was independent of prone BTT. Patients with prone BTT &gt;40 seconds had nearly 6-fold higher odds of having zero normal peristalses (p = 0.002). Increasing prone BTT was associated with increasing dysphagia (p &lt; 0.05).

Conclusion
Prone, but not upright BTT, correlates with the proportion of normal esophageal peristalses and dysphagia. The phenotype of abnormal swallows (failed, weak) appears to have minimal impact on BTT. The current perspective of manometric classification may need to be adjusted to use the proportion of normal peristalses as a criterion.
814 SMAD4 AS A POTENTIAL GATEKEEPER FOR GENOMIC INSTABILITY AND MTOR-MEDIATED TUMORIGENESIS IN ESOPHAGEAL ADENOCARCINOMA
Authors: Milne Julia , Gotovac Jovana , Fujihara Kenji , Simpson Kaylene , Duong Cuong , Phillips Wayne , Clemons Nicholas 
Published: September 2021

Abstract

Extensive genomic analysis of patient samples has identified genes whose mutation or loss map malignant progression from Barrett’s metaplasia, through low- (CDKN2A) and high-grade dysplasia (TP53), to invasive adenocarcinoma (SMAD4). Interestingly, loss of SMAD4 has been found to occur exclusively in the invasive disease stage, but the reason for this is unknown. This work aimed to characterise the role of SMAD4 in esophageal adenocarcinoma (EAC) tumorigenesis and identify novel therapeutic targets for SMAD4-deficient EAC.

Methods
We developed a novel in vivo tumorigenesis model that demonstrates progression of dysplastic Barrett’s esophagus (BE) to invasive EAC upon knockout of SMAD4. We conducted parallel genome-wide CRISPR-Cas9 knockout screens, both in vitro and in vivo, on a background of either wildtype-SMAD4 or SMAD4-knockout dysplastic BE cells to identify co-operative drivers of tumorigenesis in vivo, as well as synthetic lethal interactions to identify potential therapeutic targets in SMAD4-deficient EAC. Functional validation of hits was performed using cell-based assays and drugs targeting candidate molecular targets.

Results
We identified a synthetic lethal relationship between SMAD4-deficiency and cell cycle checkpoint inhibition, suggesting a role for SMAD4 in maintaining genomic stability and a potential novel therapeutic avenue for SMAD4-deficient EAC. A concurrent in vivo CRISPR-Cas9 tumorigenesis screen produced tumors 4-fold faster than loss of SMAD4 alone and identified regulators of mTOR signalling and SMAD4 as co-operative drivers of tumorigenesis in EAC. Interestingly, these tumorigenic cells exhibited an inherent dependency on specific translation mechanisms downstream of mTOR. Meanwhile, wildtype-SMAD4 BE cells failed to thrive in vivo with mTOR modifications alone, indicating a true co-operative effect at play with SMAD4 loss.

Conclusion
This study uncovered a potential gatekeeping role of SMAD4 in maintaining genomic stability and inhibiting mTOR-mediated EAC tumorigenesis. In sum, loss of SMAD4 was found to increase genomic instability, thereby rendering EAC cells sensitive to cell cycle checkpoint impediment, whilst simultaneously co-operating with modulated mTOR signalling to promote tumorigenesis in EAC xenograft models.
824 MOLECULAR UNDERPINNINGS OF NEUROENDOCRINE DIFFERENTIATION IN ESOPHAGEAL ADENOCARCINOMA AND ITS PROGNOSTIC SIGNIFICANCE
Authors: Wilson G , Elimova E , Yeung J , Darling G , N Kalimuthu S 
Published: September 2021

Abstract

The presence of neuroendocrine (NE) differentiation has been previously reported in both morphological subtypes, (intestinal and diffuse), of esophageal adenocarcinoma, (EAC). This is more commonly seen in the post-treatment setting and is thought to confer a more aggressive phenotype. However, the molecular underpinning and therapeutic implications of NE differentiation within EAC is poorly understood. Herein, the goal is to understand the molecular mechanisms, evolution and the prognostic significance of NE development in EAC tumours.

Methods
We interrogated a previously published transcriptome dataset with matched H&E slides, TCGA EAC (N = 86). Moreover, we have begun reviewing H&E slides from EAC patients from UHN (N = 50). We created a NE gene expression signature (N = 25 genes) from the literature as an initial proof of concept. We quantified the presence of a NET-like/organoid morphology in the matched H&E slides and correlated it with the average z-score of the NE gene signature calculated from the matched transcriptome data.

Results
NE differentiation was present in 27/86 cases with a mean of 21.01% +/− 20.9 within the tumour area. We compared the expression of our NE gene signature with the proportion of NE morphology and observed a moderate correlation between morphology with the gene expression (R^2 = 0.546, P &lt; 0.001 ordinary least squares regression), providing validation that the organoid/NET-like morphological pattern correlates with NE differentiation. Furthermore, we have validated the presence of NE morphology in a subset of the UHN samples using electron microscopy and immunohistochemistry (chromogranin and synaptophysin).

Conclusion
This is a first of a kind study to profile a specific morphology with a transcriptional signature within EAC across a large cohort of patient samples. Correlation of NE-features with clinical outcome together with treatment resistant implications is currently underway.
851 TRANSHIATAL ESOPHAGECTOMY: A SELECTIVE ROLE IN THE CURATIVE APPROACH TO ESOPHAGEAL CANCER
Authors: Butt Waqas , Donlon Noel E , Bolger Jarlath C , Donohoe Claire L , Ravi Narayanasamy , Reynolds John V 
Published: September 2021

Abstract

Surgery remains central to the curative management of esophageal cancer. At this Center, based on evidence from the literature, transthoracic en bloc surgery (TTE) is standard, however transhiatal esophagectomy (THE) is considered for predicted early stage junctional (AEG) tumors, multifocal in situ cancer, or where age or respiratory co-morbidity suggests a high risk with TTE. This audit reports this experience over 19 years.

Methods
Data was acquired from our prospectively maintained database. Patients who underwent esophagectomy with curative intent and gastric tube reconstruction for mid/distal esophageal or esophagogastric junction cancer (cT1-4aN0-3 M0) from 2000 to 2018 were included. THE was compared with TTE for operative complications (ECCG-defined), and proxy markers of oncologic quality.

Results
933 patients were included, 166 (18%) THE and 767 (82%) TTE. The median (range) age was 62(22–83) vs 67(36–86) in TTE and THE, with 43(6%) and 40(24%) over 75 respectively (p &lt; 0.01). There were significantly (p &lt; 0.01) more early tumors in the THE (58%) vs the TTE group(11%). 23% were &gt; ASA 3 in THE vs 12% TTE (p &lt; 0.01). Postoperative pulmonary complications (PPCs) were 11% and 18.3% in THE and TTE cohorts, respectively(p 0.03). In-hospital mortality was 1.2%vs3.4% in THE vs TTE (p = 0.21). Five-year survival was 67% and 40% in THE vs TTE, respectively.

Conclusion
These data are consistent with the safe and effective use of THE in selected cases. Notably, favourable major pulmonary morbidity and mortality rates for a higher risk cohort. We suggest that this approach may still be relevant in defined scenarios in an increasingly minimally invasive era.
855 OPTIMIZATION OF SURGICAL DELAY AFTER INDUCTION CHEMORADIATION FOR ESOPHAGEAL CANCER: 10 YEARS RETROSPECTIVE MULTI-CENTER STUDY
Authors: Legault-Dupuis Alexis , Bouchard Philippe , Nicodème Frederic , Gagne Jean-Pierre , Simard Serge , Lacasse Yves , Hache Pier-Luc , Couture Christian , Laliberte Anne-Sophie 
Published: September 2021

Abstract

The treatment of esophageal cancer is in constant evolution. Most of the esophageal cancer receive induction chemoradiation therapy. Surgical delay has been studied but the optimal timing has not been clarified. Through the years, surgical delay has been modified by surgeons in our institutions, going from an average of 6 weeks delay to an average of 10 weeks delay. It is time to ask if this change has a real positive impact on our patient.

Methods
In this retrospective multi-center study, we combined data from two center in Quebec city that performs oncologic esophagectomy. The surgical delay went from 6 to 10 weeks around 2014. All surgeons changed their practice at that moment. We retrospectively analysed 5 years before and after the change of practice and created two cohorts of patients. Our primary outcome compared complete pathologic response rate. Our secondary outcomes were surgical complications, anastomotic leak, disease free survival and overall survival.

Results
Thirty-eight patients had surgery under 8 weeks (mean: 6 weeks) after their induction chemoradiation compared to 64 patients that had surgery after 8 weeks (mean: 10 weeks). There was no statistical significant difference between groups for the complete pathologic response (32% vs 25%, p = 0,16). Important complications were similar, with a rate of 24% vs 28% (p = 0,69). Anastomotic leaks were less frequent in the less than 8 weeks group, but no statistical significance was obtained (13% vs 27%, p = 0,14).No difference in the disease-free survival rate and overall survival rate was noted (DFS 40% vs 55% (p = 0,32), OS 38% vs 38% (p = 0,29)).

Conclusion
The treatment of esophageal cancer is in constant evolution, induction therapy and surgical technics involve over time. Surgical delay has no impact on complete pathologic response, complication and overall survival. There is no advantage to wait longer before surgery.
93 A CASE OF G-CSF(GRANULOCYTE-COLONY STIMULATING FACTOR) PRODUCING ESOPHAGEAL CANCER WITH ENTEROBLASTIC DIFFERENTIATION
Authors: Kitamura Yu , Oshikiri Taro , Takiguchi Gosuke , Urakawa Naoki , Hasegawa Hiroshi , Yamamoto Masashi , Kanaji Shingo , Matsuda Yoshiko , Yamashita Kimihiro , Matsuda Takeru , Nakamura Tetsu , Suzuki Satoshi , Kakeji Yoshihiro 
Published: September 2021

Abstract

Granulocyte-colony stimulating factor (G-CSF) producing tumor is one type of growth factor producing tumor that induces leukocytosis. On the other hand, adenocarcinoma with enteroblastic differentiation disease is known as α-fetprotein (AFP), glypican3, and Sal-like protein 4 (SALL4) producing tumor.
We report a first case of G-CSF producing esophageal cancer with enteroblastic differentiation which has never been reported in the world.

Methods
[Case presentation]: A fifty-six year-old man was admitted to our hospital to treat esophageal carcinoma.
His body temperature was elevated. Blood biochemistry tests showed leukocytosis (WBC 14000/μl).
Gastroscopy revealed a 10-cm diameter, superficial elevated lesion in the lower thoracic esophagus.
Biopsy findings indicated a diagnosis of adenocarcinoma. No distant metastasis, but right subclavian and para esophageal lymph nodes swelling were identified via computed tomography.
Thus, we planned neo adjuvant chemotherapy (NAC) (5-FU 800 mg/m2 plus Cisplatin 80 mg/m2) before surgical resection. The patient’s hyperthermia and leukocytosis improved by not antibiotics but NAC.
Therefore, we suspected G-CSF producing tumor.

Results
The serum level of G-CSF was markedly elevated at 133 pg/ml (normal range, &lt;39 pg/ml).
Additionally, PET/CT showed abnormally high uptake of (18) F-FDG not only by the tumor itself, but also diffusely throughout the bone marrow.
The patient underwent minimally invasive esophagectomy in the prone position with two-field lymph node dissection.
Immunohistochemical studies showed G-CSF producing adenocarcinoma with enteroblastic differentiation (AFP negative, glypican3 and SALL4 positive). Pathological stage was pT2N0M0, stageII.
After resection, improvement of hyperthermia, leukocytosis, and serum level of G-CSF can be seen. Findings of (18) F-FDG throughout the bone marrow were also disappeared.

Conclusion
We experienced an extremely rare case of G-CSF producing, esophageal adenocarcinoma with enteroblastic differentiation.
Managing the Gender Wage Gap—How Female Managers Influence the Gender Wage Gap among Workers
Authors: Zimmermann Florian 
Published: September 2021

Abstract
Previous research shows that female managers narrow the gender wage gap (GWG) among workers but does not disentangle two general underlying mechanisms. First, female managers might use their organizational power to change organizational practices and make organizations more gender-equal. Second, female workers might benefit from interacting with a female manager, e.g. through homophily and mentoring. To disentangle these two mechanisms, I distinguish between female managers at the first management level, which is responsible mainly for organizational practices, and at the second management level, which mainly interacts with workers. Additionally, I consider practices enhancing gender equality, such as work-life balance practices. Using German linked employer–employee panel data and a firm fixed-effects regression, I find that female first-level managers slightly narrow the GWG. This influence is not affected by the consideration of organizational practices. Hence, female first-level managers do not affect workers’ by changing organizational practices. In contrast, female second-level managers considerably narrow the GWG among workers. In summary, female managers substantially reduce the GWG among workers, and this effect works via the manager–worker interaction mechanism. Hence, increasing the share of female second-level managers might close the GWG.
Five-year outcomes after state-of-the-art percutaneous coronary revascularization in patients with de novo three-vessel disease: final results of the SYNTAX II study
Authors: Banning Adrian P , Serruys Patrick , De Maria Giovanni Luigi , Ryan Nicola , Walsh Simon , Gonzalo Nieves , Jan van Geuns Robert , Onuma Yoshinobu , Sabate Manel , Davies Justin , Lesiak Maciej , Moreno Raul , Cruz-Gonzalez Ignacio , Hoole Stephen P , Piek Jan J , Appleby Clare , Fath-Ordoubadi Farzin , Zaman Azfar , Van Mieghem Nicolas M , Uren Neal , Zueco Javier , Buszman Pawel , Iniguez Andres , Goicolea Javier , Hildick-Smith David , Ochala Andrzej , Dudek Dariusz , de Vries Ton , Taggart David , Farooq Vasim , Spitzer Ernest , Tijssen Jan , Escaned Javier 
Published: September 2021

Abstract

Aims
The SYNTAX II study evaluated the impact of advances in percutaneous coronary intervention (PCI), integrated into a single revascularization strategy, on outcomes of patients with de novo three-vessel disease. The study employed decision-making utilizing the SYNTAX score II, use of coronary physiology, thin-strut biodegradable polymer drug-eluting stents, intravascular ultrasound, enhanced treatments of chronic total occlusions, and optimized medical therapy. Patients treated with this approach were compared with predefined patients from the SYNTAX I trial.

Methods and results
SYNTAX II was a multicentre, single-arm, open-label study of patients requiring revascularization who demonstrated clinical equipoise for treatment with either coronary artery bypass grafting (CABG) or PCI, predicted by the SYNTAX score II. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which included any revascularization. The comparators were a matched PCI cohort trial and a matched CABG cohort, both from the SYNTAX I trial. At 5 years, MACCE rate in SYNTAX II was significantly lower than in the SYNTAX I PCI cohort (21.5% vs. 36.4%, P &lt; 0.001). This reflected lower rates of revascularization (13.8% vs. 23.8%, P &lt; 0.001), and myocardial infarction (MI) (2.7% vs. 10.4%, P &lt; 0.001), consisting of both procedural MI (0.2% vs. 3.8%, P &lt; 0.001) and spontaneous MI (2.3% vs. 6.9%, P = 0.004). All-cause mortality was lower in SYNTAX II (8.1% vs. 13.8%, P = 0.013) reflecting a lower rate of cardiac death (2.8% vs. 8.4%, P &lt; 0.001). Major adverse cardiac and cerebrovascular events’ outcomes at 5 years among patients in SYNTAX II and predefined patients in the SYNTAX I CABG cohort were similar (21.5% vs. 24.6%, P = 0.35).

Conclusions
Use of the SYNTAX II PCI strategy in patients with de novo three-vessel disease led to improved and durable clinical results when compared to predefined patients treated with PCI in the original SYNTAX I trial. A predefined exploratory analysis found no significant difference in MACCE between SYNTAX II PCI and matched SYNTAX I CABG patients at 5-year follow-up.
Implementation of two policies to extend maternity leave and further restrict marketing of breast milk substitutes in Vietnam: a qualitative study
Authors: Payán Denise Diaz , Zahid Neha , Glenn Jeffrey , Tran Ha TT , Huong Tran Thi Thu , Moucheraud Corrina 
Published: September 2021

Abstract
Policy research can reveal gaps and opportunities to enhance policy impact and implementation. In this study, we use a theoretically informed qualitative approach to investigate the implementation of two policies to promote breastfeeding in Vietnam. We conducted semi-structured interviews with national and local policy stakeholders (n = 26) in 2017. Interviews were audio-recorded, transcribed verbatim and then translated to English by certified translators. Transcript data were analysed using an integrated conceptual framework of policy implementation. Respondents identified several positive outcomes resulting from implementation of an extended maternity leave policy (Labour Code No. 10/2012/QH13) and further restrictions on marketing of breast milk substitutes (Decree No. 100/2014/ND-CP). Decree No. 100, in particular, was said to have reduced advertising of breast milk substitutes in mass media outlets and healthcare settings. Key implementation actors were national-level bureaucratic actors, local organizations and international partners. Findings reveal the importance of policy precedence and a broader set of policies to promote the rights of women and children to support implementation. Other facilitators were involvement from national-level implementing agencies and healthcare personnel and strength of government relationships and coordination with non-governmental and international organizations. Implementation challenges included insufficient funding, limited training to report violations, a cumbersome reporting process and pervasive misinformation about breast milk and breast milk substitutes. Limited reach for women employed in the informal labour sector and in rural communities was said to be a compatibility issue for the extended maternity leave policy in addition to the lack of impact on non-parental guardians and caretakers. Recommendations to improve policy implementation include designating a role for international organizations in supporting implementation, expanding maternity protections for all working women, building local-level policy knowledge to support enforcement, simplifying Decree No. 100 violation reporting processes and continuing to invest in interventions to facilitate a supportive policy environment in Vietnam.