bluuebunny/crossref_metadata_2025 huggingface dataset:
488 SNAIL TRANSFECTION INDUCES EPITHELIAL-MESENCHYMAL TRANSITION WITH PROPERTIES OF CANCER STEM-LIKE CELL IN ESOPHAGEAL SQUAMOUS CELL CANCER
Authors: Tzao Ching , Wu Meng-Hsun , Chen Ben-Hen
Published: September 2021

Cancer stem-like cell (CSC) is an important player in tumorigenesis and tumor progression. Snail has been demonstrated as a key driver for epithelial-mesenchymal transition (EMT) that is closely linked with generation of stem-like cell in human cancer. We aim to investigate if Snail transfection induces EMT and properties of stem-like cell in esophageal squamous cell carcinoma (ESCC) cell lines.

Methods

A lentivirus system was used to transfect human Snail via a plasmid pLV-EF1a-hSnail-Hyg into KYSE-170 and KYSE-510 ESCC cell lines. Immunoblotting was used to determine expression of EMT associated markers including Vimentin, E-cadherin, Fibronectin and N-cadherin. Assays for cell migration and invasion were conducted in Snail-transfected cells and its vector control. Cytotoxicity (MTT) and cell proliferation assay was used to determine cell growth. Sphere formation assay and flow cytometry (FCM) were employed to characterize stem cell properties while examining expression of stemness genes by using real-time polymerase chain reaction (PCR).

Results

After Snail transfection, mesenchymal markers, Vimentin, N-cadherin increased, whereas epithelial marker E-cadherin decreased. Snail-transfected.

ESCC cells presented a significant increase in RNA expression of stemness genes such as Nanog, Oct4, ABCG2 and Sox2 with an induction in sphere formation. Moreover, ability of cell migration and invasion increased after Snail-transfection in ESCC with increased chemoresistance to cisplatin, taxol, and 5-Fluorouracil(5-FU) and an increase in radioresistance as well.

Conclusion

Our results demonstrated that Snail transfection induced EMT with properties of CSC in ESCC cell lines.
490 COLONIC INTERPOSITION FOR ESOPHAGEAL REPLACEMENT AFTER ESOPHAGECTOMY FOR CANCER—A SINGLE CENTER EXPERIENCE
Authors: Sabino Flávio , Guimarães-Filho Marco , Ribeiro Luciana , Fernandes Daniel , Felipe Pinto Luis
Published: September 2021

The standard esophageal replacement after esophagectomy for cancer treatment is a gastric conduit, as it is a simpler technique than the other options available, requiring only one anastomosis. However, when the stomach is not available, a left- or right colon graft interposition can be performed. The purpose of this study was to review our experience with colon interposition following esophagectomy for cancer and assess the surgical outcomes.

Methods

The clinical data and surgical outcomes form patients who underwent esophagectomy with colon interposition for cancer treatment, in a single institution, between January 1990 and December 2017. The results were compared with cases with gastric reconstruction.

Results

From January 1990 and December 2017, 25 cases of transhiatal esophagectomy with colon interposition were identified. In the same period, 97 cases of transhiatal esophagectomy with gastric pull-up were also performed. The patient’s clinical data and surgical outcomes are presented in Table 1. The indication for performing a colon interposition was positive distal margin in 87% of cases, gastric conduit ischemia in 8,7% and prior gastric surgery in 4,3%. The most common pull-up route was the posterior mediastinum (87%).

Conclusion

Our results are in line with the literature and demonstrate that colon interposition after esophagectomy is feasible and, despite having a significant morbimortality, appears to be a valuable alternative for the challenging situation where the stomach is not available.
492 TUMOR ASSOCIATED MACROPHAGE PROMOTES EPITHELIAL-TO-MESENCHYMAL TRANSITION IN ESOPHAGEAL SQUAMOUS CELL CANCER
Authors: Tzao Ching , Cheng Li-Yuan , Chang Chien-Chih
Published: September 2021

We aimed to investigate the role of tumor associated macrophage (TAM) in epithelial-to-mesenchymal transition (EMT) in esophageal squamous cell cancer (ESCC).

Methods

Expression of CD68 and EMT markers was determined in resected ESCC tumors by immunohistochemistry with clinicopathologic correlation. M2-polarized macrophages were generated from human U937 cells treated with 50 ng/ml phorbol myristate acetate (PMA) while cultured with PMA plus Th2 cytokines. KYSE-510 ESCC cell was co-cultured with M2 macrophages, followed by determination of expression for EMT markers by Western blot. In situ expression of E-cadherin and vimentin was determined using immunofluorescence staining Cell proliferation, invasion and extracellular matrix (ECM) adhesion assays were performed to determine phenotypic characteristics of cultured ESCC cells.

Results

High expression of CD68 in resected ESCC correlated with worse survival. In addition, expression of CD68 in resected ESCC tumors correlated positively with expression of Snail and vimentin but inversely with E-cadherin. Compared with KYSE-510 cells cultured alone, those co-cultured with M2 macrophage showed higher expression of snail, vimentin, and fibronectin with a more spindle-shaped morphology, suggesting a mesenchymal differentiation. Further, cell proliferation, invasion and ECM adhesion were significantly more pronounced in M2 macrophage co-cultured ESCC cells.

Conclusion

EMT markers correlated with the number of TAM within resected ESCC tumors, suggesting an association of cancer inflammation in promoting EMT in ESCC. A link between cancer inflammation mediated by TAM deemed to be supported by increased expression of EMT markers and phenotypic changes related to EMT in ESCC cells co-cultured with M2 macrophage. Our results suggest an important role of TAM in promoting EMT in tumor microenvironment with regards to cancer inflammation in ESCC.
532 OUTCOME OF QUILICI’S HEPATIC SHOULDER PROCEDURE TO AUGMENT LAPAROSCOPIC HIATOPLASTY IN LARGE OR RECURRENT HIATAL HERNIA
Authors: Zacherl Johannes , Kertesz Viktoria , Höfle Cordula , Gensthaler Lisa , Eltschka Bernhard , Albinni Said , Schneider Florian , Schima Wolfgang , Sitzwohl Christian , Radlspöck Wolfgang
Published: September 2021

Laparoscopic hiatoplasty and fundoplication is the gold standard of surgical treatment of GERD and hiatal hernia. However, the main drawback of laparoscopic hiatal hernia repair is a substantial recurrence rate.

Hence, prosthetic meshs have been used to reduce the risk for recurrence. But meshs may cause major complications. As a consequence we adopted the hepatic shoulder plasty described by Quilici to augment the hiatal hernia repair in patients with a high risk for hernia recurrence.

Methods

Patients with large (>4 cm) axial hiatal hernia, giant paraesophageal or with recurrent hernia consecutively underwent laparoscopic hernia repair with crural sutures and hepatic shoulder plasty. A Toupet or a floppy Nissen fundoplication was added. In patients with giant paraesophageal hernia the hernia sack was resected.

Perioperative complications were recorded. Follow-up comprised endoscopy and/or radiography and QoL-evaluation with the Eypasch score (GIQLI).

Results

Between 2012 and 2018 51 patients (mean age 71 years, 65% female) underwent Quilici’s procedure. Among them 33,3% had one or more previous hiatal hernia repair. There were no conversions. Postoperative complication rate was 7.8%. At follow-up after 2 years 6 recurrences (12%) were encountered, 4 of them were symptomatic (8%). One patient underwent reoperation due to hernia recurrence. In 84% QoL was significantly improved at follow-up.

Conclusion

In patients with high risk of recurrence, biological augmentation of the hiatal closure with the left lobe of the liver may be a valuable alternative to prosthetic reinforcement. We observed no complication attributable to liver lobe transposition.
547 THE ROLE OF HEAT SHOCK PROTEIN 90 IN HYPOXIA INDUCED ANGIOGENESIS AND EPITHELIAL-MESENCHYMAL TRANSITION OF ESOPHAGEAL SQUAMOUS CELL CANCER
Authors: Tzao Ching , Wang Chin-Kun
Published: September 2021

Hypoxia is known as an important trigger for the development of metastases in human cancers. Heat shock proteins (Hsps) are up-regulated by cellular stressors including hypoxia. To date, the functional role of Hsps within the hypoxic tumor microenvironment for esophageal squamous cell cancer (ESCC) remains poorly defined.

Methods

CoCl₂ was used to induce hypoxia in cultured ESCC cells which was confirmed by 2′,7′ –dichlorofluorescin diacetate (DCFDA) assay. 7-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), a selective Hsp90 inhibitor, was used to treat 2 ESCC cell lines, KYSE-170 and -510 cells pretreated with or without CoCl₂₂₂₂₂ in different concentrations, followed by cytotoxicity (MTT) and migration assays. In parallel, expression of Hsp90, vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1α (HIF-1α), and markers related to epithelial-mesenchymal transition (EMT) such as snail/E-cadherin, by immunoblot or ELISA while analyzing cell proliferation and migration of treated ESCC cells.

Results

CoCl₂ induced hypoxia was supported by induction of reactive oxygen species (ROS). CoCl₂ (200 μM) significantly suppressed cell viability and proliferation with a concomitant up-regulation of VEGF and HIF-1α in a dose-dependent fashion. In contrast, cell migration was significantly increased in response to CoCl₂ while down-regulating E-cadherin with a concomitant increase in Snail expression. 17-DMAG decreased expression of VEGF and HIF-1α while inhibiting cell migration and invasion.

Conclusion

Our data demonstrate that CoCl2 induced hypoxia promotes EMT and angiogensis, which are inhibited by 17-DMAG. These results suggest that hypoxia induced EMT and angiogensis is Hsp90 dependent in ESCC.
622 CORRELATION ANALYSIS BETWEEN MAJOR FOOD GROUPS' CONSUMPTION AND THE RESULTS OF 24-HOURS OESOPHAGEAL PH-IMPEDANCE STUDIES
Authors: Morozov Sergey , Kropochev Vasily , Isakov Vasily
Published: September 2021

Aim

To evaluate association of number of gastroesophageal refluxes detected with oesophageal pH-impedance study with dietary patterns.

Methods

Food frequency questionnaire (Nutrilogic, Russia) was used to assess diet of subjects enrolled in the study in terms of nutrients consumption and food groups' structure. Dietary patterns were calculated according to the Healthy Eating Index (HEI), for the following major groups of foods: grains, fruits, vegetables, dairy products, meats, fats and confectioneries. The results are shown as a quotient of a division of actual values by the recommended. Oesophageal 24-hours pH-impedance (Ohmega, Laborie, the Netherlands) parameters were analysed. Spearman rank R was used to reveal correlation between number and type of gastroesophageal refluxes (GER) and the dietary patterns assessment.

Results

Forty consecutive patients (12 with gastroesophageal reflux disease, 28 females, age: 52.2 ± 12.9 y.o.) were enrolled. Mean energy value of the ration was 2302 ± 1391 kcal/day. Pattern of major food groups consumption was as follows: grains 1.4 ± 0.7, vegetables 1.1 ± 0.7, fruits 0.8 ± 0.9, dairy products 0.6 ± 0.6, meats 1.7 ± 1.0, fats 0.6 ± 0.8, confectioneries 0.3 ± 0.5. Mean number of GERs was 43.8 ± 24.4, acid GERs—26.2 ± 20.5 a day. Pattern of dairies consumption correlated with total number of GERs (Spearman R = 0.47, p < 0.05), weak-acid GERs (R = 0.49, p < 0.05), and non-acid GERs (R = 0.62, p < 0.05). Consumption of confectioneries correlated with high (at 17 cm above LES) GERs: R = 0.47, p < 0.05.

Conclusion

Type and number of gastroesophageal refluxes correlate with major food groups consumption. This preliminary results may serve as a basis for further research in larger comparative trials and may be considered when diet modification is planned for patients with GERD.
634 ROBOTIC-ASSISTED HIATAL HERNIA AND GASTROESOPHAGEAL DISEASE SURGERY: INITIAL RESULTS AND EXPERIENCE IN A SINGLE INSTITUTION
Authors: Farrarons Sara Sentí , Font Arantxa Clavell , Bosch Cristina Albero , Martin Marta Viciano , Savall Elisenda Garsot
Published: September 2021

Gastroesophageal reflux disease, associated with sliding or large paraesophageal hiatal hernia, represents a common disease that frequently needs a surgical solution. The repair of large paraesophageal hiatal hernias is still a challenge in minimally invasive surgery but the robotic approach seems to gain widespread acceptance because offers enhanced visualization, dexterity and reach, which may facilitate the hiatal reconstruction and mediastinal dissection.

Methods

Between June 2019 and February 2021, 23 patients (5 male, 18 female) underwent robotic approach fundoplication (19 sliding hernia, 3 paraesophageal and 2 gastroesophagic reflux) after being pre operative diagnosed. All surgeries were elective. Biosynthetic tissue absorbable mesh was applied in one patient with double time recurrence hernia. Sixteen patients underwent total fundoplication (Nissen), 6 patients had Toupet fundoplication, and one patient had hiatus repair without fundoplication.

Results

The mean age of the patients was 61 years. Biosynthetic mesh was used in one patient. The mean operative time was 127 minutes (80-240) and no intraoperative complications were described. There were no conversions to open or laparoscopic procedures. Nine of the twenty-three patients underwent redo hiatal hernia repairs and the mean hospital stay was 2 days. Only one patient had a major complication (Clavien Dindo 3b) requiring urgent surgery. The early and 30 day mortality rate was 0%.

Conclusion

In our experience, robotic approach to paraesophageal repair seems safe and effective with low complication rates even in high-risk patients and those with redo surgery. Subjectively, the robotic approach provides the surgeon better vision and maneuverability during the intervention. We hope to progressively increase the number of robotic cases to analyse long-term clinical outcomes such as hiatal hernia recurrences, need of medical therapy and quality of life.
635 ROBOTIC REDO FUNDUPLICATION FOR A TWO TIME RECURRENT HIATAL HERNIA. HOW WE DO?
Authors: Font Arantxa Clavell , Farrarons Sara Sentí , Bosch Cristina Albero , Martín Marta Viciano , Savall Elisenda Garsot
Published: September 2021

In the video we perform the crural robotic reinforcement with de use of biosynthetic mesh (Gore Bio-A) without any funduplication in a 37 years-old woman with a two time hernia hiatal recurrence. Although laparoscopic surgery to treat primary hiatal hernias (HHs) is the gold standard approach, the use of robotic platforms seems to gain weight. This video aims to show the step-by-step in a redo hiatal surgery and the benefits of robotic surgery.

Methods

Here in the video we present a 37-year old woman patient who underwent previously two laparoscopic Nissen fundoplication because of hiatal hernia and gastroesophageal reflux disease. The first surgery was done in 2015 and the patient needed a laparoscopic redo due to hiatal relapse, done in 2019 with nonabsorbable mesh reinforcement. Posteriorly, the patient visited our clinic for epigastric pain and vomits. The proper study with gastroscopy, CT scan and barium swallow was ruled out, pointing a new relapse. With this results, the patient was purposed a redo cruroplasty with robotic approach.

Results

In the video we perform the crural robotic reinforcement with de use of biosynthetic absorbable mesh (Gore Bio-A) without any funduplication. This video aims to show the step-by-step in a redo hiatal surgery and the benefits of robotic surgery. In our short experience and according to the related publications we believe the robotic platform is feasible, safe and effective.

Conclusion

Although laparoscopic surgery to treat primary hiatal hernias (HHs) is the gold standard approach, the use of robotic platforms in complicated procedures such as relapsed hiatal hernias or gastroesophageal reflux disease (GERD) recurrence seems to gain weight. This is because of robotic approach may help in demanding surgeries with fibrosis and modified anatomy so it provides more precision with the articulating arms and better visualisation due to a 3D view and stable camera.

Video

https://drive.google.com/file/d/1BjwLWiEaNZWv6ULO9p-rec1LgSopfb1f/view?usp=sharing
647 THE LEFT AND RIGHT RECURRENT LARYNGEAL NERVE LYMPH NODES POSSESS DIFFERENT ANATOMICAL CHARACTERISTICS AND RISK STRATIFICATIONS OF METASTASIS
Authors: Zhang Guoqing , Zhao Shanshan , Li Qiyuan , Yuan Lulu , Gao Gen , Li Jindong , Li Xiangnan
Published: September 2021

The left and right recurrent laryngeal nerve(RLN) are asymmetrical, and the precise differences and metastasis risk stratifications based on preoperative CT scan between the left and right RLN lymph nodes have not yet been analyzed. In this study, we compared the anatomical characteristics and generated prediction models to predict the probability of left and right RLN lymph node metastasis using preoperative clinical data in patients undergoing thoracolaparoscopic esophagectomy with cervical anastomosis to guide clinical treatment.

Methods

We retrospectively reviewed the clinical data of 1660 consecutive patients with thoracic esophageal cancer who underwent esophagectomy with cervical anastomosis at the Department of Thoracic Surgery at our center between January 2015 and December 2020 and investigated the anatomical characteristics and risks of bilateral RLN lymph nodes according to preoperative CT scan and pathological examination findings.

Results

A total of 299 and 343 patients who underwent left(right) RLN lymph node dissection were included in the final analysis. By plotting ROC curves, we concluded that the cutoff values of the long and short axis to predict metastasis of the left (right) RLN lymph nodes were 10 (8 mm) and 7.5 (6.5 mm), respectively. The short axis rather than the long axis was significantly associated with left RLN lymph node metastasis. Correspondingly, the long axis was much more important than the short axis in regard to the right RLN lymph nodes.

Conclusion

There were different anatomical characteristics and precise metastasis risk stratifications between the left and right RLN lymph node metastases.
650 POSTOPERATIVE EARLY ORAL FEEDING PROGRAM ACCELERATES THE RECOVERY OF GASTROINTESTINAL FUNCTION IN ESOPHAGEAL CANCER PATIENTS
Authors: Wang Peiyu , Chen Xiankai , Li Yin , Liu Xianben
Published: September 2021

Although the early oral feeding program (EOF) pasting the esophagectomy has been demonstrated to be valuable in attenuating inflammatory responses and shortening hospital stay without increasing complications, its impacts on gastrointestinal function recovery have not been elegantly investigated. This study aimed to solve these issues.

Methods

A total of 110 esophageal cancer patients were included after reviewing a prospective database. Patients of EOF group were compared with patients of late oral feeding (LOF) group with respects to the appearance of first flatus and bowel movement after esophagectomy. Perioperative changes in serum gastrointestinal hormones were compared between EOF group and LOF group using variance analysis of repeated measurements. Multivariable logistic regression was conducted to detect risk factors for delayed recovery of gastrointestinal function after esophagectomy.

Results

Patients of EOF group showed significantly shorter time from the surgery to the appearance of first flatus (2.1 ± 0.8 d vs 3.4 ± 1.2 d, P < 0.001) and bowel movement (3.2 ± 0.9 d vs. 5.5 ± 1.5 d, P < 0.001) than those of LOF group. Patients of EOF showed increased levels of serum gastrin (P = 0.007) and motilin (P = 0.027) but decreased levels of somatostatin (P = 0.004) and cholecystokinin (P = 0.028) than patients of LOF group based on the repeated measurements on postoperative day 1, 3, and 5. Multivariable analysis demonstrated the EOF (vs. LOF) as a protective factor for delayed recovery of gastrointestinal function.

Conclusion

The postoperative EOF was demonstrated to accelerate the recovery of gastrointestinal function in esophageal cancer patients from the levels of clinical manifestation and hormone secretion. The EOF was anticipated to be highlighted in promoting perioperative managements.
655 EVALUATION OF THE MODIFIED DOR TECHNIQUE FOR SURGICAL TREATMENT OF ACALASIA
Authors: Lisboa Fernando Freire , Gomes Nathan Xavier , Silva Pedro Arthur Nascimento
Published: September 2021

Achalasia is the main esophageal motility disorder and has a significant negative impact on the patient's quality of life. Achalasia patients have dysphagia and vomiting, often associated with chest pain, leading to significant weight loss. The treatment of achalasia should be primarily to decrease the pressure of the lower esophageal sphincter. There are different therapeutic options for the treatment, and laparoscopic myotomy is the standard treatment, despite the improvement of new techniques such as POEM.

Methods

Prospective and retrospective study carried out in a university hospital with 33 patients with achalasia, operated with the wide myotomy technique associated with modified Dor fundoplication, from January 2017 to November 2020. The diagnosis was made by clinical, endoscopic, radiological and manometric studies. Symptomatic assessment and therapeutic success were performed using the Eckardt score before and after the operation. Rezende's classification was used to classify the degree of megaesophagus. The degree of megaesophagus was correlated with the result of the technique. The results were analyzed using the IBM SPSS Statistics Version 26 software.

Results

Patients with idiopathic achalasia 28 (84.8%). Preoperative Eckardt score average 5.93 points, preoperative clinical stage I = 7 (21.2%), clinical stage II = 12 (36.4%) and clinical stage III = 14 (42.4%). 48-hour postoperative hospital stay. Average postoperative Eckardt score 0.30 points, with 32 (97%) clinical stage 0, and 1 (3%) in clinical stage I in the postoperative period. Remission rate of the disease after treatment 100%. There was no correlation between the degree of the megaesophagus with the preoperative symptoms or with the therapeutic result. There were no complications or need for reintervention. There were no reports of symptoms of GERD.

Conclusion

According to clinical, radiological and endoscopic data, the technique was considered safe and effective for the treatment and regression of achalasia symptoms in all degrees of megaesophagus in the present study. In addition, the technique was also effective as an anti-reflux mechanism, preventing the onset of symptoms of iatrogenic GERD.
659 AN SINGLE-ARM OPEN-LABEL PHASE II STUDY OF CAMRELIZUMAB PLUS APATINIB AS SECOND-LINE TREATMENT FOR ADVANCED ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Wang Feng , Fan Qingxia , Wang Junsheng , Wu Tao , Hong Yonggui , Meng Xiangrui , Ren Zhonghai , Guo Yanzhen , Yang Xiuli , Shi Pei , Yang Jiamei , Yin Xianzhe , Luo Zhiquan , Xia Jin , Zhou Yue , Liu Enjie , Jiang Guozhong
Published: September 2021

Esophageal squamous cell carcinoma (ESCC) as a common malignancy is prevalent in East Asia and in eastern and southern Africa. Although pembrolizumab, nivolumab and camrelizumab are respectively recommended as second-line treatment for advanced ESCC due to improved overall survival (OS), objective response rate (ORR) was modest. New effective treatments are needed. Hence, the study of camrelizumab plus apatinib (VEGFR2 inhibitor) as second-line treatment for advanced ESCC was performed.

Methods

This ongoing phase II trial (NCT03736863) in six sites in China enrolled pts aged 18-75 with unresectable locally advanced, locally recurrent, or metastatic ESCC that progressed or were intolerant after first-line chemotherapy, and an ECOG performance status of 0-1. Pts received 200 mg camrelizumab intravenously every 2 weeks and apatinib 250 mg orally once per day in 4-week cycles until disease progression, unacceptable adverse events (AEs) or withdrawal of consent. The primary endpoint was investigator-assessed ORR. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and OS.

Results

At data cutoff (Feb 28, 2021), 52 pts were enrolled, including 42 males and 50 with distant metastases, with the median age of 62 years. In the evaluable population of 39 pts, ORR without confirmation was 43.59% and DCR was 94.87%. The median duration of response was 6.9 months (95% CI 4.57–9.23). The median PFS was 6.8 month (95% CI 2.66–10.94). The 12-month overall survival was 52.2%. A total of 80.8% of pts had treatment-related AEs (TRAEs) with 46.2% of grade ≥ 3 TRAEs. The safety profile of camrelizumab and apatinib was consistent with other anti–PD-1 antibodies and angiogenesis inhibitors.

Conclusion

This is the first study that evaluates the combination anti–PD-1 antibody and anti-angiogenesis inhibitor as a second-line therapy for advanced ESCC. Camrelizumab plus apatinib showed encouraging clinical efficacy and acceptable safety. Further phase III randomized trials are warranted.
664 BURDEN OF IN-HOSPITAL CARE IN OESOPHAGEAL CANCER: A NATIONAL POPULATION-BASED STUDY
Authors: Linder Gustav , Klevebro Fredrik , Edholm David , Johansson Jan , Lindblad Mats , Hedberg Jakob
Published: September 2021

Oesophageal cancer management requires extensive in-hospital care. This cohort study aimed to quantify in-hospital care for esophageal cancer patients in relation to intended treatment and to analyze factors associated with risk of spending a large proportion of survival time in hospital.

Methods

All patients with oesophageal cancer in three nationwide registers over a ten-year period, were included. In-hospital care during the first year after diagnosis was evaluated and the proportion of survival time spent in hospital, stratified for intended treatment (curative, palliative or best supportive care) calculated. Associations of relevant factors to a greater proportion of survival time in hospital was analyzed by multivariable logistic regression.

Results

In-hospital care was provided for a median time of 39, 26 and 15 days the first year after diagnosis of oesophageal cancer for curative, palliative and best supportive care groups respectively. Patients receiving curatively intended treatment spent a median of 12% of their survival time in hospital during the first year after diagnosis, while palliative or best supportive care patients spent 19% and 23% respectively. Factors associated with more in-hospital care included higher age, female sex, being unmarried and chronic obstructive pulmonary disease (COPD).

Conclusion

The burden of in-hospital care during the first year after diagnosis of oesophageal cancer was substantial. Important clinical and socioeconomic factors were identified that predisposed to a greater proportion of survival time spent in hospital.
709 PL11.05 NOVEL DIGITAL REFLUX SCINTIGRAPHY DETECTS PULMONARY MICROASPIRATION IN SEVERE GASTRO-OESOPHAGEAL AND LARYNGOPHARYNGEAL REFLUX DISEASE
Authors: Park Jin-soo , Burton Leticia , Van der Wall Hans , Falk Gregory
Published: September 2021

No gold-standard diagnostic test for laryngopharyngeal reflux (LPR) exists. Symptoms alone are non-diagnostic, and pH-impedance studies have poor sensitivity. Pulmonary micro-aspiration is under-recognised in LPR and gastro-oesophageal reflux disease (GORD). The present study aimed to describe the results of a novel digital technique for scintigraphic reflux studies in two groups with severe reflux: those with typical reflux symptoms and those with laryngopharyngeal manifestations of reflux.

Methods

A prospective database of severely symptomatic, treatment-resistant reflux patients was grouped based upon predominant symptom profile of typical GORD or LPR. All patients underwent novel reflux scintigraphy. Results were obtained for early scintigraphic reflux contamination of the pharynx and proximal oesophagus, and delayed contamination of the pharynx and lungs after two hours.

Results

The LPR patients were predominantly female (70.5% vs. 56.1%; p = 0.042) and older than the GORD group (median age 60 years vs. 55.5 years; p = 0.002). Early scintigraphic reflux was seen at the pharynx in 89.2% (GORD 87.7%, LPR 90.4%; p = 0.133), and at the proximal oesophagus in 89.7% (GORD 88.9%, LPR 90.4%; p = 0.147). Delayed contamination of the pharynx was seen in 95.2% (GORD 93.9%, LPR 96.2%; p = 0.468). Delayed pulmonary aspiration was seen in 46% (GORD 36.6%, LPR 53.3%; p = 0.023).

Conclusion

Reflux scintigraphy demonstrated a high rate of digitally identified reflux pulmonary aspiration. Contamination of the proximal oesophagus and pharynx was observed frequently in both groups of severe disease. The likelihood of pulmonary aspiration and potential pulmonary disease needs to be entertained in severe GORD and LPR.
723 TWO- VS. THREE-FIELD LYMPHADENECTOMY FOR ESOPHAGEAL CANCER. A SYSTEMATIC REVIEW AND META-ANALYSIS OF SHORT- AND LONG-TERM OUTCOMES.
Authors: Datrino Letícia Nogueira , Santos Clara Lucato , Tavares Guilherme , Tristão Luca Schiliró , Serafim Maria Carolina Andrade , Orlandini Marina Feliciano , Modesto Victoria Andrade , Tustumi Francisco , Bernardo Wanderley Marques
Published: September 2021

Nowadays, there is still no consensus about the benefits of adding neck lymphadenectomy to the traditional two-fields esophagectomy. An extended lymphadenectomy could potentially increase operation time and the risks for postoperative complications. However, extended lymphadenectomy allows resection of cervical nodes at risk for metastases, potentially increasing long-term survival rates. This study aims to estimate whether cervical prophylactic lymphadenectomy for esophageal cancer influences short- and long-term outcomes through a systematic review of literature and meta-analysis.

Methods

A systematic review was conducted in PubMed, Embase, Cochrane Library Central, and Lilacs (BVS). The inclusion criteria were: (1) studies that compare two-field vs. three-field esophagectomy; (2) adults (>18 years); (3) articles that analyze short- or long-term outcomes; and (4) clinical trials or cohort studies. The results were summarized by forest plots, with effect size (ES) or risk difference (RD) and 95% CI.

Results

Twenty-five articles were selected, comprising 8,954 patients. Three-field lymphadenectomy was associated to higher operation time (ES: -1.51; 95%CI -1.84, −1.18) and higher blood loss (ES: -0.24; 95%CI: −0.37, −0.11). Also, neck lymphadenectomy inputs additional risk for pulmonary complications (RD: 0.03; 95%CI: 0.01, 0.05). No difference was noted for morbidity (RD: 0.01; 95%CI: −0.01, 0.03); leak (−0.02; 95%CI: −0.07, 0.03); postoperative mortality (RD: 0.00; 95%CI: −0.00, 0.01), and hospital stay (ES: -0.05; 95%CI -0.20, 0.10). Three-field lymphadenectomy allowed higher number of retrieved lymph nodes (MD: -1.51; 95%CI -1.84, −1.18), but did not increase the overall survival (HR: 1.11; 95%CI: 0.96, 1.26).

Conclusion

Prophylactic neck lymphadenectomy for esophageal cancer should be performed with caution once it is associated with poorer short-term outcomes compared to traditional two-field lymphadenectomy and does not improve long-term survival. Future esophageal cancer studies should determine the subgroup of patients who could benefit from prophylactic neck lymphadenectomy in long-term outcomes.
847 PREOPERATIVE BRAIN MRI/CT FOR PATIENTS WITH POTENTIALLY RESECTABLE ESOPHAGEAL SQUAMOUS CELL CANCER, TO BE OR NOT TO BE ROUTINELY?
Authors: Wei Xiufeng , Li Yin , Qin Jianjun , Chen Xiankai , Zhang Ruixiang , Kang Xiaozheng , Xie Hounai , Xu Lei , Yang Yafan
Published: September 2021

There are few prospective studies of brain metastasis from esophageal squamous cell cancer (ESCC). The aim of this study was to investigate the necessity of the brain MRI/CT in the preoperative workup for patients with potentially resectable (cT1-4aN0-3) esophageal squamous cell cancer.

Methods

This was a prospective cross-section clinical trial (ChiCTR1800020304). There were a total of 468 patients who were diagnosed ESCC from October 2018 to August 2020. Of these 468 patients, 385 patients with cT1-4aN0-3 who were potentially candidates for surgical resection were consecutively enrolled into the study. Preoperative brain MRI/CT was performed preoperatively. The treatment regimen could be changed if the brain metastasis was confirmed. The primary endpoint was the incidence rate of the treatment regimen being changed because of brain metastasis.

Results

In all 385 patients, there are only 4 (1%) patients changed their treatment regimen because of brain metastasis proved by MRI/CT. The rate of positive brain MRI/CT findings is 1%. The MRI/CT diagnostic performance for brain metastasis was as follows: sensitivity, 100%; specificity, 100%; positive predictive value, 100%; negative predictive value, 100% and accuracy, 100%. There were no significant difference of bone metastasis among the Age, Sex, Tumor location and clinical stage.

Conclusion

Preoperative brain MRI/CT might help identify brain metastases in patients with esophageal cancer, but we do not recommend the brain MRI/CT in the preoperative workup for patients with potentially resectable esophageal squamous cell cancer.
Conditions to Terminate Reproductive Diapause of a Univoltine Insect:Ceratapion basicorne(Coleoptera: Apionidae), a Biological Control Agent of Yellow Starthistle
Authors: Smith Lincoln , Park Ikju
Published: September 2021

Ceratapion basicorne (Illiger) is a recently approved univoltine biological control agent that develops inside the rosette of yellow starthistle (Centaurea solstitialis L.), an invasive annual plant. Adult weevils normally emerge in early summer, and females are thought to be in reproductive diapause until the following spring, when they oviposit in rosettes. The long period of reproductive diapause constrains mass-rearing this weevil because only one generation per year can be produced. Determining the environmental conditions that regulate diapause termination may enable shortening diapause under laboratory conditions to increase production of adults to release. We tested three hibernating conditions (greenhouse [ambient temperature and photoperiod], glass door refrigerator [5°C and ambient photoperiod], and growth chamber [5°C and 24 h dark]) for three durations (4, 8, 11 wk). The highest proportion of females laying eggs came from the growth chamber, with 40% terminating diapause after 4 wk, 80% after 8 wk, and 95% after 11 wk of exposure. Our study demonstrates that duration of cold temperature is an important stimulus to terminate reproductive diapause of C. basicorne, and that exposure to ambient light had no effect at 5°C. However, 47% of females held at ambient greenhouse conditions, without any chilling period, completed diapause within 11 wk. Thus, a cold period can accelerate diapause development, but it is not necessary for its completion. Reducing the winter diapause period from about 6 mo to 11 wk should enable the production of multiple generations per year to increase the number of insects available to release.
An adolescent with Behçet’s aortitis mimicking infective endocarditis: a case report
Authors: Hattori Kaoru , Tabata Mimiko , Nojiri Tohru , Kurata Atsushi
Published: September 2021

Background

Aortic valve involvement is rare in patients with Behçet’ s disease (BD); however, recurrent prosthetic valve detachment after valve surgery has frequently been reported. We report a rare case of Behçet’s aortitis involving the aortic valve, mimicking active infective endocarditis (IE) with perivalvular abscess.

Case summary

A 16-year-old boy, with an unknown case of BD, presented with pyrexia of unknown origin, severe aortic valve regurgitation, vegetation, and perivalvular abscess in the aortic valve. All cultures tested negative for microorganisms. As we suspected IE, aortic valve replacement was performed. After the initial surgery, recurrent prosthetic valve detachment and pseudoaneurysm formation occurred, which resulted in the diagnosis of BD. The patient underwent a modified Bentall procedure, in which the valve conduit was proximally sutured to the left ventricular outflow tract instead of the aortic annulus. Immunosuppressive therapy was initiated on the 10th postoperative day. His condition became stable, and additional surgery was not required.

Discussion

The echocardiographic findings of Behçet’s aortitis involving the aortic valve resemble those of aortic valve IE. Modified Bentall procedure, combined with effective immunosuppressive therapy, may be useful in preventing prosthetic valve detachment.
Robust Cre recombinase activity in the biotrophic smut fungus Ustilago maydis enables efficient conditional null mutants in planta
Authors: de la Torre Antonio , Jurca Matteo , Hoffmann Kai , Schmitz Lara , Heimel Kai , Kämper Jörg , Pérez-Martín José
Published: September 2021

Site-specific recombinases have been used in higher eukaryotes, especially in animals, for a broad range of applications, including chromosomal translocations, large deletions, site-specific integration, and tissue-specific as well as conditional knock-outs. The application of site-specific recombination has also been demonstrated in simple eukaryotes like fungi and protozoa. However, its use in fungal research, especially in phytopathogenic fungi, has often been limited to “recycle” the marker genes used in transformation experiments. We show that Cre recombinase can be used for conditional gene deletions in the phytopathogenic fungus Ustilago maydis. Conditional gene knock-outs can be generated via the transcriptional control of the recombinase by U. maydis promoters specifically activated during the biotrophic phase of fungal growth, enabling gene deletions at defined developmental stages inside the plant tissue. Also, we show that a tamoxifen-activated Cre-recombinase allows the tight control necessary for the induced deletion of essential genes by the addition of tamoxifen. These tools will be helpful to address the function of genes under both axenic and in planta conditions for the U. maydis-maize pathosystem and should pave the way for similar approaches in other plant pathosystems.
ISA API: An open platform for interoperable life science experimental metadata
Authors: Johnson David , Batista Dominique , Cochrane Keeva , Davey Robert P , Etuk Anthony , Gonzalez-Beltran Alejandra , Haug Kenneth , Izzo Massimiliano , Larralde Martin , Lawson Thomas N , Minotto Alice , Moreno Pablo , Nainala Venkata Chandrasekhar , O'Donovan Claire , Pireddu Luca , Roger Pierrick , Shaw Felix , Steinbeck Christoph , Weber Ralf J M , Sansone Susanna-Assunta , Rocca-Serra Philippe
Published: September 2021

Background

The Investigation/Study/Assay (ISA) Metadata Framework is an established and widely used set of open source community specifications and software tools for enabling discovery, exchange, and publication of metadata from experiments in the life sciences. The original ISA software suite provided a set of user-facing Java tools for creating and manipulating the information structured in ISA-Tab—a now widely used tabular format. To make the ISA framework more accessible to machines and enable programmatic manipulation of experiment metadata, the JSON serialization ISA-JSON was developed.

Results

In this work, we present the ISA API, a Python library for the creation, editing, parsing, and validating of ISA-Tab and ISA-JSON formats by using a common data model engineered as Python object classes. We describe the ISA API feature set, early adopters, and its growing user community.

Conclusions

The ISA API provides users with rich programmatic metadata-handling functionality to support automation, a common interface, and an interoperable medium between the 2 ISA formats, as well as with other life science data formats required for depositing data in public databases.
Reproductive aging and menopause-like transition in the menstruating spiny mouse (Acomys cahirinus)
Authors: Bellofiore Nadia , George Evgenia , Vollenhoven Beverley , Temple-Smith Peter
Published: September 2021

STUDY QUESTION

Does the naturally menstruating spiny mouse go through menopause?

SUMMARY ANSWER

Our study is the first to show a natural and gradual menopausal transition in a rodent.

WHAT IS KNOWN ALREADY

Age-related depletion of the human ovarian reserve (OvR) leads to menopause, the permanent cessation of menstruation and reproduction. Current rodent models of menopause are inappropriate for inferences of the human condition, as reproductive senescence is abrupt or induced through ovariectomy. The spiny mouse is the only confirmed rodent with a naturally occurring menstrual cycle.

STUDY DESIGN, SIZE, DURATION

Histological assessment of virgin spiny mice occurred in females aged 6 months (n = 14), 1 year (n = 7), 2 years (n = 13), 3 years (n = 9) and 4 years (n = 9). Endocrinology was assessed in a further 9 females per age group. Five animals per group were used for ovarian stereology with additional ovaries collected at prenatal Day 35 (n = 3), day of birth (n = 5), postnatal Days 35 (n = 5) and 100 (n = 5) and 15 months (n = 5).

PARTICIPANTS/MATERIALS, SETTING, METHODS

Morphological changes in the reproductive system were examined using hematoxylin and eosin stains. Proliferating cell nuclear antigen immunohistochemistry assessed endometrial proliferation and sex steroids estradiol and testosterone were assayed using commercial ELISA kits.

MAIN RESULTS AND THE ROLE OF CHANCE

The proportion of females actively cycling was 86% at 6 months, 71% at 1 year, 69% at 2 years, 56% at 3 years and 44% at 4 years. Uterine and ovarian weights declined steadily from 1 year in all groups and corresponded with loss of uterine proliferation (P < 0.01). Estradiol was significantly decreased at 1 and 2 years compared to 6-month-old females, before becoming erratic at 3 and 4 years, with no changes in testosterone across any age. Fully formed primordial follicles were observed in prenatal ovaries. Aging impacted on both OvR and growing follicle numbers (P < 0.001–0.0001). After the age of 3 years, the follicle decline rate increased more than 5-fold.

LARGE SCALE DATA

N/A.

LIMITATIONS, REASONS FOR CAUTION

This is a descriptive study in a novel research rodent whereby reagents validated for use in the spiny mouse were limited.

WIDER IMPLICATIONS OF THE FINDINGS

The gradual, rather than sudden, menopausal transition suggests that the spiny mouse is a more appropriate perimenopausal model than the current rodent models in which to examine the neuroendocrine pathways that encompass all hormonal interactions in the hypothalamic–pituitary–gonadal axis. The logistic, ethical and economic advantages of such a model may reduce our reliance on primates in menopause research and enable more thorough and invasive investigation than is possible in humans.

STUDY FUNDING/COMPETING INTEREST(S)

Hudson Institute is supported by the Victorian State Government Operational Infrastructure Scheme. The authors declare no competing interests.
Emotions and the German Peasants’ War of 1524–6
Authors: Roper Lyndal
Published: September 2021

This article addresses the questions of the history of emotions to the German Peasants' War of 1524-5. The biggest popular uprising in Western Europe before the French Revolution, it overturned lordship in wide areas of Germany and beyond for about three months. It transformed the character of the Reformation as Luther condemned the peasant rebels. The revolt followed an emotional arc, shaped as much by the seasons as it was by the logic of revolution. The article argues that historians need to understand emotions and emotional cycles to understand how revolutions begin and unfold.
Recreational fishers’ perceptions of climate change
Authors: Ryan Karina L , Shaw Jenny , Tracey Sean R , Lyle Jeremy M
Published: September 2021

Shifts in marine species distributions associated with climate change occur across large spatial areas and long time periods. Marine recreational fishing occurs in most countries with many participants interacting regularly with the environment, yet there have been few studies on the views of recreational fishers towards climate change. This study aims to assess perceptions of climate change for a boat-based recreational fishery in Western Australia, where fishing occurs across a wide latitudinal range, from tropical to temperate waters. Perceptions of climate change were assessed by fisher demographics and fishing behaviour. One in two respondents noticed changes in species types and distributions, with metropolitan residents and avid fishers more likely to notice these changes. Two out of three respondents considered climate change is occurring, recognition of which was higher amongst metropolitan residents, females, and younger respondents. Males and older respondents, on the other hand considered themselves to have more knowledge of climate change science. This study provides a baseline to assist in informing policy changes that might be required to address the impacts of climate change. Studies of this kind can also build support for citizen science programs to enhance data collection across the spatial and temporal time scales required to observe climate change.
Prenatal exposure to nitrofurantoin and risk of childhood leukaemia: a registry-based cohort study in four Nordic countries
Authors: Hjorth Sarah , Pottegård Anton , Broe Anne , Hemmingsen Caroline H , Leinonen Maarit K , Hargreave Marie , Nörby Ulrika , Nordeng Hedvig
Published: September 2021

Background

Studies have suggested increased risks of childhood leukaemia after prenatal exposure to antibiotics, particularly nitrofurantoin. However, these findings may be related to the underlying maternal infection. This multinational study aimed to investigate the association between prenatal nitrofurantoin exposure and childhood leukaemia while accounting for maternal infection.

Methods

In a population-based cohort study of children born in Denmark, Finland, Norway or Sweden from 1997 to 2013, prenatal exposure to nitrofurantoin or pivmecillinam (active comparator) was ascertained from national Prescription Registries. Childhood leukaemia was identified by linkage to national Cancer Registries. Poisson regression was used to estimate incidence rate ratios (IRRs) and incidence rate differences (IRDs) with inverse probability of treatment weights applied to account for confounding.

Results

We included 44 091 children prenatally exposed to nitrofurantoin and 247 306 children prenatally exposed to pivmecillinam. The children were followed for 9.3 years on average (standard deviation 4.1). There were 161 cases of childhood leukaemia. The weighted IRR for prenatal nitrofurantoin exposure when compared with pivmecillinam was 1.34 (95% confidence interval 0.88, 2.06), corresponding to an IRD of 15 per million person-years. Higher point estimates were seen for first- and third-trimester exposure. There was no evidence of a dose–response relationship.

Conclusions

Prenatal exposure to nitrofurantoin was not substantially associated with childhood leukaemia, although a slightly elevated IRR with confidence intervals including the null was observed, corresponding to a small absolute risk. The lack of a dose–response relationship and a clear biological mechanism to explain the findings suggests against a causal association.
Foreign Policy Change from an Advocacy Coalition Framework Perspective
Authors: Haar Roberta N , Pierce Jonathan J
Published: September 2021

Why does a state change its foreign policy objectives and who is responsible for instigating such change? According to Hermann, four primary change agents are central to this process: leaders, bureaucracies, changes in domestic constituencies, and external shocks. This paper argues that the Advocacy Coalition Framework (ACF) is a complementary policy process framework that can explain foreign policy change (FPC) and that accounts for all four of these primary change agents. Additionally, it is a broader framework of the policy process that facilitates a more comprehensive understanding of the factors influencing FPC than traditional FPC research. The ACF has the potential to broaden our understanding of FPC by emphasizing the intersection of the international system with domestic politics and focusing on a myriad of policy actors coordinating their advocacy efforts to influence FPC. To support this argument, the paper discusses how FPC can benefit from the ACF and reviews past applications. It proposes a research agenda using the ACF to study FPC and draws conclusions about future challenges and directions.