bluuebunny/crossref_metadata_2025_split huggingface dataset:
DoE-Based Analytical Quality Risk Management for Enhanced AQbD Approach to Economical and Eco-Friendly RP-HPLC Method for Synchronous Estimation of Multiple FDC Products of Antihypertensive Drugs
Authors: Prajapati Pintu , Patel Ankita , Shah Shailesh 
Published: September 2021

Abstract
According to the literature review, numerous chromatographic methods have been published for estimation of fixed-dose combination products of telmisartan but no reverse-phase high-pressure liquid chromatographic (RP-HPLC) method has been published yet for synchronous estimation of fixed-dose combination (FDC) products of telmisartan to save time, cost and solvent for analysis. Hence, an economical and eco-friendly RP-HPLC method has been developed for synchronous estimation of multiple FDC products of antihypertensive drugs using the quality risk management (QRM) and DoE-based enhanced analytical quality by design approach. The analytical-QRM was started with the identification of potential method risk parameters followed by their risk assessment by risk priority number ranking and filtering. The identified critical method parameters were optimized using the DoE-based central composite design. The method operable design range was navigated and the control strategy was framed for control and mitigation of risk throughout the life-cycle of the developed method. The method was developed using Shimpack Octadecyl silane (ODS) C18 column and acetonitrile-1.0%v/v triethylamine in water (pH 6.0; 45 + 55, %v/v). The developed method was validated as per the International Council for Harmonization Q2 (R1) guideline. The developed method was applied for the analysis of seven different antihypertensive dosage forms. The developed RP-HPLC method can be used as an eco-friendly, robust and economical alternative analytical tool to several published methods for estimation of FDC products of antihypertensive drugs in the pharmaceutical industry.
A Verifiable Symmetric Searchable Encryption Scheme Based on the AVL Tree
Authors: Wang Qing , Zhang Xi , Qin Jing , Ma Jixin , Huang Xinyi 
Published: September 2021

Abstract
Verifiable symmetric searchable encryption is a keyword search technology that supports verification of search results. Many schemes improve search performance by dividing each keyword label into segments and storing them in a Trie-tree at the expense of high storage. And the index will degenerate into a linear linked list when all keyword labels have the same prefix except for the last segment. But it will greatly affect the search efficiency. In this paper, we propose a verifiable symmetric searchable encryption scheme based on the AVL Tree (abbreviated as VSSE-AVL), which uses complete keyword labels to build the index. Compared with the Trie-tree index, VSSE-AVL not only balances storage and search performance, but also avoids degradation. To verify the correctness and completeness of empty search results, we store path information in each leaf node and node with only one child node. Considering the substitution attack, we bind the file identifier and the file so that the client will find out once the server returns inconsistent search results. Rigorous security analysis shows VSSE-AVL satisfies privacy and verifiability. Compared with the verifiable SSE-2 with the same security, the experimental evaluation shows that our proposed scheme performs better on storage, search and verification.
112 ROBOT-ASSISTED MINIMALLY INVASIVE ESOPHAGECTOMY CAN BE PERFORMED EVEN IN LEARNING CURVE PERIOD; PROPENSITY SCORE MATCH ANALYSIS
Authors: Tsunoda Shigeru , Obama Kazutaka , Hisamori Shigeo , Nishigori Tatsuto , Mizuno Rei , Ganeko Riki , Okuchi Yoshihisa , Sakai Yoshiharu 
Published: September 2021

Abstract

Da Vinci Surgical System Xi was introduced in our institution in 2017. Since then we started robot-assisted minimally invasive esophagectomy (RAMIE) as private practice. Japanese national insurance system started to reimburse RAMIE in 2018. Since then, the number of RAMIE is explosively increasing. Currently the indication of RAMIE in our institution purely depends on machine availability. However, the real clinical benefit of RAMIE over conventional minimally invasive esophagectomy (MIE) remains unknown.

Methods
Between January 2015 and January 2020, data of 156 consecutive patients with esophageal carcinoma undergoing esophagectomy was retrospectively reviewed. After exclusion of 12 salvage esophagectomy for patients after definitive chemoradiotherapy (&gt;50Gy), 10 mediastinoscopic esophagectomy, 5 esophagectomy without upper mediastinal dissection, 2 two-stage esophagectomy and 1 total pharyngo-laryngo-esophagectomy, 126 patients (46 RAMIE and 80 MIE) were included in the analysis. The 1:1 propensity score match analysis was performed to compare the short-term outcomes between RAMIE and MIE.

Results
After matching, 45 RAMIE and 45 MIE were analyzed. RAMIE took significantly longer thoracic operation time (370 min vs. 288 min; P &lt; 0.0001). Intraoperative blood loss (80 g vs. 50 g; P = 0.0759), harvested thoracic nodes (22 vs 25; P = 0.1188), harvested upper mediastinal nodes (12 vs 12; P = 0.4233) were similar. RAMIE showed less severe postoperative morbidity (Clavien-Dindo Grade III or higher) (9% vs. 22%; P = 0.0810) and lower incidence of recurrent laryngeal nerve palsy (Clavien-Dindo Grade II or higher) (7% vs. 18%; P = 0.1076). There was no postoperative death in both groups.

Conclusion
Although this result contains our early learning curve period of RAMIE, short term outcome of RAMIE is acceptable from a safety point of view.
29 SIZE OF THE THORACIC INLET SPACE AS A PREDICTOR OF CERVICAL ANASTOMOTIC LEAK AFTER RETROSTERNAL RECONSTRUCTION FOLLOWING ESOPHAGECTOMY
Authors: Sato Shinsuke , Nakatani Eiji , Higashizono Kazuya , Nagai Erina , Taki Yusuke , Nishida Masato , Watanabe Masaya , Oba Noriyuki 
Published: September 2021

Abstract

Although anastomotic leak is a common postoperative complication following an esophagectomy, it is not well known whether anatomical factors increase the risk for anastomotic leak after the procedure. The purpose of this study was to clarify whether a narrow thoracic inlet is an independent predictor of cervical anastomotic leak after retrosternal reconstruction following esophagectomy.

Methods
A total of 212 patients who underwent esophagectomy with gastric conduit retrosternal reconstruction between January 2013 and March 2019 were included in this study. Computed tomography was used to measure the thickness of the sternum (TS), the thickness of the clavicle (TC), the interclavicular distance, the sternum-trachea distance (STD), the sternum-vertebral body distance (SVD), and the sternum-trachea distance/sternum-vertebral body distance ratio (STD/SVD ratio). The correlation between various factors was analyzed using Spearman’s correlation coefficient. Tree-based analysis was performed to define cutoff values. Multivariate logistic regression was used to analyze the association between various predictors and anastomotic leak.

Results
Anastomotic leak occurred in 26 patients (12.26%). Tree-based analysis identified an optimal TS cutoff value of 20.84 mm, a TC cutoff value of 23.63, and a STD/SVD ratio cut off value of 0.2138 to predict anastomotic leak. There were significant associations between the STD, STD/SVD ratio and thoracic inlet area (STD × ICD). According to multivariate analysis, STD/SVD ratio, TS, TC, and diabetes mellitus were significantly associated with increased incidence of anastomotic leak.

Conclusion
STD/SVD ratio, TS, TC, and diabetes mellitus were associated with higher rates of cervical anastomotic leak after retrosternal gastric conduit reconstruction following esophagectomy. In patients with a small thoracic inlet, posterior mediastinal reconstruction and intrathoracic anastomosis should be considered.
343 EFFECTS OF PREOPERATIVE PNI (PROGNOSTIC NUTRITIONAL INDEX) AND POSTOPERATIVE INFLAMMATORY RESPONSE ON PROGNOSIS IN PATIENTS WITH ESOPHAGEAL CANCER
Authors: Fujiwara Yoshinori , Higashida Masaharu , Kubota Hisako , Okamoto Yuko , Mineta Syumei , Okada Toshimasa , Tsuruta Atsushi , Ueno Tomio 
Published: September 2021

Abstract

The effects of preoperative nutritional status and postoperative inflammatory response on esophageal cancer patients on prognosis were unclear. In the present study, we evaluated the preoperative nutritional parameters and postoperative inflammatory responses and analyzed relationship between these parameters and cancer prognosis.

Methods
One hundred and eleven esophageal squamous cell carcinoma patients were analyzed with pathological TNM StageI-IV. Preoperative nutritional parameters: PNI (Prognostic Nutritional Index) was calculated from following formula:10 x Albumin(g/dl) +0.005 x peripheral lymphocyte counts (/mm3). Preoperative NLR (Neutrophil/Lymphocyte ratio) was defined as absolute neutrophil counts divided by the absolute lymphocyte counts. The highest CRP level was evaluated as postoperative inflammatory responses. Cut-off values of these continuous parameters were calculated by ROC, and univariate and multivariate analysis using Cox model for overall survival (OS) were examined in the parameters.

Results
Overall three or five years survivals were 60.9%, 56.28%, respectively. Cut-off value of PNI, CRP, NLR, Intraoperative blood loss were 44.8, 21.7 mg/dl,2.27,159 mL, respectively. High PNI group was significantly better survival than low group (3 years OS, 65.94 vs 45.82%, p &lt; 0.05). No association between PNI and prognosis was noted for patients with pStageI, but the low PNI patients of pStageII-IV were extremely poor prognosis (p &lt; 0.01). High CRP group was tendency to be worse survival than low group (3 years OS, 65.97 vs 38.82%, p = 0.062). The patients of low blood loss group was significantly better survival than high group (p &lt; 0.05).NLR was not associated with OS. Cox model showed that pTNM, tumor location, and PNI were independent prognostic factors.

Conclusion
Preoperative nutritional status affected the prognosis of esophageal cancer patients. But, postoperative inflammatory response was not affected the prognosis of these patients. Preoperative nutritional interventions may improve the prognosis of patients with esophageal cancer.
500 THE PATHOLOGICAL GASTROESOPHAGEAL REFLUX IN PATIENTS WITH CYSTIC FIBROSIS
Authors: Bordin Dmitry , Valitova Elen , Baymakanova Gulsara , Krasovskiy Stanislav , Berezina Olga 
Published: September 2021

Abstract

The presence of gastroesophageal reflux in patients after lung transplantation rises the risk of posttransplantant complications. The aim of our study was to evaluate the severity of gastroesophageal reflux (GER) in patients with cystic fibrosis before lung transplantation.

Methods
14 patients with cystic fibrosis, who refferred to our Centre, were included in this study, mean age 28,86 ± 2,5 (6 males and 8 females). The diagnosis of cystic fibrosis was established at the age of 1–5 y.o. according to clinic, sweet test and genetic tests. All patients were performed upper endoscopy, X-ray, esophageal manometry and 24 h impedance monitoring. PPI treatment was excluded for 7 days before monitoring. Pathologic GER was established when total number of refluxes in distal esophagus was more than 75, the total number of refluxes in proximal esophagus was more than 20% of those in the distal part.

Results
According to endoscopy, none of patients had erosions of the esophagus. Five patients had ineffective motility and one—diffuse esophageal spazm. 56% of patients had pathologic number of refluxes in distal esophagus. 80% subjects had pathologic refluxes in proximal esophagus. The mean number of total refluxes in distal part was 54,93 ± 5,7, in proximal part—27,64 ± 2,6 (it is 40% of those in distal part). The distribution of acid and non-acid refluxes in patients with pathologic refluxes was 2:1. We didn’t reveal any correlation between number of refluxes, ineffective motility and gastric emptying.

Conclusion
despite normal upper endoscopy, 56% of patients with cystic fibrosis have pathologic gastroesophageal reflux. Besides, the study showed high propagation of GER to proximal esophagus in 80% of subjects, which may play role in posttransplantation period.
599 MEDIASTINITIS SECONDARY TO ESOPHAGEAL PERFORATION: IT’S TOO LATE?
Authors: Russo Emanuele , Sorice Mario , Busiello Luigi , Morte Aniello Della , Polimeno Emilia , Beneduce Lucia , Guggino Gianluca 
Published: September 2021

Abstract

Mediastinitis secondary to esophageal perforation is a rare, progressive, and destructive disease that may often lead to an imminent risk of death. We describe a single center experience showing how early diagnosis and prompt intervention can reduce mortality and complications.

Methods
From February 2016 to December 2019, 15 consecutive patients were referred to the Emergency Unit of The AORN Cardarelli (Naples) with clinical and radiological (CT scan) diagnosis of acute mediastinitis secondary to oesophageal perforation (post endoscopy or after foreign body ingestion) and furthermore, referred to the Thoracic Surgery Unit, they underwent to early surgical treatment (cervicotomy and\or thoracotomy and chest drainage.

Results
For early detected case (occurred within 24 hours) an emergency thoracotomy/cervicotomy was performed with surgical repair. For late detected (referred from other hospitals) a Surgical esclusion (abdominal plus cervical) and toilette thoracotomy was performed in emergency. Reconstruction occurred in 5 cases with a median of 46 days after firts care. All patient were admitted to ICU unit and susbsequentily to the thoracic surgery ward. 30 days mortality occurred in two cases. Median hospital staying was 28 days, in six cases a redo surgery was necessary. Empiric antibiotic treatment was started before operation and reviewed under Infectivologist.

Conclusion
Mediastinitis secondary to esophageal perforation has a fulminating course with a potential risk of sepsis, pericarditis, and multiple organ failure. A prompt identification and an invasive treatment is the best and most successful option to reduce mortality and improve patient’s recovery.
629 IRRADIATED ESOPHAGEAL SQUAMOUS CELL CARCINOMA CELLS INDUCED THE INCREASE OF TREG BY TGF-β
Authors: Wang Yuan , Li Tao , Lyu Jiahua , Xiao Ling , Liu Yudi , Liu Xiao , Li Ke , Zhang Rongke , Chen Taiyu , Zhang Hangyue , Tang Chunhan 
Published: September 2021

Abstract

The infiltration of CD4 + CD25 + Foxp3+ regulatory T cells (Treg) in the tumor microenvironment is one of the main reasons for radiation resistance and tumor recurrence after radiotherapy. It has been established that Treg is more resistant to radiation than other T cells, but the proliferation of immune cells after radiotherapy is affected by other factors, including tumor cells. We studied the effect and mechanism of esophageal squamous cell carcinoma on Treg cells after radiation.

Methods
After low-dose irradiation, TE-1 cells were co-cultured with normal peripheral blood lymphocytes for 48 hours. Flow cytometry was used to detect Treg/CD4 + T cell frequency. The mRNA expression of TGF-β1 and TGF-β2 in TE-1 was detected by qPCR, and the protein content of TGF-β1 and TGF-β2 in the medium was detected by ELISA.

Results
Compared with non-irradiation group, the expression of TGF-β1 and TGF-β2 in TE-1 cells of irradiation group increased, and the protein content of TGF-β1 and TGF-β2 in culture medium increased, the difference was statistically significant(P &lt; 0.001). Flow cytometry showed that CD4 + CD25+/CD4 + Tcell and CD4 + CD25 + Foxp3+/CD4 + Tcell were increased in the radiotherapy group after co-culture, and the difference was statistically significant (P &lt; 0.001).

Conclusion
The expression of TGF-β1 and TGF-β2 in esophageal squamous cell carcinoma cells increased after irradiation, and the frequency of Treg induced by co-culture increased, suggesting that esophageal squamous cell carcinoma cells after radiotherapy can induce the increase of Treg cells, which may be achieved mainly through the mechanism of increasing the secretion of TGF-β1 and TGF-β2.
658 BETTER SURVIVAL IN FEMALES THAN MALES AFTER RESECTION OF OESOPHAGEAL OR GASTROESOPHAGEAL JUNCTION CANCER: A COHORT STUDY IN SWEDEN
Authors: Zhang Ji , Bellocco Rino , Ye Weimin , Johansson Jan , Nilsson Magnus , Lindblad Mats 
Published: September 2021

Abstract

Accumulating evidence points to a better survival in female patients after a curative oesophageal cancer surgery. However, there is a need for more well-designed and sufficiently powered studies for limitations in previous studies. Better understanding of sex differences in the postoperative survival may be helpful for a sex-specific treatment.

Methods
This is a population-based cohort study including all patients in Sweden with oesophageal cancer that underwent a curative surgical treatment between 2006 and 2017. Sex difference in postoperative survival was explored with excess mortality rate ratio (EMRR) and absolute difference of excess mortality rate along the whole follow-up time, using flexible parametric model. Age at the time of surgery, Charlson comorbidity index, ASA score, tumor stage, post-operative complications, marital status, education level and hospital volume were considered as covariates in the analysis model. Stratification analysis by clinical stages, perioperative neoadjuvant treatment and post-operative complications was also performed.

Results
In all, there were 1301 patients resected for oesophageal adenocarcinoma and 305 patients for oesophageal squamous cell carcinoma. For both oesophageal adenocarcinoma and oesophageal squamous cell carcinoma, female patients had a lower excess mortality rate than males (adjusted EMRR: 0.77, 95% CI: 0.58–1.01, P = 0.059; 0.53, 95% CI: 0.33–0.85, P = 0.009, respectively). This sex difference was particularly strong shortly after surgery then gradually decreased over the ensuing years (Figure) and was more profound in the early clinical stages, and in patients receiving neoadjuvant treatment and without post-operative complications.

Conclusion
Female patients seem to have a better survival shortly after esophagectomy for patients with oesophageal adenocarcinoma and oesophageal squamous cell carcinoma, and the sex difference thereafter weakened. Our results may imply a different response to oesophageal cancer surgery between the sexes, and associated pre- and post-operative treatment, thus a sex-specific strategy may be considered in further work.
67 STRATEGY FOR DEFINITIVE TREATMENT AND PRESERVING QUALITY OF LIFE IN UPPER CERVICAL ESOPHAGEAL CARCINOMA
Authors: Goto Satoru , Koji Otsuka , Fujimasa Koichiro , Saito Akira , Komoto Masahiro , Kato Rei , Motegi Kentaro , Watanabe Ryohei , Date Hiromi , Yamashita Takeshi , Ariyoshi Tomotake , Yamazaki Kimiyasu , Aoki Takeshi , Murakami Masahiko 
Published: September 2021

Abstract

In radical surgery for upper cervical esophageal carcinoma, questions such as whether the larynx should be preserved depending on the distance from the esophageal orifice to the tumor margin and risk of aspiration during swallowing arise. We report the clinical outcomes of our strategy for upper cervical esophageal carcinoma based on the goals of curability and larynx preservation.

Methods
At our institution, resectable upper cervical esophageal carcinoma in which the tumor margin on the oral side is within 3 cm of the esophageal orifice is treated with chemoradiotherapy followed by larynx-preserving esophagectomy. The reason for initially using chemoradiotherapy is to make the surgical margin on the oral side completely negative and as distal as possible for definitive treatment and to improve quality of life (QOL). From 2016 to 2019, there were 24 patients who were diagnosed with upper cervical esophageal carcinoma within 3 cm of the esophageal orifice and received chemoradiotherapy and larynx-preserving esophagectomy.

Results
All patients were eligible for chemoradiotherapy and larynx-preserving esophagectomy. Pathologically, all surgical margins on the oral side were negative and all operations were curative. In particular, 6 patients with a tumor margin within 1 cm of the esophageal orifice underwent successful curative, larynx-preserving esophagectomy with the following additional techniques: incision of the cricopharyngeus muscle, lifting of the trachea and larynx, and rotation of the larynx to the left. Regarding surgical complications, 4 patients had temporary recurrent nerve paralysis with aspiration pneumonia and 1 patient had minor anastomotic leakage.

Conclusion
The combination of chemoradiotherapy and esophagectomy with a larynx-preserving technique is a useful treatment strategy for upper cervical esophageal carcinoma in terms of both definitive treatment and QOL.
672 OESOPHAGOGASTRIC ANASTOMOTIC LEAK IN THE THORAX TREATED WITH COVERED METAL STENTS: SAFE AND HIGHLY SUCCESSFUL
Authors: Siddaiah-subramanya Manjunath , Hodson James , Ghoneim Abdulrahman , Ibrahim Ibrahim , Kamarajah Sivesh , Whiting John , Griffiths Ewen 
Published: September 2021

Abstract

Anastomotic leak (AL) develops in 5–22% of cases following oesophagectomy, and results in additional morbidity, and reduction in overall survival. The management of AL has evolved significantly with advances in endoscopic therapies. Covered cylindrical metal stents have been increasingly used, and insertion techniques have improved over time. We aimed to investigate the effectiveness and safety of modern metal stents in the management of AL.

Methods
All patients who underwent oesophagectomy with thoracic anastomosis between 2006–2020, and subsequently developed AL were retrospectively identified. Initially, treatment details and patient outcomes were assessed for the subgroup of patients where the AL was initially managed using a stent. In all cases, these were cylindrical covered metal stents. Those patients that progressed to surgery after treatment with a stent were then excluded, with the remainder compared to the subgroup of patients that underwent conservative (i.e., non-interventional) treatment for AL.

Results
Of 63 patients with AL, primary management was with stents in 32 (57%). Technical success was achieved in all stenting procedures, although three patients (9%) developed complications (stent migration). After stenting, six cases (19%) subsequently required escalation to operative management (thoracotomy). The remainder (N = 23) were then compared to those managed conservatively (N = 26) and were found to have a significantly longer length of hospital stay (median: 37 vs. 20 days, p = 0.003). The AL healing rate was 96% in both groups (p = 1.000); one conservatively managed patient died before healing, and one stented patient refused further treatment.

Conclusion
Endoscopic treatment of oesophageal AL with cylindrical covered metal stents is safe, with a high technical success rate, and low rates of stent-related morbidity. Treatment with stents also avoids the need for operative management including oesophageal disconnection in the majority of cases, whilst leading to successful healing of the AL. However, treatment with stents does significantly increase hospital stay over conservative management, particularly where multiple procedures are required.