bluuebunny/crossref_metadata_2025_split huggingface dataset:
P8 KERATIN 17 PROMOTES CELLS PROLIFERATION AND METASTASIS IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Zhun Liu , Zhimin Shen , Peipei Zhang , Shaobin Yu , Lei Gao , Sui Chen , Mingqiang Kang 
Published: November 2019

Abstract

Background
Keratin17(KRT17), as a multifunction cytoskeletal protein, associated with a multitudinous of biological processes, including cell proliferation, migration, and invasion. Previously, we have found up-expression of KRT17 genes in ESCC tissues. Currently, published kinds of researches claimed KRT17 is engaged in the tumorigenesis and progression of multiple cancers. However, the prognostic significance of KRT17 in ESCC patients and its effects in ESCC progression remains indistinct.

Methods
We verified the expression level of KRT17 in ESCC tissues by Western blotting and q-PCR and constructed KRT17 upregulated and knockdown EC9706 and Eca109 cells by Lentivirus overexpression and CAS9. The function of KRT17 in ESCC proliferation and metastasis were studied in vitro. We performed CCK-8 assays and plate colony formation assays and the plate colony formation assays to explore the effect of KRT17 on the proliferation, Moreover, the trans-well migration chamber experiment and wound healing test was taken to reveal the impact of KRT17 on migration capabilities.

Results
We verified that KRT17 is overexpressed in ESCC tissues and the role of KRT17 in the malignant behavior of ESCC in vitro and vivo . In CCK-8 assays and plate colony formation assays. We conformed proliferation capacity was notably enhanced by overexpression of KRT17 but compromised when KRT17 was knocked out. On the other hand, we used the plate colony formation assays to explore the effect of KRT17 on the proliferation of ESCC cells. KRT17 up-regulated significantly strengthened the proliferation while the KRT17 knockdown was weakened. To reveal the impact of KRT17 on migration, the trans-well migration chamber experiment was used to compare the role of down-regulation and up-regulation of KRT17 in migration; the results demonstrated that reducing expression of KRT17 significantly blocked the movement of ESCC cells as compared with the empty vector control. Otherwise, it has been confirmed that the cell migration ability employs a wound healing/scratch test because wound closure is generally a measure of cell motility. The results showed KRT17 overexpression notably reinforced the mobility of ESCC cells compared with the empty groups, whereas KRT17 knockdown cells prolonged the time to close the injury compared to blank groups. Collectively, these discoveries support that the increased expression of KRT17 in ESCC cells promoted a more proliferation and migratory phenotype in vitro.

Conclusion
The breakthrough indicated that the up-regulation of KRT17 in ESCC is closely related to malignant progression. Our data confirmed that KRT17 plays an essential role in reinforcing proliferation and metastasis in ESCC. Thence, KRT17 may serve as a significant molecular target for the diagnosis and therapy of ESCC.
P101 THE IMPACT OF PARATRACHEAL LYMPHADENECTOMY ON LYMPH NODE YIELD AND SHORT-TERM OUTCOMES IN ESOPHAGECTOMY: A NATIONAL PROPENSITY SCORE MATCHED ANALYSIS
Authors: Kingma B F , Hagens E R C , van Berge Henegouwen M I , Borggreve A S , Ruurda J P , Gisbertz S S , van Hillegersberg R 
Published: November 2019

Abstract

Aim
This study aimed to investigate the impact of paratracheal lymphadenectomy on lymph node yield and short-term outcomes in patients undergoing esophagectomy for cancer.

Background & Methods
Although the addition of paratracheal lymphadenectomy to a standard two-field lymphadenectomy possibly may provide survival benefits for patients undergoing esophagectomy for esophageal cancer, the required dissection along the recurrent laryngeal nerves might be associated with increased morbidity. To investigate the impact of paratracheal lymphadenectomy on short-term oncological outcomes and postoperative complications, this nation-wide population-based cohort study included esophageal cancer patients who underwent neoadjuvant chemoradiotherapy followed by elective transthoracic esophagectomy with at least subcarinal and para-esophageal lymphadenectomy from the Dutch Upper Gastrointestinal Cancer Audit (DUCA). After propensity score matching Ivor Lewis and McKeown approaches separately, the lymph node yield and clinical outcomes were compared between patients who underwent paratracheal lymphadenectomy versus patients who did not.

Results
Between 2011-2017, a total of 2128 patients were included. A total of 770 patients (n=385 vs. n=385) and 516 patients (n=258 vs. n=258) were matched for the Ivor Lewis and McKeown approaches, respectively. Paratracheal lymphadenectomy was associated with a higher total lymph node yield in both Ivor Lewis (23 vs. 19 nodes, P<0.001) and McKeown (21 vs. 19 nodes, P=0.015) esophagectomy. In McKeown esophagectomy, paratracheal lymphadenectomy was associated with significantly more advanced pathological nodal staging (pN0; 57% vs. 69%, pN1; 25% vs. 16%, pN2; 12% vs. 11%, pN3; 6% vs. 3%, P=0.006). No significant differences were observed regarding recurrent laryngeal nerve injury, other postoperative complications, and mortality, although a higher re-intervention rate was found after paratracheal lymphadenectomy during McKeown esophagectomy (30% vs. 18%, P=0.002) In patients undergoing Ivor Lewis esophagectomy, paratracheal lymphadenectomy was associated with increased length of stay (12 vs. 11 days, P<0.048).

Conclusion
In patients undergoing transthoracic esophagectomy for cancer, the addition of paratracheal lymphadenectomy results in a higher lymph node yield with comparable complication and mortality rates.
O112 SURVEILLANCE USING FDG-UPTAKE IN THE PRIMARY TUMOUR ON PET/CT IN PATIENTS WITH OESOPHAGEAL CANCER AND A CLINICALLY COMPLETE RESPONSE AFTER NEOADJUVANT CHEMORADIOTHERAPY
Authors: Valkema M J , van der Wilk B J , Eyck B M , Wijnhoven B P L , Spaander M C W , Lagarde S M , Nieuwenhuijzen G A P , Sosef M N , Van Lanschot J J B , Valkema R 
Published: November 2019

Abstract

Aim
In oesophageal cancer patients, clinical response to neoadjuvant chemoradiotherapy (nCRT) according to CROSS is assessed after 12 weeks, potentially followed by active surveillance in case of clinically complete response (cCR). Detection of residual tumour by FDG-PET/CT alone is inaccurate, since this cannot be distinguished reliably from post-radiation oesophagitis. We hypothesize that when inflammation diminishes, increasing FDG-uptake over time may be a sensitive parameter to detect local recurrence. We studied the detection of tumour recurrence with PET/CT during systematic follow-up in clinically complete responders beyond 12 weeks after nCRT.

Background & Methods
Patients from the preSANO- and SANO- trials were included who obtained cCR (no residual tumour on bite-on-bite biopsies and EUS with FNA of suspected lymph nodes) 12 weeks after completion of nCRT, but declined subsequent surgery. Patients were offered active surveillance, including PET/CT every 3 months. Standardised uptake values corrected for lean body mass (SUL) were measured at the primary tumour site. The percentage change in maximum SUL value (SULmax) between the last follow-up scan and the scan 12 weeks after nCRT was calculated. Tumour recurrence was defined as biopsy-proven vital tumour.

Results
Some 33 patients were eligible for analysis. In 17 of 33 (52%) patients, no biopsy-proven local recurrence was found during a median follow-up of 16 months (range 4.0-25) after CROSS. Some 16 of 33 (48%) patients had tumour recurrence within a median of 6.9 months after CROSS (range 5.3-36). We observed two different patterns of FDG uptake suggesting local recurrence. Three of 16 patients had sudden intense increase in SULmax (mean delta%-SULmax of 216%±42%). In the other 13 of 16 patients with local recurrence, an insidious gradual increase in FDG uptake was seen compared to patients without recurrence: mean delta%-SULmax of 21%±18% versus -10%±22% respectively.

Conclusion
Increasing FDG-uptake during active surveillance beyond 12 weeks after nCRT was associated with local recurrence and stable FDG-uptake with ongoing local tumour control. Thus, serial PET/CT might be a useful tool to distinguish tumour recurrence from SUL fluctuations in complete responders. To define a cut-off value of delta%-SULmax for local recurrence a larger number of patients is needed.
P113 ESOPHAGECTOMY-SPECIFIC OBJECTIVE STRUCTURED ASSESSMENT OF TECHNICAL SKILL (E-OSATS): CONSENSUS ON ESSENTIAL IVOR-LEWIS AND MCKEOWN STEPS TROUGH DELPHI METHODOLOGY
Authors: Eddahchouri Yassin , van Workum Frans , Klarenbeek Bastiaan , van den Wildenberg Frits , van Berge Henegouwen Mark , Polat Fatih , van Goor Harry , Pierie Jean-Pierre , Gisbertz Suzanne , Rosman Camiel 
Published: November 2019

Abstract

Aim
The objective of this study was to determine expert consensus on essential steps in MIE to develop an ‘Esophagectomy-specific Objective Structured Assessment of Technical Skills’ tool (E-OSATS).

Background & Methods
Minimally invasive esophagectomy (MIE) is a complex and technically demanding procedure. Studies have shown that MIE has a long learning curve which is associated with increased morbidity and mortality. To master MIE training of procedural steps is crucial. Yet, no consensus regarding the essential steps nor a structured way of assessment of MIE are available.
Essential steps were defined for both Ivor-Lewis (IL) and McKeown (MCK) approach, based on expert opinion and peer-reviewed literature. In round table discussions experts finalized the list, and an online Delphi questionnaire was sent to an international expert panel (7 European countries) of minimally invasive upper GI surgeons. Based on replies and comments steps were adjusted and rephrased and sent in iterative fashion until consensus was achieved.

Results
Two Delphi rounds were conducted, and response rates were 74% (23 out of 31 experts) for the first and 81% (27 out of 33 experts) for the second round. Consensus was achieved on 94 and 98 steps for the IL and MCK approach respectively. Cronbach’s alpha in the first round was 0,77 (IL) and 0,77 (MCK), and in the second round 0,91 (IL) and 0,87 (MCK).

Conclusion
International consensus on essential surgical steps for MIE with both intrathoracic- and cervical anastomosis was achieved. Validation of the assessment tool allows for specific and structured feedback and will potentially shorten the learning curve and decrease learning associated morbidity consequently.
P117 THE IMPACT OF ELDERLY ON SURGICAL OUTCOMES AFTER IVOR-LEWIS ESOPHAGECTOMY: REVIEW OF A SINGLE INSTITUTION EXPERIENCE
Authors: Cossu A , Parise P , Puccetti F , Palucci M , Cerchione R , Elmore U , Rosati R 
Published: November 2019

Abstract

Background
Esophagectomy is a surgical procedure burdened by a high morbidity rate. The effect of minimally invasive (MI) approach on elderly patients is still not clear. Aim of this study was to analyze the impact of MI approach on post-operative course according to the patient age.

Methods
A consecutive series of 692 patients underwent to elective oncological esophagectomy between 1997 and 2017. All data were entered into a prospective database. Patients submitted to 3-flield or trans-hiatal esophagectomy were excluded and only Ivor-Lewis open, hybrid or totally minimally invasive esophagectomy were evaluated. Patients were stratified according to age in 3 groups: Group A (≤ 50 years) 53 patients, Group B (> 51 and < 70 years) 269 and Group C (were ≥71 years) 126. Clinical and pathological factors influencing surgical outcome were evaluated. Complications were classified according to Clavien-Dindo (CD).

Results
As expected outcomes worsened with patients age (CD ≥ 3b: 7.5% group A, 13% group B and 21% group C. p=0.001), mortality (0% group A, 3% group B and 5.5% group C. p=0.035) and length of stay (10 days group A, 11 days group B and 13 days group C. p=0.001). A statistically significant higher incidence of anastomostic leaks was observed among patients submitted to totally MI esophagectomy in group C vs A and B that were respectively 12,5%, 0% and 7%. Major respiratory complications were not statistically different among these 3 three sub-group.

Conclusions
Old age has a significant impact on outcomes after esophagectomy. In this subset of patients a MI approach could also increase postoperative morbidity. Elderly patients should be carefully selected before to be submitted to MI esophagectomy.
P119 SURGICAL OUTCOMES AFTER ESOPHAGECTOMY IN THE ELDERLY POPULATION - A SINGLE CENTER COHORT STUDY
Authors: Henna Söderström , Ilkka Ilonen , Saana Andersson , Juha Kauppi , Jari Räsänen 
Published: November 2019

Abstract

Aim
To evaluate morbidity and mortality after esophagectomy among elderly patients

Background & Methods
Esophagectomy is associated with significant morbidity1, and with the aging population we are faced with an increasing number of elderly patients eligible for surgery. In this retrospective study we analyzed both minor and major postoperative complications (Clavidien-Dindo II-V), in-hospital and 90-day mortality, and overall survival in all carcinoma patients ≥75 yo undergoing esophagectomy for cancer between 2009 and 2018 at a high-volume center.

Results
47 patients underwent esophagectomy during the 10-yr. period, 95,7% either minimally invasively or with a hybrid approach. Median age was 77, and the oldest patient 85 yo. The majority were in otherwise good health, 39 had an ASA score of 1-2, and all but one was ECOG 0. 70% had adenocarcinomas, and 70% received neoadjuvant treatment.
68,1% of the patients suffered some sort of complication. 19 patients (40,4%) had a C-D III-IV complication, 9 of which were pulmonary requiring a median of 5 days in the ICU.
Only 4 patients (8,5%) had anastomotic leakage requiring an intervention, 2 were managed endoscopically, 1 early dehiscence was sutured and one required a revision and LD plasty. One patient had non-fatal gastric tube necrosis that was excised. Atrial fibrillation (34%) was the most common but easily managed issue, followed by pulmonary complications (C-D II 5pts /10,6%, C-D III-IV 10 pts / 21,3%). We had 3 re-operations for bowl herniation, and one for bleeding.
Our in-hospital and 90-day mortality were 0%, in spite of the high complication rate. 63,8% were discharged home. Mean and median survival times 68,2 mo. and 47 mo., respectively. At time of follow up, 28 patients (59,6%) were still alive.

Conclusion
Esophagectomy comes with high morbidity, but with acceptable long term results it should be considered for elderly patients otherwise fit for surgery. Our results show that in select cases age is just a number
1. Low DE, Kuppusamy MK, Alderson D, Cecconello I, Chang AC, Darling G, Davies A, D'Journo XB, Gisbertz SS, Griffin SM, Hardwick R, Hoelscher A, et al. Benchmarking Complications Associated with Esophagectomy. Ann Surg 2017;:1.
O122 INTERVAL DISTANT METASTASES DURING OR AFTER NEOADJUVANT CHEMORADIOTHERAPY FOR ESOPHAGEAL OR GASTROESOPHAGEAL JUNCTION CANCER: A NATION-WIDE POPULATION-BASED COHORT STUDY
Authors: Kroese Tiuri E , Dijksterhuis Willemieke P , van Rossum Peter S N , Verhoeven Rob H A , Mook Stella , Mohammad Nadia Haj , Ruurda Jelle P , van Laarhoven Hanneke W M , van Hillegersberg Richard 
Published: November 2019

Abstract

Aim
A certain proportion of esophageal or gastro-esophageal junction cancer patients develop interval distant metastases during neoadjuvant chemoradiotherapy (nCRT) or in the time interval after nCRT to planned surgery. The aims of this study were to assess the post-detection survival rates and prognostic factors affecting post-detection survival in patients with interval distant metastases.

Background & Methods
Esophageal and gastro-esophageal junction cancer patients who underwent nCRT and in whom distant metastases were detected during nCRT, after nCRT in the time interval to surgery or at the time of planned surgery, between 2010 and 2016, were included in this nation-wide population-based cohort study. The primary outcome measure was post-detection overall survival. Prognostic factors (including management) affecting the post-detection overall survival were studied using multivariable Cox proportional hazard models.

Results
A total of 150 patients were included in this study. The median post-detection overall survival was 6.1 months (95% confidence interval [CI] 5.1–7.7). Multivariable analysis identified signet ring cell carcinoma morphology (hazard ratio [HR] 2.88, 95%CI 1.35-6.13; p=0.021), poor tumor differentiation (HR 2.70, 95%CI 1.60-4.57; p<0.001), and palliative anti-tumor treatment as opposed to best supportive care (HR 0.38, 95%CI 0.23-0.61; p<0.001) as independent prognostic factors associated with post-detection survival. An observed survival advantage in a small selected group of 11 patients who received localized treatment with curative intent (metastasectomy and/or stereotactic body radiotherapy) did not reach statistical significance as compared to best supportive care (HR 0.62, 95% CI 0.26-1.43; p=0.263). Patient characteristics including WHO performance score, age, number of comorbidities, and characteristics of interval distant metastases including the location or number of affected locations were not significantly related to overall survival.

Conclusion
In this study the largest series of patients with esophageal or gastroesophageal junction cancer with interval distant metastases are reported. These patients have a poor prognosis with a median post-detection overall survival of 6.1 months. Prognostic factors independently associated with detrimental survival include poor tumor differentiation and signet ring cell carcinoma morphology. Anti-tumor treatment with palliative intent is associated with improved survival as compared to best supportive care.
P127 TRENDS IN CLINICOPATHOLOGICAL DATA OF ESOPHAGEAL CANCER IN GREECE. A SINGLE CENTER’S EXPERIENCE
Authors: Jose Duran Moreno , Anna Koumarianou , Aliki Liakea , Periklis Foukas , Eirini Kefalidi , Elli Tsagari , Katerina Kampoli , Nikoletta Koropouli , Manolis Kapetanakis , Periklis Tomos 
Published: November 2019

Abstract

Aim
The aim of this analysis is to describe the clinicopathological characteristics of patients (pts) with esophageal cancer diagnosed in our unit.

Background and methods
Esophageal cancer (EC) is the eighth most common malignancy. Updated data indicate that rates of adenocarcinoma are increasing while the incidence of squamous-cell carcinoma is decreasing in industrialized countries. Epidemiologic data from Greek population are scarce. We analyzed the data of pts diagnosed with EC and treated in our unit from 2009 to 2019.

Results
Thirty-one pts were diagnosed with EC in our unit, 29 males and 2 females (ratio 14.5:1). Mean age of diagnosis was 62.90±11.19 (39-82) years. Eighteen pts were diagnosed with adenocarcinoma, representing the 58.1% of the sample. Seven pts (22.6%) had squamous-cell carcinoma and 6 pts (19.4%) were classified as “other”. Lower esophagus and gastroesophageal junction were the most common location (20 pts). Four pts had tumors located in the upper esophagus and 3 pts in the medium esophagus. Eleven pts had a previous diagnosis of Barret’s esophagus, of which 7 developed adenocarcinoma, 1 squamous-cell carcinoma and 2 neuroendocrine tumors. Four pts (12.9%) presented with metastases at diagnosis. Thirteen pts were treated in peripheral hospitals after diagnosis, so treatment and follow-up data are available for 18 pts. Of them, 4 pts underwent neoadjuvant chemotherapy and 2 pts received neoadjuvant chemoradiation. Downstaging was achieved in 3 pts (2 complete responses and 1 partial response). Most common treatments applied included radical radiotherapy with chemotherapy followed by surgery in some cases. Nine pts (55.5%) presented relapse with a mean time of progression-free survival of 10.44±9.18(2-29) months. With a mean follow-up of 13.48±14.08 (1-56) months, 4 pts are alive without disease, 8 pts are alive with disease and 6 pts deceased. Mean overall survival was 15.83±11.65(4-36) months.

Conclusions
EC is a heterogeneous disease with a changing epidemiologic trend. Data from our unit are superimposable to those described worldwide and may be representative of Greek population with EC. However, prospective data at national level are needed.
O128 TGF-BETA1 AND TGF-BETA2 MEDIATED EPITHELIAL-MESENCHYMAL TRANSITION IN ESOPHAGEAL ADENOCARCINOMA CELLS
Authors: Thieme René , Chemnitzer Olga , Götzel Katharina , Mehdorn Matthias , Lyros Orestis , Gockel Ines 
Published: November 2019

Abstract

Aim
he esophageal adenocarcinoma (EAC) is characterized by an early lymphogenic dissemination and a poor prognosis. The tumor biology and the impact of autocrine, paracrine and endocrine mediators are involved in these mechanisms. For dissemination, the tumor cells need to escape the solid tumor and invade into new target structures. This mechanism is described as epitheliale-mesenchymal transition (EMT), which could be initiated by TGF-beta

Methods
Two proliferation and motility of the esophageal adenocarcinoma cell lines (OE33, OE19) were analyzed after TGF-beta1 and TGF-beta2 treatment. EMT marker gene expressions (e.g. vimentin) were assessed by qRT-PCR.

Results
TGF-beta2 led to a deceased proliferation rate compared to untreated and TGF-beta1 treated cells in OE33 cells. In OE19 cells both, TGF-beta1 and TGF-beta2 treatment resulted in an increased proliferation compared to untreated cells. In OE33 cells the motility was affected by TGF-beta1 only, while in OE19 cells the motility was increased by TGF-beta1 and TGF-beta2 compared to untreated cells. The vimentin mRNA-expression in OE33 cells was increased by TGF-beta1 and TGF-beta2 (14.7-fold and 25.9-fold). However TGF-beta1 and TGF-beta2 only led to a moderate increase in the vimentin mRNA-expression (4.0-fold and 1.8-fold) in OE19 cells.

Conclusion
TGF-beta1 and TGF-beta2 induce EMT and cellular motility in a cell line specific pattern. The responsible intracellular signaling cascades addressed by TGF-beta1 and TGF-beta2 and their contribution for dissemination in EAC patients need to be investigated with full details.