bluuebunny/crossref_metadata_2025_split huggingface dataset:
PS01.208: SURVEY ON THE MANAGEMENT OF ANASTOMOTIC LEAKAGE AFTER ESOPHAGEAL RESECTION WITH GASTRIC TUBE RECONSTRUCTION
Authors: Hagens Eliza , Anderegg Maarten , Van Berge Henegouwen Mark I , Gisbertz Suzanne 
Published: September 2018

Abstract

Background
For patients with locally advanced esophageal cancer, radical esophageal resection with gastric tube reconstruction preceded by chemo(radio)therapy offers the best chance for cure. Anastomotic leakage (AL) is one of the most severe complications following esophageal surgery, leading to significant morbidity, prolonged hospital stay, considerable costs, decreased quality of life and increased mortality. Management is complicated and not standardized. The objective is to gain insight into the different opinions on AL management among upper gastrointestinal surgeons and to verify the need for a diagnostic and treatment guideline.

Methods
Surgeons with particular interest in esophageal surgery, were invited to participate in an online questionnaire. The survey consisted of questions pertaining to the surgeons’ experience, operation characteristics, management routine and their opinion on international guidelines on the diagnosis and therapy of AL.

Results
Of the 331 invited physicians, 40% participated in the survey. 90.7% Use laboratory diagnostics and 62.8% imaging and/or endoscopy postoperatively on routine basis. In case of suspected AL, the first choice of diagnostic imaging modalities was mostly a CT scan (35.7%) or a dynamic swallow investigation (33.3%). In case of AL, indepently of the clincal manifestations (local symptoms only, medianstinal manifestations or In case of gastric conduit necrosis) the treatment strategies differed widely between surgeons (table 1). Over 70% of the responders agree that there is a need for a solid international guideline on AL management.

Conclusion
There is no general consensus in the management of AL. There is a need for an international guideline regarding the optimal management of AL.

Disclosure
All authors have declared no conflicts of interest.
PS02.012: AN IMPORTANT COMPLICATION OF MINIMALLY INVASIVE ESOPHAGECTOMIES: HIATAL HERNIA
Authors: Eroglu Atila , Aydin Yener , Ulas Ali , Daharli Coskun 
Published: September 2018

Abstract

Background
Development of hiatal hernia after esophageal resection is a known complication. However, due to the spread of minimally invasive esophagectomy, complications of hiatal hernia seems to increase. This study aimed to present our cases with hiatal hernia after Ivor Lewis minimally invasive esophagectomy.

Methods
After Ivor Lewis minimally invasive esophagectomy, five cases of hiatal hernia were observed. Patients' age, sex, symptoms, diagnosis, herniated organs, surgical method, morbidity and mortality rates and hospital stay were reviewed.

Results
Three of the patients were male and two were female. The mean age of the patients was 56.2 years (35–71 years). Hiatal hernia was detected after an average of 1.4 years with minimal invasive esophagectomies (5 months, 1 year, 1 year, 18 months and 3 years respectively). Three of the cases were symptomatic and two cases were asymptomatic. Thorax CT was used in all cases, and two cases were additionally imaged with barium esophagography. Herniated organs were: omentum in 5 cases, transverse colon in 4 cases, small bowel in two cases. All cases were laparoscopically approached. Diaphragmatic defects were repaired using nonabsorbable sutures in all cases. No complication and mortality was observed in patients. The mean length of hospital stay was 4.9 days (range, 3 to 10 days).

Conclusion
Hiatal hernia is more frequently seen in minimally invasive esophagectomies than open esophagectomies. Patients undergoing minimal esophagectomy should be closely monitored for hiatal hernia postoperatively. These cases can also be treated by minimally invasive laparoscopy.

Disclosure
All authors have declared no conflicts of interest.
PS02.024: PRIMA-1 INDUCES P53-MEDIATED APOPTOSIS BY UPREGULATING NOXA IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA WITH TP53 MISSENSE MUTATION
Authors: Furukawa Haruna , Makino Tomoki , Yamasaki Makoto , Tanaka Koji , Miyazaki Yasuhiro , Takahashi Tsuyoshi , Kurokawa Yukinori , Nakajima Kiyokazu , Takiguchi Shuji , Mori Masaki , Doki Yuichiro 
Published: September 2018

Abstract

Background
TP53 is associated with the resistance of cytotoxic treatment and patient prognosis, and the mutation rate of TP53 in esophageal squamous cell carcinoma (ESCC) is extraordinarily high, at over 90%. PRIMA-1 (p53 re-activation and induction of massive apoptosis) has recently been reported to restore wild type activity to mutant p53 and induce massive p53-dependent apoptosis. APR-246 (methylated PRIMA-1) has been tested in a phase I/II clinical trial with promising results; however, the effects and mechanism in ESCC remain unknown. This study was designed to assess the antitumor effect of PRIMA-1 treatment in both ESCC cell lines with different TP53 status and an ESCC xenograft model and uncover the molecular mechanism of PRIMA-1.

Methods
After evaluating the TP53 mutation status of a panel of eleven ESCC cell lines by Sanger sequencing, we assessed the in vitro effect of PRIMA-1 administration on cells with different p53 status by conducting cell viability and apoptosis assays. The expression levels of proteins in TP53-related pathways were examined by Western blotting, while knockdown studies were conducted to investigate the mechanism underlying PRIMA-1’s function. An ESCC xenograft model was further used to evaluate the therapeutic effect of PRIMA-1 in vivo.

Results
PRIMA-1 markedly inhibited cell growth and induced apoptosis by upregulating Noxa expression in ESCC cell lines with a TP53 missense mutation, whereas no apoptosis was induced in ESCC with wild type TP53 and with TP53 frameshift and nonsense mutations. Importantly, the knockdown of Noxa cancelled the apoptosis induced by PRIMA treatment in ESCC cell lines with a TP53 missense mutation. PRIMA-1 administration, compared with placebo, showed a significant antitumor effect by inducing Noxa in the xenograft model of an ESCC cell line with a TP53 missense mutation.

Conclusion
PRIMA-1 exhibits a significant antitumor effect, inducing massive apoptosis through the upregulation of Noxa in ESCC with a TP53 missense mutation.

Disclosure
All authors have declared no conflicts of interest.
PS02.125: NEOADJUVANT CHEMOTHERAPY PLUS SURGERY FOR NON-T4 CSTAGE II/III ESOPHAGEAL CANCER: A SINGLE INSTITUTION EXPERIENCE IN JAPAN
Authors: Ikebe Masahiko , Ohta Mitsuhiko , Sugiyama Masahiko , Morita Masaru , Toh Yasushi 
Published: September 2018

Abstract

Background
In Japan, following the results of JCOG 9907 trial, neoadjuvant chemotherapy (NAC) and radical surgery has been a standard treatment for Non-T4 cStage II/III esophageal cancer. Since 2009 we have also positioned NAC as standard treatment. We examined treatment outcomes and problems in our institute.

Methods
From 2009 to 2015, there were 64 patients with non-T4 stage II/III esophageal cancer treated with chemotherapy who are planned to undergo curative surgery. The standard NAC regimen consists of 2 courses of CDDP/5-FU (CF) therapy. As standard surgical procedure, subtotal esophagectomy, cervical anastomosis, three regional lymph node dissection were performed.

Results
The number of patients was 23/41 cases of cStage II/III respectively. 53 patients (88%) completed two courses of NAC. At the end of first course, NAC was terminated due to adverse events in 4 cases and due to the increasing tendency of tumors in 7 cases. NAC-induced adverse events of grade 3 or higher consists of myelosuppression in 27 cases (42%), appetite loss in 5 cases and so on. Surgery was performed in 61 cases (95%), of which R0 operation in 56 cases (88%), R1 operation in 3 cases and R2 operation in 2 cases. Three patients did not undergo surgery due to progressive disease. There were 7 cases (11%) of postoperative complications of Grade 3 or higher, but there was no in-hospital death. In the histological therapeutic effect, there were 5/41/7/4/3 cases for Grade 0/1a/1b/2/3, respectively. Three-year and five-year overall survival rate of all 64 patients were 68% and 47%. In 56 patients who underwent R0 surgery, they were 76% and 61% respectively.

Conclusion
From the viewpoint of adverse events and postoperative complications, NAC plus radical surgery for cStage II/III esophageal cancer could be performed safely. Considering that more than 60% of the patients belong to cStage III, this treatment strategy resulted in relatively favorable prognosis.

Disclosure
All authors have declared no conflicts of interest.
PS02.151: ESOPHAGEAL CANCER RESECTION AND AZYGOS LOBE
Authors: Nobuhisa Tetsuji 
Published: September 2018

Abstract

Background
Azygos lobe is a congenital variation of the upper lobe of the right lung and is seen in 1% of the population. Esophagectomy is usually performed through a right thoracotomy, so the 1% of the esophagectomy require a treatment for the change from azygos lobe. We report a case of the thoracoscopic approach in the prone position in patient admitted for esophageal carcinoma and azygos lobe.

Methods
We herein describe a 71-year-old male with esophageal carcinoma associated with azygos lobe. The procedures of our surgical techniques were as follows: (1) The patient was placed in prone position. (2) Two 12mm-trocars and two 5mm-trocar were used. (3) Subtotal esophagectomy and lymphadenectomy was performed with the arch of the azygos vein cutting by using the right-sided thoracoscopic approach in addition to the laparotomy. (4) Retrosternal esophagogastrostomy was performed for reconstruction.

Results
Operative time was 375 min. Blood loss was 170 g, and no perioperative transfusion was required. Postoperative recovery was uneventful. Histology showed the resection margins were clear. Surgical findings were as follows: (1) The azygos lobe was easily found in the upper mediastinum. (2) The azygos vein and the membrane was into the apex of the lung. (3) Cutting both of them, whole esophagus was clear without the arch of the azygos vein. (4) Esophagus was effectively stripped with no disturbance of the arch of the azygos vein.

Conclusion
The described procedure for esophageal carcinoma and azygos lobe is a minimally invasive alternative to the conventional thoracotomy that looks promising.

Disclosure
All authors have declared no conflicts of interest.
PS02.177: EFFECT OF PREHABILITATION ON FITNESS IN PATIENTS UNDERGOING NEOADJUVANT TREATMENT AND OESOPHAGOGASTRIC CANCER SURGERY: A RANDOMISED CONTROLLED TRIAL
Authors: Allen Sophie , Brown Vanessa , Prabhu Pradeep , Rockall Timothy , Preston Shaun , Sultan Javed 
Published: September 2018

Abstract

Background
Neoadjuvant chemotherapy (NAC) and surgery improves 5-year survival in patients with locally-advanced oesophagogastric (OG) cancer. NAC reduces fitness as assessed by cardiopulmonary exercise (CPX) testing. We aim to demonstrate improvement in CPX test performance in patients undergoing a 15-week ‘prehabilitation’ programme during and after NAC, compared those receiving ‘standard care’.

Methods
A single-centre, parallel-arm randomised controlled trial was conducted in patients undergoing NAC for OG cancer. Patients were assigned to a 15-week prehabilitation programme comprising twice weekly supervised aerobic and resistance training, a thrice weekly home exercise plan, and 6 Medical Coaching sessions (Prehab), or standard care (Control). CPX was performed at baseline (before NAC; Test 1), 2 weeks following NAC completion (Test 2), and during the preoperative week (Test 3). The primary outcome (anaerobic threshold (AT)) is powered for 48 patients (24 per group). Secondary outcomes include peak oxygen uptake (pVO2) and work rate (WR).

Results
Since December 2016, 46 patients have been recruited, with a 15% drop-out rate (7/46). All patients received NAC. To date, complete dataset is available for 27 subjects (Prehab n = 15; Control n = 12). Groups were matched for baseline demographics and AT/pVO2/WR (P = ns). At baseline: Mean AT 13.3 ± 2.91ml/kg/min, pVO2 797.85 ± 168.04ml/min/m2, and WR 148.63 ± 40.18watts. Effects of NAC (Tests 1 to 2): All subjects had a mean decline in AT (Prehab -1.41ml/kg/min vs. Control -1.69 ml/kg/min) with no difference in WR decline (Prehab -9.87watts vs. Control -9.66watts; P = 0.98). At Test 2, there was a trend towards pVO2 improvement with Prehab (+ 20.2ml/min/m2) whereas pVO2 in Controls deteriorated (-81.98ml/min/m2; P = 0.06). Effects of NAC and 5-week ‘recovery period’ (Tests 1 to 3): There was a tendency towards a smaller AT decrease from baseline with Prehab subjects (-0.6ml/kg/min) compared with Controls (-1.5ml/kg/min; P = 0.30). Compared with Test 1, Prehab patients demonstrated a non-significant trend towards improvement in pVO2 (+ 20.2ml/min/m2) and WR (+ 1.86watts) following a period of recovery. Controls observed a decrease in both parameters (pVO2 -16.48ml/min/m2, WR -3.5watts).

Conclusion
A prehabilitation programme is feasible during and after NAC. Interim analysis demonstrates a trend towards return of baseline pVO2 in patients receiving prehabilitation. Trial completion is warranted and the full dataset will be available by June 2018.

Disclosure
All authors have declared no conflicts of interest.
PS02.208: THE SHIELDING METHOD WITH POLYGLYCOLIC ACID SHEETS AND FIBRIN GLUE FOR PREVENTING ESOPHAGEAL STRICTURE AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION: A HISTORICAL CONTROL STUDY
Authors: Iizuka Toshiro , Kikuchi Daisuke , Suzuki Yugo , Hoteya Shu 
Published: September 2018

Abstract

Background
There have been several reports that steroid administration are effective at preventing strictures after ESD. However, adverse events after steroid use are of great concern. We have reported that shielding with polyglycolic acid (PGA) sheets and fibrin glue can be useful for prevention of stricture after ESD. We conducted a retrospective analysis of efficiency of shielding with PGA sheets and fibrin glue for prevention of esophageal stricture compared with intralesional steroid injection.

Methods
ESD was performed on a total of 608 lesions in 553 patients for superficial esophageal cancer from January 2012 to March 2017. Of these, 45 lesions were enrolled in the study group (PGA sheets and fibrin glue) and 40 lesions were enrolled in the control group (intralesional steroid injection). The incidence of postoperative stricture at 6 weeks and the number of sessions of endoscopic balloon dilatation (EBD) required to resolve any strictures were evaluated. Among them, patients with additional surgery were excluded in both groups when investing the outcome.

Results
The post-ESD stricture rate was 10.5% in the study group (4/38 patients), which was not significantly lower than the stricture rate of 10.8% in the historical control group (4/37 patients; P = 0.63). The mean number of EBD was 1.2 ± 4.2 in the study group and 0.68 ± 2.2 in the control group, which was not significant (P = 0.47).

Conclusion
PGA sheets and fibrin glue appear to be a promising option for the prevention of esophageal stricture similar to the effect of intralesional steroid injection.

Disclosure
All authors have declared no conflicts of interest.
PS02.226: PREDICTIVE FACTORS FOR EARLY RECOVERY OF ORAL INTAKE IN PATIENTS WHO UNDERWENT CURATIVE ESOPHAGECTOMY FOR ESOPHAGEAL CANCER
Authors: Isobe Yujiro , Kawakubo Hirofumi , Amada En , Mayanagi Shuhei , Fukuda Kazumasa , Nakamura Rieko , Wada Norihito , Suda Koichi , Ando Makiko , Ishikawa Aiko , Muraoka Kaori , Kitagawa Yuko 
Published: September 2018

Abstract

Background
Evaluating swallowing function by Videoendoscopic evaluation of swallowing (VE) and Videofluorography (VF) is vital in reintroducing oral diet to patients who underwent esophagectomy. However, performing VE and VF requires specific facility and experts. So, the aim of this study is to evaluate predictive factors for early recovery of oral intake.

Methods
One-hundred and thirty-six patients who underwent minimally invasive esophagectomy for thoracic esophageal cancer with three-field-lymph node dissection were enrolled. Patients’ characteristics, surgical and pathological factors, postoperative complications, duration from surgery to reintroducing oral intake, results of repetitive saliva swallowing test (RSST) and maximum phonation time (MPT) on seventh postoperative day (7POD) were analyzed. We classified patients that duration of reintroducing oral intake is shorter than 10 days into Normal-intake (N) group and patients that duration of oral intake is longer than 11 days into Delayed-intake (D) group.

Results
The average age of all patients was 64 ± 9 years old and average hospital stay of them was 30 ± 15 days. Three-field-lymph node dissection was performed in 96% of the cases and all patients have been performed cervical esophagogastrostomy. N group had significantly many patients who completed neoadjuvant chemo(radio)therapy (neo-C(R)Tx)) compared to D group (74% vs. 51%, P = 0.01). Also, patients in N group had significantly low level of preoperative indocyanine green test (ICG test; determined by colorimetric method at 15 minutes after injection of indocyanine green solution) and maximum postoperative serum C-reactive protein level until 7POD (max-CRP) compared to D group (P = 0.047, P = 0.001, respectively). Moreover, average time of MPT on 7POD was long in N group compared to D group (P = 0.05). In multivariate analysis, completion of neo-C(R)Tx, ICG ≤ 9, max-CRP ≤ 14.5 mg/dL was independent predictive factor of early recovery of oral intake (OR: 2.6 P = 0.023, OR: 4.6 P = 0.003, OR: 1.7 P = 0.008, respectively).

Conclusion
Preoperative good liver function, completion of neoadjuvant treatment and relatively low postoperative inflammation were considered to be predictive factors for early recovery of oral intake in patients who underwent curative esophagectomy for esophageal cancer.

Disclosure
All authors have declared no conflicts of interest.
PS02.237: IDENTIFICATION OF THREE DISTINCT BIOLOGICAL SUBTYPES IN ESOPHAGEAL AND JUNCTIONAL ADENOCARCINOMA BY RNA SEQUENCING
Authors: Krishnadath Kausilia , Hoefnagel Sanne , Calpe Silvia , Sancho-Del Serra Carmen , Van Berge Henegouwen M I , Hulshof Maarten , Van Laarhoven Hanneke , Gisbertz Suzanne , Bergman Jacques , Koster Jan 
Published: September 2018

Abstract

Background
Advances in therapy have achieved incremental improvements in overall outcome in patients with Esophageal Adenocarcinoma (EAC), but over- and undertreatment of undefined subgroups of patients might undermine these benefits. The biological diversity of EAC complicates patient selection and treatment stratification and impedes the development of new targeted agents. Further insight into the heterogeneous molecular pathology of EAC to select patients for standard chemo-radiotherapy and/or novel targeted strategies is urgent.

Methods
In our analysis, we included 110 patients with EAC and junctional adenocarcinomas diagnosed between 2012 and 2017. Patients either received neoadjuvant chemo-radiotherapy (nCRT) with carboplatin and paclitaxel, followed by surgical resection or chemotherapy only. Pre-treatment tissue samples of the tumor were collected during upper gastrointestinal endoscopy. RNA was extracted from these samples and RNA sequencing profiles were obtained. We performed unsupervised hierarchical clustering on the tumor RNA profiles to identify distinct subtypes. We used a machine learning approach to train a model with our AMC dataset. This model was applied to the a public TCGA dataset.

Results
We could identify three distinct biological subtypes. We found that that subgroup 2 and 3 had slightly poorer overall survival, although the difference was not significant. The TCGA dataset resulted in the identification of similar groups with similar signatures. One of the pathways that we discovered proved to be highly upregulated in group 2, was NOTCH signaling. Genes within the NOTCH signaling pathway can be targeted by specific antibodies that are currently in research phase for several types of cancer.

Conclusion
Our studies support the existence of three distinct EAC/junctional subtypes. Clinical use of an EAC subtype classifier might lead to identification of new therapeutic targets and improve stratification of patients for (targeted) therapies and subsequently improve outcomes. However, our results need to be further validated in independent cohorts.

Disclosure
All authors have declared no conflicts of interest.
PS02.239: SPECIFIC INHIBITION OF BONE MORPHOGENIC PROTEIN (BMP4) AS A POTENTIAL THERAPEUTIC STRATEGY FOR ESOPHAGEAL ADENOCARCINOMA
Authors: Krishnadath Kausilia , Hoefnagel Sanne , Calpe Silvia , Read Matthew , Straub Danielle , Correia Ana , Sancho-Del Serra Carmen 
Published: September 2018

Abstract

Background
In Western countries, the highly malignant Esophageal adenocarcinoma (EAC) have the most dramatically rising incidence of all malignancies. BMP4 is a growth factor important for carcinogenesis. We found that BMP4 is aberrantly expressed in Barret's esophagus, the pecursor lesion of EAC, and that together with CDX2 drives the intestinalization of epithelial metaplasia. However, its role in esophageal adenocarcinoma (EAC) remains uncertain.

Methods
Method: To elucidate whether BMP4 is involved in malignancy in EAC we used an RNA sequencing database of 56 EAC treatment naive endoscopic biopsies to investigate if there is a subgroup of cancers with high BMP signaling. We validated results by qPCR and immunohistochemistry in matching tumor samples. Next we used our recently developed effective and highly specific anti-BMP4 antibodies(1,2) to study the effect of inhibition of BMP4 on both in vitro as well as in vivo models of EAC.

Results
Using a gene set that was recently published for BMP signaling, we were able to distinguish a subgroup of EAC patients with increased BMP signaling. By IHC we confirmed that 70% of EAC tumors express BMP4 at the protein level. We found that patients with high levels of BMP4 expression tend to have a poorer recurrence-free survival compared to patients with low BMP4 expression, which suggests a more aggressive tumor behavior in BMP4 expressing EAC tumors. Most importantly, inhibition of BMP4 function in EAC cells by our recently developed anti-BMP4 antibodies lead to an increase in chemo-sensitivity and a decreased in invasive and migratory capabilities in vitro. Preclinical in vivo studies with a patient-derived tumor xenograft mouse model of an EAC tumor confirmed that anti-BMP4 antibodies can effectively reduce tumor growth and synergistically act with chemotherapy agents.

Conclusion
We identified a subgroup of EAC with increased BMP signaling. Our studies support a role of BMP4 in chemo-resistance and invasiveness in EAC, and indicate that inhibition of BMP4 with highly our specific llama-derived antibodies is an attractive therapy for improving outcomes of EAC.

Disclosure
All authors have declared no conflicts of interest.