bluuebunny/crossref_metadata_2025 huggingface dataset:
PS02.186: EUS-GUIDED FIDUCIAL MARKER INSERTION TO GUIDE RADIOTHERAPY IN ADVANCED ESOPHAGEAL CARCINOMA.
Authors: Chan Shannon , Teoh Anthony , Chi Yip Hon , Wong Vivien , Chiu Philip , Ng Enders
Published: September 2018

Background

The use of radiotherapy with or without concurrent chemotherapy is frequently required in treatment of advanced esophageal carcinomas. It can be given in an adjuvant, neoadjuvant or definitive setting. However, the margins of the tumor are often difficult to ascertain on computed tomography. Thus, EUS-guided fiducial marker insertion has an important role to aid the localization of the proximal and distal margins of the esophageal tumor. However, the optimal technique of the procedure is still uncertain.

Methods

This was a retrospective study of all patients who received EUS-guided fiducial marker insertion between March 2015 and October 2017. All patients suffering from esophageal carcinoma scheduled for radiotherapy underwent the procedure within one week of the scheduled appointment. Gold fiducial markers 5mm x 0.35mm (Visicoil, IBA Dosimetry, USA) were back loaded onto a 22-gauge needle (Vizishot, Olympus Medical, Japan) or (Expect, Boston Scientific, USA). The markers were placed under EUS guidance either intratumorally or in the normal submucosa just proximal and distal to the tumor.The submucosal planes were raised with diluted hyaluronic acid before insertion of the marker. Outcome parameters included tumor characteristics, early and late migration rates and tumor response rates.

Results

35 patients were included in the study. The mean (S.D.) age was 61.0 (9.9) years old. The mean (S.D.) length of the tumor were 7.2 (6.0) cm and and 86.2% of the patients had stage 3 disease. 27 patients had markers inserted by EBUS and 71.4% in the submucosa. When comparing fiducials that were placed in the submucosa versus intratumorally, significantly more fiducials had early (30% vs 0%, P = 0.004) and late migration (80% vs 0%, P < 0.001) in the intratumoral group. There were no differences in the stage of disease (P = 0.870), percentage of patients that completed radiotherapy (P = 0.063) and response rate (P = 0.197). There were no adverse effects in both groups.

Conclusion

In esophageal carcinomas planned for radiotherapy, EUS-guided fiducial markers should be placed in the submucosa just proximal and distal to the tumor instead of intratumorally. This may be able to increase the precision for radiotherapy.

Disclosure

All authors have declared no conflicts of interest.
PS02.188: EXPRESSION AND ROLE OF ANION EXCHANGER 2 IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Mitsuda Masato , Shiozaki Atsushi , Hikami Shoichiro , Shoda Katsutoshi , Arita Tomohiro , Kosuga Toshiyuki , Konishi Hirotaka , Morimura Ryo , Murayama Yasutoshi , Kuriu Yoshiaki , Ikoma Hisashi , Kubota Takeshi , Nakanishi Masayoshi , Fujiwara Hitoshi , Okamoto Kazuma , Otsuji Eigo
Published: September 2018

Background

Purpose: Recent studies have reported essential roles for various intracellular pH regulators in epithelial carcinogenesis and tumor progression. The aims of the present study were to investigate the role of anion exchanger 2 (AE2) in the regulation of tumor progression-related genes and the prognostic value of its expression in esophageal squamous cell carcinoma (ESCC).

Methods

In human ESCC cell lines, knockdown experiments were conducted using AE2 siRNA, and the effects on cellular movement and survival were analyzed. The gene expression profiles of cells were examined using a microarray analysis. An immunohistochemical analysis was performed on 61 primary tumor samples obtained from ESCC patients who underwent esophagectomy.

Results

AE2 was strongly expressed in KYSE170 and TE13 cells. The depletion of AE2 in these cells increased cell migration and inhibited the induction of apoptosis. The results of the microarray analysis revealed that various matrix metalloproteinase (MMP) signaling pathway-related genes, such as MMP1, MMP12, and TIMP4, were up- or down-regulated in AE2-depleted KYSE170 cells. Immunohistochemical staining showed that AE2 was primarily located in the cell membranes or cytoplasm of carcinoma cells, and its expression pattern at the invasive front (IF) of the tumor was related to the pT category. Prognostic analyses revealed that the low-grade expression of AE2 at the IF was associated with shorter postoperative survival.

Conclusion

s: The results of the present study suggest that reductions in AE2 in ESCC enhance cellular movement by affecting MMP signaling pathways and are related to a poor prognosis in patients with ESCC.

Disclosure

All authors have declared no conflicts of interest.
PS02.190: THE SIGNIFICANCE OF INTRAOPERATIVE PATHOLOGICAL OF RECURRENT NERVE NODE IN NECK-FIELD LYMPH NODE DISSECTION OF ESOPHAGEAL CANCER
Authors: Xu Jinxin , Zheng Bin
Published: September 2018

Background

The aim of this study is to explore whether the metastasis of the recurrent laryngeal nerve node can guide neck-field lymph node dissection of esophageal squamous cell carcinoma.

Methods

collected data from 58 patients who had undergone intraoperative pathological frozen of bilateral recurrent nerve node and three-field lymph node dissection in Fujian medical university union hospital, to explore the relationship between recurrent laryngeal nerve node metastasis and cervical lymph nodes metastasis.

Results

In the positive right laryngeal node group, 31.58% of the patients had metastasis in the cervical lymph nodes, and patients with negative laryngeal node, 10.26% of the patients had metastasis (P0.05). The sensitivity, specificity, accuracy, positive predictive value, negative predictive value were 70.00%, 70.83%, 70.69%, 33.33% and 91.89%. In the positive left laryngeal node group, 55.56% of the patients had metastasis, and patients with negative laryngeal node, 10.20%of the patients had metastasisP0.05. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value were 50.00%, 91.67%, 84.48%, 55.56% and 89.80%. In the positive laryngeal node group(one of the laryngeal node were positive), 33.33% of the patients had metastasis, In the negative group, 5.88% of the patients had metastasisP0.05.The sensitivity, specificity, accuracy, positive predictive value, negative predictive value were 80.00%, 66.67%, 68.97%, 33.33% and 94.12%. In the group of bilateral laryngeal node metastasis, 66.67% of the patients had metastasis. The sensitivity, specificity, accuracy, positive predictive value, negative predictive value of the preoperative neck ultrasound combined with PET/CT were 20.00%, 83.33%, 72.41%, 20.00%, 83.33%. Table 1 The statistics about the intraoperative pathological frozen of bilateral recurrent nerve node and the preoperative neck ultrasound combined with PET/CT

Conclusion

If intraoperative pathological frozen prompted positive, we can decide whether three-field lymph node dissection should be performed combined with preoperative examination, tumor location and degree of tumor infiltration to get appropriately stage and achieve the purpose of radical.Intraoperative pathological frozen state of recurrent nerve node metastasis is an indicator for the selection of neck-field dissection in thoracic esophageal carcinoma.

Disclosure

All authors have declared no conflicts of interest.
PS02.192: TWO CASES OF PRIMARY MALIGNANT MELANOMA OF ESOPHAGUS TREATED WITH SUBTOTAL ESOPHAGECTOMY
Authors: Hirohata Ryosuke , Emi Manabu , Hamai Yoichi , Ibuki Yuta , Okada Morihito
Published: September 2018

Background

Malignant melanoma of the primary esophagus is rare, in general it has high malignancy and poor prognosis. We report two cases of early-stage primary malignant melanoma of esophagus (PMME) underwent subtotal esophagectomy.

Methods

Case presentation

Results

[Case 1]A 66-year-old man was pointed out a black legion on the lower esophagus by upper gastrointestinal endoscope for screening purposes. The lesion was diagnosed as malignant melanoma by biopsy. In addition, another black lesion was also found in the pharynx, but there was no malignant cell. Other examinations did not reveal any findings of lymph node metastasis and distant metastasis. We diagnosed PMME (T1aN0M0 Stage 0) and performed surgical resection. Pathologically it was pT1a (LPM), pN0. There is no recurrence, and it is under observation. [Case 2] A 51-year-old woman was conducted upper gastrointestinal endoscopy for the purpose of scarring epigastric pain, and a black lesion was pointed out in lower esophagus. Surgical resection was performed with diagnosis of PMME (T1bN0M0 Stage I). The pathological stage was pT1a (MM), pN0.

Conclusion

The 5 year survival rate of malignant melanoma of primary esophagus is poor with about 30 to 35%, and especially in cases with lymph node metastasis, the survival rate further decreases. The both cases were discovered accidentally by endoscopic examination, leading to early diagnosis and early treatment. Therefore, long survival is expected. There is also a report that melanosis is associated with melanoma, so case 1 requires careful follow-up observation.

Disclosure

All authors have declared no conflicts of interest.
PS02.194: THE GENERATION & VALIDATION OF FOUR NEW ESOPHAGEAL CANCER CELL LINES WITH MATCHED PATIENT-DERIVED TUMOR XENOGRAFTS
Authors: Read Matthew , Liu David , Guerra Glen , Duong Cuong , Krishnadath Kausilia , Clemons Nicholas , Phillips Wayne
Published: September 2018

Background

Research into esophageal cancer, in particular adenocarcinoma, has been hampered by a paucity of relevant pre-clinical models. To date, only 13 bona fide adenocarcinoma cell lines have been published, with only six being derived from patients with confirmed Barrett's esophagus. Having so few available cell lines makes it difficult to model the genetic diversity observed in esophageal adenocarcinoma. In addition, only one of these lines has been shown to be reproducibly metastatic in xenograft models. This is in distinct contrast to the disease in the human, which is almost universally metastatic when left untreated.

Methods

Using our previously published intramuscular xenografting technique1, patient derived tumour xenografts (PDTX) were generated from endoscopic biopsies of treatment naïve esophageal adenocarcinoma and SCC biopsies. Following successful engraftment, PDTX tissue was digested in order to generate small explant pieces. Explants were then plated with media and cultured for extended periods until a dominant clone was cultured. One cell line was directly obtained from the malignant ascites of a mouse that was harboring a PDTX that had metastasized. Established cell lines then underwent validation, which consisted of short tandem repeat (STR) analysis, targeted oncogene assessment using the Illumina TruSeq cancer panel, tumorigenic assay, immunohistochemical (IHC) analysis for both adenocarcinoma and SCC markers as well as FACS analysis for both epithelial and human markers.

Results

Matched PDTX and xenograft derived cell lines were generated from two separate SCCs in addition to two separate adenocarcinomas. From one of the adenocarcinoma lines, two separate cell lines were generated, with one clone demonstrating a reproducibly metastatic phenotype, while the other remained non-metastatic. STR analysis confirmed all of the PDTXs and cell lines were derived from their respective patients and IHC analysis confirmed that they expressed the appropriate epithelial markers.

Conclusion

We have successfully generated and validated four additional esophageal cancer cell lines (two adenocarcinoma and two SCC) with matched PDTXs. The combination of both models creates a powerful tool, given the ability of PDTXs to recapitulate the heterogeneity and stromal elements of the original tumour, and the versatility of cell lines for mechanistic studies. 1. Read, M., et al. Annals of surgical oncology 2015.

Disclosure

All authors have declared no conflicts of interest.
PS02.195: CIRCULATING TUMOUR DNA HAS UTILITY IN THE CLINICAL MANAGEMENT OF ESOPHAGEAL CANCER
Authors: Phillips Wayne , Yates Michael , Dawson Sarah-Jane , Duong Cuong , Clemons Nicholas
Published: September 2018

Background

Cell-free DNA, a consequence of normal cell death and apoptosis, is found in the blood of all individuals. In cancer patients, a proportion of circulating cell free DNA will be derived from tumour cells, and is termed circulating tumour DNA (ctDNA).We have developed a blood-based ‘liquid biopsy’ to detect ctDNA in plasma of esophageal cancer patients.

Methods

Tumour, buffy-coat (germline) and plasma samples were obtained from 28 esophageal cancer patients at the time of diagnosis. Serial blood samples were collected from 8 patients. Somatic DNA mutations in 9 genes (TP53, ARID1A, SMAD4, CDKN2A, SMARCA4, NRG1, APC, PIK3CA and KRAS) were evaluated in tumour biopsies and plasma using targeted sequencing. Tumour specific mutations were confirmed by droplet digital PCR, which was used to track patient-specific ctDNA in plasma from serially collected blood samples.

Results

Somatic mutations in at least one of the targeted genes were detected in 19/28 (68%) tumour biopsies. The same mutations were detected in ctDNA from plasma in 9/19 (48%) patients. Additional mutations that were not detected in the tumour biopsies were detected in plasma DNA from 2 patients, highlighting the issues of intra-tumoural heterogeneity and sampling bias of tumour biopsies. ctDNA was more frequently detected in patients with advanced disease where it represented a greater proportion of the total cell-free plasma DNA than in patients with localised disease. In patients with serial samples, levels of ctDNA correlated with response to treatment, and rises in ctDNA could be detected prior to clinical evidence of relapse.

Conclusion

Detection of ctDNA using targeted sequencing and digital PCR is feasible in the majority of esophageal cancer patients, particularly those with advanced disease. Dynamic changes in ctDNA levels reflect response to treatment and disease relapse as determined by conventional clinical imaging. We conclude that ctDNA levels can provide supplemental evidence regarding disease staging, as well as prognostic and predictive information that can inform therapeutic pathway decisions in esophageal cancer patients.

Disclosure

All authors have declared no conflicts of interest.
PS02.196: STUDY OF BODY COMPOSITION CHANGE AFTER ESOPHAGECTOMY
Authors: Ogata Takashi , Osakabe Hiroaki , Nagasawa Shinsuke , Nakazono Masato , Hara Kentaro , Kumazu Yuta , Hayashi Tsutomu , Yamada Takanobu , Yoshikawa Takaki
Published: September 2018

Background

Esophageal cancer surgery with lymphadenectomy is known as a cause of weight loss during perioperative period, but the change of body composition is unclear.

Methods

The aim of study is to clarify the influence of body composition change after esophagectomy. 144 patients(51 cases without NAC and 93 cases with NAC: 98 cases with less than G2 perioperative complications and 46 cases with G2 or more perioperative complications: 36 cases with recurrence and 108 cases without recurrence were included) of esophageal cancer who underwent esophagectomy with lymphadenectomy from August 2011 to December 2016 and evaluated body composition examination before operation and after operation(1, 3, 6 month) were included in this study. We compared the change of body composition between with or without preoperative chemotherapy, postoperative complication, and recurrence.

Results

The weight loss rate at discharging hospital, 1,3,6 month after discharge for without NAC group/with NAC group was 3.3/3.8%, 7.8/6.8%, 10.1/9.2%, 11.1/9.1% (NS), and the lean body mass reduction rate was 4.1/4.5%, 7.1/6.6%, 6.5/6.7% (N.S.), 6.6/4.3% (P < 0.05). The weight loss rate for with less than G2 perioperative complication group/with G2 or more perioperative complication group was 2.9/4.9%(P < 0.01), 6.1/8.7%(P < 0.01), 8.4/12.1%(P < 0.01), 8.4/11.2%(P < 0.05), and the lean body mass reduction rate was 3.7/5.9%(P < 0.05), 5.9/9.0%(P < 0.01), 5.6/9.6%(P < 0.01), 4.4/5.5%(N.S.). And there was no significant differences of weight loss rate and lean body mass reduction rate at discharging hospital, 1,3,6 month after discharge between with recurrence group and without recurrence group.

Conclusion

Due to postoperative complications after esophagectomy, the rate of weight loss increased from hospital discharge to 6 months after discharge. Particularly, lean body mass was reduced within 3 months. So, we may have a strategy such as continuing enteral nutrition even after discharge for complicated cases.

Disclosure

All authors have declared no conflicts of interest.
PS02.197: UPREGULATION OF IMP3 HAS A NEGATIVE PROGNOSTIC IMPACT IN EARLY INVASIVE ESOPHAGEAL ADENOCARCINOMA
Authors: Plum Patrick , Ulase Dita , Chon Seung-Hun , Berlth Felix , Zander Thomas , Alakus Hakan , Bollschweiler Elfriede , Hölscher Arnulf , Bruns Christiane , Quaas Alexander , Löser Heike
Published: September 2018

Background

Despite improvements in perioperative treatments, the overall survival of patients with esophageal adenocarcinoma (EAC) remains low. In early invasive tumors (pT1) there is striking risk discrepancy for tumors with vascular invasion (L1/V1). As this tumor stage is potentially locally resectable, there is an urgent need for reliable pretherapeutical evaluation. High expression of IMP3 correlates with worse prognosis in colon and gastric cancer. In a small series of 30 patients with EAC, IMP3 is significantly associated with lymphovascular invasion. In our large cohort of EAC, we analyzed the immunohistochemical expression of IMP3 in correlation to clinical data.

Methods

371 patients who underwent esophagectomy due to EAC at the Department of General, Visceral and Cancer Surgery, University of Cologne between 1999 and 2012 were included. Tissue Microarrays (TMA) were retrospectively established from the formalin-fixed, paraffin embedded material of the resected specimens and immunohistochemically stained using the primary antibody specific for IMP3. The IMP3 staining intensity was scored manually according to a 3-tier-scoring system (negative, weak and strong).

Results

TMAs from 371 patients were interpretable for further analysis. 109 patients (29.3%) had superficial EAC (pT1a/pT1b) while 262 (70.7%) showed locally advanced tumors (pT2 or pT3). 67 (26.7%) patients with advanced tumors and all pT1 EAC patients did not receive neoadjuvant therapy (chemotherapy or chemo-radiotherapy) prior to surgery. 259 of the 371 EAC revealed positive immunostaining for IMP3 including 167 strongly and 92 weakly positive. For patients without neoadjuvant therapy, there was a significant trend for higher IMP3 expression in early invasive tumors (pT1a/pT1b) showing significantly higher rates of IMP3 positive tumors compared to locally advanced pT3-tumors without neoadjuvant therapy (P = 0.0015). There was no difference of IMP3 expression according to neoadjuvant therapy in patients with pretreated EAC. There is a statistically significant association between IMP3 protein expression and shortened survival in early invasive pT1-esophageal carcinomas (P = 0.045).

Conclusion

IMP3 is a feasible marker in early invasive EAC (pT1a and pT1b) and is significantly associated with worse outcome. IMP3 indicates lymph node metastases, advanced infiltration depth and higher tumor grade. Thus IMP3 might be useful for therapeutic decisions in early invasive EAC.

Disclosure

All authors have declared no conflicts of interest.
PS02.198: RELATIONSHIP BETWEEN SUPPLEMENTAL TUBE-FEEDING NUTRITION AFTER HOSPITAL DISCHARGE AND LOSS OF SKELETAL MUSCLE AFTER ESOPHAGECTOMY IN ESOPHAGEAL CANCER PATIENTS
Authors: Niihara Masahiro , Tsubosa Yasuhiro
Published: September 2018

Background

Malnutrition is common after esophagectomy in esophageal cancer, and loss of skeletal muscle has been reported as a risk factor for survival. However, the impact of nutritional intervention on postoperative changes in skeletal muscle has been poorly reported.

Methods

Patients and methods: We have reported prospective feasibility study (FAST-ERAS Trial) will provide preliminary information on the routine use of 90-day supplemental tube-feeding nutrition (STN). Between February 2015 and September 2016, 24 patients following esophagectomy were enrolled in this study. For the first 90 days after hospital discharge, the participant would administer intermittent jejunostomy (trans-gastric) tube-feeding of total 250 ml enteric nutrient (ENEVO TM) a day using catheter tip by patient himself/herself in addition of oral intakes. The completion was defined as administering 70% or more of planned nutrient. We investigated the correlation between the completion of nutritional intervention, and the decrement in the skeletal muscle in cross-sectional area (CSA) at the third lumbar vertebra before and 6 months after surgery.

Results

The ratio of patients who completed the intervention: 20/24 (83.3%). The CSA of the skeletal muscle before surgery were 58.2 ± 11.6 cm2 in the patients who completed the nutritional intervention (complete group), 64.6 ± 22.9 cm2 in the patients who did not complete (non-complete group), respectively. The decrement in CSA were -0.63 ± 5.09 cm2 in complete group, 3.77 ± 3.33 cm2 in non-complete group (P = 0.017).

Conclusion

s: The supplemental tube-feeding nutrition not only during hospitalization but also during the first 90 days after discharge at home was significantly associated with maintaining and improving skeletal muscle after esophagectomy.

Disclosure

All authors have declared no conflicts of interest.
PS02.203: CHARACTERISTICS AND RISK FACTORS OF LYMPH NODE METASTASIS IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA PATIENTS WITH PREOPERATIVE COMPUTED TOMOGRAPHY-NEGATIVE LYMPH NODES
Authors: Dai Wei , Zhang Yuanqiang , Li Xueming , Peng Lin , Han Yongtao
Published: September 2018

Background

Characteristics and risk factors of lymph node metastasis (LNM) in esophageal squamous cell carcinoma (ESCC) patients with preoperative computed tomography (CT)-negative lymph nodes are not well elucidated. This study aimed to identify the characteristics and risk factors of LNM in ESCC patients with preoperative CT-negative lymph nodes.

Methods

We conducted a retrospective analysis of consecutive ESCC patients who had preoperative CT-negative lymph nodes and received esophagectomies between August 2013 and July 2016. Lymph node with a short-axis diameter ≦10 mm on preoperative CT image was considered as CT-negative lymph node. Eligible patients included those: aged 18∼80, without neoadjuvant therapy, without other malignant tumor history, without distant metastasis, without multiple esophageal lesions, tumor locating in the thoracic esophagus, receiving McKeown esophagectomy, undergoing R0 resection, having number of lymph nodes resection≧15, pathological staging as T1a-4aN0–3. Univariate and multivariate logistic regression analyses were used to identify risk factors of LNM.

Results

Among 243 ESCC patients identified, 137 had LNM (56.4%). The median number of lymph nodes dissected and LNM were 24 (range 15–79) and 2 (range 1–14), respectively. The rates of LNM of the upper, middle and lower thoracic ESCC were 50.0%, 59.3% and 55.1%, respectively. The rates of LNM with the maximal short-axis diameter of lymph node on preoperative CT of ≦5 mm, 6 mm, 7 mm, 8 mm, 9 mm and 10 mm were 57.4%, 42.9%, 47.4%, 31.8%, 73.9% and 70.8%, respectively (P = 0.034). Univariate analysis showed that age (P = 0.041), maximal short-axis diameter of lymph node on CT (P = 0.034), cervical lymph node dissection (P = 0.031), lymphovascular invasion (P < 0.001) and perineural invasion (P = 0.017) were associated with LNM. Multivariate analysis revealed that cervical lymph node dissection (P = 0.018), lymphovascular invasion (P = 0.007) and perineural invasion (P = 0.025) were independent risk factors of LNM.

Conclusion

Our study showed that the rates of LNM were also high in ESCC patients with preoperative CT-negative lymph nodes. Standard lymph node dissection is necessary for these patients. Cervical lymph node dissection, lymphovascular invasion and perineural invasion are independent risk factors of LNM in ESCC patients with preoperative CT-negative lymph nodes.

Disclosure

All authors have declared no conflicts of interest.
PS02.207: NEUTROPHIL-LYMPHOCYTE RATIO HOLDS NO PROGNOSTIC VALUE FOR OESOPHAGEAL AND JUNCTIONAL ADENOCARCINOMA IN PATIENTS TREATED WITH NEOADJUVANT CHEMOTHERAPY
Authors: Van Hootegem Sander , Smithers Mark , Gotley David , Brosda Sandra , Thomson Iain , Thomas Janine , Gartside Michael , Wijnhoven Bas P L , Barbour Andrew
Published: September 2018

Background

Several studies have been suggesting that neutrophil-lymphocyte ratio (NLR), as it reflects systemic inflammation, could help predict survival in oesophageal and junctional carcinomas. Therefore, we aimed to determine whether baseline NLR holds prognostic and predictive value in oesophageal and junctional adenocarcinomas (OAC) for patients treated with neoadjuvant chemotherapy (nCT) followed by surgery.

Methods

We studied the data of 144 included patients that received nCT, all identified from a prospectively maintained database. Pre-treatment haematology reports were used to calculate the baseline NLR, dividing absolute neutrophil count by absolute lymphocyte count. Multiple ways of grouping patients based on NLR were tried, including determining the optimal cut-off value based off a ROC-curve and the standard threshold for elevated NLR (> 5). NLR quartiles were used to display possible differences between groups in relation to overall survival (OS), disease-free survival (DFS) and pathological response according to Mandard score. Cox regression analysis was performed to determine independent prognostic factors for OS.

Results

The ROC-curve showed that NLR has no discriminating power for survival status (area under the curve = 0.460) and therefore no optimal cut-off value could be determined. Also, using the most frequently used threshold for elevated NLR (≥ 5) to group patients did not lead to a difference in OS (P = 0.112). Median OS times for NLR quartiles were 65 (Q1), 32 (Q2), 45 (Q3) and 46 months (Q4), with no significant difference (P = 0.926). DFS showed no difference between groups either, with median DFS times of 30 (Q1), 22 (Q2), 38 (Q3) and 23 months (Q4, P = 0.973). Pathological response according to Mandard score did not vary between NLR quartiles (P = 0.925). In addition, NLR was not associated with OS in univariate analysis (P = 0.518). Multivariate analysis showed that both pathological N- and M-stage, and number of involved nodes were independent prognostic indicators for OS.

Conclusion

The present study shows that, in contrast to other recently published papers, baseline NLR holds no prognostic or predictive value for OAC patients treated with nCT. This result strongly questions the validity of NLR as a prognostic indicator and its clinical usefulness.

Disclosure

All authors have declared no conflicts of interest.
PS02.210: EVALUATION OF PREDICTION SYSTEM IN TREATMENT EFFECT AND PROGNOSIS OF ESOPHAGEAL CANCER BASED ON RADIOEPIGENOMICS THEORY
Authors: Hoshino Isamu , Ishige Fumitaka , Iwatate Yosuke , Takiguchi Nobuhiro , Ikeda Atsushi , Soda Hiroaki , Tonooka Toru , Sato Nami , Nabeya Yoshihiro
Published: September 2018

Background

We tried integrated analysis of epigenomic information (Epigenomics) and image information (Radiomics) as Ragioepigenomics for esophageal cancer.

Methods

1, Expression analysis of miR, evaluation as prognostic predictor (Epigenomics), 2, Image information analysis (Radiomics): a, Normalization of contrast CT images, feature quantities by 3D gray level co-occurrence matrix extraction. b, Normalization of SUV of FDG-PET image. Extraction of feature quantity by 3D gray level co-occurrence matrix. c, Image analysis of features. 3, Integrated analysis of Epigenomics and Radiomics information: We analyzed the relationship between miR expression level and variables obtained from image analysis.

Results

As a result of Cox regression by the selection method using elastic net, three variables were selected from contrast CT, and the results of both were consistent. Furthermore, when the survival curve and the log rank test were performed by the Kaplan-Meier method for the cluster shade high value group and the low value group, a significant difference was observed in the 2 groups.

Conclusion

A multimodal approach so called Radioepigenomics, which is a system for analyzing molecular information from image analysis will be applied to future Precision Medicine.

Disclosure

All authors have declared no conflicts of interest.
PS02.214: ANALYSIS OF PROGNOSTIC FACTORS IN RECURRENCE CASES AFTER SURGERY FOR ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Nishiyama Mitsuo , Takeda Shigeru , Kanekiyo Shinsuke , Kitahara Masahiro , Iida Michihisa , Tokumitsu Yukio , Tomochika Shinobu , Tokuhisa Yoshihiro , Suzuki Nobuaki , Yoshino Shigefumi , Hazama Shoichi , Ueno Tomio , Nagano Hiroaki
Published: September 2018

Background

Esophageal cancer is one of the most malignant gastrointestinal cancers and prognosis in recurrent cases remains extremely poor. However some studies show a relatively favorable prognosis among patients with solitary recurrence site who undergo locoregional therapy. It is important to clarify prognostic factors in postrecurrence cases.

Methods

This study included 156 patients who underwent curative resection for esophageal squamous cell carcinoma from January 2005 to December 2014. In this retrospective study we analysed relationship between clinicopathologic factors and prognosis after recurrence among these 156 patients.

Results

The average age was 65.2 years (± 8.2), 34 males, 11 females, The frequency of recurrence is pStage I: 2/36 cases (5.6%), pStage II: 7/48 cases (15%), pStage III: 21/43 cases (49%), pStage IVa: 8/11 cases (73%). Median survival time after recurrence was 377 (29 - 3266 days), and a 1 year/2 years/3 year survival rate after relapse was 50%/24%/11%. Patients with recurrent disease were offered treatment with chemotherapy + surgery (5 cases, 11%), chemotherapy + radiation (17 cases, 38%), chemotherapy (18 cases, 40%) and BSC (5 cases, 11%). MST was not reached in the chemotherapy + surgery group (741- 3266 days), 431 days (91–2324 days) in the chemotherapy + radiation group, 223 days (85–1079 days) in the chemotherapy group, and 52 days in the BSC group. There was a significant difference between each groups (P < 0.03). In univariate analysis, age (≤ 65/ > 65) single/multiple site recurrence, presence or absence of postoperative pneumonia, presence or absence of ARDS was selected as a prognostic factor after recurrence. In multivariate analysis, single/multiple site recurrence(HR 10.2, 95%CI 2.619–39.8, P = 0.0008), Postoperative pneumonia (HR 3.6, 95% CI 1.186 - 10.867, P = 0.024), postoperative ARDS (HR 5.6, 95% CI 1.209 - 26, 3, P = 0.0276) was selected.

Conclusion

Postoperative pulmonary complications might be related and aggressive local control for single site recurrence might improve the prognosis after recurrence of thoracic esophageal squamous cell carcinoma.

Disclosure

All authors have declared no conflicts of interest.
PS02.218: EFFECT OF SILENCING EGFR GENE ON RADIOSENSITIVITY OF SQUAMOUS CELL CARCINOMA AND ADENOCARCINOMA IN ESOPHAGEAL CARCINOMA
Authors: Li Jiancheng , Qiu Zidan
Published: September 2018

Background

Squamous cell carcinoma and adenocarcinoma in esophageal carcinoma have different radiosensitivity

We investigate the effect of silencing EGFR gene on radiosensitivity of Eca-109and OE-19To investigate the effect of silencing EGFR gene on radiosensitivity of Eca-109and OE-19.

Methods

SiRNA segments for EGFR gene were designed, synthesized and transfected into human Eca-109and OE-19 and authenticated by RT-PCR and Western blotting. Both the two cell lines were classified into three groups: control group, irradiation group and tranfected with EGFR-siRNA before irradiation group. Divided ECa-109, OE-19cellblank control group, only irradiation group and EGFR-siRNA1 irradiation group(irradiation 0,2,4,6,8Gy).The radiosensitivity of different groups was studied by clonogenic survival curves and SERD0ratio. Finally we analyzed cell-cycle distribution and cell-apoptosis detected by Flow cytometry.

Results

EGFR-siRNA can downregulate the EGFR expression obviously, while it can cause mild cell growth inhibition(4.9% and 4.5%). EGFR-siRNA can obviously down-regulate the espression of EGFR in two kinds of cell.The rate of cell proliferation in inhibition by transfection were less than 5% (4.9%, 4.5%). The radiosensitivity of two cell lines transfected with EGFR-siRNA were intensified, with lower SF values. Eca-109cell got a higher SERD0ratio(1.40 vs. 1.01). Flow cytometry suggested that the G2/M phase cells percentage and the apoptosis rate increased more evidently in Eca-109cell transfected with EGFR-siRNA and irradiation(P = 0.016 and P = 0.028), with S phase cells percentage decreased(P = 0.007).

Conclusion

Silencing EGFR could enhance the radiosensitivity of esophageal squamous cell carcinoma more effectively than esophageal adenocarcinoma.

Disclosure

All authors have declared no conflicts of interest.
PS02.227: A NEW POSTOPERATIVE PAIN MANAGEMENT LEADS TO ENHANCED RECOVERY AFTER ESOPHAGECTOMY: A PROPENSITY SCORE-MATCHED ANALYSIS
Authors: Nakano Yuta , Ohkura Yu , Ueno Masaki , Udagawa Harushi
Published: September 2018

Background

Opioid use is reportedly associated with delayed recovery after surgery because of gastrointestinal motility disorder and postoperative nausea and vomiting despite of acceptable efficacy for pain control.The aim of this study was to investigated the efficacy of postoperative scheduled intravenous acetaminophen to reduce the opioid use and enhanced recovery after esophagectomy.

Methods

Of 93 and 57 consecutive patients who underwent esophagectomy for esophageal cancer before and after introduction of postoperative scheduled intravenous acetaminophen, propensity score-matched population was created and short-term clinical outcomes were compared.

Results

Significant defervescence was demonstrated in Acetaminophen group (A-group) compared with control group (C-group) during the perioperative period (P < 0.05), whereas no significant difference was observed in postoperative inflammatory parameters. The incidence of postoperative complications was similar between the groups. The number of PCA pushes and the frequency of use of other non-opioid analgesics was significantly reduced in the A-group (P < 0.05). Both daily and cumulative opioid use was significantly reduced in the A-group (P < 0.05). The time to first flatus and defecation significantly decreased in the A-group (P = 0.001 and P = 0.035, respectively). The day of first walking after surgery significantly decreased in the A-group (1.0 vs. 2.0 days, P < 0.001). The ICU stay (3.05 vs. 3.62 days, P = 0.003) and the hospital stay (21.6 vs.26.8 days, P = 0.074) tended to be decreased in the A-group.

Conclusion

Scheduled postoperative intravenous acetaminophen after esophagectomy may reduce the use of opioids and might be associated with enhanced GI motility and decreased incidence of PONV. Scheduled intravenous acetaminophen may be a feasible new pain management option in ERAS protocol after esophagectomy.

Disclosure

All authors have declared no conflicts of interest.
PS02.233: PRETREATMENT PROGNOSTIC FACTORS IN PATIENTS WITH RESECTABLE CSTAGE II-IV THORACIC ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Toyokawa Takahiro , Tamura Tatsuro , Sakurai Katsunobu , Kubo Naoshi , Tanaka Hiroaki , Yashiro Masakazu , Muguruma Kazuya , Hirakawa Kosei , Ohira Masaichi
Published: September 2018

Background

Background

Advanced esophageal cancer patients often develop tumor recurrence even after curative resection. Inexpensive and easily available prognostic factors are expected in daily clinical practice. The aim of this study was to identify the prognostic factors in patients with resectable cStage II-IV thoracic esophageal squamous cell carcinoma.

Methods

Patients and Methods

The study included 118 patients who underwent esophagectomy with curative intent for resectable cStage II-IV thoracic ESCC between January 2000 and December 2014. Time-dependent receiver operating characteristic curve analyses for 3-year overall survival (OS) as the endpoint were calculated, and the maximal Youden index was estimated to set the cut-off value for continuous variables. Survival rates were calculated by Kaplan-Meier method, and survival curves were compared using log-rank test. Univariate analysis and multivariate analysis for OS were conducted with Cox proportional hazards models.

Results

Results

The median follow-up period was 33 months (1–160 months). The 5-year OS rate for the entire study population was 52.2%. In univariate analysis, age (70 < ), sex, performance statue, American Society of Anesthesiologists Physical Status (ASA), serum squamous cell carcinoma antigen level (1.2 ng/ml < ), lymphocyte count (≤ 1172/μl), serum albumin level (≤ 3.7 g/dl), total cholesterol level (≤ 193 mg/dl), and C-reactive protein level (0.28 < mg/dl) were significantly associated with OS. In multivariate analysis, ASA (HR for ASA 2: 1.457, 95%CI 0.594–3.579; HR for ASA 3: 7.427, 95%CI 2.189–25.199; P = 0.001) and total cholesterol level (HR 0.506, 95% CI 0.261–0.983; P = 0.044) were independent prognostic factors for OS. The 5-year relapse free survival (RFS), cancer specific survival (CSS) and OS were 58.4%, 74.5% and 67.5% in high- total cholesterol group, and 38.7%, 51.3% and 39.1% in low- total cholesterol group, respectively (P = 0.031 in RFS, P = 0.004 in CSS, and P = 0.002 in OS).

Conclusion

Our findings showed that pretreatment total cholesterol level and ASA are independent prognostic factors of overall survival in patients with resectable cStage II-IV thoracic esophageal squamous cell carcinoma.

Disclosure

All authors have declared no conflicts of interest.
PS02.234: POSTOPERATIVE PNEUMONIA AFTER ESOPHAGEAL RESECTION: DO WE NEED PROPHYLCATIC ANTIBIOTICS FOR PREVENTION?
Authors: Maghsoudi Tina , Wilhelm Anke , Beumer Michael , Oldhafer Karl
Published: September 2018

Background

Postoperative pulmonary complications are a common course of serious morbidity after esophageal resection. In literature rates of pneumonia are quoted up to 38%. Recent studies showed that minimally invasive esophagectomy could reduce this to 9 to 15%, but is this the only approach to lower the incidence of postoperative pneumonia?

Methods

We analysed our data from esophagectomies performed in our department between 2014 to 2017. Only procedures with thoracotomy due to malignancies were included. All patients received a single shot dose of piperacillin/tazobactam repeated after 4 hours during operation. Bronchoscopy was performed intraoperatively with bronchial toilet. Patients at risk (COPD or viscous secretion) recieved antibiotics for further 7 days. If postoperatively elevation of CRP or leucocytes ocurred, thorax CT scan was performed. Only when pulmonary infiltrates were visible pneumonia was diagnosed.

Results

151 operations due to esophageal cancer were performed. Extended gastrectomies, minimal invasive esophagectomies with thoracoscopy and transhiatal resections were excluded. Only Ivor-Lewis resectios (108), McKeown resections (8) and colon interpositions (2) were analysed. The all over pneumonia rate was 13,6% (16 patients). The 30 day mortality was 2,5%. None of the patients died due to pneumonia.

Conclusion

To reduce postoperative pneumonia rates is an important aim in esophageal surgery. Latest data showed that minimally invasive surgery is adequate to achieve this. But not every patient is suitable for this procedure. From our single center experience we could show that also intraopereative bronchial toilet together with prophylactic antibiotic therapy could achieve good results.

Disclosure

All authors have declared no conflicts of interest.
PS02.236: THE IMPACT OF PREOPERATIVE SKELETAL MUSCLE MASS ON POSTOPERATIVE OUTCOMES AFTER ESOPHAGECTOMY FOR ESOPHAGEAL CANCER
Authors: Uemura Shion , Shichinohe Toshiaki , Ebihara Yuma , Kurashima Yo , Murakami Soichi , Hirano Satoshi
Published: September 2018

Background

It is said that preoperative muscle volume is likely associated with postoperative short- and long-term outcomes in several kinds of cancer by many reports. Esophagectomy for esophageal cancer (EC) is associated with high morbidity and EC has one of the worst prognoses in several kinds of cancer. We investigated the association of preoperative skeletal muscle mass with postoperative outcomes to improve them.

Methods

We analyzed 150 patients who underwent esophagectomy from February 2002 to March 2016. The cross-sectional area of the psoas muscle index (PMI) was measured at the third lumbar vertebral level using computed tomography. Clavien-Dindo classifications were used to analyze postoperative complications. Since skeletal muscle mass is significantly different according to gender, all analyses were completed by gender (male: 124, female: 26). The Mann-Whitney U test and the chi-square test were used to compare two groups for the analysis of postoperative complications. Multivariate analysis of postoperative complications was performed using a logistic regression model. Survival analyses were performed using a Cox proportional hazard model. Differences were considered to be significant if the P value was less than 0.05.

Results

In male patients, PMI value was significantly higher in CD≦ II groups than CD≧ III groups. It was also a independent factor for predicting postoperative complications (odds ratio: 0.995, 95% confidence interval: 0.991–0.999, P = 0.02). On the other hand, there was not a significant difference between PMI and overall survival. In female patients, PMI was not associated with postoperative complications and survival. Only pulmonary function (vital capacity percentage) was associated with postoperative complications and survival.

Conclusion

Preoperative muscle mass was associated with postoperative complications in male patients with EC. In male patients, PMI can be a useful tool to predict postoperative outcomes and select patients who require preoperative nutritional intervention and rehabilitation.

Disclosure

All authors have declared no conflicts of interest.
PS02.240: COMBINED GERMAN CLINICAL CANCER REGISTRIES: FIRST EXPERIENCE WITH ANALYSES ON DEMOGRAPHY AND TREATMENT OF CANCERS OF THE ESOPHAGUS AND STOMACH
Authors: Thomaschewski Michael , Hummel Richard , Kopeleva Olga , Barlag Hagen , Keck Tobias , Wellner Ulrich
Published: September 2018

Background

One critical aspect for improvement of health care delivery to the population is a continuous monitoring of results. In this context, an increasing number of clinical cancer registries has been implemented in Germany since 2013. Main aspects of these registries include quality control, assessment of clinical outcome, support of epidemiological registries and potential implementation into clinical follow up. The ADT (Cooperation of German Cancer Centres e.V.) aims to merge data from local cancer registries into one nation-wide registry. In this context, we were able to analyse for the first time data of > 100.000 patients with malignant diseases of the stomach and esophagus.

Methods

Data from all local cancer registries in Germany were requested in the context of the National German Cancer Conference 2018 hosted by the German Cancer Society (DKG). After preparation of data, analysis included demographic and treatment aspects, and esophageal/gastric/GOJ cancers were analysed separately.

Results

From 2000–2016, 101.559 patients with cancers of the esophagus and stomach have been reported, representing approximately one quarter of the expected cancer cases in this time frame in Germany. Data quality and completeness improved over time. Incidences of esophageal and GOJ cancers increased, whereas incidence of gastric cancer decreased. Median age differed between entities with highest respectively lowest age in gastric/esophageal cancer. Further, median age increased in all three tumor types in the study period. Treatment pattern changed over time with a distinct increase of the use of neoadjuvant therapy in all cancer types. Percentage of curative intended surgery increased over time, reaching roughly 60% in gastric cancer, about 50% in GOJ and esophageal adenocarcinoma, and slightly less then 25% in esophageal squamous cell carcinoma. Finally, analysis of tumor stage dependent treatment confirmed higher rates of curative intended surgical treatment in early tumor stages, and an increased use of neoadjuvant treatment or chemo/radiotherapy approaches in higher tumor stages.

Conclusion

Combined Clinical Cancer Registries provide the unique opportunity to assess clinical relevant data of a large population based cohort of patients for purposes such as quality control and outcome measurement. Further, subgroup analyses can provide valid information on clinically relevant questions such as outcome/quality of different treatments.

Disclosure

All authors have declared no conflicts of interest.
PS02.242: SIGNET-RING CELL PERCENTAGE MAY INFLUENCE PATHOLOGICAL RESPONSE TO CHEMOTHERAPY IN ESOPHAGO-GASTRIC JUNCTION SIGNET RING CELL CARCINOMA
Authors: Zanoni Andrea , Giacopuzzi Simone , Weindelmayer Jacopo , Veltri Alessandro , Fumagalli Romario Uberto , Parise Paolo , Rosati Riccardo , De Manzoni Giovanni
Published: September 2018

Background

Like in gastric cancer, the incidence of signet-ring cell carcinoma (SRCC) is rising also in esophago-gastric junction (EGJ) adenocarcinoma Siewert type I and II. SRCC is much more studied in gastric cancer and WHO classification divides poorly cohesive gastric cancer in two subtypes, depending on the percentage of signet-ring cells: real SRCC (percentage of signet-ring cell more than 50%) and poorly cohesive non-SRCC (less than 50%). Real SRCC seems to have higher chemosensitivity and better prognosis than poorly cohesive non-SRCC. Recently, a new classification for SRCC has been proposed, which subdivides SRCC based on different cut-off percentages of signet ring cells (less than or equal to 90% vs more than 90%). Aim of this study was to compare pathological response in patients with EGJ SRCC treated with neoadjuvant chemotherapy.

Methods

Study population comprised 11 patients with Siewert I and II EGJ SRCC treated with neoadjuvant chemotherapy and surgery. We analyzed differences in pathological response to therapy between ‘pure’-SRCC (more than 90% of SRC) and ‘non-pure’-SRCC (less than or equal to 90%). Tumor regression grade (TRG) was used to define response to treatment, with TRG 1–2 defining good response to treatment and TRG 3–5 poor or absent response to treatment.

Results

Among the 11 patients with EGJ SRCC, 6 had ‘pure’-SRCC histology and 5 ‘non-pure’-SRCC. Response to treatment in ‘pure’-SRCC patients was equally splint into good and poor responders: 3 had good response to treatment (TRG 1–2) and 3 poor or absent response (TRG 3–5). On the contrary most of ‘non-pure’-SRCC had poor or absent response: 4 out of 5 patients had TRG 3–5.

Conclusion

Although the case series was too small to perform statistical analyses, our results suggest that signet-ring cell percentage may influence the outcome of neoadjuvant therapy. Probably a larger case series would allow to better define cut-offs of percentage of signet-ring cell carcinoma of the EGJ. Moreover it would allow to inspect other factors related to response to treatment. This is only a preliminary investigation and further studies are needed to better understand the characteristics of these rising in incidence types of cancer.

Disclosure

All authors have declared no conflicts of interest.