bluuebunny/crossref_metadata_2025_split huggingface dataset:
PS02.038: SAFETY AND EFFICACY OF REPETITIVE PHOTODYNAMIC THERAPY FOR RESIDUAL ESOPHAGEAL CANCER LESIONS AFTER INITIAL PHOTODYNAMIC THERAPY
Authors: Tamaoki Masashi , Amanuma Yusuke , Horimatsu Takahiro , Ohashi Shinya , Muto Manabu 
Published: September 2018

Abstract

Background
Photodynamic therapy (PDT) is an effective salvage treatment for local failure after chemoradiotherapy in patients with esophageal cancers. However, the treatment strategy for local failure after initial PDT has not been established, and the safety and efficacy of repetitive PDT for such lesions are also unknown.

Methods
We retrospectively investigated 33 esophageal cancer patients who received initial salvage PDT at Kyoto University Hospital between May 2012 and November 2017. Additionally, we examined the treatment outcomes of those patients who received repetitive PDT.

Results
Twenty-one patients (64%) achieved local complete response (CR) by initial PDT, and local recurrence did not occur in those patients. Eleven patients (33%) had residual lesions after initial PDT. Among these, 7 patients were treated with repetitive PDT, 2 patients selected best supportive care, 1 patient was treated with surgery, and 1 patient was treated with chemotherapy. Five of the 7 patients who received repetitive PDT were treated with talaporfin sodium, and 2 patients were treated with porfimer sodium. The median age of the patients who received repetitive PDT was 70 years old, and all patients were men. Regarding histology, 6 patients were squamous cell carcinoma and 1 patient was adenocarcinoma. The median period from initial PDT to repetitive PDT was 3 months (range 1–4). Lesion depth before initial PDT was T1 in 3 patients and T2 in 4 patients. Lesion depth before repetitive PDT was T1 in 5 patients, and T2 in 2 patients. Local CR rate in 7 patients treated with repetitive PDT was 42.9% (3/7). Additionally, local CR rate in T1 cases was 60% and 0% in T2 cases. Adverse events of grade 3 or higher were not observed in any patient.

Conclusion
Repetitive salvage PDT was considered to be an effective and safe treatment option in residual T1 lesions after initial PDT for local failure of esophageal cancer treated with chemoradiotherapy.

Disclosure
All authors have declared no conflicts of interest.
PS02.040: EXPRESSION OF INTESTINAL/NON-INTESTINAL DIFFERENTIATION MARKERS IN ADENOCARCINOMAS OF THE ESOPHAGUS CORRELATES WITH ESOPHAGO-GASTRIC INTESTINAL METAPLASIA
Authors: Bonora Elena , Isidori Federica , Lugaresi Marialuisa , Sala Claudia , Malvi Deborah , Fittipaldi Silvia , Castellani Gastone , Räsänen Jari , D’Errico Antonietta , Fiocca Roberto , Mattioli Sandro 
Published: September 2018

Abstract

Background
Esophageal adenocarcinomas (EAC), grouped according to the presence (+ )/absence (-) of intestinal metaplasia in esophagus (BIM) and stomach (GIM) differ in terms of nodal metastatic patterns and survival. We studied the differentiation profile in BIM/GIM categories.

Methods
In 77 EAC surgical specimens we assessed CDX-2, CK7, CK20, MUC1, MUC2, MUC5A/C, MUC6 antibodies. The expression of such markers was correlated with: BIM + GIM- (Barrett-like), BIM-GIM- (cardiopyloric-like), BIM-GIM + (gastric-like).

Results
CDX2 (P = 0.0481), CK7 (P = 0.0150), MUC2 (P = 0.0395) were differently expressed (Kruskall-Wallis test) in BIM/GIM categories. Binary relations (Mann-Whitney test) showed that CDX2 was more expressed in BIM + /GIM- than in BIM-/GIM- (P = 0.0046) tumors; CK7 was more expressed in BIM-/GIM- than in BIM-/GIM + (P = 0.0020) and in BIM + /GIM- than in BIM-/GIM + (P = 0.0101); MUC2 was more expressed in BIM + /GIM- than in BIM-/GIM- (P = 0.0061). The other investigated markers were randomly distributed among BIM/GIM categories.

Conclusion
The greater expression of intestinal markers (CDX2-MUC2) in Barrett's intestinal metaplasia associated tumors (BIM + /GIM-) compared to those with no intestinal metaplasia (BIM-/GIM-) is consistent with their predominant intestinal differentiation. In contrast, CK7, although mostly expressed in tumors not associated with intestinal metaplasia (BIM-/GIM-) was less efficient in distinguishing them from those associated with Barrett's metaplasia (BIM + /GIM-) while showed the lowest level of expression in tumors associated with gastric intestinal metaplasia (BIM-/GIM + ). In conclusion, intestinal (CDX2-MUC2) and non-intestinal (CK7) differentiation markers appear to be expressed differently in BIM/GIM categories. Those findings support the opportunity to investigate further biology of these tumors in view of clinical-prognostic implications.

Disclosure
All authors have declared no conflicts of interest.
PS02.042: PROGNOSTIC ROLE OF HPV INFECTION IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Bognar Laura , Bellyei Szabolcs , Hegedus Ivett , Gombos Katalin , Horvath Ors , Vereczkei Andras , Pozsgai Eva , Papp Andras 
Published: September 2018

Abstract

Background
The aims of this study were to evaluate whether HPV infection has a prognostic role in patients with esophageal squamous cell carcinoma who underwent oncological treatment and also to correlate the heat shock proteins (Hsp) 90, 27 and 16.2 and growth hormone-releasing hormone receptor (GHRH-R) expression patterns of the pre-treatment tumor biopsies with the HPV status and with the oncological response.

Methods
Pre-treatment tumor biopsies of 74 patients with locally advanced esophageal squamous cell carcinoma were processed retrospectively. The presence of HPV was detected by chromogenic in situ hybridization. Hsp and GHRH-R expressions were determined using immunohistochemistry. Following neoadjuvant or definitive radiochemotherapy, the patients were restaged according to the Response Evaluation Criteria in Solid Tumors. The correlation between the HPV status, response and Hsp and GHRH-R expressions were evaluated.

Results
Fourteen (19%) patients were HPV-positive. HPV-positive patients were more likely to respond poorly to multimodal therapy (71.4% were non-responders vs. 28.6% responders) and had shorter overall survival compared to HPV-negative patients (median survival of 6 months vs. 7 months), although the difference was not significant (Log Rank P = 0.898). A significantly higher number of HPV-positive patients expressed Hsp 90 and 16.2 at high levels (85.7% and 71.4%, respectively) than at low levels. Higher levels of Hsp expressions resulted in poorer response to therapy and worse overall survival.

Conclusion
We found that HPV infection resulted in poor response to therapy and decreased overall survival, and therefore proved to be a negative prognostic factor in patients with esophageal squamous cell carcinoma. There was a linear correlation between levels of Hsp 90 and 16.2 expression and HPV positivity.

Disclosure
All authors have declared no conflicts of interest.
PS02.043: OVEREXPRESSION OF HSP27 AND HSP70 ARE ASSOCIATED WITH DECREASED SURVIVAL AMONG PATIENTS WITH ESOPHAGEAL ADENOCARCINOMA
Authors: Söderström Henna , Kauppi Juha , Räsänen Jari , Rantanen Tuomo 
Published: September 2018

Abstract

Background
Heat shock protein (HSP) 27 and 70 overexpression is associated with several malignancies but reports of their incidence and association with survival among patients with esophageal carcinoma (EC) are scarce. COX-2 expression is induced by inflammation, and it has been linked to a Barrett's esophagus and a wide variety of cancers. High COX-2 expression has been linked to poor survival in EC but results regarding association to clinicopathological factors are conflicting.

Methods
Immunohistochemical analysis for HSP27, HSP70 and COX-2 was performed on 97 cancer cases, 19 Barrett cases and 5 controls treated between 1990 - 2007. Data was gathered from patient records and survival data was acquired in December 2015.

Results
Higher tumor stage was significantly associated with poorer survival (P < 0001), which was independent of HSP27, HSP70 and COX-2 immunostaining. HSP27 was moderately or strongly positive in 61,8% of the cancer cases, which was significantly associated to poorer survival (25,6 and 19 months versus 65,1 in weakly positive samples) (P = 0,01). Similar results were seen for HSP70, for which 30,4% of the cases were stained moderately or strong positive, and survival was 15 and 17,3 months compared to 41,7 months in weakly stained cases. COX-2 was negative in 83,3% of the cancer cases, and none of the samples had strong COX-2 immunostaining. COX-2 did not correlate with survival.

Conclusion
Moderate or high HSP27 and HSP70 staining intensities were associated with poor survival among patients with esophageal adenocarcinoma, which is now reported for the first time. According to previous studies opposite conclusions for esophageal squamous cell carcinoma was found. COX-2 did not impact survival in our study even though it's been found to be a negative prognostic factor in several previous studies.

Disclosure
All authors have declared no conflicts of interest.
PS02.044: A BARRETT’S CELL CULTURE MODEL, SHOWING AN INCREASED ACID TOLERABILITY OF ESOPHAGEAL ADENOCARCINOMA CELLS
Authors: Thieme René , Storz Lucie , Rolfs Franziska , Eichfeld Uwe , Dietrich Arne , Hoffmeister Albrecht , Jansen-Winkeln Boris , Gockel Ines 
Published: September 2018

Abstract

Background
Inflammation is a common in esophageal adenocarcinoma (EAC). The response of EAC to common chemotherapeutic regimes is relatively low and the 5-years-survival is poor. The influence of acidic reflux on the viability of esophageal adenocarcinoma cells is unknown.

Methods
We investigated the influence of acidified medium conditions (pH3; pH3.5; pH4) in a Barrett's cell culture model, using six cell lines representing the Barrett's sequence from normal esophageal epithelium (EPC1 and EPC2), metaplasia (CP-A), dysplasia (CP-B) and EAC (OE33 and OE19) for their tolerability against an acid pulse of 15 and 30 min as well as expression profile of the Nrf2-Keap1-signalling pathway and their downstream targets.

Results
The Barrett's sequence was characterized by an increase of acid tolerability in the more advanced cells of this sequence. The squamous epithelium cell line EPC1 has shown the highest susceptibility with a decrease of 75% of cell viability, when treated with pH4 medium for 15min, while dysplastic and EAC cells had shown only a decrease of 10–25%. The lowest susceptibility was observed in the EAC cell line OE33, which had also 90% living cell in pH3 medium after 15min and had almost 30% living cells after 30min, when all other investigated cell lines showed no more living cells. Additionally, treatment with acidified medium was accompanied with an increase of the Nrf2 target gene hemeoxygensae-1.

Conclusion
We could show an increased tolerability against acidified medium (pH3) in cells representing advanced Barrett's esophagus stages, accompanied by an activation of Keap1-Nrf2-signalling pathway. However, acidic reflux may influence inflammation and chemo-sensitivity of the EAC.

Disclosure
All authors have declared no conflicts of interest.
PS02.045: EXPRESSION AND CLINICAL SIGNIFICANCE OF LEUCINE-RICH REPEAT-CONTAINING PROTEIN 8A (LRRC8A) IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Konishi Tomoki , Shiozaki Atsushi , Fujiwara Hitoshi , Konishi Hirotaka , Kudo Michihiro , Shoda Katsutoshi , Kosuga Toshiyuki , Arita Tomohiro , Morimura Ryo , Murayama Yasutoshi , Kuriu Yoshiaki , Ikoma Hisashi , Kubota Takeshi , Nakanishi Masayoshi , Okamoto Kazuma , Otsuji Eigo 
Published: September 2018

Abstract

Background
All cells have regulatory volume decrease (RVD) function to maintain cell volume. When the cell volume changes, the anion channels on the cell membrane are activated and keep constant cell volume due to water flow. Leucine-Rich Repeat-Containing protein 8 A (LRRC8A) was first reported in 2014 as the main constituent protein of this anion channel. In normal tissues, LRRC8A is thought to control cell volume regulation and is thought to be involved in cell cycle and death. However, its expression and significance in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we examined to investigate the clinicopathological significance of its expression in ESCC and the role of LRRC8A in tumor function.

Methods
An immunohistochemical analysis was performed on 64 patients with ESCC who underwent curative surgery in our department. We carried out knockdown using siRNA to evaluate the role of LRRC8A in ESCC cells.

Results
LRRC8A was expressed in the cell membrane and cytoplasm of cancer cells. We divided ESCC patients into 2 groups by referring to the staining scores; a high expression group with staining scores ≥ 1.0, n = 53, and a low expression group with staining scores < 1.0, n = 11. In correlation analysis with clinicopathologic factors, high LRRC8A expression tended to have a positive correlation with the presence or absence of lymph node metastasis (P = 0.059). In the survival analysis, the 5-year overall survival rate of patients with high LRRC8A expression (43.4%) was significantly lower than that of patients with low LRRC8A expression (90.0%) (P = 0.013). Cox proportional hazard analysis showed that high LRRC8A expression was an independent poor prognostic factor (P = 0.013, HR = 6.67). LRRC8A was strongly expressed in TE15 and KYSE170 human ESCC cells. The depletion of LRRC8A using siRNA inhibited cell proliferation, migration, invasion and induced apoptosis.

Conclusion
The LRRC8A expression is related to worse prognosis in ESCC patients and regulates tumor progression. Nest step, we will carry out further investigation to reveal how to regulate tumor function by microarray analysis.

Disclosure
All authors have declared no conflicts of interest.
PS02.046: UNRAVELING TUMOR HETEROGENEITY OF ESOPHAGEAL ADENOCARCINOMA (EAC) THROUGH HIGH-THROUGHPUT OF SORTED TUMOR CELL POPULATIONS
Authors: Bonora Elena , Isidori Federica , Bozzarelli Isotta , Lugaresi Marialuisa , Malvi Deborah , Söderström Henna , Bolognesi Chiara , Forcato Claudio , D’Errico Antonietta , Fiocca Roberto , Seri Marco , Krishnadath Kausilia , Mattioli Sandro 
Published: September 2018

Abstract

Background
In EAC clinical, histological, immune-histochemical and genetic patterns were documented, which support the existence of biologically different sub populations. We studied genetic intra/inter tumor heterogeneity of EAC with a new technology based on sorting of specific cell populations.

Methods
Formalin embedded material obtained from 16 EAC surgical specimens, classified according to the presence/absence of intestinal metaplasia in esophagus (BIM) and stomach (GIM) in BIM + GIM- (Barret's like), BIM-GIM- (cardio-pyloric like), BIM—GIM + (gastric like) types, was processed using a high-throughput cell sorting technology. Stromal and tumor cell populations were sorted based on antibodies against vimentin/pan-cytokeratin and on DNA content. Targeted resequencing on DNA extracted from the sorted cells was performed for 63 cancer-related genes (OncoSeek panel).

Results
In 11/16 (68.75%) of cases a mutation in TP53 was detected, and in 2 we observed CDKN2A (TP53 regulator) mutations. In Barret's like and Gastric like sub types only mutations of TP53 or TP53regulator genes were present. In pyloric like type TP53 and/or other different mutations of whom 2 in HNF1A were detected (Figure 1).

Conclusion
Selective sorting led to new patterns of EAC tumor mutational status and heterogeneity, among others somatic mutations in HNF1A not previously found. Parallel analysis of unsorted samples failed to detect these specific mutations. The cardio-pyloric like sub type contains mutational patterns different than those of Barret's and gastric like types. Further research on additional cases is necessary to confirm these findings.

Disclosure
All authors have declared no conflicts of interest.
PS02.048: DECREASED EXPRESSION OF PRSS27 IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Terayama Masayoshi , Hagiwara Teruki , Yamada Kazuhiko , Soma Daisuke , Nohara Kyoko , Yamashita Satoshi , Kokudo Norihiro , Dohi Taeko , Kawamura Yuki I 
Published: September 2018

Abstract

Background
Alcohol drinking and smoking are substantial risk factors of esophageal squamous cell carcinoma (ESCC) and are supposed to induce genetic mutations and epigenetic disorders, including aberrant DNA methylation. Previously, we have conducted transcriptome and methylome analyses of a paired specimen of ESCC and adjacent non-cancerous tissues and found that both gene expression and promotor methylation of PRSS27 were perturbed in ESCC. PRSS27 was a trypsin-like serine protease (also known as marapsin) and expressed in normal esophagus; however, little is known about the significance of PRSS27 expression in ESCC. In this study, we evaluated the expression of PRSS27 in many ESCC cases in relation with clinical features and the prognosis.

Methods
ESCC tissue specimens were obtained from 80 patients who had undergone esophagectomy between April 2008 and December 2016 in our hospital and were subjected to immunostaining for PRSS27. ESCC cases were classified into PRSS27-negative and PRSS27-positive groups and difference of clinical features and the prognosis between the groups was analyzed.

Results
The mRNA expression of PRSS27 was significantly decreased in ESCC compared with those in matched normal mucosa (P < 0.0001). Histologically, PRSS27 was highly expressed in spinous cells of suprabasal cell layer but not in basal cell layer of normal esophageal mucosa. In contrast, 37 of 80 (47%) ESCC exhibited decreased intensity of PRSS27 staining when compared with that in normal mucosa, and 53% (43/80) of ESCC showed almost no staining of PRSS27. Although the prognosis of PRSS27-positive cases were worse in trend than that of PRSS27-negative cases, there was no significant difference (P = 0.0763)

Conclusion
PRSS27 gene and protein expression was both downregulated in ESCC; its functional significance in relation to malignancy is underinvestigation.

Disclosure
All authors have declared no conflicts of interest.
PS02.049: HIGH GPX1 EXPRESSION PROMOTES ESOPHAGEAL SQUAMOUS CELL CARCINOMA INVASION, MIGRATION, PROLIFERATION AND CISPLATIN-RESISTANCE BUT CAN BE REDUCED BY VITAMIN D
Authors: Gan Xiangfeng , Chen Ju , Chen Baishen 
Published: September 2018

Abstract

Background
Esophageal cancer is one of the most common cancers worldwide. Despite recent progress in the devel- opment of novel therapies, esophageal carcinoma remains an aggressive cancer associated with a poor prognosis. The glutathione peroxidase 1 (GPX1) gene located on chromosome 3p21.3 is associated with the cancer of several organs. According to available information, GPX1, a gene downstream of NF-κB, is considered to exert adverse ef- fects on tumour progression and enhance malignancy in some cancers but has not been reported in esophageal cancer. It is also reported that vitamin D (Vit. D), a widely used drug in the clinical setting, could suppress GPX1 expression through the NF-κB pathway. Thus, it is speculated that Vit. D could reduce malignancy in esophageal cancer by altering the NF-κB pathway.

Methods
Selection GPX1 high expression EC109 and EC9706 cell line K150, and K180 low expression cell lines transfected with siRNA and vector. Using RT-PCR to detect cell transfection efficiency GPX1’s, Western blot detect the expression of uPA, MMP-2, NF-κB, and CCK-8 assay inhibition or overexpression on GPX1 on ESCC cell cisplatin resistance and proliferation. Transwell assay inhibition or over-expression of GPX1 on invasive ability of ESCC cells.

Results
By CCK-8 and transwell law found within the cells expressing low GPX1 ESCC can inhibit cell proliferation, cisplatin resistance, invasion and migration, high GPX1 when the opposite phenomenon can be observed. Western blot GPX1 down when found, PTEN, Bax activity rises, PDK-1, AKT, Bcl-2, uPA, MMP-2 expression decreased, vimentin, E-cadherin, ß-catenin, snail is no significant change. After Vit.D treatment, CCK-8 assay showed that cell proliferation and drug resistance was significantly inhibited; Transwell showed cell invasion and migration also decreased. Cells was detected by Western blot after transfection, cells, PTEN, Bax increased activity, p65, PDK-1, AKT, Bcl-2, uPA, MMP-2 expression decreased, vimentin, E-cadherin, ß-catenin, snail is no significant change.

Conclusion
Treatment with vitamin D can downregulate GPX1, thus decreasing tumour cell capacity for invasion, migration, proliferation and cisplatin resistance via the NF-κB pathway. Vitamin D, already commonly used in clinical therapy, could play a greater role in the treatment of esophageal cancer patients.

Disclosure
All authors have declared no conflicts of interest.
PS02.050: TUMOR LOCATION IS AN INDEPENDENT PROGNOSTIC FACTOR OF ESOPHAGEAL ADENOCARCINOMA BASED ON THE EIGHTH EDITION OF TNM STAGING SYSTEM IN CHINESE PATIENTS
Authors: Lin Yidan , Deng Hanyu 
Published: September 2018

Abstract

Background
Whether tumor location has any impact on the survival of esophageal adenocarcinoma patients remains controversial. In this study, we tried to investigate the prognostic value of tumor location for esophageal adenocarcinoma based on the eight edition of TNM staging system, which modified the description for positioning the esophagogastric junction (EGJ)tumor, in Chinese patients for the first time.

Methods
A retrospective analysis of patients who underwent esophagectomy for esophageal adenocarcinoma was conducted. Data for analysis included demographic data, comorbidity, pathologic findings, surgical approach, adjuvant therapy, and survival time. Tumor location was simply categorized into two groups (adenocarcinomas at EGJ and adenocarcinomas at other sites of esophagus). Both univariate and multivariate analyses were applied. Propensity-score matched (PSM) analysis was also conducted to eliminate the bias effects of confounding factors during comparison.

Results
A total of 107 patients from January 2009 to December 2015 was included for analysis. After a median follow-up time of 60.0 months, the median survival time of those patients was 41.0 months. In the univariate analysis, adenocarcinomas in the EGJ (P = 0.047), early pT stages (P = 0.030), and moderate/well differentiation (P = 0.022) were significantly correlated with better survival. In the multivariate analysis, tumor site [hazard ratio (HR) = 0.545; 95% confidence interval (CI) = 0.302–0.985], pT stage (HR = 0.295; 95% CI = 0.123–0.708), and tumor differentiation (HR = 0.458; 95% CI = 0.244–0.861) were significant independent prognostic factors for overall survival of those esophageal adenocarcinoma patients. After adjusted by PSM, adenocarcinoma at the EGJ still yielded significantly longer survival than those at other sites of esophagus (P = 0.026).

Conclusion
Tumor location was an independent prognostic factor for esophageal adenocarcinoma based on the eighth edition of TNM staging system in Chinese patients, which indicates that different surgical therapeutic modalities should be applied for esophageal adenocarcinoma with different tumor locations.

Disclosure
All authors have declared no conflicts of interest.