bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proposal of new staging models for gastric cardia cancer after preoperative radiation incorporating tumor grade and LODDS.
Authors: Zhou Rui , Zeng Dongqiang , Zhang Jingwen , Sun Huiying , Liao Wangjun 
Published: September 2018

e15557 Background: Preoperative radiotherapy (Pre-RT) tends to be more frequently used for advanced gastric cardia cancer (GCC) patients. However, the prognostic values of postoperative pathologic characteristics in these patients remain unclear. This study aimed to examine the outcomes in GCC patients receiving Pre-RT to identify the predictive factors for cancer-specific survival (CSS) and overall survival (OS). Methods: A total of 1818 GCC patients undergoing Pre-RT, recorded in the Surveillance Epidemiology and End Results database from 1998-2013, were reviewed. Results: Univariate analyses showed that grade, histology type, positive lymph node (PLN), lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) classifications significantly correlated with CSS and OS. However, through the four-step multivariate analyses, only grade and LODDS were demonstrated as the final independent risk factors for survival. Next, by combining grade with lymph node status variables, we established three novel staging models namely the grade-PLN (G-P), grade-LNR (G-R), and grade-LODDS (G-L) stages. Similarly, subsequent four-step multivariate analyses also revealed that only G-L predicted CSS and OS independently. Moreover, the new G-L staging system also validated to have better discriminatory ability, monotonicity, and homogeneity for prognostic stratification, as well as a more-accurate 3-year CSS (P = 0.023) and OS (P = 0.015) prediction than AJCC staging system. Conclusions: The G-L staging system was superior in determining the prognosis of GCC patients after Pre-RT. Further large-scale prospective cohort analyses are warranted.
Combining prognostic value of nodal ratio and neutrophil to lymphocyte ratio in completely resected gastric cancer with D2 lymph node dissection.
Authors: Guevara Andres , Enriquez Daniel , Rioja Patricia Elizabeth , Pacheco Christian , Castro Victor , Montenegro Paola Catherine , Payet Eduardo 
Published: September 2018

e15565 Background: Outcomes in gastric cancer (GC) are still dismal even with complete D2 resection surgery and chemotherapy (CT), therefore identification of prognostic factors is critical to stratify patients at risk of recurrence or death. Nodal ratio (NR) has been recognized as a valuable prognostic factor and neutrophil to lymphocyte ratio (NLR) as systemic inflammation biomarker in some neoplasms. We evaluate overall survival (OS) combining NR and NLR among completely resected GC patients with D2 lymph node dissection in a Peruvian population. Methods: We reviewed retrospectively 791 medical records from GC pts with complete radical D2 resection between 2008 and 2012 at Instituto Nacional de Enfermedades Neoplasicas. We grouped according NR in < 0.2(Low), 0.2-0.5(Intermediate) and > 0.5(High), and NLR with cut-off < 3 and ≥3. We evaluated overall survival combining NR and NLR, also univariate and multivariate cox analysis were performed. OS was based on national registry and cannot evaluate DFS as long most patients return to their primary hospitals to follow-up. Results: Mean age was 60y [rank: 19-89]. Most frequent characteristics were distal localization (52.4%), intestinal subtype (52.6%) and poor differentiated histology (53%). From 791 patients, 156, 194 and 441 were diagnosed at I, II and III CS, respectively. Most patients had nodal involvement (66.8%), 21% and 28.4% received RT and CT, respectively. NLR < 3 was associated to early disease (p < 0.05). In nodal ratio groups, 68.9% had low, 23% intermediate and 8.1% high ratio, no differences were observed with NLR. At 5years median follow up, patients with NLR < 3 and low nodal ratio had better 5-year OS in this nodal group (71% vs 58% on NLR≥3; HR:0.75, 95%CI:0.49-0.94, p = 0.016]), and patients with intermediate and high nodal ratio had worse outcomes (25 and 15% 5year OS, respectively) without differences with NLR. Multivariate analysis showed higher nodal ratio had negative impact on OS. Conclusions: Neutrophil to lymphocyte ratio < 3 was associated to better OS in patients with low nodal ratio ( < 0.2), indeed this approach could be usefull to identify high risks patients with early disease in further studies.
Prognostic role of tumor-inflating lymphocytes in gastric cancer: A systematic review and meta-analysis.
Authors: Sun Der Sheng , Lee Jung Soo , Hong Soon Auck , Won Hye Sung , Ko Yoon Ho 
Published: September 2018

e15578 Background: Tumor-infiltrating lymphocytes(TILs) may act as major determinants of the host immune response to tumor cells. However, the potential prognostic value of TILs in gastric cancer remains controversial. This meta-analysis analyzed the associations between TILs and survival outcomes in gastric cancer. Methods: Eligible 24 published studies were identified by searching the PubMed and Google scholar databases. The primary clinical outcome was defined as overall survival (OS) or disease-free survival (DFS), which were analyzed by subgroups such as TILs subtype. The total of the study sample sizes in eligible 24 published studies was 3,229, which ranged from 52 to 273 (median, 120) patients. All studies were non-randomized and retrospective study. The only multivariate hazard ratio(HR) among patient survival data were pooled, and pooled multivariate HR with 95% confidence intervals (95% CI) were used to calculate the strength of this association between TILs expression and survival outcome. Results: The pooled multivariate hazard ratios suggested that high expression of TILs was associated with better overall survival outcome (pooled HR = 0.69, 95% CI 0.57–0.82), compared to low TILs expression in twenty-three eligible studies, particularly in CD8(+) lymphocytes (pooled HR = 0.63, 95% CI 0.48 –0.83). In contrast, a pooled analysis of the FOXP3 (+) T cells or Treg subgroup showed that high FOXP3 (+) expression was negatively correlated with OS (pooled HR = 1.88, 95% CI 1.34 –2.63). In an analysis of seven studies on DFS, the infiltration by TILs, CD4(+) or CD8(+) lymphocytes (pooled HR = 0.59, 95% CI 0.42 –0.81), not by the infiltration of FOXP3 (+) T lymphocytes (pooled HR = 1.82, 95% CI 1.30 – 2.53), was significantly associated with better survival outcome. Conclusions: The results from this meta-analysis suggest that TILs and TILs subsets expression can be a potential prognostic biomarker in patients with gastric cancer. Key Words: Tumor-infiltrating lymphocytes, gastric cancer, prognosis, meta-analysis
High Prevalence of Claudin 18.2 Expression in Japanese Patients with Gastric Cancer.
Authors: Tureci Özlem , Itoh Kyogo , Yamaguchi Rin , Mukhina Svetlana , Sahin Ugur , Rohde Christoph 
Published: September 2018

e15584 Background: Expression of the gastric mucosal tight junction protein, Claudin-18.2 (CLDN18.2), is altered in gastric cancer (GC). In a phase 2 clinical trial (NCT01630083; FAST), a monoclonal antibody against CLDN18.2 (IMAB362) significantly increased overall survival in European patients with CLDN18.2-positive (CLDN18.2+) gastric and gastroesophageal junction adenocarcinomas when added to an EOX chemotherapy regimen. As the GC occurrence is high in Japan, this study evaluated the prevalence of CLDN18.2 expression in Japanese patients with GC. Methods: CLDN18.2 expression was assessed in primary GC tumors and corresponding lymph node metastases (LNM) by cell membrane staining intensity using a validated, semi-quantitative, immunohistochemical assay for CLDN18.2 expression. Samples showing any positivity for specific staining with at least 1+ intensity were defined as CLDN18.2+. Correlation between percentage of CLDN18.2+cells in primary tumors and corresponding LNM was determined with Spearman’s rank correlation. Results: A total of 263 samples, including tissues from 134 primary GC tumor/LNM matched pairs, 128 primary GC tumors only, and 1 LNM only were collected at Kurume University Medical Center, Japan, between 2000 and 2012. Overall, CLDN18.2 was detected in 87% (n = 228/262) of all primary tumors and 80% (n = 108/135) of LNM. Strong CLDN18.2 expression (≥2+ membrane staining intensity in ≥40% of tumor cells; eligibility criterion in FAST) was observed in 52% (n = 135/262) of primary tumors and 45% (n = 61/135) of LNM. Individual tumor samples consisted of a mixture of tumor cells expressing CLDN18.2 at different staining intensities; samples with a high fraction of CLDN18.2 reactivity had a large proportion of tumor cells staining with 3+ intensity (Spearman r = .8413, P< .0001). In matched pairs, 72% of samples were CLDN18.2+ (n = 96/134) and 9% were CLDN18.2– (n = 12/134). The fraction of CLDN18.2+ tumor cells at any staining intensity strongly correlated in matched paired samples (Spearman r = .6942; P< .0001). Conclusions: CLDN18.2 expression is highly prevalent in Japanese GC patients, making it a targetable alteration and supporting development of IMAB362 as a therapeutic agent for this patient population.
Identification and functional characterization of long noncoding RNA NMR as biomarker for metastasis and prognosis in esophageal squamous cell carcinoma.
Authors: Li Yuan , Li Jiagen , Sun Nan , Luo Mei , Zhou Chengcheng , Shi Xuejiao , Yang Wenhui , Lu Zhiliang , Chen Zhaoli , He Jie 
Published: September 2018

e15587 Background: Long noncoding RNAs (lncRNA) have been implicated in cancer but most of them remain largely unstudied. Methods: In this study, we identified a NSUN2 methylated lncRNA (NMR), which is significantly upregulated in esophageal squamous cell carcinoma (ESCC), functions as a key regulator of ESCC tumor metastasis and drug resistance. Results: In microarray data of 119 paired ESCC and normal tissues, NMR was significantly overexpressed in ESCC (P < 0.001), and overexpression of NMR indicated poor overall survival of ESCC patients (P = 0.003); in RNA sequencing data of 20 cancer types from TCGA, including 426 head and neck squamous cell carcinoma (HNSC) patients, NMR was significantly upregulated in HNSC tissues (P < 0.01), and patients with higher T stage, N stage, and m stage had significantly higher NMR expression (P < 0.05). Dysregulation of NMR was also validated in an independent cohort with 83 ESCC patients. Consistently, NMR was significantly overexpressed in ESCC (P < 0.001), and high NMR expression was significantly associated with lymph node metastasis and poor overall survival (P < 0.05). Functional experiments demonstrated that NMR could promote tumor cell migration and invasion, inhibit cisplatin-induced apoptosis and increase drug resistance in ESCC cells. Mechanistically, transcription of NMR could be upregulated by NF-κB activation after IL-1β and TNF-α treatment. RNA sequencing after interference highlighted alterations in collagen metabolic process and ERK1 and ERK2 cascade. Further validation proved that NMR could promote the expression of MMP3 and MMP10, at least partially by ERK1/2 pathway. Conclusions: Taken together, these findings suggest that NMR functions as an oncogenic gene in ESCC and may serve as novel biomarker and therapeutic target in ESCC.
HER2 amplification and gene signal distribution in gastroesophageal cancer.
Authors: Jørgensen Jan Trøst , Nielsen Karsten Bork , Kjærsgaard Gitte , Jepsen Anna , Mollerup Jens 
Published: September 2018

e15600 Background: HER2 serves as an important therapeutic target in gastroesophageal cancer. Differences in HER2 gene signal distribution patterns can be observed at the tissue level, but how it influences the HER2 amplification status has not been studied so far. Here, we investigated the link between HER2 amplification and the different types of gene signal distribution. Methods: Tumor samples from 140 patients with gastroesophageal adenocarcinoma where analyzed using the HER2 IQFISH pharmDx™ assay. Specimens covered non-amplified and amplified cases with a preselected high proportion of HER2 amplified cases. Based on the HER2/CEN-17 ratio, specimens were categorized into amplified or non-amplified. The signal distribution patterns were divided into homogeneous, heterogeneous focal or heterogeneous mosaic. The study was conducted based on anonymized specimens with limited access to clinicopathological data. Results: Among the 140 analyzed specimens 83 had a heterogeneous HER2 signal distribution, with 62 being focal and 21 of the mosaic type. The remaining 57 specimens had a homogeneous signal distribution. HER2 amplification was observed in 63 of the 140 specimens, and nearly all (93.7%) were found among specimens with a heterogeneous focal signal distribution (p < 0.0001). The mean HER2/CEN-17 ratio for the focal heterogeneous group was 8.75 (CI95%: 6.87 – 10.63), compared to 1.53 (CI95%: 1.45 – 1.61) and 1.70 (CI95%: 1.22 – 2.18) for the heterogeneous mosaic and homogeneous groups, respectively, (p < 0.0001). Conclusions: A clear relationship between HER2 amplification and the focal heterogeneous signal distribution was demonstrated in tumor specimens from patients with gastroesophageal cancer. Furthermore, we raise the hypothesis that the signal distribution patterns observed with FISH might be related to different subpopulations of HER2 positive tumor cells.
Prognostic models in advanced gastric cancer in first and second line chemotherapy treatment in Spanish population.
Authors: Hernando-Cubero Jorge , Alvarez-Garcia Natalia , Pazo Cid Roberto A. , Martinez Trufero Javier , Alvarez Maria , Lao Romera Juan , Millastre Esther , Bernad Isabel Pajares , Madani Julia , Gimeno Joaquin , Nuno-Alves Ana , Polo Marques Eduardo , Alonso Vicente , Anton Antonio 
Published: September 2018

e15603 Background: No globally accepted prognostic score has been developed in advanced gastric cancer (AGC). The purpose of this study is to explore baseline host or tumor related prognostic factors in spanish AGC patients in first and second line chemotherapy treatment. In addition we compare our scores with previously published scores in asian and european population. Methods: A total of 166 patients with AGC treated in our institution between 2012 and 2016 were screened. 119 received first line chemotherapy (CT) and 47 of them also received second line CT and were included in the analysis. Prognostic factors were evaluated using the Cox proportional hazard model. We use as comparators four first line and three second line scores published in literature. Results: The overal survival (OS) in first line and second line patients were 9 and 5 months. To construct first line CT score we selected four risk factors: ECOG≥2, Her2 negative, Irinotecan based CT and albumin < 3,6mg/dl. OS were 23 months in low risk group, who had zero or one risk points, 15 months for patients in the moderate risk group, who had two or three risk points, and 5 months for patients in the high risk group, who had all four risk points. In the second line CT score we included four risk factors: ECOG ≥2, albumin < 3.6mg/dl, Hb < 11.5mg/dl and CA19.9 reduction less than 30% after 2 CT cycles. OS were 30 months in low risk group, who had zero or one risk points, 16 months for patients in the moderate risk group, who had two or three risk points, and 3 months for patients in the high risk group, who had all four risk points. Conclusions: In the present study, we propose two new prognostic scores for patients with AGC developed in the same cohort and including HER2 status. This prognostic model could help clinicians choose and applicable treatment based on the stimated prognosis. [Table: see text]
Is more surgery better for patients with gallbladder cancer? A survival analysis of extended versus simple cholecystectomy.
Authors: Fountzilas Christos , Mazo- Canola Marcela , Hernandez Brian , Janania Martinez Michelle , Hamal Ruchi , Datta Paromita , Mahalingam Devalingam , Michalek Joel , Arora Sukeshi Patel 
Published: September 2018

e15615 Background: Gallbladder cancer (GBC) is a rare cancer; the minority of patients have resectable tumor at diagnosis. Based on retrospective, single-institution data, extended cholecystectomy (EXT) has been recommended over simple cholecystectomy (CHOL) in >T1 tumors; however, effect of EXT on survival is unclear. Thus, we evaluated the survival of patients with resectable GBC at our institution. Methods: Retrospective analysis from 1/1/2005 to 1/1/2016 for patients with GBC. Patients with advanced or metastatic disease were excluded. The Recurrence-free survival (RFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Results: 68 patients with GBC; 26 (38%) with early disease. Twelve patients had EXT. Patient/tumor characteristics are shown in Table. Median RFS was 22 months (95% CI: 9-not reached) and OS was 25 months (95% CI: 15-not reached) for the entire cohort. Median RFS was increased in CHOL (30 months) relative to EXT (9 months); p=0.73. OS appeared similar between the two groups (25 vs. 23 months for CHOL and EXT group, respectively). Conclusions: EXT appears to improve RFS with no effect on OS in patients with early GBC. Due to the limitations of small sample size and retrospective analysis, multi-institutional collaborations are necessary to better identify optimal management. [Table: see text]
A retrospective analysis of gemcitabine and nab-paclitaxel for the treatment of metastatic cholangiocarcinoma.
Authors: Mittra Arjun , Soyano Aixa Elena , Kung Shu Ting , Borad Mitesh J. , Alberts Steven R. , Mody Kabir 
Published: September 2018

e15616 Background: Cholangiocarcinoma (CCA) is a progressively fatal disease with an annual incidence of 1-2 cases per 100,000 people in the USA. Complete surgical resection is the only curative option for CCA. However, the majority of patients (pts) have advanced disease at diagnosis, and those undergoing resection often develop local or distant recurrence. Gemcitabine and Cisplatin remains the only standard chemotherapeutic regimen for advanced CCA. Alternative and improved therapies are critically needed. Gemcitabine/nab-Paclitaxel (GA) is a regimen that has become standard therapy in advanced pancreatic cancer (PDAC). Given the morphologic and histologic similarities between PDAC and CCA, this regimen has been used in advanced CCA, but no data exists regarding its efficacy in this disease. The goal of our study is to evaluate the Mayo Clinic experience with GA for the treatment of metastatic CCA. Methods: We retrospectively analyzed records from adult pts at Mayo Clinic with metastatic cholangiocarcinoma who received at least 2 cycles of GA. Our aims were to assess the progression-free survival (PFS), overall survival (OS) and disease response. Results: We analyzed 9 pts, 3 male and 6 female. The median age at diagnosis was 50 years (range 41-64). Six pts had metastatic disease at diagnosis while 3 underwent surgery with subsequent distant disease recurrence. Pts received a median of 2 lines (range 0-5) of systemic therapy prior to receiving GA, and a median of 2 cycles (range 2-15) of GA. At the time of our analysis, 4 of the 9 pts (44%) had died. The median OS from initiation of GA was 7.3 months (95% CI 1.7- 12.9) and median PFS from initiation of GA was 4.7 months (95% CI 0.48-8.9). The best overall responses using RECIST criteria were: partial response in 1 (11%), stable disease in 5 (55%) and disease progression in 3 (33%) pts. One pt remained on therapy 14.9 months after initiating GA. Conclusions: In our study, the combination of gemcitabine and nab-paclitaxel has demonstrated similar OS and PFS as other systemic therapies. To the best of our knowledge, this is the first report of this regimen in CCA. Ongoing, prospective trials are currently evaluating this regimen in advanced CCA.
Outcomes after taranscatheter arterial chemoembolization plus radiotherapy compared with chemoembolization lone for unresectable hepatocellular carcinoma.
Authors: Bao Yong Xing , Xiao Lei , Zhao Huijie , Wu Ge , Baishan Gulizila , Mao Rui , Zhang Hua 
Published: September 2018

e15617 Background: Hepatocellular carcinoma (HCC) is the third leading cause of death globally, and it is the sixth most common malignant tumor. Recent epidemiological data showed that HCC is the most common cancer with the highest mortality in men under age 60 years in China. For HCC, inoperable and intermediate to advanced cases account for approximately 70% to 80% of all HCC cases in china. Base the BCLC guideline, transarterial chemoemolization (TACE) was the first choice for these patients, and 3-years survival approximately 30%. Therefore, treatments other than TACE are urgently needed. Methods: In order to evaluate the efficacy and safety of TACE combined with Radiotherapy (RT) or TACE monotherapy in the treatment of HCC, patients with unresectable and intermediate HCC who received the treatment of TACE puls RT (25 cases) or TACE monotherapy (50 cases) in our single center during Jan.2012 to June. 2013 were retrospectively analyzed. Results: The results showed that for the TACE combined with RT group (25 cases), the median survival time was 13 months, and the TACE group (50 cases) was 7 month respectively, Kaplan Meier survival curve and the log-rank test shows TACE combined RT group compared with TACE group with overall survival time difference is statistically significant (chi-square = 28.72, P<0.05). Conclusions: TACE combined with RT is superior to TACE with respect to the overall survival for unresectable HCC patients.
The psychosomatic state of patients with differences in the prevalence of cancer process in biliopancreatic duodenal zone and in the volume of a surgical intervention.
Authors: Zhukova Galina Vitalyevna , Kit Oleg Ivanovich , Gaziev Umar Muhmadovich , Shirnina Elena Alekseevna , Shikhlyarova Alla Ivanovna , Snezhko Alexander V. , Torpudzhyan Izabella , Mezentsev Stanislav Stanislavovich 
Published: September 2018

e15619 Background: Associations between the psychosomatic state of cancer patients and the disease course, treatment and complications are poorly studied. Our purpose was to study adaptation and mental statuses of patients with biliopancreatoduodenal cancer (BPDC) at different disease stages with various volumes of surgical intervention. Methods: Parameters of the psychosomatic state of 32 patients with BPDC were studied before treatment, 1 day after surgery and at the dismissal from hospital. Adaptation statuses were assessed by a character and intensity of the general nonspecific adaptation reactions (AR) with scoring by the Antistress program. Mental statuses were evaluated by the levels of personal (PA) and situational anxiety (SA) by the Spielberger-Khanin method. Patients with pancreatoduodenectomy (PDE, 19 patients) and those with palliative intervention for a bypass anastomosis (BA, 13 patients) were compared. Patients with stage II disease prevailed in the PDE group and stage III-IV – in the BA group. Results: Patients with PDE had a higher adaptation status than patients with BA (p < 0.05). It resulted in lower rates of most adverse AR prior to the surgery (21% vs. 61%, respectively) and a higher AR score 1 day after the surgery (187±39 and 80±24, respectively). The AR score of 18 and lower 1 day after PDE was associated with postoperative complications. A tendency to a higher number of patients with a high PA was found in the PDE group compared to the BA group (58 and 31%, respectively) which could affect the time of pathology detection in patients of different groups. Patients of the two groups showed differences in the SA dynamics determined by the volume of surgical intervention. Conclusions: The association between the psychosomatic state of BPDC patients and the disease stage and volume of surgical intervention was demonstrated. The AR scoring 1 day after the surgery allows prognosis of postoperative complications.