bluuebunny/crossref_metadata_2025 huggingface dataset:
Diffusion-weighted magnetic resonance imaging for predicting pathologic response to neoadjuvant chemoradiotherapy in esophageal squamous cell cancer.
Authors: Hao Daxuan , Yang Yuanyuan , Li Xue , Wu Xiaoyuan , Chen Yongshun , Wang Jianhua
Published: September 2018

e15510

Background: Neoadjuvant chemoradiotherapy(nCRT) followed by surgery has became the standard treatment for patients with locally advanced esophageal cancer. However, cumulating data showed that only patients who had a pathologic response to neoadjuvant treatment could benefit from the nCRT and surgery. Moreover, for patients with no pathologic response, nCRT even worsen the survival compared with surgery alone. Therefore, accurately differentiating the two groups was contributed to personalize treatment for esophageal cancer. Our study aimed to explore the potential value of diffusion-weighted magnetic resonance imaging (DWI-MRI) for the prediction of pathologic response to nCRT in esophageal squamous cell carcinoma. Methods: Nineteen patients underwent DWI-MRI within one week before and after nCRT. Tumor regression score (TRG) was assessed by two experienced pathologists after esophagetcomy. The average tumor apparent diffusion coefficient (ADC) of tumor was calculated before and after neoadjuvant treatment. The predictive potential of pre-nCRT ADC (ADCpre), post-nCRT ADC (ADCpost) and ADC change (ΔADC) for pathologic responders (TRG≥3) and good responders (pCR and near-pCR, TRG1-2) was assessed. Results: Among these patients, 12 patients showed a positive response, and 8 patients showed a good response to nCRT. The ADCpre values in responders were significantly higher than these in no-responders (2.31±0.53×10-3mm2/s vs. 1.72±0.40 mm2/s, P= 0.021). According to ROC analysis for ADCpre, an optimal cut-off value of 1.77×10-3mm2/s predicted the responders with a sensitivity of 83.33 %, specificity of 71.43 %, PPV of 83.33 %, NPV of 71.43 %. The ADCpost values in good responders were significantly higher than these in poor responders (3.44±0.62×10-3 mm2/s vs. 2.73±0.31 mm2/s, P= 0.004). The ADCpost was predictive of the good responders at a threshold of 3.21×10-3mm2/s (sensitivity of 87.50 %, specificity of 100.00 %, PPV of 100.00 %, NPV of 91.67 % ). Conclusions: ADC value can be used as a promising biomarker to predict pathologic response of esophageal squamous cell carcinoma to neoadjuvant chemoradiotherapy.
How to reduce splenic injury in laparoscopic radical gastrectomy: Criminal ligament priority separating.
Authors: Wang Wei , Xiong Wenjun , Wan Jin
Published: September 2018

e15528

Background: Iatrogenic splenic injury may lead to conversion or nontherapeutic splenectomy in laparoscopic gastrectomy. A critical point at splenic injury occurs is improper traction of spleen-omentum ligament which was called crimimal ligament (CL). We aimed to explore the efficacy of cirminal ligament priority separating (CLPS) to reduce iatrogenic splenic injury in laparoscopic radical gastrectomy. Methods: Complete videos of 540 laparoscopic radical gastrectomy in Guangdong Provincial Hospital of Chinese Medicine were reviewed. The relationship between CLPS and iatrogenic splenic injury was determined. CL was defined as the ligament between omentum and spleen. CLPS was defined as that CL was firstly separated when mobilization was in left upper quadrant. Results: CL was present in 81.5% (440/540) and were included for analysis. There was variation in the distribution pattern of CL and it mostly appeared in the lower pole of spleen (414/440). CLPS was performed in 24.5% (108/440) and 75.5% (332/440) were not (un-CLPS). In systematic review, the incidence of iatrogenic splenic injury was 10.9% (48/440). Among these patients, 79.1% (38/48) were due to improper traction of CL and they were all in un-CLPS group. Instrument injury was occurred in 2.2% (10/440) and 3 were in CLPS group and 7 were in un-CLPS group. Most iatrogenic splenic injury were successfully handled with electrocoagulation, adhesive and compression technique, except 2 patients underwent conversion to open splenectomy for serious splenic injury in un-CLPS group. Conclusions: In laparoscopic surgery for gastric cancer, iatrogenic splenic injury mostly resulted from improper traction of CL and CLPS could reduce the incidence of iatrogenic splenic injury.
Significance of Prognostic Nutritional Index in post-surgical outcomes after surgical management in gastric cancer patients.
Authors: Herrera Marytere , Sobrevilla-Moreno Nora , LYRA-GONZALEZ IVAN , Calderillo German , Diaz Consuelo , Ruiz Garcia Erika
Published: September 2018

e15535

Background: Preoperative nutritional status in gastric cancer patients is not only correlated with postoperative complications, also, prognostic nutritional index or Onodera´s nutritional index (PNI) may relate with overall survival (OS) after gastrectomy. There is no available data of preoperative nutritional status in Mexican population. We decide to explore these variables and analyze its impact in outcomes reported in our population. Methods: This is a retrospective included a total of 91 patients patients with locally advanced gastric cancer confirmed by laparoscopy treated in the National Cancer Institute in México between January 2010 and June 2016. The PNI level was determined according the following formula: 10 x serum albumin (g/dl) + 0.005 x total lymphocyte count (per mm3). The optimal cutoff value of PNI in our population was set at 38.7 according the median, we stratified patients in high (PNI > 38.7) or low (PNI < 38.7) nutritional status, clinicopathologic features were compared. Results: We analyzed 91 patients, the mean patients age was 58, 61.5% were man, the 51.6% went to total gastrectomy with D2 dissection, 56% were pathologic stage III and 61.5% of the patients received adjuvant chemotherapy. The patients with high nutritional status had a OS of 46 months vs patients with low nutritional status with 25 months (p = 0.009). Patients with body mass index (BMI) > 23 had a OS of 41 months vs patients with BMI < 23 with 19 months of OS (p = 0.001), finally the patients with albumin > 3.75 had a 39 months of OS vs 23 months with albumin < 3.75 (p = 0.011) Conclusions: The low PNI group had worse OS than the high PNI group (46 months vs 25 months, p = 0.009). Preoperative is a simple and useful marker to predict overall survival in patients with locally advanced gastric cancer
Presence of bone metastases(BM) at diagnosis is associated with poor prognosis and coagulation disorders (CD) in patients (pts) with advanced gastric cancer (AGC).
Authors: Toppo Laura , Liguigli Wanda , Senti Chiara , Tomasello Gianluca , Ghidini Michele , Ratti Margherita , Botticelli Andrea , Onesti Concetta Elisa , DI Pietro Francesca , Pizzo Claudio , Panni Stefano , Curti Alessandra , Passalacqua Rodolfo
Published: September 2018

e15538

Background: The presence of BM in AGC is a relatively uncommon finding and has a poor prognosis [Leporini C. 2015]. At diagnosis the presence of BM occurs in approximately 10-15% of pts with AGC.[Park 2011; Silvestris 2013]. Aim of this study is to describe the main features of pts with AGC and BM at diagnosis and the prognostic implications. Methods: A consecutive series of AGC followed at Cremona Oncology Division from November 2004 to Dicember 2016 and included in three consecutive prospective trials [Dalla Chiesa M. 2011; Tomasello G. 2013], were analyzed. All pts were treated with a modified DCF (docetaxel, cisplatin, fluorouracil) given as a dose-dense regimen, every 14 days. We analyzed pts with BM at diagnosis (BMaD) and pts without BMaD. We evaluated baseline clinical and pathological parameters, the presence of coagulation disorders (CD) together with efficacy measures in the two groups. Results:218 pts with AGC were identified (38 with BMaD and 180 without BMaD).Main pts characteristics and results are reported in the Table below. Conclusions: The presence of BM at diagnosis in pts with AGC is not a rare event (21%) and identifies a population with a significantly poorer outcome and a higher incidence of CD, that need a clinical monitoring of coagulation parameters. More efforts are required to understand the reasons of the different prognosis and to find specific treatments to improve the survival. [Table: see text]
IMRT-induced acute hepatic toxicity and analysis of the dose-volume effects in gastric cancer patients treated with postoperative radiation.
Authors: Jing Yu , Zhou Fuxiang , Wen-juan Yang , Jing Dai , Ling Xia , Wen-bo Wang
Published: September 2018

e15542

Background: To investigate the postoperative-IMRT-induced hepatic toxicity in gastric cancer, and analyze the correlations between liver dose-volumetric parameters and acute hepatic toxicity, so as to give a dose-limitation suggestion for postoperative-IMRT in gastric cancer patients. Methods: Between June 2013 and June 2016, 67 patients with gastric cancer treated with post-operative adjuvant IMRT were reviewed. Prescribed dose was from 45Gy to 54Gy, in a daily fraction of 1.8–2.0 Gy. Dose constraints included: liver V30 < 40%, liver V40 < 30%, a mean dose of two kidneys < 18Gy and one kidney V6 < 50% if a mean dose of another kidney is more than 18Gy or another kidney has been resected. The following clinical and dose-volumetric parameters were examined: age, gender, concurrent chemotherapy, chemotherapy cycles before IMRT, chemotherapy cycles after IMRT, total chemotherapy cycles, Dmean (mean dose to liver), V5, V10, V15, V20, V25, V30, V35, and V40. Acute hepatic toxicity was evaluated between 1 and 4 months after radiation, according to the Common Terminology Criteria for Adverse Events(CTCAE), version 3.0. Results: 46 patients developed grade 1 hepatic toxicity, and 8 patients developed grade 2 hepatic toxicity after radiation, while there was no grade 3 or more severe hepatic toxicity. On univariate analysis, chemotherapy cycles after radiation, total chemotherapy cycles, Dmean, V20, V25, V30, V35 and V40 show correlations with Grade 2 acute hepatic toxicity (p = 0.009, 0.004, 0.015, 0.040, 0.005, 0.001, 0.001, 0.001, respectively). On multivariate analyses, V40 was the only significant parameter correlated with the risk of Grade 2 acute hepatic toxicity (P = 0.002). Using ROC curves, we find that to avoid grade 2 acute hepatic injury, the dose-volumetric limitations would be: Dmean of 22.4Gy, V20 of 42.3%, V25 of 38%, V30 of 27%, V35 of 17%, and V40 of 13%. Conclusions: IMRT is safe for gastric cancer treated with postoperative-radiotherapy as to liver. The grade 2 acute hepatic toxicity could be avoided by restricting dose-volumetric parameters of liver.
Polymorphisms in the PRTOR gene in relation to gastric adenocarcinoma susceptibility in an Eastern Chinese population.
Authors: Wang Meng-Yun , Jia Ming , He Jing , Wei Qing-Yi
Published: September 2018

e15552

Background: RPTOR is an essential scaffold for MTOR complex which is necessary for the MTOR-catalyzed phosphorylation. Methods: In this study of 1,100 gastric cancer (GCa) cases and 1,137 matched cancer-free controls, we investigated associations between eight potentially functional single nucleotide polymorphisms (SNPs) (rs3751934 C > A, rs1062935 T > C, rs12602885 G > A, rs1468032 T > A, rs1468033 A > G, rs2271610 C > G, rs2271612 C > T, and rs2878052 G > A) in RPTOR and gastric cancer risk in an Eastern Chinese Population. Results: In logistic regression analysis, a significantly increased GCa risk was associated with the rs1468032 AA variant genotype (adjusted odds ratio [OR] = 1.32, 95% confidence interval [CI] = 1.09-1.60) under a dominant model, which remained significant after correction by the false-positive reporting probability. This risk was more evident in subgroups of younger subjects, females, never smokers, never drinkers, cancers of non-cardia and stage of Ⅲ+Ⅳ. We then performed SNP-mRNA expression correlation analysis in GTEx database as well as using real-time PCR in adjacent noncancerous tissues. We found that the AA variant genotype was associated with non-significantly decreased expression of RPTOR mRNA level. Conclusions: Our results suggest that the RPTOR rs1468032 A variant may be markers for GCa susceptibility. Larger, independent studies are warranted to validate our findings.
Effect of Spag5 on proliferation and sensitivity to DNA-damaging chemotherapy.
Authors: Liao Wangjun , Yuan Lezhong , Luo Yuhao , Ma Huanrong
Published: September 2018

e15556

Background: Chemotherapy based on DNA-damaging anti-cancer drugs remains the most predominant treatment for advanced gastric cancer. The predictors for their sensitivity are under development. Our data showed that sperm-associated antigen 5 (Spag5) contributed to cancer cell proliferation and decreased DNA-damaging drug sensitivity in vivo and vitro. Methods: Spag5 mRNA expression were compared in The Cancer Genome Atlas (TCGA) and GEO datasets (GSE56807, GSE63089, GSE65801), while protein level were detected in 52 patients diagnosed with gastric cancer in Nanfang Hospital by immunohistochemistry. BGC-823 and MGC-803 were transfected with spag5 and control siRNA and then subjected to MTT and EDU assay to verify proliferation rate. Cell viability and apoptosis were tested in spag5-silenced BGC-823 and MGC-803 treated with oxaliplatin, epirubicin and 5-fluorouracil independently. DNA-damaged were detected by comet assay and yH2ax level with western blot. Treatment of oxaliplatin was given intraperitoneally to nude mice carrying xerographs of Shspag5 or control BGC-823 cells every three days. Results: Spag5 mRNA level was significantly upregulated in cancer tissues compared with paired normal tissues in all of the datasets. Immunohistochemistry shows higher protein level of spag5 in paired cancer tissue. Knockdown of Spag5 BGC-823 and MGC-803 showed a significantly decreased proliferation in both MTT and EDU assay. Spag5 silencing led to increase vulnerability to oxaliplatin, epirubicin and 5-fluorouracil, thus less cell viability and more apoptosis. Spag5 knockdown BGC-823 and MGC-803 subjected to DNA-damaging drugs showed upregulated yH2ax level and increased DNA damage in comet assay. Tumor growth rate were significantly reduced in shspag5 group and treatment of oxaliplatin led to relatively higher inhibition of tumor growth. Conclusions: Spag5 serves as a candidate to predict proliferation and chemosensitivity to DNA-damaging chemotherapy.
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.
A new prognostic model based on total tumor volume to predict survival rate in locally advanced hepatocellular carcinoma patients.
Authors: Chen Zhan-Hong , Lin Jin-Xiang , Lin Qu , Li Xing , Hong Ying-Fen , Wu Xiang-yuan
Published: September 2018

e15622

Background: Many HCC patients are diagnosed as locally advanced and loco-regional therapies improved the prognosis of these patients. Survival rates of these patients vary differently. We want to research on the prognostic factors and establish a new prognostic model based on total tumor volume(TTV) to predict the survival rate in locally advanced hepatocellular carcinoma patients who receive loco-regional therapy. Methods: 214 locally advanced HCC patients who received TACE or PEJ were retrospectively studied. Univariate and multivariate analyses were used to assess the variables. A new prognostic model based on TTV was developed with independent prognostic factors. The predictive value was evaluated using receiver operator characteristic curve (ROC) analyses. Results: The median survival is 23.4 months. Univariate and multivariate analyses showed that total tumor volume (TTV), child-pugh garde, protal vein thrombosis and antivirus therapy were independent factors of overall survival. A risk model was establsihed and it is consisted of 4 factors mentioned above. 214 patients were classified into 5 stages by the new staging system. We researched on the predictive value of the new prognostic system by comparing it with CLIP, BCLC and TNM. When predicting 1-year OS, AUC of the new prognostic system, CLIP, BCLC and TNM is 0.620, 0.735, 0.527 and 0.655, respectively; CLIP is best when predicting 1-year os. When predicting 2-year OS, AUC of the new prognostic system, CLIP, BCLC and TNM is 0.623, 0.671, 0.516 and 0.577, respectively;The new prognostic system is as good as CLIP. When predicting 3-year OS, AUC of the new prognostic system, CLIP, BCLC and TNM is 0.623, 0.645, 0.504 and 0.593, respectively; The new prognostic system is as good as CLIP and is better than BCLC(P < 0.05). Conclusions: Total tumor volume is independent prognotic factors of locally advanced hepatocellular carcinoma patients who received locoregional therapies.The new prognostic system based on TTV is as good as CLIP in predicting 2-year OS and 3-year OS. A new prognostic system based on TTV TTV(CM3) < 22.5(0) ≥22.5(1) Antivirus therapy No(0) Yes(1) Child pugh Grade A(0) B(1) Portal vein thrombosis No(0) Yes(1)
Better cancer-specific survival in young patients with nonmetastatic intrahepatic cholangiocarcinoma: A retrospective study of SEER database.
Authors: Wang Zheng , Qin Lunxiu
Published: September 2018

e15637

Background: Intrahepatic cholangiocarcinoma (ICC) is a complicated and fatal malignancy. Aging plays a significant role in the occurrence and development of this liver cancer, but its prognostic role remains unclear. The purpose of this study is to compare the cancer specific survival (CSS) in young patients with elderly ones, and to further establish a nomogram, integrating age and other risk factors, to predict survival outcomes in ICC patients. Methods: Cases of intrahepatic cholangiocarcinoma diagnosed between 2004 and 2013 were extracted from SEER database. Patients were excluded if they had incomplete TNM staging, with distant metastasis (M1) or no evaluation on lymph node. The enrolled cases were divided into young (under 50 years of age) and elderly groups (50 years and over). 1-year and 3-year cancer CSS data were obtained. Kaplan-Meier methods were adopted and multivariable Cox regression models were built for the analysis of survival outcomes and risk factors. A predictive nomogram for prognosis was generated by software R, and the performance of the nomogram was assessed by C-index and validation curves. Results: There were 2385 patients meeting inclusion criteria with median follow up of 17.0 months. Compared with elderly group, young patients showed significantly higher pathological grading (P = 0.006), lower rate of lymph node invasion (P = 0.002), and early TNM stage (P = 0.005). The 1-year and 3-year CSS rates were 57.3% and 19.2% in young group, and 38.2% and 10.8% in elderly group. Both univariate analysis (P = 0.019) and multivariate analysis (P = 0.040) indicated significant difference of CSS between the two groups. The multi-factor, integrative nomogram was established to predict prognosis, whose predictive power was higher than the conventional tumor staging (AJCC 7thedition staging). And the calibration curves for the probability of 1- and 3-year CSS indicated that the nomogram-based prediction was in optimal agreement with actual observed survival. Conclusions: Compared with elderly patients, young patients with non-metastatic ICC appear to have more favorable clinicopathological characteristics and better prognosis.
Role of primary tumor resection in the prognosis of patients with resectable metastatic hepatocellular carcinoma.
Authors: Mao Kai , Wang Ruomei , Xu Qiaodong , Xiao Zhiyu , Zhang Jianlong , Liu Yingyue , Liu Jieqiong
Published: September 2018

e15642

Background: Patients with metastatic hepatocellular carcinoma (HCC) are diagnosed more frequently because of introduction of increasingly sensitive imaging modalities. The majority of these patients die of progressive intrahepatic tumor but not due to extrahepatic metastasis. There has been little information about the role of primary tumor resection (PTR) for metastatic HCC patients with resectable primary tumor. Methods: Metastatic HCC patients recommended PTR were identified in SEER registry between 2004 and 2013. The effect of PTR on overall and cancer-specific survival (OS and CSS) using log-rank test and Cox proportional hazard regression model, as well as propensity score matching was assessed. Additionally, validation was performed in another cohort from Sun Yat-sen Memorial hospital (n = 131). Results: Overall, 529 metastatic HCC patients with resectable primary tumor were included. Of those 230 patients underwent PTR but 299 did not. The percentage of PTR among resectable metastatic HCCs increased from 38.6% in 2004 to 70.3% in 2013. PTR was associated with improved OS (hazard ratio (HR) 0.310, 95% CI 0.241-0.400, P< 0.001) and CSS (HR 0.326, 95% CI 0.250-0.425, P< 0.001) in the propensity score- matched patients. This improvement in outcomes remained significant after sensitivity analyses using multiple imputation. Furthermore, consistent with observations in SEER, PTR was correlated with improved OS (HR 0.496, 95% CI 0.294-0.838, P= 0.009) and CSS (HR 0.538, 95% CI 0.307-0.945, P= 0.031) in the validation cohort from Sun Yat-sen Memorial hospital. Conclusions: This study, the first population-based analysis using propensity score matching and multiple imputation, demonstrated that PTR has a favorable impact on prognosis in patients with metastatic HCC. Further prospective randomized trials is needed to conclusively determine whether metastatic HCC patients with resectable primary tumor should be offered aggressive locoregional surgery.
Phase II trial of sorafenib combined with on-demand transarterial chemoembolization for advanced stage hepatocellular carcinoma (Barcelona Clinic Liver Cancer stage C): STAB study.
Authors: Sato Yozo , Nishiofuku Hideyuki , Yasumoto Taku , Nakatsuka Atsuhiro , Matsuo Kunihiro , Kodama Yoshihisa , Abo Daisuke , Okubo Hironao , Takaki Haruyuki , Inaba Yoshitaka , Yamakado Koichiro , Hirota Shozo
Published: September 2018

e15648

Background: Sorafenib has been acknowledged as a standard treatment for advanced stage hepatocellular carcinoma (HCC). This study was conducted to evaluate the safety and efficacy of combination therapy of sorafenib and on-demand transarterial chemoembolization (TACE) for advanced stage HCC. Methods: Inclusion criteria were advanced stage HCC (Barcelona Clinic Liver Cancer stage C), a systemic chemotherapy native status, an Eastern Cooperative Oncology Group performance status 0–1, and a Child-Pugh grade-A. Sorafenib therapy (800 mg daily) was started 4–28 days after TACE. On-demand TACE was allowed. The primary endpoint was the completion rate of protocol treatment, which was defined as sorafenib administration at least for 2 months from initial TACE. Secondary endpoints were objective response rate (ORR), disease control rate (DCR) based on modified Response Evaluation Criteria in Solid Tumors, overall survival (OS), progression-free survival (PFS), and the incidence of adverse events. Results: From July 2013 to September 2015, a total of 32 patients were registered from 9 institutions, but one patient was excluded because his tumor turned out to be combined hepatocellular carcinoma and cholangiocarcinoma. The protocol treatment was completed in 28 of 31 enrolled patients (90.3%, 28/31). The median treatment duration was 7.0 months (range 0.5–30) with the median number of TACE was 1 (range 1–4) and the median sorafenib dosage of 400 mg daily (range 154-800). The ORR and DCR were 77% and 90%, respectively. Median OS and PFS were 17.3 months [95% confidence interval (CI), 11.9–22.6] and 5.4 months (95% CI, 4.6–6.2), respectively. The most common grade-3 or -4 adverse events were increased aspartate aminotransferase (55%, 17/31), increased alanine aminotransferase (45% 14/31), and hypertension (23%, 7/31). Conclusions: Combination therapy of sorafenib and on-demand TACE was well tolerated and safe. Furthermore, this combination treatment may provide a survival benefit to patients with advanced stage HCC. Clinical trial information: UMIN000014213.