bluuebunny/crossref_metadata_2025_split huggingface dataset:
The efficacy of gastrectomy plus chemotherapy for stage IV gastric cancer.
Authors: Muto Osamu , Kotanagi Hitoshi 
Published: February 2017

132 Background: Metastatic gastric adenocarcinoma is an incurable condition. Despite the recently reported benefits of chemotherapies, the prognosis of advanced gastric cancer remains poor. The role of surgical resection is still debatable. Therefore, we investigated the efficacy of gastrectomy plus chemotherapy for stage IV gastric cancer. Methods: We retrospectively evaluated the efficacy of gastrectomy plus chemotherapy for treating stage IV gastric cancer. Among the 753 patients with gastric cancer treated with gastrectomy at our institute between 2003 and 2010, a total of 70 patients classified into stage IV and underwent gastrectomy with perioperative chemotherapy were included in this study. In the analysis, particular attention was paid to the prognostic factors of age, gender, tissue type, metastatic site, pre or postoperative chemotherapy, single agent or combination chemotherapy and the reason for gastrectomy (palliative surgery due to stenosis, bleeding or perforation and reduction surgery). The survival rate was calculated by the Kaplan Meier method and a statistical analysis was performed using the log-rank test. Survival was calculated from the beginning of the treatment until the last follow-up or death from any cause. Results: The median age was 65 years old. Peritoneal, lymph node and liver metastasis were 28, 23, and 13 patients respectively. Fifty-three patients had diffuse type. Gastrectomy followed by chemotherapy and chemotherapy were 53 patients. Single agent chemotherapy were 42 and combination were 28 patients. Thirty-one patients were underwent palliative surgery and 39 patients were reduction surgery. One-year survival rate of all patients was 43% and the median survival time was 19.9 months. In the statistical analysis, only reduction surgery plus chemotherapy demonstrated significant survival benefit. The median survival time was significantly greater in patients undergoing reduction gastrectomy group than in those undergoing palliative gastrectomy (25.3 versus 9.8 months; p=0.005). Conclusions: Long-term survival for patients with stage IV gastric cancer who are managed with reduction surgery and chemotherapy is achievable. Further study with a larger number of patients is warranted.
5-FU induced encephalopathy during 5-FU containing regimen for esophageal squamous cell carcinoma.
Authors: Kato Ken , Akiyoshi Kohei , Hokamura Nobukazu , Igaki Hiroyasu , Tachimori Yuji , Honma Yoshitaka , Iwasa Satoru , Hamaguchi Tetsuya , Yamada Yasuhide , Shimada Yasuhiro 
Published: February 2017

138 Background: 5-FU induced encephalopathy was known as uncommon toxicity during the treatment which contain with 5-FU. But there were few reports such as clinical feature and risk factors of 5-FU induced encephalopathy. We conducted retrospective case-control study to investigate the clinical feature and risk factor of them. Methods: Data was collected by medical record. The selection criteria were as follows: Pathologically proven esophageal squamous cell carcinoma, patents who received 5-FU containing regimen in our hospital. The diagnostic criteria of the 5-FU induced encephalopathy includes: (i) development of encephalopathy during or shortly after completion of 5-FU administration; (ii) exclusion of other metabolic factors that may affect consciousness and (iii) exclusion of an adverse effect by concomitant medications. 5-FU containing regimens include that 5-FU+CDDP with or without radiation, 5-FU=Nedaplatin with or without radiation and 5-FU=CDDP=docetaxel. Results: From January 2008 to March 2010, 317 patients were collected. Of 317 patients, the median age was 64 (range 36-79); male/female: 267/49; cStage I/IIA/IIB/III/IV: 63/19/53/91/85. Median and total course of 5-FU containing regimen and were 2 (range1-14) and 943. The object of first treatment was as follows; Neoadjuvant (n=114), definitive chemoradiotherapy (n=110), palliative chemotherapy (n=81) and others (N=24). Nine patients (2.8%) were diagnosed as 5-FU encephalopathy. The median course and time to onset of encephalopathy was 3 course (range1-4) and 5 days (range 3-6) from start of 5-FU. Five of 6 pts who examined NH3 were observed the elevation of NH3. All patients recovered within 1-2 days after stopping administration of 5-FU. Head CT or MRI showed no abnormality in all pts. Univariate analysis showed that only age (>60) was risk factor for encephalopathy. The other thing such as regimen and sex were not associated with encephalopathy. Conclusions: This is the first report which described 5-FU induced encephalopathy in such large population. 5-FU encephalopathy was very rare but recovered with adequate treatment. In aged patients we should pay more attention about 5-FU encephalopathy than younger patients.
Retrospective cohort study on the risk factors of admission due to serious adverse events during S-1 (tegaful, gimeracil, oteracil potassium) containing chemotherapy for gastric cancer.
Authors: Kawamoto Yasuyuki , Yuki Satoshi , Kobayashi Yoshimitsu , Oba Koji , Hayashi Hideyuki , Nakatsumi Hiroshi , Komatsu Yoshito 
Published: February 2017

141 Background: S-1 (tegaful, gimeracil, oteracil potassium) containing regimens are widely used as first line chemotherapy for metastatic or unresectable gastric cancer in Japan. Because patients often need admission due to serious adverse events (SAE) during chemotherapy, it is important to predict admission. We retrospectively investigated the risk factors of admission due to SAE during first line chemotherapy which contained S-1. Methods: We retrospectively analyzed the patients who began to receive S-1 containing chemotherapy for the first line chemotherapy at our institution from January 2005 to December 2010 by medical records. Association between baseline characteristics and admission due to SAE were evaluated by Fisher’s exact test, t-test or Mann-Whitney test. Age, sex, S-1 dose (mg/m2) and other factors which significantly associated in the univariate analysis were evaluated in the multivariate logistic regression model. Results: One hundred nine patients were assessed. Admission due to SAE were observed in 24 patients (34 times), and tended to occur before 2nd cycle had ended. Multivariate analysis suggested that hypoalbuminemia was a risk factor of admission due to all SAE (Odds ratio 0.15, 95% C.I. 0.05 - 0.44, P = 0.0005). It is suggested that S-1 dose was a risk for admission due to FU-induced colitis (Odds ratio 1.30, 95% C.I. 1.12 - 1.50, P=0.0004). Conclusions: Hypoalbuminemia might constitute a marker of admission due to SAE. FU-induced colitis occurred in S-1 dose-related fashion, and the patients had lost their weight before appropriate course. It is suggested that clinicians should pay attention to patients’ weight loss during chemotherapy, notably time of initiation of chemotherapy.
Outcomes of adjuvant chemoradiotherapy after a radical gastrectomy and D2 node dissection for gastric adenocarcinoma in INEN (Lima, Peru).
Authors: Montenegro Paola Catherine , Lopez Lourdes , Quintana Shirley , Casanova Luis Augusto , Castro Victor , Mantilla Raul 
Published: February 2017

150 Background: Adjuvant chemoradiotherapy is the standard treatment in Western countries in gastric cancer patients submitted to curative resection. INT 0116 pivotal trial established adyuvant chemoradiation as the standar care for resected high risk adenocarcionoma of the stomach in US however was hampered by suboptimal surgery. There is controversial data about efficacy of this adjuvant therapy in patients who have undergone D2 lymphadenectomy predominantly. In our hospital D2 lymphadenectomy is standar surgery for gastric cancer. Methods: Retrospective study with gastric adenocarcinoma patients stage II to IV M0 who underwent curative resection at Instituto Nacional de enfermedades Neoplasicas Lima- Peru between 2001 and 2006 Standard treatment at institution is D2 lymphadenectomy. Chemoradiotherapy according to INT 0116 was given like adjuvant therapy. Survival curves were calculated according to Kaplan-Meier method and compared with log-rank test. Multivariate analysis of prognostic factors related to survival was performed by Cox proportional hazards model adjusted for age, stage and adjuvant chemoradiotherapy. Results: 84 patients were included 60.3% male and 39.3% female. Median age was 40.5 years old. The patologic stage were T1-T2 (12.3%), T3-T4 ( 50% ), N0-N1 (10.7%), N2-N3 (89.3%). D2 lymphadenectomy was performed in all patients. The 3-year DFS was 17% and 3-year overall survivall was 23.9% years.However when we analized by subgroups the overal survival was significantly longer in group N1 ( 61%) and N2 (58.9%) that N3 (18.3%) and DFS were N1 (60%), N2 (55%) and N3 (16.3%). Conclusions: Adjuvant chemoradiotherapy decreased risk of death and relapse in patients with node positive N1-N2 , who underwent curative resection with D2 lymphadenectomy, but recurrence was most frecuent in N3 node positive, maybe is necesary improve the chemotherapy in this group of patientes for dicrease the rate of relapse.
Biomarkers in pancreatic neuroendocrine tumors.
Authors: Alistar Angela Tatiana , Warner Richard , Moshier Erin , Kim Michelle , Holcombe Randall F. 
Published: February 2017

166 Background: This study was designed to determine the role of Chromogranin A (CGA) and serotonin as prognostic biomarkers in relation with cytoreductive surgery for pancreatic neuroendocrine tumors (PNETs).The role of CGA and serotonin as biomarkers for PNETs is not fully established. Clinicians use CGA to monitor progression of disease and response to treatment; however this hasn’t been fully validated. There is no definitive data for serotonin as prognostic biomarker in PNETs. Methods: A retrospective study of patients with PNETs seen at Mount Sinai from 1980 to 2011 was performed. All patients (142) that have had CGA and serotonin concentrations measured at least once were evaluated. Data relating to diagnosis, therapies and survival outcome were noted Results: We evaluated the probability of survival post cytoreductive surgery among patients characterized by their postoperative CGA and serotonin values. 27 patients have had CGA level measured early post-op (0 to 3 months) and 30 patients have had CGA measurement late post-op (3-12 months). We identified no correlation between survival and a normal CGA early post-op (p = 0.5895). We identified a trend (p=0.1369) towards increase in survival for patients with a normal CGA late post-op with a probability in survival of 92.86% vs 65.12% at 3 years and median months to death of 80.265 for normal CGA vs 50.39 months for high CGA late post-op. For the 22 patients that had both a CGA early and late post-op the probability of survival by their change from early to late post- surgery CgA values was not statistically significant (p=0.2903). Serotonin did not correlate with survival in any of the 3 analyses: early post op, late postop or change in serotonin level. Conclusions: The role of CGA as a predictive or prospective biomarker for PNETs is worth prospective investigation. Our study shows that late post-op CGA may predict clinical outocome while CGA early postop and serotonin early, late and change post op did not have value in predicting survival.
The impact of HER2 positivity on survival in metastatic gastric and GEJ cancer.
Authors: Kumar Aalok , Zhou Chen , Huntsman David , Kollmannsberger Christian K. , Gill Sharlene , Lim Howard John 
Published: February 2017

17 Background: HER2 positive (+) gastric (GC) and GEJ adenocarcinoma (AC) has been associated with a worse survival outcome. This study examines the survival rate of patients (pts) with metastatic HER2 (+) GC and GEJ AC in the province of BC. Methods: Formalin fixed embedded tissue from pts with resected GC or GEJ AC from 2004−2011 were identified retrospectively through the BC Cancer Agency registry and prospectively for pts with a new diagnosis of advanced disease. Biopsies and resection samples were analyzed via previously validated methods. IHC scores of 3 were considered (+), 2 were equivocal and 0/1 were negative (−). 10% cut-off was used to determine (+) samples. Equivocal staining was considered (+) via FISH or SISH with a ratio of > 2.2 considered amplified. Pt characteristics were abstracted to an anonymized database. Kaplan meier curves were calculated to evaluate overall survival from time of diagnosis or relapse to death for pts with Her 2 (+) or (-) disease. Results: 164 of 294 pts were identified with metastatic or relapsed GC (49%) or GEJ (51%) AC without traztumumab treatment. 21 (13%) of pts were HER2 (+) either by IHC, FISH or SISH. See Table for pt characteristics. The HER2 (+) group was older (median age 68 yrs vs 60), more GEJ (62% vs 49% p=1.23), and a higher number of pts that did not receive treatment (52% vs. 27% p=5.09). Median survival was not significantly different among HER2 (+) and (−) disease (4.0 mo vs. 7.3 mo, p=0.089). Conclusions: The rate of HER2 positivity is similar to that seen in trial data. HER2 positivity trends to a worse prognosis but was not significant in this study. [Table: see text]
Candidate biomarkers identified in the saliva of patients with pancreatic adenocarcinoma.
Authors: Fleming Jason B. , Trajtenberg Cynthia 
Published: February 2017

173 Background: There is currently no simple test to identify patients with pancreatic ductal adenocarcinoma (PDAC). The goal of this research is to develop such a method. We hypothesized that the salivary proteome of patients with localized PDAC contains a protein set distinct from normal subjects. Methods: We collected, processed and stored stimulated whole salivary gland secretions from patients with Stage I-II PDAC and aged-matched healthy volunteers. Fluorescently-labeled proteins were separated using 2D DIGE. Overlay imaging techniques compared 2D DIGE results, and spots representing individual proteins were quantified by signal, isolated from the gels, processed and protein identified using MALDI-TOF Mass Spectrometry. The SWISS-PROT database was used to identify proteins, and the ratio of signal in cancer versus normal samples was quantified and compared using Student’s t-test. Results: Samples from 10 PDAC patients and 10 healthy subjects were compared. A total of 96 spots on the 2D-DIGE comparison were uniquely present or absent in PDAC patient saliva. MALDI-TOF Mass Spectrometry examination of these 96 characterized 53 unique proteins. After eliminating duplicates and proteins without significant differences (p-value <0.02), a total of 30 proteins were identified with levels higher (n=18) or lower (n=12) in saliva from PDAC patients versus normal subjects. Conclusions: Examination of saliva from pancreatic cancer patients identified a set of proteins unique from normal subjects. These proteins represent targets for the development of biomarkers that could be used in early detection of pancreatic cancer.
Revisiting the prognostic significance of positive peritoneal cytology in pancreatic cancer.
Authors: Chen Kathryn T. , Singla Smit , Papavasiliou Pavlos , Devarajan Karthik , Hoffman John Parker 
Published: February 2017

177 Background: Positive peritoneal cytology (PPC) in the setting of pancreatic cancer predicts a poor prognosis, such that it is considered metastatic disease in the American Joint Commission on Cancer staging guidelines. We re-evaluate the role of PPC, with particular attention to outcomes following neoadjuvant therapy. Methods: We retrospectively identified 185 patients from January 1, 2000 to present with the diagnosis of pancreatic adenocarcinoma who had undergone peritoneal washings with cytology at the time of planned resection. Data regarding demographics, tumor stage, intraoperative cytology, surgical and chemoradiation therapeutics, and clinicopathological outcomes were analyzed, with the primary endpoints being disease-free and overall survival (DFS and OS). Results: 20 patients (11%) had PPC at the time of planned resection; of these, 11 patients (55%) received neoadjuvant therapy prior to surgery. 165 patients (89%) had negative peritoneal cytology (NPC) at the time of planned resection; of these, 75 (45%) received neoadjuvant therapy prior to surgery. All patients proceeded with resection in the absence of visible metastatic disease. 42% of NPC reached 2-year survival compared to just 20% of patients with PPC. Overall, patients with PPC vs. NPC had significantly poorer DFS (p<0.0064) and OS (p<0.0135). When stratifying by neoadjuvant therapy, in those patients with stage II disease or higher who did not receive neoadjuvant therapy, multivariable CART analysis revealed that PPC predicted poorer DFS compared with NPC (p<0.004). However, among stage II or higher disease receiving neoadjuvant therapy, it failed to show a significant difference in DFS or OS between PPC and NPC. Conclusions: Overall, patients with positive peritoneal cytology are shown to have worse DFS and OS compared to patients with negative peritoneal cytology in pancreatic adenocarcinoma. However, after multivariable analysis, the prognostic significance of positive peritoneal cytology disappears in those patients with stage II and higher disease receiving neoadjuvant therapy.
The incidence and preoperative detection of nodal metastases in resected pancreatic neuroendocrine tumors.
Authors: Lindberg James M. , Walters Dustin M , Stelow Edward B , Adams Reid B , Bauer Todd W. 
Published: February 2017

178 Background: Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of rare malignancies in which surgical resection remains the only curative therapy. The optimal surgical approach (enucleation vs. pancreatectomy) is controversial. This study aims to determine the 1) incidence, 2) predictors, and 3) preoperative detection of lymph node (LN) metastases in resected pNETs to help guide surgical management. Methods: A retrospective review of prospectively collected data was performed for all patients with pancreatic neuroendocrine tumors who underwent surgical resection at the University of Virginia between 1991 and 2010. The electronic medical record, radiology reports and pathology reports were used to identify patient demographics, surgical procedure, tumor functional status, type, size, location, and LN status. Results: In all, 76 patients were identified. Most tumors were non-functioning (71%) with insulinomas (13%) and gastrinomas (5%) representing the largest groups of functioning pNETs. Nineteen tumors (25%) had LN metastases at the time of resection. LN-positive tumors were significantly larger than LN-negative tumors (4.0 ± 0.4 cm vs. 2.8 ± 0.2 cm, p=0.01). Five (11%) of 46 tumors ≤ 3 cm and one (14%) of 7 tumors ≤ 1 cm had LN metastases. There were no significant relationships between LN status and either tumor type or location (head/uncinate vs. body/tail). Of patients with LN-positive tumors, preoperative CT or MRI detected the LN metastases in only 19%. Conclusions: Twenty-five percent of pNETs are associated with LN metastasis. The only predictor of LN metastasis was tumor size, but even smaller tumors were associated with LN metastasis. The sensitivity of preoperative CT and MRI is quite poor in detecting LN metastasis. Thus, formal resection with lymphadenectomy should be considered the standard of care for pNETs. [Table: see text]
The metabolomic signature of pancreatic cancer in urine.
Authors: Davis Vanessa Wylie , Schiller Dan E. , Sawyer Michael B. 
Published: February 2017

180 Background: Pancreatic cancer is one of the leading causes of cancer-related death, due partly to the lack of early detection and screening methods. Metabolomics, the newest of the “omics” sciences, provides a means for non-invasive screening of early tumor associated perturbations in cellular metabolism. We applied metabolomic techniques to identify urinary metabolites capable of facilitating diagnosis of pancreatic cancer. Methods: Urine samples from pancreatic cancer patients (n=55) and healthy volunteers (n=25) were collected and examined using 1H-NMR spectroscopy. Targeted profiling of spectra using Chenomx NMR Suite 7.0 software permitted quantification of 66 metabolites. Unsupervised (PCA) and supervised (PLS-DA) multivariate pattern recognition techniques were applied to discriminate between sample spectra of pancreatic cancer patients and healthy volunteers using SIMCA-P (version 11, Umetrics, Umeå, Sweden). Results: Significant differences were found when comparing concentrations of 66 metabolites in urines of healthy volunteers and pancreatic cancer patients. Those metabolites contributing the most class discriminating information included choline, 2-aminobutyrate, urea and 2-oxoglutarate. Clear distinctions between pancreatic cancer patients and healthy controls were noted when PLS-DA was applied to the data set. Model parameters for both goodness of fit R2, and predictive capability Q2, were high (R2 = 0.829; Q2 = 0.76). Model validity was tested using response permutation and results were suggestive of excellent predictive power. Application of PLS-DA to the data set also revealed clear discrimination of Stage I-III and Stage IV disease states, with the following model parameters, R2 = 0.62; Q2 =0.45. Conclusions: Urinary metabolomics detected clear differences in metabolic profiles of pancreatic cancer patients and healthy volunteers. Early results presented here suggest that metabolomic approaches may facilitate discovery of novel biomarkers capable of early disease detection.
The role of NeuroD1 in the upregulation of SMYD3 by HBx.
Authors: Xu Junyao , Hong Qingqi , He Chuanchao , Wang Jie 
Published: February 2017

183 Background: SET and MYND Domain-Containing Protein 3 (SMYD3) is frequently overexpressed in hepatocellular carcinoma (HCC) exhibiting increased malignant phenotypes. It has also been known that the hepatitis B virus x protein (HBx) is strongly associated with HCC development and progression. Although overexpression of both proteins is related to HCC, the relationship between the two has not been well studied. Methods: Immunohistochemical staining was used to detect the expression of HBx and SMYD3 in HCC tumor tissues. HBx gene transfection, RNAi, and histone methyltransferase(H3-K4) activity assay were performed to reveal the transcrpitionally activation of HBx on functional SMYD3 gene expression. Chromatin immunoprecipitation (ChIP), Co-immunoprecipitation (Co-IP), Electrophoretic mobility shift assay (EMSA) were applied to investigate the underlying mechanism. Dual-luciferase reporter assay was used to search for the HBx responsive cis-element of SMYD3 gene. Results: Immunohistochemistry identified the positive correlation between HBx and SMYD3 expression in 42 HCC tissues. Up-regulation of HBx on SMYD3 expression was validated through experiments involving overexpression or knock-down of HBx in different HCC cell lines. And up-regulated SMYD3 is functionally active as histone methyltransferase. Next we found that HBx transcriptionally regulated SMYD3 gene expression by interacting with RNA polymerase IIand altering its binding site to a proximal promoter region(SD2) from a distant promoter region(SD6) of SMYD3. Truncated and mutant reporter assays revealed that the cis-element mapped in -178~-203bp in SMYD3 promotor is responsive for HBx-transactivation. And this 25bp cis-element contains a E-box 3 unit, which is a binding site for the transcriptional factor Neurogenic differentiation 1(NeuroD1). EMSA and Chip showed that HBx increased NeuroD1 binding to SMYD3 proximal promotor, however transcient expression of antisense NeuroD1 abolished HBx-induced SMYD3 expression. Conclusions: HBx transcriptionally up-regulates SMYD3 and that this process is mediated by NeuroD1 through binding to the E-box 3 site of SMYD3 promotor.