bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of helicobacter pylori on prognosis of curatively resected gastric cancers in a population with high prevalence: Short-term results of a prospective study.
Authors: Hur H. , Kim J. Y. , Kim Y. B. , Lim Y. A. , Cho Y. K. , Han S. U. 
Published: February 2017

152b Background: Although two prospective studies reported that negative H pylori is associated with good prognosis in Western countries, these results are not generally acceptable due to regional differences in H pylori virulence and incidence of gastric cancer. Here, we prospectively assessed the correlation between H pylori status of patients who underwent curative resection for treatment of gastric adenocarcinoma and their prognosis in Korea, where H pylori is highly prevalent in the population. Methods: Between 2006 and 2007, 192 patients who had undergone curative resection for treatment of gastric adenocarcinoma were prospectively enrolled. Of these patients, 18 patients were excluded due to inexact evaluation of H pylori status, and 174 patients were finally analyzed. Serologic testing for H pylori was assessed using an enzyme-linked immunosorbent assay kit for IgG, and histological presence was identified using Giemsa stain. Results: Of 174 patients, 111 patients (63.8%) who showed both serologically and histologically positive results were confirmed as having positive H pylori infection. H pylori status was not correlated with overall or disease-free survival. In term of patients who were diagnosed with AJCC stage III or IV, disease-free survival of patients with positive H pylori status was a significant predicting factor for recurrence longer than that of negative patients (p = 0.019). Negative H pylori status became a predicting factor for recurrence in multivariable analysis (RR = 2.724, 95% C.I.: 1.192-6.228). Conclusions: H pylori status did not show correlation with clinicopathologic factors of gastric adenocarcinoma in Korea. However, negative H pylori may be a predictive factor for recurrence in patients diagnosed with gastric adenocarcinoma of advanced status. Therefore, in H pylori endemic areas, patients diagnosed with locally advanced gastric cancer accompanied by negative H pylori status should be considered for an aggressive treatment strategy and close follow-up. In addition, correlation in an early stage should be confirmative through the results of longer follow-up. No significant financial relationships to disclose.
Association of RecQ1 A159C polymorphism with overall survival of patients with resected pancreatic cancer: A replication study in RTOG 9704.
Authors: Li D. , Moughan J. , Crane C. H. , Hoffman J. P. , Regine W. , Abrams R. A. , Safran H. , Freedman G. M. , Guha C. , Abbruzzese J. L. 
Published: February 2017

156 Background: To confirm whether a previously observed association between a DNA repair gene and clinical outcome of resectable pancreatic cancer patients treated with preoperative chemoradiation is reproducible in another patient population. Methods: We evaluated the RecQ1 A159C variant (rs13035) in patients with resected pancreatic cancer who were enrolled on the RTOG 9704 trial of 5FU-based chemoradiation preceded and followed by 5-FU or gemcitabine. DNA was extracted from paraffin-embedded tissue sections and genotype was determined using the Taqman method. A multivariate Cox proportional hazards model was used to determine if there is a correlation between genotype and overall survival (OS). Models were built using the stepwise selection procedure. The following variables were included in the model: genotype, treatment arm, age, gender, race, nodal involvement, tumor diameter, and surgical margin status. Results: A total of 154 out of 451 eligible patients were evaluated for the RecQ1genotype. There was no significant difference in baseline characteristics and overall survival time between patients who were and were not evaluated for the RecQ1genotype. In the 154 evaluated patients, the genotype distribution followed the Hardy-Weinberg Equilibrium, i.e. 37% had genotype AA, 43% AC, and 20% CC. The RecQ1 variant AC/CC genotype carriers were more likely to be node positive compared to the AA carrier (p=0.03). The median survival times (95% C.I.) for AA, AC, and CC carriers were 1.72 (1.36, 2.17), 1.57 (1.18, 1.80), and 1.18 (0.86, 1.75) years, respectively. On multivariate analysis, patients with the AC/CC genotypes were more likely to die than patients with AA genotype (HR=1.54, 95% C.I. = [1.07, 2.23], p=0.022). This effect is more definitive for patients on the 5-FU arm (n=82) (HR=1.64, 95% C.I. = [0.99, 2.70], p=0.055) than for patients on the gemcitabine arm (n=72, HR=1.46, 95% C.I. = [0.81, 2.63], p=0.21). Conclusions: Results of this study suggest that the RecQ1 A159C genotype is a prognostic or predictive factor for resectable pancreatic cancer patients who are treated with adjuvant chemoradiation. No significant financial relationships to disclose.
Use of gene expression analysis of periampullary carcinomas to identify biliary-like and intestinal-like subgroups of ampullary and duodenal carcinomas.
Authors: Overman M. J. , Zhang J. , Varadhachary G. R. , Hwang R. F. , Kapoor M. , Abbruzzese J. L. , Wolff R. A. , Wang H. , Broom B. 
Published: February 2017

161 Background: Though adenocarcinomas of the ampulla of Vater are classified as biliary cancers, the epithelium of origin and treatment approach for these rare tumors remains controversial. We compared the gene expression profiles of ampullary carcinomas with that of known periampullary carcinomas. Methods: We analyzed 32 fresh-frozen resected untreated periampullary carcinomas (8 pancreatic, 2 extrahepatic biliary, 8 non-ampullary duodenal, and 14 ampullary) with verified histology and >70% tumor tissue using the Affymetrix U133 Plus 2.0 genome array. Hierarchical clustering of all samples based upon pancreatic and duodenal differentially expressed genes and unsupervised hierarchical clustering was done. Ampullary and duodenal samples were analyzed for histologic subtype (pancreaticobiliary, intestinal, mixed), MSI by PCR, CDX-2 by IHC and KRAS and PI3K mutations by mass spectroscopy-based sequencing (Sequenom). Results: We identified 3 subgroups: pancreatic (8 pancreatic, 1 duodenal), biliary-like (4 duodenal, 7 ampullary, 2 biliary) and intestinal-like (3 duodenal, 7 ampullary). The intestinal-like subgroup had a significantly improved RFS (p=0.03) and OS (p =0.04) compared to the biliary-like subgroup, after stratification by grade and stage. Unsupervised clustering of only ampullary and duodenal samples identified very similar good prognostic (4 duodenal, 5 ampullary) and bad prognostic groups (3 duodenal, 9 ampullary) with 3-year RFS 75% vs. 31%, p =0.05 and 3-year OS 100% vs. 27%, p =0.01. These 2 groups showed no statistically significant differences in adenoma (56% vs 25%), poor differentiation (11% vs 42%), T4 (33% vs 25%), N1 (67% vs 100%), MSI-high (22% vs 0%), KRAS mutations (33% vs 17%), or PI3K mutations (0% vs 17%). CDX-2 expression (100% vs 50%, p=.04) and intestinal histologic subtype (100% vs 0%, p <0.01) were more common in the good prognostic group. Conclusions: Gene expression analysis classifies ampullary carcinomas with duodenal carcinomas and identifies a good prognosis intestinal-like group and a poor prognosis biliary-like group. These findings have therapeutic implications. [Table: see text]
Correlation of DPC4 status with outcomes in pancreatic adenocarcinoma patients receiving adjuvant chemoradiation.
Authors: Herman J. M. , Hsu C. C. , Fishman E. K. , Hruban R. H. , Lin S. H. , Hacker-Prietz A. , Cameron J. L. , Laheru D. , Wolfgang C. L. , Iacobuzio-Donahue C. A. 
Published: February 2017

168 Background: In an autopsy series of patients with advanced pancreatic cancer (PCA), loss of DPC4 was highly correlated with disseminated metastasis. The purpose of this study was to determine if DPC4 gene status predicts for survival and patterns of recurrence following adjuvant (adj) chemoradiation (CRT). Methods: 101 patients who underwent surgery followed by adjuvant 5-FU or gemcitabine-based CRT were studied. Imaging studies were reviewed to assess patterns of recurrence and tumor tissue obtained to determine DPC4 immunolabeling status. DPC4 status was graded as intact or lost/mutated. Kaplan-Meier estimates were used to compute survival and Cox proportional hazards were used to compare risk factors. Results: Median overall (mOS) and progression-free survival (PFS) was 22.6 mos (95% CI 18.8 to 31.6) and 14.0 mos (95% CI 11.5 to 18.4). The mOS and 1-yr OS for patients with DPC4 intact vs. lost status was 21.9 mos (95% CI 16.8-32.4) and 78.4% vs. 22.6 mos (95% CI 18.4-32.6) and 78.2%, respectively (HR: 1.05, p=0.82). After adjusting for node, margin status, tumor grade, tumor size, and age, DPC4 status did not predict for mOS (RR 1.04, 95% CI: 0.62-1.74, p=0.89). Time to first progression at any site for PCA with DPC4 intact vs. lost status was 13.8 vs. 14.0 mos (p=0.79). Local recurrence was more common in PCA with DPC4 loss than with intact status (34.4% vs. 13.7%, p=0.012). There was no difference in the rates of distant recurrence in PCA with intact vs. loss of DPC4 expression (62.8% vs. 55.7%, p=0.45); however, DPC4 loss was more commonly associated with liver recurrence (27.9% vs. 19.6%, p=0.31). Conclusions: In pancreatic cancer patients receiving adj CRT, loss of DPC4 labeling in their resected PCA indicates a greater likelihood of developing local recurrence despite having received adj CRT. Efforts to improve loco-regional control are therefore needed for these patients following surgery and adj CRT. No significant financial relationships to disclose.
Long-term survivorship in pancreatic adenocarcinoma.
Authors: Gubens M. A. , Kunz P. L. , Fisher G. A. , Ford J. M. , Lichtensztajn D. , Clarke C. A. 
Published: February 2017

175 Background: Pancreatic cancer is one of the most lethal malignancies, with an estimated 5-year survival rate of 6%, often due to advanced stage at diagnosis. However, there is a small population of patients, even with metastatic disease, who survive 3 years and beyond. Methods: Cases of pancreatic adenocarcinoma diagnosed from 1998 to 2005 were identified in the California Cancer Registry. A multivariate logistic regression model was constructed to predict the outcome of 3+ year survival according to demographic, disease and treatment variables defined a priori: age, gender, race/ethnicity, socioeconomic status (SES), histology, stage, treatment within 4 months of diagnosis (surgery, chemotherapy, and/or radiation), prior cancer history, and treatment at an academic hospital. Results: Among 54,475 cases of pancreatic cancer with ≥3 years of follow-up data available, median survival was 3.5 months. 2,855 patients (5.2%) survived at least 3 years, of whom 19% had remote stage disease at diagnosis. On multivariate analysis, advanced age was associated with decreased odds of long-term survival (p<0.01). By race, Asian/Pacific Islanders (odds ratio (OR) 1.76, p<0.01), Hispanics (OR 1.29, p=0.01) and non-Hispanic blacks (OR 1.24, p=0.14) were more likely to be long-term survivors than non-Hispanic whites. There was a gradient toward increased long- term survival for patients with higher SES (OR 1.49 for highest vs. lowest quintile, p<0.01). Mucinous tumors were associated with higher long-term survival than other adenocarcinomas (OR 2.21, p<0.01). Localized (OR 6.82) and regional stage disease (OR 2.61) showed more long-term survival than remote stage disease, both p<0.01. Surgery (OR 8.20, p<0.01), chemotherapy (OR 1.44, p<0.01), and radiation therapy (OR 1.25, p=0.02) increased the odds of long-term survival, as did treatment at an academic hospital (OR 1.54, p<0.01). Conclusions: In a well- characterized population-based registry with rigorous follow-up, we were able to identify a cohort of long-term survivors of pancreatic adenocarcinoma as well as factors associated with their exceptional survival. Planned future work with this cohort includes case-control studies making use of tumor and germline specimens, as well as survivorship research. No significant financial relationships to disclose.
The association between diabetes mellitus and HCC: Noise or real? A meta-analysis of epidemiologic evidence.
Authors: Janarthanan S. , Ditah I. C. , Tageja N. , Kutait A. 
Published: February 2017

184 Background: Diabetes mellitus (DM) has been linked to an increase in the incidence of hepatocellular carcinoma (HCC). However, these studies have yielded controversial findings. This study evaluates the association between DM and risk of HCC in a meta-analysis. Methods: Two investigators independently conducted a search of studies on the association between DM and HCC from January 1970 through August 2010 on Medline. Identified articles were manually reviewed for additional references. Only full articles that provided risk estimates for the association were selected. The most adjusted risk estimates were abstracted and synthesized using the random-effects model. A stratified analysis by study design and study region has also been done. All studies were evaluated for publication bias before analysis. Results: A total of 35 studies, 20 case-control and 15cohort studies, were eligible for analysis. The overall summary risk ratio for HCC in DM was 1.60 (95% CI 1.49, 1.70; p<0.001). Among the case-control and cohort studies, the pooled risk estimate was 1.33 (95% CI 1.21, 1.46; p<0.001) and 2.24 (2.05, 2.44; p<0.001) respectively. By geographic location, the association remained significant among the European (15) and U.S. (10) based studies with risk ratios of 2.7 (95% CI 2.37, 3.05; p<0.001) and 1.58 (95% CI 1.45, 1.7) respectively. However, among the Japanese (10) based studies there was a nonsignificant 3% reduction in the risk of HCC (RR 0.97; 95% CI 0.71, 1.24; p>0.05). There was no evidence of publication bias among the studies included. Conclusions: The evidence in support of DM as an independent risk factor for HCC remains unclear. Though not significant, the finding among the Japanese based populations raises concerns over the potential role of environmental and/or genetic factors in the observed association. Further studies with great attention to potential confounders are warranted to definitively define the association between DM and HCC. No significant financial relationships to disclose.
Prognostic impact of immunohistochemical expression of Ki-67 in patients with advanced gastric cancer who underwent curative resection.
Authors: Sym S. , Hong J. , Cho E. , Lee W. , Chung M. , Ha S. , Park Y. , Park J. , Lee J. , Shin D. 
Published: February 2017

19 Background: Ki-67, tumor proliferation marker, is an important prognostic factor in a variety of cancers. In the present study, we investigated the prognostic value of immunoexpression of Ki-67 in patient with gastric cancer who underwent curative resection. Methods: We retrospectively analyzed 241 patients who had undergone curative gastrectomy at Gachon University Gil Hospital between January 2008 and July 2009. Ki-67 proliferation index (PI) by immunohistochemistry on formalin-fixed, paraffin-embedded material and the other clinicopathologic variables were evaluated by univariate and mulvariate analysis. Results: The median follow-up from surgery was 12 months (range, 0.5-26.7 months) and mean recurrence-free survival was 23 months (95% confidence interval, 21.8-24.1 months). The mean Ki-67 PI was 40% (range, 5-90%). No significant correlation was found between Ki-67 PI and other clinicopathologic variables including histologic grade and pathologic TNM (pTNM) stage. Univariate analysis revealed that significant prognostic factors of recurrence-free survival included age, preoperative serum albumin, pre-operative hemoglobin, surgery type, pTNM, histologic grade, lymphatic vessel invasion, peri-neural invasion, and Ki-67 PI. In the multivariate analysis besides pTNM (p=0.046), lymphatic vessel invasion (p=0.024), and surgery type (p=0.047), Ki-67 PI (p=0.005) also remained as an independent prognostic factor of recurrence, whereas the other factors lost its prognostic value. Conclusions: Our results suggest that high Ki-67 PI is independent, poor prognostic factor of recurrence in patient with gastric cancer who underwent curative resection. No significant financial relationships to disclose.
Hepatitis C as a predictor of treatment outcome in patients with hepatocellular carcinoma treated with the retinoid derivative, TAC-101.
Authors: Khanijow V. , Kaseb A. O. , Hassan M. , Machicao V. I. , Hassabo H. M. , Abbruzzese J. L. 
Published: February 2017

200 Background: Most cases of HCC occur in the setting of cirrhosis secondary to alcohol abuse and hepatitis C, in the United States and Europe. Furthermore, recent data from phase III trials of sorafenib showed better survival in patients with HCV-related HCC. Animal studies suggested that TAC 101 regulates the transcription factor activated protein-1, which is constitutively activated by HCV core protein and contributes to hepatocarcinogenesis in persistent HCV infection. We hypothesized that prognostic impact of HCV-related HCC would be more pronounced in patients treated with TAC 101. Methods: This retrospective analysis included 105 patients treated in 3 clinical trials: TAC-101 (n=27), bevacizumab and erlotinib (n=48), and erlotinib alone (n=30) conducted at The University of Texas M. D. Anderson Cancer Center. Univariate and multivariate Cox regression was performed to estimate the adjusted hazard ratio (HR). Results: HCV was present in 35 (33%) patients. Multivariate survival analyses incorporating age, sex, HBV status, α-fetoprotein level, Child-Pugh classification, CLIP score, and BCLC staging did not identify a significant impact of HCV on OS or PFS. However, in patients who received TAC- 101, the presence of HCV was associated with a significantly reduced risk of disease progression (HR: 0.47, 95% CI:0.24-0.90, p= 0.024). Conclusions: These results indicate a possible beneficial interaction between HCV-related HCC and treatment with the retinoid derivative, TAC-101. HCV infection could be useful as a surrogate biomarker of the therapeutic efficacy of TAC-101. Further research is warranted to study the potential role of TAC 101 in HCV-related HCC patients. No significant financial relationships to disclose.
Effect of combination radioimmunotherapy (RAIT) and chemoimmunotherapy on therapeutic response and toxicity in xenograft models of human pancreatic carcinoma: First experimental studies.
Authors: Sharkey R. M. , Karacay H. , Govindan S. V. , Moon S. , Mostafa A. , Goldenberg D. M. 
Published: February 2017

206 Background: Preclinical and early clinical data with RAIT involving a 90Y-labeled antibody to a pancreatic mucin antigen (hPAM4, clivatuzumab tetraxetan) have shown promising therapeutic activity in combination with gemcitabine. Selective targeting of therapeutic drugs using antibody-drug conjugates (ADC) might be useful in pancreatic cancer therapy. Methods: ADCs composed of SN-38 coupled to an internalizing anti-TROP-2 antibody, an antigen found on many epithelial cancers, or to the non-internalizing anti-mucin humanized IgG, were prepared (6 SN-38/IgG). Nude mice bearing s.c. Capan-1 or BxPC3 xenografts (∼0.35 cm3) were given multiple ADC doses (twice weekly, 4 weeks) or appropriate controls of a non-targeting IgG-SN-38 conjugate or irinotecan. Other groups of animals were treated with the ADC conjugates and RAIT, using RAIT at 60% and 100% of its MTD. The endpoint was time to progress to 3.0 cm3 (TTP), with animals monitored up to 22 weeks. Results: ADCs alone were each able to inhibit tumor growth significantly compared to untreated animals. The specificity of the effect was a dose-dependent and related to antigen saturation at higher doses. When ADC was combined with RAIT, TTP improved significantly and more animals were tumor-free. An effective ADC dose could be combined even with RAIT given at its MTD, achieving enhanced efficacy with minimal additional toxicity. ADC + RAIT treatments were best when RAIT was given 1-2 weeks before, the same day, or within 1 week after the ADC treatment, but delaying RAIT for 2 weeks after ADC treatment reduced efficacy. The same anti-pancreatic mucin antibody, hPAM4, could be used in the combination treatment both as RAIT and as an ADC without losing effectiveness. Conclusions: These studies show the feasibility of using ADC for the treatment of pancreatic cancer, and for combining antibody drug- and radionuclide-targeted therapeutics for improved efficacy with minimal toxicity. Supported in part from NCI grant R01 CA115755. [Table: see text]
Study of genotypic variations and protein expression of the xCT subunit of cystine/glutamate transporter in pancreatic cancer.
Authors: Huang T. J. , Li D. , Li Y. , Kar S. P. , Krishnan S. , Abbruzzese J. L. , Wolff R. A. , Javle M. M. 
Published: February 2017

210 Background: The plasma membrane xCT cystine-specific subunit of the cystine/glutamate transporter contributes to chemotherapy resistance in pancreatic cancer by regulating intracellular glutathione levels and protecting cancer cells against oxidative stress. We previously noted that the rs7674870 single nucleotide polymorphism (SNP) of xCT correlated with overall survival in pancreatic cancer and may be predictive of platinum resistance. There are no data regarding xCT protein expression in pancreatic cancer or the functional significance of this SNP. Methods: Paraffin-embedded core and surgical biopsy tumor specimens from 49 patients with metastatic pancreatic adenocarcinoma were analyzed by immunohistochemistry (IHC) using an xCT specific antibody (Novus Biologicals). xCT protein IHC expression scores (product of intensity and percentage of staining cells) were analyzed in relation to overall survival and genotype of the patients using the one factor ANOVA test, Kaplan-Meier plot, log-rank test, and Cox regression analysis. Overall survival was measured from the date of diagnosis to the date of death or last follow-up. Results: Positive xCT expression was detected in 38 (78%) of the 49 samples, and 9 (18%) patients had high levels of expression. High xCT expression was associated with lower overall survival as compared with low expression (5.1 months versus 8.8 months; p = 0.119). In a multivariate Cox regression model with adjustment for prognostic parameters of age, sex, performance status and CA19-9 level, high xCT expression was associated with a 2.1-fold increased risk of death (p = 0.096). Performance status also correlated with overall survival (p = 0.027). Preliminary analysis on the genotype-phenotype association (n = 12) indicated that xCT expression was higher with the TT genotype than the TC/CC genotype (p = 0.115), which is consistent with the previous observation that the TT genotype was associated with reduced survival. Conclusions: These data provide supporting evidence for a possible role of cystine/glutamate transporter xCT subunit in pancreatic cancer progression and survival. Further pharmacogenomic and clinicopathologic studies are ongoing. No significant financial relationships to disclose.