bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endoscopic and endosonographic staging in the management of cancer of the stomach and the esophagogastric junction.
Authors: Töppler G. , Röper H. , Cameron S. , Füzesi L. , Beham A. , Ramadori G. 
Published: February 2017

140 Background: Staging of the primary tumor in patients with advanced adenocarcinoma of the stomach or the esophagogastric junction under chemotherapy is not generally recommended [ESMO clinical recommendations; Ann Oncol 2009]. RECIST criteria do not detect local tumor regression adequately. Standards for endoscopic staging throughout therapy have not yet been established. Methods: Here we report on20 consecutive patients with locally advanced esophago or gastric adenocarcinoma which were treated with EOX or EOF (epirubicin, oxaliplatin, capecitabine or 5-FU). After two cycles of chemotherapy, therapeutic efficacy was assessed by gastroscopy (EGD), endosonography (EUS), ultrasonography (US) and CT-scan. EGD staging criteria included luminal occlusion, the aboral length of tumor involvement, tumor exulceration, formation of polypoid tissue or superficial ulcers, and gut motility. EUS-staging criteria included uT-staging of the different layers of the esophagogastric wall as well as of the adjacent lymph-nodes. Surgery was then performed within 2 to 4 weeks after the end of the third chemotherapy cycle. Results: In all patients, an early response to chemotherapy was observed by EGD and EUS, including regression of tumor size (length and depth), and appearance: former exulcerative tissue became rather polypoid and less vulnerable, and motility was regained in areas were tumor regression was observed. For the assessment of local tumor behaviour under chemotherapy, CT-scan was of limited help, as it was only able to monitor lymphadenopathy. Only in 3/20 cases there was a concordance between the EUS and CT-scan, as verified by histopathological review of the surgical specimen. Conclusions: EGD and EUS monitor early tumor response of the primary to chemotherapy adequately in all our cases of locally advanced esophago or gastric adenocarcinoma. Endoscopic measures are helpful for the assessment of early treatment response, and might help to direct therapeutic strategies. No significant financial relationships to disclose.
A comparison of surgical resection for distal esophageal, gastroesophageal junction, and proximal gastric cancers in the Memphis metropolitan area (MMA).
Authors: Evangelist M. C. , Orr W. S. , Ul-Haq M. , Farooq A. , Khattak A. , Denbo J. , Mahmoud A. , Dilawari R. A. , Sachdev J. C. , Osarogiagbon R. U. 
Published: February 2017

147 Background: The incidence of distal esophageal (DE) and gastroesophageal junction (GEJ) tumors has increased rapidly in recent decades. They are often included in gastric cancer trials. The 7th AJCC staging has reclassified tumors of the DE, GEJ, and proximal stomach (PS) as esophageal cancers. We compared the historical management of these tumors in our community. Methods: Review of all curative-intent DE, GEJ, and PS cancer resections at two healthcare institutions in the MMA from 1999-2008. Results: Seventy patients were identified (Table). Males predominated. The histology was adenocarcinoma in 48% of DE, 91% of GEJ, and 100% of PS cancers. Preoperative endoscopic ultrasound (EUS) was performed in 10% of DE, 6% of GEJ, and 7% of PS patients. Neoadjuvant therapy was given to 29% of DE, 35% of GEJ and 0% of PS patients. R0 resection rates were similiar. Fewer DE and GEJ patients had up to 15 lymph nodes removed, yet lymph node metastasis was identified in 52% and 35% respectively, compared to 20% of PS patients (Table). Five-year survival rates were numerically higher in the DE and GEJ patients. Conclusions: We identified differences in DE, GEJ, and PS tumors in a community setting with respect to preoperative management and lymph node sampling. Reclassification of DE, GEJ, and PS tumors by the AJCC suggests these groups now be treated uniformly as esophageal cancers, a shift from previous management as gastric cancers. Further, prospective evaluation is needed to assess the patterns of management and outcomes in tumors of the DE, GEJ and PS. [Table: see text] No significant financial relationships to disclose.
Locally advanced esophageal cancer: Actual 5-year survival comparing neoadjuvant and adjuvant chemoradiation.
Authors: Davis C. S. , Johns J. R. , Abood G. J. , Baker T. A. , Zank D. , Nagda S. , Aranha G. V. , Godellas C. V. , Shoup M. 
Published: February 2017

149 Background: Patients undergoing esophagectomy for locally advanced esophageal cancer are often candidates for chemoradiotherapy (CRT). It is unclear if there is a survival advantage for CRT when administered in the neoadjuvant (NCRT) versus the adjuvant (ACRT) setting. We report a single institution experience with actual long-term follow-up of patients with resected esophageal cancer treated with NCRT or ACRT. Methods: Following IRB approval, a retrospective review of 123 patients undergoing Ivor-Lewis esophagectomy between January 1, 1990 through December 31, 2001 was conducted. Clinicopathologic variables were analyzed, and survival was determined from hospital records, the Social Security Death Index, and direct patient follow-up. All patients were followed for at least five years, and survival was assessed by Kaplan-Meier analysis. Results: Of the 123 patients, 65 had surgery alone for early esophageal cancer and were excluded from the analysis. Of the remaining 58, 31 received NCRT and 27 received ACRT. There was no difference between groups for length of operation, blood loss, or complication rate. With all patients having at least 5 years of follow-up, the overall 1-year survival was 65% and 67% (p=0.866), 3-year survival was 42% and 33% (p=0.508), and 5-year survival was 26% and 22% (p=0.755) for the NCRT and ACRT groups, respectively (Table 1). Among those in the NCRT group, patients with a complete or partial response (n=20) had an improved 1-year survival as compared to those with no response at all (n=11; p=0.025). However, this difference did not persist at 3 and 5-years (p=0.224 and p=0.896, respectively). Conclusions: In this study, all patients with locally advanced esophageal carcinoma who underwent Ivor-Lewis esophagectomy with either NCRT or ACRT were followed for at least 5 years. Not only was there no difference in perioperative morbidity or mortality, but the overall 5-year survival was almost identical between groups. Therefore, as NCRT may be better tolerated and more easily administered, we advocate its use over ACRT in those with locally advanced esophageal cancer. No significant financial relationships to disclose.
Everolimus in patients with advanced pancreatic neuroendocrine tumors (pNET): Updated results of a randomized, double-blind, placebo-controlled, multicenter phase III trial (RADIANT-3).
Authors: Shah M. H. , Ito T. , Lombard-Bohas C. , Wolin E. M. , Van Cutsem E. , Sachs C. , Winkler R. E. , Lincy J. , Hobday T. J. , Yao J. C. 
Published: February 2017

158 Background: There is an unmet medical need for effective treatments for patients with advanced pNET. Systemic therapies for advanced pNET are limited both by toxicity and efficacy. Everolimus, an oral mTOR inhibitor, has shown promising antitumor activity in 2 phase II studies, leading to further investigation in the largest phase III randomized controlled trial completed in pNET patients. Methods: Patients with advanced low- or intermediate-grade pNET were randomly assigned to everolimus 10 mg/d orally + best supportive care (BSC; n = 207) or placebo + BSC (n = 203). Long-acting somatostatin analogs (SSAs) were permitted as BSC during the study. The primary endpoint was progression free survival (PFS). At progression (RECIST), patients could be unblinded and those randomly assigned to placebo were offered open-label everolimus. Results: Compared with placebo, everolimus reduced the risk of progression by 65% and increased median PFS by more than 6 months, from 4.6 to 11.0 months (HR = 0.35; 95% CI: 0.27-0.45; p < 0.0001), by investigator review (primary endpoint). Median PFS by central review was consistent (HR = 0.34; 95% CI: 0.26 to 0.44; p < 0.001] in favor of everolimus. Eighteen-month PFS estimates were 34% for everolimus (95% CI: 26-43) vs 9% (95% CI: 4-16) for placebo. Everolimus demonstrated a significant PFS benefit across all patient subgroups according to baseline characteristics and prior SSA use. Prior SSA use was 49% in the everolimus arm and 50% in the placebo arm. Updated analyses of the impact of concomitant SSA will be reported. The most common drug-related adverse events were stomatitis, rash, diarrhea, fatigue, and infections (primarily upper respiratory); most were grade 1 or 2. Stomatitis (6.9% vs 0%), anemia (6% vs 0%), and hyperglycemia (5% vs 2%) were the most common grade 3-4 events. Conclusions: Everolimus significantly prolonged PFS compared with placebo in patients with advanced pNET in this large phase III clinical trial. This benefit was seen across all patient subgroups. Treatment resulted in a significant 6.4-month prolongation in median PFS. Everolimus had an acceptable and predictable safety profile. [Table: see text]
Influence of underlying liver disease on response to sorafenib in patients with advanced hepatocellular carcinoma (HCC).
Authors: Bouattour M. , Faivre S. J. , Dreyer C. , Paradis V. , Raymond E. 
Published: February 2017

172 Background: Based on SHARP and Asia-Pacific trials, sorafenib is the first active therapy registered in advanced-stage HCC. The clinical benefit of sorafanib was not evaluated according to underlying liver disease. We aim to evalute results of sorafenib in specific subgroups of patients with various etiology of underlying liver disease. Methods: Between Jan 2006 and Sep 2009, patients with advanced HCC treated with sorafenib in our institution were analyzed. Response evaluated by RECIST criteria, overall survival (OS) and time to progression (TTP) were assessed in each subgroup according to the etiology of liver disease. Results: At the time of analysis, 134 patients were registered. Median age was 63.4 years (range 34–85) and a majority of patients were male (80%). Diagnosis of HCC was pathologically proven in 81% of cases. Patients were classified BCLC stage B and C in 25% and 75%, respectively. Etiology of underlying liver disease was hepatitis B, hepatitis C, alcohol consumption, and NASH in 17%, 25%, 32%, and 13%, respectively (others etiologies in 13% of cases). Demographic characteristics, Child-Pugh class and BCLC tumor stage, and prior therapy were similar for each subgroup. Overall duration of sorafenib treatment was comparable in all subgroups. Among 101 patients evaluable, only two had a partial response (2 %), and median OS was 9.5 months (95% CI: 7.35-11.67). Median TTP was significantly shorter in patient with hepatitis B compared with those with hepatitis C infection (4.4 and 7.3 months respectively; p: 0.036). This difference was not observed in patients with alcohol consumption compared to those with NASH (6.4 vs. 5.2 months; p=0.7). Median OS in patients with hepatitis C infection was 8.4 months and 6.1 months in those with hepatitis B infection (p value: 0.7). No significant difference was observed in patients with alcohol abuse compared with those with NASH (14.2 and 9.9 months respectively; p: 0.72). Conclusions: Overall, clinical benefit of sorafenib does not appear to be influenced by liver disease etiology. However, in patients infected with hepatitis B, progression under sorafenib seems to occur earlier, suggesting a possible role of hepatitis B chronic disease on the outcome. No significant financial relationships to disclose.
Use of endoscopic ultrasound scoring to estimate the malignant potential of branch duct type intraductal papillary-mucinous neoplasms of the pancreas.
Authors: Lee S. , Cho J. Y. 
Published: February 2017

182 Background: Intraductal papillary-mucinous neoplasms (IPMNs) of the pancreas are characterized by intraductal papillary epithelial growth, mucin hypersecretion, and cystic dilation of main or branch pancreatic ducts. However, it is still difficult to differentiate between benign and malignant, when it only involves the branch duct. The purpose of this study was to evaluate the role of endoscopic ultrasound (EUS) scoring in predicting malignancy in branch-duct type IPMNs, thus providing a convenient guideline to a clinician before considering surgical resection. Methods: We retrospectively reviewed all patients between Dec 1997 and April 2010 who underwent diagnostic and/or preoperative EUS for IPMNs. Borderline malignancy and invasive carcinoma were defined as a malignancy. Results: Of the 32 patients (mean age, 62 years), 13 male and 19 female were identified. Twelve people underwent operation, and there were 23 benign cases, and 9 malignant cases (borderline, n=6; invasive carcinoma, n=3). Among the six parameters (age, cyst size, mural nodule, associated main pancreatic duct dilation, patulous opening, thick septum) that have been known as important parameters for predicting malignancy in main duct type IPMNs, four were significant by Fisher's exact tests—namely, cyst size (p=.002), mural nodule (p =.003), associated main pancreatic duct dilation (p =.001), patulous opening (p =.05). In sizing the cysts, we scored 0 (cyst size ≤10 mm), 1 (11-20 mm), 2 (21-30 mm), 3 (>30 mm). In sizing the mural nodules, we scored 0 (no mural nodule), 1 (<5 mm), 2 (5-<10 mm), 3 (≥10 mm). For main pancreatic duct dilation, we scored 2, if there presented any associated main pancreatic duct dilation, and 0 if not. For the patulous opening, we scored 1 for present, 0 for not. Patients were dispersed from the highest score nine, to the lowest score zero. Mean score for benign cases was 2.47 (±1.59 SD), and 6.33 (±1.87 SD) for malignant cases (p =.001). Conclusions: We strongly recommend a radical surgery for patients scoring above 7(score 7, 8, 9), and a consideration of operation for scoring between 4 and 6, and careful follow up for scoring below 3. No significant financial relationships to disclose.
Effect of body mass index (BMI) on outcomes after surgical resection and adjuvant therapy for pancreatic cancer patients.
Authors: Khawaja M. R. , Zyromski N. , Yu M. , Cardenes H. R. , Schmidt C. M. , Sandusky G. , Howard T. J. , Chiorean E. G. 
Published: February 2017

185 Background: Obesity is one of the factors commonly associated with pancreatic cancer risk, but its prognostic role for survival is debatable. This study aimed to determine the role of BMI in treatment outcomes of pancreatic cancer patients (pts) undergoing surgical resection followed by adjuvant therapy. Methods: We retrospectively reviewed 165 consecutive pts with pancreatic cancer undergoing pancreaticoduodenectomy at Indiana University Hospital between 2004 and 2008. Fifty-three pts who received adjuvant treatment [gemcitabine alone (C-group): n=19; gemcitabine + radiotherapy (CRT-group): n=34] at our institution were included in the analysis. The Kaplan-Meier method was used to estimate the disease-free survival (DFS) and overall survival (OS); log-rank test was used to compare these outcomes between BMI groups (normal 18.5-24.99 kg/m2 vs. overweight/obese ≥ 25 kg/m2). Results: The sample comprised 53 pts (28 males; median age 62 yrs) with a median follow-up of 18.6 months (mos). Thirty pts (56.6%) had their BMIs recorded before the date of surgery, and 23 pts prior to starting adjuvant therapy. Two (3.8%) pts were underweight, 21 (39.6%) had a normal BMI and 30 (56.6%) were overweight/obese. There was no statistically significant difference in the median DFS of obese/overweight and normal BMI pts irrespective of adjuvant therapy (C or CRT) (14.47 vs. 11.80 mos; p= 0.111). Obese/overweight pts had a better median OS [25.2 vs. 14.6 mos; p=0.045 overall (25.7 vs. 16.9 mos; p= 0.143 for the CRT-group and 17.3 vs. 13.4 mos; p= 0.050 for the C-group)], 1-year survival [96.7% vs. 61.9%; p < 0.0001 overall (95% vs. 64.3%; p= 0.001 for the CRT-group, and 90% vs. 57.1%; p=0.016 with C)], and 2-year survival [52.6% vs. 25.4%; p < 0.0001 overall (60.0% vs. 30.0%; p=0.0001 for the CRT-group and 37.5% vs. 14.3%; p=0.0002 for the C-group)] than patients with normal BMI. Conclusions: In our experience, overweight/obese pts undergoing surgery followed by adjuvant therapy have better survival rates than patients with normal BMI. [Table: see text] No significant financial relationships to disclose.
Extrapancreatic tumors in intraductal papillary mucinous neoplasm of the pancreas.
Authors: Park Y. J. , Lee S. 
Published: February 2017

189 Background: Intraductal papillary mucinous neoplasm (IPMN) of the pancreas has a favorable prognosis, but seems to be associated with a high incidence of extrapancreatic tumors. The purpose of this study was to evaluate the incidence and clinicopathologic features of extrapancreatic tumors associated with IPMN compared with pancreas cancer. Methods: Thirty-seven patients with IPMN of the pancreas and eighty-four patients with pancreas cancer, confirmed by surgical resection and typical findings of endoscopic ultrasonography and CT imaging between October 1, 1998, and August 31, 2009, were included. All pancreas cancers were diagnosed with surgical resection and biopsy. These patients were examined for the development of extrapancreatic tumors. Results: Of 37 patients with IPMN, 14 (38%) had 18 extrapancreatic tumors, and 10 (27%) had 13 extrapancreatic malignancies. Five, six, and two extrapancreatic malignancies had been diagnosed before, during, and after the diagnosis of IPMN. Gastric adenocarcinoma (3 patients, 23%) and colorectal carcinoma (3 patients, 23%) were the most common neoplasms. Other extrapancreatic tumors included lung cancer (n=2), prostatic cancer (n=1), renal cell carcinoma (n=1), cholangiocellular carcinoma (n=1), urinary bladder cancer (n=1), and gallbladder cancer (n=1), respectively. As benign tumor, there were two gallbladder adenoma, one gastric adenoma, one colonic adenoma and one benign ovarian cystic neoplasm, respectively. On the other side, of 84 patients with pancreas cancer, 9 (10%) had 9 extrapancreatic tumors and 2 (2%) had extrapancreatic malignancies which were stomach cancer (n=1, 1%) and breast cancer (n=1, 1%) respectively. As benign tumor, there were colon adenoma (n=3), hepatic hemangioma (n=2), gastric adenoma (n=1), and uterine myoma (n=1). Conclusions: IPMN is associated with high incidence of extrapancreatic tumors, particularly gastric and colorectal neoplasm but pancreas cancer did not show associations with extrapancreatic tumor. Upper gastrointestinal endoscopy and colonoscopy should be done, and systemic surveillance for the possible occurrence of other tumors may allow early detection of extrapancreatic tumor in patients with IPMN. No significant financial relationships to disclose.
An engineered anti-CA19-9 cys-diabody for PET imaging of pancreas cancer and targeting of polymerized liposomal nanoparticles.
Authors: Girgis M. D. , McCabe K. , Olafsen T. , Bergara F. , Kenanova V. , Federman N. , Wu A. , Tomlinson J. S. 
Published: February 2017

198 Background: Antibody-based therapeutics is a rapidly growing field. Small engineered antibody fragments, such as the cys-diabody demonstrate similar antigen affinity compared to the parental antibody but have a shorter serum half-life (4hrs) and possess the ability to be conjugated to nanoparticles. Our goal was to engineer an anti-CA19-9 cys-diabody fragment in hopes of imaging and targeting pancreatic cancer. Methods: The anti-CA19-9 cys-diabody was created by cloning the variable region of the parental antibody, engineering a C-terminus cysteine, expressing in NS0 cells followed by protein purification utilizing HPLC. Maleimide chemistry was used to conjugate the cys-diabody to PLNs through the engineered cysteine residues. Immunofluorescence and flow cytometry were used to evaluate targeting of cys-diabody and diabody conjugated PLNs to human pancreatic cancer cell lines. The cys-diabody was evaluated in a mouse xenograft model harboring CA19-9 positive (BxPC3) and negative (MiaPaca) tumors. The cys-diabody was radiolabeled with a positron emitter (I-124) and microPET/CT were performed after tail vein injection. Percent of injected dose per gram (%ID/g) of radioactivity was measured in blood and tumor to provide objective confirmation of the microPET images. Results: Immunofluorescence and flow cytometry showed specific binding of the anti-CA19-9 cys- diabody. Tumor xenograft imaging of the anti-CA19-9 cys-diabody demonstrated an average tumor:blood (%ID/g) ratio of 3.3 and positive:negative tumor ratio of 7.4. Successful conjugation of the cys-diabody to PLNs was indicated by immunofluorescence showing specific targeting of PLN-cys- diabody conjugate to human pancreatic cancer cells in vitro. Conclusions: Our results show that the anti-CA19.9 cys- diabody targets pancreatic cancer providing specific molecular imaging in tumor xenograft models. Furthermore, the PLN-cys-diabody conjugate targets human pancreatic cancer cells with the potential to deliver targeted treatment. Further studies evaluating the in vivo ability of the PLN-cys-diabody conjugate to target pancreatic cancer need to be performed. No significant financial relationships to disclose.
Association of excision repair cross-complementation group 1 (ERCC1) gene expression (GE) with outcome in stage II-III esophageal adenocarcinoma (EA) patients treated with preoperative platinum-based chemoradiation (CRT) in a phase II cooperative study (SWOG 0356).
Authors: Bohanes P. O. , Goldman B. H. , Benedetti J. , Blanke C. D. , Leichman L. P. , Iqbal S. , Thomas C. R. , Corless C. L. , Gold P. J. , Lenz H. 
Published: February 2017

2 Background: Preoperative platinum-based CRT for operable esophageal cancer has improved overall survival (OS) compared to surgery alone. The phase II SWOG 0356 trial designed to test oxaliplatin (OXP) plus infusion 5-fluorouracil (5-FU) and external beam radiation prior to surgery for potentially curable EA has produced promising centrally confirmed complete pathologic response (pCR) rate (28.3%). After surgery patients were given a second cycle of OXP and 5FU. 2-year OS was 54.2%. However, treatment efficacy may be significantly compromised as a result of interindividual variations. We tested whether intratumoral GE levels in drug metabolism (DPD, GSTPi, TS and TP) and DNA repair (ERCC1 and XPD) predicted clinical outcome (CO). We also tested whether specific pattern of 12 polymorphisms in 8 genes (drug metabolism (GSTP, MTHFR and TS) and DNA repair (ERCC1, RAD51, XPD, XRCC1 and XRCC3)) predicted CO. Methods: A total of 90 patients from the SWOG 0356 study were eligible for the molecular correlative study. mRNA was extracted from laser-capture-microdissected tumor tissue. After cDNA was prepared by reverse transcription, quantitation of the candidate genes and an internal reference gene (ß-actin) was performed using a fluorescence-based real-time detection method (TaqMan). Established GE cutoffs were tested (ERCC1 <1.7 x 10-3; TS <4.0 x 10-3). DNA was extracted from blood and genotyped using PCR-RFLP techniques. Results: In univariate analysis, we found ERCC1 GE levels to be significantly associated with progression-free survival (PFS) and OS. Patients with high ERCC1 GE levels had worse 2-year PFS (17 vs 67%, p=0.004) and 2-year OS (37 vs 72%, p=0.04) compared to low GE levels. ERCC1 GE levels were not associated with pCR. All the other GE levels tested did not show significant association with CO. None of the tested polymorphisms showed any association with CO. Conclusions: Our data suggest that GE levels of ERCC1 may help to identify patients with stage II-III EA likely to experience longer survival when treated with preoperative OXP-based CRT. No significant financial relationships to disclose.