bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of chemotherapy with cisplatin plus gemcitabine after failure of gemcitabine alone for unresectable or recurrent biliary tract cancer.
Authors: Kameda Ryo , Ando Tomoko , Kobayashi Satoshi , Ueno Makoto , Ohkawa Shinichi 
Published: February 2017

377 Background: As there was no standard chemotherapy for advanced biliary tract cancer before ABC-02, we had treated our patients with gemcitabine alone. However, recently cisplatin plus gemcitabine became standard as first line chemotherapy. We assessed the benefits of chemotherapy with cisplatin plus gemcitabine after failure of gemcitabine alone before ABC-02 era. Methods: We retrospectively examined the patients with advanced biliary tract cancer, who were treated with chemotherapy using cisplatin plus gemcitabine after failure of gemcitabine alone. The eligible patients had unresectable or recurrent biliary tract cancer, objective tumor progression after gemcitabine alone chemotherapy, adequate organ function including renal function and ECOG performance status (PS) 0-1. The treatment consisted of cisplatin (25 mg per square meter of body-surface area) plus gemcitabine (1000 mg per square meter) on days 1 and 8, every 3 weeks. Results: Between December 2010 and July 2011, 10 patients were enrolled. Their median age was 63 years, the male : female ratio was 8:2, intrahepatic bile ducts : gall bladder : extrahepatic bile duct 6:3:1, locally advanced : metastatic disease 1:9, PS0 : PS1 7:3. The objective response rate was 30%, and the tumor control rate was 60%. The median progression-free survival was 4.0 months (95% confidence interval (CI): 1.4-6.9 months) with median overall survival 6.4 months (95% CI: 3.7-7.6 months). Grade 3-4 toxicities were neutropenia (30%) and anemia (30%). Conclusions: Cisplatin plus gemcitabine can be an optional therapy for unresectable or recurrent biliary tract cancer after failure of gemcitabine alone.
Survival analysis of PETCAM: A multicenter randomized controlled trial of PET/CT versus no PET/CT for patients with resectable liver colorectal adenocarcinoma metastases.
Authors: Moulton Carol-anne , Levine Mark Norman , Law Calvin , Hart Richard , Ruo Leyo , Gu Chu-Shu , Hendler Aaron , Gulenchyn Karen Y. , Haider Masoom A. , Marcaccio Michael , Tandan Ved , Quan Douglas , Jalink Diederick , Fairfull Smith Robin , Luu Shelly , Greig Paul David , Husien Mohamed , Finch Terri , Julian Jim A , Gallinger Steven 
Published: February 2017

390 Background: An increasing proportion of patients with liver CAM are undergoing hepatic resection with curative intent. Detection of occult metastastic disease is important in this setting, and PET/CT is used to identify patients with either inoperable, or limited resectable extrahepatic disease not identified with conventional imaging. We recently reported the results related to the primary objective of PETCAM, a randomized trial for patients with resectable liver CAM, where 7.6% had a change in management based on PET/CT (ASCO 2011). As a secondary objective, we examined whether patients undergoing PET/CT derived a survival benefit, as they may be considered to be better selected. Methods: PETCAM was a multicenter trial with 404 subjects randomized 2:1 to receive PET/CT or no PET/CT once they were assessed by a hepatobiliary surgeon to have resectable CAM. Subjects were followed over 4 years for overall survival (OS). As well as the intervention, we considered the SUV, Fong Score and other baseline factors as predictors for OS. Results: After a median 2.8 years of follow-up, 107 of the 404 (26%) study subjects had died. The 270 PET/CT subjects [and the 245 of these who underwent surgery] showed no statistically significant survival advantage over the 134 No PET/CT subjects [123 who underwent surgery] with a hazard ratio (HR) of 0.85, 95% confidence interval (CI): 0.57 to 1.3; p=0.41 [HR=0.81, 95% CI: 0.52 to 1.3; p=0.34]. Fong score was a strong predictor of OS for all patients (HR=1.4, 95% CI: 1.1 to 1.6), and for those who had surgery (HR=1.4, 95% CI, 1.1 to 1.7). In the PET/CT arm, SUV is strongly predictive of OS [HR per unit SUV increase =1.11, 95% CI: 1.05 to 1.18; p=0.0007. Conclusions: The addition of PET/CT had no effect on improving overall survival for patients who did or did not have hepatic resection for CAM. SUV is strongly predictive of survival for patients who had PET/CT, and Fong score is predictive of survival for all patients. The overall role of PET/CT in patients with resectable CAM appears limited and should be reevaluated in the current era of comparative effectiveness research and health care cost containment.
Circulating tumor cells as a possible prognostic tool in newly diagnosed nonmetastatic colorectal cancer?
Authors: Scholten Loes , Terstappen Leon W. M. M. , van der Palen Job , Mastboom Walter , Tibbe Arjan , Vermes Istvan , de Groot Marco 
Published: February 2017

395 Background: The presence of circulating tumor cells (CTC) is associated with poor prognosis in patients with metastatic colorectal cancer (CRC). The current study was conducted to determine if the presence of CTC prior to surgery in patients with newly diagnosed non-metastatic CRC can identify those patients at risk for disease recurrence. Methods: In a prospective single center study 180 patients with newly diagnosed non-disseminated CRC scheduled for surgery were enrolled and followed up for a median of 41 months. CTC were enumerated with the CellSearch System in 4 aliquots of 7.5 ml of peripheral blood before undergoing surgery. The control group consisted of sixty patients with benign tumors after surgery or colonoscopy. Results: ≥1 CTC/ 30ml of blood were detected in 9 (15%) persons of the control group, and in 41 (23%) CRC patients. From the 180 CRC patients, 44 developed recurrent disease (24%) and 38 patients (21%) died during follow up. Presence of CTC correlated with disease recurrence (p= 0.040) and death (p=0.006). Patients with CTC had a significantly decreased three year Disease Free Survival (DFS) and overall survival (OS) versus those without CTC (DFS 57%vs. 78%, p=0.018 and OS 70% vs. 80%, p=0.003%). Conclusions: Patients with stage I-III CRC with CTC before surgery have a significantly lower 3 years DFS and OS. These findings warrant further development of technology to increased the sensitivity and specificity of CTC detection for incorporation as prognostic marker along side Duke Stage to assess which patients need adjuvant treatment.
Epidemiology of rectal and small intestinal carcinoids: Two distinct tumors?
Authors: Taghavi Sharven , Jayarajan Senthil N. , Gaughan John P. , Willis Alliric Isaac 
Published: February 2017

399 Background: Gastrointestinal carcinoids (GIC) are most commonly found in the small intestines. However, in this era of screening colonoscopy, the incidence of rectal carcinoids (RC) is increasing. The aim of this study was to determine if differences exist between the two most common carcinoid tumors. Methods: Small intestinal and rectal cancers were reviewed from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute from 2000-2007. Factors reviewed included age, gender, ethnicity, and survival. Results: 12,931 small intestinal cancer tumors included 4,731 (36.6%) small intestinal carcinoids (SIC). 57,850 rectal cancer tumors included 4,550 (7.9%) RC. Comparing RC and SIC, RC presented at a younger age (56.2 vs. 64.5 years, p<0.001). RC were more common among women (50.6 vs. 47.0%, p<0.001). The ethnic distribution of SIC and RC were significantly different. SIC were more common among Whites (W) (76.0 vs. 51.0%) while RC were more common among each ethnic minority group: Blacks (B) (19.9 vs. 14.3%), Hispanics (H) (13.0 vs. 6.5%), Asians (A) (14.9 vs. 2.7%), and American Indians/Alaskans (AI) (1.1 vs. 0.4%); p<0.001. RC were more common than SIC among women for every ethnic group (percentage of patients who are women W 48.1 vs. 46.8%, B 59.3 vs. 50.6%, H 50.3 vs. 44.3%, A 46.5 vs. 41.1%, AI 72.0 vs. 47.1%), although this reached significance in only Black females (p=0.001). Mean survival was better in RC (93.4 vs. 65.8 months, p<0.001) by Kaplan-Meir analysis. Conclusions: This study demonstrates that SIC and RC are epidemiologically distinct tumors with different presentations and outcomes. Minority groups and females are more likely to present with RC. In addition, RC have better prognosis. Further studies are needed to investigate potential biological differences between these two tumors. [Table: see text]
How many biopsy fragments will be necessary to assess HER2 status for gastric cancer?
Authors: Shinozaki Eiji , Yamamoto Noriko , Chin Keisho , Ogura Mariko , Suenaga Mitsukuni , Matsusaka Satoshi , Mizunuma Nobuyuki , Yamaguchi Toshiharu , Hatake Kiyohiko 
Published: February 2017

40 Background: Trastuzumab (T) has been shown to confer overall survival benefit adding to capecitabine or 5-FU and CDDP in HER2-positive advanced gastric cancer in ToGA study. Data from the study, overexpression of HER2 according to immunohistochemistry (IHC) has been confirmed as potential responders. HER2 scoring is essential to decide the strategy of the personalized therapy with T. There are some differences in details to assess HER2 score between surgically resected materials and the biopsy fragments. Moreover it is not unclear how many biopsy fragments will be necessary to assess HER2 status. In this study we attemped to prove the optimal biopsy for HER2 scoring of gastric cancer. Methods: HER2 status was evaluated in 30 cases who were scored HER2 as 3+ and 44 cases who were selected for reference as HER2 score of 2+, 1+, 0 in previous tests of surgical specimens. In total 74 cases of 232 biopsies we investigated HER2 protein expression by IHC using HercepTest (DAKO) and assessed according to Gastric Cancer Scoring System. We analyzed the concordance of HER2 score between surgically specimens and the biopsy fragments. Results: Average numbers of biopsy fragments were 3.13(1-6)/case. The concordances between surgical specimens and biopsy specimens were 80.0% in HER2 3+ group of surgical specimens, 47.8% and 47.6% in HER2 2+ and 1+ or 0. The concordances per each biopsy were 73.5%, 34.7% and 69.1%, respectively. Both concordances in HER2 positive group were significant higher than those in HER 2 negative or equivocal groups. There were not statistic differences of the concordances between 3 or less fragments of biopsy and 4 or more. Conclusions: Our data suggested in HER2 score 3+ according to surgical materials, the concordance of HER2 scoring between surgically resected materials and the prior biopsy specimens was high and at least 3 fragments were seemed enough to assess whether IHC HER2 is positive in biopsy. Other hands in HER 2 negative or equivocal groups, the concordances were low.
Is elevated preoperative CEA level a significant predictor for decreased overall survival in patients with stage I to III rectal cancer?
Authors: Guller Ulrich , Koeberle Dieter , Warschkow Rene , Schmied Bruno , Cerny Thomas , Tarantino Ignazio 
Published: February 2017

403 Background: The objective of the present investigation was to assess whether elevated pre-operative CEA level represents a significant predictor for decreased overall survival in stage I-III rectal cancer patients. Methods: The present study is based on the colorectal database of the authors` hospital, one of the largest tertiary care centers of Switzerland. All patients undergoing a resection for stage I - III rectal cancer were consecutively included between 1991 and 2008. Average follow-up time was 50.3 months. The impact of pre-operative CEA on overall survival was assessed in Cox proportional hazard regression analyses after risk-adjusting for age, gender, body mass index, performance status, tumor stage, tumor distance from the anal verge, and neoadjuvant treatment. Pre-operative CEA levels were classified as normal (< 5 µg/liter) versus elevated (>5 µg/liter). All tests were two-sided, the level of statistical significance was set at 0.05. Results: Overall, 534 consecutive patients undergoing resection for stage I - III rectal cancer were included. Median age was 65 years (range 24 to 91 years), 62% of patients were male, median ASA was II (range I – IV), median body mass index 25.3 kg/m2 (range 15.4 to 44.9 kg/m2). Pre-operative CEA levels were elevated in 21.7% of all patients. After risk-adjusting in Cox proportional hazard regression analyses pre-operative CEA level (p<0.001; odds ratio: 2.020), distance from the anal verge <5cm (p<0.001, odds ratio: 2.434), older age (p<0.001; odds ratio: 1.069) and higher tumor stage (p=0.004, odds ratio: 2.003) were all significant predictors for poor overall survival. Forward- and backward variable selection including bootstrap analyses confirmed these results. Conclusions: The present investigation based on a large cohort of consecutive stage I – III rectal cancer patients provides compelling evidence that elevated pre-operative CEA level is a strong predictor of decreased overall survival even after risk-adjusting in Cox proportional hazard regression analyses. Therefore, it is crucial that pre-operative CEA is used as a prognostic factor in the pre-operative assessment of stage I-III rectal cancer patients.
Lymphatic metastasis in well-differentiated appendiceal cancer: Prognostic factors and associations with outcome.
Authors: Hill Joshua S. , Rafeeq Safia , Katz Matthew H.G. , Overman Michael J. , Lambert Laura A. , Royal Richard E. , Mansfield Paul F. , Fournier Keith F. 
Published: February 2017

406 Background: Well-differentiated appendiceal adenocarcinomas (WDAA) are rare tumors characterized by peritoneal spread. Lymph node metastasis can occur, yet the association between nodal spread and recurrence is poorly understood. Methods: A single institution retrospective review of patients seen between August 1993 and January 2010 with a pathologic diagnosis of WDAA who underwent colectomy was conducted. Patients with zero lymph nodes found during pathologic review were excluded. Parameters evaluated included demographics, presence of lymph node metastasis, completeness of cytoreduction and time to recurrence. Results: Of 688 patients with appendiceal neoplasms, 160 (23.3%) had WDAA. The mean age at diagnosis was 50.7 years and 81 (50.6%) were male. Median follow-up after diagnosis was 58.5 months. One hundred patients (62.5%) had regional or distant metastasis present at the time of colectomy. Seventy-eight (48.8%) colectomies were performed at outside institutions. The median number of nodes examined was 12. Twelve patients (7.5%) were found to have nodal metastasis. The rate of peritoneal metastasis did not correlate with the presence of nodal metastasis (node positive 9/12, 75% versus node negative 91/148, 61.5%; p=0.35). No difference in the ability to perform complete cytoreduction existed for those with and without nodal metastasis (66% versus 51% p=0.19). Examining patients with complete cytoreduction and ≥ 12 months of follow-up, there was an increased risk of recurrence among patients with lymphatic metastasis compared to those without (5/8, 62.5% versus 15/61, 24.6%; p=0.03). In this subset, median disease-free-survival in lymph node positive patients was 53 months compared to 109.1 months in patients without nodal metastasis (p=0.08). Conclusions: Patients with WDAA tumors have an overall favorable prognosis; however, patients with lymph node metastasis appear to have an increased risk of recurrence and apparent shortened disease free survival. Right colectomy may be warranted in this patient population.
Evaluation of the role of UGT1A1 genotype testing in colorectal cancer patients administered irinotecan and the occurence of grade 3 and 4 neutropenia.
Authors: Patel Sushma M. , Chan Jim , Hui Rita L. , Spence Michele M. 
Published: February 2017

412 Background: Irinotecan is metabolized primarily in the liver by the carboxylesterase enzyme to the SN-38 active metabolite and is then inactivated through conjugation by the UGT1A1 enzyme, a polymorphic enzyme. Individuals genotyped with the homozygous allele have an increased risk for grade 3 and 4 neutropenia. Methods: A retrospective cohort analysis was conducted in the Kaiser Permanente California regions. The study period was November 1, 2005 to July 1, 2010 and included patients that were 18 years of age or older, newly initiated on irinotecan for colorectal cancer and had no previous irinotecan therapy within six months of the initiation dose. Patients were excluded if they were enrolled in clinical trials, on granulocyte-colony stimulating factor prophylaxis, and genotype tested for UGT1A1 and subsequently not treated with irinotecan. Patients tested with the UGT1A1 assay were grouped according to their genotype results: wild-type, heterozygous, or homozygous*28. The incidence of grade 3 and 4 neutropenia were compared among patients tested for UGT1A1 variant alleles by their genotype results. Results: A total of 305 (28%) patients were tested with the UGT1A1 assay with a mean age of 62 (+/- 12) years, and 52% of the population female. There were 161 (53%) wild-type, 123 (40%) heterozygous, and 21 (7%) homozygous patients. The median irinotecan dose was 150 mg/m2 (124-180 mg/m2) and median number of irinotecan cycles were 6 (3-12). The wild-type, heterozygous, homozygous*28 population had a 21% (33/161), 24% (29/123), and 48% (10/21) rate of grade 3 and 4 neutropenia. When the homozygous*28 group was compared to the heterozygous and wild-type genotype the adjusted Cox Proportional Hazard was 3.05 (95% CI, 1.55-5.99), p = 0.001. The Kaplan-Meier Log Rank Test yielded a p-value of 0.002. Conclusions: The adjusted risk for homozygous genotyped patients was three times higher compared to the wild-type and heterozygous group for grade 3 and 4 neutropenia. Additional investigational studies examining the benefits of UGT1A1 genotyping as a prognostic test and further effect of dosage adjustments in UGT1A1*28 homozygous initiated on irinotecan therapy are needed.
A new strategy for the early detection of colorectal cancer recurrence.
Authors: Motamed-Khorasani Afsaneh , Small-Howard Andrea Lee , Etemadi Hooman 
Published: February 2017

416 Background: Several biological markers have been tested for colorectal cancer (CRC) including CEA; however, they are of limited use for recurrence diagnosis due to low sensitivity. Almost 50% of CRC cases experience recurrence and more than 50% of them have low values not detectable by CEA. Therefore, an effective marker for detection of recurrence will vastly increase the quality of life and survival rate. Onko-Sure is an FDA-cleared blood test that is used for the monitoring of treatment/recurrence of CRC. This ELISA assay measures the accumulation of Fibrin/Fibrinogen Degradation products in the serum using an antibody against the DR-70. The goal of this study was to determine whether the combined usage of DR-70 and CEA will improve the sensitivity for detecting recurrences. Methods: A total of 75 serum samples were retrospectively recruited through a serum bank in two arms including the confirmed healthy control (n=39) and biopsy-confirmed recurrent CRC (n=36) groups. For each patient, the serum sample was tested for DR-70 and CEA concentrations. Results: The results showed sensitivity of 75% and specificity of 58.97% for DR-70 and CEA combined. The cut points were calculated as 1.3ug/ml for DR-70, and 3 or 5ng/ml for CEA for non-smokers and smokers; respectively. For the combined analysis, if either CEA or DR-70 was positive, the test was considered positive and if both tests were negative, the result was considered negative. The sensitivity for the combined test was much better than that of each of the markers alone (35% higher than that of CEA). Conclusions: The combined usage of DR-70 and CEA in monitoring of CRC recurrence showed a significant clinical advantage in terms of sensitivity over each marker alone. Improvement in detection of recurrence has important implications to patient treatment options and prognosis. Should an IVD increase early detection of CRC recurrence when used adjunctively with other available diagnostic markers, the annual deaths due to CRC recurrence could be reduced due to the increase in early detection and the survival rate of those early detections.
Rapid screening of SNPs in metastatic colorectal cancer (mCRC) utilizing multiplex sequencing technology (Sequenom).
Authors: Maitra Radhashree , Nayak Jay B. , Basu-Mallick Atrayee , Sood Arjun , Augustine Titto A , Mariadason John , Reynolds David M , Goel Sanjay 
Published: February 2017

418 Background: Accurate and fast screening of mutations is essential for designing individualized therapy necessary and critical for efficient disease management and better patient outcome in mCRC. Detection of hotspots by gold standard direct sequencing (DS) is time consuming and cost ineffective. Pyrosequencing (PS) technique is rapid and precisely committed towards SNP detection. Recent introduction of high throughput multiplex PCR based extension on microarray (Sequenom, SEQ) offers a robust platform capable of detecting multiple SNPs simultaneously in a rapid and cost effective manner. The current study analyzes the concordance and efficacy of the cutting edge SEQ technique to the well established DS and PS methods. Methods: DNA isolated from 122 specimens from 76 mCRC patients were sequenced by all three methods. DS and PS were performed on 4 genes at 10 hotspots. SEQ multiplexing was performed on 31 hotspots in 19 genes by 4 multiplex reactions. Results: We were able to make "calls" for all samples by DS and PS. With the multiplex system, the “calls” rate was 97.8% of successful reactions. Using PS data as our standard in the assay we calculated the percent concordance of DS and SEQ. Futhermore SEQ offered a more accurate identification of the substituted nucleotide in Kras codon 12 as compared to PS. Conclusions: The multiplexing of PCR reactions offers an excellent advantage of high throughput with strong feasibility of analyzing several samples for multiple SNPs simultaneously. The concordance rate of > 90% when compared to PS along with the ability to analyze multiple samples/ hotspots plexed together in a time effective rapid mode provided a trifold advantage of the sequenom technology. It is therefore the next generation technology for rapid genetic evaluation of cancer patients. [Table: see text]
Incidental colonic 18F-FDG uptake in gastric cancer patients: Correlation with colonoscopic and histopathologic findings.
Authors: Song Kyo Young , Shim Jung Ho 
Published: February 2017

43 Background: The ability of integrated positron emission tomography and computed axial tomography (PET-CT) to detect synchronous colonic pathology in gastric cancer patients is not fully defined. Methods: Between Jan 2009 and July 2010, total 370 patients diagnosed as primary gastric cancer underwent curative resection in our institution. Among them 147 patients had taken PET-CT and colonoscopy preoperatively. The FDG uptake pattern were reviewed and classified as focal (showed foci of FDG uptake>3.5 SUV max), diffuse (showed FDG uptake<3.5 SUVmax without any foci of uptake) and absent uptake (showed no FDG uptake pattern). Patients with history of known colonic malignancy or colon surgery were excluded. Results: Among the 18 patients who had discovered as focal incidental FDG uptake in colon without any previous colonic pathology, in six patients, has revealed unexpected colonic adenocarcinoma. The mean SUVmax value of focal uptake group(Group A) is 7.3 (±2.3), for those six patients, it was 9.4 (±2.9,p=0.02). And in the diffuse uptake group, most common colonic pathology was tubular adenoma with low grade dysplasia following hyperplastic polyp. The age, gender and primary gastric cancer stage was not differed between the groups. Conclusions: In conclusion, the focal uptake pattern in colon on preoperative PET-CT in gastric cancer patients should be followed by colonoscopy evaluation for incidental significant colonic pathology even colon cancer. However, there was no cut off SUVmax value for the mandatory colonoscopy evaluation based on PET-CT.