bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene expression profile of genes-related canceration, invasion, or conversion for metastasis in patients with poorly differentiated adenocarcinoma treated by gastric ESD.
Authors: Kawanishi Natsuko , Azuma Mizutomo , Takeuchi Atsuko , Yamane Sakiko , Watanabe Akinori , Wada Takuya , Ishido Kenji , Yano Takafumi , Katada Chikatoshi , Tanabe Satoshi , Yoshida Tsutomu , Koizumi Wasaburo 
Published: January 2019

78 Background: We encounter some cases of early gastric cancer treated by endoscopic submucosal dissection (ESD) that are out of the indication criteria after pathologic diagnosis. These cases require additional treatments because of a risk of lymph node metastasis in Japanese Classification. So further prediction factors associated with lymph node metastasis is expected. We are focusing on poorly differentiated adenocarcinomas in early gastric cancer that we treated by ESD and used these tissues to characterize their gene expression profiles related to canceration, invasion or conversion for metastasis. Methods: We examined two cases of intramucosal carcinoma and three of submucosal infiltrating carcinoma histologically diagnosed as poorly differentiated adenocarcinoma after ESD. Those samples are separated five adjacent normal tissues (N), five tumor tissues in mucosal layer (M) and three tumor tissues in submucosal layer (SM) in total 13 lesions. Formalin-fixed, paraffin-embedded tissues were dissected by the laser-captured microdissection technique and were analyzed for targeted 158 gene expressions using a quantitative real-time polymerase chain reaction (PCR) using commercial PCR plate (profile PCR array of genes related to cancer stem cells and epithelial mesenchymal transition). Results: Among genes that elevated in the cancer tissues (M or SM) against the normal tissues, five gene expressions (DKK1, TIMP1, THY1, FN1, COL1A2) were tended to much higher in the submucosal layer compared to the mucosal layer (N < M < SM). When we compared tumor gene expressions in depth of M, three gene expressions (FZD7, ZEB 2, CD 44) are higher in the tumors with submucosal invasion compared to within mucosal layer. Conclusions: Poorly differentiated adenocarcinoma of stomach had high expression level in cancer-related genes even if it was intramucosal tumor. Some of these genes tended to increase as its depth of invasion and the presence of invasion of the SM. It suggested that the biopsy specimen could be a prediction factor of invasion from the surface of gastric cancer, but additional specimens and analysis are necessary to prove these findings.
Phase I clinical trials in refractory colorectal cancer (CRC): Do older adult patients benefit?
Authors: Arora Sukeshi Patel , Ketchum Norma S. , Gelfond Jonathan , Michalek Joel , Mahalingam Devalingam 
Published: January 2019

784 Background: Current clinical trial data are largely driven by younger participants, yet half the population diagnosed with CRC are 70+. Upon progression, many CRC patients (pts) with refractory cancer are referred to phase 1 clinical trials; however, tolerability and clinical benefit is unclear in the elderly. Given our robust phase 1 program, we assessed the efficacy and safety of early therapeutics in the elderly CRC pts. Methods: A historical cohort analysis included mCRC pts enrolled amongst 44 phase I trials from 3/2004 - 9/2012. Median Progression free survival (mPFS) and overall survival (mOS) were estimated from Kaplan-Meier curves and groups were statistically compared with the log rank test. The magnitude of association between dichotomous factors and survival was estimated with the hazard ratio (HR). Results: 139 pts, median age 59 (33-81), 70+ 16.5% (n = 23); KRAS mut 39.4 %. ≥3 prior lines of therapy 73.9 %; Prior EGFR-I 75.5% (100% of KRAS wt). Location: Right 20.9 %, Left 61.9 %, Transverse 4.3 %, Unknown 12.9 %. Phase I agents: VEGF I 19.4%, EGFR/Growth Factor I 9.3%. mOS for < 70 (n = 108) vs 70+ (n = 22): 6.5 vs 4.2 months (HR 1.88, p 0.007). mPFS for < 70 (n = 116) vs 70+ (n = 23): 2.0 months vs x 1.5 months (HR 1.73, P 0.03). There was not a statistical difference between < 70 versus 70+ in regards to dose cohort, number of cycles completed, or adverse events. Survival analysis in terms of risk factors in pts 70+ are in the Table below. Conclusions: Elderly CRC pts are underrepresented (16.5%) in phase 1 clinical trials and have worse survivals than non-elderly pts. Elderly CRC pts with liver and hematologic toxicities had a trend toward worse PFS but no OS. Phase I studies should incorporate prospective assessments to identify risk factors of morbidity and mortality in elderly CRC pts. [Table: see text]
Relevance of KRAS status in relation to clinical outcome of anti-VEGF-based therapy of metastatic disease in patients with right-sided primary colorectal cancer.
Authors: Obermannova Radka , Zdrazilova-Dubska Lenka , Hejduk Karel , Chloupkova Renata , Vocka Michal , Ostrizkova Lenka , Benscikova Beatric , Kiss Igor , Petruzelka Lubos 
Published: January 2019

785 Background: Right-sided location of primary colorectal carcinoma is associated with worse prognosis and predicts worse outcome of treatment of metastatic disease. Prognostic role of KRAS status in 1st-line treatment with anti-VEGF of mCRC remains controversial. We aim to study prognostic role of KRAS in the context of primary tumor location for anti-VEGF-based therapy of mCRC. Methods: Data from 3 national comprehensive cancer centers in the Czech Republic were collected prospectively from 01/2009 - 09/2015. A retrospective analysis of outcomes of 1059 pts with mCRC with known KRAS status was performed. Patients were treated with 1st-line bevacizumab (bev) plus FOLFOX or CapOx, irrespective of the KRAS status (all-RAS since 2015). The primary objective of our retrospective analysis was assessment of OS and PFS in right-sided primary tumors in connection with KRAS status. OS and PFS were calculated using the Kaplan-Meier method. Results: KRAS mutation was significantly more common in right- vs left-sided mCRC. Unlike in left-sided subgroup, both PFS and OS was poor in right-sided subgroup irrespective of KRAS status. Targeted therapy in subsequent lines of treatment was evenly spread among primary location subgroups. 769 (71.4%) patients were treated by CTx alone. Conclusions: Known KRAS status (Table) is not relevant for the treatment with 1st-line anti-VEGF plus CTx in righ-sided primary tumors. [Table: see text]
Plasma biomarker dynamics following ramucirumab treatment and survival analysis after ramucirumab treatment failure in patients with advanced gastric cancer.
Authors: Ota Yumiko , Wakatsuki Takeru , Mashima Tetsuo , Takahari Daisuke , Chin Keisho , Ichimura Takashi , Ogura Mariko , MATSUSHIMA TOMOHIRO , Osumi Hiroki , Nakayama Izuma , Shinozaki Eiji , Suenaga Mitsukuni , Kawata Naomi , Horiike Yuki , Seimiya Hiroyuki , Fujita Naoya , Yamaguchi Kensei 
Published: January 2019

79 Background: Ramucirumab (RAM) showed significantly improved survivals of gastric cancer in the second line with paclitaxel or single use. It is known that RAM causes pharmacodynamic changes of plasma VEGF-A family levels during treatment. However, its clinical significance is still unclear. The aim of this study is to reveal the changes of plasma biomarker levels until disease progression, and to examine associations between plasma biomarker levels at disease progression and survival after RAM treatment failure. Methods: Plasma samples were collected at three points: base line, day 8, and disease progression. Nine kinds of plasma biomarker related to angiogenesis: VEGF-A, C, D, PlGF, sVEGFR-1, 2, Neuropilin-1 (NRP1), Angiopietin-1, and SDF-1α, were measured by means of ELISA. The dynamics of plasma biomarkers were compared using the ANOVA. Patients were dichotomized by optimal cut-off value in each biomarker. Survival after RAM treatment failure was estimated by Kaplan-Maier methods and compared by log-rank test. Results: Plasma samples were collected from 21 patients. Median age was 67 y.o and female was dominant (57%). Plasma VEGF-A and PlGF levels sharply increased at day 8 and these higher plasma levels were sustained until disease progression: the median VEGF-A and PlGF levels at baseline, day 8, and disease progression were 20.2, 350.2, and 596.7 pg/ml for VEGF-A (p<0.001) and 10.5, 223.4, and 261.1 pg/ml for PlGF (p<0.001), respectively. Conversely, plasma NRP1 levels consistently decreased during treatment course: the median NRP1 levels at baseline, day 8, and disease progression were 444.3, 309.2, and 230.9 mg/ml (p=0.001). The median survival after disease progression was 3.1 months (95%CI 2.5-3.7). Patients with higher VEGF-A and NRP1 levels showed shorter survival with 4.5 vs. 0.9 months (HR 3.15 95%CI 1.6-6.4 p<0.001) for VEGF-A and 8.8 vs. 2.6 months (HR 2.92 95% CI 1.4-6.3 p=0.002) for NRP1. Conclusions: Our data suggest that not only a clue of mechanism of acquired resistance of RAM but necessity of new treatment strategy after RAM treatment failure. Further understanding of molecular correlates and clinical validation are warranted.
Laparoscopic versus open surgery for locally advanced rectal cancer following neoadjuvant chemoradiotherapy with S-1: Short- and long-term outcomes of multicenter prospective phase II trials.
Authors: Hara Takao , Akagi Tomonori , Empuku Shinichiro , Nakajima Kentaro , Kentaro Iwaki , Kai Seiichiro , Etoh Tsuyoshi , Takeuchi Yu , Tahara Koichiro , Matsumoto Toshifumi , Ishikawa Koichi , Bando Toshio , Mimori Koshi , Shiraishi Norio , Inomata Masafumi 
Published: January 2019

793 Background: We have reported the effectiveness of neoadjuvant radiotherapy (RT) combined with S-1 in terms of compliance and pathologic response for locally advanced rectal cancer. In the present study, we aimed to evaluate the safety and efficacy of laparoscopic surgery for locally advanced rectal cancer following neoadjuvant RT combined with S-1 in comparison with open surgery. Methods: Two multicenter prospective phase II trials were conducted (UMIN003396, UMIN003398). A total of 63 patients with locally advanced rectal cancer classified as T3-4, N0-3, and M0 were enrolled, and neoadjuvant RT combined with S-1 and total mesorectal excision with D3 lymphadenectomy was performed. Of these, 57 patients were analyzed and divided into a laparoscopic group (LAP, n = 43) and open group (OP, n = 14). We evaluated the short- and long-term outcomes of laparoscopic surgery compared with open surgery by univariate and multivariate analyses. Results: In the patient background, there were no significant differences between the two groups except that cases with T3 and N0 were significantly higher in the LAP compared with the OP. In the operative findings, operation time was longer (mean 447 min vs. 352 min, p = 0.007) and blood loss was lesser (median 220 ml vs. 485 ml, p = 0.033) in the LAP than those in the OP. Although there were no significant differences observed in the incidence of perioperative and late complications between the two groups, reoperation within 30 days was significantly less in the LAP compared with the OP (1 case vs. 5 cases, p = 0.0004). In the multivariate analysis, a distance of the tumor from anal verge within 3 cm was the independent risk factor for reoperation within 30 days. Furthermore, estimated 5-year disease-free survival (LAP 72 % vs. OP 73 %, p = 0.945) and 5-year overall survival (LAP 76 % vs. 75 %, p = 0.836) didn’t significantly differ between the two groups in the Kaplan–Meier curve. Conclusions: The findings of this study demonstrated that laparoscopic surgery for locally advanced rectal cancer following neoadjuvant RT combined with S-1 could be an optional procedure in terms of short- and long-term outcomes. Clinical trial information: UMIN000003396, UMIN000003398.
Efficacy of daikenchuto for the intestinal hypomotility after open abdominal surgery: A pooled analysis of three randomized controlled trials.
Authors: Kono Toru , Shimada Mitsuo , Nishi Masaaki , Morine Yuji , Yoshikawa Kozo , Katsuno Hidetoshi , Maeda Koutarou , Koeda Keisuke , Morita Satoshi , Watanabe Masahiko , Kusano Mitsuo , Sakamoto Junichi , Saji Shigetoyo , Sokuoka Hiroki , Ohtake Yuya , Sato Yasuto , Kanematsu Takashi , Kitajima Masaki 
Published: January 2019

801 Background: Postoperative intestinal hypomotility (IH) is very common after open abdominal (OAS) surgery. Although several advances have been made in medical therapy, very few recognized treatment or prevention methods are currently available. Daikenchuto (DKT), a traditional Japanese prescribed medicine, peripherally stimulates the neurogenic pathway, attempted to reduce postoperative IH in three exploratory randomized controlled trials (RCT). For further analysis of whether DKT accelerates IH recovery after scheduled OAS we conducted a pooled analysis of three RCTs. Methods: A pooled retrospective subset analysis of OAS patients with colon, liver, or gastric cancer in DKT RCTs was performed; RCTs were supported by the Japanese Foundation for Multidisciplinary Treatment of Cancer (JFMC). Among all patients enrolled and randomized in the three RCTs (JFMC project numbers 39-0902, 40-1001, and 42-1002), 740 patients who were eligible were included for the efficacy analysis. The modified intent-to-treat population was 410 patients, who did not have their bowel movement before the first meal; these patients were randomized to receive either 5 g DKT (n = 214) or placebo (n = 196) orally, three times a day for up to 12 days. The primary end point of each trial was the time from the end of the surgery (extubation) to the first bowel movement; this was assessed using survival analysis. Results: Compared with the placebo group, the time from the end of the surgery to the first bowel movement was accelerated in the DKT group (p = 0.004, hazard ratio;1.337 (95% CI 1.096-1.631)), with a difference of median 14.8 h. The tolerability profiles were similar in both the groups. Conclusions: Compared with the placebo, DKT was well tolerated, and it significantly accelerated IH recovery in patients who underwent OAS. Clinical trial information: UMIN000026292.
A retrospective cohort study evaluating the safety and efficacy of TAS-102 in patients with metastatic colorectal cancer (HGCSG1503): Analysis of tumor location.
Authors: Ogawa Kohei , Yuki Satoshi , Kawamoto Yasuyuki , Yagisawa Masataka , Harada Kazuaki , Okuda Hiroyuki , Furukawa Kouichi , Honda Takuya , Dazai Masayoshi , Kato Takashi , Sasaki Takahide , Shindo Yoshiaki , Ota Sakae , Sato Atsushi , Ueda Akira , Kato Sosuke , Fukunaga Akira , Nagai Hikari , Sakata Yuh , Komatsu Yoshito 
Published: January 2019

802 Background: Recent analysis from some clinical trials showed that primary tumor location in patients with metastatic colorectal cancer (mCRC) correlates with different outcome. The J003 trial and RECOURSE trial revealed the safety and efficacy of TAS-102 for patients with metastatic colorectal cancer (mCRC). In March 2014, TAS-102 was approved in Japan. However, the impact of primary tumor location in mCRC treated TAS-102 is unclear. Methods: We retrospectively analyzed the clinical data of 411 patients who received TAS-102 in the multi-institutional retrospective study (HGCSG1503). This study was analyzed by CTCAE v4.0 for adverse events (AEs), RECIST v1.1 for response rate (RR)/disease control rate (DCR). To compare with right-sided tumor (RT : Cecum to Transverse colon) and left-sided tumor (LT : Descending colon to Rectum), Fisher’s exact test was used in terms of patient characteristics, AE, RR/DCR, and Log-rank test was used in terms of TTF, PFS and OS. Results: Patients with RT and LT were 137 and 274, respectively. The patient’ characteristics between RT and LT were generally balanced except for Gender (Male ; 45.3% in RT, 56.9% in LT ; p = 0.028), Age (Median ; 68.0y in RT, 66.0y in LT ; p = 0.007), Liver metastasis (70.8% in RT, 57.7% in LT ; p = 0.010), Peritoneal metastasis (47.4% in RT, 24.5% in LT ; p < 0.001), and KRAS exon2 status (wild ; 40.5% in RT, 59.0% in LT ; p = 0.001). The AEs between RT and LT were also generally balanced except for Platelet count decreased (≥Grade 3 ; 8.8% in RT, 2.9% in LT ; p = 0.014). RR/DCR were 0/30.9% in the RT and 0.8/40.3% in the LT (p = 1.000/0.088). Median TTF was 2.2 months in the RT and 2.1 months in the LT (HR 0.962, p = 0.712). Median PFS was 2.2 months in the RT and 2.2 months in the LT (HR 1.024, p = 0.826). Median OS was 7.3 months in the RT and 7.3 months in the LT (HR 1.114, p = 0.327). Conclusions: As a result of this analysis, efficacy was no significant difference between RT and LT for patients who were administered TAS-102 in the real-world clinical practice. This analysis suggested TAS-102 benefits mCRC patients regardless of primary tumor location. Clinical trial information: 000020551.
Predictors of rectal cancer resection at high-volume hospitals among Medicare patients.
Authors: Charlton Mary E. , Chioreso Catherine , Gribovskaja-Rupp Irena , Lin Chi , Ward Marcia M , Lynch Charles F , Chrischilles Elizabeth A. 
Published: January 2019

808 Background: Hospitals that perform high volumes of rectal cancer resections achieve superior rates of sphincter preservation and survival compared to those that do not, but many rectal cancer resections are still performed in low-volume centers. We aimed to determine the patient, provider and pathway characteristics associated with receipt of surgery from high-volume hospitals. Methods: Patient and provider characteristics were extracted from the SEER-Medicare database for Medicare beneficiaries (age 66+) with stage II/III rectal adenocarcinoma diagnosed 2007-2011 who received rectal cancer-directed surgery. Hospitals were divided into quartiles by volume of rectal cancer resections, and were also classified by NCI cancer center designation. Results: 2056 patients were included, and 57% received surgery in a high-volume hospital or NCI-designated center. Those residing in census tracts classified as rural and having higher median incomes, lower poverty, and higher levels of education more frequently received surgery in high-volume hospitals; there were no differences by age, gender, stage, or co-morbidity status. 55% of patients received surgery at the same facility where they received the colonoscopy that identified their cancer. In multivariate analyses, the strongest predictor of receiving one’s surgery in a high-volume hospital was receipt of colonoscopy at a high-volume facility (OR = 3.75, 95% CI: 2.93-4.79). Those treated in high-volume hospitals more often had guideline-recommended staging (TRUS/MRI) and treatment (neoadjuvant chemoradiation). Conclusions: Rectal cancer patients tended to stay at the facility where their cancer was diagnosed; and did not typically seek out high-volume providers if their colonoscopy was performed in a low-volume facility. This suggests that colonoscopists may have substantial influence over where patients receive surgery. Given that rurality, income and education appear to more strongly predict receipt of surgery at a high-volume hospital compared to clinical characteristics, further research is needed to understand considerations driving patient decisions and referring providers’ recommendations for care.
Outcomes after major cancer surgery: Can we predict them using parsimonious models?
Authors: Goel Neha , Ward William H. , DeMora Lyudmila , Manstein Samuel , Smaldone Marc C. , Farma Jeffrey M. , Chu Christina , Kutikov Alexander , Chen David , Lango Miriam , Viterbo Rosalia , Ridge John A. , Ross Eric A. , Uzzo Robert , Esnaola Nestor F. 
Published: January 2019

811 Background: Major cancer surgery is associated with significant risks of morbidity/mortality. Retrospective studies have demonstrated an association between Surgical Apgar Score (SAS) and postoperative risk of serious complications (SC). This study prospectively evaluated the predictive value of SAS to predict SC, as well as other adverse postoperative outcomes and length of stay (LOS), both singly and in combination with parsimonious measures of “fitness for surgery” (American Society of Anesthesiology [ASA] classification) and surgical complexity (work relative value units [wRVU]). Methods: Demographic, comorbidity, procedure, intraoperative, and outcome data was collected prospectively for 442 cancer patients undergoing elective major surgery between 2014-17. ASA and wRVU were assigned preoperatively; SAS was calculated postoperatively. Logistic regression was used to analyze association of ASA versus (vs) wRVU vs SAS vs ASA/wRVU/SAS (combined) with perioperative outcomes, including SC, return to the operating room (ROR), not being discharged to home, and unplanned readmission; areas under receiver operator characteristic curves were calculated to assess predictive accuracy. Accelerated failure time models were used to analyze associations with LOS and compared using Harrell’s concordance index. Results: Predictive accuracy of SAS for SC was modest (AUC0.655) and not improved when controlling for ASA and wRVU (both of which had poor predictive accuracy for SC). Both wRVU (AUC 0.634) and SAS (AUC 0.663) had modest predictive accuracies for ROR, whereas the predictive accuracy of ASA (AUC 0.749) surpassed that of wRVU (AUC 0.630) for not being discharged to home. All 3 measures were poor at predicting readmission. In contrast, the predictive accuracy of ASA, wRVU, and SAS for LOS was highest when combined (AUC 0.699). Conclusions: Commonly used, simple measures of comorbidity/functional status and surgical complexity can help predict risk of ROR and not being discharged to home (respectively), whereas only SAS has sufficient (albeit modest) discriminatory ability to predict risk of SC. All three measures are too coarse to predict unplanned readmission, but when used in combination, can help predict LOS.