bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of previous abdominal surgery on short-term outcomes following laparoscopic colorectal surgery.
Authors: Hotchi Masanori , Waki Yuhei , Tokuda Kazunori , Obatake Masayoshi , Kotegawa Hiroshi , Yoshiyama Hirotsugu , Harada Masamitsu , Kawasaki Hideki 
Published: February 2017

653 Background: The impact of previous abdominal surgeries on the need for conversion to open surgery and on short-term outcomes during/after laparoscopic colorectal surgery was retrospectively investigated. This retrospective cohort study was conducted from May 2004 through October 2012. This study was conducted at Tokushima University Hospital and Ehime Prefectural Central Hospital. Methods: A total of 145 consecutive patients who had undergone laparoscopic resection of the sigmoid colon and upper rectum were classified as not having previous abdominal surgery (NPAS group, n = 123) or as having previous abdominal surgery (PAS group, n = 22). Short-term outcomes were assessed between the two groups. Results: The population of previous abdominal surgery consisted of 6 appendectomy, 3 gastrectomy for gastric ulcer, 2 nephrectomy, 2 peritonitis and 11 others (2 duplication). There were no significant differences in age, gender, BMI, tumor location, tumor size, Stage, operating time, blood loss and number of lymph node harvest between the two groups. The conversion to open surgery was performed in 1 patient (4.5%) in the PAS group and 6 patients (4.9%) in the NPAS group. The intraoperative inadvertent enterotomy occurred in 1 patient in the NPAS group. There was no difference in postoperative morbility between the two groups. In the NPAS group, anastomotic leakage was observed in 3 cases. Ileus was observed in one case in the NPAS and none in the PAS. Postoperative hospital stay was 14 days in the PAS group and 16 days in the NPAS group. Conclusions: Short-term outcomes following laparoscopic surgery for sigmoid colon and upper rectal cancer with previous abdominal surgery are acceptable.
Comparative analysis of uptake for 18F-fluorodeoxyglucose (FDG) versus 18F-fluorodeoxythymidine (FLT) PET scans in rectal cancer.
Authors: Sheybani Arshin , Bhatia Sudershan , Menda Yusuf , Boles-Ponto Laura , Gross Brandie Ann , Rockey William , McGuire Sarah Marie 
Published: February 2017

657 Background: FLT PET is a novel metabolite for imaging cellular proliferation and has shown promise for treatment response monitoring. The utility of FLT PET imaging in rectal adenocarcinomas (RA) has not previously been established. We set out to compare FDG and FLT uptake in RA and correlate FLT response during treatment to tumor regression. Methods: We evaluated 6 patients with RA who were treated on an institutional prospective clinical trial (NCT01717391). Patients were treated neoadjuvantly with concurrent chemoradiation therapy per standard of care. Patients had both FDG and FLT PET scans prior to starting treatment and FLT scans after 1 and 2 weeks of radiotherapy. Tumor volumes and pelvic lymph nodes measuring greater than 6 mm were contoured on the simulation CT scan and adjusted for bladder and rectal filling based on the attenuation correction CT for each PET scan. FLT and FDG SUVs were collected from a total of 40 lymph nodes among the six patients. Pretreatment and change in tumor FLT SUVs were correlated with histopathological regression. The sensitivity of FLT and FDG for identifying lymph nodes was compared using a Student’s t-test. Results: At the time of this analysis, there were post-treatment pathological data on five patients. All but one patient had a decline in the FLT tumor SUV after 2 weeks of treatment. This non-responder was the only patient who did not have histopathological tumor regression after treatment and was the only patient whose pretreatment FLT SUV was below 2. Tumor FDG SUV (4.54 ± 1.03) was consistently higher compared to FLT (2.42 ± 0.51) values, however nodal uptake for FDG (1.89 ± 1.08) was not higher compared to FLT (1.98 ± 0.96). To account for this difference, nodal uptake was normalized to the SUV of each patient’s primary tumor for both FLT and FDG. Mean normalized lymph node FLT SUVs were significantly higher (0.80 ± 0.36) than normalized FDG SUVs (0.44 ± 0.25) (p<0.001). Conclusions: Preliminary data supports using FLT SUV as a biomarker for tumor response early during treatment. Relative FLT uptake in nodal metastasis also appears to be higher when compared to FDG. This indicates potential response and diagnostic applications for FLT PET imaging in RA Clinical trial information: NCT01717391.
The implementation of Lean Six Sigma methodology in a multidisciplinary outpatient clinic for gastrointestinal cancer.
Authors: Basta Yara , Monster Matthijs , Rohof Thomas , Tytgat Kristien M. A. J. , Klinkenbijl Jean H. G. 
Published: February 2017

659 Background: In order to reduce long waiting times, a one-stop fast-track multidisciplinary outpatient clinic for gastrointestinal malignancies was initiated. Lean Six Sigma (LSS) is a combination of Lean-management and the Six Sigma methodology. LSS incorporates means to systematically identify and address suboptimal performance of a process. Lean and Six Sigma have their origin in the manufacturing industry, like the Toyota car factory, with largely homogenous products. In contrast, a complex high care oncology facility deals with heterogeneous patients. Our aim is to use the tools and strategies of LSS to increase the number of patients with an admission time (AT) of five days or less to ≥ 85% and to ensure that ≥ 90% of referring physicians receive the decisions formulated at the Multidisciplinary Team Meeting (MDTM) within one day. Methods: We have applied the DMAIC-cycle (Define, Measure, Analyse, Improve and Control) to our processes. The DMAIC-cycle is the management cycle of Lean Six Sigma. Results were measured before implementation of LSS and after for at least one month. Results: After implementing LSS causes for lags in AT, as well as for sending the documented decisions were identified. The lags in AT included patient delay, incomplete referral, official holidays and absences due to medical conferences. After the obstacles were successfully addressed we increased the percentage of patients with an AT ≤ 5 days from 48% to 70%, a 45% improvement. Causes for lags in sending the decisions, included verifying and signing the missive. Currently 99% of referring physicians receive the decision formulated by the MDT in ≤ 1 day. This is a substantial improvement from 2% to 99%. Conclusions: Lean Six Sigma is applicable in a multidisciplinary high care medical facility. Obstacles in the logistics of a complex medical facility can be identified and greatly improved.
Comparison of cetuximab (Cmab) with panitumumab (Pmab) monotherapy in salvage line against KRAS wild-type patients with metastatic colorectal cancer (mCRC): Analysis of HGCSG0901 and 1002.
Authors: Ueda Akira , Yuki Satoshi , Sasaki Takahide , Kobayashi Yoshimitsu , Hosokawa Ayumu , Doi Ayako , Tsuji Yasushi , Okuda Hiroyuki , Kato Takashi , Watanabe Yutaka , Miyagishima Takuto , Eto Kazunori , Ohta Tomoyuki , Takahata Takenori , Ikeda Shinichiro , Nakatsumi Hiroshi , Iwai Kazuhiro , Kato Kanji , Sakata Yuh , Komatsu Yoshito 
Published: February 2017

663 Background: Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) such as Cmab and Pmab have antitumor activity and acceptable safety profiles in patients (pts) with mCRC. Monotherapy with Cmab or Pmab demonstrated the effectiveness in salvage-line, and the direct comparison was reported in ESMO 2013 (ASPECCT trial). Methods: Data of 31 pts with mCRC treated by monotherapy with Cmab (HGCSG0901) and 51 pts by monotherapy with Pmab (HGCSG1002) registered from 27 institutions in Japan. Comparison of Cmab with Pmab was retrospectively analyzed. All patients with KRAS wild type were refractory to or intolerant for 5-FU/irinotecan/oxaliplatin and also were never administered anti-EGFR-antibodies. Survival analyses were performed with Kaplan-Meier method, log-rank test, and Cox proportional hazards model. Results: Patient characteristics were as below (Cmab vs. Pmab); male/female 20/11 vs. 27/24, median age (range) 65(44-76) vs. 64(44-81), PS 0-1/2-3 21/10 vs. 46/5, number of metastatic organs 1-2/3- 22/9 vs. 25/16. Skin toxicity was common adverse events and was generally similar in two groups. MST was 8.4 months in the Cmab and 8.1 months in the Pmab (p = 0.32). PFS was 3.8 months in the Cmab, as compared with 3.1 months in the Pmab (p = 0.60); the corresponding response rate was 19.4% and 13.7% (p = 0.54). After adjusting other prognostic factors with Cox proportional hazard model, the administration of Cmab/Pmab made significant difference neither for OS (HR 0.939, 95% CI 0.783-1.128, p = 0.503), nor PFS (HR 0.972, 95% CI 0.823-1.148, p = 0.735). Conclusions: In this integration analysis of two studies, there were no significant difference in efficacy between Cmab and Pmab monotherapy in the salvage-line treatment of pts with mCRC.
The effects of H. pylori CagA on DNA amplification and protein expression status of the HER2 gene in gastric cancer.
Authors: Shim Jung Ho 
Published: February 2017

67 Background: We investigated whether Cag A contributes to the DNA copy change and expression of the HER2 gene mRNA transcript and, consequently, affects HER2 protein expression to evaluate the significance of H. pylori Cag A and HER2 amplification in gastric cancer. Methods: We used the AGS gastric cancer and HFE-145 immortalized non-neoplastic gastric mucosa cell lines to investigate whether Cag A regulates DNA copy number and HER2 expression. We also confirmed the effects of Cag A on gastric cancer tissues. Immunohistochemistry with or without fluorescence in situ hybridization (FISH) was conducted to determine the level of HER2 protein expression based on the revised criteria in the HER2 test guidelines. Results: H. pylori CagA transfected AGS cells showed a significant increase in HER2 gene copy number and expression. In addition, Cag A expression was detected in 17 (56.7%) of 30 gastric cancer (GC) tissues, and eight (47%) showed HER2 DNA amplification of more than two-fold (P = 0.013). A positive correlation was observed among DNA copy number, the mRNA transcript, and HER2 gene protein expression (p < 0.05). HER2 overexpression was detected in 12 (40%) of 30 gastric cancers by Hoffman’s criteria. Conclusions: These results suggest that H. pylori CagA may induce overexpression of the HER2 gene protein by increasing HER2 DNA and mRNA copy number. To overcome the weakness of the current HER2 assessment criteria, we propose to test HER2 DNA copy number changes with immunohistochemistry, instead of FISH.
The effect of stress on efficacy of dendritic cell therapy for esophageal squamous cell carcinoma.
Authors: Akutsu Yasunori , Qin Wei , Murakami Kentaro , Hoshino Isamu , Hanari Naoyuki , Nishimori Takanori , Mori Mikito , Isozaki Yuka , Toyozumi Takeshi , Hu Xin , Suito HIroshi , Akanuma Naoki , Takahashi Masahiko , Matsubara Hisahiro 
Published: February 2017

69 Background: Recently, abscopal effect, by which systemic anti-tumor effect by local radiation therapy (RT) was elicited, has been reported. This phenomenon was thought to be mediated by stress protein gp96, a key molecule in antigen-presenting. We tested the enhancement of dendritic cell (DC) therapy by various stress, such as radiation or modulated electro-hyperthermia (mEHT) in DC therapy for squamous cell carcinoma (SCC). Methods: Mouse SCC cells, SCCVII, were inoculated into the left femur (primary tumor) of C3H/He mice subcutaneously, and also similarly inoculated into non-treated chest subcutaneous tissue (secondary tumor). Only the primary tumor was exposed to 4 or 10 Gy of RT or 5-10 watts of mEHT. Then DCs was injected only into the primary tumor. Following that, tumor volumes of the primary and secondary tumor were measured. Next, the population of immune-related T-cells in tumor-draining lymph nodes (TDLN) and gp96 expression in the primary tumor were evaluated. Results: With intratumoral injection of DCs and RT, primary tumor growth was markedly suppressed. Furthermore, secondary tumor growth was also suppressed. On the other hand, the combination of DCs and mEHT could inhibit tumor growth at both the primary and the secondary tumor. As for the population of T-cells, the population of CD3+, CD 4+ and CD 8+T-cells in the TDLN was markedly elevated and that of FoxP3 was reduced my mEHT. Gp96 expression, a stress protein, was strongly enhanced after RT and mEHT. Conclusions: Stress, such as RT or hyperthermia can enhance the efficacy of DC therapy and can induce a strong antitumor effect by stimulating the expression of stress protein, gp96. These combination therapies can be a strong systemic immunotherapy for esophageal SCC.
Expression relationships among EGFR family members and c-Met in esophagogastric adenocarcinoma.
Authors: Chan Ellie , Alkhasawneh Ahmad , Duckworth Lizette Vila , Zuluaga Toro Tania , Lu Xiaomin , Hughes Steven J. , George Thomas J. 
Published: February 2017

75 Background: The incidence of esophagogastric adenocarcinoma is on the rise. The only targeted therapy that improves patient outcomes is the anti-HER2 antibody, trastuzumab; however, benefit is limited to cases with HER2 overexpression. Inhibition of EGFR in EGA is unsuccessful. cMet overexpression is a proposed resistance pathway for EGFR family inhibition. We sought to characterize the co-expression relationships among the EGFR family and cMet to identify potential dual therapeutic targets. Methods: This study included all sequential patients (pts) with adenocarcinoma of the esophagus and GEJ who underwent primary resection between 2001 to 2011 without neoadjuvant therapy or HER2 inhibition. Demographics, risk factors, tumor features, and outcome data were analyzed. Central blinded immunohistochemistry (IHC) was performed on FFPE tumor specimens with EGFR, HER2, HER3, HER4 and cMet expression scored as low/negative or high/positive expression. Descriptive statistics, Exact chi square test and Cox regression model were used for statistical analyses. Results: 48 pts (39 M/9 F) were eligible (median age 66yr; 37-83). Most (63%) were stage I (T1N0) and 93% had underlying Barrett’s esophagus. High expression of EGFR, HER2, HER3, HER4 and cMet were present in 70%, 43%, 77%, 38% and 56% of tumors respectively. HER3 and HER4 were commonly co-expressed (p=0.003) and moderately differentiated tumors had high expression of HER3 (p=0.01). Stage was the only variable that correlated significantly with survival (p=0.007). Conclusions: This study demonstrated that static baseline cMET expression levels are not associated with EGFR family expression profiles, although HER3/HER4 co-expression is common. No receptors demonstrated prognostic value. Further investigation into dynamic cMET expression changes related to active EGFR inhibition including prognostic and predictive value is warranted.
Prognostic stratification in esophagogastric adenocarcinoma in the revised AJCC staging (7th edition).
Authors: Zahoor Haris , Luketich James D. , Weksler Benny , Winger Dan G. , Christie Neil A. , Levy Ryan M. , Gibson Michael K. , Nason Katie S. 
Published: February 2017

92 Background: AJCC esophageal staging assigns prognostic groups based on tumor, node, and metastasis classifications. In 2010, AJCC 7th ed. separated adenocarcinoma from squamous cell histology and added tumor grade and number of involved regional nodes. Our study aim was to compare survival prognostication for esophagogastric adenocarcinoma between AJCC 7 and AJCC 6thed. stage groupings. Methods: We abstracted pathology and survival for surgically-resected esophagogastric adenocarcinoma patients (n=836; 1997 to 2011); 256 received induction therapy. AJCC stage was assigned; overall survival in months (esophagectomy to death or most recent alive contact) was analyzed. Discriminatory ability and homogeneity, by stage, was assessed with Kaplan-Meier (KM) curves. Monotonicity comparisons were evaluated with linear trend chi-squared tests. Overall survival was compared using Cox regression and Akaike Information Criterion (AIC) was used to assess model fit. Results: Compared to AJCC 6, AJCC 7 restaged 165 patients. (Table) KM log-rank statistic indicated stronger differentiation in AJCC 7 curves compared to AJCC 6 (166.128 vs 185.523 overall). Cox likelihood ratio (162.957 vs. 173.951 overall) and AIC (4,831.011 vs 4,820.016 overall) indicated better model fit to the survival data for AJCC 7 versus AJCC 6, overall and for induction subgroups (data not shown). As stage group increases, stronger linear trends for survival were observed at 24, 36 and 60 months using AJCC7 stage groupings, overall and for induction subgroups, compared to AJCC 6. Conclusions: AJCC 7 stage groupings demonstrate superior homogeneity, discriminatory ability and monotonicity compared to AJCC 6. Incorporating the extent of nodal disease, and tumor grade into the revised AJCC 7 stage classification improves prognostic stratification of surgically resected esophagogastric adenocarcinoma patients, including patients who received induction therapy. [Table: see text]
Relationship of initial quality-of-life deficit and survival in esophageal cancer (EC): The Mayo Clinic Romero Registry experience.
Authors: Anderson Bradley W. , Sio Terence Tai Weng , Liu Heshan , Ginos Brenda F. , Romero Yvonne , Jatoi Aminah , Deschamps Claude , Sloan Jeff A. , Miller Robert Clell 
Published: February 2017

97 Background: A diagnosis of EC significantly impairs patient (pt)’s survival and quality of life (QoL). We explored the relationship between pt-assessed QoL and survival. Methods: The Mayo Clinic Romero (formerly Esophageal Adenocarcinoma-Barrett's Esophagus) Registry prospectively collects clinical data during a pt's treatment course. QoL is recorded at enrollment (baseline) and annually using a validated 12-item Linear Analog Self-Assessment (LASA). A 10-pt scale is applied; ≤5 was termed clinically deficient QoL. Initial TNM staging, clinical (age, sex, prior chemotherapy, and esophagectomy), and socioeconomic variables (marital/employment status) were analyzed using Cox proportional hazards regression models. Results: 836 pts were analyzed. Median age was 64 years. 166, 506 and 164 pts had early, locally advanced, and metastatic EC, with 5-year survival rates of 75.1%, 33.6%, and 8.1%, respectively (P≤.0001). Poorer survival rates were seen in clinically QoL deficient pts in the following categories: Overall QoL (Hazard Ratio [H.R.] 0.66; 95% C.I., 0.54-0.80; P≤.0001) and LASA subsets for physical (H.R. 0.68; 95% C.I., 0.57-0.82; P≤.0001), emotional well-being (H.R. 0.69; C.I., 0.57-0.84; P=.0003), and social activity (H.R. 0.76; C.I., 0.63-0.91; P=.0028). No difference in survival was observed for marital or employment status, familial support, and financial/legal concerns. Pts with esophagectomy prior to LASA evaluation had improved survival (H.R. 0.68; 95% C.I., 0.55-0.85; P=.0005). No survival difference was observed whether pts received chemotherapy, before or after their baseline LASA evaluation. Conclusions: A strong association exists between pt’s overall survival and better overall QOL, physical, emotional well-being, and social activities. Using LASA to clinically monitor QoL at specified intervals may afford providers the opportunity to intervene when patients begin to experience QoL decline. The determinants of clinically deficit QoL and its impact on survival warrant further translational and prospective research.
RAINBOW: A global, phase III, randomized, double-blind study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in the treatment of metastatic gastroesophageal junction (GEJ) and gastric adenocarcinoma following disease progression on first-line platinum- and fluoropyrimidine-containing combination therapy rainbow IMCL CP12-0922 (I4T-IE-JVBE).
Authors: Wilke Hansjochen , Van Cutsem Eric , Oh Sang Cheul , Bodoky Gyorgy , Shimada Yasuhiro , Hironaka Shuichi , Sugimoto Naotoshi , Lipatov Oleg N. , Kim Tae-You , Cunningham David , Ohtsu Atsushi , Rougier Philippe , Emig Michael , Carlesi Roberto , Chandrawansa Kumari , Muro Kei 
Published: February 2017

LBA7 Background: RAM is a human IgG1 monoclonal antibody VEGF-receptor 2 antagonist. We conducted a global, placebo-controlled, double-blind, phase III trial to evaluate the efficacy and safety of PTX +/- RAM in patients with metastatic GEJ or gastric adenocarcinoma who had disease progression on or within 4 months after first-line platinum- and fluoropyrimidine-based combination therapy. Methods: Pts received RAM (8 mg/kg IV q2w) or placebo (PL) plus PTX (80 mg/m2 d1, 8, 15 of a 4 week cycle) until disease progression, unacceptable toxicity, or death. Eligible pts had ECOG PS ≤ 1; and adequate organ function. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), time to progression (TTP), and safety. Results: From Dec 2010 to Sep 2012, 665 pts were randomized (RAM+PTX: 330; PTX: 335). Baseline characteristics were generally balanced between arms. The OS hazard ratio (HR) was 0.807 (95% CI 0.678, 0.962; p=0.0169). Median OS was 9.63m for RAM+PTX and 7.36m for PTX. The HR for PFS was 0.635 (95% CI 0.536, 0.752; p <0.0001). Median PFS was 4.40m and 2.86m. Median TTP was 5.5m RAM+PTX; 3.0m PTX (p <0.0001). ORR was 28% RAM+PTX;16% PTX (p=0.0001). Grade ≥ 3 adverse events (AEs) occurring in >5% of patients on RAM+PTX were: neutropenia (40.7% RAM+PTX;18.8% PTX), leukopenia (17.4% vs 6.7% ), hypertension (14.1% vs 2.4%), anemia (9.2% vs 10.3%), fatigue (7.0% vs 4.0%), abdominal pain (5.5% vs 3.3%), and asthenia (5.5% vs 3.3%). Febrile neutropenia was reported in 3.1% RAM+PTX; 2.4% PTX. Conclusions: The primary endpoint of improved OS was met. A statistically significant and clinically meaningful OS benefit of > 2 months was observed for RAM+PTX vs. PTX in gastric and GEJ cancer after progression on 1st-line therapy, as were significant benefits in PFS and ORR. Neutropenia was more frequently reported in the RAM+PTX arm but incidence of febrile neutropenia was comparable between arms. Clinical trial information: NCT01170663.