bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predictive factors of residual tumor for the patients with non-curative resection after endoscopic submucosal dissection for early gastric cancer.
Authors: Sunagawa Hideki , Kinoshita Takahiro , Kaito Akio , Kaneko Kazuhiro 
Published: March 2017

32 Background: Endoscopic submucosal dissection (ESD) is commonly performed for the patients who diagnosed with early gastric cancer. Although additional gastrectomy is recommended for the patients with non-curative ESD in the points of potential risk of residual tumor, many cases have neither lymph node (LN) metastasis nor local residual tumor in surgical specimens. Clinically, it can be difficult to decide whether to perform additional surgery according to patients’ conditions. This study aimed to analyze the clinicopathological features of patients who underwent additional gastrectomy as well as to detect the predictive factors for residual tumor after non-curative ESD. Methods: The patients who underwent additional gastrectomy after non-curative ESD in our institution from January 2005 to August 2016 were retrospectively reviewed. The incidence rates of LN metastasis or local residual tumor were calculated, and furthermore the predictive factors for these outcomes were estimated. Results: 211 patients were enrolled in this study. Pathological examination after additional surgery revealed LN metastasis in 18 patients (8.5%) and local residual tumor in 26 patients (12.3%). Multivariable analysis revealed that lymphatic invasion ( p< 0.0001, odds ratio = 15.6), vascular invasion ( p= 0.042, odds ratio = 3.92) and macroscopic findings (flat/elevated type) ( p= 0.03, odds ratio = 3.53) are predictors for lymph node metastasis. All of the patients without LN metastasis revealed no lymphovascular invasion. Positive vertical margin ( p= 0.0045, odds ratio = 4.17) and horizontal margin ( p= 0.0002, odds ratio = 6.6) were predictors for local residual tumor. Conclusions: The risk of residual tumor can be estimated based on histopathology of ESD. Patients without lymphovascular invasion appear to be a low risk subpopulation for LN metastasis.
Association of hyaluronan accumulation with clinical-pathologic features in pancreatic ductal adenocarcinomas.
Authors: Larson Brent K , Pan Dana , Khanuja Jasleen , Patel Rishi , Zhou Jenny , Osipov Arsen , Guindi Maha , Müller Thomas , Li Quanlin , Jiang Ping , Tuli Richard , Hendifar Andrew Eugene 
Published: March 2017

322 Background: Pancreatic ductal adenocarcinoma (PDA) is characterized by marked stromal fibrosis and hyaluronan (HA) accumulation. Degradation of stromal HA using PEGylated recombinant human hyaluronidase (PEGPH20) in combination with anti-cancer therapeutics has demonstrated increased efficacy in preclinical models. This study used an exploratory prototype HA assay to assess HA and to explore the association of HA status with clinical and pathological variables. Methods: Sixty-four PDA samples from 49 patients treated with gemcitabine and nab-paclitaxel were stained for HA using a prototype histochemical binding assay. The tumor extracellular matrix staining for HA at any intensity above background as a proportion of the total tumor surface area was recorded. Cases were categorized as HA-high (HA score of ≥50%) or HA-low (HA score of <50%). Subgroup analyses were also performed in paired pre- and post-chemotherapy samples. Results: Twenty-six of 49 (53%) patients were determined to be HA-high. HA-high status was significantly associated with pN1 (positive node) status (p<0.001) and well/moderate differentiation (p<0.001). No correlation of HA status was observed with sex, race, primary tumor location, pT (tumor) stage, lymph-vascular invasion, pathologic stage, or initial CA19-9 levels. No trend in HA status was observed comparing pre- and post-chemotherapy specimens (n=5). Conclusions: HA status was significantly associated with nodal stage and grade.
A preclinical trial to evaluate therapies for BRCA-associated pancreatic cancer.
Authors: Park Jin Yong Patrick , Hall Anita , Hedley David W. , Tsao Ming Sound , Gallinger Steven , Zogopoulos George 
Published: March 2017

332 Background: Pancreatic ductal adenocarcinoma (PDAC) associated with germline BRCA1 or BRCA2mutations may have selective sensitivity to agents that exploit homologous recombination DNA repair defects. We hypothesized that cisplatin, a DNA-crosslinking agent, and talazoparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, monotherapies are efficacious in BRCA-associated PDAC, while combination therapies with these agents have enhanced efficacy. Methods: A preclinical trial was performed in subcutaneous patient-derived tumor xenograft (PDX) mouse models with (n = 5) and without (n = 2) germline BRCA1 or BRCA2mutations. Mice harboring PDX tumors were treated with vehicle, talazoparib, cisplatin, gemcitabine, talazoparib with cisplatin (TC), talazoparib with gemcitabine (TG), or cisplatin with gemcitabine (CG). Twelve tumors were randomized into each trial arm, treated for 28 days, and then monitored without further treatment to assess tumor regrowth. Results: Treatment with cisplatin and talazoparib monotherapies resulted in 89.8% and 88.2% tumor growth inhibition (GI) in BRCA-associated cases versus 34.0% and 34.7% GI in the cases without germline BRCAmutations, respectively. Gemcitabine-based combinations were more effective than monotherapies in BRCA-associated cases (p < 0.001), with CG and TG resulting in tumor regression in five and three BRCA-associated cases, respectively. Although we also observed the treatment effect with these combinations in non-BRCA cases, it paralleled the gemcitabine monotherapy effect in these cases (p = 0.322). Following cessation of treatment, we observed heterogeneity in tumor regrowth. CG and TG demonstrated sustained responses across all BRCA-associated cases, however, TG had greater toxicity than CG. Conclusions: Our preclinical data suggest that targeted therapy with CG is efficacious with a sustained response and less toxicity than TG in BRCA-associated PDAC.
Prognostic factor of distal bile duct cancer (DBDC) and ampullary cancer (AC) after pancreatoduodenectomy.
Authors: Tomiyasu Shinjiro , Sakamoto Keita , Inoue Mitsuhiro , Iizaka Masayoshi , Ozaki Nobuyuki , Horino Kei , Takamori Hiroshi , Hirota Masahiko , Baba Hideo 
Published: March 2017

333 Background: Ampullay cancer (AC) is relatively good prognosis in the biliary tract cancer. Such as LN metastasis, pancreatic invasion is a prognostic factor in AC. On the other hand, Distal bile duct cancer (DBDC) is somewhat good prognosis in the biliary tract cancer. Such as ductal resection margin positive is a prognostic factor in DBDC. There are few papers considered to both difference. Therefore, we conducted this study to examine the difference of AC and DBDC. Methods: To evaluate Cancer-Specific Survival (CaSS), Recurrence-Free Survival (RFS) and prognostic factors after pancreatoduodenectomy (including pylorus-preserving pancreatoduodenectomy: PPPD, subtotal stomach-preserving pancreatoduodenectomy: SSPPD) based on a series of 80 patients of AC and 36 patients of DBDC from 1996 to 2015. We reviewed and analyzed the clinicopathologic data, recurrence and survival. Results: Five years CaSS and RFS of AC were 72.3% and 72.5%. In univariate analysis, pancreatic invasion, R1or R2 resection, duodenal invasion and lymph node metastasis are significantly poor prognosis. In multivariate analysis, pancreatic invasion and R1or R2 resection are poor prognostic factors (pancreatic invasion, p = 0.0012, hazard ratio (HR) 5.65 [confidence interval (CI) 1.92-19.5 95%], R1or R2 resection, p = 0.0043, HR 6.22 [CI 1.68-40.2 95%]). On the other hand, five years CaSS and RFS of DBDC were 35.8% and 46.8%. In univariate analysis, pancreatic invasion (+) ≥ 5 mm in depth, and duodenal invasion are significantly poor prognosis. In multivariate analysis, duodenal invasion is the only poor prognostic factors (p = 0.0227, HR 2.90 [CI 1.16-7.39 95%]). Conclusions: DBDC is considerable poor prognosis compared with AC. Lymph node metastasis is not prognostic factor depends on D2 LN dissection in AC, than pancreatic invasion. Cancer cells invaded pancreatic parenchyma in AC; pancreatic invasion may be the most important prognostic factor by biology-like pancreatic cancer. Duodenal invasion in DBDC was prognostic factor reflects the degree of development of the cancer beyond pancreatic parenchyma. Further clinicopathological and biological studies are needed to confirm our findings.
Intratumoral heterogeneity of intrahepatic cholangiocarcinoma.
Authors: Walter Dirk , Döring Claudia , Feldhahn Magdalena , Battke Florian , Hartmann Sylvia , Winkelmann Ria , Schneider Markus , Bankov Katrin , Schnitzbauer Andreas , Zeuzem Stefan , Hansmann Martin-Leo , Peveling-Oberhag Jan 
Published: March 2017

335 Background: No personalized therapy regimens could demonstrate a benefit in survival in intrahepatic cholangiocarcinoma (iCCA). Since genetic heterogeneity might influence single biopsy based targeted therapy or the outcome of clinical trials, aim of the present study was to investigate intratumoral heterogeneity of iCCA by whole exome sequencing. Methods: Samples from tumor center and tumor periphery of large iCCA lesions as well as a control from healthy liver tissue were obtained from 4 patients and whole exome sequencing was performed. Mutations that occurred only in the tumor center or periphery were defined as private, whereas mutations present in both samples were regarded as common. Results: A mean of 3 non-synonymous private mutations (range 0-13) per sample compared to 31.8 common mutations per sample (range 23-39) was identified. Mean percentage of non-synonymous private mutations per sample was 12% (range 0-57). In all samples of patient 1-3 as well as the central sample of patient 4 ≤ 10% private mutations were found, whereas 57% of private mutations were identified in the peripheral sample of patient 4. In this sample, a private mutation in the DNA mismatch repair protein MSH6 as well as a spatial loss of expression of MSH6 could be identified most likely causing the high amount of private mutations. No substantial intratumoral heterogeneity was found in copy number variation analysis apart from a heterozygous duplication of chromosome 6p of patient 4. Conclusions: iCCA show a small but distinct intratumoral heterogeneity. Somatic mutations in mismatch repair proteins might contribute significantly to increased spatial tumor burden and thereby can have crucial impact on clinical management.
Role of nutritional and inflammatory status in the prognosis of advanced gastric cancer.
Authors: Cousillas Antía , Gallardo Elena , Carou Iria , Rodriguez Ángeles , Sacristán Víctor , Vázquez Lidia , López-Jato Cristina , Garcia Arroyo Francisco Ramon , Azpitarte Cristina , López-Clemente Pedro , Constenla Manuel 
Published: March 2017

35 Background: This study explores the prognosis impact of nutritional and immune status in metastatic gastric cancer (GC). Recently research has been focused on a proinflammatory status and the relevance of inmune system of the patient in GC. Neutrophil-lymphocyte ratio (NLR) and prognostic nutritional index (PNI) has showed prognostic value in local disease. Our study was assesed in metastatic disease. Methods: One hundred and twenty patients with metastatic gastric adenocarcinoma were retrospectively evaluated between 2011 and 2015. 67.2% were metastatic at diagnosis and 32.8% had a recurrence of disease. Clinical, laboratory and histopathological characteristics were selected as risk factors. The optimal cut-off levels were defined as NLR = 3, PNI (10 x albumin concentration +0.005 x total lymphocyte count) = 43.8, albumin = 3.5 g/dL, body mass index (BMI) = 25. Patients with high NLR and hypoalbuminemia were defined as 2, patients who presented only one abnormally were defined as 1 and those with neither abnormality were defined as 0. Lab data levels were related with survival by Kaplan-Meier and compared by long-rank test. Results: Among 120 patients, mean age was 69 years old, 35% female and 72.5% had no comorbidity. NLR > 3 (6.7 vs 12.5months, p = 0.001), low PNI (7.7 vs 13.1months, p = 0.01) and low albumin (6.2 vs 11.2 months, p = 0.002) were correlated with OS. Significantly, patients with an BMI < 25 had a worse prognosis compared with patients with BMI ≥ 25 (7.4 vs 12.4months, p = 0.02). Obesity in metastatic GC was related with good prognosis in our review. In the group of patients with hypoalbuminemia and h-NLR (27.6%) OS was much worse than patients with normal albumin and low-NLR, 33.6% (4.4months vs. 12.8 months, p < 0.001) Conclusions: High NLR ( > 3) and low PNI ( < 43.8), albumin ( < 3.5g/dL) were correlated with worse outcomes. Moreover, the association in a score of NLR plus albumin showed eight months OS diference. As a recent data in other cancer sites, obesity was related with good prognosis in mGC in our review.
Nab-paclitaxel plus gemcitabine or plus simplified LV5FU2 as first-line therapy in patients with metastatic pancreatic adenocarcinoma: A GERCOR randomized phase II study (AFUGEM).
Authors: Dubreuil Olivier , Bachet Jean Baptiste , Hammel Pascal , Desrame Jerome , Meurisse Aurelia , Andre Thierry , Debourdeau Philippe , Dauba Jérôme , Lecomte Thierry , Seitz Jean Francois , Tournigand Christophe , Aparicio Thomas , Guerin Meyer Véronique , Taïeb Julien , Hiret Sandrine , Volet Julien , Monier Amandine , Chibaudel Benoist , Bonnetain Franck , Louvet Christophe 
Published: March 2017

350 Background: Nab-paclitaxel plus gemcitabine regimen (NABGEM) became a standard in first-line patients (pts) with metastatic pancreatic adenocarcinoma (mPAC). The AFUGEM trial evaluated the efficacy and safety of nab-paclitaxel plus simplified LV5FU2 (NABFU). Methods: Main eligibility criteria were: untreated mPAC, ECOG PS≤2. Pts received nab-paclitaxel (125 mg/m2 on d1, 8 and 15) plus gemcitabine (1000 mg/m2 on d1, 8 and 15) or plus simplified LV5FU2 (leucovorin 400 mg/m2, 5FU bolus 400 mg/m2 followed by 2400 mg/m2 given as a 46-hour continuous infusion on d1 and 15), one cycle every 4 weeks in both arms, ratio 1:2, respectively. The primary end point was observed progression-free survival (PFS) rate at 4 months (m). A Fleming 2-stage design was used with a targeted (H1) 4m-PFS rate of 50% in NABFU arm and an uninteresting 35% rate (H0, unilateral alpha of 5% and power of 80%). Results: 114 pts were included: NABGEM n=39, NABFU n=75. Baseline characteristics were well balanced: median age 66 years (45-86), ≥2 metastatic sites 36.8%, ECOG PS 0-1 84.2% and 2 15.8%, at the exception of pain more frequent in the NABFU arm (38.5% vs 56.0%). In mITT population, the observed 4m-PFS rates were of 55.4% [95% CI, 45-63] in NABFU Vs 53.9% [95% CI, 39.6-67.7] in NABGEM. Disease control rates were 65% (95% CI, 53-76) and 62% (95% CI, 45-77) respectively. After a follow-up of 24.3m, median PFS were 5.9 [95% CI, 3.6-7.4] v 4.9 months [95% CI, 2.1-7.7] [HR=0.79, 95% CI: 0.52-1.20]. Grade 3-4 adverse events were more frequent in NABGEM (77% v 87%). At tumor progression, in the NABFU arm, 50 patients (66%) and then 13 patients (17%) received a second and third line of chemotherapy respectively, versus 22 patients (56%) and 6 patients (15%) in the NABGEM arm. Median OS were 11.4 [95% CI, 8.8-16.5] v 9.2 months [95% CI, 6.0-13.6] [HR=0.61, 95% CI: 0.40-0.95], respectively. The 12 and 18-months OS rates in NABFU vs NABGEM arm were 48% Vs 41% and 34% Vs 13%, respectively. Conclusions: Nab-paclitaxel plus simplified LV5FU2 appears at least as active as gemcitabine plus nab-paclitaxel in mPAC. The toxicity profile is safe and tolerable. This regimen deserves evaluation in a phase III trial. Clinical trial information: NCT01964534.
Actual 5-year survivors following resection of hilar cholangiocarcinoma.
Authors: Tran Thuy , Ethun Cecilia Grace , Pawlik Timothy M. , Buettner Stefan , Idrees Kamran , Isom Chelsea A , Fields Ryan C. , Krasnick Bradley , Weber Sharon M. , Salem Ahmed , Martin Robert C. G. , Scoggins Charles Raben , Shen Perry , Mogal Harveshp , Schmidt Carl Richard , Beal Eliza W , Hatzaras Ioannis , Shenoy Rivfka , Maithel Shishir Kumar , Poultsides George A. 
Published: March 2017

352 Background: Although several studies have reported on actuarial survival outcomes following resection of hilar cholangiocarcinoma, the characteristics of patients who actually reached the 5-year milestone have not been adequately described. Methods: Patients who underwent resection for hilar cholangiocarcinoma from 2000-2015 in 10 US academic institutions participating in the Extrahepatic Biliary Malignancy Consortium were analyzed. Patients alive at last encounter with less than 5 years of follow-up were excluded. The clinicopathologic characteristics, perioperative, and long-term outcomes of actual 5-yr survivors and of patients who died within 5 years were compared. Results: Of 328 patients explored, 257 (78%) underwent curative resection and had an actuarial 5-year survival of 17%. After excluding 63 survivors with < 5 years follow-up, 194 patients were further classified as 5-year survivors (n = 23, 12%) and non-5-yr survivors. None of the 5-yr survivors had preoperative systemic biliary sepsis, portal vein embolization, T3 tumors with unilateral portal vein or hepatic artery invasion, or T4 tumors necessitating main portal vein or hepatic artery resection. However, actual 5-year survival was still achieved in the setting of bile duct resection only, R1 margins, poor differentiation, lymphovascular or perineural invasion, nodal metastasis, intraoperative blood transfusion, and serious postoperative complications. Five-year survival did not equal cure, as five 5-year survivors experienced disease recurrence, 2 before and 3 after the 5-year mark. There were ten actual 7-year survivors and four actual 10-year survivors. Conclusions: Although nodal metastasis, poor differentiation, and R1 margins are established predictors of poor outcome for hilar cholangiocarcinoma, the mere presence of these factors does not preclude patients from achieving a 5-year survival. In contrast, preoperative biliary sepsis, T3 or T4 stage, and the necessity for vascular resection and reconstruction appear to be prohibitive in reaching the 5-year milestone. This information can be utilized in the perioperative counseling of patients with this challenging malignancy.
Interim results of a multicenter phase II trial of nab-paclitaxel (nab-P) plus gemcitabine (G) for patients (Pts) with locally advanced pancreatic cancer (LAPC).
Authors: Lacy Jill , Portales Fabienne , Hammel Pascal , Pazo Cid Roberto A. , Manzano Mozo Jose Luis , Kim Edward Jae-hoon , Dowden Scot D. , Borg Christophe , Sastre Javier , Bathini Venu Gopal , Terrebonne Eric , Lopez-Trabada Daniel , Rivera Fernando , Asselah Jamil , Damiani Azzurra , Hwang Jimmy J. , Ong Teng Jin , Nydam Thom , Shiansong Li Jack , Philip Philip Agop 
Published: March 2017

358 Background: Treatment options for pts with LAPC are limited and generally similar to those for metastatic PC (mPC). The phase 3 MPACT trial of pts with mPC demonstrated a > 3-fold shrinkage of primary tumors with nab-P + G vs G, suggesting the potential of nab-P + G for LAPC treatment. Here, we present interim results on disease control rate (DCR), adverse events (AEs), and quality of life (QoL) from the international phase 2 LAPACT trial. Methods: Pts with treatment-naive unresectable LAPC and ECOG performance status of 0 or 1 received 6 cycles (C) of nab-P 125 mg/m2 + G 1000 mg/m2 on days 1, 8, and 15 of each 28-day C. After the initial nab-P + G treatment phase, pts without PD and unacceptable AEs were eligible for investigator’s choice (IC) of continued treatment with nab-P + G, chemoradiation, or surgery. Surgery could occur prior to completing 6 C in the case of a major response. Pt-reported QoL was assessed via EORTC QLQ-C30 and QLQ-PAN26 questionnaires at screening and prior to infusion on day 1 of each C. Results: As of Aug 17, 2016, 47 pts completed (28/47, 60%) or discontinued (19/47, 40%) the initial nab-P + G treatment (median, 5 C). Median age was 66 years (range, 44 - 86). The most frequent reasons for discontinuation were AE (10/47 [21%], with the most common being neutropenia and abnormal liver function [2 pts each]) and PD (3/47, 6%). The most common grade ≥ 3 AEs were neutropenia (34%) and anemia (11%). The DCR ≥ 16 weeks was 76% (34/45 efficacy-evaluable pts [defined as having evaluable baseline and ≥ 1 postbaseline scan]; PR, n = 13; SD, n = 21). Twenty-two pts (47%) were assigned by the investigators to an IC treatment: 4 (9%) to continue nab-P + G, 8 (17%) to chemoradiation, and 10 (21%) to surgical resection. Mean QoL scores remained stable during the study, with improved symptom scores for appetite and pain. During the initial nab-P + G treatment phase, most patients reported a complete resolution of certain limitations, including depression (≈ 80%), constipation (≈ 62%), and nausea (≈ 93%). Conclusions: These interim results suggest that for pts with LAPC, nab-P + G is tolerable and produces a promising DCR. On average, QoL scores remained stable during nab-P + G treatments. Clinical trial information: NCT02301143.
Prognostic significance of preoperative plasma fibrinogen and Albumin Score in esophageal cancer patients.
Authors: Maeda Yusuke , Takeuchi Hiroya , Kawakubo Hirofumi , Suda Koichi , Nakamura Rieko , Wada Norihito , Kitagawa Yuko 
Published: March 2017

36 Background: The clinical outcome of esophageal cancer has recently improved. However, the relapse rate in any stages is still high. Prognostic classification in patients with esophageal cancer has not yet established. If the patients with poor prognosis could be extracted before surgery, we can add more intensive preoperative treatment, which might lead more favorable prognosis. We have previously reported clinical utility of fibrinogen (FNG) and Albumin (Alb) Score (FA score) in esophageal cancer. The purpose of this study was to analyze the utility of FA score comparing at each stage as a prognostic factor in esophageal cancer. Methods: Patient characteristics, clinicopathological factors, and preoperative biochemical markers (FNG, Alb, and CRP) were investigated in esophageal cancer patients who underwent transthoracic esophagectomy between January 2004 and November 2013. Correlation between preoperative FNG, CRP, Alb, clnicopathological factors and survival were investigated. We evaluated between recurrence-free survival (RFS), overall survival (OS) and FA score comparing at each stage. The cut-off value was defined according to previous reports; fibrinogen 350mg/dl, albumin 3.8mg/dl. Results: 252 patients were recorded. High FA score were correlated to worse OS and RFS (p < 0.001). Especially in cStageI, high FA score showed remarkably worse 5-year RFS (score0/ score1/ score2, 5-year RFS 84%/ 64%/ 33%; p = 0.038). Conclusions: FA score was significantly associated with postoperative survival in esophageal cancer patients. If the patients with poor prognosis in cStageI could be extracted before surgery, we can add more intensive preoperative treatment, which might lead more favorable prognosis.