bluuebunny/crossref_metadata_2025_split huggingface dataset:
Local failure after liver resection for hepatocellular carcinoma.
Authors: Fredman Elisha T. , Kumar Aryavarta M. S. , El-Gazzaz Galal , Aucejo Federico , Coppa Christopher , Abdel-Wahab May 
Published: March 2020

e15015 Background: Partial resection is the most common surgical management of primary hepatocellular carcinoma (HCC), yet long-term prognosis remains poor, with 3-year intrahepatic recurrence rates up to 80%. A percentage of these occur within close proximity to the original tumor site. We conducted a retrospective review of liver resections at the Cleveland Clinic to determine rates and patterns of close tumor failure to inform future treatment. Methods: 147 patients, identified from an IRB approved database, underwent partial hepatectomy for definitive treatment of HCC from 1996-2012. All were followed with CT or MRI for indications of recurrence, defined as characteristic or biopsy proven liver lesions absent from previous imaging. Patients were divided into two groups: local recurrence (≤2 cm from surgical margin, A) and non-local intrahepatic recurrence (>2 cm from surgical margin, B). Logistic regression modeling was used for statistical analysis. Results: 73 (49.7%) patients had tumor recurrence, within a median time of 11.9 months (range: 1.6-69.9 months). 5 (6.8%) had extrahepatic recurrences only and were excluded from analysis. Groups A (n=19) and B (n=49) were demographically comparable. Mean tumor size was 8.9 cm (range: 2.6-14.5 cm) and 7.5 cm (range: 1.5-20 cm) respectively. In Group A, 6 (32%) had local lesions exclusively and 13 (68%) had concurrent local and non-local intrahepatic failure. Vascular invasion correlated with overall recurrence (p = 0.01). Patients with local recurrence were more likely to have a single lesion at initial diagnosis (p = 0.02) and had a shorter median time to surgery (p = 0.02). Presence of cirrhosis, tumor size, grade, margin status and tumor rupture were not significant correlates. Conclusions: In our population, 49.7% of patients had HCC recurrence. 26% of these recurrences were local failures. Vascular invasion correlated with overall recurrence. A single lesion and shorter time from diagnosis to surgery were associated specifically with local recurrence. Our findings open the possibility of employing intra-operative and/or adjuvant radiation therapy, which have demonstrated good local control with limited toxicity in other cancers, for patients at increased risk of local failure of HCC.
A prognostic model for early recurrence prediction in hepatocellular carcinoma after liver resection.
Authors: Ruan Dan-Yun , Li Yang , Jiang Nan , Lin Ze-Xiao , Wan XiangBo , Li Xing , Wu Xiang-Yuan , Chen Guihua 
Published: March 2020

e15021 Background: Recurrence resulting in high morbidity of hepatocellular carcinoma (HCC) patients received radical liver resection, the majority of which occur within 1 to 3 years. The study aims to find risk factors and set up a prognostic model predicting early recurrence of HCC. Methods: From 2003 to 2010, 196 HCC patients underwent liver resection were retrospectively analyzed. Univariate and multivariate analyses were used to assess variables. A recurrence risk model was developed with independent prognostic factors. Area under the ROC curve (AUC) was carried out to evaluate its predictive value. Results: The median follow-up time was 33 months (1-103M), median RFS was 22 months. Total tumor volume (TTV), hepatitis B, Child-Pugh score, and portal vein tumor thrombus were independent factors of recurrence. Patients with TTV>115cm3 had worse RFS (28.9% vs 51.7%, p<0.000) and OS (64.4% vs 80.1%, p=0.032) than those TTV≤115cm3. We established a risk model consisted of the 4 parameters, and classified patients into four stages. There were significant differences between each stage, especially for the 1st year. (1-yr RFS: 80.1% vs 47.8% vs 28.6% vs 0%, p=0.000, AUC 0.682). Compared to four currently used staging systems (BCLC, TNM, CLIP, and Okuda), the new model could well predict patient’s survival with the largest AUC in both RFS and OS (Table). Conclusions: TTV has been found a preferable description of tumor burden and a prognostic factor in HCC. This prognostic model predicts early tumor recurrence and survival of patients received radical liver resection and might contributes to the selection of patients who may benefit from surgery. [Table: see text]
Association of AREG exon 1 polymorphism with worse prognosis in Japanese and U.S. patients with gastric cancer.
Authors: Wakatsuki Takeru , Zhang Wu , Yang Dongyun , Azuma Mizutomo , Ning Yan , Volz Nico Benjamin , Stintzing Sebastian , El-Khoueiry Rita Elie , Li Joseph Ethan , Wilson Peter M. D. , Labonte Melissa Janae , Maus Martin K. H. , Sunakawa Yu , Koizumi Wasaburo , Watanabe Masahiko , Iqbal Syma , Barzi Afsaneh , El-Khoueiry Anthony B. , Shah Manish A. , Lenz Heinz-Josef 
Published: March 2020

e15022 Background: Recent data suggest that Amphiregulin (AREG) and Epiregulin (EREG), ligand of EGFR pathway, is possibly a prognostic and predictive marker in gastrointestinal cancer. Previous data have shown that higher AREG and EREG gene expression levels are associated with better survival in metastatic colorectal cancer as well as gastric cancer (GC). Since polymorphisms in AREG and EREG may affect their gene expression levels or change their functions, we tested the hypothesis whether these polymorphisms could predict outcome in two ethnically and epidemiologically different GC cohorts from Japan and the US. Methods: One-hundred and sixty-nine Japanese (n=169), as a training set, and one-hundred and thirty-seven (n=137) the US patients, as a validation set, with histopathologically-confirmed localized (stage Ib to IV; AJCC-6th) GC were enrolled between 2002 and 2010. Four functional SNPs in AREG and five SNPs in EREG were selected. Genomic DNA was extracted from blood or tissue, and all samples were analyzed by PCR-based direct DNA-sequencing. Results: The median follow-up periods were 4.0 years in the Japanese cohort and 3.3 years in the US cohort, respectively. The median DFS and OS in the Japanese cohort were 4.8 and 5.8 years, whereas the median TTR and OS in the US cohort were 2.8 and 4.7 years, respectively. Only exon 1 polymorphism rs1615111 G/A was associated with outcome in Japanese cohort. Patients heterozygous G/A (n=23) showed a median OS of 2.7 years vs. 20.1 years for patients homozygous G/G (n=146) (HR: 1.83 [95%CI: 1.02-3.30], p=0.039). This result was successfully validated in the US cohort. Patients harboring at least one-A allele (n=14) showed a median OS of 2.8 years vs. 5.4 years for patients homozygous G/G (n=111) (HR: 2.54 [95%CI: 1.09-5.89], p=0.018). In the pooled multivariate analysis, these results were still conserved (HR=2.24 [95%CI: 1.36- 3.67], p=0.0015). Conclusions: AREG exon 1 polymorphism rs161511 may be negative prognostic factor in GC regardless ethnicity and regional differences in gastric cancer. Further clinical validation of SNPs in EGFR ligands are warranted.
Trans-catheter arterial p53-gene-embolization using gelatin sponge particles in treatment of patients with advanced hepatocellular carcinoma.
Authors: Zhang Yuewei 
Published: March 2020

e15024 Background: Treatment options for advanced hepatocellular carcinoma (HCC) are limited due to patients’ poor condition, and resistance to both chemo- and radio-therapy. Trans-catheter embolization (TAE) or Trans-catheter chemo-embolization (TACE) is the most widely used locoregional treatment for advanced HCC. But no solid evidences support the beneficial effect of the chemotherapy in TACE. Many advanced HCC patients also can’t tolerate the locoregional chemotherapy. The p53 gene has multiple anticancer functions and does not have any of the immune-inhibitory effects of chemo- or radio-therapy. The objectives of this study are to investigate TAE plus recombinant adenoviral human p53 gene (rAd-p53) in treatment of advanced HCC. Methods: Fifty-eight patients with advanced, unresectable HCC were randomly to two groups: TAE plus p53 group (TAE-p53G), or TAE group (TAEG). The study patients included 56 males and 2 females with an average age of 62.5 (53-89) years old and with Child-Pugh score A or B (42 or 16, respectively). The patients received 3 times of TAE plus rAd-p53 for TAE-p53G or TAE only for TAEG, once in a month for 3 months. The TAE materials consist of gelatin sponge particles (GSP) alone or plus 2-4 x 1012viral particles of rAd-p53, mixed into 30 ml suspension. The study endpoints included response rate, one-year survival, liver function, and adverse effects. Results: After 3-5 days of the first treatment, CT scan showed deceased tumor density in all the study cases. At 6 months after the first treatment, based on the RECIST standard, 31.0% (9/29) and 51.7% (15/29) patients in TAE-p53G achieved a complete response (CR) and partial response (PR), respectively, versus 17.2% (5/29) and 37.9% (11/29) of CR and PR in TAEG, respectively. One-year survival rates were 79.4% and 60.7% with median survival time of 11.7 and 8.3 months for TAE-p53G and TAEG, respectively. There are no significant changes of liver functions in both groups after treatment. Mild or median fever was observed in all the patients in TAE-p53G. No serious adverse events or complications observed. Conclusions: TAE using GSPs plus rAd-p53 is effective and safe treatments for advanced HCC.
Synergistic killing in pancreatic cancer cell lines of the combination of a MEK inhibitor and DNA methylation inhibitor.
Authors: Jeffries Matlock Arizona , Kurkjian Carla 
Published: March 2020

e15025 Background: A growing body of evidence implicates aberrant DNA methylation in the etiology of a number of cancers, including pancreatic. Previous reports link defective ERK signaling with reduced DNA methylation via DNMT1. Here, we examined the ability of the MEK inhibitor U0126 to alter expression of DNMTs in k-RAS mutant and wild type pancreatic cancer cell lines and assess additive cytotoxicity of U0126, the hypomethylating agent 5-Azacytidine and two HDAC inhibitors. Methods: DNMT levels were quantified in AsPC1 and BxPC3 lines 2 days after adding 25 umolar U0126 using real-time RT-PCR. Significance was calculated using a Student t-test. For survival, agents were added singly and in combination: U0126, 25 umol; 5-Aza, 10 umol; Valproic acid 1 mmol and Trichostatin-A 5 umol. Survival was assessed using a colorimetric MTS method at 1, 2, 3, and 4 days. Expected cell survival and synergism were calculated via relative risk ratios, and significance via a Student t-test. Results: U0126 treatment reduced expression of DNMT1 significantly in AsPC1: 2.06 ± 0.3 vs. 1.09 ± 0.08, p = 0.004 (mean ± S.D., arbitrary units). No change was seen in BxPC3. Increased expression of de novo DNMT3a and DNMT3b was seen: AsPC1 1.28 ± 0.3 vs. 3.13 ± 0.8, p = 0.02; BxPC3 1.78 ± 0.3 vs. 4.14 ± 1, p = 0.02; AsPC1 1.26 ± 0.3 vs. 2.66 ± 0.4, p = 0.006, respectively. DNMT3b in BxPC3 was not altered significantly. U0126 and 5-Aza were individually cytotoxic in both cell lines, and synergism was observed in combination. In AsPC1, the observed vs. expected combination survival was 13% ± 3% vs. 29% ± 2%, p = 0.001; for BxPC3, 7% ± 2% vs. 62% ± 3%, p = 0.002, both at 4d. No synergism was found when adding Valproic acid or Trichostatin-A. Conclusions:Treatment of k-RAS mutant pancreatic cancer cell lines with the MEK inhibitor U0126 results in significantly reduced expression of DNMT1 and increased DNMT3a and DNMT3b. U0126 combined with 5-Aza produced synergistic cytotoxicity, which may be due to enhanced hypomethylation activity. Although no significant change in expression of DNMT1 was found in the BxPC3 cells, we noted synergistic cytotoxicity when treated with both U0126 and 5-Aza.
Cetuximab combined with concurrent chemoradiotheray in Chinese patients with unresectable, locally advanced esophageal squamous cell carcinoma: A prospective, multicenter phase II trial.
Authors: Meng Xue , Wang Jianhua , Sun Xindong , Wang Lvhua , Ye Ming , Feng Ping bo , Zhu Guangying , Lu You , Han Chun , Zhu Shu chai , Liao Zhongxing X. , Yu Jinming 
Published: March 2020

e15030 Background: This multicenter phase II trial investigated cetuximab add to concurrent chemoradiotherapy for Chinese patients with esophageal squamous cell carcinoma (ESCC). Methods: Patients with unresectable locally advanced cervical, thoracic upper or mid-ESCC were eligible for this phase II trial. All patients received cetuximab (400 mg/m2 day 1 before chemoradiotherapy and 250 mg/m2 q1w × 7 weeks), paclitaxel (45 mg/m2 q1w × 7 weeks) and cisplatin (20 mg/m2 q1w × 7 weeks) with 59.4 Gy of radiation (1.8Gy/33f). The primary end point was response rate. Second end points included toxicity, overall survival (OS), progression-free survival (PFS), and KRAS mutation status. Results: Forty-five previously untreated patients (36 men, 9 women; median age, 59 year; performance status 0 or 1) with ESCC were treated and evaluated for clinical and radiographic response. After therapy, 29 patients (65%) achieved a complete response, and 15 (33%) patients achieved a partial response, the response rate was 97.7%. Non-hematological adverse events were generally grade 1 or 2, and were most often rash (94.5%), mucositis (58.2%), fatigue (45.5%), nausea (41.8%) and hepatic dyfunction (40%). Hematologic adverse events included grade 3 neutropenia (32.7%) and grade 3 anemia (1.82%). The 1-year PFS and OS rates were 87.3% and 91.1%, 2-year OS were 83.02%, respectively. No mutations were detected at KRAS codons 12 or 13 in all specimens. Conclusions: Cetuximab can be safely administered with chemoradiation for Chinese patients with esophageal cancer and may improve the clinical response rate. KRAS mutations were too rare to be analyzed as a predictor of response. Clinical trial information: NCT00815308.
A pilot study for cellular detection of circulating tumor cells and disseminated tumor cells of patients with hepatocellular carcinoma.
Authors: Minagawa Nozomi , Sakihama Hideyasu , Kobayashi Nozomi , Wakayama Kenji , Kakisaka Tatsuhiko , Tsuruga Yousuke , Shimokuni Tatsushi , Homma Shigenori , Yokoo Hideki , Kamachi Hirofumi , Takahashi Norihiko , Kamiyama Toshiya , Taketomi Akinobu 
Published: March 2020

e15038 Background: Circulating tumor cells (CTC) in peripheral blood (PB) and disseminated tumor cells (DTC) in bone marrow (BM) have been recently focused as predictive and prognostic markers in solid tumors. But hepatocellular carcinoma (HCC) usually lacks epithelial antigens, only a few reports described CTC or DTC at a cellular level. The aim of this study is to establish methodology for detecting CTC and DTC in HCC at a cellular level, and to determine to what degree DTC match the phenotype criterion of putative cancer stem cells. Methods: PB (n-17) and BM samples (n-12) were preoperatively collected from patients with HCC between October 2011 and December 2012. Mononuclear cells were collected by Ficoll gradient separation. CD45+ cell population was deleted through magnetic activated cell sorting system. Subsequently, double immunofluorescence for AFP, Arginase-1 or Hep-Par1 and CD45 was performed. PB samples from 20 healthy volunteers and BM samples from 3 patients with benign disease were used as controls. Our protocol has been approved by the ethical committee of Hokkaido University Hospital and written informed consent was obtained from all enrolled patients. Results: Positive rates of CTC and DTC were 70.5% (12/17) and 75.0% (9/12), respectively. No CTC or DTC was found in the control groups. Poorly differentiated HCC were found in 50.0% of CTC+ patients and 66.6% of DTC+ patients, whereas, 20% in CTC- patients and 0% of DTC- patients. There’re higher risk of recurrence in CTC+ or DTC+ patients, compared with that of CTC- or DTC- patients (33.3%, 55.5% vs 20%, 0%). Over 40% of DTC expressed putative stem cell marker CD133, although the median positive rate of CD133 in primary HCC was reported to be less than 1%. Conclusions: Our protocol might provide highly specific detection of CTC, DTC from HCC patients. Detection of CTC and DTC might closely correlate with histological grade of differentiation and recurrence rate.
Evaluation of EORTC QLQ-C30 and QLQ-STO22 in a phase II, placebo-controlled trial of rilotumumab (R) plus epirubicin, cisplatin, and capecitabine (ECX) in patients (pts) with locally advanced (LA) or metastatic (m) gastric (G) or esophagogastric junction (EGJ) cancer.
Authors: Tzivelekis Spiros , Loh Elwyn , Gallagher Meghan , Barlev Arie , Iveson Timothy 
Published: March 2020

e15046 Background: To select a patient-reported outcomes (PRO) instrument for use in a pivotal G/EGJ cancer study, we evaluated the characteristics of two quality of life (QoL) questionnaires in a phase II trial of R (a fully human monoclonal antibody that neutralizes HGF, the MET receptor ligand) or placebo + ECX in the first-line treatment of 121 pts with LA or mG/EGJ cancer. The trial showed trends for improved survival in the R arms, especially in pts with METHigh(> 50% cells +ve). Methods: Discriminant validity of EORTC QLQ-C30 and QLQ-STO22 was assessed by mean baseline (BL) scores grouped by ECOG PS 0 or ≥1. Responsiveness was assessed by longitudinal analyses of mean PRO score changes from BL by change in ECOG PS (better, no change, or worse). Results: Questionnaire completion was ≥ 60% for cycles 1-5. QLQ-C30 scores at BL had good discriminant validity by ECOG PS: ≥1 corresponded to lower QoL. QLQ-C30 was responsive to change from BL: higher mean QLQ-C30 scores were associated with improved ECOG PS. In contrast, QLQ-STO22 scores had poor discriminant validity and poor responsiveness to change from BL. Results were consistent across treatment arms, the intent-to-treat population, and MET expression groups. Conclusions: EORTC QLQ-C30, a global measure of QoL, correlates well with ECOG PS and is a valid and responsive QoL measure in this pt population. QLQ-STO22 is more specific for stomach-related symptoms and did not correlate with ECOG PS. QLQ-C30 will be included in a phase III, randomized, placebo-controlled trial of R + ECX for the first-line treatment of MET+ve LA or mG/EGJ cancer (NCT01697072). Clinical trial information: NCT00719550. [Table: see text]
Loss at long arm of chromosome 4 as a predictive factor for recurrence of human hepatocellular carcinoma after orthotopic living-donor liver transplantation.
Authors: Nishimura Takafumi , Mori Yukiko , Uemoto Shinji , Nishida Naoshi 
Published: March 2020

e15054 Background: Living-donor liver transplantation (LDLT) is one of the curative treatments of hepatocellular carcinoma (HCC) that confined to the liver. To extend the indication of LDLT where candidate donors are more likely to be found than in liver transplantation from brain death, the Kyoto criteria (maximum tumor diameter < 5 cm, number of tumor < 10 nodules, serum PIVKA-II < 400 mAU/ml) has been proposed in addition to Millan criteria (< 5 cm for solitary nodule, or < 3 cm and < 3 nodules). The aim of this study was to identify genetic or epigenetic changes that predict recurrence in this setting. Methods: With informed consent, tumor and non-tumor tissues were obtained from 51 patients with HCC at the time of LDLT surgery. DNA copy number alterations were determined by microsatellite analysis and single nucleotide polymorphism array analysis. Mutational analyses for TP53 and CTNNB1 were performed by direct sequencing. DNA methylation status of 18 tumors was further analyzed using BeadChip Human Methylation 450. Results: Identified factors that indicate high risk for recurrence were: exceeding the Millan criteria (p = 0.0245, Log-rank test), exceeding the Kyoto criteria (p = 0.0007), hepatitis B virus infection (p = 0.0057), poorly differentiated tumor (p = 0.0245), loss of 4q34.3 (p = 0.0003), 14q (p = 0.0003), 17p (p = 0.0103), and gain of 8q24 (p = 0.0101), and high fractional allelic loss index (p < 0.0001). In patients who exceeded the Kyoto criteria for LDLT loss of 4q were associated with recurrences (5 recurrences for 6 cases with loss of 4q vs. no recurrence for 6 cases with retaining 4q). Conclusions: Genetic and epigenetic analysis combined with clinico-pathological features may help extending the indication for LDLT in patients with HCC.
Increasing stepwise expression of p16 e pRb proteins in esophageal mucosa from patients at high risk for squamous cell carcinoma.
Authors: Muller Leandro Bizarro , Antunes Luis Carlos Moreira , Lopes Antonio de Barros , Vanazzi Sara , Meurer Luise , Fagundes Renato Borges 
Published: March 2020

e15067 Background: Squamous cell carcinoma of the esophagus is a lethal cancer which carries a poor prognosis due to late diagnosis. Identification of molecular markers may aid early diagnosis. We assessed the expression of p16 and pRb in esophageal mucosa and their associations with histology. Methods: Esophageal biopsies were collected from 38 patients with no esophageal lesion (group 1); from iodine-negative and normally staining areas from 108 alcoholic smokers (group 2); and from tumor and non-tumor areas from 41 patients with squamous cell carcinoma (group 3). The histological diagnoses were compared with immunoexpression of p16 and pRb (defined as positive staining in >10% of the cells). Results: In group 1, the biopsies showed only normal mucosa or mild esophagitis, and no expression of p16 or pRb. In groups 2 and 3 the diagnoses were: normal mucosa (38.4%); esophagitis (44.4%); dysplasia or carcinoma in situ (2.8%) and carcinoma (14.3%). The percentage of cases with immunoexpression of p16 and pRb increased in a stepwise fashion over the histologic spectrum from normal mucosa to esophagitis, dysplasia/carcinoma in situ and carcinoma (p for trend < 0.01). Conclusions: Esophageal mucosa exposed to alcohol and tobacco which expresses these proteins may be at risk for malignant transformation.
Long-term prognosis of patients with gastric cancer in stage UICC I without lymph-node involvement.
Authors: Treese Christoph , Sanchez Pedro , Anagnostopoulos Ioannis , Schlag Peter M. , Kruschewski Michael , Haase Oliver , Berger Gerd , Blaeker Hendrik , Hummel Michael , Daum Severin 
Published: March 2020

e15068 Background: Despite radical oncologic resection with extended lymph node removal, patients with adenocarcinoma of the gastro-esophageal junction or stomach in UICC stage I show only a 5-year survival of 60-80% (Hölscher et al, 2009; Siewert et al. 1998). The aim of this retrospective study was to analyze the long-term survival of caucasian patients with early stage gastric cancer as for this population exist only sparse data. Patients with lymph-node involvement were not included as this parameter is a well-known negative prognostic marker. Methods: Tissue specimens and clinical data from patients with gastric cancer treated in the years 1993 to 2010 at the Charité, Berlin were collected retrospectively. Patients with stage T1 and T2 pN0M0 gastric cancer treated only by surgery including D1- and D2-lymphnode dissection were included in this study. Patients without relapse were followed-up for a minimum period of 24 months. Results: 97 patients (w = 36, m = 61, age 29-90 years) with a follow-up time from 6 to 208 months were identified. The 5-year survival was 94.85% (for details, see Table). Conclusions: The present data indicate a much better prognosis (5-year survival of 95%) of UICC I patients than previously described (60-80%). In harmony with other studies, our data demonstrate that R1, L1 or V1 resection seem to be a risk factor for recurrence whereas signet-ring differentiation was not found as a risk factor in our patient cohort. Ongoing work involves a broad panel of immunohistochemical markers to select prognostic expression profiles which help to identify patients with early gastric cancer at higher risk. This study was supported by the Berliner Krebsgesellschaft, grant DAFF201101. [Table: see text]