ADJ Group Research Articles

Significance of Adjuvant Chemotherapy for Obstructive Colorectal Cancer After Stent Placement: A Multicenter Retrospective Study.

To explore the survival benefit of adjuvant chemotherapy for obstructive colorectal cancer (OCRC) managed by self-expandable metallic stent (SEMS) placement as a bridge to surgery (BTS). One hundred twenty-nine patients with pathological stage II/III OCRC who underwent BTS using a SEMS were included in this multicenter retrospective study. Patients were divided into the no-adjuvant chemotherapy group (No-Adj group) (n=52) and adjuvant chemotherapy group (Adj group) (n=77), and relapse-free survival (RFS) was compared. The No-Adj group had more fragile patient background factors, such as higher age, higher American Society of Anesthesiologists score, and lower preoperative albumin compared with the Adj group. The 3-year RFS rates for the overall cohort were significantly different between the No-Adj and Adj groups (56.4% and 78.5%, respectively; p=0.003). Significant RFS benefits of adjuvant chemotherapy were observed in both pathological stage II and III cancer. Characteristics of more advanced cancer, such as high carcinoembryonic antigen (CEA), pathological T4, and lymphovascular invasion, were associated with survival improvement by adjuvant chemotherapy. T4 and adjuvant chemotherapy were significantly associated with RFS in the multivariate Cox proportional analysis. To our knowledge, this is the first study to show a survival benefit of adjuvant chemotherapy in patients with OCRC undergoing BTS using a SEMS. Adjuvant chemotherapy is basically recommended regardless of the cancer stage and is strongly recommended with more advanced characteristics, such as high CEA, T4, and lymphovascular invasion.

Comparison of Growth Outcomes Between Human Milk-Fed Preterm Infants on Standard Versus Adjustable Fortification Protocols.

Background: Human milk (HM) is usually fortified using standard fortification (STD) to improve nutrition of preterm infants. However, the protein component may still be insufficient. HM could be further fortified with additional protein to improve STD. Objective: The primary objective was to compare changes in body weight (g/day, g/kg/day), length, and head circumference (mm/day) between preterm neonates fed HM with STD and those fed HM with adjustable fortification (ADJ). Methods: This study was a prospective, single-blinded, randomized controlled study in preterm infants of gestational age <32 weeks and weighing ≤1,800 g, admitted to the neonatal unit of the Queen Sirikit National Institute of Child Health. Once the infants received full HM feed with STD at 24 kcal/oz, they were randomized to either continue with STD or with ADJ group by adding additional protein to the STD and making further protein adjustments based on the blood urea nitrogen levels. Results: Thirty preterm infants completed the study and were randomized into two groups of 15 each. The baseline characteristics, total fluid, and energy intake were similar. Compared with the STD group, infants in the ADJ group exhibited significantly greater weight gain (36.46 ± 6.09 vs. 25.78 ± 8.81 g/day; p = 0.001) and greater length gain (1.93 ± 0.57 vs. 1.12 ± 0.64 mm/day; p = 0.001). Protein intake significantly correlated with both weight (r = 0.632, p < 0.001) and length gain (r = 0.577, p = 0.001); however, no correlation was found between energy intake, volume intake, and growth outcomes. Conclusion: Preterm infants fed with ADJ had significantly higher weight and length gains than those fed with STD, suggesting that additional protein intake may play an important role in growth.

Microarchitectures of Barrett's esophagus associated with DNA methylation status.

Aim: DNA methylation is involved in esophageal adenocarcinoma (EAC) and Barrett's esophagus (BE). Microarchitectures of on-neoplastic BE associated with DNA methylation status were examined using magnifying narrow-band imaging (NBI) endoscopy. Patients and methods: Using biopsies from non-neoplastic BE without cancer (n=66; N group), with EAC (n=27; ADJ group) and EAC tissue (n=22; T group), methylation of N33, DPYS, SLC16A12, miR124a3 andmiR34bc genes were quantified. MagnifyingNBI features of non-neoplastic BE were classified according to their morphologies. Results: TheADJ and T groups presented higher DNA methylation compared with theN group. Magnifying NBI endoscopic features of non-neoplastic BE also correlated with DNA methylation as an independent factor. Conclusion: Microarchitectures of BE visualized by magnifying NBI endoscopy correlated with DNA methylation.

Comprehensive DNA methylation profiling of Barrett's esophagus and esophageal adenocarcinoma in Japanese patients.

Molecular mechanisms of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) remain unclear in Japanese patients. Japanese EACs frequently have underlying short length BE: short-segment BE(SSBE), for which, neoplastic potential remains unclear. We performed comprehensive methylation profiling of EAC and BE in Japanese patients, mostly comprised with SSBE. Using three different groups of biopsies obtained from non-neoplastic BE from patients without cancer (n = 50; N group), with EAC (n = 27; ADJ group) and EAC (n = 22; T group), methylation statuses of nine candidate genes (N33, DPYS, SLC16A12, CDH13, IGF2, MLF1, MYOD1, PRDM5, and P2RX7) were examined by the bisulfite pyrosequencing. Reduced representation bisulfite sequencingwas performed to characterize the genome-wide methylation status in 32 samples (12 from N, 12 ADJ, and 8 from T groups). In the candidate approach, methylation levels of N33, DPYS, and SLC16A12 were higher in ADJ and T groups compared to that in N group. The ADJ group was an independent factor for higher DNA methylation in non-neoplastic BE. The genome-wide approach demonstrated an increase of hypermethylation from ADJ to T groups relative to N group near the transcription start sites. Among gene groups hypermethylated in ADJ and T groups (n = 645) and T group alone (n = 1438), 1/4 and 1/3 were overlapped with downregulated genes in the microarray data set, respectively. Accelerated DNA methylation is observed in EAC and underlying BE in Japanese patients, mostly comprised with SSBE, highlighting the potential impact of methylation in early carcinogenesis.

Effect of Chemotherapy on the Gut Microbiome of Breast Cancer Patients During the First Year of Treatment.

There is accumulating information of the effects of chemotherapy and weight changes on the gut microbiome of breast cancer patients. In this 1-year follow-up study, we investigated gut microbiome of 33 breast cancer patients who donated fecal samples at baseline and after completion of treatment. We compared alpha diversity and mean taxa abundance at baseline and absolute taxa abundance changes (final-baseline) by treatment (16 neoadjuvant [neoADJ], 13 adjuvant [ADJ], 4 no chemotherapy [noC]) and specific chemotherapy agent using Wilcoxon rank sum and negative binomial mixed model (NBMM) analysis. All four gut alpha diversity measures changed in association with chemotherapy treatment; they increased in the neoADJ (+16.4% OTU p = 0.03; +51.6% Chao1 p = 0.03; +7.0% Shannon index p = 0.02; +11.0% PD whole tree p = 0.09) but not in the ADJ and noC group (ADJ+noC). The difference in Chao1 index change between groups was statistically significant (pneoADJ vs. ADJ+noC=0.04). Wilcoxon p values of 0.03-0.003 were observed for five taxa. In NBMM analysis, changes in taxa abundance differed (Bonferroni-adjusted p ≤ 0.0007) for two Bacteroidetes taxa (g_Alistipes, f_S24-7) and two Firmicutes taxa (g_Catenibacterium, g_Eubacterium). NBMM analysis results remained unchanged with adjustment for weight changes. Alpha diversity changes were also found by receipt of chemotherapy agents. Consistent increases in alpha diversity were observed among those treated with TCHP (OTU p = 0.009; Chao1 p = 0.02; Shannon p = 0.02; PD whole tree p = 0.05) but not AC, Taxol or Herceptin. Those treated with TCHP or Herceptin showed increases in Verrucomicrobia (g_Akkermansia) but decreases of Bacteroidetes(g_Alistipes); the differences in changes in taxa abundance were statistically significant. Results from this pilot longitudinal study support an effect of chemotherapy, particularly neoADJ on the gut microbiome of breast cancer patients even after adjustment for weight changes. Further investigations are needed to confirm these findings in larger studies and with longer follow-up and to assess the impact of these microbiome changes on patient outcome.

Alpha-actinin-4 (ACTN4) gene amplification is a predictive biomarker for adjuvant chemotherapy with tegafur/uracil in stage I lung adenocarcinomas.

Although adjuvant tegafur/uracil (UFT) is recommended for patients with completely resected stage I non‐small‐cell lung cancer (NSCLC) in Japan, only one‐third of cases has received adjuvant chemotherapy (ADJ) according to real‐world data. Therefore, robust predictive biomarkers for selecting ADJ or observation (OBS) without ADJ are needed. Patients who underwent complete resection of stage I lung adenocarcinoma with or without adjuvant UFT were enrolled. The status of ACTN4 gene amplification was analyzed by FISH. Statistical analyses to determine whether the status of ACTN4 gene amplification affected recurrence‐free survival (RFS) were carried out. Formalin‐fixed, paraffin‐embedded samples from 1136 lung adenocarcinomas were submitted for analysis of ACTN4 gene amplification. Ninety‐nine (8.9%) of 1114 cases were positive for ACTN4 gene amplification. In the subgroup analysis of patients aged 65 years or older, the ADJ group had better RFS than the OBS group in the ACTN4‐positive cohort (hazard ratio [HR], 0.084, 95% confidence interval [CI], 0.009‐0.806; P = .032). The difference in RFS between the ADJ group and the OBS group was not significant in ACTN4‐negative cases (all ages: HR, 1.214; 95% CI, 0.848‐1.738; P = .289). Analyses of ACTN4 gene amplification contributed to the decision regarding postoperative ADJ for stage I lung adenocarcinomas, preventing recurrence, improving the quality of medical care, preventing the unnecessary side‐effects of ADJ, and saving medical costs.

Survival analysis of patients with advanced hypopharyngeal cancer comparing patients who received primary surgery to those who received chemoradiation: An analysis of the NCDB

IntroductionThe objective of this study was to use the American College of Surgeons’ National Cancer Database (NCDB) to examine the association between primary treatment and overall survival (OS) among patients with locoregionally advanced hypopharyngeal cancer. Methods6,055 adult patients diagnosed between 2004 and 2015 with stage III or IV, M0, hypopharyngeal squamous cell carcinoma were identified within the NCDB. Patients who received primary chemoradiation (CRT) were compared to those that received surgery with adjuvant radiation or chemoradiation (S + Adj). OS was compared between treatment groups using Kaplan-Meier analyses, propensity score adjustment, and Cox regression analyses. ResultsThe median survival was 22.7 months (IQR 11.0–49.0). The S + Adj group had a significantly higher comorbidity score, higher grade disease, and more advanced stage disease than the CRT group. S + Adj was associated with significantly improved survival when compared to CRT (p < 0.0001). A propensity score adjusting for facility type, facility location, care at multiple facilities, histology, and T stage was developed. S + Adj was associated with longer survival (HR: 0.72, 95% CI: 0.64–0.80) when compared to CRT in a multivariable Cox regression analysis (adjusting for age, race and ethnicity, insurance status, a comorbidity index, diagnosis year, treatment delay, N stage, and the propensity score). S + Adj was associated with significantly improved survival among those with T2 disease (p = 0.02), T3 disease (p = 0.02), and T4 disease (p < 0.0001) in sensitivity analyses examining these subcohorts independently. ConclusionsAmong patients with advanced hypopharyngeal cancer reported in NCDB, treatment with S + Adj was associated with longer survival compared to those treated with primary CRT.

Comparison Of Adjuvant Versus Salvage Therapy Among IDH Mutant Low-Grade Glioma

Timing of postoperative management in low grade glioma (LGG) is controversial. We sought to evaluate the clinical outcomes among molecularly classified LGG patients (pts) treated with adjuvant (adj) versus (v) salvage treatment (salv). We included pts ≥ 18 yrs old at diagnosis of LGG (WHO grade II) from 1980-2018 with an IDH mutation (mut) and 1p19q data allowing for molecular classification. Pts in the adj group received immediate postoperative treatment (temozolomide [TMZ] and/or radiotherapy [RT]) prior to progression. Salv pts were initially observed then received TMZ and/or RT at disease progression. Endpoints were calculated from date of first surgical resection or biopsy, and included overall survival (OS) and next intervention free survival (NIFS), defined as the date of either surgery or treatment subsequent to adj or salv, or death. 296 IDH mut pts were included. Among the 168 pts with 1p19q codel, median follow up was 8.3 yrs (range, .03 – 26), median age was 43 yrs (range, 20-78), 57% were male, and 29% had GTR (gross total resection). 100 pts (60%) received adj (TMZ, 22%; RT, 65%; TMZ+RT, 13%), which was more likely in pts who were older, had larger tumors, or underwent biopsy alone (p<.05 for each). On univariable analysis (UVA), 5 yr NIFS for adj v salv was 70% (95% CI, 61-80%) v 83% (74-93%; p = 0.06), and 5 yr OS was 90% (84-97%) v 97% (93-100%; p<0.01), respectively. However, when adjusting for high risk factors associated with selection bias on multivariable analysis (MVA, Table), adj was not associated with either NIFS or OS as compared to salv. Among the 128 pts with 1p19q intact, median follow up was 6 yrs (range, 0.04 – 19), median age was 35 yrs (range, 19-66), 52% were male, and 41% had GTR. 49 pts (38%) received adj (TMZ, 29%; RT, 26%; TMZ+RT, 45%), which was more likely in pts who were older, had larger tumors, or underwent biopsy alone (p<.05 for each). On UVA, 5-year NIFS for adj v salv was 69% (95% CI, 56-85%) v 41% (31-56%; p<0.01), and 5-year OS was 85% (75-97%) v 91% (84-98%; p = 0.7), respectively. On MVA (Table), adj remained associated with improved NIFS compared to salv, but had no association with OS. Among IDH mut 1p19q codel pts, adj was not associated with improved NIFS or OS, suggesting initial observation followed by salv at progression is appropriate for this population. In contrast, among IDH mut 1p19q intact pts, adj was associated with improved NIFS, but not OS, supporting a more individualized postoperative management approach.Abstract 3689; TableMVAIDH mut 1p19q codelIDH mut 1p19q intactNIFSOSNIFSOSHR (95% CI)pHR (95% CI)pHR (95% CI)pHR (95% CI)pAdj v salv1.2 (0.8-1.9).421.3 (0.7-2.4).380.4 (0.2-0.7)<.010.9 (0.5-1.6).69Age ≥40 v <401.5 (1.0-2.3).072.1 (1.2-3.8).011.1 (0.7-1.9).631.3 (0.7-2.5).37Biopsy.16.02.09.18GTR0.7 (0.4-1.1).130.4 (0.2-0.8).011.0 (0.5-2.3).910.6 (0.2-1.6).34STR0.7 (0.4-1.1).090.6 (0.3-1.0).051.7 (0.8-3.6).131.3 (0.6-2.7).57Female v male0.8 (0.5-1.2).340.7 (0.4-1.2).230.5 (0.3-0.9).010.5 (0.3-0.9).04 Open table in a new tab

Abstract P2-16-33: Patient characteristics and real-world treatment patterns in patients with early-stage triple-negative breast cancer receiving neoadjuvant chemotherapy

Abstract Background: For patients with stage II-III early-stage triple-negative breast cancer (ESTNBC), either neoadjuvant or adjuvant administration of chemotherapy is recommended. There is limited evidence describing the real-world patient characteristics and treatment patterns among patients receiving neoadjuvant +/- adjuvant chemotherapy for ESTNBC. Methods: We conducted a retrospective observational study to describe the demographic and clinical characteristics and treatment patterns in ESTNBC patients in the US community oncology setting. Eligibility criteria included female sex, age 18+, diagnosis of stage II, IIIA or IIIB ESTNBC between 3/2008 and 3/2016, receipt of definitive surgical resection, and neoadjuvant systemic therapy with or without adjuvant systemic therapy. Descriptive methods were used to compare demographic and clinical characteristics and treatment patterns among patients who received neoadjuvant systemic therapy only (Neo) versus patients who received neoadjuvant plus adjuvant systemic therapy (Neo+Adj). Results: 308 patients were eligible for the study. There were 236 patients (76.6%) who received Neo, while 72 (23.4%) received Neo+Adj. Mean age was 52.1 (SD 11.3), with 86.4% (n=266) of patients 65 or younger. Patients were predominantly White (56.8%, n=175) followed by African American (35.7%, n=110). Demographic characteristics did not differ by treatment group. The majority of patients were stage II at initial diagnosis (66.6%, n=205) and had ductal histology (93.5%, n=288). Over half of all patients (55.8%, n=172) had mastectomy; 44.2% (n=136) had breast conservation surgery. The majority of patients (79.5%, n=245) had no comorbid conditions and most (82.8%, n=255) had grade 3 tumors. Overall, 42.2% were peri/postmenopausal (n=130) at diagnosis. Distribution of stage at diagnosis was significantly different between groups (p=0.013). The pattern of findings suggests that the Neo group had earlier stage disease. Over one-third of patients with Neo were stage IIA at diagnosis (36.0%, n=85). Nearly one-fifth of patients with Neo+Adj were stage IIIB at diagnosis (19.4%, n=14), compared to 8.5% of patients receiving Neo (n=20). A significant difference in surgery type by treatment group was observed (p=0.035). Patients with Neo had a lower rate of mastectomy (52.5%, n=124) compared to Neo+Adj (66.7%, n=48), likely as a result of earlier stage disease at presentation. Among the Neo group, the most common neoadjuvant regimen was cyclophosphamide, doxorubicin and paclitaxel (59.3%, n=140), followed by cyclophosphamide, doxorubicin and docetaxel (14.4%, n=34). Most (85.2%, n=201) patients receiving Neo received one regimen in the neoadjuvant setting, while 13.1% (n=31) received two regimens. Among the Neo+Adj group, the most common neoadjuvant regimens were cyclophosphamide, doxorubicin and paclitaxel (38.9%, n=28) and cyclophosphamide with doxorubicin (23.6%, n=17), while the most common adjuvant regimens were paclitaxel (22.2%, n=16) and capecitabine (12.5%, n=9). Most (70.8%) patients receiving Neo+Adj received one neoadjuvant regimen followed by a different adjuvant regimen. Conclusions: In this sample of real-world patients with ESTNBC, the majority of patients were diagnosed with stage II disease, with limited or no comorbidities. This evaluation of treatment patterns confirmed that real-world treatment is limited to chemotherapy, which is consistent with the NCCN guidelines. Citation Format: Whitney C Rhodes, Santosh Gautam, Amin Haiderali, Min Huang, Jan Sieluk, Karen E Skinner, Lee S Schwartzberg. Patient characteristics and real-world treatment patterns in patients with early-stage triple-negative breast cancer receiving neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-33.

Immune responses induced by oil-adjuvanted inactivated vaccine against Flavobacterium psychrophilum in ayu Plecoglossus altivelis

Oil-adjuvant formulated formalin killed cells of Flavobacterium psychrophilum (FKC + Adj) is strongly effective against bacterial cold-water disease (BCWD) in ayu Plecoglossus altivelis. In this study, we aimed to understand mechanisms underlying the strong protection by the vaccine in ayu. Antibody titer of FKC + Adj and formalin-killed cells (FKC) group was significantly higher than those of modified cytophaga broth injected (MCY) group and MCY with the adjuvant (MCY + Adj) group. The highest antibody titer was observed in FKC + Adj group. Granulomatous inflammation without lymphocyte cuff was observed in the spleen and trunk kidney of FKC + Adj and MCY + Adj group, while the size of the granuloma was bigger in FKC + Adj than in MCY + Adj group. Gene expression level for IL-8 was significantly up-regulated in FKC + Adj group at 4 weeks after the vaccination. In contrast, IL-10 gene expression level was significantly suppressed in FKC + Adj at 4 weeks after the vaccination. F. psychrophilum was almost cleared in the spleen and trunk kidney of FKC + Adj group within 2 days after the challenge. Fluorescent immunohistochemistry showed that a lot of bacterial signals were detected in the spleen and trunk kidney of challenged fish in MCY, FKC and MCY + Adj group. However, the fluorescent signal was not detected in the organs of FKC + Adj group after the challenge. These data suggest that F. psychrophilum is immediately cleared in FKC + Adj vaccinated fish and both specific antibody and activation of phagocytes are essential to clear F. psychrophilum in ayu.

Live birth outcomes of vitrified embryos generated under growth hormone stimulation are improved for women categorized as poor-prognosis.

ObjectiveTo determine the clinical pregnancy (CP) and live birth (LB) rates arising from frozen embryo transfers (FETs) that had been generated under the influence of in vitro fertilization (IVF) adjuvants given to women categorized as poor-prognosis.MethodsA registered, single-center, retrospective study. A total of 1,119 patients with first FETs cycle include 310 patients with poor prognosis (109 treated with growth hormone [GH], (+)GH group vs. 201 treated with dehydroepiandrosterone, (–)GH group) and 809 patients with good prognosis (as control, (–)Adj (Good) group).ResultsThe poor-prognosis women were significantly older, with a lower ovarian reserve than the (–)Adj (Good) group, and demonstrated lower chances of CP (p<0.005) and LB (p<0.005). After adjusting for confounders, the chances of both CP and LB in the (+)GH group were not significantly different from those in the (–)Adj (Good) group, indicating that the poor-prognosis patients given GH had similar outcomes to those with a good prognosis. Furthermore, the likelihood of LB was significantly higher for poor-prognosis women given GH than for those who did not receive GH (p<0.028). This was further confirmed in age-matched analyses.ConclusionThe embryos cryopreserved from fresh IVF cycles in which adjuvant GH had been administered to women classified as poor-prognosis showed a significant 2.7-fold higher LB rate in subsequent FET cycles than a matched poor-prognosis group. The women with a poor prognosis who were treated with GH had LB outcomes equivalent to those with a good prognosis. We therefore postulate that GH improves some aspect of oocyte quality that confers improved competency for implantation.

What should be the protein target for adjustable Human Milk fortification in premature infants?

Objective:To assess the short- and long-term effects of the adjustable fortification (ADJ) regimen on growth parameters in premature infants and to evaluate the amount of protein supplements given to reach the targeted blood urea nitrogen (BUN) levels.Methods:In this retrospective study, preterm babies who were born at ≤32 weeks gestational age and fed with human milk, were evaluated in two groups. Infants in Group-I were fed only standard fortification (STD). Infants in Group-II were fed the ADJ regimen. The study was conducted between 2011 and 2016.Results:There were 123 infants in the STD group and 119 in the ADJ group. The mean gestational age of the patients in Group-I was 29.7±1.8 weeks, and mean birth weight was 1266.1±347.1 g. The mean gestational age of the patients in Group-II was 29.5±1.9 weeks, and the mean birth weight was 1217.5±345.5 g. The daily increase in weight and weekly increase in HC were significantly higher in the ADJ group infants. Weight and HC of infants in the ADJ group were significantly higher at 40 weeks. At one year corrected age, weight, length, and HC measurements of both groups were similar. In Group-II, 63% of patients required additional protein supplementation up to 1.6 g/day to achieve the target BUN levels.Conclusion:A higher protein intake through the ADJ regimen improves the physical growth rate of premature infants in the NICU and after discharge. However, sometimes, the targeted growth and BUN values cannot be achieved despite the administration of protein at the recommended increased doses. Increasing protein supplementation up to 1.6 g/day is safe, feasible, and beneficial for these infants.

DNA methylation accumulation in gastric mucosa adjacent to cancer after Helicobacter pylori eradication.

Molecular irreversibleness with Helicobacter pylori (H. pylori) infection might have a role in gastric tumorigenesis after H. pylori eradication. We performed comprehensive DNA methylation profiling of gastric mucosa after H. pylori eradication with or without gastric cancer. Using four different groups of biopsies obtained from gastric body without history of H. pylori infection (Hp-), gastric body without cancer after H. pylori eradication (cancer-free body), gastric body with early gastric cancer diagnosed after H. pylori eradication (EGC body) and their paired samples from adjacent mucosa of cancer (EGC ADJ), methylation status of five candidate genes (MYOD1, SLC16A12, IGF2, RORA and PRDM5) was examined by the bisulfite pyrosequencing. An Infinium Methylation EPIC BeadChip array was also used to characterize the methylation status of greater than 850,000 CpG sites. The EGC ADJ group showed highest methylation levels of five candidate genes among the four groups of biopsies. In the gastric body (cancer-free body + EGC body), methylation levels were significantly decreased in patients with longer period after eradication, while such association was not observed in EGC ADJ group. Hyper methylated samples were associated with shorter telomere, an indicator for rapid cell turnover, and higher DNMT1 protein expression, an enzyme related to methyl transfer reaction. The genome-wide methylation analysis demonstrated strikingly higher methylation levels especially at CpG islands in the EGC ADJ group. Exclusively hypermethylated promoter CpG islands in the same group frequently coded zinc finger proteins. Our data show that DNA methylation accumulation is associated with molecular irreversibleness and gastric carcinogenesis after H. pylori eradication.

PO-011 Impact of compartment-specific changes in NAD biosynthesis on diethylnitrosamine-induced liver cancer

IntroductionThe molecular irreversibleness with Helicobacter pylori (H. pylori) infection may have a role in gastric tumorigenesis after H. pylori eradication. We performed comprehensive DNA methylation profiling of gastric mucosa after H. pylori eradication with or without gastric cancer.Material and methodsFour different groups of biopsies including gastric body from subjects without history of H. pylori infection (Hp-: n=23), gastric body from cancer-free subjects after H. pylori eradication (cancer-free body: n=48), gastric body from early gastric cancer patients diagnosed after H. pylori eradication (EGC body: n=42) and its paired samples from adjacent mucosa of cancerous area (EGC ADJ: n=43) were used for the study. Methylation status of five candidate genes (MYOD1, SLC16A12, IGF2, RORA and PRDM5) was examined by the bisulfite pyrosequencing. An Infinium Methylation EPIC BeadChip array was used to characterise the methylation status of >8 50 000 CpG sites for 11 samples.Results and discussionsThe EGC ADJ group showed highest mean Z score methylation of 5 candidate genes among the four groups of biopsies. In the gastric body (cancer-free body +EGC body), mean Z score methylation was significantly decreased in patients with longer period after eradication, while such association was not observed in EGC ADJ group. Hyper methylated samples were associated with shorter telomere, an indicator for rapid cell turnover, and higher DNMT1 protein expression, an enzyme related to methyl transfer reaction. The genome-wide methylation analysis demonstrated accelerated methylation especially at CpG islands in the EGC ADJ group. Exclusively hypermethylated promoter CpG islands in the same group frequently coded zinc finger proteins.ConclusionAccelerated DNA methylation is associated with molecular irreversibleness and gastric carcinogenesis after H. pylori eradication.

PO-008 Accelerated DNA methylation in gastric mucosa adjacent to cancer after HELICOBACTER PYLORI eradication

Introduction The molecular irreversibleness with Helicobacter pylori ( H. pylori ) infection may have a role in gastric tumorigenesis after H. pylori eradication. We performed comprehensive DNA methylation profiling of gastric mucosa after H. pylori eradication with or without gastric cancer. Material and methods Four different groups of biopsies including gastric body from subjects without history of H. pylori infection (Hp-: n=23), gastric body from cancer-free subjects after H. pylori eradication (cancer-free body: n=48), gastric body from early gastric cancer patients diagnosed after H. pylori eradication (EGC body: n=42) and its paired samples from adjacent mucosa of cancerous area (EGC ADJ: n=43) were used for the study. Methylation status of five candidate genes ( MYOD1 , SLC16A12 , IGF2 , RORA and PRDM5 ) was examined by the bisulfite pyrosequencing. An Infinium Methylation EPIC BeadChip array was used to characterise the methylation status of >8 50 000 CpG sites for 11 samples. Results and discussions The EGC ADJ group showed highest mean Z score methylation of 5 candidate genes among the four groups of biopsies. In the gastric body (cancer-free body +EGC body), mean Z score methylation was significantly decreased in patients with longer period after eradication, while such association was not observed in EGC ADJ group. Hyper methylated samples were associated with shorter telomere, an indicator for rapid cell turnover, and higher DNMT1 protein expression, an enzyme related to methyl transfer reaction. The genome-wide methylation analysis demonstrated accelerated methylation especially at CpG islands in the EGC ADJ group. Exclusively hypermethylated promoter CpG islands in the same group frequently coded zinc finger proteins. Conclusion Accelerated DNA methylation is associated with molecular irreversibleness and gastric carcinogenesis after H. pylori eradication.

Inhalation of concentrated PM2.5 from Mexico City acts as an adjuvant in a guinea pig model of allergic asthma

Exposure to Particulate Matter (PM) could function as an adjuvant depending on the city of origin in mice allergic asthma models. Therefore, our aim was to determine whether inhalation of fine particles (PM2.5) from Mexico City could act as an adjuvant inducing allergic sensitization and/or worsening the asthmatic response in guinea pig, as a suitable model of human asthma. Experimental groups were Non-Sensitized (NS group), sensitized with Ovalbumin (OVA) plus Aluminum hydroxide (Al(OH)3) as adjuvant (S + Adj group), and sensitized (OVA) without adjuvant (S group). All the animals were exposed to Filtered Air (FA) or concentrated PM2.5 (5 h/daily/3 days), employing an aerosol concentrator system, PM2.5 composition was characterized. Lung function was evaluated by barometric plethysmography (Penh index). Inflammatory cells present in bronchoalveolar lavage were counted as well as OVA-specific IgG1 and IgE were determined by ELISA assay. Our results showed in sensitized animals without Al(OH)3, that the PM2.5 exposure (609 ± 12.73 μg/m3) acted as an adjuvant, triggering OVA-specific IgG1 and IgE concentration. Penh index increased ∼9-fold after OVA challenge in adjuvant-sensitized animals as well as in S + PM2.5 group (∼6-fold), meanwhile NS + FA and S + FA lacked response. S + Adj + PM2.5 group showed an increase significantly of eosinophils and neutrophils in bronchoalveolar lavage. PM2.5 composition was made up of inorganic elements and Polycyclic Aromatic Hydrocarbons, as well as endotoxins and β-glucan, all these components could act as adjuvant. Our study demonstrated that acute inhalation of PM2.5 acted as an adjuvant, similar to the aluminum hydroxide effect, triggering allergic asthma in a guinea pig model. Furthermore, in sensitized animals with aluminum hydroxide an enhancing influence of PM2.5 exposure was observed as specific-hyperresponsiveness to OVA challenge (quickly response) and eosinophilic and neutrophilic airway inflammation. Fine particles from Mexico City is a complex mix, which play a significant role as adjuvant in allergic asthma.

Telomere length in the gastric mucosa after Helicobacter pylori eradication and its potential role in the gastric carcinogenesis.

The molecular mechanisms of gastric carcinogenesis after Helicobacter pylori (H. pylori) eradication remain unclear. We examined the telomere length of gastric mucosa samples after successful H. pylori eradication in patients without and those with gastric cancer. Telomere length was measured by the real-time PCR among four different groups of biopsies: gastric body from subjects without history of H. pylori infection (Hp-: n=23), gastric body from cancer-free subjects after H. pylori eradication (cancer-free body: n=24), gastric body from early gastric cancer patients diagnosed after H. pylori eradication (EGC body: n=35) and its paired samples from adjacent mucosa of cancerous area (EGC ADJ: n=35). The Hp-group presented the longest telomeres among the all groups (Hp- vs. all others, all P<0.05). Samples from EGC body group showed shorter telomere length than the samples from cancer-free body groups (P<0.05). Conversely, samples from EGC ADJ group showed rather longer telomere length compared to the EGC body group (P<0.05), which was also confirmed by the comparison of 35 matched samples (P=0.0007). Among the samples after H. pylori eradication, shorter telomere length was associated with higher expression of IL-1B and NF-kB (P<0.0001, 0.0006, respectively). Longer telomere length was also associated with higher expression of TNF-A (P=0.01). Telomere shortening seems to be important initial steps in gastric cancer predisposition after H. pylori eradication, while it might shift to lengthening to acquire more aggressive pathway to develop cancer.

Comparison of radical surgery followed by adjuvant chemotherapy with radical surgery following neoadjuvant chemotherapy as initial treatment for patients with locally advanced thoracic esophageal squamous cell carcinoma.

187 Background: Although radical surgery with neoadjuvant chemotherapy (NAC) is a standard therapy for locally advanced thoracic esophageal squamous cell carcinoma (ESCC) in response to the result of JCOG 9907 study in Japan, there was no significant difference in survival rate at adjuvant chemotherapy and neoadjuvant chemotherapy in cStage III at subanalysis. Methods: Consecutive patients histologically diagnosed with ESCC and planned to undergo radical surgery followed by adjuvant chemotherapy (ADJ) from September 2002 to April 2007 and radical surgery following NAC from May 2007 to December 2011 as initial treatment were eligible for this retrospective study. To select patients who could tolerate transthoracic esophagectomy, respiratory function, Eastern Cooperative Oncology Group performance status, and preoperative complications were considered. As adjuvant and neoadjuvant chemotherapy, cisplatin and 5-fluorouracil were administered every 3 weeks for 2 cycles (FP). Patient characteristics, 3-year overall survival (3yOS) and non complete resection rate were investigated. We analyzed in intent-to-treat analysis. Results: Ninety patients were included in ADJ group, 98 included in NAC group. No significant differences were observed in clinicopathological factors between ADJ group (cStage IB/II/III/IV=6/22/57/5) and NAC group (cStage IB/II/III/IV=10/28/52/8). In intention-to-treat analysis, there was no significant difference in 3yOS rate by ADJ group and NAC group (ADJ group, 67.2%; NAC group, 66.0%; p = 0.301). However, non complete resection rate was significantly higher for NAC group than for ADJ group {ADJ group, 16.7% (3/90); NAC group, 3.4% (14/98); p = 0.009}. In cStage III, non complete resection rate of ADJ group was 3.5% (2/57) and NAC group was 25% (13/52). In the patients with cStage III, NAC group had a tendency for 3yOS rate to be low rather than ADJ group (ADJ group, 66.3%; NAC group, 51.1%; p = 0.09). Conclusions: In cStage III advanced ESCC, FP as NAC may be insufficient and development of the more powerful NAC is desired.

150 USING A LUTEINIZING HORMONE SURGE DETECTION TEST, PREDI&amp;apos;BOV&amp;reg;, TO OPTIMIZE THE TIME OF ARTIFICIAL INSEMINATION DURING A SUPEROVULATION PROTOCOL IN A HOLSTEIN HEIFERS HERD

Insemination of superovulated bovine donors in due time is of central importance for fertilization and embryo viability. A preliminary test focusing on LH surge detection during superovulation (unpublished datas) indicated that one quarter of the donors present LH surges 12 to 24 h before heat observation (which could correspond, in the case of AI after heat observation, to post ovulation AI). Therefore, it was hypothesised that the average number of embryos per flush could be improved by inseminating donors with early LH surge 12 h after the beginning of the LH peak whenever the heat occurs.In a donor herd station, a trial was performed with 54 Holstein heifers, equipped with Heatime® tags (system detecting the peak activity linked to the heat) collected twice or 3 times after the following superovulation protocol: D-6 to D-11 = reference heat; D0 = input of an implant of norgestomet (Crestar®); D2 8:00 = first FSH (Stimufol®) injection (FSH1); D4 8:00 = cloprostenol (Estrumate®) injection; D4 16:00 = implant removal; D5 8:00 = FSH7 and first LH surge detection test (Predi'Bov®); D5 16:00 = FSH8 and 2nd Predi'Bov® test. Two AI's at interval of 8 to 16h were done (AI's were performed either at 9:00, or between 17:00 and 19:00). For the standard protocol (= STA), thefirst AI occurred after heat observation or activity peak detection by Heatime (whatever the Predi'Bov® test results were). For the adjusted protocol (= ADJ), the first AI occurred from 11 to 16 h after the first positive Predi'Bov® test result or like STA protocol if both results were negative. Heifers followed alternately the 2 protocols, 27 beginning with the ADJ protocol, 27 others with the STA one. LH surge precocity was not repeatable among donors. In the case of an early LH surge detection (one positive Predi'Bov® test), the heat activity peak occurred from 2 to 8 h after the FSH8 for 44% of the flushes, from 8 to 24 h after FSH8 for 54% of the flushes and never for 2% of the flushes. When no early LH surge was observed, the heat activity peak occurred more than 8 h after FSH8 for 78% of the flushes. Interval of heat activity peak-FSH8, IA1-heat activity peak and IA1-early LH surge were highly variable but did not effect the mean number of viable embryos. However, we observed a significant effect (P = 0.04) of the precocity of the heat on the average number of total embryos: 13.8 ± 8.4 v. 11.1 ± 8.1 when the interval heat activity peak-FSH8 had been respectively &lt;8 h or ≥8 h, respecively. Among the 148 collections, 74 were done after the STA protocol, 74 after the ADJ protocol and 70 followed an early LH surge. The adjustment of the AI depending on the detection of an early LH surge (ADJ protocol) had a significant positive (P = 0.04) effect on the mean percentage of viable embryos per flush (52% ± 28 in STA group and 62% ± 31 in ADJ group). Nevertheless, regarding the mean number of viable embryos, this effect failed to reach significance (P = 0.23) (respectively 5.7 ± 5.1 in STA group and 6.7 ± 6.7 in ADJ group). A larger study on more animals is necessary to obtain a significant difference in the number of viable embryos.

Erratum to: Evaluating Effectiveness of Two Types of Chinese Remedial Materials for Low-Achieving and Disadvantaged Second Graders

Having access to research-based materials is an essential component for designing effective interventions for low-achieving and disadvantaged students. The purpose of this study was to compare the effectiveness of two types of reading material intervention for low-achieving and disadvantaged students. The students were divided into experimental (n = 29) and control (n = 27) groups. The students in the control group received the alternative remediation program provided by the school. The experimental group was divided into two subgroups: 19 students received “auxiliary” reading remediation materials (the AUX group), while the other 10 received “adjusted” reading remediation materials (the ADJ group). Data were gathered from the pre and post-test results of a variety of reading and writing tests. There were three major findings. First, both the AUX and ADJ groups showed advantages in attaining results, but there were no significant differences between them in terms of promoting language skills. Furthermore, the AUX group had a slight advantage with regard to overall progress and peer catch-up rate, while the ADJ group showed higher effectiveness than the AUX group in the enhancement of academic performance. Second, the language skills of the students in the two experimental groups have relatively closed the gap with the norm. Specifically, over 50 % of the students in the AUX group achieved peer-level character recognition and dictation abilities in the second-term posttest. Third, both experimental groups demonstrated better reading skills than the control group, but there were no significant differences in terms of reading comprehension. Implications of the study will be discussed based on the findings from this study.