Serum vitamin D level mitigates fractional exhaled nitric oxide linked to bisphenol-A in school-aged children.

OBJECTIVE: Previous studies on the relationship of bisphenol-A (BPA) with fractional exhaled nitric oxide (FeNO) had conflicting results, suggesting that other factors may modulate this relationship. Thus, we investigated the modulating effect of vitamin D on the relationship of BPA with FeNO in children. PATIENTS AND METHODS: This study recruited 432 children (10 to 12 years old) from the general pediatric population of Korea between June and July 2017. We conducted measurements of urinary BPA, serum vitamin D, specific serum IgE, FeNO, and data from impulse oscillometry (reactance area [AX], airway resistance at 5 Hz [Rrs5] and 20 Hz [Rrs10], and the difference of Rrs5 and Rrs20 [Rrs5-20]). RESULTS: Serum vitamin D (adjusted ß =- 0.014, p=0.002) and urinary BPA (ß = 0.006, p<0.001) level was significantly associated with FeNO. Urinary BPA level was significantly associated with FeNO in children with low vitamin D levels (≤23 ng/mL; αß = 0.006, p < 0.001), but not in children with high vitamin D levels (>23 ng/mL). The interaction of vitamin D and BPA had a significant effect on FeNO (pint = 0.005). There was no relationship with the airway lung function (Rrs5, AX, and Rrs5-20) to serum vitamin D and urinary BPA level. Vitamin D ameliorated the BPA-mediated increase of FeNO in children. CONCLUSIONS: These results suggest that children with low vitamin D levels may be more susceptible to airway inflammation due to BPA.

A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial☆.

BACKGROUND: Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC. PATIENTS AND METHODS: The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146). RESULTS: A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable. CONCLUSIONS: In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy.

MicroRNA miR-252 targets mbt to control the developmental growth of Drosophila.

Developmental growth is an intricate process involving the coordinated regulation of the expression of various genes, and microRNAs (miRNAs) play crucial roles in diverse processes throughout animal development. The ecdysone-responsive miRNA, miR-252, is normally upregulated during the pupal and adult stages of Drosophila development. Here, we found that overexpression of miR-252 in the larval fat body decreased total tissue mass through a reduction in both cell size and cell number, causing a concomitant decrease in larval size. Furthermore, miR-252 overexpression led to a delayed larval-to-pupal transition with defective anterior spiracle eversion, as well as a decrease in adult size and mass. Conversely, adult flies lacking miR-252 showed an increase in mass compared with control flies. We found that miR-252 directly targeted mbt, encoding a p21-activated kinase, to repress its expression. Notably, co-overexpression of mbt rescued the developmental and growth defects associated with miR-252 overexpression, indicating that mbt is a biologically relevant target of miR-252. Overall, our data support a role for the ecdysone/miR-252/mbt regulatory axis in growth control during Drosophila development.

Rational Design of Low Cost and High Energy Lithium Batteries through Tailored Fluorine-free Electrolyte and Nanostructured S/C Composite.

We report a new Li-S cell concept based on an optimized F-free catholyte solution and a high loading nanostructured C/S composite cathode. The Li2 S8 present in the electrolyte ensures both buffering against active material dissolution and Li+ conduction. The high S loading is obtained by confining elemental S (≈80 %) in the pores of a highly ordered mesopores carbon (CMK3). With this concept we demonstrate stabilization of a high energy density and excellent cycling performance over 500 cycles. This Li-S cell has a specific capacity that reaches over 1000 mA h g-1 , with an overall S loading of 3.6 mg cm-2 and low electrolyte volume (i.e., 10 µL cm-2 ), resulting in a practical energy density of 365 Wh kg-1 . The Li-S system proposed thus meets the requirements for large scale energy storage systems and is expected to be environmentally friendly and have lower cost compared with the commercial Li-ion battery thanks to the removal of both Co and F from the overall formulation.

Evaluation of 3D printed PCL/PLGA/ß-TCP versus collagen membranes for guided bone regeneration in a beagle implant model.

Here, we compared 3D-printed polycaprolactone/poly(lactic-co-glycolic acid)/ß-tricalcium phosphate (PCL/PLGA/ß-TCP) membranes with the widely used collagen membranes for guided bone regeneration (GBR) in beagle implant models. For mechanical property comparison in dry and wet conditions and cytocompatibility determination, we analyzed the rate and pattern of cell proliferation of seeded fibroblasts and preosteoblasts using the cell counting kit-8 assay and scanning electron microscopy. Osteogenic differentiation was verified using alizarin red S staining. At 8 weeks following implantation in vivo using beagle dogs, computed tomography and histological analyses were performed after sacrifice. Cell proliferation rates in vitro indicated that early cell attachment was higher in collagen than in PCL/PLGA/ß-TCP membranes; however, the difference subsided by day 7. Similar outcomes were found for osteogenic differentiation, with approximately 2.5 times greater staining in collagen than PCL/PLGA/ß-TCP, but without significant difference by day 14. In vivo, bone regeneration in the defect area, represented by new bone formation and bone-to-implant contact, paralleled those associated with collagen membranes. However, tensile testing revealed that whereas the PCL/PLGA/ß-TCP membrane mechanical properties were conserved in both wet and dry states, the tensile property of collagen was reduced by 99% under wet conditions. Our results demonstrate in vitro and in vivo that PCL/PLGA/ß-TCP membranes have similar levels of biocompatibility and bone regeneration as collagen membranes. In particular, considering that GBR is always applied to a wet environment (e.g. blood, saliva), we demonstrated that PCL/PLGA/ß-TCP membranes maintained their form more reliably than collagen membranes in a wet setting, confirming their appropriateness as a GBR membrane.

Genome-wide microRNA expression profiling in placentas of fetuses with Down syndrome.

INTRODUCTION: Down syndrome (DS) is the most common aneuploidy, caused by an extra copy of all or part of chromosome 21 (chr21). Differential microRNA (miRNA) expression is involved in many human diseases including DS. However, the genome-wide changes in miRNA expression in DS fetal placentas have yet to be determined, and the function of these changes is also unclear. METHODS: We profiled genome-wide miRNA expression in placenta samples from euploid or DS fetuses by using microarray technology and predicted the functions of differentially expressed miRNAs using bioinformatics tools. RESULTS: Thirty-four miRNAs were significantly differentially expressed in the DS placenta compared with the normal placenta (16 up-regulated and 18 down-regulated). However, expression of chr21-derived miRNAs did not change. Predicted target genes included 7434 genes targeted by up-regulated miRNAs and 6071 genes targeted by down-regulated miRNAs. Seventy-six of these target genes were located on chr21 (10 genes controlled by down-regulated miRNAs and 34 genes by up-regulated miRNAs, and 32 genes by both). Target genes on chr21 were significantly associated with DS and DS-related disorders, such as mental retardation, neurobehavioral manifestations, and congenital abnormalities. DISCUSSION: To our knowledge, this is the first genome-wide study to comprehensively survey placental miRNAs in DS fetuses. Our results provide new insight into miRNA expression in placentas of fetuses with DS. Additionally, our findings indicate that the differentially expressed miRNAs in the DS placenta may potentially affect various pathways related to DS pathogenesis.

Effects of Coconut Materials on In vitro Ruminal Methanogenesis and Fermentation Characteristics.

The objective of this study was to evaluate the in vitro effects of coconut materials on ruminal methanogenesis and fermentation characteristics, in particular their effectiveness for mitigating ruminal methanogenesis. Fistulated Holstein cows were used as the donor of rumen fluid. Coconut materials were added to an in vitro fermentation incubated with rumen fluid-buffer mixture and timothy substrate for 24 h incubation. Total gas production, gas profiles, total volatile fatty acids (tVFAs) and the ruminal methanogens diversity were measured. Although gas profiles in added coconut oil and coconut powder were not significantly different, in vitro ruminal methane production was decreased with the level of reduction between 15% and 19% as compared to control, respectively. Coconut oil and coconut powder also inhibited gas production. The tVFAs concentration was increased by coconut materials, but was not affected significantly as compared to control. Acetate concentration was significantly lower (p<0.05), while propionate was significantly higher (p<0.05) by addition of the coconut materials than that of the control. The acetate:propionate ratio was significantly lowered with addition of coconut oil and coconut powder (p<0.05). The methanogens and ciliate-associated methanogens in all added coconut materials were shown to decrease as compared with control. This study showed that ciliate-associated methanogens diversity was reduced by more than 50% in both coconut oil and coconut powder treatments. In conclusion, these results indicate that coconut powder is a potential agent for decreasing in vitro ruminal methane production and as effective as coconut oil.

Predictive factors for gastroduodenal toxicity based on endoscopy following radiotherapy in patients with hepatocellular carcinoma.

PURPOSE: The aim of this work was to determine predictive factors for gastroduodenal (GD) toxicity in hepatocellular carcinoma (HCC) patients who were treated with radiotherapy (RT). PATIENTS AND METHODS: A total of 90 HCC patients who underwent esophagogastroduodenoscopy (EGD) before and after RT were enrolled. RT was delivered as 30-50 Gy (median 37.5 Gy) in 2-5 Gy (median 3.5 Gy) per fraction. All endoscopic findings were reviewed and GD toxicities related to RT were graded by the Common Toxicity Criteria for Adverse Events, version 3.0. The predictive factors for the ≥ grade 2 GD toxicity were investigated. RESULTS: Endoscopic findings showed erosive gastritis in 14 patients (16 %), gastric ulcers in 8 patients (9 %), erosive duodenitis in 15 patients (17 %), and duodenal ulcers in 14 patients (16 %). Grade 2 toxicity developed in 19 patients (21 %) and grade 3 toxicity developed in 8 patients (9 %). V25 for stomach and V35 for duodenum (volume receiving a RT dose of more than x Gy) were the most predictive factors for ≥ grade 2 toxicity. The gastric toxicity rate at 6 months was 2.9 % for V25 ≤ 6.3 % and 57.1 % for V25 > 6.3 %. The duodenal toxicity rate at 6 months was 9.4 % for V35 ≤ 5.4 % and 45.9 % for V35 > 5.4 %. By multivariate analysis including the clinical factors, V25 for stomach and V35 for duodenum were the significant factors. CONCLUSION: EGD revealed that GD toxicity is common following RT for HCC. V25 for the stomach and V35 for the duodenum were the significant factors to predict ≥ grade 2 GD toxicity.

Tandem high-dose chemotherapy and auto-SCT for malignant brain tumors in children under 3 years of age.

In an effort to improve survival and reduce late adverse effects of radiation therapy (RT), 25 children <3 years of age with malignant brain tumors received tandem high-dose chemotherapy (HDCT) and auto-SCT following six cycles of induction chemotherapy. RT was either not given or deferred until 3 years of age if the patient was in CR after tandem HDCT/auto-SCT. Tumors relapsed or progressed in nine patients (five during induction treatment), and two of these patients survived after receiving salvage treatment, including RT. Two patients died due to toxicities during tandem HDCT/auto-SCT. A total of 16 patients survived to a median follow-up period of 52 months (range 18-96) from the time of diagnosis. Four of these patients did not receive RT, two received local RT (L-RT), three received craniospinal RT (CSRT), and seven received both L-RT and CSRT. The 5-year OS and EFS rates were 67.8±9.4% and 55.5±10.0%, respectively. Neuroendocrine and neurocognitive functions evaluated 3 years after tandem HDCT/auto-SCT were acceptable. Our results indicate that tandem HDCT/auto-SCT may improve survival in young children with malignant brain tumors with an acceptable level of risk of long-term toxicity.

Tandem high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk neuroblastoma: results of SMC NB-2004 study.

From January 2004 to December 2008, 50 consecutive patients with high-risk neuroblastoma were assigned to receive tandem HDCT (high-dose chemotherapy)/auto-SCT after nine cycles of induction chemotherapy. CEC (carboplatin + etoposide + cyclophosphamide) regimen and TM (thiotepa + melphalan)-TBI regimen (or TM regimen for stage 3 patients) were the first and second HDCT regimens. Local radiotherapy, differentiation therapy with 13-cis-retinoid acid and immunotherapy with interleukin-2 were given after tandem HDCT/auto-SCT. Of the 50 patients, 49 underwent a first HDCT/auto-SCT and 47 underwent a second HDCT/auto-SCT. The tumor relapsed or progressed in 14 patients, secondary malignancy developed in one patient and one patient died from chronic lung disease. Therefore, 34 patients remained event free with a median follow-up of 54.5 months (range, 14-94 months) from diagnosis. The probabilities of 5-year OS and EFS for all 50 patients were 77.0% (95% confidence interval (CI), 63.7-90.3) and 71.4% (95% CI, 58.7-84.1), respectively. However, all patients who remained event free for >3 years after tandem HDCT/auto-SCT experienced late adverse effects. Chemotherapeutic dose-escalation strategy using tandem HDCT/auto-SCT was very encouraging for survival. However, further studies incorporating newer treatment modalities are needed to reduce late adverse effects without jeopardizing the survival rate.

Evaluation of anatomical landmark position differences between respiration-gated MRI and four-dimensional CT for radiation therapy in patients with hepatocellular carcinoma.

OBJECTIVE: To measure the accuracy of position differences in anatomical landmarks in gated MRI and four-dimensional CT (4D-CT) fusion planning for radiation therapy in patients with hepatocellular carcinoma (HCC). METHODS: From April to December 2009, gated MR and planning 4D-CT images were obtained from 53 inoperable HCC patients accrued to this study. Gated MRI and planning 4D-CT were conducted on the same day. Manual image fusions were performed by matching the vertebral bodies. Liver volumes and three specific anatomical landmarks (portal vein conjunction, superior mesenteric artery bifurcation, and other noticeable points) were contoured from each modality. The points chosen nearest the centre of the four landmark points were compared to measure the accuracy of fusion. RESULTS: The average distance differences (±standard deviation) of four validation points were 5.1 mm (±4.6 mm), 5.6 mm (±6.2 mm), 5.4 mm (±4.5 mm) and 5.1 mm (±4.8 mm). Patients who had ascites or pulmonary disease showed larger discrepancies. MRI-CT fusion discrepancy was significantly correlated with positive radiation response (p<0.05). CONCLUSIONS: Approximately 5-mm anatomical landmark positional differences in all directions were found between gated MRI and 4D-CT fusion planning for HCC patients; the gap was larger in patients with ascites or pulmonary disease. ADVANCES IN KNOWLEDGE: There were discrepancies of approximately 5 mm in gated MRI-CT fusion planning for HCC patients.

Anti-IL-33 antibody has a therapeutic effect in a murine model of allergic rhinitis.

BACKGROUND: Interleukin (IL)-33 is involved in the Th2 immune response and could play an essential role in nasal allergy. Therefore, we aimed to investigate the therapeutic potential of anti-IL-33 for allergic rhinitis (AR). METHODS: Twenty-four BALB/c mice were used. In group A (control group, n = 6), mice were sensitized and challenged with saline. Group B [ovalbumin (OVA) group, n = 6] mice received intraperitoneal and intranasal OVA challenge. In group C (control IgG group, n = 6), mice were injected intraperitoneally with rabbit control IgG before OVA challenge. In group D (anti-IL-33 group, n = 6), anti-IL-33 was injected before challenge. We evaluated the number of nose-scratching events and external morphology; serum total and OVA-specific IgE; number of eosinophils, neutrophils, and lymphocytes in bronchoalveolar lavage (BAL) fluid; histopathologic examination of nasal cavity; and IL-4, IL-5, and IL-13 in BAL fluid. RESULTS: Anti-IL-33 treatment significantly reduced the nose-scratching events and ameliorated skin denudation. Serum total and OVA-specific IgE was significantly decreased in group D. The number of eosinophils in BAL fluid was also significantly decreased. Eosinophilic infiltration in the nasal cavity was significantly decreased in group D. IL-4, IL-5, and IL-13 in BAL fluid were also significantly decreased after treatment. CONCLUSIONS: Anti-IL-33 antibody has a therapeutic potential for experimental AR.

Diagnostic dilemma of pseudoprogression in the treatment of newly diagnosed glioblastomas: the role of assessing relative cerebral blood flow volume and oxygen-6-methylguanine-DNA methyltransferase promoter methylation status.

BACKGROUND AND PURPOSE: Methylation of the MGMT gene promoter is associated with a favorable prognosis in adult patients with GBM treated with TMZ. We determined the incidence of pseudoprogression according to the MGMT methylation status and the potential value of DSC perfusion MR images for predicting pseudoprogression. MATERIALS AND METHODS: New or enlarged enhancing lesions after CCRT in adult patients with newly diagnosed GBMs were prospectively assessed by measuring their rCBV by using DSC perfusion MR images. Tumor tissue was assayed to determine MGMT promoter methylation status. All patients were regularly followed up at an interval of 2 months by MR images, including DSC perfusion MR images. RESULTS: Ninety eligible patients were enrolled in this study. After CCRT, new or enlarged enhanced lesions were found in 59 of 90 patients, which were subsequently classified as pseudoprogression (26 patients, 28.9%) and real progression (33 patients, 36.7%). Overall, there was a significant difference in the mean rCBV between pseudoprogression and real tumor progression (P = .003). The ROC curve revealed that an rCBV ratio >1.47 had an 81.5% sensitivity and a 77.8% specificity. The unmethylated MGMT promoter group had a significant difference of mean rCBV between pseudoprogression and real progression (P = .009), though the methylated MGMT promoter group had no significant difference (P = .258). CONCLUSIONS: The current study suggests that rCBV measured by DSC perfusion MR images has a differential impact on the predictability of pseudoprogression in patients with GBM.

Epigenotype-phenotype correlations in Silver-Russell syndrome.

BACKGROUND: Silver-Russell syndrome (SRS) is characterised by intrauterine growth restriction, poor postnatal growth, relative macrocephaly, triangular face and asymmetry. Maternal uniparental disomy (mUPD) of chromosome 7 and hypomethylation of the imprinting control region (ICR) 1 on chromosome 11p15 are found in 5-10% and up to 60% of patients with SRS, respectively. As many features are non-specific, diagnosis of SRS remains difficult. Studies of patients in whom the molecular diagnosis is confirmed therefore provide valuable clinical information on the condition. METHODS: A detailed, prospective study of 64 patients with mUPD7 (n=20) or ICR1 hypomethylation (n=44) was undertaken. RESULTS AND CONCLUSIONS: The considerable overlap in clinical phenotype makes it difficult to distinguish these two molecular subgroups reliably. ICR1 hypomethylation was more likely to be scored as 'classical' SRS. Asymmetry, fifth finger clinodactyly and congenital anomalies were more commonly seen with ICR1 hypomethylation, whereas learning difficulties and referral for speech therapy were more likely with mUPD7. Myoclonus-dystonia has been reported previously in one mUPD7 patient. The authors report mild movement disorders in three further cases. No correlation was found between clinical severity and level of ICR1 hypomethylation. Use of assisted reproductive technology in association with ICR1 hypomethylation seems increased compared with the general population. ICR1 hypomethylation was also observed in affected siblings, although recurrence risk remains low in the majority of cases. Overall, a wide range of severity was observed, particularly with ICR1 hypomethylation. A low threshold for investigation of patients with features suggestive, but not typical, of SRS is therefore recommended.

Trastuzumab treatment improves brain metastasis outcomes through control and durable prolongation of systemic extracranial disease in HER2-overexpressing breast cancer patients.

In patients with human epidermal growth factor receptor-2 (HER2)-overexpressing breast cancer, treatment with trastuzumab has been shown to markedly improve the outcome. We investigated the role of trastuzumab on brain metastasis (BM) in HER2-positive breast cancer patients. From 1999 to 2006, 251 patients were treated with palliative chemotherapy for HER2-positive metastatic breast cancer at Samsung Medical Center. The medical records of these patients were analysed to study the effects of trastuzumab on BM prevalence and outcomes. Patients were grouped according to trastuzumab therapy: pre-T (no trastuzumab therapy) vs post-T (trastuzumab therapy). The development of BM between the two treatment groups was significantly different (37.8% for post-T vs 25.0% for pre-T, P=0.028). Patients who had received trastuzumab had longer times to BM compared with patients who were not treated with trastuzumab (median 15 months for post-T group vs 10 months for pre-T group, P=0.035). Time to death (TTD) from BM was significantly longer in the post-T group than in the pre-T group (median 14.9 vs 4.0 months, P=0.0005). Extracranial disease control at the time of BM, 12 months or more of progression-free survival of extracranial disease and treatment with lapatinib were independent prognostic factors for TTD from BM.

Tandem high-dose chemotherapy and autologous stem cell rescue in patients over 1 year of age with stage 4 neuroblastoma.

From June 1997 to August 2005, 52 consecutive newly diagnosed stage 4 neuroblastoma patients over 1 year of age were assigned to receive tandem high-dose chemotherapy and autologous stem cell rescue (HDCT/ASCR) as consolidation therapy. Fifty of the 52 patients underwent a first HDCT/ASCR and 44 patients underwent a second HDCT/ASCR. Eight patients (15.4%) died from treatment-related toxicity (seven during the second HDCT/ASCR). Total body irradiation (TBI) in the first HDCT/ASCR and a shorter interval (< 12 weeks) between the first and second HDCT/ASCR were associated with a higher rate of treatment-related death in the second HDCT/ASCR (P = 0.032 and 0.095, respectively). The tumor relapsed or progressed in 11 patients, and 33 patients remained event free with a median follow-up of 53 months (range 19-117) from diagnosis. The 5-year event-free survival (EFS) (+/- 95% confidence interval) for all 52 patients was 62.1+/-13.7%. The application of TBI and local radiotherapy, and a longer interval between the first and second HDCT/ASCR were independently associated with a better EFS (P = 0.026, 0.007 and 0.020, respectively). However, further studies will be needed to decrease the toxic death rate in the second HDCT/ASCR while reducing the relapse rate.

Patterns of failure in gastric carcinoma after D2 gastrectomy and chemoradiotherapy: a radiation oncologist's view.

The risk of locoregional recurrence in resected gastric adenocarcinoma is high, but the benefit of adjuvant treatment remains controversial. In particular, after extended lymph node dissection, the role of radiotherapy is questionable. Since 1995, we started a clinical protocol of adjuvant chemoradiotherapy after D2 gastrectomy and analysed the patterns of failure for 291 patients. Adjuvant chemotherapy consisted of five cycles of fluorouracil and leucovorin, and concurrent radiotherapy was given with 4500 cGy from the second cycle of chemotherapy. With a median follow-up of 48 months, 114 patients (39%) showed any type of failure, and the local and regional failures were seen in 7% (20 out of 291) and 12% (35 out of 291), respectively. When the recurrent site was analysed with respect to the radiation field, in-field recurrence was 16% and represented 35% of all recurrences. Our results suggest that adjuvant chemoradiotherapy has a potential effect on reducing locoregional recurrence. Moreover, low locoregional recurrence rates could give a clue as to which subset of patients could be helped by radiotherapy after D2 gastrectomy. However, in order to draw a conclusion on the role of adjuvant radiotherapy, a randomised study is needed.

Postoperative chemoradiotherapy for gastric cancer.

BACKGROUND: We report the results of postoperative chemoradiotherapy after curative resection in gastric cancer patients. PATIENTS AND METHODS: Patients with gastric cancer staged IB to IV(M0) were treated with chemoradiotherapy after curative resection with extensive (D2) lymph node dissection. Nodal metastases were observed in 261 (90%) patients. The chemotherapy consisted of fluorouracil 400 mg/m(2) plus leucovorin 20 mg/m(2) for 5 days, followed by 4500 cGy of radiotherapy for 5 weeks with fluorouracil and leucovorin on the first 4 days and the last 3 days of radiotherapy. Two 5-day cycles of chemotherapy were given 4 weeks after the completion of radiotherapy. RESULTS: Of 290 patients accrued, 229 (79%) patients completed chemoradiotherapy as planned. With a median follow-up of 49 months, 114 (34%) patients have relapsed: 33 (29%) locoregional relapses, 76 (67%) peritoneal relapses and 41 (36%) distant metastases. The 5-year overall and relapse-free survivals were 60% and 57%, respectively. Tolerance was acceptable, the main toxicity being neutropenia. CONCLUSIONS: This postoperative chemoradiotherapy after curative resection of gastric cancer was feasible, with acceptable toxicities. Whether this adjuvant therapy in gastric cancer patients that have undergone a D2 lymph node dissection impacts on survival or reduces the incidence of relapses remains to be studied.

Successive double high-dose chemotherapy with peripheral blood stem cell rescue collected during a single leukapheresis round in patients with high-risk pediatric solid tumors: a pilot study in a single center.

In total, 18 of 26 double high-dose chemotherapies (HDCT) in pediatric solid tumors were rescued with peripheral blood stem cells collected during a single leukapheresis round (single-harvest group, SHG). In the remaining eight HDCT, additional leukapheresis were necessary after the first HDCT (HDCT1) to rescue the second HDCT (HDCT2) (double-harvest group, DHG). Stem cell collection after HDCT1 was inefficient and delayed in patients who had received prior chemotherapy before HDCT1. The interval between HDCT1 and HDCT2 was shorter in SHG than in DHG (median 62.5 days vs 178.5 days, P-value=0.002). Hematologic recovery in HDCT2 was delayed compared to HDCT1. However, there was no difference in hematologic recovery between SHG and DHG. A high rate of treatment-related mortality (TRM) was recorded during HDCT2, but there was no evidence that the shorter interval caused a higher rate of TRM (P-value=0.454). The probability of disease-free survival at 2 years after HDCT2 in the SHG and DHG were 66.7 and 25.0%, respectively (P-value=0.031). Therefore, to administer the second HDCT earlier in double HDCT, and thus to improve the survival of patients with high-risk solid tumors, the single-harvest approach is recommended rather than the double-harvest approach.