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Background: In patients with hepatic artery variation (HAV), feasibility and justification of robotic pancreatoduodenectomy (RPD) for periampullary lesions have been not been well established. Methods: A total of 600 patients with periampullary lesions receiving RPD or open pancreaticoduodenectomy (OPD) were identified from our prospectively collected computer database. Surgical outcomes, oncological radicality, and survival outcomes after RPD in HAV (+) and (−) patients were compared. Results: The incidence of HAV was 16%, including 12.7% in patients with RPD and 23.0% in those with OPD. In the HAV (+) group, vascular injury rate had no statistical difference between the RPD (3.7%) and OPD (9.1%) patients, P = 0.404. Among the RPD patients, those with HAV (+) had longer operation time (8.5 ± 2.5 vs. 7.7 ± 2.0 h, P = 0.013) and higher vascular injury (3.8% vs. 0.6%, P = 0.024) when compared with the HAV (−) patients. There was no significant difference between the HAV (+) and (−) patients with RPD regarding blood loss, open conversion, vascular resection, and surgical mortality and morbidity. There was no survival difference between the HAV (+) and (−) patients with pancreatic head adenocarcinoma after RPD. There was no survival difference between RPD and OPD in the HAV (+) group. Conclusions: When compared with OPD, RPD is feasible and justifiable without increasing vascular injury rate for patients with HAV (+). Hepatic artery variation has no negative impact on surgical, oncological, and survival outcomes following an RPD, if it is accurately identified pre-operatively and appropriately managed intraoperatively. [ABSTRACT FROM AUTHOR]

The study of robotic pancreaticouodenectomy (RPD) focusing on delayed gastric emptying (DGE) is seldom reported. This study explored the incidence of DGE in RPD with extracorporeal hand-sewn gastrojejunostomy involving downward positioning of the stomach. Patients with periampullary lesions undergoing RPD or open pancreaticouodenectomy (OPD) were included for comparison. A variety of clinical factors were evaluated for the risk of developing DGE. There were 409 (68.2%) RPD and 191 (31.8%) OPD in this study. DGE occurred in 7.7% of patients after pancreaticoduodenectomy, with 4.4% in RPD and 14.7% in OPD, p < 0.001. Nausea/vomiting (12.6% vs. 6.3%) and jaundice (9.9% vs. 5.2%) were significant preoperative risk factors for DGE, while malignancy (8.7% vs. 2.2%) and lymph node involvement (9.8% vs. 5.6%) were significant pathological risk factors. Intraoperative blood loss > 200 c.c. was the other factor related to DGE (11.2% vs. 4.4% in those with blood loss ≤ 200 c.c.). None of the postoperative complications was significantly associated with DGE. Hospital stay was significantly longer in the group with DGE (median, 37 vs. 20 days in the group without DGE). After multivariate analysis by binary logistic regression, compared with OPD, RPD was the only independent factor associated with a lower incidence of DGE. RPD with extracorporeal hand-sewn antecolic, antiperistaltic, and inframesocolic gastrojejunostomy via a small umbilical wound involving careful downward positioning of the stomach was associated with a low incidence of DGE and presented as the most powerful independent predictor of this condition. [ABSTRACT FROM AUTHOR]

Background: This study is to clarify the feasibility of and justification for robotic pancreaticoduodenectomy (RPD) in patients with pancreatic adenocarcinoma. Methods: A 1-to-1 propensity score-matched comparison of RPD and open pancreaticoduodenectomy (OPD) was performed based on six covariates commonly used to predict the survival outcome for pancreatic adenocarcinoma. Results: A total of 130 patients were enrolled, with 65 in each study group after propensity score matching. The median operating time was longer for RPD (8.3 h vs. 7.0 h, P = 0.002). However, RPD was associated with less blood loss, lower overall surgical complication rate, and lower incidence of delayed gastric emptying. The resection radicality was oncologically similar between these two groups, but the median lymph node yield was higher for RPD (18 vs. 16, P = 0.038). Before propensity score matching, the 5-year survival was better in RPD (27.0% vs. 17.6%, P = 0.006). After matching, there was still a trend towards improved overall survival in the RPD group; however, the difference in 5-year survival between RPD and OPD was not significant (24.5% vs. 19.7%, P = 0.088). Conclusion: RPD is not only technically feasible with no increase in surgical risk but also oncologically justifiable without compromising survival outcome. However, unlike randomized control trials, the limitations in this propensity score-matched analysis only accounted for 6 observed covariates commonly used to predict the survival outcome in patients with pancreatic adenocarcinoma, and confounders not included in this study could also affect our results. [ABSTRACT FROM AUTHOR]

Theoretically, pancreas transplant alone in uremic (PTAU) patients could also be one of the options for those waiting for both pancreas and kidney grafts, but it has never been reported. There were 160 cases of pancreas transplant in this study, including 16% PTAU. The 5-year patient survival was 66.2% after PTAU, 94.5% after SPK, 95.8% after PAK, and 95.4% after PTA. Rejection of pancreas graft was significantly lower in PTAU group (3.8%), followed by 16.7% in pancreas after kidney transplant (PAK), 29.8% in simultaneous pancreas and kidney transplant (SPK) and 37.0% in pancreas transplant alone (PTA). Fasting blood sugar and serum HbA1c levels after PTAU were not significantly different from those by other subgroups. The 5-year death-censored pancreas graft survival was 100% after PTAU and PAK, and 97.0% after SPK and 77.9% after PTA. However, the 5-year death-uncensored pancreas graft survival was 67.0% after PTAU, 100% after PAK, 91.3% after SPK, and 74.0% after PTA. The superior graft survival in the PTAU group was achieved only if deaths with a functioning graft were censored. In conclusion, given the inferior patient survival outcome, PTAU is still not recommended unless SPK and PAK is not available. Although PTAU could be a treatment option for patients with diabetes complicated by end-stage renal disease (ESRD) in terms of surgical risks, endocrine function, and immunological and graft survival outcomes, modification of the organ allocation policies to prioritize SPK transplant in eligible patients should be the prime goal. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical outcomes of preventive covered stent placement at the gastroduodenal artery stump in patients with angiogram-negative sentinel hemorrhage after pancreaticoduodenectomy. Methods: Between July 2006 and September 2018, patients undergoing computed tomography angiography or diagnostic angiography for sentinel hemorrhage after pancreaticoduodenectomy were retrospectively reviewed. Patients having angiogram-negative angiography and undergoing preventive covered stent placement or conservative treatment were included. Clinical outcomes, technique success, and complications were evaluated. Results: A total of 25 patients (mean age 62.5 years) were evaluated, including 15 patients underwent preventive covered stent placement at the gastroduodenal artery stump and 10 patients received conservative treatments. The clinical success rates were 50% (5/10) and 86.7% (13/15) for conservative treatments and covered stent groups, respectively (p = 0.07). In the conservative treatment group, delayed massive hemorrhage occurred in five patients, two of whom died of recurrent bleeding due to gastroduodenal artery pseudoaneurysm within 16 days, and two had intraluminal hemorrhage within 5 days. In the covered stent group, one patient had inferior pancreaticoduodenal artery pseudoaneurysm 1 day after the placement of the covered stent, and one had recurrent bleeding due to duodenal ulcer within 14 days. The 30-day mortality was 40% (4/10) and 0 in the conservative treatment and covered stent groups, respectively (p = 0.02). The difference in the overall survival was nonsignificant between the two groups (p = 0.23). Conclusions: The preventive covered stent placement at the gastroduodenal artery stump is safe and reduces delayed massive hemorrhage and short-term mortality in patients with angiogram-negative sentinel hemorrhage after pancreaticoduodenectomy. [ABSTRACT FROM AUTHOR]

This study is to clarify the feasibility and justification of robotic pancreaticoduodenectomy (RPD) by comparing the outcomes between RPD and open pancreaticoduodenectomy (OPD) groups. All perioperative data and outcomes were prospectively collected. There were 304 (63.9%) RPD and 172 (36.1%) OPD. The median operation time was longer in RPD group than OPD (7.5 vs 7.0 h). The blood loss was much lower in RPD group, with a median of 130 vs. 400 c.c. in OPD group. Based on Clavien–Dindo classification, grade 0 (no complication) was 51.8% in RPD group, higher than 43.2% in OPD. Delayed gastric emptying was only 3.5% in RPD group, much lower than 13.6% in OPD. Wound infection rate was also lower in RPD group, 3.2% vs. 7.7% in OPD. The postoperative hospital stay was shorter in RPD group, with a median of 20 days, vs. 24 days in OPD. There was no significant difference regarding the lymph node yield, surgical mortality, postoperative pancreatic fistula, postpancreatectomy hemorrhage, chyle leakage and bile leakage between RPD and OPD groups. For pancreatic head adenocarcinoma, the survival outcome was better in RPD group, with 1-year, 3-year, and 5-year survival of 82.9%, 45.3%, and 26.8% respectively, as compared with 63.8%, 26.2%, and 17.4% in OPD. RPD is not only feasible but also justified without increasing the surgical risks and compromising the survival outcomes. Moreover, RPD might provide benefits of less blood loss, less delayed gastric emptying, lower wound infection rate and shorter length of postoperative stay, as compared with OPD. [ABSTRACT FROM AUTHOR]

Concomitant apical suspension should be performed at the time of hysterectomy for uterine prolapse to reduce the risk of recurrent prolapse. Native tissue repair (NTR) and sacrocolpopexy (SCP) are commonly used apical suspension procedures; however, it remains unclear which one is preferred. This study aimed to compare the treatment outcomes of NTR and SCP in terms of surgical failure, complication and reoperation rates. Surgical failure was defined as the presence of vaginal bulge symptoms, any prolapse beyond the hymen, or retreatment for prolapse. This retrospective cohort study included 523 patients who had undergone NTR (n = 272) or SCP (n = 251) along with hysterectomy for uterine prolapse and who had at least 4-month follow-up visits. During the median 3-year follow-up period, the surgical failure rate was higher in the NTR group (21.3% vs 6.4%, P < 0.01), with a low rate of retreatment in both groups. Overall complication rates were similar, but complications requiring surgical correction under anesthesia were more common in the SCP group (7.2% vs 0.4%, P < 0.01). As a result, the total reoperation rate was significantly higher in the SCP group (8.0% vs 2.6%, P = 0.02). Taken together, NTR may be a preferred option for apical suspension when hysterectomy is performed for uterine prolapse. [ABSTRACT FROM AUTHOR]

Background: To evaluate the surgical, oncological, and survival outcomes after pancreaticoduodenectomy (PD) with superior mesenteric vein (SMV)/portal vein (PV) resection by either robotic PD (RPD) or open PD (OPD).Methods: Data of patients with periampullary lesions undergoing PD were retrieved from a prospectively collected computer database. Surgical risks as well as oncological and survival outcomes were compared between patients with (vein resection group) and without SMV/PV resection (without vein resection group).Results: A total of 391 patients undergoing pancreaticoduodenectomy were enrolled, including 43 (11.0%) and 384 (89.0%) patients with and without vein resection, respectively. Eleven (25.6%) of PDs with vein resection were performed using the robotic approach. Operation time in the vein resection group was significantly longer (median of 8 vs. 7 h). Blood loss, curative resection (R0) rate, and harvested lymph node number were similar between these two groups. Surgical outcomes including postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), chyle leakage, wound infection, and hospital stay were not significantly different between the two groups. There was no survival difference between these groups, with 1- and 3-year survival rates of 92.6% and 26.5%, respectively, for vein resection group, vs. 70.3% and 37.2%, respectively, for the without vein resection group.Conclusions: PD with vein resection is technically feasible by OPD and RPD in selected patients. Additional SMV/PV would not increase the surgical risks of PD and could achieve similar survival outcomes for pancreatic head adenocarcinoma when compared to PD without vein resection. [ABSTRACT FROM AUTHOR]

Successful delivery of a photosensitizer into the skin is an important factor for effective photodynamic therapy (PDT). The effective method to increase drug penetration within short incubation time overcoming skin barrier have been investigated. This study was performed to analyze and compare the effectiveness of ablative fractional laser (FXL) pretreatment and/or sonophoresis for enhancing the penetration of 5-aminolevulinic acid (ALA) into human skin in vivo. Twenty-four identical 1 × 1 cm2 treatment areas were mapped on the backs of ten healthy male subjects. Each area received FXL pretreatment and/or sonophoresis with different energy settings and ALA incubation times. After treatments, porphyrin fluorescence reflecting the ALA penetration were measured. Application of ablative CO2 FXL pretreatment resulted to higher fluorescence intensities than the non-treatment group. Incubation times were positively correlated with the increments of ALA penetration. However, increasing pulse energy or combining with sonophoresis did not show additional positive effects on ALA penetration. Ablative CO2 FXL pretreatment effectively facilitated ALA penetration in human skin in vivo. Ablative CO2 FXL alone without sonophoresis setting pulse energy of 10 and 20 mJ with more than 60 min of ALA incubation time could be an ideal setting for ALA penetration. [ABSTRACT FROM AUTHOR]

The present study encompasses laboratory model tests, both static and cyclic loading, on fly ash sub-bases of varying thickness overlying sand subgrade. Different sub-base conditions were created by introducing a single basal bamboo geogrid beneath the sub-base as well as reinforcing the sub-base with bamboo geocell without and with single basal bamboo geogrid. The cyclic load tests indicated considerable reduction in cyclic and permanent deformations in reinforced models as compared to unreinforced models; around 44% reduction in cyclic deformation and 35% reduction in permanent deformation were achieved for fly ash sub-base reinforced with bamboo geocell mattress with single basal bamboo geogrid. [ABSTRACT FROM AUTHOR]

The grouting efficiency of cement milk injected into sandy soil is estimated by using an artificial neural network. In order to evaluate grouting efficiency, laboratory model tests were conducted on a dry sand bed. Based on the model test results, a neural network model was developed for use in computing normalized grout bulb diameter. A thorough sensitivity analysis was carried out to evaluate the parameters affecting grouting efficiency. Based on the weights of the developed model, a neural interpretation diagram is developed to find out whether the input parameters have direct or inverse effect on the output. A prediction model equation is established with the weights of the neural network as model parameters. The results of the experiment suggest that the developed model can predict grouting efficiency with reasonable accuracy. [ABSTRACT FROM AUTHOR]

Many peninsulas in the temperate zone played an important role as refugia of various flora and fauna, and the southern Korean Peninsula also served as a refugium for many small mammals in East Asia during the Pleistocene. The Asian lesser white-toothed shrew, Crocidura shantungensis, is a widely distributed species in East Asia, and is an appropriate model organism for exploring the role of the Korean Peninsula as a refugium of small mammals. Here, we investigated phylogenetic relationships and genetic diversity based on the entire sequence of the mitochondrial cytochrome b gene (1140 bp). A Bayesian tree for 98 haplotypes detected in 228 C. shantungensis specimens from East Asia revealed the presence of three major groups with at least 5 subgroups. Most haplotypes were distributed according to their geographic proximity. Pairwise FST’s and analysis of molecular variance (AMOVA) revealed a high degree of genetic differentiation and variance among regions as well as among populations within region, implying little gene flow among local populations. Genetic evidence from South Korean islands, Jeju-do Island of South Korea, and Taiwan leads us to reject the hypothesis of recent population expansion. We observed unique island-type genetic characteristics consistent with geographic isolation and resultant genetic drift. Phylogeographic inference, together with estimates of genetic differentiation and diversity, suggest that the southern most part the Korean Peninsula, including offshore islands, played an important role as a refugium for C. shantungensis during the Pleistocene. However, the presence of several refugia on the mainland of northeast Asia is also proposed. [ABSTRACT FROM AUTHOR]

Using multiple parallel sequencing on Illumina platform, we identified eight microRNAs that showed significant opposite changes of gene expression in cells of the hormone-sensitive LNCaP prostate cancer cell line and in cells of the hormone-resistant DU-145 cell line, in comparison to the microRNA expression in the normal prostate tissue cells. We found that the insulin-like growth factor 1 receptor (IGF1R) gene is a target of five microRNAs whose expression is increased in LNCaP cells and reduced in DU-145 cells. [ABSTRACT FROM AUTHOR]

Background: Polypoid lesions of the gallbladder (PLG) are common, and most are benign. Few lesions are found to be malignant, but are not preoperatively distinguished as such using common imaging modalities. Therefore, we compared characteristics of benign and malignant PLGs in depth.Methods: We enrolled 1204 consecutive patients diagnosed with PLG at Taipei Veterans General Hospital between January 2004 and December 2013. Patients underwent either surgery or regular follow-up with various imaging modalities for at least 24 months. The mean follow-up duration was 72 ± 32 months.Results: Of 1204 patients, 194 underwent surgical treatment and 1010, regular follow-up. In addition, 73 % patients were asymptomatic. The mean PLG size was 6.9 ± 7.7 (range 0.8-129) mm; the PLGs of 337 patients (28 %) grew during their follow-up periods. The majority of PLGs (90.4 %) were single lesions, and 10.5 % of patients had associated gallstones. The PLGs of 20.1 % of surgical patients were malignant. Malignant PLGs were found in 32.4 % of patients ≥50 years old and in 4.7 % of those <50 years old (p < 0.001). Right quadrant abdominal pain, epigastric pain, and body weight loss were the three most common symptoms associated with malignancy. Malignant PLGs were significantly larger than benign lesions (means: 27.5 ± 18.4 mm vs. 12.3 ± 12.3 mm, respectively, p < 0.001). Notably, the size of 5 % of malignant PLGs was 3-5 mm, and that of 8 % was 5-10 mm. The negative predictive value for gallbladder malignancy was 92.8 % based on a size ≥10 mm and 100 % based on a size ≥3 mm.Conclusions: Our study reassesses the PLG size that warrants more aggressive intervention. Cholecystectomy remains mandatory for PLGs > 10 mm, but should also be considered a definitive diagnostic and treatment modality for PLGs with diameters of 3-10 mm. [ABSTRACT FROM AUTHOR]

Purpose: Injection of adipose tissue-derived stem cells (ASCs) is a novel method for the treatment of complex perianal fistulas. We aimed to evaluate the safety and efficacy of ASCs in the treatment of complex anal fistulas not associated with Crohn's disease. Methods: A phase II clinical trial was performed comparing two different doses of ASCs (group 1: 1 × 10 cells/mL and group 2: 2 × 10 cells/mL). Eligible patients were administered an amount of ASCs proportional to the length of the fistula by injection into the submucosal layer surrounding the internal opening and inside of the fistula tract. ASCs at twice the initial concentration were administered if complete closure was not achieved within 8 weeks. The efficacy endpoint was the complete closure of fistulas 8 weeks after injection. Patients demonstrating complete closure at week 8 were subjected to follow-up for 6 months. Results: Fifteen patients were injected with ASCs; thirteen completed the study. Complete closure was observed in 69.2% (9/13) of patients at 8 weeks. Three of five patients in group 1, and six of eight in group 2 displayed complete closure; no significant differences were observed between the groups. Six of nine patients who showed complete closure participated in additional follow-up; five (83.3%) showed persistent response at 6 months. No grade 3 or 4 adverse events (AEs) were observed; observed AEs were not related to ASC treatment. Conclusion: ASCs might be a good option for the treatment of complex perianal fistulas are not healed by conventional operative procedures. [ABSTRACT FROM AUTHOR]

We studied microRNA gene expression in HeLa cells following exposure for 6 h and 8 days to Co gamma rays at a dose of 4 Gy using an approach of large-scale parallel DNA sequencing. We identified 12 microRNAs with aberrant expression which were maintained in cell generations. The analysis of radiation-induced aberrant expression of pre-microRNAs made it possible to assess the importance of nuclear and cytoplasmic stages of microRNA biogenesis for preservation of its aberrant expression. On cell treatment by 5-azacytidine, aberrant expression was maintained only in two microRNAs: miR-21-3p and miR-422a, which demonstrated an increase in expression. Radiation-induced decrease in expression in ten examined microRNAs was dependent on DNA demethylation. At the same time, expression in a microRNA set, which demonstrated inheritable alteration of the expression after gamma-radiation exposure in the untreated cells, was not dependent or was weakly dependent on DNA methylation. The obtained results suggest that ionizing radiation induces aberrant DNA methylation, which affects inherited expression changes in microRNAs in cell generations after exposure to the mutagen. [ABSTRACT FROM AUTHOR]

The dependence of expression of miRNAs and their precursors (pre-miRNAs) on the DNA methylation level in HeLa cells 8 days after mitomycin C treatment was studied. A massive parallel DNA sequencing method was applied to analyze miRNA expression. 5-Azacytidine (DNA methylation inhibitor) was added to the medium 6 days after mutagenic agent exposure. The results indicated that the change in expression for some mature miRNAs (39 of 61) was accompanied by the change in the expression of their pre-miRNAs, while there were no significant changes in the expression of pre-miRNA for other mature miRNAs (22 of 61). The aberrant expression was maintained by 8 of 61 mature miRNAs and 6 of 55 pre-miRNAs in the induced HeLa cells after 5-azacytidine treatment. In addition, the expression of more than 90% of miRNAs, which indicated a significant change in expression after mitomycin C treatment, does not depend or depends slightly on the DNA methylation level in HeLa cells without mitomycin C treatment. The results suggest that mitomycin C induces aberrant DNA methylation which affects maintenance of changes in the miRNA expression in cell generations after mutagen treatment. [ABSTRACT FROM AUTHOR]

We consider the graphs with matrices whose entries (i.e., the weights of edges) are randomly and independently chosen in an interval unbounded above and with a continuous distribution function. Probabilistic analysis is carried out of an approximation algorithm with quadratic time complexity for an exponential distribution. Some sufficient conditions for the asymptotic optimality of the algorithmare justified. Similar conditions are also obtained for a truncated normal distribution. [ABSTRACT FROM AUTHOR]

The retained austenite and solute carbon in C-Si-Mn TRIP steels were quantitatively analyzed by neutron diffractometry, and their effects on the mechanical properties of the steels were studied. The decreasing of austempering temperature increased the volume fraction of retained austenite as well as the solute carbon in an austenite phase. However, the samples containing lower silicon showed a large variation in the amount of retained austenite and solute carbon in austenite with austempering temperature. The amount of retained austenite was proportional to the solute carbon in austenite. The elongation in TRIP steel was affected by both the volume fraction of retained austenite and the solute carbon in austenite. [ABSTRACT FROM AUTHOR]

Applying the method of multiple parallel sequencing on the MiSeq platform (Illumina, United States), a comparative analysis of miRNA expression in tumor and normal colon tissue cells was performed. Forty miRNAs aberrantly expressed in cancer were detected. Among them, 15 and 25 miRNAs showed increased and decreased expression, respectively, for all or most of the cases. Sixteen miRNA clusters were identified, which showed a coordinated or incompletely coordinated aberrant expression in colorectal cancer cells. In two (miR-183/182 and miR-106b/25) and four (miR-143/145, miR-497/195, miR-30e/30c-1, and miR-30a/30c-2) miRNA clusters, respectively, a statistically significant coordinated increase or decrease in expression was registered for all miRNAs within the corresponding cluster. Three aberrantly expressed well-known miRNAs (miR-100-5p, miR-30d-5p, and miR-204-5p) were identified, which, however, had never before been associated with colorectal cancer. The obtained results demonstrate the potential and promising application of 6 miRNA clusters with coordinated aberrant expression as markers for colorectal cancer. [ABSTRACT FROM AUTHOR]

We identified 40 miRNAs with inherited aberrant expression by multiple parallel sequencing of human HeLa cells irradiated with X rays and mitomycin C. Twenty-two miRNAs were repressed and 15 miRNAs were induced after radiation and mytomycin C treatment. The expression of three miRNAs (miR-10b-5p, miR-148a-3p, and miR-340-5p) decreased after X-ray exposure and increased after mitomycin C treatment. The spectrum of aberrantly expressed miRNAs after X-ray and mitomycin C treatment is different, except for three miRNAs (mir-100-5p, miR-99b-5p, miR-501-3p), which showed the inherited decreased expression after both mutagens. It has been ascertained that for five miRNAs (miR-21-3p, miR-182-5p, miR-19b-3p, miR-30a-3p, and miR-30e-3p) with increased inherited expression, the targets are well-described tumor suppressor genes. For 9 miRNAs (miR-99b-5p, miR-148a-3p, miR-365a-3p, miR-193a-3p, miR-100-5p, miR-99a-5p, miR-29b-3p, miR-340-5p, and miR-23b-3p) with reduced inherited expression, the targets are oncogenes. The obtained results provide further support of the idea that induced epigenetic changes in the genome should be considered when assessing the long-term genetic effects of ionizing radiation and chemical compounds. [ABSTRACT FROM AUTHOR]

We conducted a genome-wide association study (GWAS) to identify single nucleotide polymorphisms (SNPs) influencing overall survival (OS) of small-cell lung cancer (SCLC) patients. We prospectively collected blood samples from 139 SCLC patients who participated in phase II studies of irinotecan and cisplatin (IP) chemotherapy as first-line therapy. Among 334 127 SNPs, which passed quality control, seven showed significant association with OS. The rs16950650CT, rs7186128AG or GG, rs17574269AG, rs8020368CC, rs4655567CC, rs2166219TT or rs2018683TT showed shorter OS compared with control alleles. Among the seven SNPs, rs4655567, rs8020368 and rs2018683 were significantly associated with a resistant relapse (RR). In the multivariate analysis, rs8020368CC was significantly associated with higher risk of RR (odds ratio=16.7, P=0.007). In vitro and in silico analysis showed that SNPs in C14orf49 might be associated with epithelial-to-mesenchymal transition. This exploratory GWAS identified candidate SNPs that may be predictive of the clinical outcome of SCLC patients receiving IP. [ABSTRACT FROM AUTHOR]

The identification of patients who are at high risk for irinotecan-related severe diarrhea and neutropenia is clinically important. We conducted the first genome-wide association study (GWAS) to search for novel susceptibility genes for irinotecan-related severe toxicities, such as diarrhea and neutropenia, in non-small-cell lung cancer (NSCLC) patients treated with irinotecan chemotherapy. The GWAS putatively identified 49 single-nucleotide polymorphisms (SNPs) associated with grade 3 diarrhea (G3D) and 32 SNPs associated with grade 4 neutropenia (G4N). In the replication series, the SNPs rs1517114 (C8orf34), rs1661167 (FLJ41856) and rs2745761 (PLCB1) were confirmed as being associated with G3D, whereas rs11128347 (PDZRN3) and rs11979430 and rs7779029 (SEMAC3) were confirmed as being associated with G4N. The final imputation analysis of our GWAS and replication study showed significant overlaps of association signals within these novel variants. This GWAS screen, along with subsequent validation and imputation analysis, identified novel SNPs associated with irinotecan-related severe toxicities. [ABSTRACT FROM AUTHOR]

Prostate cancer is initially androgen-dependent but, over time, usually develops hormone- and chemo-resistance. The present study investigated a role for p21-activated kinase 4 (PAK4) in prostate cancer progression. PAK4 activation was markedly inhibited by H89, a specific protein kinase A (PKA) inhibitor, and PAK4 was activated by the elevation of cAMP. The catalytic subunit of PKA interacted with the regulatory domain of PAK4, and directly phosphorylated PAK4 at serine 474 (S474). Catalytically active PAK4 enhanced the transcriptional activity of CREB independent of S133 phosphorylation. Stable knockdown of PAK4 in PC-3 and DU145 prostate cancer cells inhibited tumor formation in nude mice. Decreased tumorigenicity correlated with decreased expression of CREB and its targets, including Bcl-2 and cyclin A1. Additionally, in androgen-dependent LNCap-FGC cells, PAK4 regulated cAMP-induced neuroendocrine differentiation, which is known to promote tumor progression. Finally, PAK4 enhanced survival and decreased apoptosis following chemotherapy. These results suggested that PAK4 regulates progression toward hormone- and chemo-resistance in prostate cancer, and this study identified both a novel activation mechanism and potential downstream effector pathways. Therefore, PAK4 may be a promising therapeutic target in prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Gremlin 1 (GREM1) is a bone morphogenetic protein antagonist and a novel proangiogenic factor. Our aim was to evaluate the prognostic value of GREM1 expression and GREM1-related factors in tumor-associated angiogenesis in pancreatic neuroendocrine tumors (NETs). Methods: The immunohistochemical expression of GREM1 and microvessel density (MVD) were examined in 35 patients with pancreatic NETs and then compared with other clinicopathologic characteristics, including the World Health Organization classification. Results: The presence of expression of GREM1 ( p = 0.016) and high MVD ( p = 0.020) were significant and favorable prognostic factors. Moreover, GREM1 expression was significantly associated with high MVD ( p = 0.011). MVD was significantly higher in well-differentiated NETs than in well-differentiated or poorly differentiated neuroendocrine carcinomas ( p < 0.001). Conclusions: GREM1 expression was correlated with tumor-associated angiogenesis and was found to be a novel prognostic marker in pancreatic NETS. Our data support a tumor suppressor role of GREM1 in pancreatic NETs. [ABSTRACT FROM AUTHOR]

Small angle neutron scattering (SANS) was applied to analyze the nano-structure of normal and osteoporosis compact bones of Korean jaw-bones. The SANS profiles revealed the directional and regular distributions of plate-like bone crystals, lacuna rough surface and nano-sized canliculi in the compact bones. A smaller amount of bone crystals, lacuna and canliculi were present in the osteoporosis bone than in normal human bone. Microstructure observation by transmission electron microscopy and density measurement by bone densitometry supported the SANS evaluation. [ABSTRACT FROM AUTHOR]

Using affinity chromatography, two-dimensional electrophoresis, and MALDI-TOF mass spectrometry, plasminogen isoforms were separated and identified in blood plasma. Healthy donors and patients with prostate cancer in various stages of development were included in the studied sample. With the development of prostate cancer, four additional specific plasminogen isoforms are registered in blood plasma; they are characterized by lower molecular weights and higher p I values compared to isoforms found in the control group. [ABSTRACT FROM AUTHOR]

The results of experimental study of deformation properties of knitted cotton-nitron (orlon, acrylon) fabrics are reported. The efficacy of use of the new fabrics for manufacture of high-elasticity goods is shown. Use of the comprehensive designing factor with due regard for the properties of the knitted fabric and technology of manufacture of the article is recommended. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate and compare the resulting knee kinematics and stability of an anatomic superficial MCL (sMCL) reconstruction and a non-anatomic sMCL reconstruction. Methods: In a cadaveric model, normal knee stability and kinematics were compared with sMCL deficient knees and with two experimental sMCL reconstructions. The first reconstruction (AnatRecon) attempted to anatomically reconstruct the sMCL. The second reconstruction (ShortRecon) used a shorter graft to mimic the effect of failing to reproduce the anatomic length of the sMCL. Changes in position of the femur with respect to the tibia were measured with an electromagnetic tracking system during simulated active knee extension and during passive knee stability testing in the sMCL intact knee, the sMCL deficient knee, and the two experimental reconstructions. Results: Simulated active knee extension demonstrated a significant increase in external tibial rotation of ShortRecon compared to AnatRecon between 30° and 80° of knee flexion (mean difference <3.0° over the range of knee flexion angles; P < 0.008), and a significant increase in external tibial rotation of ShortRecon compared to the intact sMCL was found at 60° and 70° of knee flexion (mean difference <2.0°over the range of knee flexion angles; P < 0.008). Passive joint stability testing demonstrated that division of the sMCL produced approximately 6° of valgus laxity at 30° of knee flexion and increased external tibial rotation of approximately 5° at 30°, 9° at 60°, and 10° at 90° of knee flexion, respectively. AnatRecon restored normal knee kinematics and stability. Additionally, passive stability testing demonstrated a significant increase in external tibial rotation of ShortRecon compared to AnatRecon at 60° (mean difference = 3.7°; P < 0.05) and 90° of knee flexion (mean difference = 4.9°; P < 0.05). Conclusion: Anatomic reconstruction of the sMCL effectively restored knee kinematics and stability in the sMCL deficient knee. Altering the normal ligament length resulted in measurable changes in knee kinematics and stability. This study suggests that in cases of chronic valgus knee instability, anatomic sMCL reconstruction would provide better results than non-anatomic sMCL reconstruction. [ABSTRACT FROM AUTHOR]

It was first shown that DNA damage induction in mitomycin C-treated HeLa cells leads to a change in the selection of 5p and 3p microRNA duplex strands in the formation of the RNA-induced silencing complex (RISC). [ABSTRACT FROM AUTHOR]

To provide optimal selection of patients for preoperative endoscopic retrograde cholangiopancreatography or intraoperative cholangiography, we evaluated simple, noninvasive biochemical parameters as screening tests to predict the absence of common bile duct stones prior to laparoscopic cholecystectomy. A total of 1002 patients underwent laparoscopic cholecystectomy. Five biochemical parameters were measured preoperatively: gamma glutamyl transferase (GGT), alkaline phosphatase, total bilirubin, alanine aminotransferase, and aspartate aminotransferase. Conventional diagnostic tests, including ultrasound imaging, computed tomography, magnetic resonance imaging, common bile duct diameter, endoscopic retrograde cholangiopancreatography, and serum amylase were performed. Along with the five biochemical tests above, these diagnostic tests were scrutinized and compared as potential predictors for common bile duct stones. Eighty-eight (8.8%) patients with gallstone disease who underwent laparoscopic cholecystectomy had concurrent common bile duct stones. Among all diagnostic tests, endoscopic retrograde cholangiopancreatography had the highest sensitivity (96.0%), specificity (99.1%), probability ratio (107.3), accuracy (98.0%), and positive predictive value (98.8%) in detecting common bile duct stones. At least one abnormal elevation among the five biochemical parameters had the highest sensitivity (87.5%). Total bilirubin had the highest specificity (87.5%), highest probability ratio (3.9), highest accuracy (84.1%), and highest positive predictive value (27.4%). All five biochemical predictors had high negative predictive values; gamma glutamyl transferase was highest (97.9%), while the lowest was total bilirubin (94.7%). Multivariate analysis showed only gamma glutamyl transferase, alkaline phosphatase, and total bilirubin to be independent predictors; gamma glutamyl transferase appeared to be the most powerful predictor (odds ratio 3.20). Biochemical tests, especially gamma glutamyl transferase with 97.9% negative predictive value, are ideal noninvasive predictors for the absence of common bile duct stones in patients undergoing laparoscopic cholecystectomy. We suggest that unnecessary, costly, or risky procedures such as endoscopic retrograde cholangiopancreatography can be omitted prior to laparoscopic cholecystectomy in patients without abnormal elevation of these biochemical values. [ABSTRACT FROM AUTHOR]

Essential hypertension (EH) is considered a typical polygenic disease, so the evaluation of gene–gene interactions rather than the determination of single gene effects is crucial to understanding any genetic influences. The G-protein β3-subunit (GNB3) 825T allele, associated with enhanced G-protein signalling, is a strong candidate for interactions with polymorphisms, such as insertion/deletion (I/D) polymorphism of angiotensin I-converting enzyme (ACE) gene. We investigated whether there is an association between GNB3 C825T and ACE I/D polymorphisms for the development of EH. We carried out a case–control study of 688 hypertensive and 924 normotensive subjects recruited from South Korea. The GNB3 C825T and ACE I/D genotypes were determined by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism methods, respectively. The distributions of alleles and genotypes for the GNB3 C825T and ACE I/D polymorphisms were not found to be significantly associated with hypertensive status in either males or females. Logistic regression analysis indicated that the GNB3 825T allele carriers were positively associated with EH in males (odds ratio (OR) for TT/CT, 1.459; 95% confidence interval (CI), 1.048–2.033, P=0.0255). In analysis of gene–gene interaction, we found that there was a significant interaction between the GNB3 825T and ACE D alleles (P<0.05). OR for EH was significantly higher in 825T allele carriers with ACE D allele (OR, 1.490; 95% CI, 1.117–1.987, P=0.0067). A significant interaction between the GNB3 825T and the ACE D alleles may contribute to the predisposing effect for the development of EH in Koreans.Journal of Human Hypertension (2007) 21, 159–166. doi:10.1038/sj.jhh.1002110; published online 26 October 2006 [ABSTRACT FROM AUTHOR]

This paper pertains to the application of optimization technique in the stability analysis of creeping slopes reinforced with passive piles. A method of stability analysis of the pile-reinforced slopes has been derived by extending the friction circle method of slope stability analysis in conjunction with the pile stability analysis proposed by Ito and Matsui. The problem has been cast into a mathematical programming. The solutions have been isolated by formulating the problem as one of non-linear programming. The applicability of the developed method has been verified by comparing the predicted failure surfaces with those results, reported in literature. [ABSTRACT FROM AUTHOR]

Results of large-scale laboratory model tests conducted to determine the permanent settlement due to cyclic load of the railroad bed for a proposed high-speed train route extending from Seoul to Pusan in South Korea are reported. The possibility of using geogrid layers as reinforcement to reduce settlement of the subbase layer was investigated. Based on the present model test results, it appears that practically all permanent settlement due to cyclic load is completed after application of 105 cycles of load. The most beneficial effect of reinforcement is derived when one layer of geotextile and one layer of geogrid are placed at the interface of the subgrade soil and subbase course. [ABSTRACT FROM AUTHOR]

Results of small-scale laboratory model tests to determine the ultimate bearing capacity of a strip foundation supported by sand with multiple layers of geogrid reinforcement are presented. Tests were conducted with only one type of geogrid and a sand compacted to one relative density. The embedment ratio of the foundation was varied from zero to 0.6. It is found that, for the given reinforcement-depth ratio, the bearing capacity ratio with respect to ultimate load increases with embedment. The relationship between the bearing capacity ratio at ultimate load and at limited levels of settlement (less than or equal to 5% of foundation width) is also presented. The bearing capacity ratio at limited levels of settlement is smaller than the value at ultimate load. [ABSTRACT FROM AUTHOR]

We report the case of a 38-year-old woman who underwent surgery for stage III-b breast cancer, and whose liver metastasis failed to respond to both docetaxel (administered at 30–40 mg/m2 every 2 weeks as a 1-h intravenous infusion) and epirubicin (administered as a 40–60 mg/m2 bolus hepatic arterial infusion). For subsequent treatment, this patient was managed with weekly paclitaxel. The regimen showed some usefulness for the treatment of the liver metastasis, as indicated by an improvement in performance status and tolerable toxicity. This case demonstrates that weekly paclitaxel may be well tolerated and useful for patients with extensive metastatic breast cancer that was resistant to treatment. Our findings also suggest that paclitaxel could be used as a salvage therapy in patients with anthracycline- and docetaxel-resistant breast cancer. [ABSTRACT FROM AUTHOR]

Epidemiological studies have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs) decrease the incidence of and mortality from colon cancer. In addition, NSAIDs reduce the number and the size of polyps in patients with familial adenomatous polyposis. The mechanisms responsible for the antineoplastic effect of NSAIDs are not yet completely understood, but one of the possible mechanisms is an induction of apoptosis. We explored the role of caspase-3, a major apoptosis-executing enzyme, in NSAID-induced apoptosis of colon cancer cell line HT-29. Treatment of HT-29 cells with indomethacin induced a dramatic increase in caspase-3-like protease activity measured by a cleavage of the fluorogenic substrate Ac-DEVD-AMC. Western blot analysis showed that indomethacin treatment led both to decrease in pro-caspase-3 and to cleavage of its substrate poly(ADP-ribose) polymerase (PARP). Furthermore, the caspase- 3-like protease inhibitor Ac-DEVD-CHO attenuated indomethacin- induced DNA fragmentation dose dependently. However, mRNA expression of CASP genes was not affected by the addition of indomethacin, highlighting the importance of posttranslational modification of this enzyme for the activation. These results suggest that NSAIDs, including indomethacin, induce apoptosis in colon cancer cells through a caspase-3 dependent mechanism which may contribute to the chemopreventive functions of these agents. [ABSTRACT FROM AUTHOR]

Transpedicular screw fixation has recently been shown to be successful in stabilizing the middle and lower cervical spine. Controversy exists, however, over its efficacy, due to the smaller size of cervical pedicles and the proximity of significant neurovascular structures to both lateral and medial cortical walls. To aid the spinal surgeon in the insertion of pedicle screws, a number of studies have been performed to quantify the gross dimensions and angulations of the cervical pedicle. Notwithstanding these quantitative studies, there has been a conspicuous absence of research reporting the qualitative characteristics of the cervical pedicle. The purpose of our study was to provide comparative graphical data that would systematically document the anatomic variability in cervical pedicle morphology. Such information should better elucidate the complexity of the pedicle as a three-dimensional structure and provide the spinal surgeon with a more complete understanding of cervical pedicle architecture. Twenty-six human cervical vertebrae (C3-C7) from six fresh-frozen spines were secured to a thin sectioning apparatus to produce three 0.7-mm-thick pedicle slices along its axis. Radiographs taken of these pedicle slices were scanned, digitized, and traced to facilitate visual comparison. The pedicle slices were found to exhibit substantial variability in composition and shape, not only between individual spines and vertebral levels, but also within the pedicle axis. However, the lateral cortex was consistently found to be thinner than the medial cortex in all samples. These physical findings must be noted by surgeons attempting transpedicular screw fixation in the cervical spine. [ABSTRACT FROM AUTHOR]

Background. In patients with early stage breast cancer who have breast-conserving therapy (BCT), the impact of local recurrence on the risk of distant metastasis is still controversial. Local recurrence after BCT is an uncommon event, so it is impossible to determine a standard treatment method by a clinical trial because not enough patients can be enrolled. Methods. Between February 1988 and December 1997, 399 patients with clinical stage I and II breast cancer underwent BCT in our department. Of these 399 patients, 22 developed local recurrence during this period. To assess the relationship between their clinical characteristics and prognosis, we performed a retrospective review of these 22 patients. Results. The 5-year overall survival rate after local recurrence was 66.7%. All four patients who had cutaneous or inflammatory type recurrence developed distant metasta-sis after salvage treatment. Of three patients with multiple recurrence, two developed disseminated disease after salvage treatment. Two of four patients treated by repeat lumpectomy developed further local recurrence after salvage lumpectomy. Conclusion. To improve prognosis in patients with multiple, cutaneous, or inflammatory recurrence, aggressive adjuvant systemic therapy may be required after salvage surgery. [ABSTRACT FROM AUTHOR]

Background. The prognostic significance of c-erb B-2 in breast cancer remains controversial. The aim of this study was to determine the practical prognostic significance of c-erb B-2 protein status in breast cancer extracts, using an enzyme immunoassay. Methods. An enzyme immunoassay was used to measure levels of c-erb B-2 protein prospectively in 360 patients with breast cancer, using cytosol fractions prepared for steroid receptor assay. The status of c-erb B-2 protein was assessed using a cut-off value for positivity of 18 ng/mg protein. Univariate and multivariate analyses were performed. To evaluate the prognostic significance of c-erb B-2 protein status. Results. Levels of c-erb B-2 protein in tumor tissue extract ranged from 0 to 213.0 ng/mg protein (mean, 15.5 ng/mg protein). In 52 tumors (14.4 %) more than 18.0 ng/mg protein was detected, and these tumors were regarded as c-erb B-2 protein-positive. Correlations were found between c-erb B-2 protein positivity and large tumor size (>3 cm; P = 0.0095), higher histological grade ( P < 0.0001), estrogen receptor negativity ( P < 0.0001), and progesterone receptor negativity ( P < 0.0001). There was also a marginally significant correlation between c-erb B-2 protein positivity and lymph node positivity. Multivariate analysis showed that c-erb B-2 protein status was a significant independent prognostic factor for disease-free survival, being strongly significant in patients with positive lymph nodes. Conclusion. c-erb B-2-positive breast cancers are biologically more aggressive and c-erb B-2 protein status could be a candidate as a prognostic factor for patients with breast cancer, being particularly valuable in patients with positive lymph nodes. [ABSTRACT FROM AUTHOR]

Laboratory model tests for the settlement of a surface square foundation supported by a medium dense sand and subjected to cyclic loading of low frequency (1 cps), and transient loading have been presented. These tests were conducted with and without geogrid reinforcement in the soil. Only one type of soil and one type of geogrid were used for all tests. The maximum permanent settlement due to the cyclic and transient loads in reinforced and unreinforced soils have been compared. Based on the present test results, it appears that geogrid reinforcement can act as a settlement retardant for dynamic loading conditions on the foundations. [ABSTRACT FROM AUTHOR]

Background. Breast-conserving therapy has been widely accepted as a standard treatment for early breast cancer both in Western countries and in Japan. In Western countries, many studies have investigated the risk factors for local recurrence after breast-conserving therapy (BCT), but few such studies have been done in Japan. Methods. To determine the risk factors for local recurrence in 399 breast cancer patients (stage I and II, n = 396; stage III, n = 3) who had undergone BCT with or without postoperative radiation therapy, we evaluated their clinicopathological features by univariate and multivariate analyses. The patients were treated at Osaka National Hospital between February 1988 and December 1997. Results. Univariate analysis showed that a young age (≤45 years; P = 0.0005) was a significant risk factor for local recurrence, while radiation therapy ( P = 0.0058) and adjuvant endocrine therapy ( P = 0.0041) significantly reduced the risk of local recurrence. In patients with BCT, without radiation therapy a positive surgical margin significantly increased the risk of local recurrence ( P = 0.0470). Multivariate analysis showed that a young age ( P = 0.0285) was a significant independent risk factor for local recurrence, while radiation therapy ( P = 0.0457) significantly decreased recurrence. In patients with a negative surgical margin, radiation therapy ( P = 0.0158) and adjuvant endocrine therapy ( P = 0.0421) significantly reduced the relative risk of local recurrence, to 0.160 and 0.366, respectively. In patients with a positive surgical margin, radiation therapy marginally significantly ( P = 0.0756) reduced the relative risk of local recurrence, to 0.181, and adjuvant endocrine therapy significantly ( P = 0.0119) reduced the risk, to 0.076. Conclusions. Young age and lack of radiation therapy or adjuvant endocrine therapy were risk factors for local recurrence in breast cancer patients treated with breast-conserving therapy, with surgical margin status also being a possible risk factor. [ABSTRACT FROM AUTHOR]

Using the 1960 and 1970 census data, this paper analyzes the net effects of the interregional migration of black males on the educational levels of the resident black male population at the regions of origin and destination. Significant variations are observed in the educational selectivity of out-migrants from each region, by region of destination. Comparing the educational levels of the return migrants to the South with those of the resident population in the nonsouthern regions provides no evidence that the return migrants are "failed" migrants. The net effect of interregional migration on the educational levels of the black male resident population at the regions of origin and destination is insignificant in most age groups, for both the 1955--1960 and 1965--1970 periods. In particular, in-migration from the South to nonsouthern regions has little effect on the educational levels of the resident population in most age groups. In fact, for nonsouthern regions, out-migration is more detrimental to the educational level of the resident black male population than is in-migration from the South. Furthermore, the net effect of interregional migration has declined from the 1955--1960 period to the 1965--1970 period. [ABSTRACT FROM AUTHOR]

This paper examines the trends and variations in the black-white differentials in infant mortality in ten selected Southern states during the 1940-1970 period. The patterns observed from the Southern states are compared with those observed from seven selected Northern states and the country as a whole. The ratios of black to white infant mortality rates and Fein's "time-lag" statistics are used as measures of the extent of black-white differentials. The gaps between blacks and whites in both neonatal and postneonatal mortality rates have widened in the Southern states between 1940 and 1970. No significant differences between the Southern states and the Northern states in the extent of black-whites differentials in infant mortality were observed. A positive association between variations among the Southern states in postneonatal mortality differentials and income differentials was found, while neonatal mortality differentials had a weak inverse relationship with income inequality. A series of general explanations of the observed trends and variations have been presented. Also, a detailed methodological consideration of the possible influence of artifacts of the data upon the trends and variations had been made. [ABSTRACT FROM AUTHOR]

Investigates the effects of learner control and of advisement in a hypertext learning environment with second-grade students who had different levels of prior knowledge about the content. Treatment conditions; Computer-delivered lessons; Issues associated with hypertext systems; Hypertext instruction.