Randomized phase II study of TX followed by XELOX versus the reverse sequence for chemo-naive patients with metastatic gastric cancer.

This research found that the clinical outcomes (PFS, ORR, OS) of the non-platinum-based doublet regimen (docetaxel capecitabine combination) were similar to those of the platinum-based (oxaliplatin capecitabine combination) when used as first line therapy for MGC patients. Background: Docetaxel, platinum and fluorouracil are the three most important drugs in the treatment of MGC. This study was to compare clinical outcomes of the docetaxel capecitabine combination and the oxaliplatin capecitabine combination as first-line therapy in MGC patients. Methods: In this phase II trial, MGC patients were randomly assigned and treated with either TX (capecitabine 1000 mg/m2/twice daily/1-14 days and docetaxel 60/75 mg/m2 on the 1st day) (because of toxicity, the dose of docetaxel was reduced to 60 mg/m2) or XELOX (capecitabine the same dose with TX and oxaliplatin 130 mg/m2 on the 1st day) as first-line therapy. After progression, patients were crossover to the other group as second-line treatment. Results: Total 134 MGC patients were randomized (69 in TX, 65 in XELOX). There was no significant difference between the PFS of the two groups (TX vs XELOX, 4.6 months vs 5.1 months, p=0.359), and the SFS (9.3 months vs 7.5 months, p=0.705), OS (13.1 months vs 9.6 months, p=0.261), and ORR (46.4% vs 46.2%) were also similar. Among patients with ascites, the TX group had significantly longer PFS and OS than the XELOX group. A total of 85 patients (48 in TX, 37 in XELOX) received second-line treatment, with overall survival of second-line chemotherapy (OS2) of 8.0 m and 5.3 m (p=0.046), respectively. Grade 3 to 4 treatment-related adverse events of first line treatment occurred more in TX group than that in XELOX group(60.6% vs 55.4%). Conclusion: TX regimen is an alternative choice of first-line treatment for MGC patients. We still need to explore the large number of cohort to confirm this results.

A Single-Visit Technique for Fabricating Interim, Immediately Loaded Implant-supported Full-arch Prostheses with Prefabricated Rigid Connecting Bars: a Case Report.

Traditional techniques for fabricating interim, immediately loaded implant-supported full-arch prostheses are complex and time-consuming. The present study presents an efficient technique for fabricating interim prostheses with prefabricated multipurpose rigid connecting bars. This technique can minimise the misfit attributed to the polymerisation shrinkage of resin and expansion of the working cast, and simultaneously facilitate impression taking and occlusal records in one visit, thus reducing laboratory and chair time. Due to its ease of use and clinical efficiency, the present technique is considered particularly beneficial for immediate loading rehabilitation.

XELOX doublet regimen versus EOX triplet regimen as first-line treatment for advanced gastric cancer: An open-labeled, multicenter, randomized, prospective phase III trial (EXELOX).

BACKGROUND: There is no consensus on whether triplet regimen is better than doublet regimen in the first-line treatment of advanced gastric cancer (AGC). We aimed to compare the efficacy and safety of oxaliplatin plus capecitabine (XELOX) and epirubicin, oxaliplatin, plus capecitabine (EOX) regimens in treating AGC. METHODS: This phase III trial enrolled previously untreated patients with AGC who were randomly assigned to receive the XELOX or EOX regimen. The primary endpoint was non-inferiority in progression-free survival (PFS) for XELOX as compared with EOX on an intention-to-treat basis. RESULTS: Between April 10, 2015 and August 20, 2020, 448 AGC patients were randomized to receive XELOX (n = 222) or EOX (n = 226). The median PFS (mPFS) was 5.0 months (95% confidence interval [CI] = 4.5-6.0 months) in the XELOX arm and 5.5 months (95% CI = 5.0-6.0 months) in the EOX arm (hazard ratio [HR] = 0.989, 95% CI = 0.812-1.203; Pnon-inferiority = 0.003). There was no significant difference in median overall survival (mOS) (12.0 vs. 12.0 months, P = 0.384) or objective response rate (37.4% vs. 45.1%, P = 0.291) between the two groups. In patients with poorly differentiated adenocarcinoma and liver metastasis, the EOX arm had a significantly longer mOS (P = 0.021) and a trend of longer mPFS (P = 0.073) than the XELOX arm. The rate of grade 3/4 adverse events (AEs) was 42.2% (90/213) in the XELOX arm and 72.5% (156/215) in the EOX arm (P = 0.001). The global health-related quality of life (QoL) score was significantly higher in the XELOX arm than in the EOX arm during chemotherapy. CONCLUSIONS: This non-inferiority trial demonstrated that the doublet regimen was as effective as the triplet regimen and had a better safety profile and QoL as a first-line treatment for AGC patients. However, the triplet regimen might have a survival advantage in patients with poorly differentiated adenocarcinoma and liver metastasis.

Modified Cortex Mori Capsules improving the successful rate of functional filtering blebs after reclinical glaucoma filtering surgery.

BACKGROUND: The major reason for filtering bleb failure or scarring of the bleb site is due to excessive scarring after glaucoma filtration surgery in the clinic. Traditional Chinese medicine has preeminence in the prevention of fibrosis formation through the regulation of systemic circulation and improvement of the properties of the inflammatory cells in the blood. AIM: To examine the clinical efficacy of using the Modified Cortex Mori Capsules (MCMC; Chinese name: Jiawei Sangbaipi Capsules) in the success rate of functional filtering blebs after glaucoma filtering surgery in clinical patients. METHODS: Sixty resurgery glaucoma patients were randomly divided into two groups: 30 patients in surgery with the placebo group and 30 patients in surgery with the MCMC group. Patients took either the placebo or the MCMC 2 wk before and after surgery. Postoperative morphology and function filtering bleb, visual acuity, intraocular pressure, postoperative complications, the success rate of filtration surgery and clinical efficacy were observed. RESULTS: Fifty patients completed the study. The percentage of functional filtering blebs in the surgery plus MCMC group was 84% at 6 mo after surgery, which was higher than surgery plus placebo group (64%, P < 0.05). The surgical success rate in the MCMC and placebo groups were 79% ± 8.3% and 57% ± 10.6% respectively (P < 0.05). The visual acuity, intraocular pressure and the postoperative complications in the two groups had no significant differences. CONCLUSION: Glaucoma filtering surgery while taking MCMC not only reduced excessive scar formation and increased the success rate of functional filtering blebs but also improved the success of glaucoma filtration operations.

Prognostic alternative mRNA splicing signature in hepatocellular carcinoma: a study based on large-scale sequencing data.

Most genes are alternatively spliced and increasing number of evidences show that alternative splicing (AS) is modified and related to tumor progression. Systematic profiles of AS signature in hepatocellular carcinoma (HCC) is absent and urgently needed. Here, differentially spliced AS transcripts between HCC and non-HCC tissues were compared, prognosis-associated AS events by using univariate Cox regression analysis were selected. Our gene functional enrichment analysis demonstrated the potential pathways enriched by survival-associated AS. Prognostic AS signatures were then constructed for HCC prognosis prediction by Lasso regression model. We also analyzed splicing factors (SFs) regulating underlying mechanisms by Pearson correlation and then built corresponding regulatory networks. In addition, we explored the performance of AS signature in the mutated HCC samples. Genome-wide AS events in 377 HCC patients from TCGA were profiled. Among 34 163 AS events in 8985 genes, 3950 AS events in 2403 genes associated with overall survival (OS) significantly for HCC were detected. In addition, computational algorithm results showed that metabolic and ribosome pathways may be the potential molecular mechanisms regulating the poor prognosis. More importantly, survival-associated AS signatures revealed high performance in predicting HCC prognosis. The area under curve for AS signature was 0.806 in all HCC and 0.944 in TP53 mutated HCC samples at 2000 days of OS. We submitted prognostic SFs to build the AS regulatory network, from which we found prognostic AS events were significantly enriched in metabolism-related pathways. A robust AS signature for HCC patients and revealed the regulatory splicing networks contributing to the potential significantly enriched metabolism-related pathways.

Comparative efficacy and safety between ablative therapies or surgery for small hepatocellular carcinoma: a network meta-analysis.

BACKGROUND: Major treatments for small hepatocellular carcinoma (SHCC) include percutaneous ethanol injection (PEI), percutaneous acetic acid injection (PAI), radiofrequency ablation (RFA), or surgical resection (SR). We aimed to compare these therapies concerning with effectiveness and safety. METHODS: Cochrane Library, PubMed, and Embase were searched for randomized controlled studies (RCTs) from inception to 30 April 2017. Odds ratios (OR) for proportion dead (PD), local recurrence (LR) and adverse events (AEs). RESULTS: Fourteen RCTs were identified. Compared with SR, PEI (OR 2.79, CrI 1.25, 6.45, p < 0.01) provided a significantly increased risk of PD. Similarly, PEI (OR 4.29, CrI 1.18, 18.35, p < 0.01) yielded more LR than SR. Also, SR significantly conferred more AEs than RFA (OR 0.10; CrI 0.02, 0.35, p < 0.01), PEI (OR 0.06; CrI 0.01, 0.31, p < 0.01). Besides, RFA conferred the highest efficacy for survival, time to recurrence, and new development of HCC. CONCLUSIONS: SR was superior to PEI. Although SR achieved highest cumulative ranking probabilities in clinical efficacy, it obtained a low benefit-to-risk ratio for patients. RFA was superior to the other ablative therapies. For tumor sizes > 2 cm or ≤ 2 cm in diameter, SR conferred non-significant effects compared with other therapies for SHCC.

MDM4 genetic variants and risk of gastric cancer in an Eastern Chinese population.

MDM4 is a p53-interacting protein and plays an important role in carcinogenesis. In this study of 1,077 gastric cancer (GCa) cases and 1,173 matched cancer-free controls, we investigated associations between three tagging single nucleotide polymorphisms (SNPs) (rs11801299 G>A, rs1380576 C>G and rs10900598 G>T) in MDM4 and gastric cancer risk in an Eastern Chinese Population. In logistic regression analysis, a significantly decreased GCa risk was associated with the rs1380576 GG variant genotype (adjusted odds ratio [OR] =0.74, 95% confidence interval [CI] =0.56-0.98) under a recessive model, which remained significant after correction by the false-positive reporting probability. This risk was more evident in subgroups of older subjects, males, never smokers, never drinkers and cancers of non-cardia. We then performed SNP-mRNA expression correlation analysis and found that the GG variant genotype was associated with significantly decreased expression of MDM4 mRNA in normal cell lines for 44 Chinese (P=0.032 for GG vs. CC) as well as for 269 multi-ethnic subjects (P<0.0001 for GG vs. CC). Our results suggest that the MDM4 rs1380576 G variant may be markers for GCa susceptibility. Larger, independent studies are warranted to validate our findings.

Influence of delayed initiation of adjuvant chemotherapy on breast cancer survival is subtype-dependent.

PURPOSE: The optimal time from surgery to initiation of adjuvant chemotherapy of breast cancer is still controversial. We investigated the influence of time to adjuvant chemotherapy on survival outcomes according to breast cancer subtype. RESULTS: Longer delay of initiation of adjuvant chemotherapy (≤4 weeks versus >8 weeks)) significantly decreased the DFS (adjusted hazard ratio [HR] of 1.86; 95% confidence interval [CI], 1.19-2.90) and OS (adjusted HR of 2.02; 95% CI, 1.10-3.71). However, a moderate delay (≤4 weeks versus 4-8 weeks) did not significantly influence the survival. We further investigated the effect of time to adjuvant chemotherapy (≤8 versus >8 weeks) on survival according to subtypes. Patients with luminal-A tumors who received delayed chemotherapy had no increased risk of recurrence (HR of 1.15; 95% CI, 0.54-2.43). In contrast, patients with luminal-B, triple-negative, or trastuzumab-untreated HER2-positive tumors would have decreased DFS because of delayed chemotherapy, with HR of 1.93 (95% CI, 1.10-3.34), 2.55 (95% CI, 1.25-5.18), and 2.41 (95% CI, 1.36-4.26), respectively. METHODS: Operable women with stage I-IIIa breast cancer between 2003 and 2006 in our institution were included. 1,408 patients were divided into 3 groups according to the time to adjuvant chemotherapy: ≤4 weeks, 4-8 weeks, and >8 weeks. Disease-free survival (DFS) and overall survival (OS) were calculated. CONCLUSION: Longer delay of adjuvant chemotherapy was associated with worse survival and early initiation of adjuvant chemotherapy should be performed for patients with aggressive tumor subtypes.

Is there a dose-dependent effect of genetic susceptibility loci for gastric cancer on prognosis of the patients?

Literature suggests that genetic variants associated with increased susceptibility to gastric cancer (GCa) are mostly located in genes involved in carcinogenesis and possibly tumor progression. Therefore, we hypothesize that high genetic susceptibility is also associated with prognosis of the patients. To test this hypothesis, we selected a total of 42 common genetic variants that were reportedly associated with GCa risk with a high level of evidence obtained from either genome-wide association studies (GWASs) or meta-analyses and performed survival analysis of patients used in a case-control analysis. We first used 1115 GCa cases and 1172 cancer-free controls of ethnic Han Chinese to construct a weighted genetic risk score (GRS). Then, we included 633 GCa cases with available clinical information, fit GRS in a fractional polynomial Cox proportional hazards regression model to investigate whether there is a dose-dependent effect of GRS on risk of death in survival analysis. Dynamic predictive value of genetic risk for prognosis was also calculated. The results showed that the increase of GRS had no effect on risk of death in these GCa patients. Compared with GCa patients with the medium GRS, there was no significant difference in survival in patients with either a low (P = 0.349) or a high (P = 0.847) GRS. The results unchanged when data were stratified by tumor stage and Lauren's classification. Time-dependent predictive value for prognosis in considering both clinical factors and GRS was comparable with that in considering clinical factors alone, for either all patients (P = 0.986) or stage- and Laruen type-based subgroups (P > 0.05 for all). In conclusion, higher polygenic susceptibility loci for GCa may not indicate worse prognosis of Chinese patients. Additional variants of relevant genes modulating GCa patients' survival need to be further identified.

Associations of genotypes and haplotypes of IL-17 with risk of gastric cancer in an eastern Chinese population.

Interleukin-17 plays a crucial role in inflammation-related carcinogenesis. We hypothesize that genetic variants in IL-17 are associated with gastric cancer (GCa) risk, and we genotyped five potentially functional single nucleotide polymorphisms (SNPs) (rs1974226 G > A, rs2275913 A > G, rs3819024 A > G, rs4711998 A > G, and rs8193036 C > T) of IL-17 in 1121 GCa patients and 1216 cancer-free controls in an eastern Chinese population. Logistic regression analysis was used to calculate odds ratios (OR) and 95% confidence intervals (CI). Meta-analysis and genotype-mRNA expression correlation were performed to further validate positive associations. We found that an increased GCa risk was independently associated with rs1974226 (adjusted OR = 2.60, 95% CI = 1.27-5.32 for AA vs. GG + GA) and rs2275913 (adjusted OR = 1.33, 95% CI = 1.03-1.72 for GA + AA vs. GG), while a decreased GCa risk was independently associated with rs3819024 (adjusted OR = 0.72, 95% CI = 0.54-0.96 for GG vs. AA + AG). Additional meta-analyses confirmed the observed risk association with rs2275913. We also found that two IL-17 haplotypes (G-G-G-A-C) and (A-G-G-A-C) (in the order of rs1974226, rs2275913, rs3819024, rs4711998 and rs8193036) were associated with a reduced GCa risk (adjusted OR = 0.64, 95% CI = 0.46-0.89 and adjusted OR = 0.38, 95% CI = 0.17-0.81, respectively). However, the expression Quantitative Trait Locus (eQTL) analysis for the genotype-phenotype correlation did not find mRNA expression changes associated with either the genotypes. In conclusions, genetic variants of IL-17 are likely to be associated with risk of GCa, and additional larger studies with functional validation are needed to explore the molecular mechanisms underlying the observed associations.

Associations of potentially functional variants in IL-6, JAKs and STAT3 with gastric cancer risk in an eastern Chinese population.

The interleukin-6 (IL-6)/JAK/STAT3 signaling pathway plays a central role in inflammation-mediated cancers, including gastric cancer (GCa). We evaluated associations between 10 potentially functional single nucleotide polymorphisms (SNPs) of four essential genes in the pathway and GCa risk in a study of 1,125 GCa cases and 1,221 cancer-free controls. We found that a significant higher GCa risk was associated with IL-6 rs2069837G variant genotypes [adjusted odds ratios (OR) = 1.33; 95% confidence interval (CI) = 1.12-1.59 for AG + GG vs. AA)] and JAK1 rs2230587A variant genotypes (adjusted OR = 1.20; 95% CI = 1.02-1.43 for GA + AA vs. GG). We also found that a significant decreased GCa risk was associated with STAT3 rs1053004G variant genotypes (adjusted OR = 0.84; 95% CI = 0.71-0.99 for AG + GG vs. AA). The combined analysis of IL-6 rs2069837G and JAK1 rs2230587A variant risk genotypes revealed that individuals with one-or-two risk genotypes exhibited an increased risk for GCa (adjusted OR = 1.34; 95% CI = 1.13-1.59). Genotypes and mRNA expression correlation analysis using the data from the HapMap 3 database provided further support for the observed risk associations. Larger studies are warranted to validate these findings.

Genetic variant of miR-146a rs2910164 C>G and gastric cancer susceptibility.

The single nucleotide polymorphism (SNP) rs2910164 G>C within miR-146a has been reported that is associated with the increased risk of gastric cancer (GCa). However, the results are inconclusive, espicially among Asian populations, which probably due to small sample size in each single study. To validate this association and get a more precise estimation, we conducted a large GCa study including 1,125 cases and 1,196 controls in an eastern Chinese population. Our results showed that this SNP was not associated with GCa risk in either of the three genetic models [co-dominant model: CG vs. CC, odds ratio (OR) = 0.99, 95% confidence interval (95%CI): 0.83-1.19; GG vs. CC, OR = 1.03, 95%CI: 0.81-1.32; dominant model: (CG+GG) vs. CC, OR = 1.00, 95%CI = 0.84-1.19; recessive model: GG vs. (CG+CC), OR = 1.04, 95%CI = 0.83-1.29]. Stratified analysis by age, gender, smoking status, drinking status, or tumor location confirmed this non-significant association. In summary, these results suggest that the miR-146a SNP rs2910164 may not be a risk factor for GCa in this Chinese population. Larger and well-designed, preferably prospective studies are needed to further confirm our findings.

PSCA polymorphisms and gastric cancer susceptibility in an eastern Chinese population.

The prostate stem cell antigen (PSCA) gene, which encodes a prostate-specific antigen (PSA), was identified as a gene involved in cell adhesion and proliferation. The associations between the PSCA rs2294008 and rs2976392 single nucleotide polymorphisms (SNPs) and gastric cancer (GCa) susceptibility were still controversial. To derive a more precise estimation of the associations, we conducted a case-control study of 1,124 cases and 1,192 controls in an eastern Chinese population. We found that the rs2294008T variant genotypes were associated with an increased GCa risk in this study population (CT vs CC, OR=1.59, 95% CI=1.33-1.89 and CT+TT vs CC, OR=1.38, 95% CI=1.17-1.62). For SNP rs2976392, the variant A genotypes were also associated with an increased GCa risk (AG vs GG, OR=1.61, 95% CI=1.35-1.91 and AG+AA vs GG, OR=1.47, 95% CI=1.25-1.74). The results were further validated by a meta-analysis. In conclusion, the results indicated that the PSCA rs2294008 T and rs2976392 A alleles were low-penetrate risk factors for GCa in this study population. However, large and well-designed studies are warranted to validate our findings.

Genetic variant rs4072037 of MUC1 and gastric cancer risk in an Eastern Chinese population.

Published data on the association between the MUC1 rs4072037A > G polymorphism and gastric cancer (GCa) risk were inconclusive. To derive a more precise estimation of the association, we conducted a large GCa study of 1,124 cases and 1,192 controls to confirm this association in an Eastern Chinese population. Our results showed that the G allele was strongly associated with a decreased GCa risk in the study population [GG vs. AA, odds ratio (OR) = 0.47, 95% confidence interval (CI) = 0.31-0.73; AG/GG vs. AA, OR = 0.82, 95% CI = 0.68-0.99; GG vs. AA/AG, OR = 0.48, 95% CI = 0.32-0.74]. These associations remained significant in subgroups of age, tumor site, drinking and smoking status. Moreover, this association was supported by an additional meta-analysis of published studies. In summary, these results suggest that the MUC1 rs4072037G allele may be a low-penetrating protection factor for GCa risk in Chinese populations.

Genetic variant of PRKAA1 and gastric cancer risk in an eastern Chinese population.

Published data on the association between PRKAA1 rs13361707 T > C polymorphism and gastric cancer (GCa) susceptibility were inconclusive. To derive a more precise estimation of the association, we conducted a large-scale GCa study of 1,124 cases and 1,194 controls to confirm this association in an eastern Chinese population. Our results showed that the C allele of PRKAA1 rs13361707 increased the GC risk in the study population [CT vs. TT, odds ratio (OR) = 1.72, 95% confidence interval (CI) = 1.40-2.12; CC vs. TT, OR = 2.15, 95%CI = 1.70-2.71; CT/CC vs. TT, OR = 1.86, 95%CI = 1.53-2.26; CC vs.TT/CT, OR = 1.49, 95%CI = 1.24-1.79]. In addition, the association of C allele with an increased GCa risk was still significant in subgroups, when stratified by age, sex, tumor site, drinking and smoking status. Moreover, the findings in the present study were validated by our further meta-analysis. In summary, these results indicated that the C allele of PRKAA1 rs13361707 was a low-penetrate risk factor for GCa.

Genetic variations in the mTOR gene contribute toward gastric adenocarcinoma susceptibility in an Eastern Chinese population.

BACKGROUND AND AIM: Genetic variants in the mammalian target of rapamycin (mTOR) gene have become an interesting topic for the study of genetic susceptibility to cancer, but their associations with the risk of gastric cancer have not been fully investigated. MATERIALS AND METHODS: In a hospital-based case-control study of 1002 gastric cancer patients and 1003 cancer-free controls, we genotyped four potentially functional single nucleotide polymorphisms (SNPs) (rs1034528G>C, rs17036508T>C, rs3806317A>G, and rs2295080T>G) of mTOR and assessed their associations with the risk of gastric cancer using univariate and multivariate logistic regression analyses. We also used the multifactorial dimension reduction analysis to explore possible interactions and the false-positive report probabilities to assess significant findings. RESULTS: We found that rs1034528 CG/CC and rs3806317 GA/GG variant genotypes were associated with an increased risk of gastric cancer under a dominant model (adjusted odds ratio=1.27 and 1.22, respectively). In the combined analysis of all four SNPs under investigation, patients with 3-4 risk genotypes of mTOR had a significantly increased risk of gastric cancer (adjusted odds ratio=1.46, 95% confidence interval=1.19-1.79) compared with those with 0-2 risk genotypes. Stratified analysis indicated that this risk was more pronounced in subgroups of men, never-smokers, never-drinkers, and clinical stages III+IV. The multifactorial dimension reduction analysis suggested some evidence of interactions between the combined genotypes and other risk factors for gastric cancer. CONCLUSION: These findings suggest that potentially functional SNPs of mTOR may individually or collectively contribute to the risk of gastric cancer. Larger studies with diverse ethnic populations are warranted to validate our findings.

Efficacy of Chinese eye exercises on reducing accommodative lag in school-aged children: a randomized controlled trial.

PURPOSE: To evaluate the efficacy of Chinese eye exercises on reducing accommodative lag in children by a randomized, double-blinded controlled trial. METHODS: A total of 190 children aged 10 to 14 years with emmetropia to moderate myopia were included. They were randomly allocated to three groups: standard Chinese eye exercises group (trained for eye exercises by doctors of traditional Chinese medicine); sham point eye exercises group (instructed to massage on non-acupoints); and eyes closed group (asked to close their eyes without massage). Primary outcome was change in accommodative lag immediately after intervention. Secondary outcomes included changes in corrected near and distant visual acuity, and visual discomfort score. RESULTS: Children in the standard Chinese eye exercises group had significantly greater alleviation of accommodative lag (-0.10 D) than those in sham point eye exercises group (-0.03 D) and eyes closed group (0.07 D) (P = 0.04). The proportion of children with alleviation of accommodative lag was significantly higher in the standard Chinese eye exercises group (54.0%) than in the sham point eye exercises group (32.8%) and the eyes closed group (34.9%) (P = 0.03). No significant differences were found in secondary outcomes. CONCLUSION: Chinese eye exercises as performed daily in primary and middle schools in China have statistically but probably clinically insignificant effect in reducing accommodative lag of school-aged children in the short-term. Considering the higher amounts of near work load of Chinese children, the efficacy of eye exercises may be insufficient in preventing myopia progression in the long-term. TRIAL REGISTRATION: ClinicalTrials.gov NCT01756287.

[Implanting the edentulous jaws with "All-on-4" immediate reconstruction: a preliminary clinical observation].

OBJECTIVE: To evaluate the treatment outcome of the "All-on-4" immediate loading protocol via survival rate of the implants,survival rate of the prosthesis,marginal bone, postoperative complications and patient satisfaction. METHODS: In our study, 40 patients with 49 edentulous jaws (31 mandibles and 18 maxillae) were enrolled. Each jaw was restored by the shortened dental arch prosthesis supported by only 4 implants according to the All-on-4 protocol (All-on-4, Nobel Biocare AB, Goteborg, Sweden). For all the patients enrolled in the study, the loading was applied within 12 hours of surgery. The provisional prosthesis could be replaced by the final restorations within 6 to 12 months. In the present study, the survival rate of the both implants and restorations were calculated and analyzed. The radiographic evaluation of marginal bone level changes was measured. The values of the marginal bone level changes of the angled and axial implants were analyzed by the statistic software. RESULTS: In the present study, totally 196 implants were inserted, of which 13 implants failed during the whole following up periods, with 11 implants of the maxillae and 2 of the mandibles. The survival rate of the prosthesis was 95.9% (47/49). The implant survival rate of the maxillae was 85.5% (65/76)while that for the mandibles was 98.3%(118/120). The implant survival rate of the angled implants was 91.8% (90/98), while that for the straight implants was 95.0% (93/98). No significant difference in marginal bone loss was found between angled and axial implants in the 12-month evaluation according to the Wilcoxon rank sum test (P>0.05). During the follow-up period,mechanical complications as fracture of the provisional prostheses, loose of the retain screw, or crack of the artificial teeth were found in 20 prostheses. CONCLUSION: The present preliminary data of the short term observation suggest that the "All-on-4" immediate loading protocol is a viable treatment modality for the edentulous jaws. However, long term clinical random controlled trials with large samples are still needed to confirm the validity of the technique.

The All-on-Four implant therapy protocol in the management of edentulous Chinese patients.

PURPOSE: To evaluate the outcome and special characteristics of immediate implant rehabilitation using the All-on-Four treatment concept in completely or potentially completely edentulous Chinese patients. MATERIALS AND METHODS: A convenience sample consisted of 69 consecutive patients (37 men, 32 women; mean age: 56.7 years) treated with immediate implant placement and full-arch prosthodontic provisional prostheses between April 2008 and December 2011. Of 344 implants (192 mandibular, 152 maxillary), 240 implants were placed in fresh extraction sites. The remaining 104 implants were placed in healed sites. Implants were immediately loaded with a fixed full-arch provisional prosthesis. Implant survival rate, marginal bone loss, abutment selection, complications, and subjective patient responses were recorded during follow-up. RESULTS: Implant survival rate was 96.2% at 33.7 months of mean follow-up (range: 12 to 56 months). A statistically significantly higher implant survival rate was found in the mandible (99.0% vs 92.8%) (P < .05). No significant difference existed between survival rates for implants placed in postextraction sites and healed sites (P > .05). Peri-implant marginal bone loss around upright implants and tilted implants was 0.7 ± 0.2 mm and 0.8 ± 0.4 mm, respectively. All patients reported satisfactory treatment outcomes. CONCLUSIONS: The modified All-on-Four treatment concept provides predictably favorable outcomes in completely or potentially completely edentulous patients and is well suited to the sociodemographic needs of Chinese patients. Exploratory use of a surgical guide was limited because of mouth opening, and more angulated abutments were needed in anterior upright implants of the maxilla.

Association of LEP G2548A and LEPR Q223R polymorphisms with cancer susceptibility: evidence from a meta-analysis.

BACKGROUND: Numerous epidemiological studies have examined associations of genetic variations in LEP (G2548A, -2548 nucleotide upstream of the ATG start site) and LEPR (Q223R, nonsynonymous SNP in exon 6) with cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis to comprehensively evaluate such associations. METHODS: We searched published literature from MEDLINE, EMBASE, Web of Science and CBM for eligible publications. We also assessed genotype-based mRNA expression data from HapMap for rs7799039 (G2548A) and rs1137101 (Q223R) in normal cell lines derived from 270 subjects with different ethnicities. RESULTS: The final analysis included 16 published studies of 6569 cases and 8405 controls for the LEP G2548A and 19 studies of 7504 cases and 9581 controls for the LEPR Q223R. Overall, LEP G2548A was statistically significantly associated with an increased risk of overall cancer (AA vs. GG: OR=1.27, 95% CI=1.05-1.54; recessive model: OR=1.19, 95% CI=1.00-1.41). Further stratifications by cancer type showed an increased risk for prostate cancer (recessive model: OR=1.26, 95% CI=1.05-1.51) but not for other cancers. For LEPR Q223R, no statistical evidence for an association with risk of cancer was found for all; however, further stratification by ethnicity showed an increased risk for Africans but not for other ethnicities. No significantly differences in LEP and LEPR mRNA expression were found among genotypes or by ethnicity. CONCLUSIONS: Despite some limitations, this meta-analysis found some statistical evidence for an association between the LEP 2548AA genotype and overall risk of cancer, particularly for prostate cancer, but given this variant did not have an effect on mRNA expression, this association warrants additional validation in large and well-designed studies.