Diosmin ameliorates renal fibrosis through inhibition of inflammation by regulating SIRT3-mediated NF-κB p65 nuclear translocation.

BACKGROUND: Renal fibrosis is considered an irreversible pathological process and the ultimate common pathway for the development of all types of chronic kidney diseases and renal failure. Diosmin is a natural flavonoid glycoside that has antioxidant, anti-inflammatory, and antifibrotic activities. However, whether Diosmin protects kidneys by inhibiting renal fibrosis is unknown. We aimed to investigate the role of Diosmin in renal interstitial fibrosis and to explore the underlying mechanisms. METHODS: The UUO mouse model was established and gavaged with Diosmin (50 mg/kg·d and 100 mg/kg·d) for 14 days. HE staining, Masson staining, immunohistochemistry, western blotting and PCR were used to assess renal tissue injury and fibrosis. Elisa kits were used to detect the expression levels of IL-1ß, IL-6, and TNF-α and the activity of SIRT3 in renal tissues. In addition, enrichment maps of RNA sequencing analyzed changes in signaling pathways. In vitro, human renal tubular epithelial cells (HK-2) were stimulated with TGF-ß1 and then treated with diosmin (75 µM). The protein and mRNA expression levels of SIRT3 were detected in the cells. In addition, 3-TYP (selective inhibitor of SIRT3) and SIRT3 small interfering RNA (siRNA) were used to reduce SIRT3 levels in HK-2. RESULTS: Diosmin attenuated UUO-induced renal fibrosis and TGF-ß1-induced HK-2 fibrosis. In addition, Diosmin reduced IL-1ß, IL-6, and TNF-α levels in kidney tissues and supernatants of HK-2 medium. Interestingly, Diosmin administration increased the enzymatic activity of SIRT3 in UUO kidneys. In addition, Diosmin significantly increased mRNA and protein expression of SIRT3 in vitro and in vivo. Inhibition of SIRT3 expression using 3-TYP or SIRT3 siRNA abolished the anti-inflammatory effects of diosmin in HK-2 cells. Enrichment map analysis by RNA sequencing indicates that the nuclear factor-kappa B (NF-κB) signaling pathway was inhibited in the Diosmin intervention group. Furthermore, we found that TGF-ß1 increased the nuclear expression of nuclear NF-κB p65 but had little significant effect on the total intracellular expression of NF-κB p65. Additionally, Diosmin reduced TGF-ß1-caused NF-κB p65 nuclear translocation. Knockdown of SIRT3 expression by SIRT3 siRNA increased the nuclear expression of NF-κB p65 and abolished the inhibition effect of Diosmin in NF-κB p65 expression. CONCLUSIONS: Diosmin reduces renal inflammation and fibrosis, which is contributed by inhibiting nuclear translocation of NF-κB P65 through activating SIRT3.

Emerging role of air pollution in chronic kidney disease.

Chronic kidney disease (CKD), a global disease burden related to high rates of incidence and mortality, manifests as progressive and irretrievable nephron loss and decreased kidney regeneration capacity. Emerging studies have suggested that exposure to air pollution is closely relevant to increased risk of CKD, CKD progression and end-stage kidney disease (ESKD). Inhaled airborne particles may cause vascular injury, intraglomerular hypertension, or glomerulosclerosis through non-hemodynamic and hemodynamic factors with multiple complex interactions. The mechanisms linking air pollutants exposure to CKD include elevated blood pressure, worsening oxidative stress and inflammatory response, DNA damage and abnormal metabolic changes to aggravate kidney damage. In the present review, we will discuss the epidemiologic observations linking air pollutants exposure to the incidence and progression of CKD. Then, we elaborate the potential roles of several air pollutants including particulate matter and gaseous co-pollutants, environmental tobacco smoke, and gaseous heavy metals in its pathogenesis. Finally, this review outlines the latent effect of air pollution in ESKD patients undergoing dialysis or renal transplant, kidney cancer and other kidney diseases. The information obtained may be beneficial for further elucidating the pathogenesis of CKD and making proper preventive strategies for this disease.

Elevated levels of serum IL-36α in patients with systemic lupus erythematosus.

The present study aimed to investigate the levels of IL-36α and its association with disease activity in patients with systemic lupus erythematosus (SLE). A total of 60 patients with SLE and 29 healthy controls were enrolled in the present study. Disease activity was evaluated using the SLE disease activity index (SLEDAI). The serum levels of IL-36α, IL-36 receptor antagonist (IL-36Ra) and IL-17 were assessed using ELISA. The levels of IL-36α in patients with SLE were significantly higher compared with those of healthy controls. There was a significant increase in IL-36α in the active SLE group (SLEDAI score ≥5) compared with that of the healthy controls (P<0.001). The serum IL-36α levels were higher in patients with active SLE than in patients with quiescent disease (P=0.012). IL-36Ra was downregulated in patients with SLE (P=0.007). The serum IL-17 levels were elevated in patients with SLE (P=0.036), and a positive correlation was observed between the IL-36α and IL-17 levels (r=0.453, P=0.003). The serum IL-36α levels were associated with SLEDAI (r=0.374, P=0.003), proteinuria (r=0.329, P=0.010) and complement 3 (r=-0.336, P=0.009). Patients who were receiving glucocorticoid treatment had lower IL-36α levels than those who were not receiving glucocorticoid treatment (P=0.003). Patients with lupus nephritis had higher serum IL-36α levels compared with those found in patients without lupus nephritis (P=0.037). The serum IL-36α concentration was elevated in patients with SLE, and was correlated with disease activity and IL-17 levels. The aberrant serum IL-36α levels observed in the present study and its clinical association with SLE suggest the important role of IL-36α in onset and progression of SLE. In addition, the association of IL-36α with IL-17 level indicates its involvement in the regulation of T helper 17 cytokines.

Effects of bamboo shoots (Phyllostachys edulis) dietary fibers prepared by different processes on the adsorption characteristics of polyphenols.

In this work, adopting bamboo shoots as raw materials, three kinds of bamboo shoots dietary fibers were prepared by physical, chemical, and enzymatic methods, termed BSPDF, BSCDF, and BSEDF, respectively, and then investigating their adsorption characteristics for polyphenols through soaked them in different concentrations and different types of polyphenol solutions. The results of the adsorption kinetics showed that the adsorption amounts of polyphenols significantly increased during the initial 30 s of soaking, and the subsequent adsorption rate became slower and slower achieving adsorption kinetics after 2 hr. Moreover, their adsorption isotherms met well with the Langmuir model, but differences in saturated adsorption capacity and adsorption rate. More impressively, the maximum adsorption capacities Qmax of them to polyphenols followed the order of catechin > phlorizin dihydrate > chlorogenic acid > gallic acid. In addition, BSPDF, BSCDF and BSEDF all could adsorb a large amount of free catechin with the saturated adsorption capacity of 15.77, 14.69 and 16.76 mg/g, respectively and which exhibited blue and green characteristic fluorescence emission signals in the presence of catechin. Therefore, compared with the other two methods, the enzymatic hydrolysis method retains the spatial network structure of the fibrils, has a larger surface area and porosity, retains the original bound phenol of fibrils, with stronger physiological activity and more potential applications. PRACTICAL APPLICATIONS: Polyphenols are easy to oxidize in vitro, and are easily affected by gastric acid and various enzymes in vivo, which reduce their physiological activity. However, dietary fibers can resist the destruction of various enzymes and acids in the gastrointestinal tract. It is increasingly being realized that dietary fibers play a very important role in adsorbing polyphenols into its network structure, which can achieve the purpose of protecting polyphenols. In this contest, the bamboo shoots dietary fibers prepared by different methods had different adsorption characteristics for polyphenols. The aim of current study was to compare the saturated adsorption capacity of three kinds of dietary fibers to polyphenols, and screen suitable processing technology. We believed that our findings could be to provide basis for the development of new functional foods.

The efficacy of rituximab in the treatment of refractory nephrotic syndrome: a meta-analysis.

OBJECTIVE: The evidence from epidemiological research on whether the efficacy of rituximab in treatment of refractory nephrotic syndrome (NS) is better than other agents is inconsistent. This meta-analysis aimed to assess the efficacy of rituximab in the treatment of NS compared with other immunosuppressive agents. METHODS: Relevant literatures were identified and evaluated for quality before October 2019 through multiple search strategies on PubMed and EMBASE. Statistical evidence of the symmetry of the funnel plot obtained from Begg's test was indicated by Egger's linear regression and a sensitivity analysis identified heterogeneity. A fixed- or a random-effects model was applied to calculate the pooled SMDs and RRs. RESULTS: A total of 12 studies, involving 383 patients and 354 controls, were included. Compared with other agents, rituximab significantly improved complete remission both in children and adults [Overall: RR = 1.313, 95% CI = 1.170-1.475, P < 0.001; Adult: RR = 1.359, 95% CI = 1.053-1.753, P = 0.019 Children: RR = 1.354, 95% CI = 1.072-1.709, P < 0.001], and dramatically decreased the relapse rate in children [Overall: RR = 0.349, 95% CI = 0.166-0.732, P < 0.001; Children: RR = 0.286, 95% CI = 0.176-0.463, P < 0.001]. CONCLUSIONS: Rituximab might be a promising treatment for refractory NS. Compared with other agents, rituximab significantly improves the complete remission and decreased the relapse rate. However, to confirm the efficacy of rituximab in the treatment of refractory NS, more high-quality, large sample, and multicenter randomized controlled trials are needed.

[Accuracy of paralleling technique in measuring the depth of approximal infrabony pocket].

OBJECTIVE: To assess the accuracy of paralleling technique in measuring the depth of approximal infrabony pocket after periodontal flap surgery by comparing the measured and actual depths. METHODS: The study population included 26 patients with infrabony defects who had undergone periodontal flap surgery, bone graft surgery, and guided tissue regene-ration. The measured and actual depths of approximal infrabony pocket after periodontal flap surgery were compared. The 26 infrabony defects were categorized into the following groups according to tooth position: anterior teeth, premolar, and molar groups, and according to type of infrabony pocket: one-walled, two-walled, and three-walled infrabony pocket groups. Paired t-test was used to detect the difference between the two values. RESULTS: Depth measurements of the approximal infrabony pocket depth of the anterior teeth and premolar were not significantly different (P>0.05), whereas those of the molar group were significantly different (P<0.05). In addition, depth measurements in one-walled and two-walled infrabony pocket groups showed no significant differences (P>0.05), whereas those in the three-walled infrabony pocket group were significantly different (P<0.05). CONCLUSIONS: Paral-leling technique can accurately measure the depth of approximal infrabony pockets of anterior teeth and premolar teeth that are one- or two-walled. However, this method cannot accurately measure the approximal infrabony pockets of molar teeth and three-walled infrabony pockets as indicated by significant differences in their depth measurements.

Increased Serum Levels of Soluble B7-H4 in Patients with Systemic Lupus Erythematosus.

BACKGROUND: Members of B7 family are reported to regulate lymphocytes activation, transmit both costimulatory and co-inhibitory signals, control T cell-mediated immune responses and tolerance. Among which B7-H4 is reported to regulate the immune response negatively. OBJECTIVE: To investigate the plasma concentration of soluble B7-H4 (sB7-H4) and its clinical significance in systemic lupus erythematosus (SLE). METHODS: Fifty-six SLE patients with or without active SLE (ASLE) and 29 age- and gender-matched healthy volunteers were recruited. Plasma concentration of sB7-H4 was measured using sandwich ELISA kits. RESULTS: Compared with healthy subjects, the concentration of sB7-H4 was significantly higher in patients with SLE (p=0.006). Plasma sB7-H4 concentration in patients with lupus nephritis (LN) were also significantly higher than healthy subjects (p=0.008), but no difference was found between LN and SLE patients without LN (non-LN). Additionally, the sB7-H4 concentration in patients was negatively correlated with the SLE disease activity index score (SLEDAI) (r=-0.3055, p=0.022). Compared with inactive disease, the concentration of sB7-H4 in ASLE patients was significantly lower (p=0.002). There were statistical significances between the positive and negative groups with decreased leukocytes or thrombocytes (p=0.012; p=0.033; respectively), but no statistically significant difference was found in other positive and negative serum laboratory indicators. CONCLUSIONS: The increased level of sB7-H4 in patients suggests that this pathway might be involved in the pathogenesis of SLE. However, the exact mechanism or physiological role of sB7-H4 in SLE pathogenesis remains to be investigated.

Increased ratio of Th17 cells to SIGIRR+CD4+ T cells in peripheral blood of patients with SLE is associated with disease activity.

To investigate the clinical significance of the ratio of T helper cell 17 (Th17) cells to single immunoglobulin IL-1-related receptor (SIGIRR)+ cluster of differentiation (CD4)+ T cells in patients with systemic lupus erythematosus (SLE), novel data and data from previous studies were analyzed. The frequency of Th17 cells in peripheral blood mononuclear cells (PBMCs) and their correlation with clinical data were evaluated in 48 patients with SLE and 38 healthy controls through flow cytometry. Compared with healthy controls, the percentage of Th17 cells was significantly increased in the PBMCs of patients with SLE (Z=-5.82, P<0.001). Compared with inactive SLE (ISLE), the percentage of Th17 cells in active SLE (ASLE) were significantly increased (Z=-4.26, P<0.0001). Compared with patients without lupus nephritis, the frequency of Th17 cells was significant increased (Z=-2.20, P=0.028). The frequency of Th17 cells was inversely correlated with the frequency of SIGIRR+CD4+ T cells (r=-0.61, P<0.001). The ratio of Th17 cells to SIGIRR+CD4+ T cells in ASLE was significantly increased compared with healthy controls or patients with ISLE (P<0.001) and was inversely correlated with complement component 3 and complement component 4, and positively correlated with SLE disease activity index and 24-h proteinuria (P<0.05). In summary, increased numbers of Th17 cells and decreased numbers of SIGIRR+CD4+ T cells in patients with SLE suggested that SIGIRR+CD4+ T and Th17 cells may be involved in the pathogenesis of SLE.

Decreased Serum/Plasma Vitamin D levels in SLE Patients: A Meta-Analysis.

BACKGROUND AND OBJECTIVE: The evidence regarding the association between serum/plasma vitamin D (VitD) concentrations and systemic lupus erythematosus (SLE) is inconsistent. The study was based on relevant results from literatures that were identified and evaluated. The aim of this meta-analysis is to determine circulating VitD in SLE patients and explore influencing factors. METHODS: Studies examining VitD levels in SLE patients were identified through targeted searches in the PubMed and EMBASE databases (up to December 2017). Data extracted from eligible studies was synthesized to calculate the standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI). A fixed or a random effects model was applied to calculate the pooled SMDs and ORs depending on heterogeneity across studies. RESULTS: A total of 24 studies, including 6017 patients and 18,417 controls were included. The pooled analysis suggested that VitD levels were significantly lower in SLE patients compared with those in controls [SMD= -0.09, 95%CI= -0.12 to -0.06, P < 0.001]. When the studies were stratified by ethnicity, VitD concentrations were also significantly lower in Asian, Caucasian and African patients. When the studies were stratified by age, gender, VitD level was lower in patients than that in controls. Subgroup analyses stratified by measurement type (expect for radioimmunoassay) also demonstrated consistent results. Moreover, VitD insufficiency was more prevalent in SLE patients than healthy controls [OR=6.57, 95%CI=4.64-9.29]. CONCLUSION: Compared with healthy controls, SLE patients had lower concentration of VitD. Additionally, the prevalence of VitD insufficiency is more common in SLE patients.

Failure patterns and prognostic factors of patients with primary mucosal melanoma of the nasal cavity and paranasal sinuses.

OBJECTIVES: To analyse the failure patterns and prognostic factors influencing survival in patients with primary mucosal melanoma of the nasal cavity and paranasal sinuses. MATERIALS AND METHODS: Fifty-one patients were analysed retrospectively. Forty-eight, 33, 10, and 13 patients underwent surgery, radiotherapy, chemotherapy, and immunotherapy, respectively. Failure events, including local recurrence, regional relapse, distant metastases, and death, were examined. RESULTS: During follow-up (median: 59.0 months), 36 patients experienced failure after treatment, including local (n = 17), regional (n = 8), and distant organ (n = 23) metastases. The median failure times for local, regional, and distant metastases were 13.0, 14.0, and 8.0 months, respectively. The median survival times from local, regional, and distant failure to death were 10.5, 8.0, and 4.0 months, respectively. The 5-year overall survival rates of patients with and without distant organ metastases were 14.4% and 72.6%, respectively (p < .001). Multivariate analyses showed that radiotherapy increased local recurrence-free and regional relapse-free survival. Patients with stage IV tumours had reduced distant metastasis-free and overall survival compared to patients with stage I-III tumours. CONCLUSIONS: Distant metastasis was mainly owing to failure. Radiotherapy and the disease stage were prognostic factors for survival.

Restless legs syndrome in maintenance hemodialysis patients: an epidemiologic survey in Hefei.

OBJECTIVE: To investigate the prevalence of restless legs syndrome (RLS) in maintenance hemodialysis (MHD) patients and its possible influencing factors. METHODS: MHD patients were consecutively enrolled from five hemodialysis centers in Hefei. Clinical, demographics, and laboratory data were recorded from December 2013 to March 2014. RLS diagnosis scale, Zung Self-Rating Depression Scale (SDS), Zung Self-Rating Anxiety Scale (SAS), Pittsburgh Sleep Quality Index (PSQI), and kidney disease and quality of life (KDQOLTM-36) were used for analysis. RESULTS: A total of 269 MHD patients (81 women, 188 men) were enrolled, among which 39 patients were diagnosed as RLS. The median duration of dialysis therapy was 33 months and the prevalence of RLS was 14.5%. Compared with RLS-negative patients, RLS-positive patients had lower hemoglobin level (98.67 ± 13.50 vs 106.34 ± 17.75, P = 0.011) and higher alkaline phosphatase concentration [131.0 (98.0, 226.0) vs 94.0 (69.8, 157.5), P = 0.001]. The multivariate logistic regression showed that high hemoglobin level (OR 0.975, 95% CI 0.956-0.995, P = 0.015) was a protective factor for RLS, while high alkaline phosphatase (OR 1.003, 95% CI 1.001-1.005, P = 0.018) was an independent risk factor for RLS. RLS patients had significantly higher PSQI scores (P < 0.001), reduced subjective sleep quality (P < 0.001), increased sleep latency (P < 0.007), shorter sleep duration (P < 0.001), lower sleep efficiency (P = 0.001), higher sleep disturbances (P < 0.001), and increased daytime dysfunction (P = 0.019). CONCLUSION: Our findings demonstrated that the prevalence of RLS was 14.5% in Hefei. High hemoglobin level was a protective factor for RLS, and high alkaline phosphatase was an independent risk factor. RLS affects many aspects of quality of life and sleep quality, which may contribute to the presence of depression and anxiety.

Lower maternal and fetal vitamin D status and higher placental and umbilical vitamin D receptor expression in preeclamptic pregnancies.

OBJECTIVE: To explore associations between maternal and fetal vitamin D status in preeclamptic pregnancies. METHODS: A case-control experiment was carried out with proportion ratio of 1:1 (controls: n = 60 vs cases: n = 60). Blood collection of both maternal and cord were performed before and during delivery, respectively, and 25(OH)D measurement was conducted. Difference analysis was performed according to returned data. Immunohistochemical analysis, together with semi-quantitative Western blot, was also performed to determine protein expression of vitamin D receptor in placenta and cord tissues of ESPE. RESULTS: Mean ± SD values of maternal 25(OH)D in control and PE group were 38.06 ± 6.28 and 33.05 ± 4.10, respectively, and significant differences with P < 0.0001 were found between control and PE in both continuous and categorical variables, especially in ESPE subtype (32.96 ± 4.49). The deficiency category (< 30 nmol/L) showed increased odds of PE (OR, 2.83, 95% CI, 1.32-6.08) in both maternal 25(OH)D and cord 25(OH)D in multivariable logistic regression. Semi-quantitative analysis showed that expression of placenta VDR in the ESPE subgroup was significantly higher than that in control group with P < 0.001, while expression of umbilical vein VDR in ESPE subgroup was significantly higher than that in control group with P < 0.05. CONCLUSIONS: The present study finds that lowest maternal and fetal vitamin D status in ESPE existed in the preeclampsia subsets. The VDR expression in placenta and fetus in ESPE were higher than that of normal pregnancy, which indicated that it might be related to placenta compensatory mechanism and is worthy of further research.

Noninvasive chromosome screening of human embryos by genome sequencing of embryo culture medium for in vitro fertilization.

Preimplantation genetic screening (PGS) is widely used to select in vitro-fertilized embryos free of chromosomal abnormalities and to improve the clinical outcome of in vitro fertilization (IVF). A disadvantage of PGS is that it requires biopsy of the preimplantation human embryo, which can limit the clinical applicability of PGS due to the invasiveness and complexity of the process. Here, we present and validate a noninvasive chromosome screening (NICS) method based on sequencing the genomic DNA secreted into the culture medium from the human blastocyst. By using multiple annealing and looping-based amplification cycles (MALBAC) for whole-genome amplification (WGA), we performed next-generation sequencing (NGS) on the spent culture medium used to culture human blastocysts (n = 42) and obtained the ploidy information of all 24 chromosomes. We validated these results by comparing each with their corresponding whole donated embryo and obtained a high correlation for identification of chromosomal abnormalities (sensitivity, 0.882, and specificity, 0.840). With this validated NICS method, we performed chromosome screening on IVF embryos from seven couples with balanced translocation, azoospermia, or recurrent pregnancy loss. Six of them achieved successful clinical pregnancies, and five have already achieved healthy live births thus far. The NICS method avoids the need for embryo biopsy and therefore substantially increases the safety of its use. The method has the potential of much wider chromosome screening applicability in clinical IVF, due to its high accuracy and noninvasiveness.

High-risk factors of parotid lymph node metastasis in nasopharyngeal carcinoma: a case-control study.

BACKGROUND: Although parotid-sparing IMRT decreased the dose distribution of parotid, parotid region recurrence has been reported. Prophylactic irradiation in parotid area would be necessary in patients with high risk of parotid lymph node metastasis (PLNM). This study was to detect the high-risk factors of PLNM in nasopharyngeal carcinoma. METHODS: This was a 1:2 case-control study. All patients in this study were newly diagnosed NPC with N2-3 classification from January 2005 to December 2012. Cases were 22 sides with ipsilateral PLNM. Controls were 44 patients who were randomly selected from N2-3 disease in database. RESULTS: 20/1096 (1.82 %) NPC patients were found PLNM. Sum of the longest diameter for multiple lymph nodes (SLD) in level II was larger in case group than that in control group (6.0 cm vs. 3.6 cm, p = 0.003). Level II lymph node necrosis, level Va/b involvement, and rare neck areas involvement were more common in case group (p = 0.016, p = 0.034, and p < 0.001, respectively). RPN, level III, and level IV metastases showed no significant difference between the two groups. Multivariate analysis in logistic regression showed that only SLD ≥5 cm in II area (OR = 4.11, p = 0.030) and rare neck areas involvement (OR = 3.95, p = 0.045) were associated with PLNM in NPC patients. CONCLUSIONS: PLNM was an uncommon event in NPC patients. SLD ≥5 cm in level II and involvement in rare-neck areas may be potentially high-risk factors for PLNM. Sparing parotid in IMRT was not recommended for NPC patients with high risks of PLNM.

Association between rs6887695 and 3'-untranslated region polymorphisms within the interleukin-12B gene and susceptibility to autoimmune diseases in Asian and European population: A meta-analysis.

BACKGROUND: The associations between rs6887695 and 3'-untranslated region (3'-UTR) single-nucleotide polymorphisms (SNPs) within interleukin-12B (IL-12B) and autoimmune diseases (ADs) remain controversial and inconclusive. The aim of this study was to evaluate the association between IL-12B (3'-UTR A/C and rs6887695 C/G SNPs) and ADs by meta-analysis. METHODS: PubMed and EMBASE were exhaustively searched for studies on the association between IL-12B SNPs and ADs. Publication bias was examined by a funnel plot and Egger's test. The robustness of the pooled results was assessed by sensitivity analysis. A fixed- or a random-effects model was applied to calculate the pooled odds ratios (ORs). RESULTS: A total of 34 studies were included in this meta-analysis. The pooled results demonstrated that IL-12B rs6887695 SNPs were significantly associated with the risk of ADs. However, there was no significant association between IL-12B 3'-UTR SNPs and ADs. When the studies were stratified by ethnicity, significant association between IL-12B 3'-UTR SNPs and ADs was observed in both Asian and European population. In addition, allele A within 3'-UTR of IL-12B gene was found to be a protective factor for T1DM, but a risk factor for psoriasis. CONCLUSION: The IL-12B 3'-UTR and rs6887695 SNPs are associated with susceptibility to ADs.

Prognostic effect of symptomatic extracranial lesions on survival of recursive partitioning analysis Class III brain metastatic patients treated with stereotactic radiotherapy.

OBJECTIVE: To explore the outcome and prognostic factors of recursive partitioning analysis (RPA) Class III brain metastatic patients treated with stereotactic radiotherapy (SRT). MATERIALS AND METHODS: Fifty-six consecutive patients with metastatic brain tumors and Karnofsky performance scale (KPS) scores <70 treated with SRT from January 2008 to October 2013 were involved in the analysis. Twenty-five patients (44.6%) were with symptomatic extracranial lesions (SELs), and the other 31 patients (55.4%) were without SELs. The detailed follow-up data of KPS scores were available in 44 patients. The KPS score drop time (KDT) was calculated as the time between SRT and 10 points drop of KPS scores compared to the baseline. Kaplan-Meier and Cox proportional hazards regression analyses were performed for univariate and multivariate analyses. RESULTS: The median overall survival time was 5.0 months (95% confidence interval [CI] 3.42-6.59) for the whole group. In multivariate analysis, the presence of SELs (P = 0.007, relative risk = 4.44, 95% CI 1.036-20.818) was the independent prognosis factor for survival. Median survival time was 3 months for the patients with SELs, 8 months for the patients without SELs. The median KDT of the 44 patients was 3.0 months (95% CI, 1.927-4.073 months). Again only the presence of SELs (P = 0.001, OR = 6.622, 95% CI, 2.108-20.801) was significantly related to KDT in multivariate analysis. The median KDT of the patients with SELs was 1.5 months, which was 5 months for the patients without SELs. CONCLUSION: The presence of SELs was a negative prognosis factor for the survival of RPA Class III brain metastatic patients. If RPA Class III brain metastatic patients were without SELs, SRT may be a reasonable treatment option, but if they had SELs, SRT may not be a reasonable treatment due to the short overall survival time and KDT.

Long-term outcomes of patients with esthesioneuroblastomas: A cohort from a single institution.

OBJECTIVE: Esthesioneuroblastoma is a rare cancer. The purpose of this study was to review the long-term outcomes of patients with esthesioneuroblastomas (ENBs) who were treated at a single institution. MATERIALS AND METHODS: One hundred thirteen patients with biopsy-proven ENBs between June of 1979 and November of 2014 were retrospectively reviewed. There was 1 patient at stage A, 23 stage B and 89 stage C according to Kadish classifications. The initial treatments included pre-operative radiotherapy (RT) followed by surgery in 11 patients, surgery followed by post-operative RT in 51, primary RT in 47, and surgery in 3, and only a single patient was treated with palliative chemotherapy alone. RESULTS: The median follow-up was 75months, 5-year overall survival (OS), loco-regional control rate (LRC) and distant metastasis-free survival were 65%, 73% and 67%, respectively. The OSs at 5years were 91% in the pre-operative RT group, 82% in the post-operative RT group, and 50% in the primary RT group (p<0.001). Regarding the patients in early disease stages (Kadish A/B), no survival differences were observed between primary RT and combination treatment. Regarding the node-negative Kadish C disease patients, combination of surgery and RT elicited superior survival, and pre-operative RT yielded the best prognoses. Distant failure rate is over 60% for N-positive disease, chemotherapy may play a more important role. CONCLUSIONS: The optimal treatment policy for ENBs remains the combination of surgery and radiotherapy. When choosing the most adequate therapy for ENBs, disease stage, age and lymph nodes status should be taken into consideration.

Intensity-modulated radiotherapy for cervical esophageal squamous cell carcinoma: clinical outcomes and patterns of failure.

The objective of the study was to report clinical outcomes and patterns of failure for these patients with cervical esophageal squamous cell carcinoma (CESCC) treated with intensity-modulated radiotherapy (IMRT). A total of 64 patients with CESCC treated with definitive IMRT from May 2005 to March 2012 in our center were analyzed. Forty-two patients received radiotherapy alone and 22 patients received concurrent chemoradiotherapy. The location and extent of locoregional failures were transferred to the pretreatment planning computed tomography for dosimetry analysis. For all patients, the overall 2-year local failure-free survival, regional failure-free survival, distant failure-free survival, and overall survival rate was 74.5, 88.0, 66.6 and 42.5 %, respectively. Twenty-eight patients had developed treatment failure. Of the 28 patients, 14, 5, and 18 had developed local failure, regional failure, and distant metastasis, respectively. All of the 14 local failures were considered in-field failures. Of the five regional failures, three were considered in-field failures and two were marginal failures. The most frequently observed acute toxicity was mainly Grade 1 or 2. The incidence of acute Grade 3 mucositis (including pharyngitis), skin reaction, and leukopenia was 4.7, 12.5 and 10.9 %, respectively. IMRT provides satisfactory locoregional control for CESCC. Distant metastasis remains the predominate pattern of failure and the predominate pattern of locoregional failures is in-field failure.

Nasopharyngeal carcinoma with intracranial extension in the era of intensity-modulated radiotherapy: case-control study using propensity score matching method.

The objective of the study was to evaluate long-term survival outcomes and toxicity of T4 classification nasopharyngeal carcinoma (NPC) with intracranial extension (IE group) or without intracranial extension (non-IE group) after intensity-modulated radiotherapy (IMRT) using the propensity score matching method. After generating propensity scores given the covariates of age, sex, N classification, and concurrent chemotherapy, 132 patients in each group were matched. The 5-year local failure-free survival rate and the 5-year overall survival rate in the IE group were lower than the patients in the non-IE group (74.6 vs. 88.9 %, p = .008; 51.1 vs. 71.9 %, p = .005). Grade 2 hypothyroidism was more common in the IE group (13.2 vs. 3.4 %, p = .029). For patients with T4 classification NPC after IMRT, patients with intracranial extension need more attention to the thyroid gland function and are more likely to experience local failure and death than patients without intracranial extension.

Spread patterns of lymph nodes and the value of elective neck irradiation for esthesioneuroblastoma.

OBJECTIVES: This study was aimed to characterize patterns of lymphatic spread and assess the value of prophylactic elective neck irradiation (ENI) for esthesioneuroblastoma (ENB). METHODS: A retrospectively analysis of 116 patients with newly diagnosed ENB at our institution over 35-year period was undertaken. RESULTS: 32 patients (28%) presented lymph node metastasis at initial diagnosis, the common sites involved were level II, Ib, level III and VIIa. Among 80 N-negative patients staged in Modified Kadish B/C, 50 patients were delivered with ENI, 30 patients were not. The 5-year regional failure-free survival was 98% in patients treated with ENI and 75% in patients without ENI (p=0.005), regional failure rate decreased significantly from 23% (7/30) to 2% (1/50) after ENI (p=0.002). Multivariate analysis also suggested that ENI was an independent favorable predictor for regional controlling (HR, 0.102; 95% CI: 0.012-0.848; p=0.035). CONCLUSIONS: This is the largest cohort of ENB so far in a single institute, and also the first detailed description of nodal spread patterns of N-positive ENB. Elective neck irradiation reduced the regional failure significantly and should be recommended as a part of initial treatment strategy for patients staged with Modified Kadish B/C.