Low ERCC1 expression is associated with prolonged survival in patients with bladder cancer receiving platinum-based neoadjuvant chemotherapy

PurposeExcision repair cross-complementation group 1 enzyme (ERCC1) plays a key role in the removal of platinum induced DNA adducts and cisplatin resistance. Prognostic role of ERCC1 expression in the neoadjuvant setting in bladder cancer has not been reported before. We evaluated the prognostic role of ERCC1 expression in bladder cancer receiving platinum-based neoadjuvant chemotherapy.Materials and methodsThirty-eight patients with muscle invasive bladder cancer who received neoadjuvant platinum-based chemotherapy were included. Clinical and histopathologic parameters along with immunohistochemical ERCC1 staining were examined and correlated with response rates and survival.ResultsPathologic complete response rates were similar between patients with low and high ERCC1 expression. Median disease-free survival (DFS) was 9.3 vs. 20.5 months (P = 0.186) and median overall survival (OS) was 9.3 vs. 26.7 months (P = 0.058) in patients with high ERCC1 expression compared with those with low expression, respectively. In multivariate Cox regression analysis: pathological complete response (pCR) after chemotherapy (hazard ratio (HR) 0.1, 95% CI 0.012–0.842, P = 0.034) and high ERCC1 expression (HR 3.7, 95% CI 1.2–11.2, P = 0.019) were significantly associated with DFS. Patient age (>60 vs. ≤60 years) (HR 3.4, 95% CI 1.2–9.4, P = 0.018), the presence of pCR (HR 0.11, 95% CI 0.014–0.981, P = 0.048) and high ERCC expression (HR 6.1, 95 CI 1.9–19.9, P = 0.002) were significantly associated with OS.ConclusionsOur results showed that high ERCC1 expression was independently associated with shorter disease-free and overall survival in patients with bladder cancer who received neoadjuvant platinum-based chemotherapy. ERCC1 may represent a potential predictive marker for platinum-based treatment in bladder cancer.     

Decreased Activity and Genetic Polymorphisms of CYP2C19 in Behçet's Disease

Behçet's disease (BD) is a systemic autoimmune disorder. Cytochrome P450 enzymes (CYPs) are responsible for various drug metabolism reactions as well as those of endogenous substances which may be associated with autoimmune disease susceptibility. Recently, we reported that in patients with BD, CYP2C9 seems to be down‐regulated due to inflammation. In the same Turkish patients with BD, we investigated whether also CYP2C19 activity is decreased. Lansoprazole (30 mg) was given as a probe drug to evaluate CYP2C19 activity in 59 patients with BD and 27 healthy control volunteers. An HPLC method was used to determine plasma lansoprazole and its metabolite, 5‐hydroxy lansoprazole, concentrations. The genotyping for CYP2C19 *2, *3 and *17 polymorphisms was made using PCR‐RFLP. The median lansoprazole/5‐hydroxy lansoprazole metabolic ratio (MR) in patients with BD was 2.6‐fold higher as compared to the healthy control group (p = 0.001, 22.6 (1.3–26) and 8.8 (0.5–140) as median and range, respectively). The CYP2C19*17*17 genotype frequency was found to be significantly less in the BD group as compared to the healthy controls (1.7% versus 14.8% in controls, p = 0.01). Additionally, colchicine treatment did not affect the CYP2C19 enzyme activity in six patients (p = 0.43). In conclusion, the patients with BD had lower CYP2C19 enzyme activity and lower frequency of the CYP2C19*17 allele as compared to those of the healthy controls. Further studies are warranted on the mechanisms underlying this relation. This study should also be applied to other autoimmune diseases similarly characterized by local or systemic inflammation.     

A decision analysis to identify the ideal treatment for adult spinal deformity: is surgery better than non-surgical treatment in improving health-related quality of life and decreasing the disease burden?

Background

Adult spinal deformity (ASD) is a major public health problem. There are pros and cons of the available treatment alternatives (surgical or non-surgical) and it had been difficult to identify the best treatment modality.

Aim

To construct a statistical DA model to identify the optimum overall treatment in ASD.

Methods

From an international multicentre database of ASD patients (968 pts), 535 who had completed 1 year follow-up (371 non-surgical—NS, 164 surgical—S), constitute the population of this study. DA was structured in two main steps of: (1) baseline analysis (assessing the probabilities of outcomes, assessing the values of preference—utilities-, combining information on probability and utility and assigning the quality adjusted life expectancy (QALE) for each treatment) and (2) sensitivity analysis.

Results

Four hundred and thirty-two patients (309 NS, 123 S) had baseline and 1 year follow-up ODI measurements. Overall, 104 (24.1 %) were found to be improved (a decrease in ODI > 8 points), 225 (52.1 %) unchanged (?8 > ODI > 8) and 65 deteriorated. Surgery presented with a higher chance of improvement (54.2 %) versus NS (9.7 %). The overall QALE ranged from 56 to 69 (of 100 years) and demonstrated better final QALE in the NS group (60 vs. 65, P = 0.0038), this group having started with higher QALE as well (56 vs. 65 years, P < 0.0001). There were improvements in overall QALE in both groups but this was significant only in the surgical group (S from 56 to 60 years, P < 0.0001; NS from 65 to 65 years, P = 0.27). In addition, in the subgroup of patients with significant baseline disability (ODI > 25) surgery appeared to yield marginally better final QALE (58 vs. 56 years, P = 0.1) despite very a similar baseline (54 vs. 54 years, P = 0.93).

Discussion and conclusions

This study demonstrated that a single best treatment modality for ASD may not exist. Conservative treatment appears to yield higher (up to 6 %) QALE compared to surgery, most probably secondary to a higher baseline QALE. On the other hand, surgery provides a significantly higher increase in QALE. Especially in patients with significant disability at baseline, the final QALE tended higher in the S group (although not significant). Finally, chances of a relevant improvement at first year turned out to be significantly lower with NS treatment.

     

Evaluation of obstructive sleep apnea symptoms in pregnant women with chronic disease

Objective: Obstructive sleep apnea syndrome (OSAS) is a disease which is estimated to be undiagnosed to a large extent. Hence, the prevalence of OSAS in pregnant women is unknown. We aimed to evaluate the symptoms of obstructive sleep apnea in pregnant women with chronic diseases.

Methods: In the study, 97 pregnant women with chronic diseases and 160 healthy pregnant women were included. A form questioning socio-demographic characteristics and pregnancy characteristics, Epworth scale and the Berlin questionnaire to evaluate the risk of OSAS were applied to participants.

Results: It has been determined that 10–12.5% of healthy pregnant women, 34–45.4% of pregnants with chronic diseases and 20.6–23.3% of all pregnant women had a high risk of OSAS, the pregnants with chronic disease compared to healthy pregnant women had statistically significant higher risk of OSAS. The risk of OSAS was found to be significantly higher especially in pregnant women with hypertension and diabetes.

Conclusions: OSAS can lead to the adverse consequences in pregnancy, should be questioned for all pregnants especially those with chronic diseases. Pregnant women with OSAS should be monitored more carefully in terms of diabetes and hypertension in antenatal care.     

Low level of Nesfatin-1 is associated with gestational diabetes mellitus

Introduction: Gestational diabetes mellitus (GDM) occurs in ～10–25% of pregnancies. Nesfatin-1, plays a role in carbohydrate metabolism by inhibiting glucagon secretion, besides has a glucose-dependent insulinotropic effect. Explanation of the GDM pathogenesis is important due to preventing gestational complications. We aimed to investigate relationship between GDM and Nesfatin-1.

Material and methods: Seventy-nine pregnant subjects were randomly allocated to either GDM group (GDG, n?=?38) or control group (CG, n?=?41). For GDM diagnosis, 50 and 100?g oral glucose tolerance test (OGTT) were used. Nesfatin-1, insulin and other parameters were measured for all subjects. The homeostasis model assessment-insulin resistance (HOMA-IR) was calculated.

Results: Nesfatin-1 was found lower and insulin was found higher in GDG than CG. Negative correlation has been founded between Nesfatin-1 with weight, BMI, fasting glucose, serum glucose level at first hour of the 50?g OGTT and HOMA-IR.

Conclusion: In this study, patients with GDM had lower Nesfatin-1 levels than without GDM. Therefore, when the Nesfatin-1 effects on the GDM pathogenesis is clear, it may be contributed to diagnosis and treatment of the GDM.