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.     

Epistasis effects of dopamine genes on interval timing and reward magnitude in humans

We tested human participants on a modified peak procedure in order to investigate the relation between interval timing and reward processing, and examine the interaction of this relation with three different dopamine-related gene polymorphisms. These gene polymorphisms affected the expression of catechol-o-methyltransferase, which catabolizes synaptic dopamine primarily in the prefrontal cortex (COMT Val158Met polymorphism), D2 dopamine receptors primarily in the striatum (DRD2/ANKK1-Taq1a polymorphism), and dopamine transporters, which clear synaptic dopamine in the striatum (DAT 3′ VNTR variant). The inclusion of these polymorphisms allowed us to investigate dissociable aspects of the dopamine system and their interaction with reward magnitude manipulations in shaping timed behavior. These genes were chosen for their roles in reward processing and cortico-striatal information processing that have been implicated for interval timing. Consistent with recent animal studies, human participants initiated their timed anticipatory responding earlier when expecting a larger reward in the absence of any changes in the timing of response termination or perceived time. This effect however was specific to two out of four evaluated COMT and DRD2 polymorphism combinations that lead to high prefrontal dopamine coupled with high D2 density and low prefrontal dopamine coupled with low D2 density. Larger rewards also decreased timing precision indices, some of which interacted with the COMT polymorphism. Furthermore, the COMT polymorphism that leads to higher prefrontal dopamine resulted in weaker manifestation of memory variability (relative to threshold variability) in timed behavior. There was no effect of DAT polymorphisms on any of the core behavioral measures. These results suggest that the reward modulates decision thresholds rather than clock speed, and that these effects are specific to COMT and DRD2 epistasis effects that presumably constitute a balanced prefrontal and striatal dopamine transmission.     

Facial defects restored with extraoral implant-supported prostheses

A facial defect results in cosmetic, functional, and psychologic problems and acts as a difficult and challenging procedure for the maxillofacial surgeon and the prosthodontist. Retention of a facial prosthesis is an important key in the patient's satisfaction and acceptance. The introduction of extraoral implant applications have been accepted as an advanced retention method. The purpose of this article is to report the results from our clinical experience with patients wearing facial prostheses anchored to extraoral ITI implants (Straumann, AG, Basel, Switzerland).     

Total aesthetic reconstruction of postburn bilateral breast loss using transverse myocutaneous gracilis free flaps: A case report and literature review

Reconstruction of breast burns are challenging, as it includes both functional and aesthetic components. Transverse myocutaneous gracilis (TMG) flap has been used for postmastectomy breast reconstruction in the absence of abdominal donor site availability. Use of this flap for the breast burns is limited. A 32-year-old female sustained 54% second and third degree burns resulting with bilateral total breast loss. Anterior and posterior thorax, upper and mid abdomen, neck, shoulders, and bilateral upper extremities were also involved. Inner medial thighs had an ample amount of tissue and had never been used as donor sites. The left TMG (28 × 12 cm, 1,413 g) was used for right, and the right TMG (30 × 14 cm, 1,635 g) was used for the left breast, 3 months apart. The contracture on the chest wall was completely excised. Venous anastomosis to the venae commitantes was performed using a 2.5 mm coupler, followed by an end-to-end arterial anastomosis to the internal mammary artery. Flaps were inset in a fashion so that the inferior part became the inframammary fold, and the anterior and posterior wings were joined in the upper pole, creating a conical shape. Minimal wound dehiscence in the postoperative course healed with dressing changes and both flaps survived completely. Nipple reconstruction and areolar tattooing was performed. The patient was very happy with the outcome at seventh year follow-up. TMG may be a valuable option even in bilateral cases of microsurgical autologous free tissue transfer for total aesthetic reconstruction of postburn breast loss.     

Predisposing factors for erectile dysfunction and response to treatment in younger males: Are they different from those of older men? An observational-comparative study

We aimed to correlate the predisposing demographic and clinical factors for erectile dysfunction (ED) in young men and treatment response in these men with data from older men. The patients were divided into two groups: <40 years (group I, n = 58) and ≥40 years (group II, n = 73). ED was evaluated with the International Index of Erectile Function-5 (IIEF-5) questionnaire, and Beck's Depression Inventory (BDI) questionnaire was used to evaluate mood status. The number of patients with morning rigidity and normal libido was higher in group I (70.7% vs. 16.4%, p = .039 and 72% vs. 37%, p = .047). The increase in scores other than IIEF-Orgasmic Function and Sexual Desire domain scores after treatment was higher in the first group (p = .029, p = .035 and p < .001 respectively). In multivariate analysis, the factors predicting the low IIEF-Erectile Function domain score in young men were testosterone level and BDI score (p = .026 and p = .034). Although psychogenic factors contribute significantly to the aetiology of ED, hormone profile is more preserved in young men than in older men.     

New use of teflon to reduce bleeding in modified bentall operation

We analyzed the postoperative short- and mid-term outcomes of a series of patients with annuloaortic ectasia who underwent a modified Bentall operation in our clinic from September 2000 through March 2006. The study included 44 patients. Their average age was 53.4 +/- 14.1 years. The underlying disease was degenerative aortic aneurysm in 42 patients (95.5%) and acute aortic dissection in 2 patients (4.5%). Six patients (13.6%) had Marfan phenotype. Aortic insufficiency was moderate in 30 patients (68.2%) and severe in 14 patients (31.8%). In our modification of the Bentall technique, we completed the resection of the aortic root while leaving 5 to 10 mm of native aortic wall tissue to support the anastomosis. A long piece of Teflon felt (width, 0.5-1 cm) was laid on the annulus, and nonpledgeted 2-0 polyester sutures were passed in turn through the Teflon felt, the preserved aortic tissue, and the aortic annulus. A thin piece of Teflon felt was also used in the coronary artery reimplantation sites. Fibrin glue was routinely applied to all anastomoses. There were no intraoperative deaths. One patient died in the hospital after surgery for acute type I aortic dissection. Another patient died 1 year after the operation from prosthetic-valve endocarditis. No patient required surgical correction of excessive postoperative bleeding. Kaplan-Meier curves showed overall survival of 0.94 (95% confidence intervals, 0.9-0.99). We consider our approach an easy, effective way to minimize bleeding from the anastomoses and at the aortic root--a common challenge in aortic surgery.