The potential role of herbal extract Wedelolactone for treating particle-induced osteolysis: an in vivo study.

BACKGROUND: Osteolysis is one of the most prevalent clinical complications affecting people who undergo total joint replacement (TJR). Wedelolactone (WDL) is a coumestan compound derived from the Wedelia chinensis plant and has been demonstrated to exhibit anti-inflammatory properties. This study aimed to investigate the oral administration of WDL as a potential treatment for particle-induced osteolysis using a well-established mice calvarial disease model. METHODS: Thirty-two C57BL/6 J mice were randomized into four groups: Sham, vehicle, osteolysis group with oral WDL treatment for 4 weeks (WDL 4w), and osteolysis group treated for 8 weeks (WDL 8w). Micro-CT was used to quantitatively analyze the bone mineral density (BMD), bone volume/tissue volume (BV/TV) and trabecular bone thickness (Tb.Th). Osteoclast numbers were also measured from histological slides by two investigators who were blind to the treatment used. RESULTS: The results from micro-CT observation showed that BMD in the WDL 8w group improved significantly over the vehicle group (p < 0.05), but there was no significant difference between WDL 4w and 8w for BV/TV and Tb.Th. Osteoclast numbers in the WDL 4w group were also lower than the vehicle group (p < 0.05), but the difference between WDL 8w and 4w groups was not significant. CONCLUSIONS: Particle-induced osteolysis is an inevitable long-term complication after TJR. The results of this animal study indicate that an oral administration of WDL can help reduce the severity of osteolysis without adverse effects.

Evaluation of graphene-derived bone scaffold exposure to the calvarial bone_in-vitro and in-vivo studies.

Graphene is a novel material which has recently been gaining great interest in the biomedical fields. Our previous study observed that graphene-derived particles help induce bone formation in a murine calvarial model. Here, we further developed a blended graphene-contained polycaprolactone (PCL/G) filament for application in a 3D-printed bone scaffold. Since implants are expected to be for long-term usage, in vitro cell culture and in vivo scaffold implants were evaluated in a critical-size bone defect calvarial model for over 60 weeks. Graphene greatly improved the mechanical strength by 30.2% compared to pure PCL. The fabricated PCL/G scaffolds also showed fine cell viability. In animal model, an abnormal electroencephalogram power spectrum and early signs of aging, such as hair graying and hair loss, were found in the group with a PCL/G scaffold compared to pure PCL scaffold. Neither of the abnormal symptoms caused death of all animals in both groups. The long-term use of graphene-derived biomaterials for in-vivo implants seems to be safe. But the comprehensive biosafety still needs further evaluation.

Enhanced expression of coxsackievirus and adenovirus receptor in lipopolysaccharide-induced inflammatory macrophages is through TRIF-dependent innate immunity pathway.

AIMS: Inflammatory macrophages have been proposed as a therapeutic target for joint disorders caused by inflammation. This study aimed to investigate the expression and regulation of coxsackievirus-adenovirus receptor (CAR) in lipopolysaccharide (LPS)-stimulated inflammatory macrophages whereby to evaluate the feasibility of virus-directed enzyme prodrug therapy (VDEPT). MAIN METHODS: Macrophage cell lines (RAW264.7 and J774A.1) and primary macrophage cells derived from rat spleen were used to evaluate the expression of CAR protein or CAR mRNA. Specific inhibitors for TLR4 pathway were used to investigate the regulation of CAR expression. CAR expression in rat joints was documented by immunohistochemistry. Conditionally replicating adenovirus, CRAd-EGFP(PS1217L) or CRAd-NTR(PS1217H6), and non-replicating adenovirus CTL102 were used to transduce genes for enhanced green fluorescent protein (EGFP) or nitroreductase (NTR), respectively. The expression of EGFP, NTR, and the toxicity induced by CB1954 activation were evaluated. KEY FINDINGS: The in vitro experiments revealed that CAR upregulation was mediated through the TLR4/TRIF/IRF3 pathway in LPS-stimulated inflammatory macrophage RAW264.7 and J774A.1 cells. The inflammatory RAW264.7 cells upregulated CAR expression following LPS stimulation, leading to higher infectability, increased NTR expression, and enhanced sensitization to CB1954. In animal experiments, the induction of CAR expression was observed in the CD68-expressing primary macrophages and in the CD68-expressing macrophages within joints following LPS stimulation. SIGNIFICANCE: In conclusion, we report an enhanced CAR expression in inflammatory macrophages in vitro and in vivo through the immune response elicited by LPS. Thus, the TLR4/TRIF/IRF3 pathway of macrophages, when activated, could facilitate the therapeutic application of adenovirus-mediated VDEPT.

Effect of material selection on tibial post stresses in posterior-stabilized knee prosthesis.

AIMS: The material and design of knee components can have a considerable effect on the contact characteristics of the tibial post. This study aimed to analyze the stress distribution on the tibial post when using different grades of polyethylene for the tibial inserts. In addition, the contact properties of fixed-bearing and mobile-bearing inserts were evaluated. METHODS: Three different grades of polyethylene were compared in this study; conventional ultra high molecular weight polyethylene (UHMWPE), highly cross-linked polyethylene (HXLPE), and vitamin E-stabilized polyethylene (VEPE). In addition, tibial baseplates with a fixed-bearing and a mobile-bearing insert were evaluated to understand differences in the contact properties. The inserts were implanted in neutral alignment and with a 10° internal malrotation. The contact stress, von Mises stress, and equivalent plastic strain (PEEQ) on the tibial posts were extracted for comparison. RESULTS: The stress and strain on the tibial post for the three polyethylenes greatly increased when the insert was placed in malrotation, showing a 38% to 56% increase in von Mises stress and a 335% to 434% increase in PEEQ. The VEPE insert had the lowest PEEQ among the three materials. The mobile-bearing design exhibited a lower increase in stress and strain around the tibial posts than the fixed-bearing design. CONCLUSION: Using VEPE for the tibial component potentially eliminates the risk of material permanent deformation. The mobile-bearing insert can help to avoid a dramatic increase in plastic strain around the tibial post in cases of malrotation. The mobility allows the pressure to be distributed on the tibial post and demonstrated lower stresses with all three polyethylenes simulated. Cite this article: Bone Joint Res 2020;9(11):768-777.

In vitro and in vivo Biological Responses to Graphene and Graphene Oxide: A Murine Calvarial Animal Study.

BACKGROUND: Graphene and its derivatives have recently gained popularity in the biomedical field. Previous studies have confirmed that both the mechanical strength and wear resistance of graphene-containing polyethylene have been greatly improved. Therefore, it is being considered as an alternative for artificial joint replacement liners. Based on the literature, the wear debris generated from the traditional polymers used for orthopedic liners could lead to particle-induced osteolysis and, consequently, failure of joint replacement. However, the biological response of this novel graphene-based polymer is still unclear. Therefore, the current study aimed to investigate the in vitro and in vivo biological effects of graphene and graphene oxide (GO) particles on bone. MATERIALS AND METHODS: The biological responses of graphene and GO particles were tested via in vitro and murine calvarial in vivo models. In the in vitro model, murine macrophage cells were mixed with particles and hydrogel and printed into two differently designed scaffolds; the induced proinflammatory cytokines were then tested. In the murine in vivo model, the particle size distribution was measured via SEM, and these particles were then administrated in the calvarial area, referring to our established model. A micro-CT and histological analysis were performed to examine the biological effects of the particles on bone health. The data were analyzed via the one-way analysis of variance to determine the differences between the groups. RESULTS: Both graphene and GO induced significantly higher TNF-α and IL-6 secretion compared with the control in the three-dimensional in vitro model. In the murine calvarial in vivo test, the graphene and GO particles increased the bone mass compared with the sham groups in the micro-CT analysis. Bone formation was also observed in the histological analysis. CONCLUSION: In these in vivo and in vitro studies, the graphene and GO wear debris did not seem to induce harmful biological response effect to bone. Bone formation around the skull was observed in the calvarial model instead. Graphene-containing biomaterials could be a suitable new material for application in orthopedic prostheses due to their benefit of eliminating the risk of particle-induce osteolysis.

Augmentation Plate Fixation for Treating Subtrochanteric Fracture Nonunion.

BACKGROUND: The treatment of subtrochanteric fracture nonunion is challenging. Although revision with either an intramedullary or extramedullary device had been advocated with acceptable results, complications that require secondary procedures still arise. The use of an intramedullary device with augmentation plate fixation is a well-known approach for femoral or tibial diaphyseal nonunion. However, this approach has not previously been reported for subtrochanteric fracture nonunion. MATERIALS AND METHODS: A series of 21 cases of subtrochanteric fracture nonunion treated with an intramedullary device in combination with augmentation side plating were collected and retrospectively reviewed after an average of 18 months of followup. Fourteen patients with a prior well-fixed intramedullary device were treated with side plating and bone grafting. Seven patients underwent revision nailing in addition to side plating and bone grafting. RESULTS: All fractures united well without major complication. The average time to union was 7.1 months. CONCLUSION: The use of an intramedullary device with augmentation plate fixation is a reliable and decisive procedure for treating subtrochanteric fracture nonunion that produces satisfactory results with a low complication rate.

Early versus late surgical stabilization of severe rib fractures in patients with respiratory failure: A retrospective study.

INTRODUCTION: The timing of surgical stabilization of rib fractures remains controversial. We hypothesized that early surgical stabilization (within 3 days of injury) can improve clinical outcome in patients with severe rib fractures and respiratory failure. The aim of this study was to analyze the impact of early surgical stabilization of rib fractures on the perioperative results, clinical outcomes, and medical costs of patients with severe rib fractures and respiratory failure. METHODS: This was a retrospective comparative study based on a prospectively collected database at a single institute. Patients with severe rib fractures and respiratory failure who underwent surgical stabilization were classified into early (within 3 days of injury) and late (more than 3 days after injury) groups. Outcome measures included operation time, duration of mechanical ventilation, intensive care unit stay, hospital stay, complication rate, mortality rate, and medical cost. RESULTS: A total of 33 patients were enrolled (16 and 17 in the early and late groups, respectively). The demographics, trauma mechanism, associated injuries, and severity of trauma were comparable in both groups. The early group had significantly shorter duration of mechanical ventilation (median 36 vs. 90 hours, p = 0.03), intensive care unit stay (median 123 vs. 230 hours, p = 0.004), and hospital stay (median 12 vs. 18 days, p = 0.005); and lower National Health Insurance costs (median 6,617 vs. 10,017 US dollars, p = 0.031). The early group tended to have lower rates of morbidity and mortality, but the difference was not statistically significant. CONCLUSION: Early surgical stabilization of rib fractures in selected patients may significantly shorten their duration of mechanical ventilation, and intensive care unit and hospital stays, while incurring less medical costs.

Severe prostate enlargement with severe lower urinary tract symptoms in poorly controlled acromegaly successfully treated with 5α-reductase inhibitors: A 15-year longitudinal case report.

Acromegaly is a rare disease associated with an increased risk of prostate enlargement. Severe prostate enlargement with severe lower urinary tract symptoms (LUTS) in an acromegalic patient is even more uncommon. Herein we report on a 55-year-old man who was diagnosed with acromegaly and prostate enlargement at 40 years of age. Transsphenoidal surgery, postoperative radiotherapy, and octreotide medical therapy failed to control the acromegaly, and growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels remained elevated. When the patient was 53 years of age, severe LUTS and prostate enlargement (prostate volume = 128 mL) were noted. However, LUTS improved and prostate volume decreased markedly after 5α-reductase inhibitors were used, despite the poorly controlled acromegaly (elevated GH and IGF-1 levels). This is the first long-term observation of LUTS and prostate enlargement in a poorly controlled acromegalic patient. Although the GH-IGF-1 axis was a factor contributing to prostate enlargement, the present case suggests that androgens may still play an essential role in prostate enlargement and symptoms in active acromegalic patients >50 years of age. Indeed, we should be aware that suppressing the GH-IGF-1 axis is not the only treatment choice for prostate enlargement in acromegalic patients, and even in poorly controlled acromegalic patients in whom suppression of the GH-IGF-1 axis is difficult. Symptomatic prostate enlargement in cases of active acromegaly can be treated with 5α-reductase inhibitors, as in general benign prostate hyperplasia populations.

Elastoplastic behavior of highly cross-linked and vitamin E-stabilized polyethylene - A biomechanical study.

BACKGROUND: Vitamin E-stabilized cross-linked polyethylene has been touted to alleviate the negative effects of oxidation. Although it has demonstrated significant improvements in wear resistance, bio-tribology, and oxidative resistance, little is known about the effect of antioxidants and dosage of cross-linking on the mechanical strength. This study aimed to evaluate the mechanical properties of these novel materials, which are commonly used in orthopedic implants. METHODS: Samples of different polymers were prepared with various levels of cross-linking and with or without vitamin E-stabilization and then tested according to ASTM D695 and D638. The elastoplastic characteristics under compression and tension were compared between the groups. FINDINGS: Vitamin E-stabilized cross-linked polyethylene showed a significant increase in elastic modulus over other groups, with a maximum increase of 26% in compression and 40% in tension when compared to the highly cross-linked group without vitamin E stabilization. The elastoplastic behavior under compression differed to that in tension for all polymers, demonstrating the anisotropic characteristics of these polymers. INTERPRETATION: The lower mechanical strength of highly cross-linked polyethylene has been a complication with the use of this polymer in orthopedic liners. This current study suggests that vitamin E-stabilized cross-linked polyethylene could be a suitable alternative material for knee implants because of its improved strength in resisting external forces.

Stress distribution of the patellofemoral joint in the anatomic V-shape and curved dome-shape femoral component: a comparison of resurfaced and unresurfaced patellae.

PURPOSE: Whether to resurface the patella in knee replacement remains a controversial issue. The geometrical design of the trochlear groove in the femoral component could play an important role in determining the stress distribution on the patellofemoral joint, but this has not been sufficiently reported on. This study attempted to determine the effect of implant design on contact mechanics by means of a finite element method. METHODS: Two designs, an anatomical V-shape design (VSD) and a dome-shape design (DSD), for the anterior trochlear surface in a contemporary femoral component were chosen for examining the contact characteristics. The use and absence of patella resurfacing was simulated. The stress and strain distribution on the patellar bone and the polyethylene component were calculated for comparison. RESULTS: Without patellar resurfacing, the maximal compressive strain in the patellar bone in the VSD model was about 20 % lower than the DSD model. On the other hand, with resurfacing, the maximal strain for the VSD model was 13.3 % greater than for DSD. Uneven stress distribution at the bone-implant interface was also noted for the two designs. CONCLUSION: The femoral component with a V-shape trochlear groove reduced the compressive strain on the unresurfaced patella. If resurfacing the patella, the femoral component with a curved domed-shape design might reduce the strain in the remaining patellar bone. Uneven stress could occur at the bone-implant interface, so design modifications for improving fixation strength and medialization of the patellar button would be helpful in reducing the risk of peg fracture or loosening. LEVEL OF EVIDENCE: III.

MCM10 overexpression implicates adverse prognosis in urothelial carcinoma.

Urothelial carcinoma (UC) occurs in the upper urinary tract (UTUC) and the urinary bladder (UBUC). The molecular pathogenesis of UC has not been fully elucidated. Through data mining of a published transcriptome of UBUC (GSE31684), we identified Minichromosome Maintenance Complex Component 2 (MCM2) and MCM10 as the two most significantly upregulated genes in UC progression among the MCM gene family, the key factors for the initiation of DNA replication. To validate the clinical significance of MCM2 and MCM10, immunohistochemistry, evaluated by H-score, was used in a pilot study of 50 UTUC and 50 UBUC samples. Only a high expression level of MCM10 predicted worse disease-specific survival (DSS) and inferior metastasis-free survival (MeFS) for both UTUC and UBUC. Correspondingly, evaluation of MCM10 mRNA expression in 36 UTUCs and 30 UBUCs showed significantly upregulated levels in high stage UC, suggesting its role in tumor progression. Evaluation of 340 UTUC and 296 UBUC tissue samples, respectively, demonstrated that high MCM10 immunoexpression was significantly associated with advanced primary tumors, nodal status, and the presence of vascular invasion in both groups of UCs. In multivariate Cox regression analyses, adjusted for standard clinicopathological features, MCM10 overexpression was independently associated with DSS (UTUC hazard ratio [HR]=2.401, P = 0.013; UBUC HR=4.323, P=0.001) and with MeFS (UTUC HR=3.294, P<0.001; UBUC HR=1.972, P=0.015). In vitro, knockdown of MCM10 gene significantly suppressed cell proliferation in both J82 and TCCSUP cells. In conclusion, MCM10 overexpression was associated with unfavorable clinicopathological characteristics and independent negative prognostic effects, justifying its potential theranostic value in UC.

Matrix metalloproteinase-11 as a marker of metastasis and predictor of poor survival in urothelial carcinomas.

BACKGROUND AND OBJECTIVES: Urothelial carcinomas (UC) of urinary bladder (UB) and upper urinary tract (UT) are heterogeneous diseases with high morbidity and mortality. We looked for genes with metalloendopeptidase activity in a published UBUC transcriptomic database (GSE31684):MMP-11 was the most significant, showing stepwise up-regulation. We analyzed MMP-11 expression and association with clinicopathologic factors and survival in our well-characterized cohort of UCs. METHODS: We determined MMP-11 expression in 295 UBUCs and 340 UTUCs with immunohistochemistry, evaluated by H-score. In a retrospective study, MMP-11 expression was correlated with clinicopathologic features and with disease-specific survival (DSS) and metastasis-free survival (MeFS). The statistical significance was evaluated with univariate and multivariate analyses. RESULTS: High MMP-11 expression was significantly associated with advanced pT status, nodal metastasis, high histological grade, vascular and perineural invasion, and frequent mitoses. In multivariate Cox regression analyses, which adjusted for standard clinicopathologic characteristics, MMP-11 expression was independently associated with cancer-specific mortality (hazard ratio [HR] in UTUC:3.027, P = 0.005; in UBUC: 2.631, P = 0.010) and with metastasis development (HR in UTUC:2.261, P = 0.018; in UBUC:1.801, P = 0.026). CONCLUSIONS: MMP-11 overexpression is associated with aggressive tumor phenotype and unfavorable clinical outcome in UTUC and UBUC, suggesting it may serve as a novel prognostic and therapeutic target. J. Surg. Oncol. 2016;113:700-707. © 2016 Wiley Periodicals, Inc.

In vivo biological response to highly cross-linked and vitamin e-doped polyethylene--a particle-Induced osteolysis animal study.

Polyethylene particle-induced osteolysis is the primary limitation in the long-term success of total joint replacement with conventional ultra high molecular weight polyethylene (UHMWPE). Highly cross-linked polyethylene (HXLPE) and vitamin E-doped cross-linked polyethylene (VE-HXLPE) have been developed to increase the wear resistance of joint surfaces. However, very few studies have reported on the incidence of particle-induced osteolysis for these novel materials. The aim of this study was to use a particle-induced osteolysis animal model to compare the in vivo biological response to different polymer particles. Three commercially available polymers (UHMWPE, HXLPE, and VE-HXLPE) were compared. Osseous properties including the bone volume relative to the tissue volume (BV/TV), trabecular thickness (Tb. Th), and bone mineral density (BMD) were examined using micro computed tomography. Histological analysis was used to observe tissue inflammation in each group. This study demonstrated that the osseous properties and noticeable inflammatory reactions were obviously decreased in the HXLPE group. When compared with the sham group, a decrease of 12.7% was found in BV/TV, 9.6% in BMD and 8.3% in Tb.Th for the HXLPE group. The heightened inflammatory response in the HXLPE group could be due to its smaller size and greater amount of implanted particles. Vitamin E diffused in vivo may not affect the inflammatory and osteolytic responses in this model. The morphological size and total cumulative amount of implanted particles could be critical factors in determining the biological response.

The potential role of strontium ranelate in treating particle-induced osteolysis.

Ultra high molecular weight polyethylene (UHMWPE) wear-particle-induced osteolysis is one of the major issues affecting the long-term survival of total joint prostheses. Currently, there are no effective therapeutic options to prevent osteolysis from occurring. The aim of this study was to evaluate the role of strontium ranelate (SR) in reducing the risk of particle-induced osteolysis. Forty-eight C57BL/6J ultra-high molecular weight polyethylene (UHMWPE) particle-induced murine calvarial osteolysis models were used. The mice were randomized into four groups as: sham (Group 1), UHMWPE particles (Group 2), and SR with UHMWPE particles (Group 3 and Group 4). Groups 1 to 3 were sacrificed at two weeks and group 4 was sacrificed at the fourth week. The skulls were then analyzed with a high-resolution micro-CT. Histological evaluation was then conducted and osteoclast numbers were analyzed for comparison. Based on the micro-CT, percentage bone volume and trabecular thickness were found to be significantly higher in Group 4 than in Group 2 (p<0.001). Osteoclast numbers in SR treated groups (Group 3 and Group 4) were reduced when compared to groups that did not receive SR treatment (Group 2). These results indicated that SR treatment helps to increase bone volume percentage and trabecular thickness and also suppresses osteoclast proliferation. It is suggested that oral SR treatment could serve as an alternative therapy for preventing particle-induced osteolysis.

Clinical predictor of survival following docetaxel-based chemotherapy.

Prostate cancer (PCa) is the most common type of cancer in males in the USA and the incidence is increasing. For castration-resistant PCa (CRPC), previous studies have identified docetaxel-based chemotherapy as the first-line therapy. In the present study, the efficacy of docetaxel-based chemotherapy was investigated in a population of patients with CRPC. This study included 26 individuals (mean age, 73 years) with CRPC who were patients between July 2007 and October 2012 at the Kaohsiung Medical University Hospital (Kaohsiung, Taiwan). The regimen consisted of intravenous docetaxel (70 mg/m2) once every four weeks plus oral prednisolone (5 mg) twice daily for five days. Prostate-specific antigen (PSA) response (defined as a PSA decrease of >50% over four weeks), time to PSA progression, PCa-specific survival and overall survival (OS) were evaluated. For these 26 patients, the mean PSA level prior to chemotherapy treatment was 335.58 ng/ml. During follow-up, the average number of cycles of chemotherapy was approximately seven and 15 patients (58%) achieved a PSA response. PSA response was found to significantly correlate with OS and PCa-specific survival (P=0.014 and P=0.028, respectively). The mean value of the PSA nadir level was 89.97 ng/ml and time to PSA nadir was five months. The most common adverse event was leucopenia, which affected 88% of the patients. The results indicated that the length of time to PSA nadir and the occurrence of leucopenia may impact the PSA response. The docetaxel-based chemotherapy was a feasible and effective treatment regimen in patients with CRPC. However, the occurrence of adverse events, particularly the high incidence of leucopenia, may be cause for concern.

Patellofemoral kinematics during deep knee flexion after total knee replacement: a computational simulation.

PURPOSE: Actions requiring deep knee flexion, such as kneeling and squatting, are challenging to perform after total knee replacement (TKR), though many manufactures emphasize that their knee prostheses could safely achieve high flexion. Little is known about the patellofemoral kinematics during deep flexion. This study aimed to track the movement of the patella during kneeling and squatting through dynamic computational simulation. METHODS: A validated knee model was used to analyse the patellar kinematics after TKR, including shifting, tilting and rotation. The data were captured from full extension to 135° of knee flexion. For kneeling, an anterior force of 500 N was applied perpendicularly on the tibial tubercle as the knee flexed from 90° to 135°. For squatting, a ground reaction force was applied through the tibia from full extension to 135° of flexion. RESULTS: This study found that patellar shifting and rotation in kneeling were similar to those while squatting. However, during kneeling, the patella had a greater medial tilt and showed signs of abrupt patellar tilt owning to an external force being concentrated on the tibial tubercle. CONCLUSIONS: In terms of squatting and kneeling movements, the latter is a more strenuous action for the patellofemoral joint after TKR due to the high forces acting on the tibial tubercle. It is suggested that overweight patients or those requiring high flexion should try to avoid kneeling to reduce the risk of the polyethylene wear. Further modification of trochlear geometry may be required to accommodate abrupt changes in patellar tilting. LEVEL OF EVIDENCE: II.

Laparoendoscopic single-site retroperitoneoscopic adrenalectomy versus conventional retroperitoneoscopic adrenalectomy: initial experience by the same laparoscopic surgeon.

PURPOSE: The purpose of this study was to demonstrate our initial experience with and the feasibility of laparoendoscopic single-site retroperitoneoscopic adrenalectomy (LESS-RA). PATIENTS AND METHODS: 54 patients undergoing conventional retroperitoneoscopic adrenalectomy were compared with 27 patients undergoing LESS-RA. The adrenal tumors were considered to be benign preoperatively and <6 cm. Age, sex, laterality, body mass index, surgical indications, time to resuming oral intake, tumor size, operation time, estimated blood loss, intravenous or intramuscular analgesics (pethidine) and postoperative hospital stay were compared between the two groups. Analysis of covariance was applied to analyze postoperative hospital stay and time to resuming oral intake. RESULTS: The length of postoperative hospital stay was significantly higher in the conventional retroperitoneoscopic adrenalectomy group in the adjusted and unadjusted model. The time to resuming oral intake was significant shorter in the LESS-RA group, but was not significant after adjusting opioid analgesics dosage. No conversions to an open or conventional retroperitoneoscopic approach were necessary. There were neither complications nor blood transfusions in both groups. CONCLUSIONS: LESS-RA for benign adrenal tumors is a feasible surgical procedure when tumors are <6 cm. Further clinical research is warranted to define the role of LESS in adrenal surgery and to prove its efficacy over conventional laparoscopic surgery.

Neoadjuvant chemotherapy improves survival rate in advanced urothelial carcinoma.

Radical surgery (RS) with adjuvant chemotherapy (AC) or radiotherapy has been conventionally used for patients with advanced urothelial carcinoma (AUC). Recent research has indicated that systemic neoadjuvant chemotherapy (NC) with RS yields better outcomes than RS alone for patients with locally advanced bladder cancer. However, there are no reports indicating whether NC or AC would be beneficial for patients with AUC. The present study compared the survival rate for AUC patients receiving NC or AC. A retrospective analysis was conducted using data for 64 patients with AUC who underwent RS and systemic chemotherapy at our institution between March 2002 and March 2011. Of the 64 patients, 30 received NC before RS and 34 received RS followed by systemic AC. Pathologic stages (p=0.002), grades (p=0.018) and lymphovascular invasion (p=0.047) were significantly lower in the patients who received NC first than in those who received RC first. Furthermore, analysis of the surgical specimens revealed that 26.7% of patients who received NC before RS had complete remission. There were no significant differences in demographic data, surgical complications, and chemotoxicity between the two patient groups. The progression-free survival (PFS) and overall survival (OS) of patients who received initial NC were significantly better than those of patients who received initial RC (p=0.002 and 0.018, respectively). Our results indicate that NC administration before RS significantly improved the PFS and OS of AUC patients, without increasing surgical complications and chemotoxicity. Further prospectively controlled trials need to be conducted to confirm the effectiveness of NC for AUC patients.

Molecular markers in sex hormone pathway genes associated with the efficacy of androgen-deprivation therapy for prostate cancer.

Although most advanced prostate cancer patients respond to androgen-deprivation therapy (ADT), the efficacy is widely variable. We investigated whether the host genetic variations in sex hormone pathway genes are associated with the efficacy of ADT. A cohort of 645 patients with advanced prostate cancer treated with ADT was genotyped for 18 polymorphisms across 12 key genes involved in androgen and estrogen metabolism. We found that after adjusting for known risk factors in multivariate Cox regression models, AKR1C3 rs12529 and AR-CAG repeat length remained significantly associated with prostate cancer-specific mortality (PCSM) after ADT (P ≤ 0.041). Furthermore, individuals carrying two unfavorable genotypes at these loci presented a 13.7-fold increased risk of PCSM compared with individuals carrying zero (P<0.001). Our results identify two candidate molecular markers in key genes of androgen and estrogen pathways associated with PCSM after ADT, establishing the role of pharmacogenomics in this therapy.

Risk factors survey for extracorporeal shockwave lithotripsy-induced renal hematoma.

BACKGROUND AND PURPOSE: Shockwave lithotripsy (SWL) is a widely used treatment for patients with renal and ureteral stones because of its noninvasive approach. Although minor complications occur in most patients, a relative severe complication, perirenal or subcapsular hematoma, may also occur. We evaluate the possible risk factors for perirenal hematoma after SWL. PATIENTS AND METHODS: Between 2001 and 2011, a total of 10,887 SWL treatments were performed for urolithiasis. All SWL procedures were performed using a Siemens Lithostar multiline lithotripter at a frequency of 2/sec under intermittent fluoroscopic guidance. All these patients underwent outpatient treatment without general anesthesia, but pethidine was administered for pain control. Treatment episodes were retrospectively reviewed for medical history, patient age, sex, body mass index (BMI), mean arterial pressure at induction, location of stone, total number of shockwaves, and peak shockwave intensity. We also compared the hematoma group with the control group (no hematoma formation after SWL with matched age and sex) for various factors. RESULTS: After 10,887 treatment episodes on a total of 6177 patients during this period, subcapsular or perirenal hematoma developed in 20 patients for a total incident rate of 0.32%. Eighteen patients had the symptom of flank pain, and 2 patients received a diagnosis accidentally without symptoms. Four patients received a blood transfusion because of low hemoglobulin concentration. All of them received conservative and supportive treatment without surgical exploration. Ten (50%) patients had a history of hypertension. Renal hematoma developed in 11 patients at the second or third SWL treatment. Hypertension, higher BMI, and larger stone size are predisposing risk factors (P=0.022, 0.026 and 0.026, respectively) for renal hematoma. CONCLUSIONS: Renal hematoma is a rare (incidence rate, 0.32%) but possibly lethal complication. The most common symptoms of renal hematoma are severe flank pain and hematuria. A history of hypertension and higher BMI are important predisposing factors to perirenal hematoma.