PTEN/AKT signaling mediates chemoresistance in refractory acute myeloid leukemia through enhanced glycolysis.

Primary refractory acute myeloid leukemia (AML) and early recurrence of leukemic cells are among the most difficult hurdles to overcome in the treatment of AML. Moreover, uncertainties surrounding the molecular mechanism underlying refractory AML pose a challenge when it comes to developing novel therapeutic drugs. However, accumulating evidence suggests a contribution of phosphatase and tensin homolog (PTEN)/protein kinase B (AKT) signaling to the development of refractory AML. To assess PTEN/AKT signaling in AML, two types of AML cell lines were evaluated, namely control HL60 cells and KG1α cells, a refractory AML cell line that is resistant to idarubicin and cytarabine (AraC) treatment. Changes in the expression level of glycolysis­ and mitochondrial oxidative phosphorylation­related genes and proteins were evaluated by reverse transcription­quantitative polymerase chain reaction and western blot analyses, respectively. The mitochondrial oxygen consumption and extracellular acidification rates were measured using an XF24 analyzer. CCK8 assay and Annexin V/PI staining were used to analyze cell viability and cellular apoptosis, respectively. The PTEN protein was found to be depleted, whereas AKT phosphorylation levels were elevated in KG1α cells compared with HL60 cells. These changes were associated with increased expression of glucose transporter 1 and hexokinase 2, and increased lactate production. AKT inhibition decreased the proliferation of KG1α cells and decreased extracellular acidification without affecting HL60 cells. Notably, AKT inhibition increased the susceptibility of KG1α cells to chemotherapy with idarubicin and AraC. Taken together, the findings of the present study indicate that activation of AKT by PTEN deficiency sustains the refractory AML status through enhancement of glycolysis and mitochondrial respiration, effects that may be rescued by inhibiting AKT activity.

Rethinking of ureteral stent removal using an extraction string; what patients feel and what is patients' preference? : a randomized controlled study.

BACKGROUND: Ureteral stent removal using an extraction string is advantageous because it can obviate an invasive cystoscopy, but there is a paucity of data on how patients feel about it, and how bothersome or beneficial it is. We performed this study to evaluate patients' preference for stent removal using an extraction string and which parameters could affect it. METHODS: In total, 114 consecutive patients undergoing ureteral stent insertion after ureteroscopic stone removal (URS) for unilateral recurrent ureter stones were enrolled. Patients were randomized to a string group or a no string group. Stent removal was performed on the first visit within 7 days postoperatively. All patients were asked to complete the ureteral stent symptom questionnaire, to rate the degree of pain during stent removal using a visual analog scale (VAS) and to answer to questions regarding their preference. RESULTS: No significant differences were found in domain total scores including urinary symptoms (p = 0.17), pain (p = 0.62), general health (p = 0.37), work performance (p = 0.41). However, regarding separate questions for 'dysuria' and 'difficulties with heavy physical activity', there were significant intergroup differences (p = 0.03 and p = 0.04, respectively). Particular, a significantly higher proportion of patients in the string group checked 'stoppage of sexual intercourse due to stent-related problems' than in the no string group (p = 0.03). VAS score on stent removal was significantly higher in the no string group than the string group (p = 0.005). Among the patients who remember the experience of an indwelling ureteral stent in the past, 85% (17/20) of the no string group answered 'No' to the question of 'difference between the methods used in this time and in the past'. On the contrary, 84.2% (16/19) answered 'Yes' to the same question in the string group. And, all 16 patients of the string group who noted differences between the methods preferred ureteral stent removal using an extraction string to the past method. CONCLUSIONS: Despite of minor increased morbidity related to the extraction string, patients preferred ureteral stent removal using the extraction string after URS. The patients with the extraction string felt less pain on stent removal than flexible cystoscopic stent removal. TRIAL REGISTRATION: KCT0001700 . The trial was registered in the Clinical Research Information Service (CRiS), Republic of Korea; registration date: 18/11/2015.

The initial experience of pneumovesicoscopic bladder stone removal using a laparoscopic entrapment sac.

INTRODUCTION: In this article, we aim to present our novel experience of bladder stone removal under pneumovesicoscopic field using a laparoscopic entrapment sac. TECHNICAL CONSIDERATIONS: We retrospectively reviewed the medical records of 21 patients who had pneumovesicoscopic bladder stone removal to assess a variety of patient characteristics and surgical outcomes. We considered stone burden, stone removal time including pneumovesicoscopic procedure time, postoperative catheter indwelling duration, postoperative hospital stay, and complications. The procedure was performed in the following steps: Under cystoscopy filled with saline solution, a 10-mm suprapubic transvesical trocar was inserted. After changing optical transmission medium from saline to CO(2) gas, pneumovesicoscopic procedure was performed to put stones in an entrapment sac inserted through the trocar. The stones trapped in the sac were extracorporeally broken with a lithotripter via the suprapubic route. The mean patient age was 58.95 ± 22.03 years. The mean stone burden was 4.88 ± 2.63 cm. Eleven patients had a single stone, whereas 10 had multiple stones. All stones were completely removed. The mean operative time was 31.66 ± 7.25 minutes, including the pneumovesicoscopic procedure time of 13.81 ± 7.30 minutes. In all but 6 patients with a cystostomy or a combined transurethral resection of the prostate, the urethra catheter was removed on the day after surgery; the mean postoperative hospital stay was 1.67 ± 0.49 days. There were 5 postoperative complications of Clavien grade I or II. CONCLUSION: We report the technical feasibility of pneumovesicoscopic bladder stone removal using a laparoscopic entrapment sac as a minimally invasive method. This technique will likely become more important as a useful option for treating bladder stones.

Comparison of Non-contrast-Enhanced Computed Tomography and Intravenous Pyelogram for Detection of Patients With Urinary Calculi.

PURPOSE: The aim of this study was to investigate the changing pattern in the use of intravenous pyelogram (IVP), conventional computed tomography (CT), and non-contrast-enhanced computed tomography (NECT) for evaluation of patients with acute flank pain. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 2,180 patients with acute flank pain who had visited Bundang Jesaeng General Hospital between January 2008 and December 2012 and analyzed the use of IVP, conventional CT, and NECT for these patients. RESULTS: During the study period there was a significant increase in NECT use (p<0.001) and a significant decrease in IVP use (p<0.001). Conventional CT use was also increased significantly (p=0.001). During this time the proportion of patients with acute flank pain who were diagnosed with urinary calculi did not change significantly (p=0.971). CONCLUSIONS: There was a great shift in the use of imaging study from IVP to NECT between 2008 and 2012 for patients with acute flank pain.

Optimal shock wave rate for shock wave lithotripsy in urolithiasis treatment: a prospective randomized study.

PURPOSE: We aimed to compare the effects of a fast shock wave rate (120 shocks per minute) and a slow shock wave rate (60 shocks per minute) on the shock wave lithotripsy (SWL) success rate, patient's pain tolerance, and complications. MATERIALS AND METHODS: A total of 165 patients with radiopaque renal pelvis or upper ureter stones were included in the study. Patients were classified by use of a random numbers table. Group I (81 patients) received 60 shock waves per minute and group II (84 patients) received 120 shock waves per minute. For each session, the success rate, pain measurement, and complication rate were recorded. RESULTS: No statistically significant differences were observed in the patients according to age, sex, body mass index, stone size, side, location, total energy level, or number of shocks. The success rate of the first session was greater in group I than in group II (p=0.002). The visual analogue pain scale was lower in group I than in group II (p=0.001). The total number of sessions to success and the complication rate were significantly lower in group I than in group II (p=0.001). CONCLUSIONS: The success rate of SWL is dependent on the interval between the shock waves. If the time between the shock waves is short, the rate of lithotripsy success decreases, and the pain measurement score and complications increase. We conclude slow SWL is the optimal shock wave rate.

Simple anchoring of the penopubic skin to the prepubic deep fascia in surgical correction of buried penis.

PURPOSE: The aim of this study was to categorize concealed penis and buried penis by preoperative physical examination including the manual prepubic compression test and to describe a simple surgical technique to correct buried penis that was based on surgical experience and comprehension of the anatomical components. MATERIALS AND METHODS: From March 2007 to November 2010, 17 patients were diagnosed with buried penis after differentiation of this condition from concealed penis. The described surgical technique consisted of a minimal incision and simple fixation of the penile shaft skin and superficial fascia to the prepubic deep fascia, without degloving the penile skin. RESULTS: The mean age of the patients was 10.2 years, ranging from 8 years to 15 years. The median follow-up was 19 months (range, 5 to 49 months). The mean penile lengths were 1.8 cm (range, 1.1 to 2.5 cm) preoperatively and 4.5 cm (range, 3.3 to 5.8 cm) postoperatively. The median difference between preoperative and postoperative penile lengths was 2.7 cm (range, 2.1 to 3.9 cm). There were no serious intra- or postoperative complications. CONCLUSIONS: With the simple anchoring of the penopubic skin to the prepubic deep fascia, we obtained successful subjective and objective outcomes without complications. We suggest that this is a promising surgical method for selected patients with buried penis.

Rethinking suprapubic cystostomy in voiding dysfunction: new trial with timed drainage.

PURPOSE: Today, many patients with voiding dysfunction select suprapubic cystostomy (SPC) instead of clean intermittent catheterization (CIC) for practical reasons. There is thus a need to reconsider SPC as a management for voiding dysfunction. We designed SPC with timed drainage (TSPCD) and evaluated its effectiveness compared with continuous drainage with a urine bag (CSPCD). MATERIALS AND METHODS: Between January 2006 and January 2010, a total of 82 patients underwent SPC. Patients undergoing SPC were randomly assigned to CSPCD or TSPCD. Patient characteristics, complications, and the results of urine cultures were compared between the two groups through retrospective chart reviews. Also, preferences for CSPCD and TSPCD in another 15 patients who had experienced both CSPCD and TSPCD were investigated. RESULTS: The CSPCD and TSPCD groups comprised 46 and 36 patients, respectively. In a comparison of complications between the two groups, the incidence of acute symptomatic cystitis was significantly lower in the TSPCD group than in the CSPCD group (43% vs. 20%, p=0.032). The incidence of symptomatic urinary tract infection (UTI) was lower in the TSPCD group. Positive urine culture rates were 89.7% and 72.4% in groups 1 and 2, respectively. There was a significant difference between the two groups (p=0.004). In another 15 patients who experienced both CSPCD and TSPCD, 14 patients (93%) stated a preference for TSPCD after converting from CSPCD to TSPCD, and one patient (7%) returned to CSPCD only at night. CONCLUSIONS: In this study, TSPCD had the advantages of less morbidity as UTI and being more preferable by patients with relatively good daily activity compared with CSPCD. TSPCD is an alternative to CSPCD for the treatment of voiding dysfunction.

Chronic kidney disease among men with lower urinary tract symptoms due to benign prostatic hyperplasia.

OBJECTIVE: To analyse potential association of various clinical characteristics of benign prostatic hyperplasia (BPH) with chronic kidney disease (CKD) among men presenting with lower urinary tract symptoms (LUTS) secondary to BPH of varying severity. PATIENTS AND METHODS: We reviewed the data of 2741 consecutive patients who presented to our clinic with LUTS secondary to BPH. For our analysis, CKD was defined by an elevated serum creatinine level or decreased estimated glomerular filtration rate (eGFR). Univariate and multivariate logistic regression analyses were used to address associations of CKD with various clinical characteristics. RESULTS: Of the 2741 patients, 161 (5.9%) were initially classified as having CKD (serum creatinine > or =133 micromol/L). In multivariate analysis, peak flow rate (P = 0.001) and a history of hypertension and/or diabetes (both P < 0.001) were significantly associated with CKD, whereas age, body mass index, prostate-specific antigen level, prostate volume, postvoid residual, or International Prostate Symptom Score (IPSS) were not. When individual symptoms from the IPSS were analysed, only weak stream (P = 0.041) and hesitancy (P = 0.048), both obstruction-related, were significantly associated with CKD status in age and comorbidity-adjusted analyses. The results of secondary analysis with CKD defined as an eGFR of <60 mL/min/1.73 m(2) were similar. CONCLUSION: Our results show that decreased peak flow rate and a history of hypertension and/or diabetes are significantly associated with CKD in men seeking management for LUTS from BPH of varying severity.