Hong Koo Ha

Clinical significance of CXCL16/CXCR6 expression in patients with prostate cancer

We hypothesized that the CXCL16-CXCR6 ligand-receptor system may play an important role in prostate cancer progression. Levels of CXCL16 and CXCR6 expression were evaluated in prostate cancer cell lines (PC-3 and LNCaP) and normal prostate epithelial cells (PrEC), as well as in tissues from 354 patients. The immunohistochemical expression of CXCL16/CXCR6 was greater in the PC-3/LNCaP cells than in the PrEC cell line. The expression of CXCL16/CXCR6 was significantly higher in prostate cancer than in benign prostatic hypertrophy. Using RT-PCR, the expression of CXCL16/CXCR6 was found to be greater in the PC-3/LNCaP cells than in the PrEC cell line. CXCL16/CXCR6 was weakly detected in lung and liver tissues, whereas CXCL16 was highly expressed in specimens of bone metastasis. CXCL16 immunostaining was related to Gleason score, T stage, tumor volume, perineural invasion and lymph node metastasis. However, biochemical PSA recurrence was not related to the expression of CXCL16/CXCR6. High CXCL16/CXCR6 expression may be related to aggressive cancer behavior, and high CXCL16 expression to bone metastases.

Recovery of overall exercise ability, quality of life, and continence after 12-week combined exercise intervention in elderly patients who underwent radical prostatectomy: a randomized controlled study.

OBJECTIVE To examine the changes from a combined exercise intervention after radical prostatectomy (RP) in elderly patients with prostate cancer, because randomized controlled trials addressing exercise intervention after RP have been lacking. METHODS From May 2009 to May 2010, all patients who underwent laparoscopic RP were assessed for eligibility. A total of 66 patients were randomized to an exercise or a control group. The exercise group received a combined exercise intervention (resistance, flexibility, and Kegel exercises) twice a week for 12 weeks, and the control group received only Kegel exercises. The primary outcome was physical function, and the secondary outcomes were continence status and quality of life after the exercise intervention. RESULTS A total of 49 patients completed follow-up to the end of study. After the 12-week exercise intervention, except for grip strength, all physical functions were better in the exercise group than in the control group. The 24-hour pad test results (12.2 g in the exercise group, 46.2 g in the control group) and continence rate (73.1% in exercise group, 43.5% in the control group) recovered more promptly in the exercise group. On a questionnaire study using the International Consultation on Incontinence questionnaire, Beck Depression Inventory, and Medical Outcomes Study 36-item short-form health survey, only the exercise group showed improvement at the last follow-up visit. CONCLUSION A 12-week combined exercise intervention after RP results in improvement of physical function, continence rate, and quality of life. These results could help with prompt recovery of daily activities.

Prediction of Perineural Invasion and Its Prognostic Value in Patients with Prostate Cancer

Purpose The prognostic significance of perineural invasion by prostate cancer is debated. We investigated the association between perineural invasion and clinicopathological factors and the effect of perineural invasion on survival in patients with prostate cancer. Materials and Methods A total of 361 patients with prostate cancer without any neoadjuvant therapies prior to surgery from 1999 to 2010 were analyzed retrospectively. Whole-mount sections of surgical specimens from all patients who underwent radical prostatectomy were evaluated. Positive perineural invasion was defined as infiltration of cancer cells in the perineurium or neural fascicles. The relationship of perineural invasion with clinicopathological features and prognosis of prostate cancer was studied. We also researched preoperative factors that were associated with perineural invasion. Results Perineural invasion in a prostatectomy specimen (PNIp) was positive in 188 of 361 patients (52.1%). In the multivariate analysis of the preoperative variables, PNIp was related to the primary Gleason grade (p=0.020), the number of positive cores (p=0.008), and the percentage of tumor cells in positive cores (p=0.021), but not to perineural invasion of a prostate biopsy. In the evaluation between PNIp and pathologic findings of the prostatectomy specimen, PNIp was related to the Gleason score (p=0.010), T-stage (p=0.015), and lymphovascular invasion (p=0.019). However, by multivariate analysis, the PNIp was not an independent prognostic factor of biochemical serum recurrence (p=0.364) or cancer-specific survival (p=0.726). Conclusions PNIp was significantly related to biologically aggressive tumor patterns but was not a prognostic factor for biochemical serum PSA recurrence or cancer-specific survival in patients with prostate cancer.

Malignant Inflammatory Myofibroblastic Tumor of the Bladder with Rapid Progression

A 71-year-old man was referred for painless hematuria and a bladder tumor. Cystoscopy and computed tomography revealed a 3-cm oval nodular mass on the left lateral side of the bladder. The patient underwent a complete transurethral resection of the lesion and histology showed a proliferation of atypical spindle cells with inflammation consistent with a myofibroblastic tumor. After 4 and 7 months, follow-up cystoscopy demonstrated nodular mass lesions and transurethral resection of bladder tumor was done, which showed chronic cystitis and a recurred myofibroblastic tumor, respectively. Five months later, multiple lymph node, bone, and soft tissue metastases were found by positron emission tomography. The patient was treated first with palliative chemotherapy, including doxorubicin and cisplatin. After that, radiologic studies showed disease progression but the patient refused further treatment and died 6 months later.

Vesico-Appendiceal Fistula Misdiagnosed as Meckel's Diverticulum: A Laparoscopic Approach

A 26-year-old man complained of a vague low abdominal discomfort for the previous 2 months. Radiologic evaluations demonstrated that there was tubular structure connected with the right side wall of the bladder, suggesting Meckels diverticulum with fistula formation to the bladder as well as a mass-like bladder wall thickening. With an impression of Meckels diverticulum with fistula with the bladder, laparoscopic surgery was performed to confirm a diagnosis and to manage the Meckels diverticulum with fistula with the bladder. The distal tip of the appendix was firmly attached to the right side of the bladder. The final diagnosis was corrected by laparoscopy followed by laparoscopic appendectomy and fistula repair. Vesico-appendiceal fistula is an uncommon type of vesico-enteral fistula and a rare complication of unrecognized appendicitis. Additionally, this report showed the significant value of laparoscopy as a diagnostic and therapeutic tool to this entity.

Expression of E-cadherin and α-catenin in a varicocele-induced infertility rat model.

The roles of E-cadherin and α-catenin were evaluated in the development of varicocele-induced infertility. Analysis of the association between the expression of E-cadherin/α-catenin and clinical/pathological parameters was performed. Thirty 10-week-old male rats (experimental group) were used for the experiments; the left renal vein was ligated to form a varicocele. The abdomen was incised in 30 rats (control group) and no procedure was performed on 10 rats (baseline group). The weights of the left testis, serum reactive oxygen species (ROS), testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and degenerative changes in the seminiferous tubules after 4 and 8 weeks were recorded. The expression of E-cadherin and α-catenin was evaluated by immunohistochemical (IHC) staining and Western blot analysis. The ROS increased in the 8-week experimental group, compared with the baseline and control groups (P < 0.001 for both). Additionally, FSH significantly increased in the 4- and 8-week experimental group compared with the control groups (P = 0.013 and P = 0.032, respectively). The ratio of degenerative changes in the seminiferous tubules of the experimental groups increased. The IHC staining showed that the expression of E-cadherin and α-catenin decreased in the 4- and 8-week experimental groups. Similar to the IHC staining, the experimental group had decreased reactivity on Western blot analysis. The expression of E-cadherin and α-catenin was significantly associated with the ROS and degenerative changes in the seminiferous tubules. The results of this study suggest that damage to the blood-testis barrier (BTB) is associated with varicocele-induced male infertility, and that ROS may cause damage to the BTB.

Synergistic induction of cancer cell migration regulated by Gβγ and phosphatidylinositol 3-kinase

Phosphatidylinositol 3-kinase (PI3K) is essential for both G protein-coupled receptor (GPCR)- and receptor tyrosine kinase (RTK)-mediated cancer cell migration. Here, we have shown that maximum migration is achieved by full activation of phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 (P-Rex1) in the presence of Gβγ and PI3K signaling pathways. Lysophosphatidic acid (LPA)-induced migration was higher than that of epidermal growth factor (EGF)-induced migration; however, LPA-induced activation of Akt was lower than that stimulated by EGF. LPA-induced migration was partially blocked by either Gβγ or RTK inhibitor and completely blocked by both inhibitors. LPA-induced migration was synergistically increased in the presence of EGF and vice versa. In correlation with these results, sphingosine-1-phosphate (S1P)-induced migration was also synergistically induced in the presence of insulin-like growth factor-1 (IGF-1). Finally, silencing of P-Rex1 abolished the synergism in migration as well as in Rac activation. Moreover, synergistic activation of MMP-2 and cancer cell invasion was attenuated by silencing of P-Rex1. Given these results, we suggest that P-Rex1 requires both Gβγ and PI3K signaling pathways for synergistic activation of Rac, thereby inducing maximum cancer cell migration and invasion.

Nomogram for prediction of prostate cancer with serum prostate specific antigen less than 10 ng/mL.

Although prostate-specific antigen (PSA) is a very useful screening tool, prostate biopsy is still necessary to confirm prostate cancer (PCA). However, it is reported that PSA is associated with a high false-positive rate and prostate biopsy also has various procedure-related complications. Therefore, the authors have devised a nomogram, which can be used to estimate the risk of PCA, using available clinical data for men with a serum PSA less than 10 ng/mL. Prostate biopsies were obtained from 2,139 patients from January 1998 to March 2011. Of them, 1,171 patients with a serum PSA less than 10 ng/mL were only included in this study. Patient age, PSA, free PSA, prostate volume, PSA density and percent free PSA ratio were analyzed. Among 1,171 patients, 255 patients (21.8%) were diagnosed as PCA. Multivariate analyses showed that patient age, prostate volume, PSA and percent free PSA had statistically significant relationships with PCA (P < 0.05) and were used as nomogram predictor variables. The area under the (ROC) curve for all factors in a model predicting PCA was 0.759 (95% CI, 0.716-0.803). Graphical Abstract

Clinical application of calculated split renal volume using computed tomography-based renal volumetry after partial nephrectomy: Correlation with technetium-99m dimercaptosuccinic acid renal scan data

To evaluate the clinical application of computed tomography‐based measurement of renal cortical volume and split renal volume as a single tool to assess the anatomy and renal function in patients with renal tumors before and after partial nephrectomy, and to compare the findings with technetium‐99m dimercaptosuccinic acid renal scan.

Learning Curve of Robot-Assisted Laparoscopic Radical Prostatectomy for a Single Experienced Surgeon: Comparison with Simultaneous Laparoscopic Radical Prostatectomy

Purpose Despite the large number of analytical reports regarding the learning curve in the transition from open to robot-assisted radical prostatectomy (RARP), few comparative results with laparoscopic radical prostatectomy (LRP) have been reported. Thus, we evaluated operative and postoperative outcomes in RARP versus 100 simultaneously performed LRPs. Materials and Methods A single surgeon had performed more than 1,000 laparoscopic operations, including 415 cases of radical nephrectomy, 85 radical cystectomies, 369 radical prostatectomies, and treatment of 212 other urological tumors, since 2009. We evaluated operative (operation time, intraoperative transfusion, complications, hospital stay, margin status, pathological stage, Gleason score) and postoperative (continence and erectile function) parameters in initial cases of RARP without tutoring compared with 100 recently performed LRPs. Results Mean operation time and length of hospital stay for RARP and LRP were 145.5±43.6 minutes and 118.1±39.1 minutes, and 6.4±0.9 days and 6.6±1.1 days, respectively (p=0.003 and p=0.721). After 17 cases, the mean operation time for RARP was similar to LRP (less than 2 hours). Positive surgical margins in localized cancer were seen in 11.1% and 8.9% of cases in RARP and LRP, respectively (p=0.733). At postoperative 3 months, sexual intercourse was reported in 14.0% and 12.0%, and pad-free continence in 96.0% and 81.0% in patients with RARP and LRP, respectively (p=0.796 and p=0.012). Conclusions Previous large-volume experience of LRPs may shorten the learning curve for RARP in terms of oncological outcome. Additionally, previous experience with laparoscopy may improve the functional outcomes of RARP.