Toshitaka Shin

Autocrine expression of neurotrophins and their receptors in prostate cancer

Abstract Previously, it has been demonstrated that the neurotrophins and their receptors are present in human prostate tissue, but neither their functional role nor localization is clearly understood. We studied the expression of neurotrophins and their receptors in prostate cancer. Between 1990 and 1999, 48 prostate cancer specimens were obtained from patients undergoing radical prostatectomy, of whom 25 received neoadjuvant hormonal therapy (NHT) and 23 were untreated. The specimens were analyzed immunohistochemically for neurotrophins (nerve growth factor, brain derived neurotrophic factor, neurotrophin 3, neurotrophin 4/5) and their receptors (TrkA, TrkB, TrkC, p75NTR). Immunohistochemical studies revealed that both benign and malignant prostate gland epithelial cells expressed the neurotrophins and their receptors to various degrees, but no obvious immunopositive reaction was observed in stromal cells. In benign epithelial cells, the neurotrophins were localized to secretory cells and the receptors were localized to basal cells. The neurotrophins, TrkA and TrkC were expressed to a similar extent in prostate cancer specimens obtained from patients both with and without NHT. In contrast, the expression of TrkB was down‐regulated and the expression of p75NTR was up‐regulated in prostate cancer after hormonal therapy. These findings suggest that neurotrophins are secreted by prostate cancer cells in an autocrine fashion. Neurotrophins may be involved, through their receptors, in the escape mechanism from cell death after androgen depletion found in prostate cancer.

Dual targeting of heat shock proteins 90 and 70 promotes cell death and enhances the anticancer effect of chemotherapeutic agents in bladder cancer

Heat shock proteins (HSPs), which are molecular chaperones that stabilize numerous vital proteins, may be attractive targets for cancer therapy. The aim of the present study was to investigate the possible anticancer effect of single or dual targeting of HSP90 and HSP70 and the combination treatment with HSP inhibitors and chemotherapeutic agents in bladder cancer cells. The expression of HSP90 and the anticancer effect of the HSP90 inhibitor 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) coupled with cisplatin, docetaxel, or gemcitabine were examined using immunohistochemistry, quantitative real-time PCR, cell growth, flow cytometry, immunoblots and caspase-3/7 assays. The expression of HSP70 under HSP90 inhibition and the additive effect of HSP70 inhibitor pifithrin-μ (PFT-μ) were examined by the same assays and transmission electron microscopy. HSP90 was highly expressed in bladder cancer tissues and cell lines. 17-AAG enhanced the antiproliferative and apoptotic effects of each chemotherapeutic agent. 17-AAG also suppressed Akt activity but induced the upregulation of HSP70. PFT-μ enhanced the effect of 17-AAG or chemotherapeutic agents; the triple combination of 17-AAG, PFT-μ and a chemotherapeutic agent showed the most significant anticancer effect on the T24 cell line. The combination of 17-AAG and PFT-μ markedly suppressed Akt and Bad activities. With HSP90 suppression, HSP70 overexpression possibly contributes to the avoidance of cell death and HSP70 may be a key molecule for overcoming resistance to the HSP90 inhibitor. The dual targeting of these two chaperones and the combination with conventional anticancer drugs could be a promising therapeutic option for patients with advanced bladder cancer.

Three-dimensional Printed Model of Prostate Anatomy and Targeted Biopsy-proven Index Tumor to Facilitate Nerve-sparing Prostatectomy

dimension is the same as that for standard laparoscopy (5 mm) and smaller than that of the da Vinci system (8 mm). ALF-X has different safety tools: a go/no-go foot pedal to control movements, control of the highest usable force during surgery, a sensitive grip for precise manipulation, restricted movement speed, and an emergency stop with warning lights and sounds. ALF-X includes a large set of fully reusable instruments, which could offer specific advantages in terms of cost with respect to the da Vinci system, for which each instrument is designed for a limited number of procedures. In addition, different laparoscopic instruments can be adapted for ALF-X robotic arms. A possible limitation of ALF-X is the lack of wristed instrumentation (except for the RADIA needle driver), which represents the main strength of the da Vinci robot. We found no limitations in performing RALPN with ALF-X compared with a similar procedure using the da Vinci system, as the RADIA needle driver enabled a wristed suturing procedure. In our experience, the system was versatile during each step of RALPN, and the operative times reduced dramatically along the learning curve. According to these experimental experiences on pig models, we state that RALPN using ALF-X is a safe, feasible, and reproducible procedure. BecauseALF-X is currently on the market and is used in gynecology, colorectal surgery, and soon in the urologic field, further results on humans are needed and about to come.

Umbilical laparoendoscopic single-site technique for complete excision of urachal remnant.

BACKGROUND Infected urachal remnant is an uncommon benign disease but is generally symptomatic and commonly recurs. The standard of care for this disease is complete resection of all anomalous tissue including a bladder cuff to avoid recurrence. Recent minimally invasive laparoscopic techniques can effectively manage this disease, but multiport laparoscopic techniques are reported to still leave scars outside the umbilicus. SUBJECTS AND METHODS A novel technique of umbilical laparoendoscopic single-site (LESS) surgery for 2 patients with symptomatic urachal remnant is presented in this study. RESULTS In both cases, the entire urachal tissues from the umbilicus to the anterior bladder dome were successfully excised by the umbilical LESS technique without any extra ports or needlescopes. An articulating needle holder enabled water-tight bladder closure, resulting in early removal of the indwelling catheter. Without any signs of infection, the wound healings were completed 4 weeks after surgery in both cases. The patients had no complaints of symptoms at 6 months and 4 months, respectively, after surgery,and they were quite satisfied with their cosmetic results. CONCLUSIONS We propose that the umbilical LESS technique is a promising surgical option for patients with a symptomatic urachal remnant and that this technique provides satisfactory cosmetic results.

Retroperitoneoscopic treatment of ovarian vein syndrome.

In this paper, we describe a case of ovarian vein syndrome (OVS) successfully treated with retroperitoneoscopic techniques. A 41-year-old woman complained with right flank pain, especially with a recumbent position. OVS was diagnosed and ureterolysis and ovarian vein resection were successfully performed, using retroperitoneoscopic techniques. The patient has been completely pain free for 36 months of follow-up. To our knowledge, no previous reports have described the retroperitoneoscopic treatment of OVS. With the minimally invasive approach, postoperative recovery and patient quality of life were markedly improved.

Tumor-to-Tumor Metastasis to Chromophobe Renal Cell Carcinoma: A First Report

Tumor-to-tumor metastasis is a rare phenomenon. From our review of the international literature, around 150 cases have been reported since it was first documented by Campbel in 1868. Renal clear cell carcinoma is well known to be the most common recipient of tumor-to-tumor metastasis in all tumors. However, renal chromophobe cell carcinoma has not been reported to be a recipient. Here, we report a first case of colorectal carcinoma metastatic to chromophobe renal cell carcinoma.

Does Computed Tomography Still Have Limitations to Distinguish Benign from Malignant Renal Tumors for Radiologists

Objectives: To evaluate the current accuracy of CT for diagnosing benign renal tumors. Materials and Methods: We retrospectively reviewed 905 patients who underwent preoperative CT followed by surgical resection. The final pathology was benign in 156 patients (17%). After exclusions, 140 patients with 163 benign tumors were included and 3 sets of the CT interpretations by radiologists with varying levels of experience were analyzed. Results: The histological breakdown was as follows: oncocytomas (54.6%), angiomyolipomas (AMLs; 30.7%), renal cysts (8.0%), other miscellaneous benign tumors (6.7%). The sensitivities of diagnosing oncocytomas were 3.4, 9.0, and 13.5% in primary radiological reports, second blinded reviews, and third non-blinded reviews, respectively (p = 0.055). The sensitivities of diagnosing AMLs were 46.0, 58.0, and 62.0% in the 3-sets of CT interpretations, respectively (p = 0.246). As for renal cysts, the sensitivities were 69.2, 92.3, and 100% in the 3-sets of CT interpretations, respectively (p = 0.051). In primary reports, the positive predictive values were 95.8% in lipid poor (lp)-AMLs, 60.0% in oncocytomas, 69.2% in renal cysts, respectively (p < 0.05). Conclusions: Current conventional CT imaging still has limitations in differentiating oncocytomas and lp-AMLs from renal cell carcinomas, even when images were re-examined by experienced radiologists.

Detection of prostate cancer using magnetic resonance imaging/ultrasonography image-fusion targeted biopsy in African-American men

To assess the diagnostic yield of targeted prostate biopsy in African‐American (A‐A) men using image fusion of multi‐parametric magnetic resonance imaging (mpMRI) with real‐time transrectal ultrasonography (US).

Munchausen Syndrome in the Act of Creating and Enacting Macroscopic Hematuria

transfusion, that her anemia did not improve despite blood transfusion, and that during transfusion hematuria would begin again, led the authors to suspect Munchausen syndrome. On beginning detailed observation of her behavior during blood transfusion, we witnessed her using a dirty syringe ( fig. 1 ), which she had hidden on her person, to remove some of the transfusion blood and inject it into her own bladder, thus leading to the confirmed diagnosis. We diagnosed her Munchausen synWe report the rare experience of discovering a patient in the act of creating and enacting macroscopic hematuria and thereby reaching a confirmed diagnosis of Munchausen syndrome. The patient was a 27-year-old female. She presented complaining mainly of macroscopic hematuria. She had been treated for the same main condition by some previous physicians, and she had undergone a laparoscopic right nephrectomy under the diagnosis of arteriovenous malformation. Post-surgery, macroscopic hematuria continued and the cause of the hematuria remained unclear in spite of numerous examinations. The patient was treated with more than 200 units of packed red blood cell transfusion to treat severe anemia and frequently suffered from septicemia. At her own request, the patient attended our department. Despite various tests, the cause of the hematuria remained indeterminate, and she was subjected to repeated packed red blood cell transfusion and continued to experience septicemia. After a certain period of time, the patient’s behavior, including the facts that no organic disorder could be identified, that the patient experienced cumulative septicemia after blood transfusion, that she would close the curtains for long periods during Received: December 5, 2013 Accepted: December 10, 2013 Published online: February 27, 2014

A Case of Urethral Duplication Arising from the Posterior Urethra to the Scrotum with Urinary Stone in a 6-Year-Old Male

Urethral duplication is a rare congenital anomaly. We report a 6-year-old male with type IIA2 (Y-type) using Effmanns classification. The accessory urethra, in which a urinary stone existed, arose from the posterior urethra to the scrotum. Because of recurrent urinary tract infection and urinary discharge from the accessory urethra, surgical removal of the accessory urethra through a scrotal incision was performed. At 7-month postoperative follow-up the patient was completely free from urinary incontinence and urinary tract infection.