Jun Miki

Staphylococcal Nuclease Domain-Containing Protein 1 as a Potential Tissue Marker for Prostate Cancer

Using high molecular-weight proteomic analysis, we previously showed that Staphylococcal nuclease domain-containing protein 1 (SND1) is highly expressed in recurrent androgen-insensitive prostate cancer tissues. SND1 is a component of the RNA-induced splicing complex that mediates RNA interference, leading to degradation of specific mRNAs. The objective of this study was to further characterize SND1 expression and to investigate its biological potential in prostate cancer. Radical prostatectomy specimens were obtained from 62 prostate cancer patients. SND1 immunohistochemical staining patterns were evaluated using an in-house polyclonal antibody. We confirmed SND1 mRNA expression in prostate cancer cells using an in situ hybridization technique. To determine the importance of SND1 mRNA, we knocked down SND1 in vitro with small interfering RNA and observed a significant decrease in cell growth. SND1 was expressed in 60 of 62 prostate cancers (97%), appearing in the cytoplasm as small, granular structures; it was also present at high levels in prostate cancer specimens, while in hyperplasia specimens and normal epithelium, it was weakly or negatively expressed. SND1 expression intensity increased with increasing grade and aggressiveness of the cancer. As SND1 mRNA was overexpressed in cancer cells, the growth of these cells was suppressed following SND1 knockdown in vitro, thus representing a promising prostate cancer biomarker and therapeutic target.

The role of lymph node dissection in the management of prostate cancer

Lymph node dissection is a standard procedure for treatment of several cancers, but its role in prostate cancer (PCa) as an adjunct of radical prostatectomy is still debated and controversial. Pelvic lymph node dissection (PLND) is currently the most reliable means of diagnosis of lymph node metastases. A uniform PLND surgical template cannot be determined, but recent evidence shows that extended PLND provides more lymph nodes, increases the accuracy of detection of lymph node metastases, and affects decision making with regard to adjuvant therapy. Several nomograms have been developed to predict those who may need more extensive PLND, while sparing the rest. Importantly, no prospective data indicate that extension of PLND improves cancer control or benefits survival. A well designed prospective randomized study is needed to resolve these issues. We present a comprehensive literature review and critical discussion of the diagnostic and therapeutic role of PLND in PCa.

Upfront transection and subsequent ligation of the dorsal vein complex during laparoscopic radical prostatectomy

Laparoscopic radical prostatectomy for localized prostate cancer offers several advantages, including creation of a pneumoperitoneum that results in less blood loss than is seen with the corresponding open procedure. Transection of the deep dorsal vein complex remains among the most challenging aspects, however. Safe and secure completion of this procedure is important to minimize blood loss and maximize the chance of cure. Liberal use of coagulation for hemostasis at the dorsal vein complex (DVC) risks thermal damage to the sphincteric muscle. DVC ligation before transection, though commonly performed, can cause loss of some sphincteric fibers and potentially result in delayed recovery of urinary continence. Furthermore, ligation may at times prove difficult, especially in obese patients with a short and broad DVC, a large prostate gland, and a narrow pelvis. The presence of prominent pubic tubercles may further increase the difficulty. We have found that bleeding from the DVC is easily controlled without suture ligation through a combination of a modest pneumoperitoneum with pinpoint coagulation of one or two small arteries that are consistently found in the superficial layer of the complex. Precise, even‐level transection is possible under direct vision with no more than modest blood loss. A stitch in a Z‐shaped fashion is then applied to the entire transected stump of the DVC. This procedure is simple and easily performed, even by those with limited experience. Here we provide an overview of our current technique.

Investigations of prostate epithelial stem cells and prostate cancer stem cells

Although both prostate epithelial stem cells and prostate cancer stem cells are implicated in the differentiation of the normal prostate gland and carcinogenesis of prostate cancer, there has, until recently, been little information regarding their biology. This review summarizes the recent advancements in cell biological research including various in vitro culture systems that have offered the characterization and isolation of prostate epithelial stem cells and prostate cancer stem cells. In addition, the stromal niche or microenvironment of stem cells plays an essential role in proliferation and differentiation of normal stem cells. Stroma surrounding cancer cells, which also provide another unique niche, may involve the initiation and development of cancer stem cells. Investigation of stem cells and their microenvironments in the prostate should lead to the elucidation of biological features and the development of novel treatments for prostate cancer.

Extracorporeal shock wave treatment for Peyronie's disease using EDAP LT-02 ; preliminary results

Abstract Background : Peyronie’s disease is an idiopathic fibrosis of the tunica albuginea of the penis, which often causes erectile dysfunction. No effective therapy except surgery has been available for Peyronie’s disease. We investigated the clinical efficacy of extracorporeal shock wave treatment (ESWT) using EDAP LT‐02 as an alternative method of treatment for Peyronie’s disease.

Lactate dehydrogenase predicts combined progression‐free survival after sequential therapy with abiraterone and enzalutamide for patients with castration‐resistant prostate cancer

An array of clinical issues remains to be resolved for castration‐resistant prostate cancer (CRPC), including the sequence of drug use and drug cross‐resistance. At present, no clear guidelines are available for the optimal sequence of use of novel agents like androgen‐receptor axis‐targeted (ARAT) agents, particularly enzalutamide, and abiraterone.

Safety of fondaparinux for prevention of postoperative venous thromboembolism in urological malignancy: A prospective randomized clinical trial.

To prospectively evaluate the safety of postoperative fondaparinux in comparison with low molecular weight heparin in patients undergoing uro‐oncological surgery.

Successful treatment of nephrotic syndrome caused by recurrent IgA nephropathy with chronic active antibody-mediated rejection three years after kidney transplantation.

Yaginuma T, Yamamoto H, Mitome J, Kobayashi A, Yamamoto I, Tanno Y, Hayakawa H, Miyazaki Y, Yokoyama K, Utsunomiya Y, Miki J, Yamada H, Furuta N, Yamaguchi Y, Hosoya T. Successful treatment of nephrotic syndrome caused by recurrent IgA nephropathy with chronic active antibody‐mediated rejection three years after kidney transplantation.
Clin Transplant 2011: 25 (Suppl. 23): 28–33.
© 2011 John Wiley & Sons A/S.

Successful treatment of recurrent Henoch–Schönlein purpura nephritis in a renal allograft with tonsillectomy and steroid pulse therapy

We report a case of recurrent Henoch–Schönlein purpura nephritis (HSPN) treated successfully with a tonsillectomy and steroid pulse therapy in a kidney transplant patient. A 29‐year‐old woman was admitted to our hospital for an episode biopsy; she had a serum creatinine (S‐Cr) of 1.0 mg/dL and 1.34 g/day proteinuria 26 months after kidney transplantation. Histological examination revealed increased amounts of mesangial matrix and mesangial hypercellularity with IgA deposition. Of note, one glomerulus showed focal endocapillary proliferation and tuft necrosis. We diagnosed active recurrent HSPN. Considering both the histological findings and refractory clinical course of the native kidney, she was treated for 3 consecutive days with steroid pulse therapy and a tonsillectomy. The patients proteinuria decreased gradually to less than 150 mg/day 6 months later. A second biopsy 6 years after kidney transplantation showed an excellent response to treatment and revealed a marked reduction in both the mesangial matrix and mesangial hypercellularity, with trace IgA deposition. We conclude that a tonsillectomy and steroid pulse therapy appeared to be useful in this patient with active recurrent HSPN. This paper is the first to report a tonsillectomy and steroid pulse therapy as a therapeutic option for active recurrent HSPN. Further studies are needed to elucidate the efficacy and mechanisms of tonsillectomy with recurrent HSPN in kidney transplant patients.

Subclinical antibody-mediated rejection due to anti-human-leukocyte-antigen-DR53 antibody accompanied by plasma cell-rich acute rejection in a patient with cadaveric kidney transplantation.

A 56‐year‐old man who had undergone cadaveric kidney transplantation 21 months earlier was admitted to our hospital for a protocol biopsy; he had a serum creatinine level of 1.2 mg/dL and no proteinuria. Histological features showed two distinct entities: (i) inflammatory cell infiltration, in the glomerular and peritubular capillaries and (ii) focal, aggressive tubulointerstitial inflammatory cell infiltration, predominantly plasma cells, with mild tubulitis (Banff 13 classification: i2, t1, g2, ptc2, v0, ci1, ct1, cg0, cv0). Immunohistological studies showed mildly positive C4d immunoreactivity in the peritubular capillaries. The patient had donor specific antibody to human‐leucocyte‐antigen‐DR53. We diagnosed him with subclinical antibody‐mediated rejection accompanied by plasma cell‐rich acute rejection. Both antibody‐mediated rejection due to anti‐ human‐leucocyte‐antigen ‐DR53 antibodies and plasma cell‐rich acute rejection are known to be refractory and have a poor prognosis. Thus, we started plasma exchange with intravenous immunoglobulin and rituximab for the former and 3 days of consecutive steroid pulse therapy for the latter. Three months after treatment, a follow‐up allograft biopsy showed excellent responses to treatment for both histological features. This case report considers the importance of an early diagnosis and appropriate intervention for subclinical antibody‐mediated rejection due to donor specific antibody to human‐leucocyte‐antigen‐DR53 and plasma cell‐rich acute rejection.