Seiji Moroi

Occludin is concentrated at tight junctions of mouse/rat but not human/guinea pig Sertoli cells in testes

Occludin is the only integral membrane protein identified to date as a component of tight junctions (TJs). Here, we examined the distribution and expression of occludin in murine testis bearing well-developed TJ. In the adult mouse testis, occludin was concentrated at TJ strands, which are located at the most basal regions of lateral membranes of Sertoli cells. In immunoblotting, occludin showed a characteristic multiple banding pattern, suggesting that occludin is highly phosphorylated in the testis. In 1-wk-old mouse testis, occludin was distributed diffusely at the lateral membranes of Sertoli cells, and even at this stage, highly phosphorylated occludin was detected. With development, occludin gradually became concentrated at the most basal regions of Sertoli cells. The same results were obtained in rat, but unexpectedly occludin was not detected in human or guinea pig Sertoli cells by immunofluorescence microscopy as well as by immunoblotting. Inasmuch as TJs are also well developed in Sertoli cells of these species, we concluded that, at least in the testes of these species, there are some Sertoli cell-specific isoforms of occludin or other TJ-associated integral membrane proteins that differ from occludin.Occludin is the only integral membrane protein identified to date as a component of tight junctions (TJs). Here, we examined the distribution and expression of occludin in murine testis bearing well-developed TJ. In the adult mouse testis, occludin was concentrated at TJ strands, which are located at the most basal regions of lateral membranes of Sertoli cells. In immunoblotting, occludin showed a characteristic multiple banding pattern, suggesting that occludin is highly phosphorylated in the testis. In 1-wk-old mouse testis, occludin was distributed diffusely at the lateral membranes of Sertoli cells, and even at this stage, highly phosphorylated occludin was detected. With development, occludin gradually became concentrated at the most basal regions of Sertoli cells. The same results were obtained in rat, but unexpectedly occludin was not detected in human or guinea pig Sertoli cells by immunofluorescence microscopy as well as by immunoblotting. Inasmuch as TJs are also well developed in Sertoli cells of these species, we concluded that, at least in the testes of these species, there are some Sertoli cell-specific isoforms of occludin or other TJ-associated integral membrane proteins that differ from occludin.

α-Catenin-Deficient F9 Cells Differentiate into Signet Ring Cells

It has been demonstrated that alpha-catenin is frequently lost in diffuse type adenocarcinomas. We have isolated alpha-catenin-deficient mouse teratocarcinoma F9 cells by gene targeting. Wild-type F9 cell aggregates cultured in the presence of retinoic acid differentiated into embryoid bodies with an outer layer of epithelial cells. In contrast, cell aggregates of alpha-catenin-deficient cells did not develop outer layers under the same conditions. The outer surface cells of alpha-catenin-deficient cell aggregates, however, differentiated into epithelial cells as determined by their expression of epithelial marker proteins. These differentiated cells scattered from aggregates and showed signet ring cell morphology, which is frequently observed in diffuse type adenocarcinomas. We have provided clear evidence that a single mutation in the alpha-catenin gene may be a direct cause not only of the scattered properties of cells but also of signet ring cell formation in diffuse type adenocarcinoma.

Assessment of a protocol for prophylactic antibiotics to prevent perioperative infection in urological surgery: a preliminary study.

Background: The aim of the present study was to assess the usability and efficacy of our new protocol of prophylactic antibiotic use to prevent perioperative infection in urological surgery.

Anaphylaxis following administration of intravenous methylprednisolone sodium succinate in a renal transplant recipient

Abstract Methylprednisolone sodium succinate (MPS) is widely used in the management of renal transplantation. Of interest is the rare occurrence of anaphylaxis and anaphylactoid reaction to MPS. We report on a patient who developed anaphylaxis following the intravenous administration of MPS during a renal transplant operation. Intracutaneous testing was carried out with MPS and a strong positive reaction was observed. Histamine and tryptase concentrations were high after the anaphylactic reaction. Including the present case, there have been 13 reports of anaphylactic or anaphylactoid reactions to MPS, occurring in renal transplant recipients. Clinicians should be aware of the potential risk of MPS administration. If transplant patients undergo skin testing against MPS prior to transplant, they may benefit from an alternative medication with other corticosteroids. To use MPS without severe adverse reactions, lower administration rates and dosages are very important.

Radical Prostatectomy for Clinically Localized Prostate Cancer: Local Tumor Extension and Prognosis

Background: This study was performed to evaluate the frequency of local tumor extension and its effect on disease progression after radical prostatectomy.

Long-term results of definitive treatment in elderly patients with localized prostate cancer.

Background: The indication and effectiveness of definitive local treatment for prostate cancer in patients with a limited life expectancy remains to be established. This study is a retrospective analysis of the long‐term clinical outcome of elderly patients with localized prostate cancer treated by radiotherapy or a radical prostatectomy.

Micropapillary variant of transitional cell carcinoma of the bladder

Abstract A 77‐year‐old man visited the Kobe City General Hospital complaining of macroscopic hematuria. A computed tomography scan found a bladder tumor with left iliac and para‐aortic lymph node metastasis. Two courses of cisplatin, cyclophosphamide and doxorubicin chemotherapy resulted in a minimal response. Radical cystectomy and a retroperitoneal lymph node dissection with bilateral ureterocutaneostomy reconstruction were then performed. A pathological examination revealed a micropapillary variant of transitional cell carcinoma (Grade 3, pT1pN2M1). The patient died of pelvic recurrence 7 months after the initiation of chemotherapy. Peritonitis carcinomatosa and lung metastases were observed at autopsy.

Laparoscopic intracorporeal ileal conduit after laparoscopic radical cystectomy: A modified technique to facilitate ureteroenteric anastomosis

DOI: 10.1111/iju.13782 ICUD has the potential benefits of a smaller incision, reduced pain, decreased bowel exposure, reduced risk of fluid imbalance and early postoperative recovery. Indeed, ICUD is gaining popularity during RARC, but purely laparoscopic ICUD has seldom been reported because of the technical difficulty, particularly precise intracorporeal suturing. We herein describe our modified technique to facilitate ureteroenteric anastomosis during pure laparoscopic intracorporeal IC after LRC and evaluate perioperative outcomes. From 2007 to 2017, 66 patients underwent LRC with pelvic lymphadenectomy with IC diversion at three institutions (35 intracorporeal IC, 31 extracorporeal). Total intracorporeal IC began in May 2014. LRC started using a five-port, fan shaped, transperitoneal approach. After lymphadenectomy and radical cystectomy, the left ureter was delivered under the sigmoid mesocolon to the right side. A 15-cm ileal segment of the bowel was harvested as previously described during RARC. The schema of ureteroenteric anastomosis and intraoperative findings are shown in Figure 1 and Video S1. After inserting a guidewire from a 3-mm port placed just superior to the pubic symphysis, a 6-Fr single-J ureteral stent was placed in the ureter. A conduit was irrigated using a 22-Fr catheter to minimize spillage of bowel contents. A single-J ureteral stent attached to the ureter was passed through two enterotomies in the proximal conduit and 12-mm assistant port. Ureteroenteric anastomosis was carried out using a continuous running suture method comprising two running 4-0 synthetic absorbable polyglyconate sutures. The first stitch was placed on the tip of spatulation of the ureter and IC. The second stitch was placed on the end opposite to the first stitch, and both stitches were tied. Then, the short tails of the two stitches were pulled by two laparoscopic graspers inserted from the port above the pubis and assistant port. The traction of the short tails of the two sutures could adjust the suture line parallel to a laparoscopic needle holder in the surgeon’s right hand, which makes carrying out running suture easier. The long tail of the second stitch was used for the anterior part of ureteroenteric anastomosis with three or four stitches using the running suture method, and it was tied to the first stitch. The posterior part of anastomosis was inverted by pulling the short tail of both stitches, and running suture was carried out in the same manner. A 3–4-cm skin incision was made at the supraumbilical site, and the specimen was removed. As for extracorporeal IC, a 5–7-cm skin incision was made at the infraumbilical site. The isolated ileum for conduit was washed outside the incision, and ureteroenteric anastomosis was carried out using a continuous running suture method. Perioperative data were compared between the intracorporeal and extracorporeal IC groups using propensity score matching. The primary study end-point was postoperative early (within 90 days) complication rates. In total, 28 matched pairs were evaluated. No significant difference in preoperative data was found (Table S1). The operative time for intracorporeal IC diversion and ureteroenteric anastomosis was 187 31 and 74 17 min, respectively. The median total operative time in intracorporeal groups was significantly longer, but the total median blood loss significantly decreased compared with that in extracorporeal groups (560 vs 1165 mL, respectively, P < 0.001). Importantly, the postoperative early complication rate in the intracorporeal group was significantly lower than that in the extracorporeal group (39% vs 71%, P = 0.016; Table S2). Similarly, the postoperative early major complication rate (Clavien grade 3–5) tended to decrease in the intracorporeal group (7% vs 29%, respectively, P = 0.036). The details are summarized in Table S3. As for postoperative recovery of bowel function, the mean days to regular oral food intake were 4 and 7 days in the intracorporeal and extracorporeal groups, respectively (P < 0.001). The Kaplan–Meier method showed no significant difference in ureteroenteric strictures between both groups (P = 0.60; Fig. S1). Urological Notes

CLINICAL OUTCOMES OF EXTERNAL-BEAM RADIOTHERAPY COMBINED WITH NEOADJUVANT ANDROGEN DEPRIVATION THERAPY FOR HIGH-RISK PROSTATE CANCER

(Purpose) We investigated the outcome of external-beam radiotherapy (EBRT) with neoadjuvant androgen deprivation therapy (NeoADT) for high-risk prostate cancer defined by National Comprehensive Cancer Network (NCCN) guideline. (Patients and method) From 2002 to 2013, 70 patients with high-risk prostate cancer (PSA ≥20 ng/ml or clinical T stage ≥T3a, Gleason score ≥8) were treated with NeoADT and EBRT. EBRT consisted of three-dimensional conformal or intensity modulated radiotherapy with or without whole-pelvic radiation. Biochemical failure was defined according to the Phoenix definition. Biochemical progression-free survival (bPFS) and overall survival (OS) were calculated by Kaplan-Meier method, and prognostic factors for bPFS were analyzed by using the Cox proportional hazard model. (Result) The median age and initial prostate-specific antigen (PSA) level were 72 years old and 25.2 ng/ml, respectively. 43 patients had PSA level ≥20 ng/ml, 51 patients had clinical stage ≥T3a, 27 patients had Gleason score ≥8. The number of risk factors patients possessed was 1 (RiskN-1) in 31 patients, 2 (RiskN-2) in 27 patients and 3 (RiskN-3) in 12 patients. Median EBRT dose and duration of Neo ADT were 74 Gy and13.0 months, respectively. Whole-pelvic radiation was administered in 7 patients. After median follow-up of 4.8 years, biochemical and clinical failure occurred in 23 and 2 patients, respectively. No patients died of cancer. Five-year/8-year bPFS and OS were 63%/54% and 100%/91%, respectively. In multivariate analysis, three high-risk factor of NCCN guideline (PSA, clinical stage, Gleason score) did not predict outcome after EBRT independently, but RiskN (-1 vs -2, 3, HR 35.35, 95%CI 2.51-498.05, p<0.01) and pre-EBRT PSA (continuous, hazard ratio 1.31, 95%CI 1.01-1.71, p<0.05) were the significant predictors of bPFS. Five-year/8-year bPFS in RiskN-1 group and RiskN-2 or -3 group were 89%/79% and 47%/39%, respectively. Grade 3/4 adverse events (CTCAE ver4.0-JCOG) occurred in 2 patients. (Conclusion) Median dose of 74 Gy EBRT with intermediate-term NeoADT was safe and beneficial for high-risk prostate cancer. The number of risk factors and pre-EBRT PSA level were the independent prognostic factors for biochemical progression-free survival.