Sorbitol Is a Severity Biomarker for PMM2-CDG with Therapeutic Implications.

OBJECTIVE: Epalrestat, an aldose reductase inhibitor increases phosphomannomutase (PMM) enzyme activity in a PMM2-congenital disorders of glycosylation (CDG) worm model. Epalrestat also decreases sorbitol level in diabetic neuropathy. We evaluated the genetic, biochemical, and clinical characteristics, including the Nijmegen Progression CDG Rating Scale (NPCRS), urine polyol levels and fibroblast glycoproteomics in patients with PMM2-CDG. METHODS: We performed PMM enzyme measurements, multiplexed proteomics, and glycoproteomics in PMM2-deficient fibroblasts before and after epalrestat treatment. Safety and efficacy of 0.8 mg/kg/day oral epalrestat were studied in a child with PMM2-CDG for 12 months. RESULTS: PMM enzyme activity increased post-epalrestat treatment. Compared with controls, 24% of glycopeptides had reduced abundance in PMM2-deficient fibroblasts, 46% of which improved upon treatment. Total protein N-glycosylation improved upon epalrestat treatment bringing overall glycosylation toward the control fibroblasts' glycosylation profile. Sorbitol levels were increased in the urine of 74% of patients with PMM2-CDG and correlated with the presence of peripheral neuropathy, and CDG severity rating scale. In the child with PMM2-CDG on epalrestat treatment, ataxia scores improved together with significant growth improvement. Urinary sorbitol levels nearly normalized in 3 months and blood transferrin glycosylation normalized in 6 months. INTERPRETATION: Epalrestat improved PMM enzyme activity, N-glycosylation, and glycosylation biomarkers in vitro. Leveraging cellular glycoproteome assessment, we provided a systems-level view of treatment efficacy and discovered potential novel biosignatures of therapy response. Epalrestat was well-tolerated and led to significant clinical improvements in the first pediatric patient with PMM2-CDG treated with epalrestat. We also propose urinary sorbitol as a novel biomarker for disease severity and treatment response in future clinical trials in PMM2-CDG. ANN NEUROL 20219999:n/a-n/a.

Laparoscopic Non-clamping Tumor Enucleation of Renal Hilum Schwannoma in a Single Kidney: A Case Report.

A 56-year-old woman underwent laparoscopic right nephrectomy due to pyonephrosis associated with right ureteral stones. Moreover, the patient developed a brain stem hemorrhage and became bedridden. At the time of nephrectomy, a renal tumor, with a size of 24 × 24 × 20 mm, was observed in the left renal hilum; the tumor did not show contrast enhancement on computed tomography. After 3 years, the tumor gradually grew to a size of 45 × 35 × 34 mm, and therefore, laparoscopic non-clamping tumor enucleation was performed. Pathological examination confirmed a diagnosis of renal schwannoma.

Leiomyoma in Retzius' space: An unusual location.

We report the case of a 54-year-old woman who presented to our hospital with microscopic hematuria. An imaging study revealed a tumour in the Retzius' space. The tumour was surgically removed by an abdominal approach. Pathological examination revealed a leiomyoma. This case demonstrates a leiomyoma in an unusual location.

Spontaneous renal artery aneurysm rupture in a patient with neurofibromatosis type 1 without risk factors for renal artery aneurysm rupture.

Vascular abnormalities in neurofibromatosis type 1 (NF-1) are rare but sometimes fatal. We report a case of spontaneous rupture of a left renal artery aneurysm in a patient with NF-1. A 41-year-old nonpregnant normotensive woman known to have NF-1 presented to our emergency department with left flank pain. Computed tomography showed a large retroperitoneal hematoma due to left renal artery aneurysm rupture. She was treated with selective transcatheter coil embolization and fully recovered.

[Laparoscopic excision of infected urachal remnant: a case report].

A 18-year-old man presented with fever and periumbilical nodule. Computed tomography (CT) showed complicated abscess of urachal remnant and laparoscopic surgery was performed transperitoneally via 3 ports. Laparoscopic excision of urachal remnant was first demonstrated in 1992 by Neufung et al, and in Japan first case was reported in 1998 by Ohmori et al. Some cases of laparoscopic surgery for urachal remnant were reported, but the surgical techniques, including port configuration, have not been standardized. In this case, we performed laparoscopic surgery with camera port in the umbilicus and two working ports in the bilateral positions. Our port configuration may be promising in ensuring good viewing during surgery and excising urachal remnant completely including umbilicus.

Influence of hospital surgical volume of radical prostatectomy on quality of perioperative care.

PURPOSE: We investigated the relationships between hospital surgical volume, surgical outcome, care plans indicated in critical pathways and actual perioperative care using data from a nationwide survey for radical prostatectomy. MATERIALS AND METHODS: In this study, urologists from 155 hospitals in Japan cooperated in submitting the data of 4,029 patients who underwent radical prostatectomy in 2007, and the perioperative care plan in critical pathways. Of these, we analyzed data of 3,499 patients undergoing open radical prostatectomy and minimum incision endoscopic radical prostatectomy. RESULTS: Increasing hospital volume was associated with decreased proportion of open radical prostatectomy (p < 0.001). As the hospital volume increased, surgical duration was significantly shorter (p < 0.001) and bleeding volume decreased (p < 0.004). Analyses of perioperative care suggested that low-volume hospitals (<15 patients annually) were likely to have longer care than medium-volume (15-29 patients per year) or high-volume (≥30 patients per year) hospitals, and the length of actual care was prolonged in the low-volume hospitals. Multivariate logistic regression analysis suggested that the occurrence of postoperative complications was significantly associated with surgeon's volume (p = 0.004), patient age (p = 0.001), preoperative anticoagulant therapy (p = 0.045), coexistent diabetes mellitus (p = 0.009), surgical duration (p = 0.002) and bleeding volume (p < 0.001), but not hospital volume. CONCLUSIONS: Urologists in high-volume hospitals appeared to attempt new types of surgery. Hospital surgical volume was strongly associated with the surgical duration, bleeding volume and planned and actual perioperative care; however, it was not associated with postoperative complications.

[Clinical assessment of perioperative course of patients undergoing laparoscopic nephrectomy or adrenalectomy without perioperative bowel management].

Thirty-one patients underwent laparoscopic radical nephrectomy and 27 patients underwent laparoscopic adrenalectomy from January, 2005 to September, 2009 by a single surgeon authorized by the Japanese Society of Endourology and ESWL. Six patients (radical nephrectomy in 3, adrenalectomy in 3) received perioperative and 52 patients (radical nephrectomy in 28, adrenalectomy in 24) did not. The time of pneumoperitoneum, amount of blood loss, postoperative body temperature and complications revealed no obvious problems in the cases without bowel management. Perioperative bowel management is commonly applied to the patients, but without clinical evidence. Based on the present study, we concluded that bowel management may be safely omitted for laparoscopic redical nephrectomy and adrenalectomy and it may save medical cost including labor cost.

Guideline for the prevention of health care-associated infection in urological practice in Japan.

For developing the Japanese guideline for the prevention of health care-associated infection in urological practice, we surveyed the literature including standard precautions, environmental considerations in both the inpatient and outpatient settings, the management of urinary catheters, endoscopy techniques, and the disinfection and sterilization of instruments used in endoscopies and related procedures. The concept of this guideline is to show the minimum precautions that urologists and other medical professionals should observe when they work in the urological field. Standard precautions based on hand hygiene and the use of personal protective equipment should be observed in both the inpatient and outpatient settings. In the inpatient setting, the management of the toilet is important. Collecting urine should be restricted only when it is necessary to determine a patient's urinary output. The management for urinary catheter and infection are created based on the "European and Asian guidelines on management and prevention of catheter-associated urinary tract infections". In addition, we propose that nephrostomy should be carried out after maximum barrier precautions have been taken. Urinary catheters are replaced in the event of an occlusion or if there are signs that an occlusion might occur, but the same catheter cannot be left in place for more than 2 months. Regarding the handling of urine containing Mycobacterium tuberculosis, airborne infection countermeasures are unnecessary, except for the laboratory personnel. For the procedures using urological endoscopes, aseptic techniques are recommended. Endoscopes and related devices should be used by sterilization or high-level disinfection, but formaldehyde gas cannot be used.

Enhanced antitumor effect of combination intravesical mitomycin C and bacillus Calmette-Guerin therapy in an orthotopic bladder cancer model.

Intravesical immunotherapy with bacillus Calmette-Guerin (BCG) is currently the most successful adjuvant agent for the treatment and/or prophylaxis of non-muscle-invasive bladder cancer (NMIBC). However, NMIBCs recur in 60-70% of cases and 30% of these recurrent tumors present with a higher grade and more invasive properties. Patients that do not respond to intravesical BCG therapy are considered to be a challenge for urologists. Thus, novel conservative possibilities should be explored. To test the efficacy of a novel therapeutic approach, we examined the antitumor effect of combination therapy by intravesical administration of mitomycin C (MMC) plus BCG, infusing the two drugs simultaneously, in an orthotopic bladder cancer model. Intravesical BCG and MMC administration showed a dose-dependent survival (n=8 per group). The combination of MMC and BCG provided a significant survival advantage compared to the BCG-alone (p=0.035) and MMC-alone groups (p=0.040) (n=8 per group). The group with combined MMC/BCG exhibited a survival period similar to that achieved with an amount eight times higher that of BCG (n=10 per group). Ki-67 labeling index of cancer cells, showing tumor proliferation, was significantly lower in the combined group compared to the BCG-alone (p<0.05), MMC-alone (p<0.01) and control groups (p<0.01). No difference was detected between the combined group and the BCG-alone group with regard to CD3, T-cell infiltration and CD68 macrophage activity. The combined MMC/BCG treatment decreased the tumor appearance rate, improved the survival period and reduced the cellular proliferation rate in tumors compared to the BCG-alone treatment. The results suggest that the combined intravesical MMC/BCG treatment induced an enhanced antitumor effect against bladder tumors. The combined MMC/BCG treatment also showed a survival period similar to that achieved using a dose eight times higher of BCG-alone.

Enhanced antitumor effect of coincident intravesical gemcitabine plus BCG therapy in an orthotopic bladder cancer model.

OBJECTIVES: To evaluate the antitumor effect of the coincident administration of intravesical gemcitabine (Gem) plus bacillus Calmette-Guérin (BCG) in an orthotopic bladder cancer model. METHODS: We evaluated the cytotoxic effect of gemcitabine against MBT-2 cells in vitro. Orthotopic tumors were established by implanting MBT-2 cells into the bladder of syngeneic female C3H mice. Intravesical Gem administration was evaluated at various doses: 0 mg (control); 1, 2, 4, and 8 mg (n = 8 for each group). Next, a comparative evaluation of tumor growth among the control, Gem-alone, BCG-alone, and combined Gem + BCG groups was performed (n = 16 for each group). Therapy was administered at 3-day intervals starting on day 5 and repeated 6 times. To evaluate the proliferative activity among the groups, Ki-67 immunostaining of the tumor was performed. RESULTS: Gemcitabine exhibited a dose-dependent antitumor effect. Of the 8 mice in each group treated with a dose of 0, 1, 2, 4, or 8 mg of Gem, 1, 4, 4, 4, 5, and 4 mice failed to develop tumors and survived, respectively. The combination of Gem + BCG (54.1 ± 9.4 days) provided a significant survival advantage compared with BCG-alone (39.0 ± 16.4 days) (P = .02). Ki-67 expression, representing tumor proliferation, was significantly lower in the combined Gem + BCG group than in the BCG-alone group (P < .01). CONCLUSIONS: Our results suggest that intravesical Gem + BCG treatment induces an enhanced antitumor effect against bladder tumors.

Leiomyoma of the bladder presenting as acute urinary retention in a female patient: urodynamic analysis of lower urinary tract symptom; a case report.

BACKGROUND: Most bladder tumors are derived from the urothelium. Benign mesenchymal tumors are rare. Leiomyoma of the bladder is the most common benign neoplasm. We present a case of leiomyoma of the bladder presenting with acute urinary retention in a female patient and report on the post-operative change in urodynamic findings. To our knowledge, few cases of this kind have been reported. CASE PRESENTATION: A 56-year-old woman presented with acute urinary retention. Evaluations including ultrasound, magnetic resonance imaging, cystoscopy, and urodynamics contributed to a diagnosis of leiomyoma of the bladder. Various medications were ineffective for solving her lower urinary tract symptoms; therefore, a transurethral resection was performed. The final pathological report was leiomyoma. After the operation, her symptoms resolved; this improvement was confirmed by an urodynamic analysis. The postoperative urodynamics demonstrated a lower frequency of detrusor overactivity during filling cystometry and an increase in the uroflow rate, with reduced detrusor pressure in a pressure flow study. CONCLUSIONS: Leiomyoma of the bladder can cause female outlet obstruction. A review of the literature and disease management is discussed.

Impact of hospital volume on postoperative complications and in-hospital mortality after renal surgery: data from the Japanese Diagnosis Procedure Combination Database.

OBJECTIVES: Previous studies on the relationship between nephrectomy volume and outcomes focused mainly on operative mortality. Little is known about the association between operative volume and postoperative complications. This study analyzed the influence of hospital volume on postoperative complications and in-hospital mortality after nephrectomy or nephroureterectomy. METHODS: Using the Diagnosis Procedure Combination database in Japan, 7988 patients undergoing nephrectomy or nephroureterectomy between July and December in 2006 and 2007 were identified. The cases were divided into low (≤26/y), medium (27-64), or high (≥65) hospital volume groups. Logistic regression analyses were performed to model the concurrent effects of hospital volume and other factors on postoperative complications and in-hospital mortality. RESULTS: In-hospital mortality was 0.84%. The overall postoperative complication rate was 7.4%. Factors associated with mortality or morbidity were age, hypertension, chronic lung diseases, cardiac diseases, chronic renal failure, and duration of anesthesia. Video-assisted surgery showed a significantly lower rate of mortality (odds ratio [OR], 0.28; P <.01) and postoperative complications (OR, 0.47; P <.01) than open surgery. The difference of mortality between high and low-volume groups was not significant (0.5% vs 1.0%) (OR, 0.48; P = .089). Although higher hospital volume was associated with fewer postoperative complications (OR, 0.72; P = .014), the difference was slight (7.1% vs 7.8%). CONCLUSIONS: Less comorbidity and invasive surgery and shorter anesthesia were associated with lower mortality and morbidity after renal surgery. Despite volume disparities, the magnitude of difference was only 0.7% in complications and 0.5% in mortality.

[A case of retroperitoneal Mullerian cyst resected laparoscopically].

A 67-year-old female patient had a cystic mass, 6 cm in diameter, which was incidentally detected on the dorsal side of the cecum in the retroperitoneum. A laparoscopic tumor excision was performed. Microscopically, the majority of the cystic wall consisted of Mullerian type serous epithelium, partially including the columnar epithelium containing round nuclei and mucin production. The columnar epithelium was similar to the uterocervical epithelium, and there was proliferation of dense collagen fibers resembling ovarian stroma under the epithelium. These microscopic findings were consistent with ovarian seromucinous cystadenoma. Therefore, the cyst was diagnosed to be a retroperitoneal Mullerian cyst. This is the 15th case of a cyst of this type reported and is the first case in which a laparoscopic excision was performed.

Influence of hospital and surgeon volumes on operative time, blood loss and perioperative complications in radical nephrectomy.

OBJECTIVES: We conducted a nationwide multi-center survey using medical record-based data to investigate the relationship between hospital/surgeon volumes and various outcomes, including operative time, volume of blood loss, and incidence of perioperative complications, in radical nephrectomy for renal cell carcinoma. METHODS: We investigated a total of 1704 patients who underwent radical nephrectomy at 461 hospitals in Japan between November 2006 and February 2007. The association between hospital/surgeon volumes and operative time, volume of blood loss, and incidence of perioperative complications were independently analyzed using multivariate regression analysis against age, gender, operation site, cancer stage, serum creatinine levels, comorbid conditions, and surgical technique (open surgery or minimally invasive surgery). RESULTS: Neither hospital volume nor surgeon volume was a significant predictor of operative time or volume of blood loss. We did not identify any association between hospital volume and perioperative complications. High-volume (> 100) surgeons were unlikely to have perioperative complications compared to low-volume (< 20) surgeons, but the relation was not significant (odds ratio, 0.50; 95% confidence intervals, 0.14-1.87; P = 0.30). CONCLUSIONS: Volume-outcome relationships were not confirmed for radical nephrectomy. According to our study, the justification of regionalizing radical nephrectomy to centers of excellence is not yet clear.

Suppressive action of pituitary adenylate cyclase activating polypeptide (PACAP) on proliferation of immature mouse Leydig cell line TM3 cells.

We aimed in the current study to understand the participation of PACAP in stage-specific Leydig and Sertoli cell functions. For this purpose, clonal cell lines TM3 (Leydig) and TM4 (Sertoli) cells, derived from the testis of immature BALB/c mice, were used. PACAP-specific receptors were detected in TM3 cells, but not in TM4 cells, which were characterized as PAC1 (type I) receptors. Stimulation of cAMP accumulation and testosterone secretion were observed in TM3 cells during 1-2 h treatment with PACAP38 (10(-10)-10(-7) M) or PACAP27 (10(-11)-10(-7) M). After around 10 h treatment with 10(-11)-10(-7) M PACAP38 or PACAP27, proliferation of TM3 cells was suppressed in time- and dose-dependent manners, which was confirmed by real-time cell electronic sensing (RT-CES) system and phase-contrast microscopy. At 6 h after the addition of PACAP38, the percent cell population in G(2)/M phases increased significantly, while that in S phase showed significant decrease with little change in G(0)/G(1) phases. The results revealed that PACAP exerts, in addition to early stimulatory effect on cAMP formation-steroidogenesis, sustained suppressive effect on cell proliferation in TM3 cells by controlling progression of the cell cycle. The suppressive action of PACAP on proliferation in TM3 cells supports the stage-specific participation of the peptide in differentiation of immature mouse Leydig cells.

[The use of the PlasmaKinetic TUR system in the treatment of benign prostate hyperplasia: results of 1-year follow up].

INTRODUCTION AND OBJECTIVE: The goal of this study was to evaluate the efficiency of the PlasmaKinetic (PK) system by comparing the preoperative and postoperative results in patients with benign prostate hyperplasia (BPH) treated in this hospital. METHODS: From June 2004 to November 2006, the PK system was utilized for 46 cases of TUR-P in this Hospital. The patients International prostate symptom score (IPSS), QOL score, uroflowmetry, measurement of residual urine amount and ultrasonography were compared before and after the surgery (first month, third month and first year). In addition, the operation times, urethral catheterization times, preoperative and postoperative hemoglobin and serum sodium values of the patients were compared before and after the operations. RESULTS: At 1 and 3 months and 1 year, the IPSS decreased from 28.2 +/- 7.4 to 6.1 +/- 5.9, 2.7 +/- 3.5 and 6.6 +/- 5.3, respectively. The QOL score, decreased from 5.4 +/- 1.0 to 0.9 +/- 1.2, 0.6 +/- 0.9 and 1.3 +/- 1.1, respectively. The maximum urinary flow increased from 3.7 +/- 4.0 ml/s to 19.5 +/- 9.6, 17.9 +/- 7.3 and 18.7 +/- 9.9 ml/s, respectively. The post void residual urine decreased from 104.8 +/- 83.6 ml to 19.4 +/- 25.0, 11.1 +/- 24.7 and 17.9 +/- 28.5 ml, respectively. CONCLUSIONS: Acceptable outcomes with normal recovery from TUR-P were obtained using the PK system.

[Clinical importance of guideline for decontamination of endoscopes in urological field: verification of 3 processes].

UNLABELLED: Clinical guideline for decontamination of endoscopes in urological field has not been provided, although endoscopic examination should be done in aseptic circumstance. MATERIAL AND METHOD: From decontamination processes, following 3 points were selected for verification: 1) Volume of residual water in flexible scope after rinsing, estimated by weight change. 2) Concentration of eluted disinfectant from flexible scope after standard rinsing procedure for gastrointestinal endoscope. 3) Observation of possible damage of telescope, caused by repeat autoclaving. RESULTS: Wet condition of flexible scope could be suspected in 60 hours in room temperature. Eluted disinfectants were detected, but in harmless level. Repeated autoclaving merely caused minor damage, which does not interfere clinical use. CONCLUSION: We obtained a couple of evidences with cautions in decontamination processes for endoscopes. Urgent requirement of standardization in this field should be discussed widely.

Testicular seminoma after the complete remission of extragonadal yolk sac tumor : a case report.

BACKGROUND: Between 2% and 5% of malignant germ-cell tumors in men arise at extragonadal sites. Of extragonadal germ cell tumors, testicular carcinoma in situ (CIS) are present in 31-42% of cases, and CIS are reported to have low sensitivity to chemotherapy in spite of the various morphology and to have a high likelihood of developing into testicular tumors. A testicular biopsy may thus be highly advisable when evaluating an extragonadal germ cell tumor. CASE PRESENTATION: A 36-year-old man was diagnosed as having an extragonadal non-seminomatous germ cell tumor, that was treated by cisplatin-based chemotherapy, leading to a complete remission. In the meantime, testicular tumors were not detected by means of ultrasonography. About 4 years later, a right testicular tumor was found, and orchiectomy was carried out. Microscopically, the tumor was composed of seminoma. CONCLUSIONS: We herein report a case of metachronous occurrence of an extragonadal and gonadal germ cell tumor. In the evaluation of an extragonadal germ cell tumor, a histological examination should be included since ultrasonography is not sufficient to detect CIS or minute lesions of the testis.