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Vaginal reconstruction using the posterior vaginal wall is required following radical cystectomy in women with resection of the uterus, adnexa, and anterior vaginal wall. Roll closure and clamshell closure are two widely known techniques. Of these, clamshell closure is recommended because roll closure has a high likelihood of breakdown or a resultant canal that is too narrow for sexual intercourse. In clamshell closure, however, folding the posterior vaginal wall anteriorly can be difficult. Therefore, we devised Mercedes-Benz closure, in which the vaginal wall is sutured from three directions to form a Mercedes-Benz shape, for anastomosis without tension on the vaginal wall. The present study was performed to investigate the efficacy of this alternative surgical technique for vaginal reconstruction.Twenty-six patients who underwent vaginal reconstruction following robot-assisted radical cystectomy were divided into two groups: 15 underwent clamshell closure and 11 underwent Mercedes-Benz closure. The patients' characteristics and surgical outcomes were compared between the two groups.There were no significant differences in clinical characteristics, including age, body mass index, and prior abdominal surgery between the two groups. The median vaginal reconstruction time tended to be longer in the Mercedes-Benz closure group than in the clamshell closure group (35.0 vs. 27.0 min, p = 0.102). No complications associated with vaginal reconstruction were identified.The surgical outcomes were comparable between Mercedes-Benz closure and clamshell closure. If vaginal reconstruction with clamshell closure is difficult, Mercedes-Benz closure is a valuable alternative technique.

The micropapillary variant of urothelial carcinoma (MPUC) is an aggressive form of urothelial carcinoma with high metastatic potential and a poor prognosis. Although various therapies have been reported, there is still no established treatment strategy for MPUC due to its rarity. The incidence of urinary tract malignancies is higher in patients undergoing hemodialysis (HD) than in healthy individuals. Here, we report the case of an 82-year-old man on HD with end-stage kidney disease who visited our hospital for macrohematuria. Cystoscopy followed by computed tomography and urine cytology revealed a sessile papillary tumor around the left bladder wall. We performed transurethral resection of the bladder tumor. Based on histopathological and imaging findings indicative of clinical-stage T3N0M0 MPUC, we performed radical cystectomy. Histopathology revealed a pathological stage T4aN0M0 MPUC. Two months after the cystectomy, the patient complained of constipation and painful defecation due to local recurrence and rectal invasion. While colostomy was performed to improve defecation 3 months after cystectomy, he did not receive any chemotherapy due to his progressively worsening general condition. Six months after cystectomy, he died following rapid metastases. Our findings, in this case, confirm that bladder cancer in HD patients tends to be pathologically more advanced. Therefore, regular screening is recommended for its early detection in HD patients.

Introduction The nested variant of urothelial carcinoma is rare and shows poor prognosis. We report a case of complete response to pembrolizumab in recurrent nested variant. Case presentation A 50-year-old man visited another hospital with hematuria and weight loss. Clinical stage T4aN0M0 bladder cancer and acute renal failure were diagnosed. He was referred to our hospital and underwent radical cystectomy. Histological examination showed pathological stage T4aN2 nested variant of urothelial carcinoma. He received 3 cycles of gemcitabine and carboplatin adjuvant chemotherapy. However, para-aortic lymph node metastasis appeared 7 months after cystectomy. He received pembrolizumab as systemic chemotherapy. After 10 cycles, the lesion remained undetectable and we evaluated the response as complete. He has received 18 cycles in total and no recurrences or metastases have been observed. Conclusion Pembrolizumab may offer effective treatment for nested variant of urothelial carcinoma.

Introduction Emphysematous cystitis is a rare pathology characterized by gas bubbles within the bladder wall and lumen from gas-producing bacteria. Sepsis-associated purpura fulminans is also rare and shows poor clinical outcomes. Case presentation A 73-year-old man was hospitalized at a nearby hospital due to chronic subdural hematoma, symptomatic epilepsy, and diabetes mellitus. He was transferred to our hospital with fever, low blood pressure, and cyanosis of the legs, and was diagnosed with septic shock due to emphysematous cystitis with purpura fulminans. He underwent intensive treatment, including retroperitoneal drainage. Urine culture was positive for Citrobacter freundii. His general condition gradually improved and diffuse air decreased after surgery, but progressive purpuric skin necrosis became evident on the legs, which could not be salvaged. He died on the 25th hospital day. Conclusion Sepsis-associated purpura fulminans caused by emphysematous cystitis shows a very poor prognosis irrespective of intensive treatment, including retroperitoneal drainage.

The influence of the console surgeon on the feasibility and outcome of various robot-assisted surgeries has been evaluated. These variables may be partially affected by the skills of the patient-side surgeon (PSS), but this has not been evaluated using objective data. This study aimed to describe the surgical techniques of the PSS in robot-assisted radical cystectomy (RARC) and intracorporeal ileal conduit (ICIC) urinary diversion and objectively examine the changes in surgical outcomes with increasing PSS experience. During a 3-year period, 28 men underwent RARC and ICIC urinary diversion. Clinical characteristics and surgical outcomes were compared between patients who underwent surgery early (first half group) or late in the study period (second half group). The pre-docking incision enabled easy specimen removal. The glove port technique widened the working space of the PSS. The stay suture allowed the PSS to control the distal portion of the conduit, facilitating the passage of the ureteral stents. During stoma creation, pneumoperitoneum pressure was lost by opening the abdominal cavity. To overcome this problem, the robotic arm was used to lift the abdominal wall to maintain the surgical field and facilitate the PSS procedure. Compared with the first half group, the second half group had significantly shorter times for urinary diversion (202 min vs 148 min, p p p

To compare the postoperative outcomes of robot-assisted partial nephrectomy when only the inner layer is sutured (single-layer technique with soft coagulation) with those when sutures are placed in the inner and outer layers (double-layer technique) in patients with and without complex renal tumors.This retrospective three-institution study included 371 patients with renal tumors who underwent robot-assisted partial nephrectomy with a double-layer technique or a single-layer technique with soft coagulation. Tumors that were cT1b, completely embedded, located in the renal portal, or had a RENAL score of ≥10 were considered complex. Relevant data were collected from hospital records. Propensity score matching was performed to minimize selection bias.Propensity score matching created 83 patient pairs with non-complex tumors and 32 with complex tumors. Regardless of tumor complexity, there was no significant difference in operation time, console time, warm ischemia time, positive surgical margin rate, or length of hospital stay between the double-layer and single-layer groups. Although Clavien-Dindo grade I-II urinomas not requiring intervention were significantly more common in the single-layer group regardless of tumor complexity, there was no significant between-group difference in the rate of decline in renal function or grade III-IV complications.Single-layer suturing with soft coagulation achieves renal function and perioperative outcomes comparable to those of double-layer suturing regardless of complexity.

The complications of ileal conduit urinary diversion were reported to be urinary tract infections, bowel obstruction, and delayed wound healing, but ileal conduit-enteric fistula is rare. We report a case of ileal conduit-enteric fistula after robotic intracorporeal ileal conduit urinary diversion. An 81-year-old man with muscle-invasive bladder cancer underwent robot-assisted radical cystectomy and intracorporeal ileal conduit urinary diversion. Twenty-two days after the surgery, we identified the presence of fecaluria. Loopography revealed an ileal conduit-enteric fistula. He underwent conservative treatment with fasting and intravenous hyperalimentation. Loopography was performed 48 days after the surgery. However, the fistula remained. Therefore, fistula closure surgery was performed 51 days after the surgery. Here we review the characteristics of 4 ileal conduit-enteric fistula cases reported in Japan.

(Objectives) While robot assisted radical cystectomy (RARC) has been associated with improved perioperative outcomes such as blood loss, hospital stay, and improved convalescence, much of the criticism has been attributable to the longer operative time. Opinions are divided regarding whether intracorporeal urinary diversion (ICUD) or extracorporeal urinary diversion (ECUD) should be performed. The aim of this study is to evaluate the utility of RARC and ICUD by comparing with the conventional method. (Patients and methods) From December 2014 to July 2018, 14 patients underwent laparoscopic radical cystectomy (LRC) and 16 patients underwent RARC at our institution. Among the 30 patients, 23 underwent ileal conduit or orthotopic bladder; these patients were divided into two groups: an ICUD patient group (n=10) and an ECUD patient group (n=13). Treatment outcomes were compared between groups. (Results) Compared to patients who underwent LRC those treated with RARC had older (75 vs. 67, P=0.031). There was a trend of high-risk cases (American Society of Anesthesiologists' physical status classification ≥3) more frequently (31.3% vs. 7.1%, P=0.176). Patient treated with RARC had less blood loss (150 vs. 544 ml, P=0.003). There was no significant difference in the intra- and postoperative complication rates (12.5% vs. 21.4%, P=0.642). Compared to patients who underwent ECUD, those treated with ICUD included a longer operative time for urinary diversion (222 vs. 181 minutes, P=0.007) but less maximal incision length without perineal incision (3.0 vs. 6.0 cm, P=0.002). (Conclusions) Our data suggests that RARC is a safe procedure with potential advantages in terms of reduced blood loss. ICUD has longer operative time but is a procedure with excellent cosmetic results.

Emphysematous cystitis is a rare disease involving infection caused by gas-producing bacteria is characterized by air storage in the bladder wall and lumen. Approximately 90% of the affected cases are treated using medical therapy alone, and approximately 10% require combined surgical treatment. Here we report a case of emphysematous cystitis with septic shock that could be treated using multimodal therapy with retroperitoneal drainage. A 76-year-old woman was hospitalized at a nearby hospital owing to lumbar compression fracture. She was transferred to our hospital owing to altered consciousness and low blood pressure. She was diagnosed with emphysematous cystitis, and conservative treatment was performed using an indwelling bladder catheter and by administering antibiotics or vasopressors. The patient had septic shock; hence, retroperitoneal drainage was performed. After surgery, the patient's general condition improved. In this study, we review the characteristics of five cases of emphysematous cystitis requiring surgical treatment in Japan.

Gender difference in obesity-associated cardiovascular complication could be derived from divergent chronic inflammation. We evaluated depot- and gender-specific regulation of the innate immune system in human adipose tissues. Pair samples were obtained from subcutaneous (SAT) and visceral adipose tissue (VAT) during elective surgery (Male: 35; Female: 27). Expressions of pro- and anti-inflammatory adipocytokines were evaluated by semi-quantitative qPCR. Adipose cell-size distribution was obtained from tissue samples fixed in osmium tetroxide and analyzed by Beckman Coulter Multisizer. Levels of adiponectin were higher in SAT and VAT of female than those of male (P

Although patients on long-term hemodialysis frequently develop renal cell carcinoma, mucinous tubular and spindle cell carcinoma (MTSCC) is rare in incidence. Here, we report a case of MTSCC occurring in a patient under hemodialysis. The patient was a 72-year-old man with end stage renal failure due to diabetic nephropathy. Hemodialysis was initiated in 2003. He presented with macrohematuria. Contrastenhanced computed tomography (CT) revealed a right renal tumor. Laparoscopic right nephrectomy was performed accordingly in June 2017. Pathologically, the tumor was diagnosed as MTSCC. Six months after the surgery, the patient remains free of recurrence and metastasis. Here we review the characteristics of 5 MTSCC cases in patients on hemodialysis reported in Japan.

For anesthetic management during renal transplantation, it is necessary to maintain the blood flow and function of the transplanted kidney by performing massive fluid management and stabilizing blood pressure. We report anesthetic management for renal transplantation with a less-invasive circulatory monitoring system (Edwards Life Sciences Co., Ltd., Irvine, California, U.S.A.). In November 2010, renal transplantation was started in our hospital, and performed in 6 patients. In the first patient, fluid/circulatory management was conducted by connecting a standard arterial line and a standard central venous (CV) line. In the second patient, a FloTrac(TM) system and a standard CV line were used. In the third patient, a standard arterial line and a PreSep(TM) CV Oximetry Catheter were used. In the fourth and fifth patients, a FloTrac(TM) and a PreSep(TM) were used. In the latest patient, FloTrac(TM) and PreSep(TM) were connected to an EV1000(TM) Clinical Platform for fluid/circulatory management. The establishment of high-visibility monitors was useful for evaluating the condition and confirming the effects. As there are marked changes in hemodynamics, the CV pressure, which has been used as a parameter of fluid management, is not reliable in renal failure patients with a high incidence of cardiovascular complications. Advances in noninvasive circulatory monitoring with dynamic indices may improve the safety of anesthetic management during renal transplantation.

Recent accumulating evidence suggests that innate immunity is associated with obesity-induced chronic inflammation and metabolic disorders. Here, we show that a Toll-like receptor (TLR) protein, radioprotective 105 (RP105)/myeloid differentiation protein (MD)-1 complex, contributes to high-fat diet (HFD)-induced obesity, adipose tissue inflammation, and insulin resistance. An HFD dramatically increased RP105 mRNA and protein expression in stromal vascular fraction of epididymal white adipose tissue (eWAT) in wild-type (WT) mice. RP105 mRNA expression also was significantly increased in the visceral adipose tissue of obese human subjects relative to nonobese subjects. The RP105/MD-1 complex was expressed by most adipose tissue macrophages (ATMs). An HFD increased RP105/MD-1 expression on the M1 subset of ATMs that accumulate in eWAT. Macrophages also acquired this characteristic in coculture with 3T3-L1 adipocytes. RP105 knockout (KO) and MD-1 KO mice had less HFD-induced adipose tissue inflammation, hepatic steatosis, and insulin resistance compared with wild-type (WT) and TLR4 KO mice. Finally, the saturated fatty acids, palmitic and stearic acids, are endogenous ligands for TLR4, but they did not activate RP105/MD-1. Thus, the RP105/MD-1 complex is a major mediator of adipose tissue inflammation independent of TLR4 signaling and may represent a novel therapeutic target for obesity-associated metabolic disorders.

Objectives: To compare perioperative outcome of transperitoneal and retroperitoneal approaches during laparoscopic radical nephrectomy (LRN) and to identify selection criteria for each approach. Methods: Over a 7-year period, 100 consecutive patients (median age 62 years, range 20–80) underwent LRN for a renal tumor with clinical stage T1a–T3a. The first choice approach was retroperitoneal. The transperitoneal approach was chosen in selected cases based on tumor characteristics. Thirty-three patients underwent the transperitoneal approach, and 67 had the retroperitoneal approach. Perioperative parameters including operative time, blood loss and complications and pathology data were retrospectively analyzed. Results: Overall, 33 transperitoneal laparoscopic radical nephrectomies (TLRN) and 67 retroperitoneal laparoscopic radical nephrectomies (RLRN) were carried out. There was a statistically significant difference between the two groups in terms of size (5.3 vs 3.0 cm, P

Objectives: We retrospectively evaluated our experience with a relatively uncommon procedure, the laparoscopic ureterolithotomy, for the treatment of ureteral stones. Methods: Between April 2002 and October 2006, a total of 74 patients (56 males, 18 females) with upper (54 cases), middle (18 cases) and lower (two cases) ureteral stones underwent laparoscopic ureterolithomy. The mean age was 39.4 years (range, 19–74). The stones were in the right side in 44 cases (59.5%) and in the left side in 30 (40.5%) cases. The mean stone size was 1.8 cm (range 1.5–2.8). The procedure was retroperitoneal in 66 cases (89.2%) and transperitoneal in eight (10.8%) cases. Laparoscopic guided flexible ureterorenoscopic extraction of kidney stone was carried out in one case as an adjuvant procedure. The ureter was stented and not sutured in 64 cases (86.5%). Results: The procedure was successfully completed in 94.6% of cases and an open conversion was carried out in four (5.4%) patients. The mean operative time was 58.7 min, and the mean blood loss was 90.6 mL. No major complications were encountered. Prolonged urinary leakage occurred in one patient. The mean hospital stay was 6.4 days. One patient developed ureteral stricture during follow up and was treated by endoscopic dilatation and stenting. Conclusion: In our experience laparoscopic ureterolithotomy represents a safe and effective treatment option for ureteral stones either as primary for large impacted stones or as a salvage procedure after failed shock wave lithotripsy or ureteroscopy. This procedure fulfills the advantages of minimal blood loss and analgesia requirements, good cosmetic appearance, short hospital stay and convalescence period.

We evaluated the safety and efficacy of laparoscopic nephropexy for symptomatic nephrotosis.Between May 2000 and December 2005, 6 women (mean age, 43.1 years) underwent laparoscopic nephropexy of 8 kidneys (6 right, 2 left). Mean body mass index was 19.6 kg/m(2). Two patients displayed ureteropelvic junction obstruction (UPJO). Preoperative evaluation was performed by intravenous urography (IVU) and isotope renography in both the supine and erect positions. Four patients (6 renal units) underwent retroperitoneoscopic nephropexy, with a dismembered pyeloplasty in 1 patient (1 renal unit). The transperitoneal approach was performed in 2 patients, the first case and another with UPJO due to an aberrant vessel. The kidney was mobilized, then fixed to the back muscles with nonabsorbable sutures.Mean operative time was 139.4 minutes (range, 95-200), and mean blood loss was 30 mL (range, 10-60). No perioperative complications were encountered. Mean hospital stay was 6.4 days. Postoperative IVU and isotope renography correctly confirmed a fixed kidney and no obstruction in the UPJO cases. All patients reported a symptomatic improvement during follow-up (range, 11-81 months).As pain is the presenting symptom in these cases, a laparoscopic approach seems to represent the gold standard for treatment owing to low morbidity and good cosmetic results.

No adequate serum predictive biomarker currently exists, which can identify the activity of renal cell carcinoma (RCC). We investigate the association of serum hepatocyte growth factor (HGF) and serum vascular endothelial growth factor (VEGF) levels with clinicopathologic parameters in untreated clear cell RCC patients. We measured serum levels of HGF and VEGF in 45 patients with untreated clear cell RCC and 45 healthy controls using an enzyme-linked immunosorbent assay (ELISA). Patients with clear cell RCC had significantly higher serum HGF and VEGF concentrations than healthy subjects : median, 1070.7 versus 728.3 pg/ml (p1150 pg/ml) was significantly reduced compared to patients with low serum HGF concentrations (p=0.0044). In patients with nuclear grade 2 or high stage RCC, the higher serum HGF group exhibited significantly lower cause-specific survival (p= 0.0087 and p

Gender difference in obesity-associated cardiovascular complication could be derived from divergent chronic inflammation. We evaluated depot- and gender-specific regulation of the innate immune system in human adipose tissues. Pair samples were obtained from subcutaneous (SAT) and visceral adipose tissue (VAT) during elective surgery (Male: 35; Female: 27). Expressions of pro- and anti-inflammatory adipocytokines were evaluated by semi-quantitative qPCR. Adipose cell-size distribution was obtained from tissue samples fixed in osmium tetroxide and analyzed by Beckman Coulter Multisizer. Levels of adiponectin were higher in SAT and VAT of female than those of male (P 0.001 and P = 0.011, respectively). NLRP3, IL1β-IL18, TLR2 were comparable in SAT and VAT between genders. However, TLR4 and TLR9 were increased in female SAT and VAT and HMGB1 in female VAT. Levels of adiponectin were not correlated with mean diameter of adipocyte (φ, μm) in SAT and VAT of male, but negatively well correlated in those of female (r = -0.392 and r = -0.616). Such negative correlations were also observed between levels of TLR2, TLR4, and HMGB1 and φ in female. Levels of NLRP3 and IL1β were positively correlated with φ in male, but not in female. In conclusion, Innate signals were differentially expressed in male and female adipose tissues, suggesting that the depot- and gender-specific signals could be related to gender difference in chronic inflammation. © 2016 BioFactors, 42(4):397-406, 2016.

TRAIL/Apo2L is a pro-apoptotic cytokine that is capable of inducing apoptosis in a wide variety of cancer cells but not in normal cells. Among various molecular strategies by which cancer cells evade apoptosis, PI3K/Akt signaling represents a dominant survival pathway. In this report, we investigated the role of PI3K/Akt pathway in TRAIL-induced apoptotic death in human bladder cancer cells. We observed that RT4 cells had very low level of constitutively active Akt and were sensitive to TRAIL, whereas UM-UC-3 and T24 cells had higher levels of constitutively active Akt and were resistant to TRAIL. Downregulation of constitutively active Akt by PI3K inhibitors, wortmannin and LY294002, reversed cellular resistance to TRAIL. However, transfecting constitutively active Akt into RT4 cells increased Akt activity and inhibited TRAIL-induced apoptosis. These results suggest that elevated Akt activity protects UM-UC-3 and T24 cells from TRAIL-induced apoptosis, and the PI3K/Akt signaling might inhibit apoptotic signals. Thus, the modulation of Akt activity by combining pharmacological drugs or genetic alterations of the Akt expression could induce cellular responsiveness to TRAIL and PI3K/Akt signaling pathway could serve as a novel target for therapeutic intervention in bladder cancer.

Aim: Laparoscopic adrenalectomy is currently indicated for biochemically and clinically functional adrenal tumors and potentially malignant tumors of the adrenal glands. Non-functional adenomas greater than 5 cm in diameter of the adrenal gland are generally considered to represent potentially malignant tumors. The present study shows indications of laparoscopic adrenalectomy for non-functional adrenal tumors with hypertension in a retrospective fashion. Methods: Between 1994 and 2004, 110 laparoscopic adrenalectomies were performed at Tokushima University Hospital. All 110 patients underwent detailed endocrinological examination before surgery. Medical and operative records of these 110 patients (57 men, 53 women), including operative parameters, histopathological findings and pre- and postoperative hypertension, were reviewed. Forty-five patients underwent laparoscopic adrenalectomy for non-functional adrenal tumors, and [131I]6β-iodomethyl-19-norcholest-5(10)-en-3β-ol (NP-59) scintigraphy was performed for patients with preoperative hypertension. Results: Mean patient age was 55.0 years (range, 22–77 years). Mean maximum tumor diameter was 42 mm (range, 20–105 mm). All adrenal tumors were removed successfully by laparoscopic surgery. Hypertension was postoperatively improved in seven of the 11 patients with preoperative hypertension, without subclinical Cushing syndrome. Importantly, all patients who improved hypertension after adrenalectomy displayed strong accumulation in adrenal tumors with visualization of the contralateral gland on NP-59 scintigraphy. Conversely, blood pressure did not improve in four patients for whom scintigraphy yielded negative results. Conclusions: The indication of laparoscopic adrenalectomy for non-functional adrenal tumors is generally considered for lesions more than 5 cm diameter. However, the present study suggests that laparoscopic surgery should be considered even in patients with tumors less than 5 cm in diameter, if both hypertension and accumulation in tumors on NP-59 scintigraphy are present.

Background: The flexible ureterorenoscope (URS) and associated devices have developed rapidly. However, despite its therapeutic benefits, URS may be associated with some complications. To the best of our knowledge, there are no studies discussing the complications of flexURS during the learning curve. Methods: A retrospective review of the records of patients who underwent flexURS from January 2005 to June 2013 was performed. To compare the complications after the introduction of flexURS, patients were divided into four groups based on the surgeon's training experience, that is, based on the number of cases performed by the surgeon. A total of 219 cases underwent flexURS. Groups 1, 2, 3, and 4 included 35, 50, 50, and 84 cases, respectively. The complications were classified using the Clavien system (I-IV). Results: The mean operation time and stone-free rate were significantly different (p < 0.001, p = 0.013, respectively). The total complication rates were 13.6, 10, 8.3, and 3.2%, respectively (p = 0.068). The more the surgeon's experience, the less was the complication rate. Despite our best efforts, the incidence of urosepsis was not reduced (p = 0.902). Conclusions: To reduce severe complications, it is necessary to have performed about 100 cases. Increased surgeon experience tended to decrease the risk of severe complications, but the incidence of urosepsis was not reduced.

Introduction : We evaluated changes in levels of prostate-specific antigen (PSA) and testosterone following discontinuation of long-term hormone therapy for non-metastatic prostate cancer. Patients and Methods : Treatment was discontinued in 31 patients with non-metastatic prostate cancer (clinical stage B-C) after≧5 years of hormone therapy, during which time PSA level had been maintained less than 0.5 ng/ml. PSA and testosterone levels were measured after discontinuation of therapy. PSA>4.0 ng/ml was defined as PSA relapse in this study. Results : Mean age at discontinuation of hormone therapy was 78.7 years (range, 66-90). Mean duration of follow-up after discontinuation of therapy was 25.5 months. PSA non-relapse rate was quite high (87.1%). 4 of the 31 patients showed PSA relapse, after 12-24 months. Testosterone level exceeded castration level (

A 66-year-old man with superficial bladder cancer was treated with transurethral resection (TURBT) in October 2011. The pathological diagnosis was urothelial carcinoma (UC), grade 2, T1. A second TURBT was performed one month later. The pathological diagnosis was UC, grade 3, T1. He was treated with intravesical bacillus Calmette-Guerin (BCG) after TURBT. His progress was satisfactory, but a small superficial bladder cancer was found on cystoscopy in August 2012. He was going to be treated with TURBT, but the serum alkaline phosphatase level was abnormally high on preoperative evaluation. Bone scintigraphy showed multiple bone metastases from non-muscle invasive bladder cancer (NMIBC) without local invasion. He was started on combined chemotherapy with 1,000 mg/m2 gemcitabine on days 1, 8 and 15 and 70 mg/m2 cisplatin on day 2 every four weeks. He received denosumab for multiple bone metastases at the same time. Although he subsequently developed severe hypocalcemia, treatment was continued, and he completed four courses of chemotherapy. Bone scintigraphy and contrast-enhanced computed tomography showed reduction of the multiple bone metastases, and alkaline phosphatase decreased to the normal range. It is rare for NMIBC without local invasion to metastasize to other organs. Thus, it is necessary to consider distant metastases in patients with NMIBC.

Objectives : Mineralocorticoid receptor (MR) is known to play physiological and pathophysiological roles in the cardiovascular system, and MR activation directly damages these organs. The aim of this study was to evaluate the expression of MR and 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) in the human penile corpus cavernosum. Methods : MR and 11β-HSD2 expression was assayed in human penile tissues, and also in human renal tissues as a positive control. Expressions of MR mRNA and 11β-HSD2 mRNA were evaluated using reverse transcription polymerase chain reaction (RT-PCR). MR and 11β-HSD2 were visually identified using immunofluorescence analysis. Results : MR mRNA expression in human penis was confirmed by RT-PCR. On quantitative RT-PCR analysis, 11β-HSD2 mRNA expression was detected at minimal levels in penile tissue. Immunofluorescence analysis revealed positive staining for MR and negative staining for 11β-HSD2 in smooth muscle cells of the corpus cavernosum. Conclusions : This study demonstrated the presence of MR and the absence of 11β-HSD2 in human penile corpus cavernosum. Considering that MR activation causes various organ damages, MR blockade in human penile corpus cavernosum may have therapeutic benefits. Investigations for the penile effects of MR activation have the potential to provide new treatment approaches for erectile dysfunction.

BACKGROUND: Gas6 is a growth factor that causes proliferation of mesangial cells in the development of glomerulonephritis. Gas6 can bind to three kinds of receptors; Axl, Dtk, and Mer. However, their expression and functions are not entirely clear in the different glomerular cell types. Meanwhile, representative cell cycle regulatory protein p27 has been reported to be expressed in podocytes in normal glomeruli with decreased expression in proliferating glomeruli, which inversely correlated with mesangial proliferation in human IgA nephropathy (IgAN). METHODS: The aim of this study is to clarify Gas6 involvement in the progression of IgAN. Expression of Gas6/Axl/Dtk was examined in 31 biopsy proven IgAN cases. We compared the expression levels with histological severity or clinical data. Moreover, we investigated the expression of Gas6 and its receptors in cultured podocytes. RESULTS: In 28 of 31 cases, Gas6 was upregulated mainly in podocytes. In the other 3 cases, Gas6 expression was induced in endothelial and mesangial cells, which was similar to animal nephritis models. Among 28 podocyte type cases, the expression level of Gas6 correlated with the mesangial hypercellularity score of IgAN Oxford classification and urine protein excretion. It also inversely correlated with p27 expression in glomeruli. As for the receptors, Axl was mainly expressed in endothelial and mesangial cells, while Dtk was expressed in podocytes. In vitro, Dtk was expressed in cultured murine podocytes, and the expression of p27 was decreased by Gas6 stimulation. CONCLUSIONS: Gas6 was uniquely upregulated in either endothelial/mesangial cells or podocytes in IgAN. The expression pattern can be used as a marker to classify IgAN. Gas6 has a possibility to be involved in not only mesangial proliferation via Axl, but also podocyte injury via Dtk in IgAN.

We conducted this study to determine whether substitution with anti-androgen (SOA) and tegafur-uracil (a pro‑drug of 5-FU) combination therapy is more effective than SOA alone after relapse from initial hormonal therapy. Patients who were histologically confirmed and relapsed after initial hormonal therapy were included. All patients were randomly allocated into two groups: SOA alone (group A) or SOA combined with tegafur-uracil (group B). The mRNA expression of four enzymes, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phospho-ribosyltransferase (OPRT) and thymidine phosphorylase (TP), in prostate cancer cells was analyzed by quantitative reverse-transcription polymerase chain reaction. Fifty-two patients were enrolled in this study. The median age was 77 (range: 47-92) years. The PSA response rate in group B (61.5%) tended to be higher compared to that in group A (34.6%) (p=0.095). Group B (median: 15.9 months) had a significantly longer time to PSA progression (TTP) compared to group A (6.4 months) (p=0.014). In patients with a lower TS expression or a higher OPRT expression, group B demonstrated a higher PSA response rate compared to group A (p=0.019 and p=0.041, respectively). In addition, in the patients with a lower TS expression, group B demonstrated a significantly longer TTP compared to group A (p=0.018). There were no severe adverse events in either treatment group. After relapse from initial hormonal therapy, SOA combined with tegafur-uracil is effective and well tolerated. The TS mRNA expression level may be a predictive factor for this combination therapy.

INTRODUCTION AND OBJECTIVES: Low-temperature sensitive liposomes (LTSLs) release their encapsulated drug into targeted tissue when activated by a source of hyperthermia. The efficacy of an LTSL formulation of docetaxel (DOC) or doxorubicin (DOX) was compared against prostate cancer in a xenograft mouse model. METHODS: Under an approved IACUC protocol, Luciferase transfected human prostate PC-3M-luciferase cells were inoculated (3 10 6 cells) subcutaneously in the right hind leg of 8 wk old female athymic nude mice. When tumors reached a volume of 200–300 mm 3, mice were randomized to receive one intravenous injection of saline, Stealth liposomal DOX (5 mg/kg), LTSL DOX (5 mg/kg), or LTSL DOC (15 mg/kg), with or without hyperthermia treatment (LTSL DOX and LTSL DOC were supplied by Celsion Corp., Columbia, MD). Mice undergoing hyperthermia treatment were anesthetized and stabilized in a holder that allowed for only the leg with tumor to be heated to 41–42C that triggered LTSL drug release. Mice were monitored daily for tumor volume and body weight. Study end-points included growth of tumor to 5x the initial treatment volume or monitoring of survival for 60 days. RESULTS: The LTSL DOC delayed tumor growth longer (20 days) than DOX (7 days) or LTSL DOX (9 days) with hyperthermia (P 0.05). Mice treated with LTSL DOC and hyperthermia survived longest (60 days) compared to all other mice (range 6–8 days, P 0.05). LTSL in the setting of hyperthermia demonstrated complete regression of tumor in 57% of mice. CONCLUSIONS: LTSL DOC with hyperthermia delayed tumor growth more than all other treatments. Survival studies suggest LTSL DOC is a more effective temperature sensitive delivery system against PC-3M prostate tumors.

Solitary adrenal metastasis from endometrial adenocarcinoma is extremely rare. We report herein the case of a laparoscopically resected solitary adrenal metastasis originating from endometrial adenocarcinoma. The patient was a 55-year-old woman who had undergone total abdominal hysterectomy for stage IIIc endometrial carcinoma, followed by 7 courses of adjuvant chemotherapy comprising carboplatin and paclitaxel. However, the patient developed an isolated right adrenal metastasis 15 months postoperatively. The solitary adrenal metastasis (diameter, 5.7 cm) was removed laparoscopically. The patient has now been in good health without recurrence for 5 years and 7 months after laparoscopic surgery. To the best of our knowledge, this is the first case of solitary adrenal metastasis originating from endometrial adenocarcinoma that is controlled for the long term by successful laparoscopic resection.

A 40-year-old woman was referred to our hospital because of pain extending from the left lateral abdomen to the left inferior limb. The abdominal computed tomography (CT) revealed an 8x7x12 cm retroperitoneal serous cystic mass. The serum carcinoembryogenic antigen (CEA) level was slightly elevated to 2.7 ng/ml. Therefore, we suspected it to be malignant, and we performed laparoscopic resection carefully. The retroperitoneal cyst was not adherent to the surrounding tissues and was easily dissected and removed under laparoscopy. Carbohydrale antigen (CA)19-9, CA125 and CEA levels in the fluid were elevated, but a cytology of the fluid was negative and no malignant sign was seen in the cyst wall. To our knowledge, this is the second reported case of retroperitoneal serous cyst resected by laparoscopic surgery in the Japanese literature.

A 41 year-old man with a history of diabetes mellitus underwent computed tomography for screening on August 2007. The CT revealed an enhancing 3.0 cm mass in the middle pole of the left kidney. We diagnosed as renal cancer, clinical stage T1aN0M0. Then he underwent laparoscopic left partial nephrectomy. The pathological result was renal cell carcinoma, G2 > G1, pT1a. On post operative day 12, he appeared a gross hematuria and dysuria, then he was rehospitalized due to drop of hemoglobin and bladder tamponade. Enhanced CT showed left renal artery pseudoaneurysm. He underwent selective coil embolization of left renal artery pseudoaneurysm. After that he repeated gross hematuria, and appeared bladder tamponade again. On POD 65 he underwent selective coil embolization again. Since then the patient recovered uneventfully.

Between January 1996 and December 2007, 111 patients with prostate cancer underwent radical prostatectomy, including 34 who received preoperative hormonal therapy. In this study, we reviewed 77 patients who did not undergo neoadjuvant hormonal therapy. The mean age was 65.5 years old and followup time was 40.7 months. The clinical stage was T1c in 60 patients, T2 in 16, and T3 in 1. Prostate specific antigen (PSA) at diagnosis ranged from 3.44 to 46.08 ng/ml (mean 10.18). At our institution, PSA failure after surgery was defined as PSA elevation above 0.2 ng/ml. The pathological stage was pT2 in 59 patients, pT3a in 11, pT3b in 7 and pN + (obturator lymph node) in none. The surgical margin was positive in 29.3% of the pT2 patients and 68.8% of the pT3 patients. Sixteen patients (20.8%) had PSA failure. PSA values at diagnosis and pathological T stage were significantly relevant to PSA failure. Patients with PSA failure underwent radiation therapy or hormonal therapy as a salvage adjuvant therapy. The PSA level was controlled well in majority of the patients. Only one patient died of cancer. In conclusion, 33 out of 111 patients who underwent radical prostatectomy had PSA failure. Sixteen of the 77 patients who were not given neoadjuvant therapy had PSA failure. The significant factors related to PSA failure were PSA values at diagnosis and pathological T stage.