Female intravesical foreign body penetrating the bladder wall: A rare case of traditional Asian hair stick kanzashi.

A female in her thirties inserted an Asian traditional hair stick, kanzashi, into her urinary bladder for sexual gratification. We need to know that everyday objects can become bladder foreign bodies and how to manage them properly.

Testis-expressed gene 11 inhibits cisplatin-induced DNA damage and contributes to chemoresistance in testicular germ cell tumor.

Testicular germ cell tumor (TGCT) is a rare cancer but the most common tumor among adolescent and young adult males. Patients with advanced TGCT often exhibit a worse prognosis due to the acquisition of therapeutic resistance. Cisplatin-based chemotherapy is a standard treatment for advanced TGCTs initially sensitive to cisplatin, as exemplified by embryonal carcinoma. The acquisition of cisplatin resistance, however, could be a fatal obstacle for TGCT management. To identify cisplatin resistance-related genes, we performed transcriptome analysis for cisplatin-resistant TGCT cells compared to parental cells. In two types of cisplatin-resistant TGCT cell models that we established from patient-derived TGCT cells, and from the NEC8 cell line, we found that mRNA levels of the high-mobility-group nucleosome-binding gene HMGN5 and meiosis-related gene TEX11 were remarkably upregulated compared to those in the corresponding parental cells. We showed that either HMGN5 or TEX11 knockdown substantially reduced the viability of cisplatin-resistant TGCT cells in the presence of cisplatin. Notably, TEX11 silencing in cisplatin-resistant TGCT cells increased the level of cleaved PARP1 protein, and the percentage of double-strand break marker γH2AX-positive cells. We further demonstrated the therapeutic efficiency of TEX11-specific siRNA on in vivo xenograft models derived from cisplatin-resistant patient-derived TGCT cells. Taken together, the present study provides a potential insight into a mechanism of cisplatin resistance via TEX11-dependent pathways that inhibit apoptosis and DNA damage. We expect that our findings can be applied to the improvement of cisplatin-based chemotherapy for TGCT, particularly for TEX11-overexpressing tumor.

Clinicopathological and Preclinical Patient-Derived Model Studies Define High Expression of NRN1 as a Diagnostic and Therapeutic Target for Clear Cell Renal Cell Carcinoma.

BACKGROUND: Acquired therapeutic resistance and metastasis/recurrence remain significant challenge in advance renal cell carcinoma (RCC), thus the establishment of patient-derived cancer models may provide a clue to assess the problem. We recently characterized that neuritogenesis-related protein neuritin 1 (NRN1) functions as an oncogene in testicular germ cell tumor. This study aims to elucidate the role of NRN1 in RCC. METHODS: NRN1 expression in clinical RCC specimens was analyzed based on immunohistochemistry. NRN1-associated genes in RCC were screened by the RNA-sequencing dataset from The Cancer Genome Atlas (TCGA). RCC patient-derived cancer cell (RCC-PDC) spheroid cultures were established and their viabilities were evaluated under the condition of gene silencing/overexpression. The therapeutic effect of NRN1-specific siRNA was evaluated in RCC-PDC xenograft models. RESULTS: NRN1 immunoreactivity was positively associated with shorter overall survival in RCC patients. In TCGA RCC RNA-sequencing dataset, C-X-C chemokine receptor type 4 (CXCR4), a prognostic and stemness-related factor in RCC, is a gene whose expression is substantially correlated with NRN1 expression. Gain- and loss-of-function studies in RCC-PDC spheroid cultures revealed that NRN1 significantly promotes cell viability along with the upregulation of CXCR4. The NRN1-specific siRNA injection significantly suppressed the proliferation of RCC-PDC-derived xenograft tumors, in which CXCR4 expression is significantly repressed. CONCLUSION: NRN1 can be a potential diagnostic and therapeutic target in RCC as analyzed by preclinical patient-derived cancer models and clinicopathological studies.

HIF1α inhibitor 2-methoxyestradiol decreases NRN1 expression and represses in vivo and in vitro growth of patient-derived testicular germ cell tumor spheroids.

Testicular germ cell tumor (GCT) is the most common type of malignancy in young males. Patients with nonseminomatous GCT still have poor prognosis. To identify new therapeutic targets, we generated patient-derived cells (PDCs) and their xenograft (PDCX) models from 3 distinct GCT patients' specimens. The pathological features of GCT PDCs and PDCX tumors recapitulated those of nonseminomatous components exhibiting in the corresponding patients' specimens. Notably, stemness-related markers and hypoxia-related genes, including hypoxia inducible factor 1α (HIF1A) and neuritin 1 (NRN1), were abundantly expressed in three-dimensional spheroid cultures of GCT PDCs. We identified functional HIF1α response elements in the NRN1 promoter and defined that their transcriptional activities were substantially activated by hypoxia. HIF1α inhibition by siRNAs or an inhibitor, 2-methoxyestradiol, significantly suppressed NRN1 expression and decreased the in vitro and in vivo growth of PDC spheroids. Moreover, NRN1 knockdown efficiently suppressed PDC proliferation. These results suggest that HIF1α and NRN1 are potential diagnostic and therapeutic targets, and that 2-methoxyestradiol could be applied to clinical management of GCT. Overall, our GCT PDC and PDCX models would be useful as preclinical models for precision medicine targeting each patient.

Proposal for a Simple Anatomical Classification of the Pelvicaliceal System for Endoscopic Surgery.

We herein propose a nomenclature for renal calices and anatomical classification of the renal pelvis for endoscopic surgery. We prospectively collected data on a total of 270 patients (540 kidneys) who underwent CT-urography. We then constructed three-dimensional images of the renal pelvis and examined their morphologic classification. Forty-eight kidneys were excluded from this study because of severe hydronephrosis or large renal cysts. The remaining 492 kidneys were included. We systematically categorized each minor calix into five levels: top, upper, middle, lower, and bottom. The upper, middle, and lower calices were typically found in pairs: anterior and posterior. The most common total number of minor calices was eight (51%), followed by seven (30%). We also classified the form of the pelvis into type I: single pelvis (58%) and type II: divided pelvis (42%), according to the branch patterns of the renal pelvis. In type II, the renal pelvis is always bifurcated into the upper branch (top and upper) and lower branch (middle, lower, and bottom). Type I was subclassified into three types: type Ia (43%), the standard type; type Ib (4%), with a wide pelvis; and type Ic (11%), with a narrow pelvis. This anatomical classification can divide the renal pelvis into two major types (subdivided into four types) and name each minor calix. This simple classification enables to share common intrarenal information, thus leading to the development of concrete treatment strategies.

Predictive risk factors for systemic inflammatory response syndrome following ureteroscopic laser lithotripsy.

The objective of this study was to investigate risk factors for the development of systemic inflammatory response syndrome following ureteroscopic laser lithotripsy. We retrospectively collected data of 469 patients who underwent ureteroscopic laser lithotripsy at our single institution from February 2008 to June 2016. Details for the patient, the stone, and the surgical factors that potentially contributed to postoperative infection were extracted. Using a logistic regression model, we analyzed how the clinical factors affected the incidence of systemic inflammatory response syndrome. Twenty-seven patients (5.7%) were postoperatively diagnosed with systemic inflammatory response syndrome; of these, 25 patients were diagnosed within 24 h after ureteroscopy. One patient required intensive care unit admission, but no death was reported. A preoperative stent was significantly associated with postoperative systemic inflammatory response syndrome only on univariate analysis, and the reasons for stenting were varied. Multivariate analysis revealed that obstructive pyelonephritis, a positive preoperative bladder urine culture result, and female gender were significantly associated with postoperative systemic inflammatory response syndrome. Patients who experienced obstructive pyelonephritis preceding ureteroscopic laser lithotripsy or had a positive preoperative bladder urine culture result were at an increased risk of systemic inflammatory response syndrome despite receiving appropriate preoperative antibiotic therapy. Regarding the impact of a preoperative stent on postoperative infection, further investigation focusing on reasons for stenting is needed.

Appropriate kidney stone size for ureteroscopic lithotripsy: When to switch to a percutaneous approach.

Flexible ureteroscopy (fURS) has become a more effective and safer treatment for whole upper urinary tract stones. Percutaneous nephrolithotomy (PNL) is currently the first-line recommended treatment for large kidney stones ≥ 20 mm and it has an excellent stone-free rate for large kidney stones. However, its invasiveness is not negligible considering its major complication rates. Staged fURS is a practical treatment for such large kidney stones because fURS has a minimal blood transfusion risk, short hospitalization and few restrictions on daily routines. However, as the stone size becomes larger, the stone-free rate decreases, and the number of operations required increases. Therefore, in our opinion, staged fURS is a practical option for kidney stones 20 to 40 mm. Miniaturized PNL combined with fURS should be considered to be a preferred option for stones larger than 40 mm. Moreover, URS is an effective treatment for multiple upper urinary tract stones. Especially for patients with a stone burden < 20 mm, URS is a favorable option that promises a high stone-free rate after a single session either unilaterally or bilaterally. However, for patients with a stone burden ≥ 20 mm, a staged operation should be considered to achieve stone-free status.

[Clinicopathological analysis of 3 cases in which pulmonary metastasis from the urothelial carcinoma was resected].

We describe 3 cases in which the pulmonary metastasis from the urothelial carcinoma of the bladder and upper urinary tract was resected. The duration from the operation of the primary lesion to the occurrence of the pulmonary metastasis was 19, 11, and 4 years in each of the 3 cases. Repeated treatment of the local recurrence was performed in all the 3 cases. Local recurrence in the bladder membrane was observed in 1 case. In 2 cases, computed tomography( CT) scans revealed that the cavitation had penetrated the tumor. Histological findings of the surgical specimen obtained from the 3 cases revealed severe tumor necrosis. Immunostaining of the surgical specimen resulted in a definitive diagnosis of pulmonary metastasis from the urothelial carcinoma in 2 cases in which a differential diagnosis could not identify the primary lung cancer from the pulmonary metastasis. The prognoses in terms of survival in each of the 3 cases were shorter than 32, 19, and 6 months from the operation of the pulmonary metastasis. However, the prognoses could be improved by multidisciplinary treatment, including the resection of the pulmonary metastasis.

Single-session ureteroscopy with holmium laser lithotripsy for multiple stones.

Multiple stones are found in 20-25% of patients with urolithiasis. The stone multiplicity is a powerful adverse factor influencing the treatment outcome after shockwave lithotripsy, although guidelines for the treatment of multiple stones have not been well established yet. Herein we report our most recent experience of a single-session ureteroscopy for multiple stones. Between September 2008 and December 2011, 51 patients with multiple stones (total 146 stones) in different locations (37unilateral, 14 bilateral) underwent a total of 65 ureteroscopic procedures. Operative time, stone-free rates and complications were evaluated. Stone-free status was defined as no fragments in the ureter and the absence of >2 mm fragments in the kidney. The mean stone number per patient was 2.9 ± 1.7 and the mean stone burden (cumulative stone length) was 21.5 ± 11.6 mm. The mean number of procedures was 1.3 ± 0.6. Overall, the stone-free rate after a single session was 80% (41/51). In patients with stone burden <20 mm and ≥20 mm, stone-free rates after a single session were 92% (23/25) and 69% (18/26), respectively. Multivariate analysis showed that the stone burden and the presence of impacted stones were the factors significantly influencing the treatment outcome. Stone location did not have a strong influence on the outcome. No major intraoperative complications were identified. Our findings suggest that ureteroscopy is an efficient treatment for multiple stones. For patients with stone burden <20 mm, either unilaterally or bilaterally, a single session of ureteroscopy is a favorable treatment option with a high stone-free rate.

Successful outcome of flexible ureteroscopy with holmium laser lithotripsy for renal stones 2 cm or greater.

Although percutaneous nephrolithotomy has been recommended as the first-line treatment for renal stones larger than 2 cm, its major complication rate is not negligible and less invasive approaches are to be explored. Thanks to the recent advances in endoscopic technology, flexible ureteroscopy has become another option in this setting. Herein we report our most recent experience with flexible ureteroscopy for large renal stones. Between September 2008 and May 2011, 20 patients with renal stones ≥ 2 cm underwent a total of 28 procedures of ureteroscopy with holmium laser lithotripsy, using the Olympus URF-P5 and a ureteral access sheath. The number of procedures, operative time, stone-free rates, stone compositions and complications were evaluated. Stone-free status was defined as the absence of fragments or fragments of ≤ 4 mm. Mean stone size was 3.1 cm (range 2.0-5.0). The average number of procedures was 1.4. One, two and three procedures were required in 13, six and one patients, respectively. Overall, the stone-free rate was 90%. The stone-free rate for preoperative stone size of 2 to ≤ 4 cm and >4 cm was 100% (14/14) and 67% (4/6), respectively. No major intraoperative complications were identified. Postoperative high-grade fever was observed in three patients, including one patient who developed sepsis. All these patients were successfully treated conservatively. Our findings suggest that ureteroscopy represents a favorable option for selected patients with renal stones, especially those 2 to ≤ 4 cm in size.

[Transurethral lithotripsy with rigid and flexible ureteroscopy for renal and ureteral stones: results of the first 100 procedures].

We evaluated the clinical outcome of transurethral lithotripsy (TUL) using rigid & flexible ureteroscopy and holmium : yttrium-aluminum-garnet (YAG) laser in our hospital. We retrospectively reviewed 100 consecutive transurethral lithotripsy procedures performed on 82 patients from May 2008 to June 2010 at our hospital. Twenty-five patients (30%) had multiple stones and 10 patients (12%) had bilateral stones. The main stones were located in the renal pelvis, ureteropelvic junction, upper ureter, middle ureter, and lower ureter in 14, 12, 26, 3, and 27 cases, respectively. Median operative time was 75 minutes (range, 18-238 minutes). Operative complications were 5 cases of pyelonephritis and 1 case of ureteral perforation that was managed conservatively with percutaneous nephrostomy. The average number of procedures was 1.22 with 65 patients requiring one, 16 requiring two, and 1 requiring three procedures. Three patients had shock wave lithotripsy (SWL) and two patients had minipercutaneous nephrolithotomy (mini-PNL) after first TUL. However, all of these patients eventually needed additional TUL. The overall success rate was 99% (81/82). Rigid & flexible ureteroscopy and holmium : YAG laser lithotripsy achieved excellent results of treatment for urolithiasis. TUL gave a high stone-free rate with low complication rates. In Japan, where shock wave lithotripters are widely used, trend of treatment for urolithiasis will shift from SWL to TUL.

[A case of urachal carcinoma with transverse colon fistula].

A 61-year-old woman was admitted to our hospital because of abdominal pain. Computed tomography showed an abscess in the anterior abdominal wall and an intraabdominal tumor. Biopsy from bladder dome presented adenocarcinoma. We diagnosed the tumor as urachal carcinoma and operation was performed. The resected specimen showed transverse fistula. In Japan, there is no report of urachal carcinoma with fistula to digestive duct. We think it is a cause of strong infiltration of the carcinoma. Curative resection for urachal carcinoma with fistula can lead to a better prognosis, in spite of its invasive character.

[Two cases of intrascrotal tumors complicated acute scrotum].

We report 2 rare cases of intrascrotal tumors complicated acute scrotum. Case 1: A 15-year-old adolescent presented to our emergency room with acute right scrotal pain. Testicular torsion was suspected, and surgical exploration was performed. A spermatocele with 180 degrees torsion on its pedicle was observed. The patient was diagnosed with torsion of a spermatocele, and it was excised. Case 2: A 25-year-old man presented with acute left scrotal pain. Testicular torsion was suspected, and manual detorsion relieved the pain effectively. However, scrotal swelling did not subside after detorsion, and surgical exploration was performed. The left testis was stony hard on palpation, and intraoperative ultrasound revealed a mosaic echo pattern. A testicular tumor was highly suspected and left high orchiectomy was performed. Histopathological examination revealed seminoma pT1. Torsion of a testicular tumor was diagnosed. Although these 2 cases are extremely rare, they should be considered for the differential diagnosis of acute scrotum.

[A case bilharziasis in a Japanese male].

Bilharziasis is an endemic disease distributed mostly in African countries and the Middle East, and causes severe disturbances of urinary tract secondarily. Although it used to be a very rare disease in Japan, modern human mobility and jet travel have brought this tropical disease into our country far from endemic areas. A 25-year-old Japanese male presented to our hospital with macroscopic hematuria. He had an experience of traveling to Malawi two years before. Cystourethroscopy demonstrated so-called 'bilharzial tubercles', many yellowish specks of mucosa at the posterior wall and dome of the bladder. The diagnosis of bilharziasis was made by detection of Schistosoma haematobium eggs in urine and histological specimen obtained by transurethral biopsy. In this case, radiographic and pathological examinations revealed neither obstructive uropathy nor urothelial malignancy. He was treated with praziquantel, and the disease is under good control.