Successful Pregnancy Outcome in a Patient with Juvenile Idiopathic Arthritis in Adulthood, Amyloid A Amyloidosis, and Chronic Kidney Disease Using Tocilizumab with Strict Blood Pressure Control.

Pregnancies with chronic kidney disease (CKD) and high disease activity in rheumatic diseases are high-risk events with adverse outcomes for both the mother and fetus. We herein report a 35-year-old woman with juvenile idiopathic arthritis (JIA), amyloid A (AA) amyloidosis related to JIA, and CKD stage G4A2 who wished to have children. She achieved a successful pregnancy, even in the presence of these multiple risk factors, using tocilizumab to control the disease activity of JIA and AA amyloidosis, along with antihypertensive drugs to control her blood pressure before and during pregnancy.

Herlyn-Werner-Wunderlich syndrome (HWWS)-associated gynecological malignancies: A case report and literature review.

Herlyn-Werner-Wunderlich syndrome (HWWS) is a rare congenital urogenital anomaly characterized by uterine didelphys, unilateral blind hemivagina, and ipsilateral renal agenesis. We present a very rare case of HWWS-associated cervical cancer in which the presence of a genital anomaly was not noticed until the patient experienced postmenopausal vaginal bleeding. A 74-year-old nulliparous Japanese woman presented with vaginal bleeding. Pre-treatment workup revealed uterine didelphys, obstructed hemivagina/hemicervix, renal agenesis, and cancer development from the remnant-obstructed hemivagina/hemicervix. The patient was diagnosed with HWWS and HWWS-associated vaginal or cervical cancer, treated with radical surgery, and a diagnosis of clear cell carcinoma (CCC) of the uterine cervix was histopathologically confirmed. A literature review revealed an increased incidence of CCC in women with HWWS.

A phase I/II study of GLIF combination chemotherapy for taxane/platinum-refractory/resistant endometrial cancer (GOGO-EM2).

PURPOSE: Development of new treatment strategies for endometrial cancer that has become refractory or resistant to taxane/platinum is a critical need. The present study was a phase I/II study of gemcitabine, levofolinate, irinotecan, and 5-fluorouracil (5-FU) (GLIF) combination chemotherapy to determine optimal dosages, safety, and efficacy. METHODS: Taxane/platinum-resistant or -refractory endometrial disease was defined as tumor progression within 6 months after a taxane/platinum-based regimen. Maximum tolerated dose was investigated by a 3 + 3-designed phase I study. The phase II study was conducted using the recommended doses determined in the phase I study. RESULTS: The dosages recommended for the phase II trial were determined, in the phase I trial, to be: gemcitabine 800 mg/m2, levofolinate 100 mg/m2, irinotecan 80 mg/m2, and 5-FU 1000 mg/m2. Thirty patients were enrolled, including the three patients who received GLIF therapy at the same dose as the recommended phase II dose in the phase I study. Two patients were excluded at this point due to study protocol violations, and the remaining 28 patients were included for analysis. Phase II revealed that the response and disease control rates were 7.1% (2/28) and 39.3% (11/28), respectively, and that the median PFS and OS were 3 months [95% confidence interval (CI) 3-7] and 12 months (95% CI 9-17), respectively. Febrile or grade 4 neutropenia was observed in 14% (4/28) of the cases. Grade 3 or 4 thrombocytopenia was not observed. CONCLUSION: We found that GLIF combination chemotherapy is potentially a useful treatment option for endometrial cancers refractory or resistant to taxane/platinum-based chemotherapy.

Combination chemotherapy with irinotecan and gemcitabine for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancer: a multicenter phase I/II trial (GOGO-Ov 6).

PURPOSE: To develop a new therapeutic strategy for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancers, we evaluated the feasibility and efficacy of irinotecan and gemcitabine combination chemotherapy. METHODS: Patients with taxane/platinum-resistant/refractory cancer received escalating doses of irinotecan and gemcitabine (level 1: 80 and 800 mg/m2, respectively; level 2: 100 and 1000 mg/m2) on days 1 and 8 on a 21-day cycle. Genotyping for UGT1A1*6 and *28 polymorphisms was performed for possible adverse irinotecan sensitivity. RESULTS: A total of 35 patients were enrolled. The recommended dose was defined as 100 mg/m2 irinotecan and 1000 mg/m2 gemcitabine (level 2). The observed common grade 3/4 toxicities were neutropenia (60%), anemia (17.1%), diarrhea (8.6%), thrombocytopenia (5.7%) and nausea (5.7%). Groups homozygous for UGT1A1*6 or *28 were associated with grade 3/4 neutropenia and diarrhea. Objective responses were 20%, including one complete response and six partial responses. In 29 patients treated with the recommended dose, the median progression-free survival and overall survival were 3.8 months (95% CI 2.1-6.0 months) and 17.4 months (95% CI 9.9-21.9 months), respectively, while the 1-year survival rate was 58.6%. CONCLUSIONS: Combination chemotherapy with irinotecan and gemcitabine represents a safe and effective treatment combination for taxane/platinum-resistant/refractory ovarian and primary peritoneal cancers.

A case of laparoscopic surgery for endometrial cancer in a patient previously treated with a transvaginal mesh procedure for pelvic organ prolapse.

Transvaginal mesh (TVM) surgery is an effective treatment option for women with pelvic organ prolapse (POP). Because the TVM procedure preserves the uterus, it is possible for endometrial cancer to occur at a later date. We herein present the first report of such an endometrial cancer, diagnosed well after TVM surgery for POP, and the use of laparoscopic surgery to conduct a simple total hysterectomy to treat it.

Drosophila Sulf1 is required for the termination of intestinal stem cell division during regeneration.

Stem cell division is activated to trigger regeneration in response to tissue damage. The molecular mechanisms by which this stem cell mitotic activity is properly repressed at the end of regeneration are poorly understood. Here, we show that a specific modification of heparan sulfate is crucial for regulating Drosophila intestinal stem cell (ISC) division during normal midgut homeostasis and regeneration. Loss of the extracellular heparan sulfate endosulfatase Sulf1 resulted in increased ISC division during normal homeostasis, which was caused by upregulation of mitogenic signaling including the JAK-STAT, EGFR and Hedgehog pathways. Using a regeneration model, we found that ISCs failed to properly halt division at the termination stage in Sulf1 mutants, showing that Sulf1 is required for terminating ISC division at the end of regeneration. We propose that post-transcriptional regulation of mitogen signaling by heparan sulfate structural modifications provides a new regulatory step for precise temporal control of stem cell activity during regeneration.

[The Vaginal Metastasis of Ureteral Carcinoma after Left Nephroureterectomy: A Case Report].

69-year-old woman underwent left nephroureterectomy for left ureteral cancer (urothelial carcinoma (UC), high grade, pT3pN0) in September 2013. She returned to our hospital presenting with asymptomatic macrohematuria in July 2014. Cystoscopy showed tiny papillary tumors in the bladder. We also found genital bleeding from multiple papillary tumors on the vaginal wall. We performed transurethral resection of the bladder tumor and a biopsy of the vaginal wall demonstrated non-invasive UC, high grade. Pelvic magnetic resonance imaging after the operation showed no infiltration outside the bladder wall and vaginal wall. Therefore, we performed endoscopic excision of the vaginal tumor. However we could not resect all vaginal tumors. Irradiation of the vagina and uterus was performed under the diagnosis of metastasis of UC tovagina. Vaginal UC is extremely rare and this is the 26th case report in the literature.

A phase II study of postoperative concurrent carboplatin and paclitaxel combined with intensity-modulated pelvic radiotherapy followed by consolidation chemotherapy in surgically treated cervical cancer patients with positive pelvic lymph nodes.

OBJECTIVES: A phase II study was conducted to evaluate the efficacy and toxicity of carboplatin plus paclitaxel (TC)-based postoperative concurrent chemoradiotherapy (CCRT) followed by TC-based consolidation chemotherapy in surgically-treated early-stage cervical cancer patients. METHODS: Women with surgically-treated early-stage cervical cancer with positive pelvic lymph nodes were eligible for this study. The patients were postoperatively treated with pelvic intensity modulated radiotherapy (50.4Gy) and concurrent weekly carboplatin (AUC: 2) and paclitaxel (35mg/m(2)) (TC-based CCRT). Three cycles of consolidation chemotherapy involving carboplatin (AUC: 5) and paclitaxel (175mg/m(2)) were administered after TC-based CCRT. RESULTS: Thirty-one patients were enrolled and treated. Overall, the treatment was well tolerated, and 26 patients (83.9%) completed the planned TC-based CCRT. The most frequently observed acute grade 3/4 hematological toxicities were leukopenia and neutropenia, and diarrhea was the most common acute grade 3/4 non-hematological toxicity. After a median follow-up period of 36.5months, 2 patients (6.5%) had developed recurrent disease. The patients' estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 88.5% and 93.8%, respectively. In comparisons with historical control groups, TC-based CCRT followed by TC-based consolidation chemotherapy was found to be significantly superior to CCRT involving a single platinum agent in terms of PFS (p=0.026) and significantly superior to extended-field radiotherapy in terms of both PFS (p=0.0004) and OS (p=0.034). CONCLUSIONS: In women with surgically treated early-stage cervical cancer, pelvic TC-based CCRT followed by TC-based consolidation chemotherapy is feasible and highly effective. Future randomized trials are needed to verify the efficacy of this regimen.

[Non-muscle invasive bladder cancer with multiple bone metastasis without local invasion : a case report].

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.

Substitution of anti-androgens and tegafur-uracil combination therapy for castration-resistant prostate cancer: results of a multi-center randomized phase II study.

We conducted this study to determine whether substitution with anti-androgen (SOA) and tegafur-uracil (a pro­drug 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.

[Adrenal cortical adenoma with increased uptake of 18F-fluoro-deoxy-glucose on PET/CT suspected as an adrenal metastasis from the cervical cancer : a case report].

A 61-year-old woman was referred to our department with a diagnosis of left solitary adrenal metastasis from cervical cancer in September 2011. She presented with postmenopausal bleeding in September 2010. The patient received seven courses of paclitaxel (175 mg/m2) and carboplatin (6 mg/GFR＋25) for stage IV cervical cancer with paraaortic, bilateral common iliac, mediastinal lymph node metastases and left adrenal metastasis from October 2010 to April 2011. Paraaortic radiation (50.4 Gy) was subsequently administered from May 2011 to July 2011. Abdominal nonenhanced computed tomography (CT) revealed a left 26×21 mm adrenal mass with regular margins (attenuation values 53 HU). On enhanced CT, the mass showed heterogeneous enhancement. F fluoro-2-deoxy D-glucose (FDG) positron emission tomography/CT images showed moderately increased FDG-avid uptake in the left adrenal tumor which was high enough to be suspicious of malignant tumor (standardized uptake value max : SUVmax 6.8). There were no other foci of pathologic uptake of FDG in the whole body. The plasma endocrinological examinations was all normal. Left laparoscopic adrenalectomy was performed. The final pathologic evaluation revealed adrenal cortical adenoma.

Drosophila heparan sulfate 6-O-endosulfatase Sulf1 facilitates wingless (Wg) protein degradation.

Heparan sulfate proteoglycans regulate various physiological and developmental processes through interactions with a number of protein ligands. Heparan sulfate (HS)-ligand binding depends on the amount and patterns of sulfate groups on HS, which are controlled by various HS sulfotransferases in the Golgi apparatus as well as extracellular 6-O-endosulfatases called "Sulfs." Sulfs are a family of secreted molecules that specifically remove 6-O-sulfate groups within the highly sulfated regions on HS. Vertebrate Sulfs promote Wnt signaling, whereas the only Drosophila homologue of Sulfs, Sulf1, negatively regulates Wingless (Wg) signaling. To understand the molecular mechanism for the negative regulation of Wg signaling by Sulf1, we studied the effects of Sulf1 on HS-Wg interaction and Wg stability. Sulf1 overexpression strongly inhibited the binding of Wg to Dally, a potential target heparan sulfate proteoglycan of Sulf1. This effect of Drosophila Sulf1 on the HS-Wg interaction is similar to that of vertebrate Sulfs. Using in vitro, in vivo, and ex vivo systems, we show that Sulf1 reduces extracellular Wg protein levels, at least partly by facilitating Wg degradation. In addition, expression of human Sulf1 in the Drosophila wing disc lowers the levels of extracellular Wg protein, as observed for Drosophila Sulf1. Our study demonstrates that vertebrate and Drosophila Sulfs have an intrinsically similar activity and that the function of Sulfs in the fate of Wnt/Wg ligands is context-dependent.

Glypicans regulate JAK/STAT signaling and distribution of the Unpaired morphogen.

In Drosophila, ligands of the Unpaired (Upd) family activate the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. The JAK/STAT pathway controls many developmental events, including multiple functions in the ovary. These include an early role in the germarium for specification of stalk cells and a later role in the vitellarium to pattern the follicular epithelium surrounding each cyst. In this latter role, graded JAK/STAT activation specifies three distinct anterior follicular cell fates, suggesting that Upd is a morphogen in this system. Consistent with the JAK/STAT activation pattern in the vitellarium, Upd forms a concentration gradient on the apical surface of the follicular epithelium with a peak at its source, the polar cells. Like many morphogens, signaling and distribution of Upd are regulated by the heparan sulfate proteoglycans (HSPGs) Dally and Dally-like. Mutations in these glypican genes and in heparan sulfate biosynthetic genes result in disruption of JAK/STAT signaling, loss or abnormal formation of the stalk and significant reduction in the accumulation of extracellular Upd. Conversely, forced expression of Dally causes ectopic accumulation of Upd in follicular cells. Furthermore, biochemical studies reveal that Upd and Dally bind each other on the surface of the cell membrane. Our findings demonstrate that Drosophila glypicans regulate formation of the follicular gradient of the Upd morphogen, Upd. Furthermore, we establish the follicular epithelium as a new model for morphogen signaling in complex organ development.

Up-regulation of plakophilin-2 and Down-regulation of plakophilin-3 are correlated with invasiveness in bladder cancer.

OBJECTIVE: To examine plakophilin proteins (Pkp) and 3 expression levels in bladder cancer, in particular their levels during cellular growth and invasion. Pkp is associated with the binding of cadherin to intermediate filaments of the cytoskeleton. METHODS: The relative mRNA and protein expression levels of Pkp2 and 3 in bladder cancer cell lines were determined using quantitative real-time polymerase chain reaction and Western blot analyses. The cellular localization of Pkp2 and 3 proteins in bladder cancer cells was also assayed using immunohistochemistry. The proliferation and invasive activities of bladder cancer cells were evaluated using cell growth and in vitro cell invasion assays, and were compared with those of bladder cancer cells treated with Pkp2 and 3 small interfering RNAs. RESULTS: Pkp2 mRNA and protein levels were elevated, and those of Pkp3 were reduced, in bladder cancer cells that are known to exhibit increased proliferation and invasive activity. Pkp2/3 protein expression was predominantly observed in the cytoplasm of invasive bladder cancer cells and tissues. Pkp2 knockdown inhibited, and Pkp3 knockdown enhanced, invasion of bladder cancer cells, but these knockdowns did not alter cell proliferation. CONCLUSION: We conclude that high Pkp2, and low Pkp3, expression is associated with bladder cancer cell invasion and that neither Pkp2 nor Pkp3 is associated with cell proliferation. We further hypothesize that accumulation of Pkp2 and 3 in the cell cytoplasm, rather than their recruitment to the cell membrane, is related to an increased ability of the tumor to invade and metastasize.

Cell death and selective adhesion reorganize the dorsoventral boundary for zigzag patterning of Drosophila wing margin hairs.

Animal tissues and organs are comprised of several types of cells, which are often arranged in a well-ordered pattern. The posterior part of the Drosophila wing margin is covered with a double row of long hairs, which are equally and alternately derived from the dorsal and ventral sides of the wing, exhibiting a zigzag pattern in the lateral view. How this geometrically regular pattern is formed has not been fully understood. In this study, we show that this zigzag pattern is created by rearrangement of wing margin cells along the dorsoventral boundary flanked by the double row of hair cells during metamorphosis. This cell rearrangement is induced by selective apoptosis of wing margin cells that are spatially separated from hair cells. As a result of apoptosis, the remaining wing margin cells are rearranged in a well-ordered manner, which shapes corrugated lateral sides of both dorsal and ventral edges to interlock them for zigzag patterning. We further show that the corrugated topology of the wing edges is achieved by cell-type specific expression and localization of four kinds of NEPH1/nephrin family proteins through heterophilic adhesion between wing margin cells and hair cells. Homophilic E-cadherin adhesion is also required for attachment of the corrugated dorsoventral edges. Taken together, our results demonstrate that sequential coordination of apoptosis and epithelial architecture with selective adhesion creates the zigzag hair alignment. This may be a common mechanism for geometrically ordered repetitive packing of several types of cells in similarly patterned developmental fields such as the mammalian organ of Corti.

Coexistent intramedullary spinal cord and choroidal metastases in ovarian cancer.

Involvement of intramedullary spinal cord and the choroid by ovarian cancer is rare, and coexistence of metastases at these sites is extremely rare and has never been reported. This condition rapidly progresses to a neurological emergency; however, an efficient standard treatment method is not available for this rare condition. The case presented herein is of a female patient with stage II, poorly differentiated serous cystadenocarcinoma of the ovary. She presented with blindness and other neurologic complaints during the course of treatment for a recurrence at 50 months after the primary surgical treatment for the tumor. Magnetic resonance imaging (MRI) revealed intramedullary spinal cord metastasis and choroidal metastasis, coexisting with multiple brain metastases and intra-abdominal lesions. Neurological emergency was prevented by administering whole-brain irradiation therapy followed by systemic chemotherapy. Early diagnosis and multidisciplinary treatment, including radiotherapy and chemotherapy, may offer good palliation for such unusual metastases of ovarian cancer.

E-cadherin prolongs the moment for interaction between intestinal stem cell and its progenitor cell to ensure Notch signaling in adult Drosophila midgut.

Intestinal stem cells (ISCs) are required for maintenance of the proper cell composition in the adult intestine. To ensure permanent recruitment of newly differentiated cells, the ISC undergoes asymmetric cell division that generates an ISC itself and a progenitor cell. In the Drosophila midgut, cell fate for the absorptive cell is determined by Notch (N) signal in the progenitor cells that receive a ligand Delta (Dl) produced by the ISCs. Although most of the ISCs and progenitor cells are distantly located, they should retain their attachment when N is activated because the Dl-N interaction requires cell adhesion. Furthermore, N cannot be activated before completion of cell division. Thus, the moment after cell division and before cell separation should be prolonged for certain N activation, although the mechanism for this remains unclear. Here, we demonstrate that E-cadherin (E-cad) is required for stable attachment between the two cells. When E-cad does not function, N is not activated and cell differentiation is attenuated. We also show that the ISC tumor by N inactivation is assisted by a defect in E-cad down-regulation. These findings reveal one of the normal N functions used to inhibit tumorigenesis through lowering of E-cad for proper midgut cell turnover.

[Folic acid reduces the risk of neural tube defects: awareness and folate intake among pregnant women in 2006].

Folic acid plays an important role in proliferating cells and tissues of the fetus. A randomized control trial demonstrated in 1991 that 4 mg of folic acid supplements successfully prevented 72% of recurrence of neural tube defects (NTDs) in women who had had afflicted pregnancy. In 2000, the Japanese Government recommended women of childbearing age to take 400 microgram of folate supplements per day from 4 weeks prior to and 12 weeks after conception. A questionnaire study was performed in pregnant women by post on their awareness of the role folic acid plays, their life style, and folate intake by dietary consumption. Thirty-five percent of 1,251 pregnant women were aware of the important role of folic acid in the critical stage of fetal development and 31% actually took the supplement. Information on folic acid was obtained through mass media in 47% of the women, through the internet in 17%, through healthcare providers in 13% and so forth. The food record analysis revealed that the dietary intake of folic acid averaged 341 microg/day that was 60 microg less than what was recommended by the Government and that 33 of 86 women took the supplement. Overall, a half of pregnant women are required to take 400 microg folate supplement per day. It is to be stressed that primary prevention of NTDs by periconceptional intake of folic acid is a major public health opportunity and that prevention is more important than cure in the management of NTDs.

Drosophila T-box transcription factor Optomotor-blind prevents pathological folding and local overgrowth in wing epithelium through confining Hh signal.

Aberration of morphogen signaling leads directly to inappropriate cell differentiation and secondarily causes various pathological phenotypes such as abnormal morphogenesis and tumorigenesis. However, mechanisms for linking morphogen signaling and the higher order phenotypes have not been fully elucidated. Here we focus on the Drosophila T-box gene optomotor-blind (omb), a transcriptional target of a long-range morphogen Decapentaplegic (Dpp). Genetic analyses of omb function revealed that a negative feedback loop, where omb plays a crucial role, exists between Dpp and its upstream regulator Hedgehog (Hh), a short-range morphogen. Consequently, dysfunction of omb elicits hyperactivation of Hh signaling that causes an ectopic folding and local overgrowth in the wing columnar epithelium, neither of which are the direct results of reduced Dpp response. In the case of the local overgrowth, it was never seen in mutants for thick veins (tkv) encoding a Dpp receptor, suggesting that the Dpp signaling pathway is divided into two antagonistic branches, one of which contains Omb. Thus defect in feedback between the two morphogens explains both phenotypes, and disruption of a balance between the morphogen targets further accounts for the local overgrowth. These are the mechanisms for generating secondary phenotypes when a single signaling factor Omb fails to function.

Bladder tumor found by tension-free vaginal tape procedure.

BACKGROUND: Tension-free vaginal tape (TVT) is thought to be a most effective therapy against stress urinary incontinence. It is rare to find a bladder tumor by the TVT procedure. CASE: A 76-year-old woman with stress urinary incontinence underwent a TVT procedure. Cystoscopy performed in conjunction with the TVT procedure detected a papillary tumor. Transurethral resection of the bladder tumor was performed after the TVT procedure. CONCLUSION: Taking the possible presence of bladder tumors into consideration, TVT-related cystoscopy procedures should be performed carefully. Moreover, the case reported here suggests, at least in the short term, not only that the TVT device does not adversely affect the operability of transurethral resection of the bladder tumor, but also that the transurethral resection of the bladder tumor procedure does not lead to increased levels of urinary incontinence.