Intravesical mitomycin C (MMC) and MMC + cytosine arabinoside for non-muscle-invasive bladder cancer: a randomised clinical trial.

OBJECTIVES: To compare the urinary pH, recurrence-free survival (RFS), and safety of adjuvant intravesical therapy in patients with non-muscle-invasive bladder cancer (NMIBC) receiving mitomycin C (MMC) therapy and MMC + cytosine arabinoside (Ara-C) therapy. PATIENTS AND METHODS: A total of 165 patients with NMIBC from six hospitals were randomly allocated to two groups: weekly instillation of MMC + Ara-C (30 mg/30 mL + 200 mg/10 mL) for 6 weeks and the same instillation schedule of MMC (30 mg/40 mL). The primary outcome was RFS, and secondary outcomes were urinary pH and toxicity in the two groups. RESULTS: A total of 81 and 87 patients were randomised into the MMC and MMC + Ara-C groups, respectively. Overall, the RFS in the MMC + Ara-C group was significantly longer (P = 0.018) than that in the MMC group. A similar significant difference was detected in patients with intermediate-risk NMIBC, but not in those with high-risk NMIBC. The mean (SD) urinary pH was significantly higher in the MMC + Ara-C group than in the MMC group, at 6.56 (0.61) vs 5.78 (0.64) (P < 0.001), and the frequency of a urinary pH of >7.0 in the MMC and MMC + Ara-C groups was 6.3% and 26.7%, respectively (P < 0.001). Multivariate analysis models including clinicopathological features and second transurethral resection demonstrated that increased urinary pH was associated with better outcomes (hazard ratio 0.18, 95% confidential interval 0.18-0.038; P < 0.001). In all, there were 14 and 10 adverse events in the MMC and MMC + Ara-C groups, respectively, without a significant difference (P = 0.113). CONCLUSIONS: Our randomised clinical trial suggested that intravesical therapy with MMC and Ara-C is useful and safe for patients with intermediate-risk NMIBC. Increase in urinary pH with Ara-C is speculated as a mechanism for increased anti-cancer effects.

Pathological significance and prognostic role of microvessel density, evaluated using CD31, CD34, and CD105 in prostate cancer patients after radical prostatectomy with neoadjuvant therapy.

BACKGROUND: Neoadjuvant hormonal therapy (NHT) is performed to improve the outcome in organ-confined prostate cancer. However, there is little information regarding the relationship between angiogenesis and NHT. The aim of this study was to identify a suitable method to evaluate the angiogenic status of tissue, and to determine the prognostic value of this method for biochemical recurrence in patients who had undergone radical prostatectomy after NHT. METHODS: We analyzed 108 formalin-fixed specimens from patients treated by radical prostatectomy. NHT was administered in 48 patients (52.9%) and 60 patients who had a similar Gleason score and pT stage were selected as a non-NHT treated control group. Microvessel density (MVD) was measured using anti-CD31, anti-CD34, and anti-CD105 antibodies. The expressions of vascular endothelial growth factor (VEGF)-A and thrombospondin (TSP)-1 were also evaluated by immunohistochemistry. The prognostic value of CD31-, CD34-, and CD105-MVD for biochemical recurrence was investigated. RESULTS: The mean/SD of CD105-MVD in the NHT group (13.3/4.7) was significantly (P < 0.001) lower than that in the non-NHT group (125.8/7.3). In the NHT group, CD105-MVD was associated with pT stage and it was positively correlated with VEGF-A expression (r = 0.56, P < 0.001) and negatively correlated with TSP-1 expression (r = 0.42, P = 0.003). CD105-MVD was identified as a significant predictor of biochemical recurrence (BCR) in patients treated with NHT (log rank test, P < 0.001). Although CD31- and CD34-MVD were significantly associated with pT stage or Gleason score in non-NHT group, they were not associated with pathological features and BCR in NHT group. CONCLUSIONS: Our results indicate that CD105-MVD reflects the angiogenic conditions in prostate cancer tissues treated with NHT. CD105-MVD was also identified as a significant and independent predictor of biochemical recurrence in prostate cancer patients who underwent radical prostatectomy with NHT.

[A case of extramammary Paget's disease with urethral invasion treated by construction of continent urinary diversion based on the Monti principle using the sigmoid colon].

Extramammary Paget's disease occurring in the female vulva is occasionally associated with invasive disease to urethra and bladder mucosa. For such cases, ensuring adequate surgical margin is essential. Not only adequate removal of tumor, but also urinary diversion is important for patient's quality of life. A 77- year-old woman was treated with excision of vulvar tumor, urethra, vagina, rectum and anus. The determination of excision area was decided according to the result of mapping biopsy including urethra and bladder. Then she received reconstruction of vulva using the gracilis muscle skin flap. We applied a technique of channel formation for intermittent catheterization using the retubularized sigmoid colon based on the Monti principle. The tube was implanted submucosally into the bladder to prevent the reflux of urine. Fifteen days after operation, self-intermittent catheterization was started successfully. Surgical margins were negative in urethra, skin, vagina and rectum. There are no obvious recurrence or metastasis 1 year after surgery.

Feasibility and safety of a virtual 3-Fr sheathless-guiding system for percutaneous coronary intervention.

OBJECTIVES: To evaluate the feasibility and safety of a virtual 3-Fr system [5-Fr sheathless-guiding catheter (GC)] for percutaneous coronary intervention (PCI). BACKGROUND: The use of miniaturized devices for PCI is gaining popularity because of increased patient comfort and decreased risk of access site complications. METHODS: From July 2010 to December 2012, consecutive patients who underwent elective PCI (planned or ad hoc PCI) at our hospital were enrolled. PCI using the virtual 3-Fr system was attempted as our initial strategy, unless a 6-Fr or larger GC was considered to be suitable [lesions with heavy calcification, large (>2 mm) side branches, or chronic total occlusion]. RESULTS: Five hundred sixty-six patients underwent elective PCI during the study period, and 132 patients who met the criteria underwent PCI using the virtual 3-Fr system. Procedures using the virtual 3-Fr system were successful in 126 patients (95%); 111 (84%) were performed using the transradial approach, 110 (83%) were ad hoc procedures, and 45 (31%) were complex coronary lesions (type B2 or C). Six patients required conversion to a conventional 5- or 6-Fr sheath and catheter system. No intraoperative complications occurred, and radial artery patency was achieved in all patients who underwent transradial procedures. CONCLUSIONS: PCI using the virtual 3-Fr system is a feasible and viable alternative to conventional procedures that use a sheath and GC in appropriately selected patients. This small-caliber system may minimize endovascular trauma, particularly during transradial coronary procedures.

Deoxycorticosterone-producing adenoma concomitant with aldosterone-producing microadenoma: a challenging combination.

OBJECTIVE: To describe the challenging case of a 59-year-old male with a deoxycorticosterone (DOC)-producing adrenal adenoma concomitant with an aldosterone-producing microadenoma. METHODS: We measured the patient's aldosterone and progesterone levels during adrenal venous sampling (AVS). The steroidogenic enzyme expression was studied with in situ hybridization (ISH). Steroids profiles were determined in the peripheral serum obtained before and after the operation, as well as in the main adrenal tumor. RESULTS: The patient was diagnosed with primary aldosteronism (PA) based on typical clinical findings. He had an adrenal tumor located at the lower pole of the left adrenal gland. The aldosterone concentration in the adrenal vein proximal to the adrenal tumor was higher than that of the ipsilateral adrenal vein distal to the tumor during the AVS. Progesterone was only elevated in the adrenal vein proximal to the tumor, suggesting that the tumor produced steroids other than aldosterone. The postoperative findings revealed that the main tumor was accompanied by 2 microadenomas. The main adrenal tumor was diagnosed as a DOC-producing adenoma, and one of the microadenomas was diagnosed as aldosterone-producing based on the ISH and the determination of the steroid profiles. CONCLUSIONS: Concomitant PA masked the key findings of a DOC-producing tumor; the suppression of aldosterone in this patient. Multiple sampling in the adrenal vein considering the location of the adrenal tumor provided a clue to the diagnosis. Progesterone measurement during AVS is easy and may be useful in diagnosing rare adrenal tumors that produce intermediate products in adrenal steroid biosynthesis.

Stability of [-2]Pro-PSA in whole blood and serum: analysis for optimal measurement conditions.

BACKGROUND: The clinical usefulness of [-2]pro-PSA (where PSA is prostate-specific antigen) in prostate cancer diagnosis has been emphasized in recent studies. To determine proper blood sample handling conditions for [-2]pro-PSA evaluation, we analyzed the preanalytical stability of [-2]pro-PSA. METHODS: Blood samples from 22 Japanese males were stored under various conditions before total PSA (tPSA), free PSA, and [-2]pro-PSA concentrations were measured, and the preanalytical stability of [-2]pro-PSA and the changes in the Prostate Health Index (phi) were assessed. RESULTS: [-2]Pro-PSA was stable in serum for at least 24 hr at both room temperature (RT) and at 4°C. However, [-2]pro-PSA levels in whole blood increased rapidly over time, particularly at RT. Mean recovery (%) of [-2]pro-PSA in whole blood at RT was >110% at 1 hr after drawing of blood. The phi tended to increase over time in a pattern similar to the change in[-2]pro-PSA. CONCLUSIONS: Preanalytical stability was lower for [-2]pro-PSA than for free PSA or tPSA. Whole-blood [-2]pro-PSA increased in a time-dependent manner, particularly at RT. Thus, whole blood samples collected at RT should be centrifuged within 1 hr after drawing. The [-2]pro-PSA in serum is stable for at least 24 hr at both RT and at 4°C.

[Clinical evaluation of ureteral stenting for managing extrinsic ureteral obstruction due to gynecological and gastrointestinal cancer].

We retrospectively reviewed patients who were treated with an indwelling ureteral stent to manage extrinsic ureteral obstruction due to advanced gynecological and gastrointestinal cancers. A total of 34 patients, including 17 with gynecological cancer and 17 with gastrointestinal cancer, underwent a successful initial ureteral stent placement from January 2007 to December 2011. Functional ureteral stent failures, which required percutaneous nephrostomy within 3 months after initial ureteral stenting, occurred in 14 of the 34 patients (41%) during follow-up. The risk factors of functional ureteral stent failure were bilateral ureteral obstruction, elevated serum creatinine level, poor performance status, subsequent therapy for primary cancer after ureteral stent placement, presence of peritonitis carcinomatosa, and gastrointestinal cancer. Patients with gastrointestinal cancer had a higher rate of stent failure than did those with gynecological cancer (p = 0.01). Median survival from the diagnosis of hydronephrosis for patients with gastrointestinal and gynecological cancers was 9 and 23 months, respectively (p = 0. 02). Retrograde ureteral stenting is a useful treatment for malignant ureteral obstruction. However, patients with gastrointestinal cancer had a high stent failure rate and a short survival time from the diagnosis of hydronephrosis. Indications for retrograde ureteral stenting for malignant ureteral obstruction should be carefully considered while taking into account stent failure risk, patient prognosis and quality of life.

Unplanned hemodialysis initiation: A retrospective analysis of patient characteristics and prognosis in an emergency hospital.

INTRODUCTION: Functional decline occurs during dialysis initiation, particularly in unplanned cases. To prevent unplanned hemodialysis, we aimed to identify associated factors from the first referral to the nephrology department to hemodialysis initiation and assess patient prognosis post-unplanned hemodialysis initiation. METHODS: This retrospective study involved 257 Japanese patients initiating hemodialysis and compared patient characteristics based on whether hemodialysis was planned or unplanned at a single center. Patient outcomes were evaluated in collaboration with maintenance hemodialysis centers. RESULTS: Unplanned hemodialysis initiation correlated with heart failure history (p < 0.05) and infections like pneumonia (p < 0.001). Patients with unplanned hemodialysis initiation had a worse prognosis than those with planned initiation (p < 0.001), and multivariable Cox regression showed it as an independent risk factor for death (p < 0.05). CONCLUSIONS: Hygiene and careful attention to heart failure may reduce unplanned hemodialysis and improve patient well-being and healthcare efficiency. This retrospective analysis highlights crucial considerations for optimizing the initiation of hemodialysis.

Transcollateral retrograde approach with rendezvous technique for recanalization of chronically occluded tibial arteries.

PURPOSE: To describe a novel technique using an antegrade wire in a retrograde microcatheter advanced through a transcollateral vessel for recanalization of challenging infrapopliteal chronic total occlusions. TECHNIQUE: A 75-year-old diabetic man presented with critical limb ischemia manifested as nonhealing ulcers on the toes. Baseline angiography revealed a blunt, long, total occlusion of the anterior tibial artery. A retrograde microcatheter was advanced over a guidewire tracking the collateral channel from the planter artery. Antegrade and retrograde microcatheters were aligned inside the occluded lesion. An antegrade wire was then advanced further down through the retrograde microcatheter. Final angiography of the anterior tibial artery following balloon dilation demonstrated a satisfactory result, without evidence of significant residual stenoses or flow-limiting dissections. Complete wound healing was achieved at 3 weeks. CONCLUSION: This alternative wire method may be useful when traditional interventional approaches are unfeasible.

[AN ABSCESS OF CORPUS SPONGIOSUM CAUSED BY CANDIDURIA: A CASE REPORT].

An 88-year-old man was treated with a urethral bougie after balloon dilation for urethral stricture in 2019. In December 2020, the patient was referred to our hospital with a fever and voiding disturbance. The patient was diagnosed with a urinary tract infection at the time of admission and was treated with an antibacterial agent. Candia glabrata was detected in both the blood and urine cultures obtained on admission. However, antifungal therapy was not administered because the blood culture was negative on reexamination. Sixteen days after admission, magnetic resonance imaging revealed an abscess in the corpus spongiosum. Cystostomy and abscess drainage were performed because the corpus spongiosum abscess was worsening. Candia glabrata was detected in the abscess; therefore, we treated the patient with antifungal therapy. After 14 days of antifungal agent treatment, the corpus spongiosum abscess disappeared. An abscess of the corpus spongiosum caused by candiduria is exceedingly rare; this is the first reported case in Japan.

Bladder perforation with rectal impalement injury: Usefulness of exploratory laparoscopy for excluding intraperitoneal perforation.

A 24-year-old man presented with anal bleeding after accidentally falling on a table leg. Computed tomography showed free air in the bladder and around the rectum with a high-density area without intraperitoneal free air. The patient was suspected of having extraperitoneal bladder perforation with rectal impalement, and he underwent transanal rectal repair, colostomy, and urethral catheter placement after intraperitoneal bladder perforation was excluded by exploratory laparoscopy. Postoperative course was uneventful, and the urethral catheter was removed 19 days after surgery. Three months after the operation, colostomy reversal was performed, and the patient did not experience any complications.

The Pathological Significance and Prognostic Roles of Thrombospondin-1, and -2, and 4N1K-peptide in Bladder Cancer.

BACKGROUND/AIM: Thrombospondins (TSPs) play a role as inhibitors of angiogenesis under various pathological conditions. The aim of the study was to evaluate the pathological significance and prognostic role of the 4N1K-peptide (KRFYVVMWKK), which is derived from TSP-1 and -2, in bladder cancer. MATERIALS AND METHODS: Two-hundred and six bladder cancer tissues were examined for expression of TSP-1, TSP-2, and 4N1K-peptide by immunohistochemistry. Cancer cell proliferation, apoptosis, angiogenesis and matrix metalloproteinase (MMP)-9 immunoreactivity were also examined. RESULTS: Expression of TSP-2 and 4N1K-peptide was negatively associated with T stage, metastasis, and grade. TSP-2 expression was negatively associated with cancer cell proliferation and MMP-9 expression, whereas 4N1K-peptide was significantly associated with apoptosis, angiogenesis, and MMP-9 expression. Multivariate analysis showed that 4N1K-peptide expression was a significant predictor of metastasis (hazard ratio=3.90, p=0.002). CONCLUSION: TSP-2 and 4N1K peptide played important roles in malignant aggressiveness and progression of bladder cancer via complex mechanisms involving cell proliferation, apoptosis, angiogenesis, and MMP-9.

Expression of Class III Beta-tubulin Predicts Prognosis in Patients with Cisplatin-resistant Bladder Cancer Receiving Paclitaxel-based Second-line Chemotherapy.

BACKGROUND/AIM: Class III beta-tubulin (TUBB3) expression is recognized as a predictive marker for chemosensitivity to cisplatin- and taxane-based chemotherapies in various malignancies. The aim of this study was to clarify the predictive value of TUBB3 expression for the anticancer effects of first-line cisplatin-based chemotherapy and second-line paclitaxel-based chemotherapy in patients with urothelial cancer (UC). PATIENTS AND METHODS: We reviewed 116 patients with UC (90 with bladder cancer and 27 with upper urinary tract cancer) treated with first-line cisplatin-based chemotherapy. Among them, 42 patients received a paclitaxel-based regimen as second-line chemotherapy for advanced cisplatin-resistant UC. TUBB3 expression was evaluated using immunohistochemistry, and survival analyses were performed using Kaplan-Meier survival curves and multivariate Cox proportional hazard analysis. RESULTS: TUBB3 was mainly detected in the cytoplasm of cancer cells, and 64 patients (55.2%) were judged as having positive TUBB3 expression. TUBB3 expression was significantly associated with tumour grade (p<0.001). TUBB3 expression was not associated with time to progression after first-line cisplatin-based chemotherapy. However, positive expression of TUBB3 was significantly associated with unfavourable overall survival in patients receiving second-line paclitaxel-based chemotherapy (p=0.021). In addition, a multivariate analysis model including T-stage and metastasis at the beginning of second-line therapy and regimen showed that TUBB3 expression was an independent predictor of poorer survival (hazard ratio(HR)=3.44, 95% confidential interval(CI)=1.15-10.33, p=0.027). CONCLUSION: TUBB3 expression was identified as a useful predictive factor for survival after second-line paclitaxel-based therapy in patients with cisplatin-resistant UC. Our results are useful for determining treatment strategies for such patients.

Pathological significance and prognostic significance of FES expression in bladder cancer vary according to tumor grade.

PURPOSE: The feline sarcoma oncogene protein (FES) is a non-receptor tyrosine kinase implicated in both oncogenesis and tumor suppression. Here, cancer cell lines and human tissues were employed to clarify the pathological and prognostic significance of FES in bladder cancer. METHODS: The relationship between FES expression and cancer aggressiveness was investigated using 3 cell lines (T24: corresponding to grade 3, 5637: corresponding to grade 2, and RT4: corresponding to grade 1) and 203 tissues derived from human bladder malignancies. Proliferation, invasion, and migration of cancer cells were assessed following the knockdown (KD) of FES expression by the siRNA method. Relationships between FES expression and pathological features, aggressiveness, and outcome were investigated. RESULTS: FES-KD inhibited the proliferation, migration, and invasion of T24 cells but not of RT4 cells and 5637 cells. Considering all patients, FES expression demonstrated a negative relationship with grade but no association with muscle invasion or cancer cell proliferation. However, it was positively correlated with pT stage and cell proliferation in high-grade tumors (p = 0.002); no such association was found for low-grade tumors. In addition, elevated FES expression was a negative prognostic indicator of metastasis after radical surgery for patients with high-grade tumors (p = 0.021) but not for those with low-grade malignancies. CONCLUSIONS: FES appeared to act as a suppressor of carcinogenesis, being associated with low tumor grade in the overall patient group. However, its expression correlated with cancer aggressiveness and poor outcome in high-grade bladder cancer. FES, therefore, represents a potential therapeutic target and useful prognostic factor for such patients.

Comparison Between a Combined Transrectal and Transperineal Approach and a Transrectal Approach for Prostate Rebiopsy.

AIM: To evaluate whether a combination method involving the transrectal (TR) and transperineal (TP) approach can increase the cancer detection rate relative to the TR approach regarding repeat prostate biopsy. PATIENTS AND METHODS: One thousand and nineteen patients underwent initial prostate biopsies and 298 repeat prostate biopsies. All initial biopsies were conducted transrectally. Of the repeat biopsies, 179 (60.1%) were performed using the combined transrectal and transperineal (TR+TP) approach; 113 (37.9%) were carried out transrectally. All biopsies were performed under ultrasound guidance using a 16-gauge core biopsy needle; 651 were diagnosed as prostate cancer; 224 patients underwent radical prostatectomies (RPs). We evaluated the cancer detection rates between the biopsy methods in the repeat biopsy cohort and compared the clinical and pathological features of the RP specimens between the initial and repeat biopsy groups. RESULTS: A median of 12 and 20 cores were obtained in the initial and repeat biopsy patients, respectively. Cancer detection rates regarding biopsies 1, 2, 3, 4 and 5 were 49.2% (551/1,119), 34.7% (75/216), 33.3% (20/60), 26.7% (4/15) and 14.3% (1/7), respectively. There were no significant differences between the TR and the TR+TP approach (32.7% vs. 33.5%). RP specimens diagnosed using repeat biopsies showed more anterior dominant tumors relative to those diagnosed using the initial biopsies (59.5% vs. 35.9%; p<0.001). CONCLUSION: The TR+TP combination approach could not increase cancer detection rates relative to the TR approach in the repeat biopsy cohort. However, 16-gauge needle biopsy demonstrated acceptable cancer detection rates in the comparatively small number of biopsy cores.

Real-time transesophageal echocardiography facilitates antegrade balloon aortic valvuloplasty.

We report two cases of severe aortic stenosis (AS) where antegrade balloon aortic valvuloplasty (BAV) was performed under real-time transesophageal echocardiography (TEE) guidance. Real-time TEE can provide useful information for evaluating the aortic valve response to valvuloplasty during the procedure. It was led with the intentional wire-bias technique in order to compress the severely calcified leaflet, and consequently allowed the balloon to reach the largest possible size and achieve full expansion of the aortic annulus.

Pheochromocytoma multisystem crisis treated with emergency surgery: a case report and literature review.

BACKGROUND: Pheochromocytoma is a neuroendocrine tumor that predominantly presents with hypertension, palpitations, and tachycardia due to excessive catecholamine excretion. Although pheochromocytoma multisystem crisis (PMC) is relatively rare, urologists and clinicians should focus on early diagnosis as delay in initiating the appropriate treatment can lead to mortality CASE PRESENTATION: A 70-year-old man developed ileus after a few days of medication for hypertension. Computed tomography incidentally revealed a left adrenal mass. This finding together with his clinical course was compatible with pheochromocytoma. An α-blocker was administered immediately, and his blood pressure was well controlled. However, his general condition and laboratory data deteriorated rapidly, and the patient was diagnosed with PMC with lethal status. Thus, emergency adrenalectomy was performed without confirmation of catecholamine levels. From the resected specimen, his tumor was judged as pheochromocytoma. On immunohistochemical analysis, the proliferation index evaluated by Ki-67 staining was 9.7 %. This case report was approved by the Human Ethics Review Committee of the Nagasaki University Hospital. CONCLUSION: The present case of PMC was successfully treated with emergency surgery. The benign pheochromocytoma also presented with high cell proliferation potential, which may be a cause of the extreme aggressiveness of PMC.

Preferential Conduction Properties Along The Left Lateral Ridge And The Arrhythmogenicity Of The Left Pulmonary Veins In Patients With Atrial Fibrillation.

PURPOSE: In this study, we examined the hypothesis that the preferential conduction property along left lateral ridge (LLR) might affect the arrhythmogenicity of left pulmonary veins (LPVs). METHODS: The study population included 40 consecutive AF patients. Radiofrequency energy (RF) was sequentially delivered along the LLR from a lower to upper manner during postero-lateral CS pacing during an isoproterenol infusion. RESULTS: The conduction time during pacing from the CS was significantly prolonged during radiofrequency (RF) deliveries (before vs. after, upper; 91±26ms vs. 127±38ms, p<0.001, lower; 86±21ms vs. 103±22ms, p<0.001). Remarkable prolongation of more than 30ms was observed in 19 of 40 patients (48%) (both LPVs, 6; only the upper LPVs, 12; and only the lower LPV, 1). Sites with a remarkable prolongation were observed at the carina between the LPVs,[4] anterior site of the upper LPV carina,[10] anterior wall of the lower LPV,[3] and bottom of the lower LPVs [2] Thirty-three arrhythmogenic foci (AMF) from the LPVs were observed in 23/40 patients (56%). The conduction time during pacing from the LPVs during the RF delivery was significantly longer in the patients with AMF from the upper LPV than in those patients without (107±36ms vs. 146±40ms, p<0.01). CONCLUSION: The LLR includes the preferential conduction properties between the CS and LPVs, and the observation of the serial changes during the RF delivery could provide us information about the LPVs arrhythmogenicity.