[TREATMENT OUTCOMES OF BLADDER NECK CONTRACTURE AFTER TRANSURETHRAL PROSTATE SURGERY].

(Introduction) A known complication of the surgical treatment of benign prostatic hyperplasia (BPH) is bladder neck contracture (BNC). BNC is often treated using transurethral incision of the bladder neck (TUI-BN); however, there are few reports on the outcomes of TUI-BN. Therefore, we examined the outcomes of patients who underwent TUI-BN after transurethral prostate surgery. (Material and methods) We retrospectively examined 25 patients who underwent TUI-BN between February 2015 and January 2021 for the following: (1) patients' characteristics; (2) the time from transurethral prostate surgery to TUI-BN; (3) the trigger of BNC diagnosis; (4) surgical procedure of BNC repair/perioperative course; (5) micturition function immediately after TUI-BN; and (6) Postoperative outcomes. (Results) The median age of the patients was 77 years, and the surgical procedures for BPH were transurethral resection of the prostate (TURP) in four cases, transurethral resection in saline plasma vaporization of the prostate (TURisP) in nine cases, and transurethral enucleation with bipolar (TUEB) in 12 cases. The median time to onset of BNC symptoms was 364 days, and 18 patients (72%) were diagnosed within 2 years. The trigger of BNC diagnosis was urinary symptoms in 21 cases, of which 16 patients had exacerbation of urination. The median duration of the surgical procedure of BNC repair was 14 min, and the incisions most frequently used (in 44% of cases) were at the 4 o'clock and 8 o'clock positions. Transient stress urinary incontinence was observed as a complication in three cases. In the 4 o'clock and 8 o'clock incisions, the maximum urine flow rate improved significantly (11.1 mL/s perioperatively vs. 20.9 mL/s postoperatively; P=0.004). These symptoms improved in 16 of the 21 symptomatic cases, and the maximum urine flow rate improved significantly (P< 0.01). The median observation period after surgery was 170 days; eight postoperative patients were lost to follow up. There were two cases of recurrence. (Conclusions) BNC is likely to develop within 2 years after transurethral prostate surgery. In this study, the success rate of the initial TUI-BN was 92%, as reoperation was required in two cases; however, the overall prognosis was good.

[OUTCOMES OF CHRONIC UNILATERAL HEMATURIA TREATED USING DIGITAL FLEXIBLE URETEROSCOPE].

(Objectives) We examined the treatment outcomes in cases of chronic unilateral hematuria treated using flexible ureteroscope for observation and hemostasis. (Methods) The study included 14 patients (7 men and 7 women) with a median age of 56.5 years who underwent ureteroscopy using a digital flexible ureteroscope for chronic unilateral hematuria between March 2014 and August 2019. All the patients presented with macroscopic hematuria as a clinical symptom, but in one patient, the hematuria was accompanied by anemia and required a blood transfusion. In addition, bleeding occurred on the left side in 8 patients and on the right side in 3 patients; however, for the remaining 3 patients, the affected side could not be identified. Fourteen patients were examined on the basis of the ureteroscopic findings, number of bleeding sites, hemostatic intervention, treatment effect, and presence or absence of recurrences. (Results) The ureteroscopic findings showed a hemangioma in 7 patients and minute venous rupture in 3, but the remaining 4 patients showed no clear findings. The site of the findings was in the superior calyces in 8 cases, middle calyces in 4 cases, inferior calyces in 4 cases, and renal pelvic wall in 1 case. In addition, the findings were located at multiple sites in 6 cases, including all renal calyces in 2 cases. Ten patients with findings underwent hemostatic interventions (electrocoagulation and laser treatment). The median postoperative follow-up period was 32.4 months (range, 6.4-65.4 months). In all the cases, the hematuria disappeared after treatment. One of the 2 patients with findings in all renal calyces showed recurrence of macroscopic hematuria at 1 year and 6 months, which disappeared after conservative treatment. (Conclusions) In this study, observation using digital flexible ureteroscope was useful in the treatment of chronic unilateral hematuria, and the hemostatic interventions performed on the bleeding sites in the renal pelvis were effective.

Accelerated modification of the zona pellucida is the primary cause of decreased fertilizability of oocytes in the 129 inbred mouse strain.

We investigated whether the small litter size in the 129 inbred mouse strain results from a reduction in oocyte fertilizability. Sensitivity of the zona pellucida to α-chymotrypsin was examined for oocytes collected at 14 h (shortly after ovulation), 17 h, and 20 h after hCG injection. Passage of spermatozoa through the zona pellucida (using an in vitro fertilization (IVF) technique) and the density of cortical granules were examined for oocytes collected at 14 and 17 h after hCG injection. The capability of the oolemma to fuse with the sperm plasma membrane was also evaluated by IVF using zona-free eggs. The zona pellucida became markedly resistant to the enzyme 17 h after hCG injection. IVF rates significantly decreased at this time. In addition, there was a significant reduction in the density of cortical granules. When zona-free oocytes were inseminated, high fertilization rates were obtained at both 17 and 14 h after hCG injection. These results indicate that accelerated modification of the zona pellucida primarily causes a decreased fertilizability of oocytes in 129 mice, resulting in the low reproductive performance of this strain.

Pathological characteristics and clinical course of bladder tumour developing after nephroureterectomy.

OBJECTIVES: To determine the pathological features and clinical course of intravesical recurrence after nephroureterectomy (NU) for upper urinary tract (UUT) cancer. PATIENTS AND METHODS: Among 325 patients undergoing NU with bladder cuff excision for UUT cancer, in this retrospective multi-institutional study we evaluated 113 who developed bladder tumour after NU. Excluding patients with (i) perioperative systemic chemotherapy or radiotherapy for UUT cancer; (ii) a history of previous or synchronous bladder cancer at the time of NU; (iii) distant metastasis at the time of NU; (iv) a follow-up of <1 year after the initial bladder cancer recurrence; or (v) missing data, 74 patients were included in this study. We compared the pathology between UUT cancer and the first bladder cancer recurrence, using Fisher's exact test. Further intravesical recurrence and bladder cancer progression was analysed using the Kaplan-Meier method, with the log-rank test used to assess significance. A Cox proportional hazard model was used for multivariate analysis. RESULTS: The grade of the first bladder cancer recurrence strongly correlated with that of the UUT tumour (P < 0.001) and the carcinoma in situ (CIS) lesion with the first bladder cancer recurrence correlated with high grade (grade 3) UUT tumour (P < 0.001). In all, 56 of the assessable 70 patients further developed intravesical recurrence at a median interval of 7 months after the first bladder cancer recurrence. There were no clinicopathological factors that predicted the second recurrence. Progression occurred in 14 patients, at a median interval of 25 months. A CIS lesion with the first bladder cancer recurrence was a risk factor for progression on multivariate analysis. CONCLUSIONS: A large proportion of the patients who developed bladder tumour after NU had further intravesical recurrence, which indicated its refractory nature. Especially when a CIS lesion is detected in the initial intravesical recurrence, a careful follow-up is mandatory to detect bladder cancer progression.

Low fertility in vivo resulting from female factors causes small litter size in 129 inbred mice.

PURPOSE: 129 inbred mice show poor reproductive ability, as evidenced by small litters; however, the exact cause of this is unknown. In the present in vivo study we examined fertility and subsequent post-implantation development in an attempt to clarify the cause of small litter size in 129 mice. METHODS: 129 or C57BL/6J females that displayed vaginal plugs 1 day after mating with males of the same strain were examined for the presence of fertilized eggs. Reciprocal matings were also performed between 129 and C57BL/6J mice. Subsequent post-implantation development of fertilized eggs was examined by dissecting females 18-19 days after the vaginal plugs were found. RESULTS: Mean numbers of recovered eggs were 7.9 and 8.0 in 129 and C57BL/6J mice, respectively. Half of the recovered eggs were unfertilized in 129 mice, whereas all were fertilized in C57BL/6J mice. Mean numbers of live fetuses 18-19 days after mating were significantly lower in 129 mice (4.7) than in C57BL/6J mice (7.3). In different types of pairings using both strains of mice, the fertility was significantly lower whenever 129 females were used. CONCLUSIONS: The small litter size in 129 mice is caused by low fertility resulting from female factors.

Survival and prognostic classification of patients with metastatic renal cell carcinoma of bone.

OBJECTIVES: We retrospectively analyzed the survival of renal cell carcinoma patients with bone metastases, and identified prognostic factors and a model predictive for survival in these patients. METHODS: Fifty patients with renal cell carcinoma with osseous metastases were treated at Hokkaido University Hospital between 1980 and 2004. The relationship between several clinical features and survival was examined univariately. The Cox proportional hazards model was then used to form a multivariate model. RESULTS: The median survival time from the diagnosis of bone metastasis was 12 mo, and overall survival at 2 yr was 37%. Clinical features correlated with longer survival in the multivariate analysis were a long interval (24 mo or more) between the diagnosis of kidney cancer and that of osseous metastasis (hazard ratio [HR]: 2.608; 95% confidence interval [CI], 1.031-6.599) and the absence of extraosseous metastases (HR: 2.523; 95%CI, 1.023-6.220). By combining these two favorable factors, renal cell carcinoma patients with osseous metastases could be categorized into two different groups. The median time to death in 20 patients with zero favorable factors (poor prognosis) was 5 mo. On the other hand, 30 patients had one or two favorable factors (good prognosis); the median survival time in this group was 30 mo. There was a significant difference in survival duration between the two groups (p<0.001). CONCLUSIONS: Two prognostic factors predicting survival were identified and used to categorize renal cell carcinoma patients with bone metastasis into two prognostic groups.

Expression patterns of the implantation-associated genes in the uterus during the estrous cycle in mice.

The mRNA expression patterns of EGF, HB-EGF, Amphiregulin, EGF receptor, IGF-1, CSF-1, IL-1 alpha, IL-1 beta, IL-1 receptor type 1, IL-1 receptor antagonist, LIF, COX-1, COX-2, Mucin-1, calcitonin, and rat USAG-1 mouse homologue, all of which are involved in the process of conceptus implantation to the endometrium, were examined during the estrous cycle by means of real-time quantitative PCR. COX-2, HB-EGF, LIF, Mucin-1, CSF-1, IL-1 alpha, IL-1 beta, and IL-1 receptor antagonist were temporally regulated during the estrous cycle and highly expressed during the estrous stage. In the case of COX-1, EGF, IGF-1, and EGF receptor, the highest mRNA expression was during the diestrous stage. In contrast, the rat USAG-1 mouse homologue mRNA expression did not change during the estrous cycle. These results indicate that rat USAG-1 mouse homologue expression at implantation might be specifically regulated by embryonic factors rather than the maternal environment.

Exposure of C57BL/6J male mice to an electric field improves copulation rates with superovulated females.

It is well-known that there are considerable strain differences in the relative copulation rates between male and superovulated female mice. In particular, the C57BL/6J strain of mice has a lower rate of successful copulation. We examined the effect of exposure to an electric field on sexual behavior in C57BL/6J male mice. When C57BL/6J males were exposed to a 50 Hz, 45 kV/m electric field for 30 min per day for 11 days and placed in a cage with a superovulated female of the same strain, the successful copulation rates of males was significantly improved compared with unexposed males (P<0.05). These results suggest that the exposure of C57BL/6J male mice to an electric field improves their sub-fertility activity in mating with superovulated females.

Possible expansion of "Window of Implantation" in pseudopregnant mice: time of implantation of embryos at different stages of development transferred into the same recipient.

Blastocyst implantation and successful establishment of pregnancy require delicate interactions between the embryo and maternal environment. It is believed that the growth of transferred embryos of different ages is synchronized during preimplantation development and that such embryos are implanted in the uterus at the same time. To define the time of synchronization for developing embryos of different ages, embryos at two different stages of development were transferred separately into the oviducts of the same recipient. We then examined the subsequent development of the embryos at various time intervals after transfer. Pronucleus (PN) stage eggs were transferred separately to the right or left oviduct of recipients on Day 0, while eight-cell embryos (8C) were transferred to the other oviduct. For 8C, 5%, 63%, and 74% of transferred embryos were implanted in the uterus at 42, 66, and 90 h posttransfer, respectively. In contrast, none of the transferred PN was implanted until 90 h posttransfer. At 90 h posttransfer, 59% of the PN had successfully implanted. Histological examination revealed that developmental stage of the embryos in both groups synchronized around 162 h posttransfer, even though the implantation was accelerated in 8C compared with PN. Our results indicate that embryos of advanced stage transferred to the oviduct implant in the uterus in advance of younger embryos and that the uterine development is synchronized at the neural plate, presomite stage. Our results strongly suggest that uterine receptivity for implantation is expandable in pseudopregnant mice.

Comparison of macrophage scavenger receptor-A knockout mice with wild type ones in the immune response against repeated infestation with Haemaphysalis longicornis.

Using macrophage scavenger receptor-A knockout (SRKO) mice, we examined the role of macrophage class A scavenger receptors (MRS-A) on the immune response and acquisition of host resistance against repeated infestation with Haemaphysalis longicornis. Except for one batch of nymphs that infested one of the SRKO (SR-/-) mice and showed no appreciable reduction in body weight, all the other groups of nymphs manifested significant decrease in body weight. Both SR-/- and wild type (SR+/+) mice showed a sustained increase in anti-tick antibody titers, but SR+/+ mice showed significantly higher titers. The IFN-gamma assayed in SR-/- mouse immune sera was substantially less compared with that in SR+/+ mice. Immune sera from SR-/- and SR+/+ mice recognized the 51 and 44 kDa, and 44 kDa proteins, respectively, of the salivary gland antigen. The difference in the level of anti-tick resistance manifested by both groups of mice may be influenced by less efficient trapping and processing of tick antigens by macrophages in mice lacking for the macrophage scavenger receptors, and consequently affected the cascade of Th1 and Th2 responses. We have thus obtained valuable data that strongly infer the role of MSR-A in enhancing host defense against repeated infestation with H. longicornis.

Immune responses of interferon gamma (IFN-gamma) knock out mice to repeated Haemaphysalis longicornis (Acari: Ixodidae) nymph infestations.

To investigate the immunological mechanisms of acquired resistance to tick infestation, interferon gamma (IFN-gamma) deficient mice (IFN-gamma mice) were used to assess interleukin-4 (IL-4) and antibody production levels against tick salivary gland antigen on three successive infestations with Haemoaphysalis longicornis Neumann nymphs. The engorged body weight of the ticks decreased during the second and third infestations. Similar observations were noted in IFN-gamma+/+ mice. However, the engorged body weight of the ticks from IFN-gamma +/+ mice were considerably lower than those from IFN-gamma-/- mice. A marked increase in antibody production during the second and third infestations was observed indicating that IFN-gamma-/- mice could acquire immunological resistance against H. longicornis nymphs. Moreover, IL-4 levels were higher during the first and third infestations but decreased during the second infestation. IL-4 levels were significantly higher in IFN-gamma-/- mice than in IFN-gamma+/+ mice. We have shown here that the statistically significant high IL-4 levels observed in IFN-gamma-/- mice may be a result of type 2 helper cell (Th2) polarization. However, the apparently higher IL-4 levels during the first and third infestations and the notable decline during the second infestation suggest that other cytokines or factors in the host immune system may play a part in regulating IL-4 levels.

Immunohistochemical localization and possible physiological roles of tumor necrosis factor-α in mouse cumulus-oocyte complexes.

Tumor necrosis factor-α (TNF-α), a cytokine which is produced by activated macrophages, has been shown to participate in the regulation of ovarian functions. In the course of our investigation on the mechanism of maturation, fertilization and degeneration of mouse oocytes, immunoreactivity to TNF-α was found in the cytoplasm of the cells surrounding the maturing oocytes and of granulosa cells facing the antral cavity. Immunoblot analysis with the specific antibody to TNF-α identified the 17 kDa Mr band in the extract of cumulusoocyte complexes. Various concentrations of TNF-α (mouse, recombinant) and anti TNF-α antiserum (polyclonal rabbit anti-mouse recombinant TNF-α) were then used to determine their effect on the germinal vesicle breakdown (GVBD), polar body extrusion, fertilization and fragmentation of mouse oocytes/eggs. TNF-α at concentrations of 10 ng/mL or less and anti-TNF-α antiserum at concentrations of 10% or less, had no effect on the spontaneous GVBD and polar body extrusion of mouse oocytes in culture. Mouse follicular oocytes cultured for more than 72 h in modified Krebs-Ringer solution in vitro undergo spontaneous fragmentation, which is a degenerative change to form 'blastomeres' with or without nuclear fragments or chromatin. Ghost-like blastomeres were also identified in the space among fragmented 'blastomeres'. The spontaneous fragmentation of mouse follicular oocytes was suppressed in the presence of TNF-α at concentrations of 1 ng/mL or greater. Anti-TNF-α antiserum (1%) accelerated the induction of fragmentation of oocytes cultured in vitro. The addition of anti TNF-α antiserum (10%) to the culture medium did not influence the fertilization rates of the eggs surrounded by the expanded cumulus. These results appear to indicate that the process of degeneration of mouse oocytes/eggs is modulated by TNF-α accumulated in the expanded cumulus during oocyte maturation.

Morphological Differentiation of the Microvasculature During Follicular Development, Ovulation and Luteinization of Mouse Ovaries: (microvasculature/ovarian follicles/corpus luteum/mouse ovary).

The chronological changes of the microvasculature during follicular development, ovulation and luteinization of mouse ovaries were examined by observation of serial histological sections, lectin angiographs and resin-corrosion casts. Graafian follicles possessing oocytes with germinal vesicles were surrounded by a few layers of basket-like capillary wreath adjacent to the follicular basement membrane. Just before ovulation 11-12 hr after hCG administration, some theca cells differentiated into hypertrophic cells, and the follicular basement membrane underwent fragmentation. Then the capillaries within the theca interna became dilated, and hyperpermeable and appeared to be injured. The capillary wreath extended into the follicle via the hypertrophied theca interna. After ovulation, the follicular wall became markedly edematous. Capillary branches invaded the granulosa cell layer of the ruptured follicle from the region of extravasation to form an intricate capillary network. The capillary network occupied the whole corpus luteum until 24 hr after hCG administration.