Is transvaginal mesh surgery with polytetrafluoroethylene mesh ORIHIME® feasible for anterior pelvic organ prolapse?-Randomized comparative study between ORIHIME® and Polyform™.

OBJECTIVE: Transvaginal mesh surgery for pelvic organ prolapse has been widely performed in Japan, but polypropylene mesh has not been used in Japan since the ban on TVM using polypropylene mesh in the United States. Currently, polytetrafluoroethylene mesh ORIHIME® is the only mesh available for TVM in Japan. Although polytetrafluoroethylene is a safe material, its low coefficient of friction and insufficient adhesion to the surrounding tissue make it difficult to maintain the mesh position when it is used in the transvaginal mesh surgery. The aim of this study was to evaluate the feasibility of TVM-A2 using ORIHIME®. METHODS: One hundred cases of TVM-A2 were included in the study. The patients were randomly assigned to two groups: the ORIHIME® group (Group O) and the PolyformTM group (Group P). With 50 patients in each group, the complications and recurrences up to the fourth year were compared. Surgeries were performed using the TVM-A2 method. Statistical analysis was performed using EZR. RESULTS: There were no significant differences in baseline parameters between the two groups. We observed no perioperative complications, and saw one case of postoperative abscess formation in Group O, which resolved successfully after incision and drainage. The 4-year recurrence rate was significantly higher in Group O. CONCLUSION: As the recurrence rate was significantly higher in Group O, we conclude that TVM-A2 using ORIHIME® which is the same procedure as TVM-A2 using polypropylene mesh is not feasible in repairing the pelvic organ prolapse.

Mitotic Spindle Positioning (MISP) Facilitates Colorectal Cancer Progression by Forming a Complex with Opa Interacting Protein 5 (OIP5) and Activating the JAK2-STAT3 Signaling Pathway.

Patients with inflammatory bowel disease (IBD) who experience long-term chronic inflammation of the colon are at an increased risk of developing colorectal cancer (CRC). Mitotic spindle positioning (MISP), an actin-binding protein, plays a role in mitosis and spindle positioning. MISP is found on the apical membrane of the intestinal mucosa and helps stabilize and elongate microvilli, offering protection against colitis. This study explored the role of MISP in colorectal tumorigenesis using a database, human CRC cells, and a mouse model for colitis-induced colorectal tumors triggered by azoxymethane (AOM)/dextran sodium sulfate (DSS) treatment. We found that MISP was highly expressed in colon cancer patient tissues and that reduced MISP expression inhibited cell proliferation. Notably, MISP-deficient mice showed reduced colon tumor formation in the AOM/DSS-induced colitis model. Furthermore, MISP was found to form a complex with Opa interacting protein 5 (OIP5) in the cytoplasm, influencing the expression of OIP5 in a unidirectional manner. We also observed that MISP increased the levels of phosphorylated STAT3 in the JAK2-STAT3 signaling pathway, which is linked to tumorigenesis. These findings indicate that MISP could be a risk factor for CRC, and targeting MISP might provide insights into the mechanisms of colitis-induced colorectal tumorigenesis.

Direct evaluation of polarity of the ligand binding pocket in retinoid X receptor using a fluorescent solvatochromic agonist.

High selectivity of small-molecule drug candidates for their target molecule is important to minimize potential side effects. One factor that contributes to the selectivity is the internal polarity of the ligand-binding pocket (LBP) in the target molecule, but this is difficult to measure. Here, we first confirmed that the retinoid X receptor (RXR) agonist 6-(ethyl(1-isobutyl-2-oxo-4-(trifluoromethyl)-1,2-dihydroquinolin-7-yl)amino)nicotinic acid (NEt-iFQ, 1) exhibits fluorescence solvatochromism, i.e., its Stokes shift depends on the polarity of the solvent, and then we utilized this property to directly measure the internal polarity of the RXRα-LBP. The Stokes shift of 1 when bound to the RXRα-LBP corresponded to that of 1 in chloroform solution. This finding is expected to be helpful for designing RXR-selective ligands. A similar approach should be appliable to evaluate the internal polarity of the LBPs of other receptors.

Corticobasal syndrome mimicking Foix-Chavany-Marie syndrome with suggested 4-repeat tauopathy by tau PET.

BACKGROUND: Corticobasal syndrome (CBS) is a neurodegenerative disease diagnosed based on clinical manifestations such as asymmetrical parkinsonism, limb apraxia, and speech and language impairment. The background pathology of CBS is commonly a variety of proteinopathies, but association with cerebrovascular disease has also been reported. Foix-Chavany-Marie syndrome (FCMS) is a rare neurological disorder characterized by facio-pharyngo-glossal diplegia with automatic-voluntary movement dissociation presenting with bilateral paresis of the facial, lingual, pharyngeal and masticatory muscles. FCMS is commonly attributable to stroke. Transactive response DNA binding protein of 43 kD (TDP-43) proteinopathy is also known as the pathological background of FCMS, while the pathological background of the majority of CBS cases consists of diverse tauopathies instead of TDP-43 proteinopathy. In this report, we describe a case mimicking FCMS that was finally diagnosed as CBS with suggested 4-repeat tauopathy. CASE PRESENTATION: A 68-year-old female started experiencing difficulty speaking followed by difficulty writing, and especially texting, several years before her visit. Her impairment had been gradually worsening, and she came to our hospital. On neurological examination, she demonstrated the facial apraxia, frontal lobe dysfunction, and upper motor neuron signs. She presented some characteristics suggestive of FCMS. Her symptoms exhibited rapid progression and myoclonus, parkinsonism, and left-side dominant cortical sensory deficit occurred, resulting in the fulfillment of diagnostic criteria for CBS after 9 months. Tau PET imaging displayed notable ligand uptake in the brainstem, subthalamic nuclei, basal ganglia, and bilateral subcortical frontal lobe, suggesting that her pathological background was 4-repeat tauopathy. As a result of her progressive dysphagia, she became unable to eat and passed away after 12 months. CONCLUSION: We hereby present an atypical case of CBS showing clinical features mimicking FCMS at first presentation. TDP-43 proteinopathy was suspected based on the clinical symptoms in the early stages of the disease; however, the clinical course and imaging findings including tau PET suggested that her pathological background was 4-repeat tauopathy.

Investigation of predictive factors for the presence of voiding dysfunction after transvaginal mesh surgery-Can the flow curve shape on uroflowmetry be a predictor?

PURPOSE: This study established the prognostic significance of the uroflowmetry flow curve shape in the presence of voiding dysfunction following transvaginal mesh surgery. METHODS: This is a retrospective study of 439 symptomatic cystocele patients who underwent anterior wall repair with transvaginal mesh surgery. Uroflowmetry and postvoid residual were used to evaluate voiding function both preoperatively and 12 months postoperatively. The patients were divided into two groups: those with and without postoperative voiding dysfunction, and the predictors of postoperative voiding dysfunction were analyzed. The shape of the urine flow curve was analyzed for its influence on the presence of postoperative voiding dysfunction. RESULTS: Thirty-five participants were in the voiding dysfunction group, while 404 were in the nonvoiding dysfunction group. Multivariate analysis was conducted by adding an interrupted-shaped curve to age, Qmax, and postvoid residual, which showed significant differences in univariate analysis, found that age 68 years or older (odds ratio [OR]: 7.68, 95%CI 1.02-58, p = 0.048), postvoid residual ≥110 mL (OR: 2.8, 95%CI 1.25-6.29, p = 0.013) and interrupted-shaped curve (OR: 2.47, 95%CI 1.07-5.69, p = 0.034) were discovered to be independent risk factors for the presence of voiding dysfunction after transvaginal mesh surgery. CONCLUSIONS: Following transvaginal mesh surgery for cystocele, three variables were found to be predictive of voiding dysfunction: the old age, excessive postvoid residual, and an interrupted-shaped flow curve. The uroflowmetry flow curve shape has the potential to be a new predictor of postoperative voiding dysfunction.

Molecular and Pathological Analyses of IARS1-Deficient Mice: An IARS Disorder Model.

Most mitochondrial diseases are hereditary and highly heterogeneous. Cattle born with the V79L mutation in the isoleucyl-tRNA synthetase 1 (IARS1) protein exhibit weak calf syndrome. Recent human genomic studies about pediatric mitochondrial diseases also identified mutations in the IARS1 gene. Although severe prenatal-onset growth retardation and infantile hepatopathy have been reported in such patients, the relationship between IARS mutations and the symptoms is unknown. In this study, we generated hypomorphic IARS1V79L mutant mice to develop an animal model of IARS mutation-related disorders. We found that compared to wild-type mice, IARSV79L mutant mice showed a significant increase in hepatic triglyceride and serum ornithine carbamoyltransferase levels, indicating that IARS1V79L mice suffer from mitochondrial hepatopathy. In addition, siRNA knockdown of the IARS1 gene decreased mitochondrial membrane potential and increased reactive oxygen species in the hepatocarcinoma-derived cell line HepG2. Furthermore, proteomic analysis revealed decreased levels of the mitochondrial function-associated protein NME4 (mitochondrial nucleoside diphosphate kinase). Concisely, our mutant mice model can be used to study IARS mutation-related disorders.

Are anterior mesh arms necessary in Japanese-style transvaginal mesh surgery for cystocele?

AIM: In this study, we retrospectively analyzed the medium-term efficacy and safety of surgery with transobturator two-arm transvaginal mesh for cystocele and to verify whether the anterior arms are necessary for Japanese-style transvaginal mesh surgery. METHODS: The study included 203 patients with cystocele who underwent transobturator two-arm transvaginal mesh at our hospital between August 2015 and June 2017 and received appropriate follow-up care for at least 48 months after surgery. RESULTS: The Pelvic Organ Prolapse Quantification stage was III in all the patients. Intraoperative complications included two cases of bladder injury and one case of more than 200 mL of blood loss. The mean observation period was 51.9 months, and prolapse recurred in the operated compartment in nine patients (4.4%). No cases of mesh exposure were observed. In comparing the preoperative characteristics of the 9 patients with prolapse recurrence at the surgical site with those of the other 194 patients, we found that the recurrence rate was significantly higher among patients in whom point Ba being 3.5 cm or more and among patients younger than 66 years. CONCLUSIONS: Transobturator two-arm transvaginal mesh for cystocele was as good and safe as the procedure previously reported with four-arm mesh; thus, it was possible to omit the anterior mesh arms in Japanese-style transvaginal mesh surgery. Patients should be informed preoperatively that prolapse recurs at a significantly higher rate among younger patients and in those whose point Ba being 3.5 cm or more.

Development of Scaled-Up Synthetic Method for Retinoid X Receptor Agonist NEt-3IB Contributing to Sustainable Development Goals.

Small-molecular drugs, which are generally inexpensive compared with biopharmaceuticals and can often be taken orally, may contribute to the Sustainable Development Goals (SDGs) adopted by the United Nations. We previously reported the retinoid X receptor (RXR) agonist 4-(ethyl(3-isobutoxy-4-isopropylphenyl)amino)benzoic acid (NEt-3IB, 1) as a small-molecular drug candidate to replace biopharmaceuticals for the treatment of inflammatory bowel disease. The previous synthetic method to 1 required a large amount of organic solvent and extensive purification. In line with the SDGs, we aimed to develop an environmentally friendly, inexpensive method for the large-scale synthesis of 1. The developed method requires only a hydrophobic ether and EtOH as reaction and extraction solvents. The product was purified by recrystallization twice to afford 99% pure 1 at 100 mmol scale in about 30% yield. The optimized process showed a 35-fold improvement of the E-factor (an index of environmental impact) compared to the original method. This work, which changes the solvent used to environmentally preferable ones based on the existing synthetic method for 1, illustrates how synthetic methods for small-molecular drugs can be adapted and improved to contribute to the SDGs.

Is transvaginal mesh procedure a potential measure for pelvic organ prolapse repair when performed by expert surgeons?

OBJECTIVES: The aim of this study was to verify the safety and efficacy of transvaginal mesh by analyzing the 2-year follow-up data of patients performed by a surgeon with a high volume of procedures. METHODS: A total of 617 patients with pelvic organ prolapse underwent transvaginal mesh by a single surgeon. Complications and anatomical status of each patient were examined up to 24 months after surgery. Risk factors for the recurrence were also analyzed. RESULTS: Regarding complications, we experienced 10 patients (3.8%) of bladder injuries in anterior transvaginal mesh and eight (3.4%) in anterior and posterior transvaginal mesh. Massive blood loss was observed in four patients, but there was no case of blood transfusion. Mesh exposures were seen in seven patients (1.2%). A total of 100 patients (16.2%) had prolapse recurrence, defined as the Pelvic Organ Prolapse Quantification System stage ≥II. As to recurrences on the operated compartments, we observed five patients (2.0%) for anterior transvaginal mesh, three (6.5%) for posterior transvaginal mesh, five (7.4%) for combined transvaginal mesh, and 31 (14.2%) in anterior and posterior transvaginal mesh. Regarding Point C before operation in the anterior and posterior transvaginal mesh, the recurrence rates were more than 23% in patients with a Point C of 4 or more. Binominal regression analyses showed that higher body mass index, younger age, and higher stage of uterine prolapse were significant risk factors. CONCLUSIONS: The transvaginal mesh surgery is safe when conducted by experts. However, the recurrence rate may exceed 20% for high-stage uterine prolapse even when conducted by experts.

Evolution of Ribosomal Protein S14 Demonstrated by the Reconstruction of Chimeric Ribosomes in Bacillus subtilis.

Ribosomal protein S14 can be classified into three types. The first, the C+ type has a Zn2+ binding motif and is ancestral. The second and third are the C- short and C- long types, neither of which contain a Zn2+ binding motif and which are ca. 90 residues and 100 residues in length, respectively. In the present study, the C+ type S14 from Bacillus subtilis ribosomes (S14BsC+) were completely replaced by the heterologous C- long type of S14 from Escherichia coli (S14Ec) or Synechococcus elongatus (S14Se). Surprisingly, S14Ec and S14Se were incorporated fully into 70S ribosomes in B. subtilis However, the growth rates as well as the sporulation efficiency of the mutants harboring heterologous S14 were significantly decreased. In these mutants, the polysome fraction was decreased and the 30S and 50S subunits accumulated unusually, indicating that cellular translational activity of these mutants was decreased. In vitro analysis showed a reduction in the translational activity of the 70S ribosome fraction purified from these mutants. The abundance of ribosomal proteins S2 and S3 in the 30S fraction in these mutants was reduced while that of S14 was not significantly decreased. It seems likely that binding of heterologous S14 changes the structure of the 30S subunit, which causes a decrease in the assembly efficiency of S2 and S3, which are located near the binding site of S14. Moreover, we found that S3 from S. elongatus cannot function in B. subtilis unless S14Se is present.IMPORTANCE S14, an essential ribosomal protein, may have evolved to adapt bacteria to zinc-limited environments by replacement of a zinc-binding motif with a zinc-independent sequence. It was expected that the bacterial ribosome would be tolerant to replacement of S14 because of the previous prediction that the spread of C- type S14 involved horizontal gene transfer. In this study, we completely replaced the C+ type of S14 in B. subtilis ribosome with the heterologous C- long type of S14 and characterized the resulting chimeric ribosomes. Our results suggest that the B. subtilis ribosome is permissive for the replacement of S14, but coevolution of S3 might be required to utilize the C- long type of S14 more effectively.

A single amino acid substitution in PRKDC is a determinant of sensitivity to Adriamycin-induced renal injury in mouse.

Adriamycin (ADR)-induced nephropathy is frequently utilized in rodent models of podocytopathy. However, the application of this model in mice is limited to a few strains, such as BALB/c mice. The most commonly used mouse strain, C57BL/6 (B6), is resistant to ADR-induced nephropathy, as are all mouse strains with a B6 genetic background. Reportedly, the R2140C variant of the Prkdc gene is the cause of susceptibility to ADR-induced nephropathy in mice. To verify this hypothesis, we produced Prkdc mutant B6 mice, termed B6-PrkdcR2140C, that possess the R2140C mutation. After administration of ADR, B6-PrkdcR2140C mice exhibited massive proteinuria and glomerular and renal tubular injuries. In addition, there was no significant difference in the severity between B6-PrkdcR2140C and BALB/c. These findings demonstrated that B6-PrkdcR2140C show ADR-induced nephropathy susceptibility at a similar level to BALB/c, and that the PRKDC R2140C variant causes susceptibility to ADR-induced nephropathy. In future studies, ADR-induced nephropathy may become applicable to various kinds of genetically modified mice with a B6 background by mating with B6-PrkdcR2140C.

New inducible mast cell-deficient mouse model (Mcpt5/Cma1DTR).

Mast cell-deficient mice are helpful for understanding the roles of mast cells in vivo. To date, a dozen mouse models for mast cell deficiency have been reported. However, mice with a specific depletion of all populations of mast cells have not been reported. We generated knock-in mice, termed Mcpt5/Cma1DTR mice, expressing human diphtheria toxin A (DT) receptor under the endogenous promoter of Mcpt5 (also known as Cma1), which encodes mouse mast cell protease-5. Flow cytometry and histological analysis showed that intraperitoneal injection of DT induced almost complete depletion of mast cells in heterozygote Mcpt5/Cma1DTR/+ mice. The deletion rates of mast cells in peritoneal cavity, mesentery, abdominal skin, ear skin, and glandular stomach were 99.9%, 100%, 98.7%, 97.7%, and 100%, respectively. Passive cutaneous anaphylaxis reaction also revealed mast cell deficiency in ear skin after DT treatment. Other than mast cells, a small percentage of marginal zone B cells in Mcpt5/Cma1DTR/+ mice were killed by DT treatment. In conclusion, the Mcpt5/Cma1DTR/+ mouse model is valuable for achieving conditional depletion of all populations of mast cells without inducing a marked reduction in other cells.

Cancer Awareness and Understanding of Students in Japan: What Do Students Having Close Relatives with Cancer Think About the Disease?

Students have become more familiar with cancer because of media, such as television or the Internet, reporting on celebrity cancer cases. Moreover, with Japan's increasing age and cancer rates, the number of students whose parents/relatives develop cancer is likely to increase. This study examined cancer awareness and understanding among students aged 10 to 16 or more. A cross-sectional nationwide survey was conducted using a self-administered questionnaire. Cancer awareness and cancer understanding were assessed using a self-administered questionnaire. We collected a total of 9139 questionnaires and excluded those with missing data. Thus, we analyzed the responses of 8701 students: 2135, 2902, and 3664 from elementary, junior, and high school, respectively. Data were analyzed using a multivariable model adjusted for gender and grade. Approximately 30% of respondents had parents/relatives with cancer. In addition, there was a significant association between having parents/relatives with cancer and cancer awareness; however, students having parents/relatives with cancer had more negative awareness (i.e., "I think cancer is scary," "I think I will get cancer in the future," and "I think cancer is preventable"). Furthermore, there was a significant association between cancer understanding and awareness. These findings suggest that cancer education could have a desirable effect on students whose parents/relatives have cancer. Further, cancer education offers benefits to students who are naive about cancer and ill prepared to cope when a family member discloses a cancer diagnosis.

Sensitivity to change and responsiveness of the Balance Evaluation Systems Test (BESTest), Mini-BESTest, and Brief-BESTest in patients with subacute cerebral infarction.

[Purpose] To compare the sensitivity to change and responsiveness of the Balance Evaluation Systems Test, Mini-Balance Evaluation Systems Test, and Brief-Balance Evaluation Systems Test in patients with subacute cerebral infarction. [Participants and Methods] Thirty patients with subacute cerebral infarction participated in this study. The Balance Evaluation Systems Test, Mini-Balance Evaluation Systems Test, Brief-Balance Evaluation Systems Test, Berg Balance Scale, and ambulatory ability were assessed on admission and discharge. Sensitivity to change was calculated using the effect size, standardized response mean, and relative efficiency. Responsiveness was analyzed by comparing the ability of the difference between the scores of the balance assessments at admission and discharge in classifying the participants' ambulatory independence. [Results] All assessments showed significant improvement from admission to discharge. The effect size of the three versions of the Balance Evaluation Systems Test ranged from 0.41 to 0.69. The standardized response mean ranged from 0.75 to 1.28. The cutoff score was 16.7% for the Balance Evaluation Systems Test, 5.5 points for the Mini-Balance Evaluation Systems Test, 1.5 points for the Brief-Balance Evaluation Systems Test, and 3.5 points for the Berg Balance Scale. [Conclusion] The sensitivity to change of the three versions of the Balance Evaluation Systems Test was high or moderate. However, the Mini-Balance Evaluation Systems Test had the highest responsiveness, as determined with the extent of ambulatory independence.

A partial agonist for retinoid X receptor mitigates experimental colitis.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is an intractable disease of the gastrointestinal tract. Multiple environmental factors, including food ingredients, have been implicated in the development of these diseases. For example, animal fat-rich diets are predisposing factors for ulcerative colitis, whereas n-3 unsaturated fatty acids such as docosahexaenoic acid (DHA) show protective effects in experimental colitis and are negatively correlated with the incidence of ulcerative colitis and Crohn's disease. Given that DHA exhibits agonistic activity on retinoid X receptor (RXR), activation of RXR could be a therapeutic strategy for IBD. However, conventional full RXR agonists are known to show considerable adverse effects. We therefore took advantage of a partial RXR agonist, CBt-PMN, to minimize the adverse effects, and evaluated its efficacy in dextran sodium sulfate-induced colitis. Administration of CBt-PMN efficiently ameliorated the symptoms of colitis. This effect was attributed to the down-regulation of pro-inflammatory cytokines such as Tnf and Il6 in colon-infiltrating monocytes. Down-regulation of pro-inflammatory cytokines by CBt-PMN was also evident in lipopolysaccharide-stimulated bone marrow-derived macrophages (BMDMs). Among many RXR-associated nuclear receptors, activation of peroxisome proliferator-activated receptor δ (PPARδ) and nuclear hormone receptor 77 (Nur77) suppressed cytokine production by BMDMs. These observations suggest that the activation of PPARδ/RXR and Nur77/RXR heterodimers by CBt-PMN through the permissive mechanism is responsible for diminishing the monocyte-mediated inflammatory response in the gut. Our data highlight the importance of RXR activation in the regulation of colitis.

Cerebellar Volumes Associate with Behavioral Phenotypes in Prader-Willi Syndrome.

The objective of this study was to investigate lobule-specific cerebellar structural alterations relevant to clinical behavioral characteristics of Prader-Willi syndrome (PWS). We performed a case-control study of 21 Japanese individuals with PWS (age; median 21.0, range 13-50 years, 14 males, 7 females) and 40 age- and sex-matched healthy controls with typical development. Participants underwent 3-Tesla magnetic resonance imaging. Three-dimensional T1-weighted images were assessed for cerebellar lobular volume and adjusted for total intracerebellar volume (TIV) using a spatially unbiased atlas template to give a relative volume ratio. A region of interest analysis included the deep cerebellar nuclei. A correlation analysis was performed between the volumetric data and the clinical behavioral scores derived from the standard questionnaires (hyperphagia, autism, obsession, and maladaptive index) for global intelligence assessment in paired subgroups. In individuals with PWS, TIV was significantly reduced compared with that of controls (p < 0.05, family-wise error corrected; mean [standard deviation], 1014.1 [93.0] mm3). Decreased relative lobular volume ratios were observed in posterior inferior lobules with age, sex, and TIV as covariates (Crus I, Crus II, lobules VIIb, VIIIa, VIIIb, and IX). However, increased ratios were found in the dentate nuclei bilaterally in individuals with PWS (p < 0.01); the mean (standard deviation) × 10-3 was as follows: left, 1.58 (0.26); right, 1.67 (0.30). The altered lobular volume ratios showed negative correlations with hyperphagic and autistic characteristics and positive correlations with obsessive and intellectual characteristics. This study provides the first objective evidence of topographic patterns of volume differences in cerebellar structures consistent with clinical behavioral characteristics in individuals with PWS and strongly suggests a cerebellar contribution to altered functional brain connectivity in PWS.

Persistence Rate with Tadalafil for Treatment of Male Lower Urinary Tract Symptoms.

OBJECTIVES: We examined the persistence rate with tadalafil for treatment of male lower urinary tract symptoms (LUTS) and explored the factors relevant to withdrawal. PATIENTS AND METHODS: We retrospectively collected the data of male patients who received tadalafil treatment for LUTS. The persistence rate and the reason for withdrawal were investigated. RESULTS: A total of 155 patients were examined. Mean age and mean observation period were 71.9 (48-93) years and 15.1 (1-52) months, respectively. During the observation period, 74 patients (48%) withdrew tadalafil. The Kaplan-Meier curve indicated a 58% persistence rate at 1 year. The reasons for withdrawal included insufficient efficacy (31 patients, 42%), adverse events (21 patients, 28%), or symptom improvement (8 patients, 11%). Patients who continued tadalafil were significantly younger than those who withdrew it due to insufficient efficiency (71.4 ± 9.6 vs. 74.9 ± 9.1 years). CONCLUSIONS: Most patients withdrew tadalafil due to insufficient efficacy. Older patients are likely to withdraw the treatment because of insufficient efficacy, thus, tadalafil for male LUTS could be more effective for younger patients.

[The Clinical Course of α1 Blocker Discontinuation in Patients with LUTS/BPH Receiving Combination Therapy of Dutasteride and α1 Blocker].

We retrospectively investigated the clinical course of α1 blocker discontinuation in patients who had lower urinary tract symptoms with benign prostate hypertrophy (LUTS/BPH) and received combination therapy ofdutasteride and α1 blocker. Among the patients with LUTS/BPH who had been receiving combination therapy, those who wished to reduce the number ofprescribed drugs and discontinue the use of α1 blocker because ofsymptom improvement were recruited in this study. Symptom scores including International Prostate Symptom Score (IPSS) and overactive bladder symptom score (OABSS), parameters ofuroflowmetry and prostate volume (PV) were evaluated at the time of α 1 blocker discontinuation. Twenty-two patients discontinued the use of α 1 blocker. The mean PV at the time of α 1 blocker discontinuation was 43.2 ml, and the mean duration ofcombination therapy was 39.4 months. In 11 (50%) patients, dutasteride monotherapy without α1 blocker was maintained for a mean follow-up of 10.5 months (9-12 months) after α1 blocker discontinuation (Non-resumption group). In the other 11 patients (50%), α1 blocker was resumed because ofthe patient's request to resume the use of α1 blocker (Resumption group). The mean length ofdutasteride monotherapy was 4. 5 months (1-8 months) in the resumption group. Compared with the non-resumption group, IPSS total score and storage sub-score ofIPSS at the time of α1 blocker discontinuation were significantly higher in the resumption group. Based on the ROC curve, IPSS total score <16, IPSS voiding/storage symptom score <7, OABSS <7 and PV 54 ml or more at the time of α1 blocker discontinuation were predictors ofnon-resumption of α1 blocker. These results suggest that if LUTS is controlled by a long-term combination therapy ofdutasteride and α1 blocker and still PV is large enough, α1 blocker can be discontinued.

[Initial Experiences of Dynamic Sentinel Lymph Node Biopsy (DSNB) in Patients with Penile Cancer].

We present 2 cases of penile cancer in which the inguinal lymph node was not palpable and inguinal lymph node dissection (ILND) could be safely avoided by conducting dynamic sentinel lymph node biopsy (DSNB). The first case was in a 54-year-old man complaining of penile tumor for at least 3 months. We performed partial penectomy and DSNB. The pathological diagnosis was squamous cell carcinoma (SCC), pT2-3. There was no cancer metastasis in sentinel nodes (0/2). There has been no recurrence for 6 years after operation. The second case was 65-year-old man suffering from penile tumor for at least 6 months. We performed partial penectomy and DSNB. The pathological diagnosis was SCC,pT2. There was no cancer metastasis in sentinel nodes (0/3). There has been no recurrence for 1 year after operation. ILND has been recommended for intermediate and high-risk penile cancer even in patients with non-palpable inguinal lymph nodes. However,the complication of ILND is very high. DSNB has the potential to avoid ILND if there is no cancer metastasis in sentinel nodes.

[Relationship between Early Complications after Radical Cystectomy and Psoas Muscle Mass].

Psoas muscle mass index (PMI) is related to sarcopenia. We examined whether PMI is associated with early complications after radical cystectomy. Seventy one male and 29 female patients who were 65 years old or older and who had undergone radical cystectomy at our hospital from April 2005 to March 2018 were retrospectively analyzed. Psoas muscle section area was measured manually on preoperative computed tomography (CT) scan and normalized by patient's height. Early postoperative complications of grade 3 or more occurred in 12 male (16.9%) and 5 female (17.2%) patients. PMI was lower in male patients who had early postoperative complications of grade 3 or more than in those without complications (5.61 vs 6.54 cm2 /m2, p=0. 08), although the difference was not statistically significant. There was suggested to be a relationship between early postoperative complications after radical cystectomy and preoperative PMI in elderly male patients.