Efficacy of Transvaginal Surgery Using an ORIHIME Mesh With Wider Arms and Adjusted Length.

INTRODUCTION: Transvaginal mesh surgery (TVM) is an effective treatment measure for pelvic organ prolapse (POP). However, the ORIHIME mesh (Kono Seisakusho, Japan, Tokyo), which has the disadvantage of poor adherence to tissues, is currently the only product available for this procedure. Our research team has previously developed a modified ORIHIME mesh with wider arms with the aim of minimizing the risk of POP recurrence. Additionally, the length of the mesh behind the anterior vaginal wall has been adjusted to prevent urinary incontinence. The current study aims to examine the efficacy of this modified mesh in minimizing postoperative complications in patients undergoing uphold-type TVM. METHODS: The data of 84 patients who underwent TVM using ORIHIME at our hospital since July 2019 were retrospectively analyzed. The patients were divided into three groups as follows: (a) normal arms (NA; arm width < 6 cm; n = 29 cases); (b) wide arms without length adjustment (WA and LA (-); arm width > 6 cm; n = 27 cases); and (c) wide arms with length adjustment (WA and LA (+); n = 28 cases). Data were collected using various questionnaires, and the residual urine volume was measured before and after surgery. Additionally, the 60-minute pad test was performed where possible, and the recurrence and complication rates were recorded. RESULTS: The incidence of mesh exposure and urinary incontinence in daily life tended to be lower in the WA and LA (+) groups, although this difference was not statistically significant. The one-year postoperative POP recurrence rate, residual urine volume, International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score were significantly lower in the WA and LA (+) groups compared to the other groups. CONCLUSION: Uphold-type TVM using the modified ORIHIME mesh with wider arms and adjusted length was associated with better postoperative treatment outcomes compared to TVM using the traditional ORIHIME mesh.

Favorable Postoperative Outcomes After Transvaginal Mesh Surgery Using a Wide-Arm ORIHIME® Mesh.

Introduction Transvaginal mesh surgery (TVM) is an effective treatment option for pelvic organ prolapse (POP). Although ORIHIME®, the only available mesh product, is thin, soft, and easy to handle, it has the disadvantages of sliding off or mildly adhering to the surrounding tissues. The current study compared the efficacy of using wide-arm ORIHIME (Kono Seisakusho, Japan, Tokyo), non-wide arm ORIHIME, Gynemesh PS (Johnson and Johnson, Japan, Tokyo), and Polyform (Boston Scientific Japan, Japan, Tokyo) meshes for TVM. Methods The study included 116 patients who underwent TVM (Prolift with Gynemesh PS (n = 14); Elevate with Polyform (n = 43); Uphold with non-wide-arm ORIHIME (n = 24); Uphold with wide-arm ORIHIME (n = 35)) at our hospital. Pre- and post-surgical changes in symptoms were measured using questionnaires and 60-minute pad weight testing and compared by mesh type and surgical methods used. Results The residual urine volume, 60-minute pad weight testing, international prostate symptom score (IPSS), overactive bladder symptom score (OABSS), and international consultation on incontinence questionnaire-short form score (ICIQ-SF) significantly improved one year postoperatively in the TVM with the wide-arm ORIHIME group. Comparison of pre and one-year postoperative findings by mesh type and surgical methods used showed no significant differences in the 60-minute pad test, IPSS, Quality of Life (QOL), OABSS, and urinary incontinence in daily life scores, and improvement in residual urine volume, ICIQ-SF, and mesh exposure and POP recurrence rates in the TVM with the wide-arm ORIHIME group. Conclusion TVM with wide-arm ORIHIME had better postoperative outcomes compared to TVM with other mesh products.

Experience with pre-diluted plasma exchange therapy for hyperviscosity syndrome.

INTRODUCTION: Plasma exchange therapy (PE) is useful for patients with primary macroglobulinemia and multiple myeloma who present with hyperviscosity syndrome. However, hyperviscous blood may coagulate in the circuit during treatment, and in that case necessitate discontinuation of the treatment. This time, we report that we were able to prevent coagulation in the circuit by adding some ideas during the membrane separation method. METHODS: Physiological saline is injected in front of the plasma separation membrane to pre-dilute the blood, followed by filtration through the plasma separation membrane. RESULTS: As a result of pre-diluting with physiological saline to reduce the viscosity entering the separation membrane, it was possible to process the planned target amount. CONCLUSION: In patients with hyperviscosity syndrome who showed intracircuit coagulation during plasma exchange therapy, devising a predilution method should be considered as one of the ways to continue treatment.

Copy number gain of ACTN4 is associated with poor prognosis in patients with upper urinary tract urothelial carcinoma.

α-Actinin4 (ACTN4), an isoform of non-muscular α-actinin, is involved in enhancing cell motility and promoting cancer infiltration and metastasis in various cancers. However, information remains limited regarding the pathological significance of ACTN4 expression in upper urinary tract urothelial carcinomas (UUTUCs). We obtained tumor samples from 168 consecutive patients with newly diagnosed UUTUCs (92 with renal pelvic cancers and 76 with ureteral cancers), who were treated with nephroureterectomy or partial ureterectomy, and analyzed the expression of the ACTN4 protein and the amplification of ACTN4 using immunohistochemistry and fluorescence in situ hybridization (FISH), respectively. The median follow-up duration was 65 months. Among 168 cases, 49 (29%) showed ACTN4 protein overexpression and 25 (15%) showed copy number gain (≥4 copies per cell) of ACTN4. The copy number gain of ACTN4 detected using FISH significantly correlated with ACTN4 protein overexpression and several adverse clinicopathological factors, including higher pathological T stage, lymphovascular invasion, lymph node metastasis, positive surgical margin, concomitant subtype histology, and non-papillary gross finding. Cox univariate regression analyses revealed that both copy number gain of ACTN4 and ACTN4 protein overexpression were significant risk factors for extraurothelial recurrence and death (each p < 0.0001), but multivariate analysis revealed that only copy number gain of ACTN4 was an independent risk factor for extraurothelial recurrence and death (p = 0.038 and 0.027, hazard ratio = 2.16 and 2.17, respectively). This is the first study demonstrating the aberrant expression status of ACTN4 in UUTUC and indicating its putative usefulness as a prognostic indicator in patients with UUTUC.

Composite pheochromocytoma-ganglioneuroma: a case with two distinct components radiographically.

Composite pheochromocytoma is an extremely rare tumor that comprises a pheochromocytoma and an embryologically related neurogenic tumor, such as ganglioneuroma, ganglioneuroblastoma, neuroblastoma, or peripheral nerve sheath tumor. A 46-year-old male with hypertension, elevated plasma catecholamine levels, and suspected pheochromocytoma presented to the National Defense Medical College Hospital. CT and MRI showed two adjacent masses in the left adrenal gland; one was a 6 cm cephalic lesion and the other was a 1.5 cm caudal lesion. Only the 1.5 cm caudal mass showed uptake on 123I-metaiodobenzylguanisine single photon emission CT/CT. Pheochromocytoma was suspected and a left adrenalectomy was performed. Pathology confirmed that the 6 cm mass was a ganglioneuroma and the 1.5 cm mass a pheochromocytoma, with cellular intermingling at their border. The two masses were diagnosed as a composite pheochromocytoma-ganglioneuroma. This is the first report in which the two components of a composite pheochromocytoma can be clearly distinguished in the pre-operative images. If a patient with clinically suspected pheochromocytoma has different components from a typical pheochromocytoma, composite pheochromocytoma should be considered.

Prognostic impact of stromal periostin expression in upper urinary tract urothelial carcinoma.

BACKGROUND: Periostin is an extracellular matrix protein that has been known to be implicated in fibrillogenesis and cell migration, including cancer metastasis. Periostin overexpression in cancer cells and/or intervening stroma is usually related to tumor progression and poor patient outcomes in various human cancers; however, its role in urothelial carcinoma, especially upper urinary tract urothelial carcinomas (UTUCs), remains inconclusive. METHODS: Samples from 126 consecutive cases of invasive UTUC (69 renal pelvic cancers and 57 ureteral cancers) were histologically reviewed and analyzed for periostin expression using immunohistochemistry. The intensities of immunoreactivity and the fraction of positive cancer cells and stroma (i.e., epithelial and stromal expression, respectively) were classified into four categories each (intensity, 0-3; fraction, 0-25% = 1; 26-50% = 2; 51-75% = 3; and > 75% = 4). The overall score was determined by multiplying both scores, and overall scores ≥ 6 were considered to indicate high periostin expression. RESULTS: Among 126 UTUCs, 55 (44%; 27 renal pelvic and 28 ureteral cancers) showed high stromal periostin expression. None of the cases were considered to have high epithelial periostin expression. High stromal periostin expression was associated with non-papillary gross findings, higher pathological T category, lymphovascular invasion, concomitant carcinoma in situ, subtype histology, lymph node metastasis, positive surgical margins, high tumor budding, and high tumor-associated immune cell status. Multivariate analysis revealed that high stromal periostin expression was an independent predictor of overall survival (p = 0.00072, hazard ratio = 3.62), and lymphovascular invasion and high stromal periostin expression were independent predictors of cancer-specific survival (p = 0.032 and 0.020, hazard ratio = 2.61 and 3.07, respectively). CONCLUSIONS: Stromal periostin expression was often observed in invasive UTUCs with adverse clinicopathological factors and may be a useful predictor of patient outcomes.

Evaluation of the efficacy of perineal urethrostomy for patients with anterior urethral stricture: insights from surgical and patient-reported outcomes.

PURPOSE: To examine the efficacy of perineal urethrostomy (PU) in patients with anterior urethral stricture. METHODS: Patients who underwent PU for anterior urethral stricture between 2013 and 2020 were retrospectively reviewed (n = 56). Surgical success was defined as no need for additional intervention. Uroflowmetry and measurement of residual urine volume (PVR) were examined postoperatively, and the patients were asked to fill out sexual health inventory for men (SHIM) and the validated Urethral Stricture Surgery Patient-reported Outcome Measure questionnaires before and after PU. The overall patient satisfaction was also assessed. RESULTS: PU was successful in 92.9% of patients (n = 52), with a median follow-up of 34 months. Two of four were salvaged by re-do PU, and one was salvaged by forming a composite stoma using a penile skin graft. Thirty-nine patients (69.6%) filled out the questionnaires 6 months after surgery. The mean maximum flow rate, PVR, lower urinary tract symptoms (LUTS)-total score, LUTS-specific quality of life, and EuroQol-visual analog scale scores improved significantly from 3.8 mL/s, 77.6 mL, 12.9, 2.6, and 53.6 at baseline to 17.6 mL/s, 21.3 mL, 4.1, 0.9, and 74.9 postoperatively (p = 0.003, p = 0.004, p = 0.005, p < 0.0001, p < 0.0001, respectively). The SHIM score did not change significantly (from 2.6 at baseline to 2.3 postoperatively; p = 0.59). As for patient satisfaction, 84.6% of patients (33/39) were "satisfied" (46.1%) or "very satisfied" (38.5%) with the outcome. CONCLUSIONS: PU had a high surgical success rate, and significantly improved patients' subjective symptoms and achieved a high level of satisfaction.

Tumor budding in upper urinary tract urothelial carcinoma: a putative prognostic factor for extraurothelial recurrence and overall survival.

Tumor budding, defined as a single cancer cell or clusters of fewer than five cancer cells observed at the tumor invasion front, has been reported to be associated with poor prognosis in various types of cancers. However, limited information regarding the pathological and prognostic significance of tumor budding in upper urinary tract urothelial carcinoma (UUTUC) is available. We investigated 135 consecutive patients with newly diagnosed invasive UUTUCs (73 with renal pelvic cancers and 62 with ureteral cancers) treated with nephroureterectomy or partial ureterectomy between 1999 and 2018 in our hospital. Under a × 200 magnification, tumors with 10 or more budding foci were defined as "high tumor budding". The median follow-up period was 53.6 months. Among the 135 patients, 41 (30%; 16 with renal pelvic cancers and 25 with ureteral cancers) showed high tumor budding. High tumor budding was related to adjuvant chemotherapy status, higher pathological T stage, lymphovascular invasion, lymph node metastasis, tumor location, concomitant variant histology, and non-papillary gross finding. The multivariate Cox analysis revealed that LVI and high tumor budding were independent predictors for extraurothelial recurrence (P = 0.039 and 0.014, hazard ratio = 2.50 and 2.88, respectively), and high tumor budding was an independent predictor for overall survival (P = 0.024, hazard ratio = 2.33). Tumor budding can be easily introduced in clinical practice with no need for immunohistochemical analysis, may be an important clinicopathological factor of UUTUC, and is suggested to be useful as a novel predictive prognostic factor of patients with invasive UUTUC.

[CLINICAL ANALYSIS OF 95 CASES OF PERCUTANEOUS CYSTOSTOMY].

(Introduction) Percutaneous cystostomy is a standard urological procedure; however, very few reports have focused on the many cases of this procedure performed in Japan. We analyzed the background of the procedure and its approach as well as the incidence of its complications at our institution. (Material and methods) We examined 95 patients who underwent percutaneous cystostomy between April 2010 and March 2019. A comparative analysis was conducted for each type of procedure performed. Furthermore, cases that experienced accidental catheter extraction before the first catheter replacement were analyzed, and the three patient groups were compared based on the type of procedure performed and cases that needed another operation. (Result) The indications for cystostomy were urethral stricture (56.3%), neuropathic bladder (13.5%), and prostatic hyperplasia (11.5%). The complications included hemorrhage, peritoneal injury, urinary tract infection, and catheter damage caused by a puncture needle. The overall complication rate was 10.5%. Based on type of the procedure performed, the incidence of hemorrhage was found to be as high as 25% in patients who underwent the procedure using a cannula puncture needle. Accidental catheter extraction before the first catheter replacement occurred most frequently in patients treated with Seldinger technique (17.0%). The rate of complications including accidental catheter extraction ranged from 25.0% to 25.4% among the three groups. (Conclusion) We prefer the Seldinger technique for the first placement of the cystostomy catheter because of its low rate of hemorrhage, but a cannula puncture needle may also be used by using exploratory puncture if vascular damage and accidental catheter extraction are avoided.

Identification of transgene integration site and anatomical properties of fluorescence intensity in a EGFP transgenic chicken line.

Transgenic birds are commonly used for time-lapse imaging and fate mapping studies in developmental biology. When researchers use transgenic birds expressing fluorescent protein, they need to understand the integration site of the transgene in the genome and the intensity of fluorescence in the tissues of interest. In this study, we determined the integration site of the transgene and fluorescence property of developing organs in our transgenic chicken line generated by lentivirus infection. The transgene was localized between exons 3 and 4 of MED27. Some homozygotes and heterozygotes appeared to be lethal at early embryonic stages. We performed histological analysis of EGFP expression in transgenic embryos at St. 14, 17, and 24 by immunohistochemistry with anti-GFP antibody on paraffin sections. Next, we cut cryosections and quantified direct EGFP intensity from the transgene in each tissue without performing immunohistochemistry. These results revealed that EGFP intensity in each tissue was unique in developing embryos and changed according to developmental stages. Finally, we demonstrated that EGFP-expressing cells in a micromass culture with co-culturing wild-type cells were clearly distinguishable via live cell imaging. These results provide essential information on the potential of our transgenic line and indicate that these transgenic chicken lines are useful for research associated with developmental biology.

Brilliant Blue as an alternative dye to Fast Green for in ovo electroporation.

Chick embryo electroporation is a powerful tool for the introduction of transgenes into tissues of interest for the study of developmental biology. This method often uses Fast Green to visualize the injected area by staining the solution containing DNA green. Here, we show that Fast Green fluoresces in a red color after electroporation, suggesting that researchers need to be cautious when detecting red fluorescence. Fast Green solution did not show any fluorescence before injection into chick embryos, but fluoresced red within 3 min post-injection into chick embryos. We identified Brilliant Blue as suitable alternative dye for use as an indicator of injection sites in ovo electroporation. We found that 0.2% of Brilliant Blue was sufficient to track the area of DNA injection. In addition, this chemical did not show red fluorescence after electroporation. Our findings demonstrate that Brilliant Blue can be used for detecting red fluorescent proteins introduced into chick embryos by electroporation. Our study also shows useful examples for the application of Brilliant Blue for the precise quantification of two fluorescence intensities after EGFP and mCherry co-electroporation.

Penile-preserving surgery for male distal urethral carcinoma followed by buccal mucosa urethroplasty.

INTRODUCTION: We report a case of distal urethral carcinoma treated with segmental urethral excision and reconstruction by staged buccal mucosa urethroplasty. CASE PRESENTATION: A 60-year-old man presented with difficulty urinating and a palpable mass on the ventral side of his penis. He was diagnosed as having localized distal urethral carcinoma (cT2N0M0) and underwent penile-preserving surgery with staged urethroplasty using buccal mucosa as substitute tissue. The pathological diagnosis was squamous cell carcinoma of the urethra (T2) with negative surgical margin. At 2 years of follow-up, there was no recurrence or metastasis, he could void in a standing position with an acceptable urinary stream, and he found the appearance of his external genitalia acceptable. CONCLUSION: In cases of distal primary urethral carcinoma, urethroplasty using buccal mucosa graft could be alternative treatment option providing a better postoperative quality of life.

[A CASE OF EMPHYSEMATOUS PYELONEPHRITIS WHO PRESENTED THE PRESERVATION OF THE IPSILATERAL KIDNEY FOLLOWING OPEN DRAINAGE].

We report a case of a 53-year-old woman with emphysematous pyelonephritis who presented the preservation of the ipsilateral kidney following open drainage. She was transferred to our hospital with chief complaints of right back pain and high fever. On diagnosis, diabetes mellitus and a stone in the right ureter were confirmed, and she was followed up at a local clinic. Computed tomography revealed the presence of gas in the right renal pelvis, and the stone led to right hydronephrosis. Additionally, her hemoglobin A1c level was 11.3%. Hence, we diagnosed the patient with emphysematous pyelonephritis. Although right percutaneous nephrostomy was performed immediately after her admission, the gas in the right renal pelvis extended to the renal parenchyma one day later. Therefore, we performed open drainage of the right kidney to control severe inflammation. The gas disappeared after the procedure, and her systemic status gradually improved. We hypothesize that emphysematous pyelonephritis is treated with open drainage instead of nephrectomy while preserving the ipsilateral kidney.

[A CASE OF PELVIC FRACTURE URETHRAL INJURY REPAIRED BY FOURTH URETHROPLASTY].

Pelvic fracture urethral injury (PFUI) is relatively rare injury, and delayed urethroplasty is the gold standard for its repair. Because a failed urethroplasty results in increased scarring and reduced length of the available urethral segment, the salvage urethroplasty is a urologic challenge. We herein report the case of male patient with PFUI who could be salvaged after three failed urethroplasties. A 22-year-old male who had received a PFUI when he was 4 years old was referred for salvage urethroplasty after two perineal anastomotic urethroplasties and one transpubic urethroplasty had failed, leaving him unable to void and forced to keep having a suprapubic tube placed. The meatus was iatrogenically obliterated due to repeated treatments. Through an incision from the scrotum and right side of the root of the penis to the lower abdomen, the anterior urethra was circumferentially mobilized and transected at the distal urethral stump. The proximal urethral end was identified by palpitation with a metallic sound inserted through the suprapubic tube tract. The covering fibrotic scar tissue was completely removed and 8 anastomotic 4-0 polydioxanone sutures were placed to reapproximate the urethral mucosa. A pedicled gracilis muscle flap was created and wrapped around the anastomosis site and intrapelvic segment of the mobilized anterior urethra. A urethrogram 8 months after urethroplasty showed a wide caliber at the anastomosis site and a ventral midline meatotomy was subsequently performed. He is currently free from any instruments and can void well without the need for further intervention.

Primary Realignment for Pelvic Fracture Urethral Injury Is Associated With Prolonged Time to Urethroplasty and Increased Stenosis Complexity.

OBJECTIVE: To compare the clinical courses of patients with pelvic fracture urethral injury (PFUI) according to initial management strategy. METHODS: We reviewed the clinical courses of 63 patients with PFUI who were initially treated elsewhere and underwent delayed anastomotic urethroplasty by a single surgeon between 2008 and 2015. Patients were grouped according to their initial treatment: by suprapubic tube placement alone (49 patients, SPT group) or primary realignment (14 patients, PR group). Time to urethroplasty was defined as the period between injury and delayed urethroplasty. Clinical data regarding the status of urethral stenosis, urethroplasty procedure, and treatment outcome were analyzed. RESULTS: The mean time to urethroplasty in the PR group was about 3 times than that in the SPT group (133 months vs 47 months, P = .035). Fifty percent of the PR group (7 of 14) had a history of repeated urethrotomy or dilation before referral, a percentage significantly higher than that of the SPT group (20.4%, 10 of 49, P = .027). The percentage of patients having a false passage and iatrogenic scar was significantly higher in the PR group (42.9% vs 16.3%, P = .035), but there was no significant between-group difference in urethral stenosis length, operative time, operative blood loss, or the percentage of patients requiring inferior pubectomy or urethral rerouting. CONCLUSION: PR does not facilitate delayed urethroplasty, and patients who undergo PR are at high risk of having a more complicated stenosis and longer time to urethroplasty, presumably because of repeated transurethral procedures.

Inactivation of Sonic Hedgehog Signaling and Polydactyly in Limbs of Hereditary Multiple Malformation, a Novel Type of Talpid Mutant.

Hereditary Multiple Malformation (HMM) is a naturally occurring, autosomal recessive, homozygous lethal mutation found in Japanese quail. Homozygote embryos (hmm-/-) show polydactyly similar to talpid2 and talpid3 mutants. Here we characterize the molecular profile of the hmm-/- limb bud and identify the cellular mechanisms that cause its polydactyly. The hmm-/- limb bud shows a severe lack of sonic hedgehog (SHH) signaling, and the autopod has 4 to 11 unidentifiable digits with syn-, poly-, and brachydactyly. The Zone of Polarizing Activity (ZPA) of the hmm-/- limb bud does not show polarizing activity regardless of the presence of SHH protein, indicating that either the secretion pathway of SHH is defective or the SHH protein is dysfunctional. Furthermore, mesenchymal cells in the hmm-/- limb bud do not respond to ZPA transplanted from the normal limb bud, suggesting that signal transduction downstream of SHH is also defective. Since primary cilia are present in the hmm-/- limb bud, the causal gene must be different from talpid2 and talpid3. In the hmm-/- limb bud, a high amount of GLI3A protein is expressed and GLI3 protein is localized to the nucleus. Our results suggest that the regulatory mechanism of GLI3 is disorganized in the hmm-/- limb bud.

Development of an Isolator System for PET Drug Compounding with Sterilization and Dispensing Units.

To maintain sterility of PET drug is the most important for in-house positron emission tomography (PET) drug manufacturing, and sanitary control of the laboratory to perform aseptic procedure is the key point for the sterility of PET drugs. However, rigorous sanitary control affects both the high cost and the low efficiency. To conquer those, we developed an isolator system especially for PET drug compounding including sterilization and dispensing units. This system consists of a HEPA unit for inlet and outlet, positive regulation of the ear inside isolator, a sterilizer with vapored hydrogen peroxide and a dispenser with self-shield for radiation. We set the materials for the dispenser through gloves, and the compounding such as sterilization and dispensing PET drugs to the containers is performed automatically without radiation. High level assurance of PET drug sterility is expected to be accomplished in the PET centers of the hospitals without high level sanitary control.