Utility of the web excision with pre-membranous incision for congenital intestinal atresia-type I and stenosis.

PURPOSE: This study analyzed the efficacy of web excision combined with a pre-membranous incision on the dilated proximal segment for congenital intestinal atresia with type I and stenosis (CIA-I/S). PATIENTS AND METHODS: Twenty-six patients underwent surgery for CIA-I/S from January 1990 to June 2022. Patients were categorized into 3 groups according to the surgical procedure: Group A, web excision with pre-membranous incision of the dilated intestine (n = 14); Group B, enteroplasty with a trans-membranous vertical incision (n = 7) and Group C, diamond-shaped anastomosis (n = 5). To minimize the impact of obstruction location on outcomes, we specifically examined 17 cases of duodenal atresia/stenosis: Group D-A, (n = 6); Group D-B, (n = 6) and Group D-C, (n = 5). We retrospectively compared the operative and postoperative parameters among the three groups. RESULTS: No patient experienced anastomotic leakage or obstruction. There were no significant differences in operative duration or blood loss among the 3 Groups. The median time to feeding initiation was 4, 6.5, and 5 days in Groups A, B, and C, respectively (p = 0.04) and was 4, 6.5, and 5 days in Groups D-A, D-B, and D-C, respectively (p = 0.04). CONCLUSION: Web excision, when compared to enteroplasty and diamond-shaped anastomosis, showed comparable results in terms of the operative duration and postoperative complications. However, it may allow for an earlier initiation of enteral nutrition.

Preoperative analysis of factors associated with prolonged pneumoretroperitoneum time during retroperitoneal laparoscopic nephroureterectomy for upper tract urothelial carcinoma.

BACKGROUND: Prolonged laparoscopic nephroureterectomy (LNU) for upper tract urothelial cancer (UTUC) can increase the frequency of intravesical recurrence after surgery. Therefore, it is important for urological surgeons to have knowledge on preoperative risk factors for prolonged LNU. However, few studies have investigated the risk factors for prolonged LNU. We hypothesized that the quantity of perirenal fat affects the pneumoretroperitoneum time (PRT) of retroperitoneal LNU (rLNU). This study aimed to investigate the preoperative risk factors for prolonged PRT during rLNU. METHODS: We reviewed the data of 115 patients who underwent rLNU for UTUC between 2013 and 2021. The perirenal fat thickness (PFT) observed on preoperative computed tomography (CT) images was used to evaluate the perinephric fat quantity. Preoperative risk factors for PRT during rLNU were analyzed using logistic regression models. The cutoff value for PRT was determined based on the median time.The cutoff values for fat-related factors influencing PRT were defined according to receiver operating characteristic curve analysis. RESULTS: The median PRT for rLNU was 182 min (interquartile range, 155-230 min). The cutoff values of posterior, lateral, and anterior PFTs were 15 mm, 24 mm, and 6 mm, respectively. Multivariate analysis revealed that a posterior PFT ≥ 15 mm (odds ratio [OR], 2.72; 95% confidence interval, 1.04-7.08; p = 0.0410) was an independent risk factor for prolonged PRT. CONCLUSIONS: Thick posterior PFT is a preoperative risk factor for prolonged PRT during rLNU. For patients with UTUC and thick posterior PFT, surgeons should develop optimal surgical strategies, including the selecting an expert surgeon as a primary surgeon and the selecting transperitoneal approach to surgery or open surgery.

Association between response to enfortumab vedotin and peripheral neuropathy in urothelial carcinoma patients: a multicenter retrospective study.

BACKGROUND: Enfortumab vedotin (EV) was approved for patients with metastatic urothelial carcinoma (mUC) who progressed after anticancer therapy on September 2021 in Japan. The association between the occurrence of EV-related side effects and clinical outcome remains to be elucidated. METHODS: We identified 97 mUC patients treated with EV therapy at our five institutions from the date of approval to March 2023. The median follow-up period was 7.0 months. We retrospectively analyzed the efficacy and safety of EV. RESULTS: The median age of the patients was 71 years old, 39% had PS of 1 or more, and 56.7% had primary tumor in upper urinary tract. Overall response rate (ORR) to EV therapy, median progression-free survival (PFS), and overall survival (OS) were 43.3%, 7.52 months, and 12.78 months, respectively. Any grade of treatment-related skin disorder, dysgeusia, peripheral neuropathy, gastrointestinal disorder, and hyperglycemia occurred in 61 (62.9%), 36 (37.1%), 34 (35.1%), 29 (29.9%), and 18 (18.6%) patients, respectively. The patients with EV-associated peripheral neuropathy had significantly higher ORR (58.8% vs. 34.9%, P = .032) and longer median PFS (8.05 vs. 6.31 months, P = .017) and OS (not reached vs. 11.57 months, P = .008, respectively) than those without. The occurrence of peripheral neuropathy after EV treatment and the presence of peritoneal dissemination were factors independently associated with PFS (hazard ratio = 0.46, P = .008 and hazard raito = 3.83, P = .004, respectively) and OS (hazard ratio = 0.30, P = .005 and hazard raito = 4.53, P = .002, respectively). CONCLUSIONS: The occurrence of EV-related peripheral neuropathy might be associated with the efficacy of EV therapy in mUC patients.

snRNAs from Radical Prostatectomy Specimens Have the Potential to Serve as Prognostic Factors for Clinical Recurrence after Biochemical Recurrence in Patients with High-Risk Prostate Cancer.

In patients with high-risk prostate cancer (HRPC) after radical prostatectomy (RP), biochemical recurrence (BCR) increases the risk of distant metastasis. Accordingly, additional prognostic biomarkers are required to identify the subpopulation of patients with HRPC who develop clinical recurrence (CR) after BCR. The objective of this study was to identify biomarkers in formalin-fixed paraffin-embedded (FFPE) RP samples that are prognostic for CR in patients with HRPC who experience BCR after RP (post-RP BCR). First, we performed a preliminary RNA sequencing analysis to comprehensively profile RNA expression in FFPE RP samples obtained from patients with HRPC who developed CR after post-RP BCR and found that many snRNAs were very abundant in preserved FFPE samples. Subsequently, we used quantitative polymerase chain reaction (qPCR) to compare the expression levels of highly abundant snRNAs in FFPE RP samples from patients with HRPC with and without CR after post-RP BCR (21 CR patients and 46 non-CR patients who had more than 5 years of follow-up after BCR). The qPCR analysis revealed that the expression levels of snRNA RNU1-1/1-2 and RNU4-1 were significantly higher in patients with CR than in patients without CR. These snRNAs were significantly correlated with clinical recurrence-free survival (RFS) in patients with HRPC who experienced post-RP BCR. Furthermore, snRNA RNU1-1/1-2 could serve as an independent prognostic factor for clinical RFS in post-RP BCR of HRPC cases where known prognostic factors (e.g., Gleason score) cannot distinguish between CR and non-CR patients. Our findings provide new insights into the involvement of snRNAs in prostate cancer progression.

Index tumor location affected early biochemical recurrence after radical prostatectomy in patients with negative surgical margin: a retrospective study.

BACKGROUND: Index tumors are the most aggressive tumors of the prostate. However, their clinical significance remains unclear. This study aimed to assess the incidence of index tumor location according to the zonal origin and whether these locations affect the prognosis after radical prostatectomy in patients with negative surgical margins. METHODS: This single-centered, retrospective study evaluated 1,109 consecutive patients who underwent radical prostatectomies. An index tumor was defined as the largest tumor in the prostate gland. We detected these locations based on McNeal's zonal origin using whole-mount sections. Biochemical recurrence (BCR) free survival curves were generated using the Kaplan-Meier method. Univariate and multivariate analyses using the Cox proportional hazards model were performed to determine the predictive factors for early BCR (within 1-year). RESULTS: A total of 621 patients with negative surgical margins who did not receive adjuvant therapy were included in this study. The index tumor were located in the transitional zone in 191 patients (30.8%), the peripheral zone in 399 patients (64.3%), and the central zone in 31 patients (5.0%). In total, 22 of 621 patients (3.5%) experienced early BCR and 70 patients (11.2%) experienced overall BCR at a median follow-up of 61.7 months. According to the index tumor location, the early BCR-free rates were 99.5%, 95.7 %, and 83.3% in the transitional, peripheral, and central zones, respectively. On multivariate analysis, the index tumor in the central zone was an independent predictor of early BCR with negative surgical margins following radical prostatectomy, followed by prostatectomy pathological grade, index tumor in the peripheral zone, and high prostate-specific antigen level. CONCLUSIONS: We assessed the significance of index tumor location in patients with negative surgical margins following radical prostatectomy. Index tumors located in the central zone, although infrequent, were the strongest predictive factors for early BCR. Our results may allow urologists and patients to reconsider the therapeutic strategies for prostate cancer.

Mitral Valve Regurgitation in Klippel-Feil Syndrome With Related Thoracic Deformity.

Klippel-Feil syndrome, characterized by congenital fusion of any 2 or more cervical vertebrae, is a rare disorder in which skeletal and other organ system-related abnormalities have been reported. This article reports a case of mitral valve regurgitation in a patient with Klippel-Feil syndrome and related thoracic deformity who underwent mitral valvuloplasty. Postoperatively, the mitral valve regurgitation disappeared, and there has been no recurrence for 3 years. This case highlights mitral valvuloplasty via median sternotomy as an excellent treatment for mitral valve regurgitation in a patient with thoracic deformity related to Klippel-Feil syndrome.

The Sum of the Leg Length Discrepancy and the Difference in Global Femoral Offset Is Equal to That of the Contralateral Intact Side and Improves Postoperative Outcomes after Total Hip Arthroplasty: A Three-Dimensional Analysis.

Background/Objectives: Global femoral offset (GFO) and leg length discrepancy (LLD) affect outcomes after total hip arthroplasty (THA). Moreover, the sum of the difference in GFO between the THA and non-surgical sides and LLD (SGL) reportedly affects the outcomes in a two-dimensional evaluation. We examined the association of the GFO, LLD, and SGL with the Harris Hip Score (HHS) using a three-dimensional (3D) evaluation. Methods: We retrospectively surveyed 172 patients with hemilateral hip osteoarthritis who underwent THA. The GFO, LLD, and SGL were measured using the 3D pelvis and femur models; these models were adjusted for the pelvis and femur, and the coordinate systems were parallelized. Furthermore, their relationship with the modified HHS (mHHS) 1 year after THA was determined. Results: Significant correlations were found among mHHS, GFO, and SGL in the binomial group, whereas LLD was not significantly correlated. The optimal values of GFO and SGL were 1.01 mm and 0.18 mm/100 cm body height, respectively, which were considered optimal when the SGL values were approximately equal to those of the non-operative side. The optimal ranges for GFO and SGL were -1.65 to 3.67 mm and -4.78 to 5.14 mm/100 cm, respectively. Conclusions: Our findings were obtained after adjusting the pelvis and femur to a unified coordinate system. Therefore, the results of this study can be directly applied to 3D planning.

Determining the clinicopathological significance of the VI-RADS ≧4 group: a retrospective study.

BACKGROUND: The Vesical Imaging Reporting and Data System (VI-RADS) is widely used for predicting muscle-invasive bladder cancer (MIBC). This study aimed to determine the clinicopathological significance of the VI-RADS ≧4 (VI≧4) group. METHODS: Patients who underwent transurethral resections of bladder tumors during the study period and preoperative magnetic resonance imaging were considered. The patients were pathologically diagnosed with urothelial carcinoma (UC). We first compared the results of patients with VI-RADS scores of 3 and 4 to determine the cut-off score for MIBC; thereafter, the patients were divided into the VI≧4 and VI-RADS ≦3 (VI≦3) groups using VI-RADS. The clinicopathological significance of the VI≧4 group was examined retrospectively by comparing the characteristics of each group. RESULTS: In total, 121 cases were examined, of which 28 were pathologically diagnosed with MIBC. Of the 28 MIBC cases, three (10.7%) had a VI-RADS score of ≦3, and 25 (89.3%) had a VI-RADS score of ≧4. Of the 93 NMIBC cases, 86 (92.5%) had a VI-RADS score of ≦3, and seven (7.5%) had a VI-RADS score of ≧4. The diagnostic performance of the VI-RADS with a cut-off score of 4 was 89.3% for sensitivity, 92.5% for specificity, and an area under the curve (AUC) of 0.91. Contrastingly, for a cut-off score of 3, the sensitivity was 89.3%, specificity was 62.0%, and AUC was 0.72. A VI-RADS score of ≥ 4 could predict MIBC. In the VI≧4 group, 30 of 32 (93.8%) patients had high-grade tumors. The VI≧4 group had significantly more high-grade bladder cancers than the VI≦3 group (p < 0.001 OR = 31.77 95%CI:8.47-1119.07). In addition, the VI≧4 group had more tumor necrosis (VI≧4 vs VI≦3, p < 0.001 OR = 7.46 95%CI:2.61-21.34) and more UC variant cases (VI≧4 vs VI≦3, p = 0.034 OR = 3.28 95%CI:1.05-10.25) than the VI≦3 group. CONCLUSIONS: This study suggests that VI-RADS has a high diagnostic performance in predicting MIBC and that VI-RADS could diagnose high-grade tumors, necrosis, and UC variants.

Semantic and Geometric-Aware Day-to-Night Image Translation Network.

Autonomous driving systems heavily depend on perception tasks for optimal performance. However, the prevailing datasets are primarily focused on scenarios with clear visibility (i.e., sunny and daytime). This concentration poses challenges in training deep-learning-based perception models for environments with adverse conditions (e.g., rainy and nighttime). In this paper, we propose an unsupervised network designed for the translation of images from day-to-night to solve the ill-posed problem of learning the mapping between domains with unpaired data. The proposed method involves extracting both semantic and geometric information from input images in the form of attention maps. We assume that the multi-task network can extract semantic and geometric information during the estimation of semantic segmentation and depth maps, respectively. The image-to-image translation network integrates the two distinct types of extracted information, employing them as spatial attention maps. We compare our method with related works both qualitatively and quantitatively. The proposed method shows both qualitative and qualitative improvements in visual presentation over related work.

Real-World Insights into Efficacy and Safety of Enfortumab Vedotin in Japanese Patients with Metastatic Urothelial Carcinoma: Findings, Considerations, and Future Directions.

This study presents the enfortumab vedotin (EV) treatment analysis at our institution. We retrospectively analyzed patients with metastatic urothelial cancer (mUC) treated with EV between January 2021 and October 2023. EV was administered at 1.25 mg/kg on days 1, 8, and 15 in a 28-day cycle. Whole-body computed tomography scans were performed to assess the treatment response. Patient characteristics, treatment histories, response rates, progression-free survival, and adverse events were evaluated. Response rates were determined, and adverse events were recorded. Among the 20 patients, 70% were male and 65% had bladder tumors. Most patients had lung (65%) or lymph node (65%) metastases. The median follow-up was 11.2 months, with 45% of the patients succumbing to the disease. The overall response rate was 55%. The median progression-free and median overall survivals were 10.5 and 12.9 months, respectively. Severe adverse events occurred in 35% of patients. In this real-world study, EV demonstrated promising efficacy and manageable safety profiles in Japanese patients with mUC. The study's results were consistent with previous clinical trials, although a longer follow-up was required. Our findings support EV use as a treatment option for patients with mUC who exhibit disease progression after platinum-based chemotherapy and immune-checkpoint inhibitor therapy.

Usefulness of the spectral shaping dual-source computed tomography imaging technique in posterior corrective fusion for adolescent idiopathic scoliosis.

PURPOSE: Since childhood exposure to radiation has been demonstrated to increase cancer risk with increase in radiation dose, reduced radiation exposure during computed tomography (CT) evaluation is desired for adolescent idiopathic scoliosis (AIS). Therefore, this retrospective study aimed to investigate the radiation dose of dual-source CT using a spectral shaping technique and the accuracy of the thoracic pedicle screw (TPS) placement for posterior spinal fusion (PSF) in patients with AIS. METHODS: Fifty-nine female patients with thoracic AIS who underwent PSF using CT-guided TPSs were included and divided into two groups comprised of 23 patients who underwent dual-source CT (DSCT) with a tin filter (DSCT group) and 36 who underwent conventional multislice CT (MSCT group). We assessed the CT radiation dose using the CT dose index (CTDIvol), effective dose (ED), and accuracy of TPS insertion according to the established Neo's classification. RESULTS: The DSCT and MSCT groups differed significantly (p < 0.001) in the mean CTDIvol (0.76 vs. 3.31 mGy, respectively) and ED (0.77 vs. 3.47 mSv, respectively). Although the correction rate of the main thoracic curve in the DSCT group was lower (65.7% vs. 71.2%) (p = 0.0126), the TPS accuracy (Grades 0-1) was similar in both groups (381 screws [88.8%] vs. 600 screws [88.4%], respectively) (p = 0.8133). No patient required replacement of malpositioned screws. CONCLUSION: Spectral shaping DSCT with a tube-based tin filter allowed a 75% radiation dose reduction while achieving TPS insertion accuracy similar to procedures based on conventional CT without spectral shaping.

A case of renal abscess mimicking metastatic lesion in a patient with lung carcinosarcoma.

Renal abscesses require prompt diagnosis and appropriate intervention, as they can be life-threatening. However, diagnosis based solely on clinical findings is often challenging. We present the case of a 69-year-old woman with left renal masses on follow-up computed tomography (CT) after surgery for pT2aN0M0 lung carcinosarcoma. The masses were localized only in the left kidney without suspected metastatic lesions at other sites. The patient was referred to our department for further evaluation and treatment under a diagnosis of suspected metastatic lung carcinosarcoma of the left kidney. On enhanced CT, the left renal masses, the largest of which had a diameter of 40×36 mm had thick irregular walls gradually enhanced by the contrast media and an internal low-attenuation area. The masses showed heterogeneous signal intensity with a pseudocapsule on T2-weighted magnetic resonance imaging. Clinical symptoms such as fever or costovertebral angle tenderness were absent, and blood and urine tests were not sufficiently inflammatory to suggest a renal abscess. Histopathological findings on CT-guided renal biopsy revealed only inflammatory tissue and no tumor cells. However, because lung carcinosarcoma metastatic nodules could not be ruled out, laparoscopic left nephrectomy was performed for a definitive diagnosis and curative intent. The pathological diagnosis was renal abscess without malignant lesions. Here, we present a case of renal abscess mimicking metastatic lesions in a patient with lung carcinosarcoma. Accurately differentiating renal abscesses from metastatic renal tumors before treatment is often difficult. Renal abscess diagnosis should be considered through a comprehensive evaluation of the clinical findings of individual cases.

A case of marked rectal stenosis due to Douglas' pouch metastasis of renal pelvic carcinoma successfully treated with salvage enfortumab vedotin: correlation between serum KL-6 levels and tumor response.

Introduction: We report a rare case of marked rectal stenosis due to Douglas' pouch metastasis of renal pelvic urothelial carcinoma successfully treated with enfortumab vedotin. Case presentation: A 77-year-old female presented with difficulty in defecation and abdominal distension. She had received two courses of cisplatin plus gemcitabine followed by four courses of maintenance avelumab for postoperative lymph node metastasis of renal pelvic urothelial carcinoma. KL-6 levels were elevated, and a computed tomography scan revealed an irregularly shaped large mass occupying Douglas' pouch, with marked rectal stenosis. Metastatic urothelial carcinoma was pathologically diagnosed, and enfortumab vedotin was initiated after colostomy. After 12 courses of enfortumab vedotin, metastatic lesions showed marked shrinkage and KL-6 levels decreased. Conclusion: Enfortumab vedotin elicited a remarkable response in treating rectal stenosis due to metastasis of renal pelvic urothelial carcinoma in Douglas' pouch. Furthermore, serum KL-6 levels were correlated with the severity of metastatic urothelial carcinoma.

Primary leiomyoma of the bladder radiologically mimicking a retroperitoneal tumor - a case report.

The case presented is of a 47-year-old patient with an extravesical pedunculated bladder leiomyoma, which was difficult to distinguish from a retroperitoneal tumor. Preoperatively, it was suspected to be a retroperitoneal tumor and a laparotomy with tumor resection was performed. lntraoperatively, the bladder and tumor were connected by a cord-like tissue. A retrospective review of preoperative images revealed that cord-like tissue, identified intraoperatively, was also present. Bladder leiomyomas can grow as extravesical pedunculated tumors. Therefore, when the continuity between the bladder and tumor is only a cord-like object, the finding ofcontinuity is useful to diagnose with bladder leiomyoma. J. Med. Invest. 70 : 513-515, August, 2023.

The effect of Dunaliella tertiolecta supplementation on diet-induced obesity in UCP1-deficient mice.

We previously demonstrated that dietary supplementation with Dunaliella tertiolecta (DT) increases uncoupling protein 1 (UCP1) expression in brown adipose tissue (BAT) and improves diet-induced obesity (DIO) in C57BL/6 J mice at thermoneutrality (30 °C). Here, we investigated whether DT improves DIO in a thermoneutral UCP1-deficient (KO) animal. KO mice were fed a high-fat diet supplemented with DT for 12 weeks. Compared to control group without DT, body weight was significantly reduced in DT group with no difference in food intake. Dunaliella tertiolecta-supplemented mice exhibited lower adiposity and well-maintained multilocular morphology in BAT, in which a significant increase in gene expression of PR domain containing 16 was detected in DT group compared to control group. Moreover, increase in UCP2 level and/or decrease in ribosomal protein S6 phosphorylation were detected in adipose tissues of DT group relative to control group. These results suggest that DT supplementation improves DIO by stimulating UCP1-independent energy dissipation at thermoneutrality.

Perirenal fat stranding as a predictor of disease progression after radical nephroureterectomy for renal pelvic urothelial carcinoma: a retrospective study.

BACKGROUND: To investigate the impact of Perirenal fat stranding (PRFS) on progression after radical nephroureterectomy (RNU) for renal pelvic urothelial carcinoma (RPUC) without hydronephrosis and to reveal the pathological findings of PRFS. METHODS: Clinicopathological data, including computed tomography (CT) findings of the ipsilateral PRFS, were collected from the medical records of 56 patients treated with RNU for RPUC without hydronephrosis between 2011 and 2021 at our institution. PRFS on CT was classified as either low or high PRFS. The impact of PRFS on progression-free survival (PFS) after RNU was analyzed using the Kaplan-Meier method and log-rank test. In addition, specimens including sufficient perirenal fat from patients with low and with high PRFS were pathologically analyzed. Immunohistochemical analysis of CD68, CD163, CD3, and CD20 was also performed. RESULTS: Of the 56 patients, 31(55.4%) and 25 (44.6%) patients were classified as having low and high PRFS, respectively. Within a median follow-up of 40.6 months postoperatively, 11 (19.6%) patients showed disease progression. The Kaplan-Meier method and log-rank test revealed that patients with high PRFS had significantly lower PFS rates than those with low PRFS (3-year PFS 69.8% vs 93.3%; p = 0.0393). Pathological analysis revealed that high PRFS specimens (n = 3 patients) contained more fibrous strictures in perirenal fat than low PRFS specimens (n = 3 patients). In addition, M2 macrophages (CD163 +) infiltrating fibrous tissue in perirenal area were observed in all patients with high PRFS group. CONCLUSIONS: PRFS of RPUC without hydronephrosis consists of collagenous fibers with M2 macrophages. The presence of ipsilateral high PRFS might be a preoperative risk factor for progression after RNU for RPUC patients without hydronephrosis. Prospective studies with large cohorts are required in the future.

Deep Voxelized Feature Maps for Self-Localization in Autonomous Driving.

Lane-level self-localization is essential for autonomous driving. Point cloud maps are typically used for self-localization but are known to be redundant. Deep features produced by neural networks can be used as a map, but their simple utilization could lead to corruption in large environments. This paper proposes a practical map format using deep features. We propose voxelized deep feature maps for self-localization, consisting of deep features defined in small regions. The self-localization algorithm proposed in this paper considers per-voxel residual and reassignment of scan points in each optimization iteration, which could result in accurate results. Our experiments compared point cloud maps, feature maps, and the proposed map from the self-localization accuracy and efficiency perspective. As a result, more accurate and lane-level self-localization was achieved with the proposed voxelized deep feature map, even with a smaller storage requirement compared with the other map formats.

Vesicocutaneous fistula due to vesical diverticulitis with stones: A case report and literature review.

Introduction: We encountered an extremely rare case of a vesicocutaneous fistula due to vesical diverticulitis with stones. Case presentation: A 78-year-old male patient presented to our department with complaints of suppurative discharge in the suprapubic area. Computed tomography revealed an enlarged prostate, a vesical diverticulum with stones located on the ventral side, and an aberrant connection between the anterior bladder wall and the external surface of the skin. The patient was diagnosed with a vesicocutaneous fistula due to vesical diverticulitis and was successfully treated with a multidisciplinary approach including vesical diverticulectomy with stone removal and nonviable tissue debridement. The patient continues to receive regular outpatient follow-ups with urinary catheter changes. Conclusion: Vesicocutaneous fistulas due to vesical diverticulitis with stones are extremely rare. We should be aware that a vesical diverticulum with stones located on the ventral side might pose a high-risk factor for the formation of a vesicocutaneous fistula in elderly patients.

Development of an osteosarcoma model with MYCN amplification and TP53 mutation in hiPS cell-derived neural crest cells.

Mesenchymal stem cell- or osteoblast-derived osteosarcoma is the most common malignant bone tumor. Its highly metastatic malignant phenotypes, which are often associated with a poor prognosis, have been correlated with the modulation of TP53- and cell-cycle-related pathways. MYC, which regulates the transcription of cell-cycle modulating genes, is used as a representative prognostic marker for osteosarcoma. Another member of the MYC oncoprotein family, MYCN, is highly expressed in a subset of osteosarcoma, however its roles in osteosarcoma have not been fully elucidated. Here, we attempted to create an in vitro tumorigenesis model using hiPSC-derived neural crest cells, which are precursors of mesenchymal stem cells, by overexpressing MYCN on a heterozygous TP53 hotspot mutation (c.733G>A; p.G245S) background. MYCN-expressing TP53 mutated transformed clones were isolated by soft agar colony formation, and administered subcutaneously into the periadrenal adipose tissue of immunodeficient mice, resulting in the development of chondroblastic osteosarcoma. MYCN suppression decreased the proliferation of MYCN-induced osteosarcoma cells, suggesting MYCN as a potential target for a subset of osteosarcoma treatment. Further, comprehensive analysis of gene expression and exome sequencing of MYCN-induced clones indicated osteosarcoma-specific molecular features, such as the activation of TGF-ß signaling and DNA copy number amplification of GLI1. The model of MYCN-expressing chondroblastic osteosarcoma was developed from hiPSC-derived neural crest cells, providing a useful tool for the development of new tumor models using hiPSC-derived progenitor cells with gene modifications and in vitro transformation.

CREG1 stimulates AMPK phosphorylation and glucose uptake in skeletal muscle cells.

The cellular repressor of adenovirus early region 1A-stimulated gene 1 (CREG1) is a secreted glycoprotein involved in cell differentiation and energy metabolism. It also binds to insulin-like growth factor 2 receptor (IGF2R), a protein implicated in muscle regeneration. However, whether CREG1 regulates the regeneration and metabolism of skeletal muscles via IGF2R remains unclear. This study investigates the role of CREG1 in skeletal muscle regeneration and glucose uptake in C2C12 myotubes and a cardiotoxin (CTX)-induced mouse skeletal muscle regeneration model. CTX-treated skeletal muscle showed significantly higher levels of IGF2R, CREG1, phospho-AMPKα Thr172, and GLUT4 proteins. Similarly, treatment of myotubes with CREG1 also stimulated AMPKα phosphorylation and GLUT4 expression. CREG1-induced AMPKα phosphorylation and 2DG uptake in myotubes were suppressed by IGF2R knockdown and Compound C, an AMPK inhibitor. These results suggest that CREG1 stimulates glucose uptake in skeletal muscles partially through AMPK activation. Hence, CREG1 plays an essential role in muscle regeneration by affecting glucose metabolism in skeletal muscles.