Maternal diet during gestation affect prostatic tissue component in SHR/Izm offspring.

BACKGROUND: Numerous studies have investigated the associations between maternal nutritional status and various diseases, with the underlying mechanism often attributed to epigenetic changes. However, limited research has been conducted on the relationship between maternal nutrition and benign prostatic hyperplasia (BPH). In this study, we aimed to explore the potential association between maternal nutrition and BPH using an animal experiment and evaluating the findings through fluorescent immunostaining and genetic analysis. METHODS: Female spontaneously hypertensive rats (SHR/Izm) were randomly assigned to three groups at the start of pregnancy: a standard diet group (SD; 17% protein, 7% fat), a low-protein diet group (LPD; 6% protein, 7% fat), and a high-fat diet group (HFD; 22% protein, 35% fat). The diets were maintained throughout gestation. After giving birth, both the mothers and their pups were exclusively fed a standard diet. Male pups were euthanized at 48 weeks, and their prostates were removed. The composition of the ventral prostate (VP) was evaluated using fluorescent immunostaining with antibodies for cytokeratin, vimentin, and Ki-67. Microarray analysis, real-time RT-PCR, and DNA methylation analysis using pyrosequencing were performed. Statistical analysis was conducted using one-way ANOVA and Tukey's multiple comparison test, with a significance level set at p < 0.05. RESULTS: Pups in the LPD group exhibited significant underweight from birth (1 day; SD vs. LPD vs. HFD: 4.46 vs. 4.08 vs. 4.35, p = 0.04) until weaning (21 days; SD vs. LPD vs. HFD: 30.8 vs. 27.4 vs. 29.2, p = 0.03). However, they exhibited catch-up growth, and there was no significant difference at 48 weeks (p = 0.84). The epithelial area in the ventral prostate was significantly increased in the LPD group (SD vs. LPD vs. HFD: 39% vs. 48% vs. 37%, p = 0.01), while the stromal area was significantly increased in the HFD group (SD vs. LPD vs. HFD: 11% vs. 11% vs. 15%, p < 0.01). Gene ontology analysis of the gene expression microarray showed increased activity in developmental processes (SD vs. LPD: p = 6.3E-03, SD vs. HFD: p = 7.2E-03), anatomical structure development (SD vs. LPD: p = 6.3E-03, SD vs. HFD: p = 5.3E-03), and cell differentiation (SD vs. LPD: p = 0.018, SD vs. HFD: p = 0.041) in both the LPD and HFD groups. Real-time RT-PCR revealed high expression levels of the transcription factors NFκB (p < 0.01) and Smad3 (p < 0.01) in both the LPD and HFD groups. XIAP, an apoptosis inhibitor, was increased in the LPD group (p = 0.02). The TGF beta pathway, associated with epithelial mesenchymal transition (EMT), and vimentin (p < 0.01) were upregulated in the HFD group. Pyrosequencing DNA methylation analysis of the TGF beta pathway indicated hypomethylation of TGFb1, TGFbR1, and Smad3 in all groups, although there were no significant differences. CONCLUSIONS: Our findings suggest that both maternal undernutrition and obesity influence the prostatic development of offspring. Maternal consumption of a low protein diet promotes epithelial hyperplasia through the upregulation of apoptosis inhibitors, while a high fat diet leads to increased stromal growth through the induction of EMT.

Pre-first-line chemotherapy risk stratification for overall survival in advanced urothelial carcinoma in sequential therapy era.

PURPOSE: To explore pre-treatment risk factors for overall survival (OS) in advanced urothelial carcinoma (UC) patients treated with first-line (1L) chemotherapy in sequential therapy (ST) era. Additionally, to evaluate the proportion of patients who were not able to undergo subsequent immune checkpoint inhibitor (ICI) therapy according to the subgroups stratified by the risk factors. METHODS: A multicenter retrospective study was conducted. Metastatic or locally advanced UC patients treated between 2017 and 2022 were included. The Kaplan-Meier method with the log-rank test and multivariate Cox regression models were used to address OS. RESULTS: Three hundred and fourteen patients treated with 1L chemotherapy were included in the study and 57 (18.2%) patients were not able to proceed to subsequent ICI therapy. Pre-chemotherapy risk factors for OS in 314 patients were ECOG-PS 1 or more, having no primary site resection, C-reactive protein (CRP) level of 3 mg/dL or more, and non-cisplatin-based regimen. Patients having 3 or 4 risk factors had higher risk for not being able to receive ST (Mann-Whitney U test, P < 0.001). As risk factors for OS in 230 patients who were able to receive ST, having no primary site resection, a neutrophil to lymphocyte ratio of 3 or more, and the presence of liver metastasis were identified. CONCLUSION: We reported the risk factors for OS in advanced UC patients treated with 1L chemotherapy in ST era. Patients with high risk for OS may not be able to proceed to subsequent ICI therapy even in the ST era.

Comparison of perioperative outcomes and complications between intracorporeal, extracorporeal, and hybrid ileal conduit urinary diversion during robot-assisted radical cystectomy: a comparative propensity score-matched analysis from nationwide multi-institutional study in Japan.

BACKGROUND: To investigate the impact of different urinary diversion (UD) techniques on the peri- and postoperative complications of robot-assisted radical cystectomy (RARC) with ileal conduit. METHODS: We retrospectively analyzed 373 patients undergoing RARC with ileal conduit at 11 institutions in Japan between April 2018 and December 2021. Propensity score weighting was performed to adjust for confounding factors such as age, sex, body mass index, performance status, American Society of Anesthesiologists score, previous abdominal surgery, neoadjuvant chemotherapy, and preoperative high T stage (≥ cT3) and high N stage (≥ cN1). Perioperative complications were then compared among three groups: extracorporeal, intracorporeal, and hybrid urinary diversion (ECUD, ICUD, and HUD, respectively). RESULTS: A total of 150, 68, and 155 patients received ECUD, HUD, and ICUD, respectively. Bowel reconstruction time and UD time were significantly shorter in the ECUD group (p < 0.001), and console time was significantly longer and blood loss was significantly higher in the ICUD group (p < 0.001). For postoperative complications (Clavien-Dindo Classification grade ≥ 3), surgical site infection (p = 0.004), pelvic abscess (p = 0.013), anastomotic urine leak (p = 0.007), and pelvic organ prolapse (p = 0.011) significantly occurred in the ECUD group. For all grades, ileus was more common in the HUD group, whereas anastomotic stricture was more common in the ECUD group compared with the other groups (p < 0.05). CONCLUSIONS: Severe complications did not increase after HUD and ICUD compared with ECUD; however, console time tended to be longer and blood loss was slightly higher during RARC.

Intrinsic and extrinsic factors causing hyperplasia of the prostate.

Prostatic hyperplasia is very common in elderly men and is a typical disease that reduces quality of life. Histologically, hyperplasia of the prostate gland causes obstruction at the bladder outlet, resulting in symptoms such as a weak urine stream. Various factors have been considered to cause histological enlargement of the prostate, but the underlying cause is still unknown. The factors that cause prostate hyperplasia can be broadly classified into intrinsic and extrinsic ones. Extrinsic factors include things that we directly come into contact with such as bacteria and food. On the other hand, intrinsic factors are those that cause changes in functions originally provided in the body due to some cause, including extrinsic factors, such as chronic inflammation and an imbalance of sex hormones. A large number of reports have been made to date regarding the etiology of prostatic hyperplasia, although they have not yet clarified the fundamental cause(s). The various factors currently known should be outlined for future research. Should it be possible to prevent this highly prevalent prostatic hyperplasia which is mainly cause of dcreasing quality of life, there is no doubt that it would be a huge contribution to humanity.

Development and preliminary evaluation of a novel procedure for creation of an ileal conduit stoma aimed at preventing parastomal hernia.

OBJECTIVES: Our previous study suggested that the operative procedure is critical for the development of parastomal hernia. We developed a novel procedure for the creation of an ileal conduit stoma to prevent parastomal hernia. Herein we evaluate the efficacy and safety of the procedure. METHODS: A total of 113 Japanese patients underwent radical cystectomy and ileal conduit diversion for bladder cancer from January 2017 through December 2021 at our institution. After excluding those with incomplete data, 103 patients consisting of 46 (44.7%) with the conventional procedure and 57 (55.3%) with the novel procedure were consecutively enrolled. The main points of the novel procedure are as follows: (1) the passage of the ileal conduit is ≤2.4 cm in diameter in principle; (2) the posterior rectus sheath and peritoneum are vertically incised 2 cm laterally from the middle of the stoma site to make an oblique passage for the ileal conduit; and (3) the anterior rectus sheath and posterior rectus sheath with peritoneum are fixed to the ileal conduit separately. RESULTS: Radiography-based parastomal hernia was observed in 11 patients (10.7%) with a median follow-up of 22.0 months. The incidences of parastomal hernia were 3.5% and 19.6% in the novel and the conventional procedure groups, respectively (p = 0.011). The former had a significantly lower cumulative incidence of parastomal hernia (p = 0.008, log-rank test). No specific complications associated with the procedure were observed. CONCLUSIONS: The results of the preliminary cohort study suggest that the novel procedure is safe and effective for the prevention of parastomal hernia.

[A Case of Neuropathic Lower Urinary Tract Dysfunction Due to Spina Bifida Occulta Discovered at the Age of 19 Years and Successfully Treated with Multidisciplinary Therapy].

A 19-year-old man had been aware of dysuria and urinary incontinence since childhood but did not seek medical attention. He was diagnosed with acute pyelonephritis due to lower urinary tract dysfunction associated with spina bifida occulta and tethered cord syndrome (TCS) due to spinal cord lipoma. After placement of a urethral catheter and antibacterial chemotherapy, the patient was cured of acute pyelonephritis. He was treated with solifenacin and started clean self-intermittent catheterization (CIC). Shortly after the start of CIC, the acute pyelonephritis flared up again, and he was managed with a reinserted urethral catheter until an untethering operation. Preoperative video urodynamics showed that the bladder morphology was Ogawa classification grade III with vesicoureteral reflux (VUR) at 92 ml infusion. With the combination of an untethering operation and additional mirabegron, the functional bladder capacity was increased to 353 ml and VUR improved, allowing for safe urinary management of the CIC. TCS can be diagnosed at any age and requires appropriate urinary management and therapeutic intervention as early as possible after diagnosis.

[Two Cases of Retroperitoneal Synovial Sarcoma].

We experienced two cases of renal primary synovial sarcoma. Case 1: A 29-year-old man underwent laparoscopic radical nephrectomy and was originally diagnosed with renal cell carcinoma. Case 2: A 25-year-old man was treated by open radical nephrectomy since radiographical findings indicated tumor invasion to the ureter causing hydronephrosis. Both cases were pathologically diagnosed as renal synovial sarcomas, and were followed using computed tomography. Recurrence was observed within a year in both cases.

Prevention of local symptoms in muscle invasive bladder cancer patients: clinical significance of local radiation therapy.

PURPOSE: To evaluate the significance of local radiation therapy (LRT) for prevention of local symptoms (LSs) caused by muscle-invasive bladder cancer (MIBC). METHODS: We retrospectively reviewed the clinical records of 133 patients from 13 hospitals. MIBC patients with or without metastases who were treated with LRT alone from January 2015 through December 2020 were enrolled. Exclusion criteria were urinary diversion (UD) prior to LRT, non-MIBC, or lack of clinical information. LSs were defined as hematuria requiring invasive treatment or transfusion, UD after LRT, bladder tamponade, and opioid use for bladder pain. RESULTS: One hundred fourteen patients were finally enrolled in the study. During the median follow-up period of 13.5 months, 30 patients (26.3%) had LSs. Risk factors of LSs in multivariate analysis were a prior history of non-MIBC (NMIBC) (hazard ratio [HR] 2.99; 95% confidence interval [CI], 1.36 to 6.56; P < 0.01), radiation dose of less than 50 Gray (Gy) (HR 3.99; 95% CI, 1.80 to 8.82; P < 0.01), and tumor stage 3 or more (HR 2.43; 95% CI, 1.14 to 5.21; P = 0.02). Risk factors of overall survival (OS) in multivariate analysis were being female (HR 3.32; 95% CI, 1.68 to 6.58; P < 0.01), an age-adjusted Charlson Comorbidity index of 6 or more (HR 2.19; 95% CI, 1.18 to 4.10; P = 0.01), distant metastases (HR 3.20; 95% CI, 1.39 to 6.58; P < 0.01), and tumor size of 40 mm or more (HR 2.38; 95% CI, 1.34 to 4.52; P < 0.01). Toxicity (all grades) occurred in 40.4% of the patients, 4.8% with grade 3 or more and 95.2% with lower grades. CONCLUSIONS: We determined the risk factors for LSs in MIBC patients treated with LRT alone. An escalated-dose of 50 Gy or more may contribute to prevention of LSs caused by MIBC. Thus, dose-escalated LRT for MIBC patients who can expect favorable survival may be a good option to avoid future annoying LSs.

[Evaluation of the Effects of Long-Term Indwelling Ureteral Stents on Preserving Renal Parenchyma and Function in Patients with Ureteral Stenosis].

Although ureteral stenting is a common conservative treatment for ureteral stricture, it is unclear whether a long-term indwelling ureteral stent protects the kidney against parenchymal atrophy and functional deterioration. In this study, we evaluated the changes in renal parenchymal thickness (RPT) and estimated the glomerular filtration rates (eGFR) in patients with indwelling ureteral stents for one year or more. As a control, we also evaluated changes in RPT associated with indwelling percutaneous nephrostomy (PNS) for one year or more. Polymer ureteral stents were used and replaced every three months. RPT was measured using computed tomography (CT). Totally, 69 renal units in 55 patients with baseline and follow up CT scans available were enrolled. The median follow-up period was 29 months. The etiologies of ureteral obstruction were malignant and benign disease in 27 and 28, respectively. RPT was reduced obviously in most cases. At 1 year, the median reduction rate of RPT was 17.3% in unilateral cases, which was significantly higher than that in the healthy contralateral kidney. There was a strong correlation between eGFR and total RPT including the contralateral kidney. The reduction rate of RPT in kidneys with ureteral stents including bilateral cases was also significantly higher than that in 39 renal units of 35 patients with PNS. The results of this study suggest that the long-term efficacy of indwelling ureteral stents in preserving renal function is limited. Regular imaging may be essential to evaluate the residual renal function.

[Urological Comorbidities in an HIV-Infected Patient: A Case Report].

We report a case of a patient who developed several urological comorbidities associated with HIV infection. A 53-year-old male was diagnosed with HIV infection and AIDS. After 13 years, microhematuria was found and computed tomography (CT) revealed urolithiasis and a left renal tumor suspected of being renal cell carcinoma. Initially, he underwent transurethral lithotripsy. Stone analysis indicated that the stone was made of atazanavir. Then he received laparoscopic left partial nephrectomy. The pathological diagnosis was papillary type 2 renal cell carcinoma. Three years later, follow-up CT revealed a right renal pelvic tumor. Since right ureteroscopy showed that the tumor was papillary we diagnosed it as renal pelvic cancer and decided to perform laparoscopic right radical nephroureterectomy. His renal pelvic tumor was determined to be urothelial carcinoma by the pathological diagnosis. Intravesical recurrence occurred twice after the nephroureterectomy. His renal function gradually deteriorated during follow-up and we suspected that HIV nephrosis was one of the reasons for the deterioration. Hemodialysis was initiated at the age of 71.

[A Patient Who Had Postoperative Three-Field Lymph Node Recurrence of Cancer of the Esophagogastric Junction Obtains Complete Response by DCF Treatment].

A 64-year-old woman underwent left-thoracoabdominal esophagectomy and esophagojejunostomy for cancer of the esophagogastric junction. The pathological examination of the resected specimen showed a poorly squamous cell carcinoma (SCC). The pathological stage was pT3, pN1, sM0, and fStage Ⅲ. Three months after surgery, an SCC antigen related to a tumor marker was found to be outside the normal range, and CT showed lymph node recurrence of the three fields(No. 101R, No. 104RL, No. 106recRL, No. 106pre, and No. 16b1). Because the lymph node recurrence was in the three fields, we performed systemic chemotherapy with docetaxel, cisplatin(CDDP), and 5-fluorouracil(5-FU)(collectively, DCF). After the patient received 2 courses of DCF therapy, the lymph nodes where the recurrent occurred decreased in size(partial response), and SCC became within normal range. She received additional chemotherapy with 2 courses of DCF and achieved a complete response. Currently, she has been alive without recurrence for 7 years and 9 months after 4 courses of DCF therapy. We think that we can select DCF therapy as a first-line treatment for lymph node recurrence alone but not for CRT with FP.

Tumor-infiltrating CD8+ T cells recognize a heterogeneously expressed functional neoantigen in clear cell renal cell carcinoma.

Immune checkpoint inhibitors (ICIs) are used in cancer immunotherapy to block programmed death-1 and cytotoxic T-lymphocyte antigen 4, but the response rate for ICIs is still low and tumor cell heterogeneity is considered to be responsible for resistance to immunotherapy. Tumor-infiltrating lymphocytes (TILs) have an essential role in the anti-tumor effect of cancer immunotherapy; however, the specificity of TILs in renal cell carcinoma (RCC) is elusive. In this study, we analyzed a 58-year-old case with clear cell RCC (ccRCC) with the tumor showing macroscopic and microscopic heterogeneity. The tumor was composed of low-grade and high-grade ccRCC. A tumor cell line (1226 RCC cells) and TILs were isolated from the high-grade ccRCC lesion, and a TIL clone recognized a novel neoantigen peptide (YVVPGSPCL) encoded by a missense mutation of the tensin 1 (TNS1) gene in a human leukocyte antigen-C*03:03-restricted fashion. The TNS1 gene mutation was not detected in the low-grade ccRCC lesion and the TIL clone did not recognized low-grade ccRCC cells. The missense mutation of TNS1 encoding the S1309Y mutation was found to be related to cell migration by gene over-expression. These findings suggest that macroscopically and microscopically heterogenous tumors might show heterogenous gene mutations and reactivity to TILs.

Improvement in Surgical Outcomes Using 3-Dimensional Printed Models for Lateral Pelvic Lymph Node Dissection in Rectal Cancer.

BACKGROUND: Lateral pelvic lymph node dissection for rectal cancer is challenging due to the complexity of the pelvic wall anatomy, and incomplete lateral pelvic lymph node dissection may result in local recurrence in the lateral pelvis. Although 3-dimensional printed organ models are useful for understanding spatial anatomy, it is currently unclear whether they improve surgical outcomes. OBJECTIVE: We aimed to assess whether the surgical effectiveness of lateral pelvic lymph node dissection is increased by the use of individualized 3-dimensional printed pelvic models. DESIGN: This was a retrospective study using a propensity matching analysis. SETTINGS: This study was conducted at a university hospital in Japan. PATIENTS: In total, 115 patients comprising 184 pelvic sides (right, 85 sides; left, 99 sides) who underwent lateral pelvic lymph node dissection for colorectal adenocarcinoma between January 2012 and December 2019 were enrolled. INTERVENTIONS: We compared surgical outcomes using 3-dimensional printed pelvic models with control outcomes. MAIN OUTCOME MEASURES: The primary outcome was the number of harvested lateral pelvic lymph nodes on 1 pelvic side after the propensity matching analysis. RESULTS: After matching, 35 pelvic sides each were allocated to the 3-dimensional model and control groups, and no significant differences were observed in patient characteristics between the 2 groups. The number of harvested lateral pelvic lymph nodes was significantly higher in the 3-dimensional model group (median, 9; range, 3-16) than in the control group (median, 6; range, 0-22; p = 0.047). LIMITATIONS: This was a retrospective study using propensity score matching. However, historical backgrounds were not matched, and the majority of lateral pelvic lymph node dissection procedures in the 3-dimensional model group were recently performed. This limitation may have influenced surgical outcomes. CONCLUSION: The present study demonstrated that, by referring to individualized 3-dimensional printed pelvic models, colorectal surgeons harvested a larger number of lateral pelvic lymph nodes during lateral pelvic lymph node dissection. This result suggests that 3-dimensional printed models help surgeons to complete more detailed procedures. See Video Abstract at http://links.lww.com/DCR/B776. MEJORA DE LOS RESULTADOS QUIRRGICOS MEDIANTE EL USO DE MODELOS IMPRESOS EN D PARA LA DISECCIN LATERAL DE LOS GANGLIOS LINFTICOS PLVICOS EN EL CNCER DE RECTO: ANTECEDENTES:La disección lateral de los ganglios linfáticos de la pelvis en el cáncer de recto es un desafío debido a la complejidad de la anatomía de la pared pélvica; la disección incompleta de las mismas puede resultar en una recidiva local en dicha zona. Aunque la impresión tridimensional de modelos de órganos es útil para comprender la estructura anatómica espacial, actualmente no está claro si mejoran los resultados quirúrgicos.OBJETIVO:Nuestro objetivo fue evaluar si la efectividad quirúrgica de la disección de los ganglios linfáticos laterales de la pelvis aumenta mediante el uso individualizado de modelos pélvicos impresos en 3D.DISEÑO:Este fue un estudio retrospectivo que utilizó un análisis de coincidencia de propensión.AJUSTE:Este estudio se realizó en un hospital universitario de Japón.PACIENTES:En total, se enrolaron 115 pacientes que comprendían 184 lados pélvicos (85 de lado derecho; 99 de lado izquierdo) que fueron sometidas a disección lateral de ganglios linfáticos de la pelvis por adenocarcinoma colorrectal entre enero de 2012 y diciembre de 2019.INTERVENCIONES:Comparamos los resultados quirúrgicos mediante modelos pélvicos tridimensionales impresos con los resultados de control.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue el número de ganglios linfáticos laterales pélvicos extraídos en un lado pélvico después del análisis de coincidencia de propensión.RESULTADOS:Después del emparejamiento, se asignaron 35 lados pélvicos cada uno, tanto al modelo tridimensional como al grupo de control; no se observaron diferencias significativas con respecto a las características de los pacientes entre los dos grupos. El número de ganglios linfáticos pélvicos laterales extraídos fue significativamente mayor en el grupo del modelo tridimensional (mediana, 9; rango 3-16) que en el grupo de control (mediana, 6; rango, 0-22) (p = 0.047).LIMITACIONES:Este fue un estudio retrospectivo que utilizó el emparejamiento por puntuación de propensión. Sin embargo, antecedentes históricos no fueron encontrados y la mayoría de los procedimientos de disección de los ganglios linfáticos laterales pélvicos en el grupo del modelo tridimensional se realizaron recientemente. Esta limitación pudo haber influido en los resultados quirúrgicos.CONCLUSIONES:El presente estudio demostró que al referirse a modelos pélvicos individualizados impresos en 3D, los cirujanos colorrectales recolectaron un mayor número de ganglios linfáticos laterales de la pelvis durante la disección lateral. Este resultado sugiere que los modelos tridimensionales impresos ayudan a los cirujanos a completar procedimientos más detallados. Consulte Video Resumen en http://links.lww.com/DCR/B776.

Genome evolution in the allotetraploid frog Xenopus laevis.

To explore the origins and consequences of tetraploidy in the African clawed frog, we sequenced the Xenopus laevis genome and compared it to the related diploid X. tropicalis genome. We characterize the allotetraploid origin of X. laevis by partitioning its genome into two homoeologous subgenomes, marked by distinct families of 'fossil' transposable elements. On the basis of the activity of these elements and the age of hundreds of unitary pseudogenes, we estimate that the two diploid progenitor species diverged around 34 million years ago (Ma) and combined to form an allotetraploid around 17-18 Ma. More than 56% of all genes were retained in two homoeologous copies. Protein function, gene expression, and the amount of conserved flanking sequence all correlate with retention rates. The subgenomes have evolved asymmetrically, with one chromosome set more often preserving the ancestral state and the other experiencing more gene loss, deletion, rearrangement, and reduced gene expression.

Demographic characteristics of children with growth hormone deficiency from 1996 to 2015 in Japan: 20 years of data from the foundation for growth science in Japan.

Growth hormone (GH) deficiency (GHD) in children is a heterogeneous condition that includes several entities of various severities. GH treatment has been affected by various factors. Because comprehensive analyses for Japanese children with GHD over time are scarce, we investigated the baseline characteristics of patients with GHD at the start of GH treatment between 1996 and 2015 using data from the Foundation for Growth Science in Japan. During the registration period, 19,717 subjects were determined to be eligible for GH treatment as GHD. Overall analyses revealed that there were twice the number of male patients as female patients, and the etiology was idiopathic in 91.1%, central nervous system (CNS) tumor at the hypothalamus-pituitary area in 1.7%, CNS tumor distant from the hypothalamus-pituitary area in 0.68%, other tumors in 0.91%, congenital CNS malformations in 0.83%, and other diseases in 1.1% with their specific characteristics. The latest average age, height standard deviation score (SDS), insulin-like growth factor-1 SDS, and proportion of severe GHD at GH treatment initiation were 8.8 years, -2.76, -1.42, and 19.5%, respectively. The proportions of breech delivery and asphyxia gradually decreased, whereas that of caesarean section gradually increased during the registration period with the latest values of 2.2%, 4.9%, and 14.0%, respectively (all analyses: p < 0.0001). In contrast, the proportion of idiopathic GHD with breech delivery seemed to reach the lowest level among those with a birth year before 2000. This study identified the characteristics and changes of patients with GHD over 20 years.

Early growth hormone treatment accelerates delayed onset of puberty in patients with growth hormone deficiency.

We investigated whether growth hormone (GH) treatment could accelerate the onset of puberty in patients with isolated GH deficiency (GHD). Of the 135 boys and 89 girls who started GH treatment before the onset of puberty and were followed up at Tanaka Growth Clinic, 83 boys and 51 girls who started GH treatment sufficiently earlier than the average age at onset of puberty of GHD patients (<10 years vs. 11.7 years for boys; <9.5 years vs. 11.4 years for girls) were analyzed. Age at onset of puberty significantly positively correlated to age at the start of GH treatment (boys: r = 0.427, p < 0.0001; girls: r = 0.302, p < 0.05). When the subjects were divided into two groups each: for boys, Groups A (n = 45) and B (n = 39), treatment was started at age <8 and 8 to <10 years, respectively; for girls, Groups A (n = 26) and B (n = 21), treatment was started at age <7 and 7 to <9.5 years, respectively, age at the onset of puberty was significantly lower in Groups A than in Groups B by the Mann-Whitney U test (boys: p < 0.01; girls: p < 0.05) and Kaplan-Meier log-rank test (boys: p < 0.01; girls: p < 0.05). These results indicate that GH treatment accelerates the delayed onset of puberty in patients with GHD. Heights at the onset of puberty in Groups A and B were not significantly different, suggesting that early treatment does not increase adult height.

Management of hydronephrosis after radical cystectomy and urinary diversion for bladder cancer: A single tertiary center experience.

OBJECTIVES: To clarify the incidence of postoperative hydronephrosis and verify the validity of diagnostic and therapeutic approaches for hydronephrosis after cystectomy and urinary diversion for bladder cancer. METHODS: Totally, 290 patients receiving urinary diversion from 2005 through 2017 with complete data were enrolled, including 258 (89.0%) with an ileal conduit and 32 (11.0%) with an ileal neobladder. Postoperative radiographic images were reviewed. In patients with postoperative hydronephrosis, antegrade pyelography and ureteroscopy were performed to exclude malignant etiology. Balloon dilation and open surgical revision were performed according to the conditions. RESULTS: Forty-six patients (58 renal units) developed postoperative hydronephrosis. The cumulative incidence was 11.4% by a median follow-up of 59.5 months. Ureteral recurrence was detected by antegrade examinations in two patients, whereas malignant strictures were subsequently revealed in three patients. Thus, malignant etiology was found in hydronephrosis in five renal units (12.8%) of five patients (16.1%). The median times to diagnosis of hydronephrosis were 0 (interquartile range [IQR] 0-4) and 14 months (IQR 9-12) for benign and malignant strictures, respectively (p = 0.003). Of them, 31 patients (39 renal units) received interventions. Balloon dilation was performed in 13 renal units with benign strictures, and was successful in two (15.4%). Open surgical revision was performed in eight patients (11 renal units), including two with failed balloon dilation, all of which was successful. CONCLUSIONS: Postoperative hydronephrosis is potentially associated with recurrent disease. Accurate differential diagnosis is challenging although antegrade procedures may be helpful in some cases. Open surgical revision is highly effective to treat benign strictures.

Are there differences in the characteristics of patients who respond to gemcitabine plus cisplatin chemotherapy and those who respond to pembrolizumab therapy for metastatic urothelial carcinoma? Multicenter retrospective study.

OBJECTIVES: To evaluate factors to predict overall survival of metastatic urothelial carcinoma patients treated with gemcitabine plus cisplatin chemotherapy or pembrolizumab therapy. METHODS: We retrospectively evaluated two metastatic urothelial carcinoma cohorts treated with (i) gemcitabine plus cisplatin or (ii) pembrolizumab. The gemcitabine plus cisplatin cohort was treated from December 2005 through December 2014 while the pembrolizumab cohort was treated from January 2018 through December 2020. Using multivariate analyses, we evaluated the risk factors for overall survival in each cohort and compared them. None of the gemcitabine plus cisplatin cohort patients were treated with pembrolizumab. All patients in the pembrolizumab cohort were treated with prior platinum-based chemotherapy. RESULTS: There were 184 patients in the gemcitabine plus cisplatin cohort and 91 in the pembrolizumab cohort. The mean follow-up periods were 714 and 284 days, respectively. In multivariate analysis, the risk factors for overall survival in the gemcitabine plus cisplatin cohort were liver metastasis, worse Eastern Cooperative Oncology Group performance status (1 or more), no primary site resection, and a high prognostic index (1 or more). In the pembrolizumab cohort, liver metastasis, bone metastasis, and worse Eastern Cooperative Oncology Group-performance status (1 or more), and high prognostic index (1 or more) were the risk factors for overall survival. In the pembrolizumab cohort, patients with a complete response or partial response during prior platinum-based chemotherapy had better overall survival with the following pembrolizumab treatment than those with stable or progressive disease (P = 0.004). CONCLUSIONS: Considering the similarity of these risk factors in two sequential treatments, it may be possible to predict the response to pembrolizumab according to the response to prior chemotherapy.

Summary of the Clinical Practice Guidelines for Penile Cancer 2021 by the Japanese Urological Association.

Penile cancer is a rare cancer for which no medical guidelines have been established before in Japan. These guidelines aim to standardize, as much as possible, the therapeutic modality for penile cancer, for which empirical evidence is limited on a global scale, thereby bolstering therapeutic outcomes for patients with penile cancer. The new guidelines conform to the Minds Guide for Developing Clinical Practice Guidelines (2017) as much as possible. However, virtually no randomized comparative studies and meta-analyses based on such randomized studies have been conducted. Therefore, only the findings available at present were listed after conducting an exhaustive literature review of items with extremely low evidence levels and for which bodies of evidence and grades of recommendation were not evaluated. Clinical questions were set for items with a relatively large number of studies, including retrospective studies. However, since it is virtually impracticable to summarize bodies of evidence by systematic reviews, recommendation grades and evidence levels were discussed and determined by the consensus panel of the Preparatory Committee. The following were outlined: epidemiological, pathological, diagnostic, therapeutic, follow-up, and quality of life-related findings. Additionally, seven clinical questions were established to determine recommendation grades and evidence levels. We hope that these guidelines will prove to be useful to medical professionals engaged in clinical practice related to penile cancer in Japan and anticipate that critical reviews of the guidelines will lead to further refinement of the next edition.

[Clinical Investigation of Immune Checkpoint Inhibitor-Associated Kidney Injury in Patients with Urologic Cancers].

We investigated the clinical characteristics of patients who developed kidney injury after starting treatment with immune checkpoint inhibitors (ICI) for urologic malignancies. The study included 118 patients who were treated with ICI at our hospital. They consisted of 65 with renal cell carcinoma, 52 with urothelial carcinomas and 1 with adrenocortical carcinoma with high-frequency microsatellite instability. Immune-related kidney injury was observed in 13 patients (11.0%), including stage 1, 2 and 3 kidney injuries in 9, 0 and 4 patients, respectively. In univariate analyses, ≥stage 4 chronic kidney disease (CKD) before ICI treatment and proton pump inhibitor use were significantly associated with all stages of kidney injury, whereas ≥stage 4 CKD and ICI combination therapy were significantly associated with kidney injury at ≥ stage 2. Of the 4 patients who developed ≥stage 2 kidney injury, histological examination was done only for 2 because renal biopsy was contraindicated in the other 2 due to prior nephrectomy. Steroid pulse therapy was performed for 3 patients but provided complete recovery only in 1. We should be aware of the risk for immune-related kidney injury in patients with baseline CKD (≥stage 4) and receiving ICI combination therapy. Precise diagnosis by histological examination can often be challenging due to a history of nephrectomy.