Identifying optimal puncture position by a real-time image analysis for Piezo-ICSI: a prospective randomized sibling oocyte study.

RESEARCH QUESTION: Would the use of the intracytoplasmic sperm injection (ICSI) position detector (IPD) make it possible to identify the optimal puncture position on oolemma during Piezo-ICSI and reduce oocyte degeneration and unintentional membrane rupture (UMR)? DESIGN: This sibling oocyte study included 917 inseminated oocytes from 113 infertile patients undergoing Piezo-ICSI. Oocytes were randomly divided into two groups: with or without IPD. The rates of UMR, degeneration, fertilization and embryonic development were compared between the two groups. As a secondary analysis, non-IPD oocytes were retrospectively assessed as appropriate or non-appropriate injection sites and analysed alongside prospective 'appropriate' injections. RESULTS: The rates of UMR (7.0% versus 12.9%, P = 0.004) and degeneration (2.4% versus 6.1%, P < 0.01 = 0.008) were significantly lower in the IPD group than in the non-IPD group. No significant differences, however, were observed in the rates of fertilization (two pronuclei, 83.8% versus 78.9%), blastocyst formation (48.5% versus 48.8%) or good-quality blastocysts (22.5% versus 20.5%). Additionally, no significant differences were observed in the rates of pregnancy (29.4% versus 35.1%) or live births (26.5% versus 29.7%) in a single embryo transfer setting with or without IPD. Comparing all 'appropriate' injections with 'non-appropriate' injections also showed a significantly decreased rate of UMR and degeneration (both P ≤ 0.001). CONCLUSIONS: The present study demonstrated that a real-time image analysis during Piezo-ICSI markedly reduced oocyte degeneration by avoiding areas associated with a high risk of UMR. Therefore, IPD may increase the number of embryos available for treatment.

A Genome-Wide Association Study of Prostate Cancer Susceptibility Using Occupational and Environmental Factors as Confounding Factors.

Background In addition to genetic predisposition, occupational and environmental factors are important for the risk of prostate cancer. We investigated the effect of single nucleotide polymorphisms (SNPs) on the development of prostate cancer in Japan, including occupational and industrial history as confounding factors in addition to age, smoking, and alcohol drinking. Methods We enrolled 210 prostate cancer patients and 504 male control patients. We conducted four genome-wide association study (GWAS) patterns for prostate cancer development. In the association test, logistic regression models incorporated age, smoking history, alcohol consumption history, and each pattern of industrial/occupational classification. Results No SNPs satisfying the genome-wide significance level of 5×10-8 were detected in GWAS. SNPs with a suggestive association level of 1×10-6 were found near the long intergenic non-protein coding RNA 1824 (LINC01824) and tripartite motif family like 2 (TRIML2) genes in the GWAS using occupational history as a confounder and near the ribosomal protein S2 pseudogene 25 (RPS2P25) gene in the GWAS using industrial history as a confounder. No SNPs that met the suggestive association level were observed in the GWAS that did not include occupational and industrial history. Conclusion By adding occupational and industrial history to the confounding factors, there were SNPs detected in the GWAS for prostate cancer development. The consideration of occupational and industrial history may increase the usefulness of GWAS.

Comparison of the Fixation Strengths of Screws between the Traditional Trajectory and the Single and Double Endplate Penetrating Screw Trajectories Using Osteoporotic Vertebral Body Models Based on the Finite Element Method.

STUDY DESIGN: This is a finite element (FE) study. PURPOSE: To compare the fixation strength of traditional trajectory (TT) and single and double endplate penetrating screw trajectories (SEPST/DEPST) to the osteoporotic vertebral body model based on the FE method. OVERVIEW OF LITERATURE: SEPST/DEPST have been developed to enhance the fixation strength in patients with diffuse idiopathic hyperostosis (DISH). This technique was also applied to patients with osteoporosis. However, determining the superiority of SEPST/ DEPST is difficult because of the heterogeneous patient backgrounds. METHODS: Twenty vertebrae (T12 and L1) from 10 patients with osteoporosis (two males and eight females; mean age, 74.7 years) were obtained to create the 10 FE models. First, a single screw was placed with TT and SEPST/DEPST, and the fixation strength was compared by axial pullout strength (POS) and multidirectional loading tests. Second, two screws were placed on the bilateral pedicles with TT and SEPST/DEPST, and the fixation force of the vertebrae in the constructs in flexion, extension, lateral flexion, and axial rotation was examined. RESULTS: SEPST and DEPST had 140% and 171% higher POS values than TT, respectively, and the DEPST result was statistically significant (p =0.007). The multidirectional fixation strength was significantly higher in DEPST and SEPST than in TT in the cranial, caudal, and medial directions (p <0.05) but not in the lateral direction (p =0.05). The vertebral fracture strength at the lower instrumented vertebra of the DEPST tended to be higher than that of TT. The vertebral motion angles in SEPST and DEPST were significantly smaller in lateral bending (p =0.02) and tended to be smaller in flexion and extension than in TT (p =0.13). CONCLUSIONS: This study may provide useful information for spine surgeons in deciding whether to choose the SEPS or DEPS technique for augmenting fixation in osteoporotic vertebral fracture surgery.

Hypomethylation of a CpG Site in the CpG Island of the Aquaporin 1 Gene May Be Involved in the Formation of Adult-Onset Non-communicating Hydrocele Testis.

Background Water channel aquaporin 1 (AQP1) protein expression is enhanced in the tunica vaginalis of patients with adult-onset non-communicating hydrocele testis and may contribute to the development of non-communicating hydrocele testis. We performed genetic and epigenetic analyses of the AQP1 gene in the tunica vaginalis of patients with adult-onset non-communicating hydrocele testis to elucidate the cause of enhanced AQP1 protein expression. Methodology The genotype was determined for Tag single-nucleotide polymorphisms (SNPs) representing the AQP1 gene and SNPs in the 5'-upstream region of the AQP1 gene. Then, by performing association analysis, the applicability of various genetic models was investigated for each SNP. Moreover, the methylation rate of CpG sites was examined for the CpG island related to the AQP1 gene. Results There was no significant association between each SNP and hydrocele testis for any of the genetic models. The average methylation rate of the 17 CpG sites evaluated was not significantly different between controls and hydrocele testis, but the methylation rate was lower in hydrocele testis than in controls at one CpG site. Conclusions There was a significant decrease in the methylation rate at one of the CpG sites in the CpG island associated with the AQP1 gene in the tunica vaginalis of patients with non-communicating hydrocele testis. This may increase AQP1 protein expression and contribute to the formation of hydrocele testis. SNPs related to the AQP1 gene were not associated with hydrocele testis.

A radiation-related second primary gastrointestinal stromal tumor in the bladder.

A 69-year-old man underwent 78 Gy/39 Fr of intensity-modulated radiation therapy for prostate cancer. Seven years after radiotherapy, a nonpapillary bladder tumor was identified. Transurethral resection of the bladder tumor was performed, and the pathological diagnosis was spindle cell sarcoma. Immunostaining revealed KIT-, DOG1++, CD34-, Actin++, Cytokeratin-, Desmin-, S100 protein-, and Vimentin++. No tumor recurrence was observed until 17 months after tumor resection. DOG1 is strongly and specifically expressed in gastrointestinal stromal tumors. This was a rare case of bladder gastrointestinal stromal tumor as a radiation-related second primary tumor.

Structural Analysis of the Colony-Stimulating Factor 3 Gene of Granulocyte Colony-Stimulating Factor-Producing Urothelial Cancer.

Background Granulocyte colony-stimulating factor (G-CSF) is a member of the CSF family of glycoproteins that regulate the proliferation, differentiation, and mobilization of neutrophils. G-CSF-producing malignant cancers have been reported to occur in various organs and are mostly associated with poor clinical prognosis. Here, we analyzed the structure of the CSF3 gene encoding the G-CSF protein to delineate the mechanism of G-CSF production by the cancer cells. Methodology Two cases of G-CSF-producing urothelial cancers and three cases of G-CSF-nonproducing bladder cancers were enrolled for genetic analysis. Results In one case of G-CSF-producing bladder cancer, six somatic mutations were detected in the 5'- upstream region of the CSF3 gene. No somatic mutations in the CSF3 gene were detected in another case of G-CSF-producing renal pelvic cancer and G-CSF-nonproducing bladder cancers. Copy numbers of the CSF3 gene were not increased in G-CSF-producing urothelial cancers. Conclusions Somatic mutations in the 5'- upstream region of the CSF3 gene may cause G-CSF protein overproduction.

Iterative Synthesis of Oligosilanes Using Methoxyphenyl- or Hydrogen-Substituted Silylboronates as Building Blocks: A General Synthetic Method for Complex Oligosilanes.

Organosilanes have attracted the attention of researchers for more than 150 years due to their unique properties, and they have become indispensable industrial assets. However, many synthesized oligosilanes with multiple Si-Si bonds are relatively simple, i.e., they often only contain a single repeating unit. More laborious customized synthetic routes can lead to more complex oligosilanes, but compared to carbon-based molecules, their structural diversity remains limited. The development of effective and practical synthetic routes to complex oligosilanes that contain mixed substituents constitutes a long-standing challenge. Here, we describe an iterative synthesis of oligosilanes using methoxyphenyl- or hydrogen-substituted silylboronates, which were obtained via transition-metal-catalyzed Si-H borylation reactions. The first key reaction is a cross-Si-Si bond-forming reaction between chloro(oligo)silanes and silylboronates activated by MeLi. The second key reaction is the selective chlorination of the methoxyphenyl group or the hydrogen atom at the terminal of the oligosilanes. Iteration of these two key reactions enables the synthesis of various oligosilanes that are otherwise difficult to access. As a demonstration of the synthetic utility of this iterative synthetic approach, oligosilanes with different sequences were prepared by simply changing the order of the reaction of four different silicon units. Furthermore, a bespoke tree-shaped oligosilane is easily obtained via the present iterative synthesis. The solid-state structures of several of these oligosilanes were unequivocally determined using single-crystal X-ray diffraction analysis.

Relationship between the Reduced Expression of Zinc Finger Protein 668 in Bladder Cancer and Its Invasiveness.

The zinc finger protein 668 (ZNF668) gene encodes a Kruppel C2H2-type zinc-finger protein with 16 C2H2-type zinc fingers. The ZNF668 gene functions as a tumor suppressor gene in breast cancer. We histologically analyzed ZNF668 protein expression in bladder cancer and examined mutations of the ZNF668 gene in 68 cases of bladder cancer. In bladder cancer, the ZNF668 protein was expressed in the nuclei of cancer cells. In bladder cancer with submucosal and muscular infiltration, the expression of ZNF668 protein was significantly lower than that without submucosal and muscular infiltration. Eight heterozygous somatic mutations were detected in exon3 in five cases, and five of the mutations resulted in amino acid sequence mutations. Mutations resulting in amino acid sequence alterations also resulted in lower ZNF668 protein expression in bladder cancer cell nuclei, but no significant association with bladder cancer infiltration was detected. Decreased ZNF668 expression in bladder cancer was associated with submucosal and muscle invasion of cancer cells. Somatic mutations resulting in amino acid mutations in ZNF668 were found in 7.3% of the bladder cancer cases.

Evaluation of intraoperative coronal alignment using a computer-assisted rod bending system (CARBS) without intraoperative radiation exposure in adult spinal deformity surgery: a technical note and preliminary results.

PURPOSE: Intraoperative radiographs and fluoroscopy are used in adult spinal deformity (ASD) surgery to prevent postoperative coronal malalignment but with limited accuracy. Therefore, we applied a computer-assisted rod bending system (CARBS: Bendini®) for an intraoperative coronal alignment evaluation. The purpose of this study is to introduce this novel technique and validate its accuracy. METHODS: Fifteen ASD patients were included in the study. The heads of the bilateral S1 pedicle screws (S1), the S1 spinous process, and the bilateral greater trochanter (GT) and the C7 spinous process were recorded with CARBS for an intraoperative coronal alignment evaluation. The lines which connect the bilateral S1 and GT were used as references. The C7-center sacral vertical line (C7-CSVL) on the CARBS monitor was checked, and the C7-CSVL from the intraoperative CARBS recording and postoperative standing whole spine radiograph were compared. RESULTS: Intraoperative C7-CSVL with CARBS was 35.1 ± 31.6 mm when the S1 pedicle screws were used as the reference line and was 16.6 ± 17.8 mm when the GTs were used. Postoperative C7-CSVL by radiograph was 15.1 ± 16.5 mm. In addition, the intraoperative C7-CSVL with CARBS and the postoperative C7-CSVL showed a strong positive correlation in both GT (R = 0.86, p < 0.01) and in S1(R = 0.79, p < 0.01), with a better correlation found in GT than in S1. CONCLUSION: Intraoperative C7-CSVL with CARBS was found to be highly accurate in ASD surgery. Our results suggest that this novel technique can be useful as an alternative to intraoperative radiography and fluoroscopy and may reduce radiation exposure.

Subclassification of pT3 upper tract urothelial carcinoma: a multicenter retrospective study.

PURPOSE: The prognosis of patients with pT3 upper tract urothelial carcinoma (UTUC) varies. The current study aimed to further classify patients with pT3 UTUC into different survival outcome groups based on tumor location and site of invasion. METHODS: This retrospective study included 323 patients with pT3 UTUC who underwent nephroureterectomy at 11 hospitals in Japan. Histological and clinical data were obtained via a chart review. Univariate and multivariate Cox proportional hazards analyses showed the effect of different variables on recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: The median age of the patients was 72 years. Patients with pT3 UTUCs were divided into two groups: those with renal parenchymal invasion only (pT3a, n = 95) and those with peripelvic or periureteral fat invasion (pT3b, n = 228). pT3b UTUC was significantly associated with hydronephrosis, low preoperative estimated glomerular filtration rate (eGFR), histological nodal metastasis, nuclear grade 3, lymphovascular invasion (LVI), carcinoma in situ, and positive surgical margin. Based on the univariate analyses, patients with pT3b UTUC had a significantly lower 5-year RFS (42.4% vs. 70.1%, p < 0.0001), 5-year CSS (54.3% vs. 80.0%, p = 0.0002), and 5-year OS (47.8% vs. 76.8%, p < 0.0001) than those with pT3a UTUC. According to the multivariate analyses, nodal metastasis, LVI, adjuvant chemotherapy, preoperative eGFR, nuclear grade (RFS only), surgical margin (RFS only), and Charlson comorbidity index (OS only), but not pT3b stage, were associated with survival. CONCLUSION: Compared with pT3a UTUC, pT3b UTUC was significantly associated with worse histological features, consequently resulting in unsatisfactory survival outcomes.

Optimal puncture position for ICSI can be detected by image analysis using Local Binary Pattern.

RESEARCH QUESTION: One of the problems during the intracytoplasmic sperm injection (ICSI) procedure is unintentional membrane rupture (UMR), which often predisposes to subsequent oocyte degeneration. Can the ICSI Position Detector (IPD) be useful in identifying the optimal puncture location to prevent UMR during ICSI? DESIGN: A total of 709 mature oocytes were included. Conventional ICSI was carried out and images were recorded by IPD; these were analysed retrospectively. RESULTS: Inseminated oocytes were retrospectively grouped according to the IPD, irrespective of whether oolemma was punctured at an area in which UMR is likely (non-appropriate group) or unlikely (appropriate group). In the appropriate group, rates of UMR (5.3% versus 18.2%) and degeneration (2.5% versus 8.7%) were significantly lower than those of the non-appropriate group, whereas rate of fertilization (87.1% versus 69.7%) was significantly higher than those of the non-appropriate group, respectively (P < 0.001). These differences remained even after propensity score matching to adjust for potential differences in characteristics between appropriate and non-appropriate groups. CONCLUSIONS: This study demonstrated that the IPD is useful to identify the optimal puncture location to circumvent UMR during the ICSI procedure, resulting in reduced UMR and oocyte degeneration, thereby, generating more embryos available for transfer or cryopreservation.

Occupational disparities in tumor grade and cytosolic HMGB1 expression in renal cell cancer.

OBJECTIVES: We sought to examine occupational disparities in tumor grade and cytosolic expression of high-mobility group box-1 (HMGB1) among renal cell cancer (RCC) patients. METHODS: This retrospective study included 318 RCC patients with complete information on occupation and pathology in Kanagawa Cancer Registry (KCR). Longest-held occupations were grouped into manual workers (e.g., manufacturing, construction) versus "others." Odds ratios (OR) and 95% confidence intervals (CI) for high-grade histology were estimated by logistic regression, adjusted for age and sex. We also examined a sub-sample of 74 low-grade RCC inpatients to estimate the OR for positive cytosolic HMGB1 expression in manual workers, adjusting for age, sex, and other available covariates. RESULTS: High-grade tumors were more prevalent in manual workers compared to other occupations: 23.0% (14/61) versus 10.9% (28/257, p = .01) with an adjusted OR of 2.28 (95% CI, 1.11-4.69). In the sub-sample of low-grade RCCs, positive cytosolic HMGB1 expression was more prevalent in manual workers compared to other occupations: 71.4% (10/14) versus 38.3% (23/60, p = .03) with a sex- and age-adjusted OR of 3.76 (95% CI, 1.03-13.7). CONCLUSIONS: Manual workers are associated with increased risks of high-grade renal cell tumors and cytosolic HMGB1 expression.

Clinical relevance of a newly developed endometrial receptivity test for patients with recurrent implantation failure in Japan.

Purpose: To assess the clinical efficacy of personalized embryo transfer (pET) guided by a new endometrial receptivity test, ERPeakSM, in patients with recurrent implantation failure (RIF). Methods: Recurrent implantation failure patients of all ages at two private Japanese clinics from April 2019 to June 2020 were retrospectively analyzed. The intervention group (n = 244) received pET in accordance with endometrial receptivity testing results and was compared to control group (n = 306) receiving standardized timing, non-personalized embryo transfer (npET). In propensity score matching analysis, the clinical pregnancy rate (CPR) and live birth rate (LBR) were compared between groups, and a subanalysis of advanced maternal age (AMA) (≥38 years old) versus non-AMA (<38 years old) patients was also conducted. Results: The CPR and LBR of the pET group were significantly higher than those of the npET group (37.7% vs. 20.0%, adjusted OR: 2.64; 95%CI, 1.70-4.11, p < 0.001 and 29.9% vs. 9.7%, adjusted OR: 4.13; 95%CI, 2.40-7.13, p < 0.001, respectively). Furthermore, in the subanalyses, the CPR and LBR of the pET group were significantly higher than those of the npET group in both the AMA non-AMA patients. Conclusions: The new ERPeakSM endometrial receptivity test is a useful alternative diagnostic tool for poor-prognosis patients, regardless of age.

Genome-Wide Association Study Adjusted for Occupational and Environmental Factors for Bladder Cancer Susceptibility.

This study examined the effects of single-nucleotide polymorphisms (SNPs) on the development of bladder cancer, adding longest-held occupational and industrial history as regulators. The genome purified from blood was genotyped, followed by SNP imputation. In the genome-wide association study (GWAS), several patterns of industrial/occupational classifications were added to logistic regression models. The association test between bladder cancer development and the calculated genetic score for each gene region was evaluated (gene-wise analysis). In the GWAS and gene-wise analysis, the gliomedin gene satisfied both suggestive association levels of 10-5 in the GWAS and 10-4 in the gene-wise analysis for male bladder cancer. The expression of the gliomedin protein in the nucleus of bladder cancer cells decreased in cancers with a tendency to infiltrate and those with strong cell atypia. It is hypothesized that gliomedin is involved in the development of bladder cancer.

Radiological Evaluation of Combined Anteroposterior Fusion with Vertebral Body Replacement Using a Minimally Invasive Lateral Approach for Osteoporotic Vertebral Fractures: Verification of Optimal Surgical Procedure.

The combined anteroposterior fusion with vertebral body replacement (VBR) using a wide footplate expandable cage with a minimally invasive lateral approach has been widely used for pseudoarthrosis after osteoporotic vertebral fractures. The purpose of this study is to evaluate the radiological results of combined anteroposterior surgery using VBR and to recommend the optimal procedure. Thirty-eight elderly patients were included in this study. The mean preoperative local kyphosis angle was 29.3°, and the mean correction loss angle was 6.3°. Cage subsidence was observed in ten patients (26.3%), and UIV or LIV fracture in twelve patients (31.6%). Patients with cage subsidence were compared to those without cage subsidence to determine the causal factors. The mean number of fixed vertebrae was 5.4 vertebrae with cage subsidence and 7.4 vertebrae without cage subsidence. In addition, to precisely clarify the optimal number of fixed vertebrae, those patients with two above-two below fixation were compared to those with less than two above-two below fixation, which revealed that the correction loss angle was significantly less in two above-two below fixation (p = 0.016). Based on these results, we recommend at least two above-two below fixation with VBR to minimize the correction loss angle and prevent cage subsidence.

Occupational disparities in survival from common cancers in Japan: Analysis of Kanagawa cancer registry.

BACKGROUND: Little is known about occupational disparities in survival for common cancer sites in Japan. METHODS: Using data from a population-based cancer registry, we identified 32,870 cancer patients diagnosed during 1992-2011. We followed the patients for 5 years (median follow-up time 5.0 years). For each individual, we classified their longest-held occupation into 5 classes (upper non-manual, lower non-manual, manual, farmer, and others) following the Erikson-Goldthorpe-Portocarero scheme. Poisson regression models were used to estimate overall and site-specific mortality rate ratios (MRRs) and 95% confidence intervals (CI) for each occupational class, adjusted for sex, age, and diagnosis year. Upper non-manual workers served as the reference group. Additionally, using a binary categorization of occupations (manual workers versus non-manual workers), a causal mediation analysis with 4-way decomposition was performed to investigate the potential mediation of the association between occupation and overall mortality by cancer stage. RESULTS: Overall prognosis was good in this population (5-year overall survival was 81.7%). Compared with upper non-manual workers, both overall and cancer-specific mortality was higher in lower non-manual workers (MRR=1.14, 95% CI 1.05-1.24) and manual workers (MRR=1.40, 95% CI 1.29-1.53). After adjusting for the mediating influence of prognostic factors (stage and treatment), the observed occupational differences were attenuated but remained significant in manual workers: MRR = 1.23 (95% CI 1.08-1.39). Observed occupational disparities tended to be attributable to common cancers, i.e., stomach and lung among men and female breast cancer. Additionally, manual workers had 1.25 times higher odds for advanced stage. In the mediation analysis, the overall proportion explained by mediating effect of cancer stage was 29% (4% due to mediated interaction and 25% due to pure indirect effect). CONCLUSION: We documented occupational disparities in survival from commonly-occurring cancers in Japan. Occupational differences in cancer stage may explain one-third of the survival disparities.

Synthesis of hydrosilylboronates via the monoborylation of a dihydrosilane Si-H bond and their application for the generation of dialkylhydrosilyl anions.

The synthesis of a series of hydrosilylboronates via the selective iridium- or nickel-catalyzed monoborylation of dihydrosilane Si-H bonds is described. The synthesized silylboronates, which bear a single Si-H bond, can be used as novel silicon nucleophiles in the presence of transition-metal catalysts or bases. The first 29Si{1H} NMR spectroscopic evidence for the formation of (t-Bu)2HSiLi, generated by the reaction of (t-Bu)2HSi-B(pin) with MeLi, is reported as the first example of a dialkylhydorosilyl lithium species.

Falloposcopic tuboplasty: an easy, quick, and safe technique.

OBJECTIVE: To describe our simplified technique for falloposcopic tuboplasty (FT) and demonstrate its principle and results. DESIGN: A step-by-step description of the technique and demonstration of its principle using a clay model. SETTING: Private infertility clinics in Osaka and Tokyo operated by 10 physicians. PATIENT(S): A total of 431 infertile women with a diagnosis of unilateral or bilateral proximal tubal occlusion (6 cm from the uterotubal ostia), between October 2013 and February 2019 were included. These patients underwent routine work-ups for infertility, including a semen analysis, hysterosalpingography, antimüllerian hormone, basal luteinizing hormone/follicle-stimulating hormone and prolactin concentrations during menstruation, postcoital test in the periovulatory period, and estradiol and progesterone concentrations in the middle of the luteal phase. Physicians performed hysterosalpingography to evaluate tubal patency and uterine shape. Saline infusion sonography was not conducted because it does not accurately identify regions of tubal occlusion and/or stenosis. INTERVENTION(S): The principle of our simplified technique for FT is that a hole is located at the side of the FT catheter tip. Therefore, the balloon and fiberscope move away from the catheter line (Fig. 1). The uterotubal ostium is located at the tip-end of the triangle of the uterine cavity. When a balloon is inserted while visualizing the uterotubal ostium at the nearest position to the ostium, the balloon hits the uterine wall. When a balloon is inserted 5-10 mm from the uterotubal ostium without visualization, the balloon may be easily placed in the ostium through its convex angle, allowing it to slide into the uterine wall (Figs. 2 and 3). Step 1: Confirm anteflexion or retroflexion of the uterus by ultrasound. Step 2: Confirm the direction of the uterotubal ostia by hysteroscopy. Step 3: Adjust the angle of the FT catheter according to steps 1 and 2, insert the catheter into the end of the uterus, pull it back 5-10 mm (without visualizing the uterotubal ostia), and then fix it to the forceps. Catheter placement away from the tubal ostium is confirmed by the residual length of the moving part of the catheter. An attending instructor should ask the operator about the feeling of rigidity when the catheter does not advance and then suggest whether to proceed or stop. In the latter case, the catheter is not moved, saline is infused for 1 minute for lubrication, the balloon is pulled back using the fiberscope to remove the bunching of the balloon, and balloon pressure is changed as follows: 6→8→6→10→6 mmHg. Our institutional review board stated that approval was not required because the video describes the technique of our routine procedure. MAIN OUTCOME MEASURE(S): A description of the FT technique using a clay model and a demonstration of its application in our clinic. RESULT(S): The average operative time was 15.4 minutes, and the clinical pregnancy rate was 24.4% (natural conception and intrauterine insemination without in vitro fertilization). No significant differences were observed in the operative time or pregnancy rate among physicians. Approximately 17 FT procedures may be performed using one fiberscope. CONCLUSION(S): Our simplified technique, which was described and demonstrated in this video article, is a feasible and practical approach for performing FT. It provides excellent cost performance by saving fiberscopes. The most important point is "Introduce the balloon and fiberscope 5-10 mm away from the uterotubal ostia without visualizing it." To facilitate learning this technique, we recommend watching the video and then practicing FT without searching for the uterotubal ostia. Physicians master FT without any assistance by an attending instructor in ≤3 attempts.

Smaller decline of renal function after nephroureterectomy predicts poorer prognosis of upper tract urothelial carcinoma: a multicentre retrospective study.

PURPOSE: Renal function is frequently impaired in the patients with upper tract urothelial carcinoma. We aimed to evaluate the impact of renal function and its change after surgery on survival rates in patients with upper tract urothelial carcinoma after nephroureterectomy. METHODS: The study cohort comprised 755 patients with upper tract urothelial carcinoma who underwent nephroureterectomy between 1995 and 2016 at nine hospitals in Japan. Estimated glomerular filtration rate was calculated using the three-variable Japanese equation for glomerular filtration rate estimation from serum creatinine level and age. Outcomes were recurrence-free, cancer-specific and overall survivals. Univariate and multivariate Cox proportional hazards regression analyses were used. RESULTS: Median patients' age was 72 years old. Pre- and post-surgical median estimated glomerular filtration rate were 55.5 and 42.9 ml/min/1.73 m2, respectively. Median estimated glomerular filtration rate decline after surgery, which represents function of the affected side kidney, was 13.1 ml/min/1.73 m2. The 5-year recurrence-free, cancer-specific and overall survivals were 68.3, 79.4 and 74.0%, respectively. Multivariate analysis indicated that lower preoperative estimated glomerular filtration rate and estimated glomerular filtration rate decline were associated with poorer recurrence-free, cancer-specific and overall survivals, but post-operative estimated glomerular filtration rate was not. Estimated glomerular filtration rate decline was more significant poor-prognosticator than preoperative estimated glomerular filtration rate. Proportions of the patients with estimated glomerular filtration rate <60 ml/min/1.73 m2 before surgery were 50.6 and 73.2% in organ-confined disease and locally advanced disease, respectively (P < 0.0001). After surgery, they were 91.6 and 89.8%, respectively (P = 0.3896). CONCLUSIONS: Lower preoperative renal function, especially of the affected side kidney, was significantly associated with poor prognosis after nephroureterectomy for upper tract urothelial carcinoma. Many patients with locally advanced disease have reduced renal function at diagnosis and even more after surgery.

Serum alanine aminotransferase as an early marker of outcomes in patients receiving anti-PD-1 or anti-CTLA-4 antibody.

Immune-oncology (IO) drug therapy is effective against various types of cancer. Although several, potential, clinical predictive markers have been identified, none so far have proven reliable. Herein we evaluated changes in serum alanine aminotransferase (ALT), which is upregulated by the accumulation of activated CD8+T cells in the liver, as a potentially reliable predictive marker. We retrospectively analyzed 265 patients with advanced malignancies at three institutions between 2016 and 2019. The patients received IO drug therapy. We defined the ALT ratio (ALR) as the serum ALT value at baseline / the highest serum ALT during IO drug therapy, then determined whether the ALR correlated with the objective response rate or progression-free survival. The median follow-up was 3.1 months. We observed objective responses in 65 patients. The ALR ranged from 0.19 to 32.2 (median 1.5), and a significant ALR increase was observed in responders (p < 0.001). In receiver operating characteristic analysis, ALR = 1.55 had the highest sensitivity and specificity. The patients with ALR < 1.55 had a significantly poorer PFS than those with ALR ≥ 1.55. A high ALR was associated with a tumor response and good PFS in patients with advanced malignancies. The ALR based on activated cytotoxic T lymphocyte dynamics is therefore a reliable predictive marker.