Effects of different combinations of radical nephroureterectomy and bladder cuff excision procedures for upper tract urothelial carcinoma on bladder recurrence

ABSTRACT Purpose: To compare the effects of different combinations of radical nephroureterectomy (RNU) and bladder cuff excision (BCE) surgical procedures on intravesical recurrence (IVR) in patients with upper tract urothelial carcinoma (UTUC). Materials and Methods: This retrospective observational study included 452 patients who underwent RNU with BCE for UTUC between January 2010 and December 2020. The patients were classified into three groups based on different combinations of RNU and BCE surgical procedures: open RNU with open BCE (group 1, n=104), minimally invasive (MIS) RNU with open BCE (group 2, n=196), and MIS RNU with intracorporeal BCE (group 3, n=152). Data on demographics, body mass index, history, preoperative renal function, perioperative status, tumor characteristics, histopathology, and recurrence conditions were collected. Multivariate Cox regression analyses were performed to determine the impact of the surgical procedures on IVR. P-values <0.05 were considered statistically significant. Results: After a median follow-up of 29.5 months, the IVR rate was 29.6% and the IVR-free survival rate was the lowest in group 2 (group 1 vs. group 2 vs. group 3: 69.0% vs. 55.1% vs. 67.5%; log-rank P=0.048). The overall survival rate was comparable among the three groups. Multivariate analysis revealed that group 2 had a significantly higher risk of IVR than group 1 (hazard ratio=1.949, 95% confidence interval=1.082–3.511, P=0.026), while groups 1 and 3 had similar risks. Conclusions: For patients with UTUC, MIS RNU with open BCE is associated with a higher risk of IVR than open RNU with open BCE and MIS RNU with intracorporeal BCE

Electromagnetic Wave Theory and Applications

Contains table of contents for Section 3 and reports on five research projects.U.S. Department of Transportation Contract DTRS-57-88-C-00078TTD13U.S. Department of Transportation Contract DTRS-57-88-C-00078TTD30Defense Advanced Research Projects Agency Contract MDA972-90-C-0021Digital Equipment CorporationIBM CorporationJoint Services Electronics Program Contract DAAL03-89-C-0001Joint Services Electronics Program Contract DAAL03-92-C-0001Schlumberger-Doll ResearchU.S. Navy - Office of Naval Research Grant N00014-90-J-1002U.S. Navy - Office of Naval Research Grant N00014-89-J-1019National Aeronautics and Space Administration Grant NAGW-1617National Aeronautics and Space Administration Grant 958461National Aeronautics and Space Administration Grant NAGW-1272U.S. Army Corp of Engineers Contract DACA39-87-K-0022U.S. Navy - Office of Naval Research Grant N00014-89-J-110

Electromagnetic Wave Theory and Applications

Contains table of contents for Section 3, reports on four research projects and a list of publications.National Aeronautics and Space Administration Grant NAGW-1617National Aeronautics and Space Administration Agreement 958461National Aeronautics and Space Administration Grant NAGW-1272U.S. Army Corp of Engineers Contract DACA39-87-K-0022U.S. Navy - Office of Naval Research Grant N00014-89-J-1107U.S. Navy - Office of Naval Research Grant N00014-92-J-1616Digital Equipment CorporationJoint Services Electronics Program Contract DAAL03-92-C-0001U.S. Navy - Office of Naval Research Grant N00014-90-J-1002U.S. Navy - Office of Naval Research Grant N00014-89-J-1019U.S. Department of Transportation Agreement DTRS-57-88-C-00078TTD13U.S. Department of Transportation Agreement DTRS-57-88-C-00078TTD30U.S. Department of Transportation Agreement DTRS-57-92-C-00054TTD1DARPA/Consortium for Superconducting Electronics Contract MDA972-90-C-0021National Science Foundation Fellowship MIP 88-5876

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Testicular carcinoid tumor: A case report and literature review

We present a case of a 46-year-old man with an incidental finding of a right testicular tumor on magnetic resonance imaging. He received radical orchiectomy, and the pathological report showed a testicular carcinoid tumor. He has remained in a stable condition 3 years after the operation. Carcinoid tumors of the testis are extremely rare and account for less than 1% of testicular tumors and carcinoids. A painless mass or prominent testis enlargement is the most distinctive presentation. Less than 1–3% of patients demonstrate carcinoid syndrome. Nuclear scintigraphy scan and computed tomography scan have a diagnostic value in excluding carcinoid from other sites. Radical orchiectomy is the treatment of choice, and the prognosis is good for localized carcinoid tumors after resection. Adjuvant chemotherapy or radiotherapy for advanced disease shows only minimal benefits

Suprapubic mini-laparoscopy-assisted transurethral thulium laser excision of intravesical mesh after anti-incontinence sling procedures

Objectives: We present our innovative technique of excising intravesically exposed mesh resulting from anti-incontinence sling procedures using transurethral thulium laser assisted by a suprapubic transvesical mini-laparoscopic grasper. Methods: Two patients agreed to anti-incontinence sling surgery for stress urinary incontinence several years ago prior to presentation. Because of symptom recurrence, they underwent repeat anti-incontinence sling surgery. One patient developed dysuria and mild lower abdominal pain gradually 1 month after the operation. Cystoscopy was performed and revealed exposed mesh at the left anterolateral wall, which might have resulted from missed intraoperative bladder perforation. The other patient presented with dysuria 2 years following the second sling procedure. Cystoscopy demonstrated a calcified mass attached to the right lateral wall. Bladder erosion by a previously implanted mesh was thought to be the cause. Intravesical mesh was removed transurethrally with thulium laser assisted by a suprapubic transvesical mini-laparoscopic grasper for the former patient. Vesicolithotripsy was performed for the latter patient first and the intravesical mesh was removed in the same manner as in the former patient. Results: The intravesical mesh was removed smoothly with thulium laser with the assistance of a suprapubic mini-laparoscopic grasper. As the procedure was minimally invasive, both patients recovered well after removal of the intravesical mesh. The irritative voiding symptoms also subsided following removal of the mesh. Conclusion: Removal of eroded or misplaced intravesical mesh after anti-incontinence sling procedures can be accomplished by transurethral laser excision with the assistance of suprapubic transvesical mini-laparoscopic instruments. The procedure is safe, effective, and minimally invasive, with a fast recovery

Proteomic Analysis of Testicular Interstitial Fluid in Men with Azoospermia

Background: The primary microenvironment of the testis comprises testicular interstitial fluid (TIF) surrounding the seminiferous tubules and testicular interstitial tissue. The pathological alterations of germ and Sertoli cells could affect the TIF composition and might contain putative biomarkers for monitoring active spermatogenesis. Objective: We identified differentially expressed proteins in the TIF of patients with obstructive (OA) or nonobstructive (NOA) azoospermia to elucidate the underlying etiology of defective spermatogenesis. Design, setting, and participants: We prospectively enrolled nine patients, including three men with OA and six with NOA with (n = 3) and without (n = 3) successful sperm retrieval. Their TIF was collected during the testicular sperm extraction procedure. Outcome measurements and statistical analysis: TIF was analyzed using liquid chromatography-tandem mass spectrometry to identify differentially expressed proteins specific to OA and NOA with or without successful sperm retrieval. The dysregulated protein was further validated using Western blotting. Results and limitations: Among the 555 TIF proteins identified in NOA patients, 14 were downregulated relative to OA patients. These proteins participate in biological processes such as proteolysis, complement activation, and immune responses; complement and coagulation cascade pathways were also enriched. Furthermore, 68 proteins with significantly higher levels were identified in the TIF of NOA patients with successful sperm retrieval than in those with failed sperm retrieval; these are mainly implicated in oxidation-reduction processes. The expression of calreticulin, which can distinguish successful and failed testicular sperm retrieval in the NOA group, was validated by Western blotting. Conclusions: We provide the first scientific evaluation of TIF protein composition in men with azoospermia. These findings will help identify the physiological and pathological roles of each protein in regulating sperm production. Thus, our study underscores the potential of TIF in sperm retrieval biomarker discovery and would serve as a foundation for further studies to improve treatment strategies against azoospermia. Patient summary: Using a proteomic approach, we identified and analyzed the total protein content of testicular interstitial fluid in humans with defective spermatogenesis for the first time and discovered altered protein expression patterns in patients with nonobstructive azoospermia (NOA). Proteins related to oxidation-reduction processes were upregulated in NOA patients with successful sperm retrieval compared with those with failed sperm retrieval. This can aid the development of novel diagnostic tools for successful testicular sperm retrieval

Oncogenic Roles of Polycomb Repressive Complex 2 in Bladder Cancer and Upper Tract Urothelial Carcinoma

Cancers of the urinary tract are one of the most common malignancies worldwide, causing high morbidity and mortality, and representing a social burden. Upper tract urothelial carcinoma (UTUC) accounts for 5–10% of urinary tract cancers, and its oncogenic mechanisms remain elusive. We postulated that cancers of the lower and the upper urinary tract may share some important oncogenic mechanisms. Therefore, the oncogenic mechanisms discovered in the lower urinary tract may guide the investigation of molecular mechanisms in the upper urinary tract. Based on this strategy, we revisited a high-quality transcriptome dataset of 510 patients with non-muscle invasive bladder cancer (NMIBC), and performed an innovative gene set enrichment analysis of the transcriptome. We discovered that the epigenetic regulation of polycomb repressive complex 2 (PRC2) is responsible for the recurrence and progression of lower-track urinary cancers. Additionally, a PRC2-related gene signature model was discovered to be effective in classifying bladder cancer patients with distinct susceptibility of subsequent recurrence and progression (log-rank p p = 0.026). Immunohistochemical staining revealed the presence of PRC2 components (EZH2, EED, and SUZ12) and methylated PRC2 substrates (H3K27me3) in the archived UTUC tissues. The H3K27me3 exhibited higher intensity and area intensity product in stage T3 UTUC tissues than in stage Ta/T1 tissues (p = 0.006 and 0.015, respectively), implicating stronger PRC2 activity in advanced UTUC. The relationship between H3K27 methylation and gene expression is examined using correlations. The H3K27me3 abundance is positively correlated with the expression levels of CDC26, RP11-2B6, MAPK1IP1L, SFR1, RP11-196B3, CDK5RAP2, ANXA5, STX11, PSMD5, and FGFRL1. It is also negatively correlated with CNPY2, KB-1208A12, RP11-175B9, ZNF692, RANP8, RP11-245C17, TMEM266, FBXW9, SUGT1P2, and PRH1. In conclusion, PRC2 and its epigenetic effects are major oncogenic mechanisms underlying both bladder cancer and UTUC. The epigenetically regulated genes of PRC2 in urothelial carcinoma were also elucidated using correlation statistics