Abstract Background and Aims Acute kidney injury caused by renal ischemia/reperfusion (I/R) is a major clinical problem in many aspects of urology fields such as kidney transplantation and partial ...nephrectomy, but there is no effective treatment. Linaclotide, a guanylate cyclase C agonist clinically approved as a laxative, has recently been shown to be renoprotective in a chronic kidney disease (CKD) model. Therefore, the present study investigated the possibility that the renoprotective effects of linaclotide in renal I/R may extend beyond its gastrointestinal effects. Method The left renal pelvis of adult male Wistar rats was clamped for 45 minutes to induce renal I/R injury. Kidney tissue, colon, and blood were collected 24 hours and 14 days later. Linaclotide was administered for 14 days preoperatively and until postoperative tissue collection. Tissue sections were stained with standard histologic techniques such as HE, Sirius Red, F4/80, etc. As genes associated with I/R, TGF-β and related fibrosis markers α-SMA, MMP2, TIMP1 and inflammatory cytokines TNF, IL-1β and IL-6 were analyzed by quantitative PCR analysis. Results Serum creatinine levels decreased significantly after linaclotide administration, indicating improved renal function. Histologic examination showed less tubular damage and less collagen deposition on Sirius Red staining. Further analysis showed decreased expression of TGF-β and related fibrosis markers α-SMA, MMP2 and TIMP1, suggesting downregulation of the fibrotic TGF-β pathway by linaclotide. Furthermore, 1 day after I/R injury, linaclotide significantly reduced macrophage infiltration and suppressed key proinflammatory cytokines such as TNF, IL-1β, and IL-6. Conclusion These results suggest that linaclotide, with its established safety profile, could extend its benefits beyond gastrointestinal issues and potentially serve as a therapeutic intervention in many aspects of kidney surgeries. In addition, it could provide immediate and practical insights into the selection of laxatives for the management of patients with AKI or CKD, regardless of cause, and for those receiving dialysis or transplant therapy.
Although photodynamic diagnosis is a powerful tool for the detection of flat urothelial tumors, false-positive fluorescent mucosa still requires further elucidation. Thus, we aimed to study the ...significance of nonmalignant fluorescent mucosa by a cytogenetic approach.
Sixty specimens of bladder mucosa were collected from 20 patients who were suspected of having carcinoma in situ by fluorescence cystoscopy with 5-aminolevulinic acid. To detect the copy number aberrations, the multi-color fluorescence in situ hybridization technique was performed, and the variant fractions (total fractions other than those of the modal copy number) of chromosomes 7, 9 and 17 and the chromosomal instability were determined. To delineate the relevant gene to the fluorescent mucosa, a comparative genomic hybridization technique was applied for 8 established bladder cancer cell lines, and these results were compared with the in vitro fluorescent expression experiment.
Fluorescent mucosa was detected in 33 of the 34 malignant tissue specimens (16 carcinoma in situ, 18 other transitional cell carcinomas) and in 11 of the 26 nonmalignant tissue specimens (6 dysplasia, 20 normal mucosa), with a false-positive rate of 42.3%. The variant fraction of chromosome 9 was significantly higher in fluorescent than in non-fluorescent mucosa, not only for all tissues (33 vs. 17%; p = 0.0069), but also for nonmalignant tissues (28 vs. 15%; p = 0.0225). There was no alteration in chromosome 9 in 1 cell line without fluorescent mucosa, while 5 of the 7 cell lines with fluorescent mucosa had a common deleted region on 9q24.1.
These data suggest that a substantial portion of nonmalignant fluorescent mucosa harbors alterations in chromosome 9.
The number of reported cases of alpha-fetoprotein (AFP)-producing gastric cancer has gradually increased, with a reported prevalence of 1.3-1.5% of all gastric cancer cases. However, reports of ...gastric cancer accompanied by elevated serum levels of both AFP and protein induced by vitamin K antagonist-II (PIVKA-II) are rare. The prognosis of AFP- and PIVKA-II-producing gastric cancer has been reported to be very poor because the tumor cells were considered to have a high malignant potential and the cancer progressed rapidly. We described a case of gastric cancer producing AFP and PIVKA-II in which chemotherapy was effective and resulted in prolonged survival, and these two tumor markers were useful for monitoring the treatment response. Routine health screening using upper abdominal ultrasonography revealed hepatic tumors in an apparently healthy 65-year-old man. Whole-body computed tomography (CT) revealed multiple hepatic tumors, and an esophagogastroduodenoscopy (EGD) revealed a Bormann type 3 tumor in the lower stomach. A biopsy specimen confirmed that the tumor was immunohistochemically positive for AFP, PIVKA-II, and human epidermal growth factor receptor 2. After chemotherapy, the gastric tumor appeared as a small elevated lesion on EGD, and CT revealed a remarkable reduction in the size of the metastatic liver tumors. The patient is still alive, 35 months after the initial chemotherapy.
We investigated whether centrosome amplification (CA) obtained from bladder washing cytology (BWC) specimens may be a useful prognostic biomarker for patients with non-muscle invasive bladder cancer ...(NMIBC). The study cohort included 78 patients with pathologically confirmed NMIBC. BWC specimens were obtained from all patients during transurethral resection of bladder tumor (TURBT), and CA was evaluated by immunofluorescence staining using a pericentrin polyclonal antibody. A positive case of CA was defined as a specimen in which >5% of cells contained ≥3 centrosomes per cell. CA was detected in 26.9% (21 of 78) of BWC specimens obtained from NMIBC patients. Disease progression was observed in 11.5% (9 of 78) of patients, with a median follow-up of 32 months. In univariate analyses, CA obtained from BWC specimens, initial or recurrent, and washing cytology were significantly associated with progression-free survival ( P = 0.009, 0.02, and 0.03, respectively). Multivariate Cox model analyses revealed that CA was the most significant prognostic factor for disease progression (hazard ratio: 2.22, 95% confidence interval: 1.13–4.90, P = 0.022). These data suggest that analysis of CA using bladder washing cytological specimens may provide crucial predictive information regarding disease progression in NMIBC.
To clarify the oncological benefit of zoledronic acid for hormone-naïve metastatic prostate cancer, patient outcome of androgen deprivation therapy with zoledronic acid (ADT + Z) and androgen ...deprivation therapy alone (ADT) was compared.
Fifty-two patients with pathologically confirmed metastatic prostate cancer were prospectively enrolled and treated with combined androgen blockade (goserelin and bicalutamide) with zoledronic acid (4 mg every 4 weeks for 24 months). A propensity score-match with logistic regression analysis was applied to select 50 pair-matched cohorts (both from ADT + Z and from historical control cohorts who had undergone ADT alone), and patient outcomes were compared.
Patients with ADT + Z had significantly longer time to progression (TTP) than those with ADT (median TTP; 24.2 vs. 14.0 months, p = 0.0092), while no significant difference of overall survival between two groups (p = 0.1502). Multivariate analysis for biochemical recurrence revealed treatment with ADT was the sole independent prognostic factor (HR: 1.724, 95% CI: 1.06–2.86, p = 0.0297).
Combination of zoledronic acid with ADT may prolong time to castration resistant prostate cancer.
The number of geriatric bladder cancer patients is now increasing in spite of little is known regarding the safety and efficacy of standard treatment for the patients due to luck of data in geriatric ...patients. Although they should be treated by modified standard treatment adjusted for their deteriorated physical activity, such treatment regimens are not established. Bladder preservation therapy could be recommended for geriatric patients with invasive bladder can- cer, which shows comparable survival benefit with radical cystectomy. Although chemother- apy could be a treatment option for geriatric patients, geriatric assessment before treatment is recommended to choose appropriate candidates to modify therapeutic regimens. Standard treatment for geriatric patients with cancer would be established based on clinical trials in- volving geriatric assessment.
A 40-year-old male underwent tube placement surgery for continuous ambulatory peritoneal dialysis(CAPD).A2-cm skin incision was made,and the peritoneum was reflected enough to perform secure ...fixation.A swannecked,double-felted silicone CAPD catheter was inserted,and the felt cuff was sutured to the peritoneum to avoid postoperative leakage.An adequate gradient for tube fixation to the abdominal wall was confirmed.The CAPD tube was passed through a subcutaneous tunnel.Aeroperitoneum was induced to confirm that there was no air leakage from the sites of CAPD insertion.Two trocars were placed,and we confirmed that the CAPD tube led to the rectovesical pouch.Tip position was reliably observed laparoscopically.Optimal patency of the CAPD tube was confirmed during surgery.Placement of CAPD catheters by laparoscopic-assisted surgery has clear advantages in simplicity,safety,flexibility,and certainty.Laparoscopic technique should be considered the first choice for CAPD tube insertion.
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