Improving Surgical Safety in Living Donor Renal Transplantation With Antiseptic Skin Preparation, Bladder Irrigation, Corner-Saving Vascular Anastomosis, DJ Stenting, and Extravesical Ureteroneocystostomy Modifications: A Comprehensive Approach.

Introduction The antiseptic skin preparation, bladder irrigation, corner-saving vascular anastomosis, DJ stenting, and extravesical ureteroneocystostomy (ABCDE) approach encompasses a range of modifications applied during different stages of the surgical procedure in renal transplantation. These modifications include the following: A, antiseptic skin preparation sequentially with cetrimide 3.35%, chlorhexidine scrub 4%, spirit, and povidone-iodine 10%; B, bladder irrigation with amikacin and betadine solution; C, corner-saving end-to-side vascular anastomosis; D, DJ stenting with early postoperative removal within three weeks; and E, extravesical ureteroneocystostomy using our institute's modified Lich-Gregoir technique. Methods This prospective observational study was conducted at our institution between March 2021 and May 2023. Data were collected from the patients' medical records and analyzed using Statistical Package for the Social Sciences (SPSS) (IBM SPSS Statistics, Armonk, NY, USA). Statistical tests, including t-test, Mann-Whitney test, chi-square test, and Fisher's exact test, were used for analysis. The study assessed various recipient, donor, intraoperative, and post-transplant factors, as well as surgical complications and stent-related factors. Results Out of 72 renal transplantations, 12 (16.6%) had the following surgical complications: urinary (n = 4; 5.5%), wound-related (n = 3; 4.1%), and lymphocele (n = 5; 6.9%). The most common complications were lymphocele (n = 5; 6.9%) and urinary leak (n = 4; 5.5%). Surgical complications were more common in male recipients (91.6% versus 8.3%), as well as in recipients with longer dialysis duration (24 ± 17 versus 11.0 ± 7 months) and had extended hospitalization time (16.4 ± 8.6 versus 8.0 ± 2.9 days) (p < 0.05). Wound infection correlated with longer surgeries (>300 minutes) and other complications. Lymphocele patients had higher drain output (>500 mL) on day 1 and longer hospital stays (>15 days). Urinary tract infections (UTIs) were linked to dialysis duration (>24 months), diabetes, and longer indwelling times of DJ stents and urinary catheters. Early DJ stent removal (<3 weeks) reduced UTI incidence and symptoms (p < 0.05). All complications were categorized as minor (3a or less), according to the Clavien-Dindo classification. Conclusion The modified ABCDE surgical approach in renal transplantation decreased the complications, showing favorable outcomes compared to those in the literature.

Differential expression of SLITRK6 gene as a potential therapeutic target for urothelial carcinoma in particular upper tract cancer.

BACKGROUND: Urinary bladder urothelial carcinoma (UBUC) and upper tract urothelial carcinoma (UTUC) harbor analogous morphology with comparable cytogenetic changes as well as prognostic factors but their similar biological activities still remain controversial. SLITRK6 gene has been demonstrated to have distinct role in urothelial cancers with a distinction between UTUC and UBUC. METHOD: The study included a total of 80 patients of urothelial carcinoma including 60 UBUC and 20 UTUC cases. The tumor tissues from both the groups were evaluated for gene expression at mRNA level by qRT-PCR, and protein expression by immunohistochemistry (IHC) and western blot. RESULTS: Significantly more than 4-fold high mRNA expression of SLITRK6 was observed in UTUC against 1.2-fold in UBUC (p < 0.0001). The overall SLITRK6 expression by IHC was observed in 80% of the UBUC cases in comparison to 100% strong expression in UTUC patients and among two groups expression exhibited a significant difference for moderate to strong expression (p = 0.0005). The protein expression by western blot analysis in UTUC samples was considerably higher as compared to UBUC samples (1.64 vs. 0.76 respectively: p = 0.01). A strong concordance exhibited for the higher mRNA and protein expression in both UTUC and UBUC cases (∼75%) wherein 80%, 75% and 70% higher expression of SLITRK6 was detected by qRT-PCR, Western blot and IHC respectively. CONCLUSION: To conclude, although SLITRK6 exhibits a strong expression in both UTUC and UBUC but was considerably observed higher in majority of UTUC cases. Therefore, SLITRK6 appears as a promising novel possible gene target for urothelial carcinoma in particular UTUC.

Implications of risk conferred by 5p15.33 loci genetic variants; human telomerase reverse transcriptase rs2736098 and rs2736100 in predisposition of bladder cancer.

Background: The polymorphic variations of human telomerase reverse transcriptase (hTERT) gene play an important role in predisposition to carcinogenesis. The current study aimed to elucidate the genetic predisposition to bladder cancer in two important variants, rs2736098 and rs2736100 of hTERT gene. Materials and methods: Confirmed 130 patients of bladder cancer and 200 healthy controls were genotyped by PCR-RFLP to determine different variants of hTERT rs2736098 and rs2736100. Results: hTERT rs2736098 homozygous variant AA genotype frequency was observed to significantly differ 2-fold between cases and controls (26.15% vs. 13.5%) (p = 0.02). In addition, rare 'A' allele significantly differed among two groups (cases: 47% versus controls: 39%: p = 0.03). hTERT rs2736098 was observed to be presented significantly more in high stage tumors (p = 0.02). hTERT rs2736100 genotype AA or variant allele A showed no significant difference between cases and controls. Haplotype CA displayed significantly different pattern of frequency as 0.5 in cases as compared to 0.16 in controls (p < 0.0001). Combination of variant A/G haplotype frequency implicated more in cases than in controls (0.34 vs. 0.14, p = 0.001). Conclusions: It is concluded that hTERT rs2736098 polymorphic variant has a vital role to confer a strong risk to bladder cancer in our population. Further, hTERT haplotypes CA and AG inhTERT could prove to be a promising tool to screen the risk for bladder cancer.

Significant Implications of APOA1 Gene Sequence Variations and Its Protein Expression in Bladder Cancer.

Apolipoprotein A1 (APOA1) is a potential biomarker because of its variable concentration in different types of cancers. The current study is the first of its kind to evaluate the association between the APOA1 genotypes of -75 G/A and +83 C/T in tandem with the APOA1 protein expression in urine samples to find out the risk and potential relationship for differentially expressed urinary proteins and APOA1 genotypes. The study included 108 cases of bladder tumors and 150 healthy controls that were frequency matched to cases with respect to age, sex, and smoking status. Genotyping was performed using PCR-RFLP and the urinary expression of the APOA1 protein was done using ELISA. Bladder tumor cases were significantly associated with the APOA1 -75 AA genotype (p < 0.05), while the APOA1 +83 C/T heterozygotes showed an association with cases (p < 0.05). The overall distribution of the different haplotypes showed a marked difference between the cases and controls in GT when compared with the wild type GC (p < 0.03). Bladder tumor cases that carried the variant genotype APOA1 -75AA were found more (70.0%) with a higher expression (≥20 ng/mL)of the APOA1 urinary protein and differed significantly against wild type GG (p = 0.03). Again, in low grade bladder tumors, urinary APOA1 protein was exhibited significantly more (52.4% vs. 15.4% high grade) with a higher expression (≥20 ng), while high grade tumor cases (84.6% vs. 47.5% low grade) showed a lower APOA1 expression (<20 ng/mL) (O.R = 6.08, p = 0.002). A strong association was observed between APOA1 -75G/A and risk for bladder tumor and its relation to urinary protein expression, which substantiates its possible role as a marker for the risk assessment of the disease and as a promising diagnostic marker for different grades of malignant bladder tumors.

A Comparative Study of Epidural Anesthesia with Dexmedetomidine Infusion versus General Anesthesia for Percutaneous Nephrolithotomy.

Background: There has been considerable debate regarding the ideal anaesthetic technique for Percutaneous Nephrolithotomy (PCNL). PCNL is usually performed under general anaesthesia (GA) in prone position. The prone position under GA is associated with various complications. To address these complications, our study was carried out to determine whether epidural anaesthesia [EA] with dexmedetomidine sedation can be a better alternative to GA for PCNL. Aims and Objectives: To compare the efficacy and feasibility of performing PCNL under EA in combination with dexmedetomidine infusion. Methods and Material: Out of 225 patients observed in this study, 115 patients (group A) underwent PCNL under EA with dexmedetomidine infusion and 110 patients (group B) underwent PCNL under GA. Results: Mean time to the first dose of rescue analgesia was significantly increased in Epidural group (328.17 ± 63.74) compared to GA group (72.09 min, p < .0001) and the mean Visual analog scale [VAS] scores were significantly lower in epidural compared to GA group at different time intervals during the first 24 h after surgery (p<0.05). Patients in epidural group had significantly less post-operative nausea, vomiting (6.1 % vs 13.6 %), and significantly less shivering (12.2% vs 33.6%). Mean patient satisfaction score in epidural group was significantly higher (8.75 ± 1.29 vs 8.14 ± 1.39, p=0.001); however, the mean surgeon satisfaction score was comparable among the two groups (8.76 ± 1.39 in Group A and 8.61 ± 1.35 in Group B, p=0.421). Conclusions: Our study shows that EA is an equally effective alternative to GA for PCNL, with more patient satisfaction, less postoperative pain, early ambulation and postoperative recovery, less systemic analgesic requirements and less adverse effects.

Analysis of MNS16A VNTR polymorphic sequence variations of the TERT gene and associated risk for development of bladder cancer.

BACKGROUND: The MNS16A variable number tandem repeat (VNTR) polymorphism of the human telomerase reverse transcriptase (hTERT) gene acts as a regulator of hTERT promoter activity and has been shown to have a role in the predisposition toward various cancers. The current study aimed to investigate the association between MNS16A VNTR alleles and genetic predisposition to bladder cancer in the Kashmir region of northern India. MATERIALS AND METHODS: A total of 130 patients with bladder cancer and 170 age- and gender-matched healthy controls were included in this study. Primer-specific polymerase chain reaction was used to genotype the different variants of VNTR alleles of the MNS16A VNTR polymorphism. RESULTS: Short allele VNTR-243 (SS) genotype frequency significantly differed between cases (9.23%) and controls (3.52%) (OR = 3.08 [95% CI = 1.10-8.61], p = 0.042). The VNTR-243 short allele (S) was found significantly more frequent in bladder cancer cases (28.46%) than controls (20.88%) (OR = 1.50 [95% CI = 1.03-2.19], p = 0.034). Likewise, the long allele (LL) hTERT MNS16A genotype was distributed more frequently in low stage disease versus high stage disease (60.29% vs. 39.70%) (OR = 0.79 [95% CI = 0.39-1.60], p = 0.595). CONCLUSION: The MNS16A VNTR short allele (S) was associated with a higher risk for bladder cancer in our population as compared to long alleles.