ABSTRACT
INTRODUCTION AND IMPORTANCE: Primary urethral carcinoma (PUC) is exceedingly uncommon and accounts for 0.02 % of all female cancers and <1 % of female genitourinary tract malignancy. PUC in female usually presents late with a higher disease stage and, hence, has higher cancer-specific mortality. Due to its rarity, the current recommendation for the management of PUC is still unclear. CASE PRESENTATION: This study reports two rare cases of 59-year-old and 65-year-old women with PUC, presenting with chief complaint of hematuria. Urethrocystoscopy and biopsy were performed. Pathology results revealed mucinous adenocarcinoma (AC) and urothelial carcinoma (UC) of the urethra, respectively. Radiological imaging was conducted for staging. Both were diagnosed with cT4N2M0. The first patient underwent anterior pelvic exenteration with bilateral ureterocutaneoustomy (UCS), while the second patient received cisplatin-based chemotherapy before the surgery. Radiological follow-up was planned 3 months after the surgery. CLINICAL DISCUSSION: Both mucinous AC and UC are considered incredibly unusual subtypes, with no defined treatment guidelines. Anterior exenteration with or without neoadjuvant chemotherapy may be opted for advanced PUC affecting the proximal urethra and adjacent organs. Following the previous studies, in this case series, both patients (locally advanced) underwent anterior exenteration. Additionally, the UC subtype received multimodal treatment with neoadjuvant chemotherapy which was shown to improve overall survival. CONCLUSION: In conclusion, PUC is extremely rare, and the choice of management remained various. Long-term follow-up for these patients is mandatory to improve understanding of this incredibly uncommon disease.
ABSTRACT
Background: Currently, animal models of urethral stricture are not standardized. Transforming Growth Factor Beta 1 (TGF-ß1) regulates extracellular matrix deposition in homeostatic and pathological responses. Objective: The aim of this study was to present the potential model to be developed as a urethral stricture. Methods: True experimental laboratory research was conducted by using Male New Zealand rabbits (Oryctolagus cuniculus), which were divided into 5 groups; control, placebo, and 3 treatment groups (TGF-ß1 injection of 1 µg, 2 µg, 4 µg). Urethrography, histopathological analysis, and evaluation of total collagen formation of the urethral wall were performed after 6 weeks. Results: An increase in the dose of TGF-ß1 decreased the mean rabbit's urethral lumen diameter (29.3% in the 2µg group and 34% in the 4µg group) compared to controls. Three rabbits decreased as much as ≤ 50% in urethral lumen diameter. Significant increases in total collagen density in the periluminal and peripheral urethral spongiosum were noted by increasing doses of TGF-ß1. The percentage of urethral lumen diameter has a strong negative correlation with periluminal total collagen density (r = -0,798; p = 0,000) and very strong negative correlation with peripheral spongiosa total collagen density (r = -0,748, p = 0,000). Conclusion: TGF-ß1 plays a role in changing total collagen compositions of the rabbit's urethral wall, decreasing the urethral lumen diameter. Further research with increasing doses of TGF-ß1 is needed to determine the effective dose of TGF-ß1 in inducing urethral stricture.
Subject(s)
Urethral Stricture , Male , Rabbits , Animals , Transforming Growth Factor beta1 , Urethra , Collagen , Models, AnimalABSTRACT
Background: Presently, there's a lack of standardization in animal models used for studying urethral stricture. Transforming Growth Factor Beta 1 (TGF-ß1) is known to regulate the deposition of extracellular matrix in both normal and pathological conditions. This factor holds promise as a potential model for simulating urethral stricture. Objective: This study aims to investigate the impact of Transforming Growth Factor Beta 1 (TGF-ß1) on Collagen I and Collagen III within the urethral wall of New Zealand Rabbits (Oryctolagus cuniculus) in the context of developing urethral stricture in animal models. Methods: We conducted genuine laboratory experiments using Male New Zealand rabbits (Oryctolagus cuniculus), which were categorized into five groups: control, placebo, and three treatment groups (TGF-ß1 injections of 1 µg, 2 µg, 4 µg). After a duration of 6 weeks, we conducted urethrography, histopathological analysis, and assessed the formation of collagen I and collagen III within the urethral wall. Results: Elevating the dosage of TGF-ß1 led to a reduction in the average urethral lumen diameter of rabbits (29.3% in the 2µg group and 34% in the 4µg group) compared to the control group. In fact, three rabbits experienced a decrease of ≤ 50% in their urethral lumen diameter. As the doses of TGF-ß1 increased, we observed significant increases in the density of collagen I, and collagen III in both the periluminal and peripheral regions of the urethral spongiosum. Additionally, there was a tendency for the collagen I/collagen III ratio to decrease in the periluminal region, with collagen III density surpassing that of collagen I. In the peripheral spongiosa area, notable mean differences were observed between the control group, 1T, and 2T groups, with collagen I density tending to be higher than that of collagen III. Furthermore, the percentage of urethral lumen diameter exhibited a robust negative correlation with periluminal collagen I density (r = -0.672, p = 0.001), peripheral spongiosa collagen I density (r = -0.603, p = 0.005), periluminal collagen III density (r = -0.717, p = 0.001), and an exceptionally strong negative correlation with collagen III density of peripheral spongiosa (r = -0.804, p = 0.000). Conclusion: TGF-ß1 exerts an influence on altering the composition of collagen I and collagen III within the urethral wall of rabbits, leading to a reduction in the diameter of the urethral lumen. Further research is warranted to determine the optimal dose of TGF-ß1 required to induce urethral stricture effectively.
