Pathophysiology of persistent LUTS after BPH surgery An investigation on causes and factors involved
References 1. Emberton M, Neal DE, Black N, Fordham M, Harrison M, McBrien MP, et al. The effect of prostatectomy on symptom severity and quality of life. Br J Urol 1996;77:233–47. 2. Neal DE, Ramsden PD, Sharples L, Smith A, Powell PH, Styles RA, et al. Outcome of elective prostatectomy. BMJ 1989;299:762–7. 3. Mirone V, Imbimbo C, Longo N, Fusco F. The Detrusor Muscle: An Innocent Victim of Bladder Outlet Obstruction. Eur Urol 2007;51:57–66. 4. Hu H, Zhang W, Liu X, Wang H, Fang Z, Liang C, et al. Nerve Growth Factor Levels are Associated with Overactive Bladder Symptoms and Long-Term Treatment Outcome after Transurethral Resection of the Prostate in Patients with Benign Prostatic Hyperplasia. Journal of Urology 2018;200:620–5. Sunday, 12 March 11:24-11:40 Thematic Session: Male LUTS/BPO surgery: Where do we stand? eURO Auditorium 2, Yellow Area
growth factor), EGF (epidermal growth factor), BMP (Bone morphogenetic protein), PAR-2 (Protease-activated receptor 2) and MMP (matrix metalloproteinase) [3]. Among these, NGF plays a significant role (Figure 2). This molecule is involved in the activation of many other pathways that determines neuronal differentiation and growth, and promotion of proliferation. As of consequence of its major release, NGS increase is able to induce overactive bladder (OAB), modify bladder sensitivity and neuroplasticity. A study published by Hu, et al. in 2018 demonstrated that the urinary NGF levels were different between moderate and severe LUTS (10.513 vs. 12.334 pg/μmol, P=0.002) and in patients with non-OAB, mild, moderate, and severe OAB (8.132 vs. 10.128 vs. 13.232 vs. 14.029 pg/μmol, P<0.001). A year after TURP, compared with the good outcome group, the LUTS persistent group had higher one-year NGF (10.847 vs. 7.850 pg/μmol, P<0.001), and
smaller NGF postsurgical change (1.472 vs. 3.165 pg/μmol, P=0.031) [4].
Prof. Giorgio Ivan Russo University of Catania, Catania (IT)
In conclusion, LUTS persistence after surgery is a common health issue and urologists should continue to address and resolve it. Identifying patients who could benefit from surgery to avoid complaints is crucial. In those patients with LUTS persistence after surgery, a good medical history of the past and a correct diagnosis framework are key to resolve symptoms and avoid further complications. "Reasons for LUTS persistence after surgery are now under investigation and they can be related to several factors." To know more, join the state-of-the-art lecture “Reasons/pathophysiology of persistent LUTS after BPH surgery” during the Thematic Session "Male LUTS/BPO surgery: Where do we stand?".
giorgioivan1987@ gmail.com
The prevalence of lower urinary tract symptoms (LUTS) associated with benign prostatic enlargement (BPE) increases with age. The impact of LUTS on patients relates directly to their quality of life (QOL), and, therefore, avoiding such symptoms should be a primary consideration when choosing a therapy. Although many options have been introduced as BPE treatment modalities in the surgical area, transurethral resection of the prostate (TURP) is still considered the benchmark of surgical therapy for BPE [1,2]. However, previous studies have reported that 25% to 30% of patients who undergo prostatectomy have an unfavorable outcome. "LUTS persistence after surgery is a common health issue and urologists should continue to address and resolve it." Reasons for LUTS persistence after surgery are now under investigation and they can be related to several factors. At first, it is important to understand that the pathophysiology of LUTS secondary to BPE occurs in a very long period and it influences many aspects. The induced mechanical stretches of bladder secondary to BPE (Figure 1) determines a modification of different pathways that influence genomic expression of proteins, including, NGF (nerve
Figure 1. Mechanical stretches induced by benign prostatic hyperplasia (BPH)
Figure 2. Pathways involved in the NGF mechanism of action
Wound healing and PROs in Fournier's gangrene Study findings, major challenges and potential solutions
We also identified some essential points for a registry study such as histological confirmation of the disease. Additionally, we performed a comparable survey in European hospitals where the practice in FG is very heterogenic and mostly case-based in Europe, e.g. vacuum-assisted wound closure (VAC) is mostly used (n=50; 42.7%) as adjunct wound therapy, 41 (35.0%) do not use an additional therapy for the wound, and in 17 (14.5%) of the cases, hyperbaric oxygenation (HBO) is used. The major challenges in FG are the short time from diagnosis to treatment, standardisation, establishment of guidelines and disease awareness. Consequently, we concluded that there is no standard of care in the diagnosis, treatment and long-term care of FG in Europe. As already mentioned, the disease is very difficult to predict. Further research could be conducted with a prospective registry supplemented by online predictive and educational tools. Therefore, improving the outcome is the first major challenge in FG, but improving survival is only one aspect of this severe disease. What about the long-term situation of FG patients, such as wound situation, quality of life or general health status? To our knowledge, there is only very sparse data reflecting these issues. Suijker et al. performed a retrospective cohort study on the quality of life in patients surviving necrotizing soft tissue infection. They found statistically significant decreased scores in Short Health Form 36 questionnaire for the domains of physical functioning, role physical functioning, and general health in comparison to the Dutch reference population. They concluded that necrotizing soft tissue infections negatively affect the quality of life, especially in physical domains. Naturally, if the outcome is improved, research about long-term aspects such as the wound situation or quality of life is absolutely warranted.
In our opinion, improving health-related quality of life (HRQoL) and the wound situation of FG patients are the second major challenges in FG. Consequently, we performed a multicentric retrospective study in male long-term survivors of FG with the primary aim to describe patient-reported outcomes (PROs) and HRQoL, especially concerning the wound. In the study, we included 39 patients with a median age of 65 years (IQR 53– 74). Twenty patients were already deceased (51.3%), nine patients were lost to follow up (23.1%), and 10 patients participated in the survey (25.6%). The median survival time was 27 months (IQR 9 – 60). The median IPSS (International Prostate Symptom Score) was 13.5 (IQR 4.3 – 22.3), five patients (50%) had severe erectile dysfunction. Three patients (30%) reported problems with the wound, two (20%) complained about wound pain and one (10%) about the wound healing situation. The mean global health score in WOUND-QoL was 1.83 (SD 1.1), which is significantly less than in the German reference population (p<0.001). In the FLQA-w the mean subscales were for physical aliment 1.8 (SD 1.1), everyday life 1.5 (SD 0.5), social life 1.6 (SD 0.8) and psychological well-being 1.8 (SD 1.2). The mean general health score in SF-36 was 64.0 (SD 10.5). In summary the wound situation of long-term FG survivors has a deeply negative impact on HRQoL especially in physical domains. Further research is essential to ensure the quality of care. One first approach could be the development of a disease- specific validated QoL questionnaire for FG patients, specifically addressing the wound situation and physical impairment. Looking to the literature, adjunct wound therapy is discussed especially with VAC, HBO, and the therapy with larvae (Lucilla sericata larvae), but it remains unclear if these adjunct therapies could improve outcome, wound situation or even HRQoL. Furthermore, it remains unclear which patients will benefit from these specific therapies.
As a whole, there are two major challenges in the treatment and care of FG patients: improving the outcome and the establishment of long-term survival, and bettering the wound situation as well as HRQoL. Unfortunately, there is no standard of care in the diagnosis, treatment and long-term care of FG all over Europe. Additionally, the disease is very difficult to predict and there are more challenges in FG such as awareness of FG and time to treatment and the standardisation of care. For these reasons, further robust research on a rare disease is essential. This can be done with a prospective international online registry. Due to modern data integration solutions, the registry could be accompanied by online predictive tools and educational information which, could be the steps for the solution of the first two major challenges in FG. Therefore, our approach is the establishment of a prospective FG registry study and data base for improvement of patient care. We would also like to underscore that the development of antimicrobial resistance (AMR) all over Europe is alarming, even in rare infectious disease such as FG. Antimicrobial stewardship (ABS) as well as improving disease management are absolutely necessary. Additionally, we as urologists should bear therapy of infectious disease in mind because it is an essential part of our specialisation. We need to be precise and cautious about prescription of antibiotic therapy.
Dr. Laila Schneidewind University Hospital Rostock Dept. of Urology, Rostock (DE)
laila.schneidewind@ med.uni-rostock.de
Fournier's gangrene (FG) is a sporadic, life- threatening, necrotizing, bacterial infection affecting the perineum, perineal region, and genitals. Hence, the incidence is very low (1.6 cases per 100,000 male patients in the United States). Most of the limited knowledge about FG arises from retrospective single-institutional studies with very small patient cohorts. Furthermore, the prognosis, survival and outcome of FG have not improved in recent years, despite more intensive critical-care therapy for those patients. Our own multicentre retrospective study of 154 cases showed that survival time did not improve in recent years (p=0.268) with up to 15.4% of the patients dying during inpatient treatment. The key points for successful treatment of FG are immediate surgical debridement, accompanied by intensified antibiotic therapy and intensive care medical management. However, further research to improve the outcome of FG is desperately needed. Unfortunately, due to the rareness of the disease, it is challenging to perform robust prospective clinical studies. We completed a survey about the practice patterns in diagnostics and treatment of FG in German academic medicine to describe the situation and identify implications for planning a prospective clinical registry. Overall, we concluded that the contemporary practice patterns in FG are very heterogenous, but the outcome is still problematic and the disease is difficult to predict.
References can be requested from the corresponding author.
Saturday, 11 March 16:15 - 16:25 ESIU Meeting: Urogenital infections in urology Yellow Area, Amber 3
European Urology Today
10
February/March 2023
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