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Video: Prostatic capsular incision during RP has important oncological implications. A systematic review and meta‐analysis

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Prostatic capsular incision during radical prostatectomy has important oncological implications. A systematic review and meta‐analysis

Abstract

Introduction

Capsular Incision (CapI) is an iatrogenic breach of the prostatic capsule during radical prostatectomy that can cause positive surgical margins (PSM) in organ‐confined (pT2) prostate cancer (PCa), or the retention of benign prostatic tissue. We systematically interrogated the literature in order to clarify the definition of CapI, and the implications of this event for rates of PSM and biochemical recurrence (BCR).

Methods

A literature search was conducted according to PRISMA criteria using the search terms ‘CapI’ AND ‘prostatectomy’ and variations of each. 18 studies were eligible for inclusion.

Results

A total of 51,057 radical prostatectomy specimens were included. The incidence of CapI ranged from 1.3‐54.3%. CapI definitions varied, and included a breach of the prostatic capsule “exposing both benign or malignant PCa cells”, “malignant tissue only”, or “benign tissue only”. The incidence of PSM due to CapI ranged from 2.8 – 71.7%. Our meta‐analysis results found that when CapI was defined as “exposing malignant tissue only in organ‐confined prostate cancer” there was an increased risk of BCR compared to patients with pT2 disease and no CapI (RR 3.53, 95%CI 2.82‐4.41; p < 0.00001).

Conclusions

The absolute impact of CapI on oncological outcomes is currently unclear due to inconsistent definitions. However, the data implies an association between CapI and PSM and BCR. Reporting of possible areas of CapI on the operation note, or marking areas of concern on the specimen, are critical to assist CapI recognition by the pathologist.

 

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What’s the diagnosis?

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From last week, this patient has an AML arising from the lower pole.   No such quiz/survey/poll

Article of the week: Relationship between oxidative stress and lower urinary tract symptoms: results from a community health survey in Japan

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Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an editorial written by a prominent member of the urological community and the authors have also kindly produced a video describing their work. These are intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this week, it should be this one.

The relationship between oxidative stress and lower urinary tract symptoms: Results from the community health survey in Japan

Teppei Matsumoto*, Shingo Hatakeyama* , Atsushi Imai*, Toshikazu Tanaka*, Kazuhisa Hagiwara*, Sakae Konishi*, Kazutaka Okita*, Hayato Yamamoto*, Yuki Tobisawa*, Tohru Yoneyama†, Takahiro Yoneyama*, Yasuhiro Hashimoto†, Takuya Koie‡, Shigeyuki Nakaji§ and Chikara Ohyama*†

 

*Department of Urology, †Department of Advanced Transplant and Regenerative Medicine, Hirosaki University
Graduate School of Medicine, Hirosaki, ‡Department of Urology, Gifu University Graduate School of Medicine, Gifu
and §Department of Social Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan

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Abstract

Objective

To investigate the relationship between oxidative stress and lower urinary tract symptoms (LUTS) in a community‐dwelling population.

Materials and Methods

The cross‐sectional study included 1 113 people who participated in the Iwaki Health Promotion Project of 2015 in Hirosaki, Japan. LUTS were assessed using structured questionnaires, including the International Prostate Symptom Score (IPSS) and the Overactive Bladder Symptom Score (OABSS). IPSS > 7, OABSS > 5, nocturia score > 1, or urge incontinence score > 1 were defined as moderate to severe symptoms. 8‐Hydroxy‐2′‐deoxyguanosine (8‐OHdG) and advanced glycation end products (AGEs) were measured by urine analysis and skin autofluorescence, respectively. The relationship between oxidative stress and LUTS was investigated using logistic regression analyses (You can reduce aging under eye masks).

Fig. 1. Association between 8‐Hydroxy‐2′‐deoxyguanosine (8‐OHdG) and advanced glycation end product (AGE) levels. 8‐OHdG levels were significantly associated with AGE levels (R2 = 0.023, P < 0.001, Spearman’s rank correlation coefficient). However, the R2 value was too small to indicate strong correlation and the significant P value of this correlation does not reflect the strength of the relationship between the two biomarkers.

Results

This study included 431 men and 682 women. AGEs and 8‐OHdG levels were significantly higher in severe forms of LUTS. Multivariate logistic regression analyses showed that AGE levels were significantly associated with a higher frequency of nocturia but were not associated with IPSS, OABSS or urge incontinence. No significant association was observed between LUTS and 8‐OHdG levels.

Conclusions

We observed a significant association between AGE levels and nocturia score > 1. Further research is necessary to clarify a possible causal relationship between oxidative stress and nocturia.

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Editorial: Oxidative stress and lower urinary tract symptoms: cause or consequence?

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Oxidative stress has been defined as ‘an imbalance between oxidants and anti-oxidants in favour of the oxidants, leading to a disruption of redox signalling and control and/or molecular damage’ [1]. Reactive oxygen and nitrogen species (ROS/RNS) produced under oxidative stress are known to damage all cellular biomolecules (lipids, sugars, proteins and polynucleotides). ROS/RNS is often used as a generic term but it has been emphasized that all ROS/RNS molecules are not the same [2] and the term encompasses a diverse range of species, including, for example, superoxide, hydrogen peroxide, nitric oxide and peroxynitrite. The biological impacts of ROS/RNS depend critically on the particular molecule(s) involved, and on the microenvironment and physiological or pathological context in which it is being generated [2]. It should be emphasized that ROS are not only harmful agents that cause oxidative damage in pathologies but they also have important roles as regulatory agents in a range of biological phenomena. They are normally generated as by-products of oxygen metabolism; however, environmental stressors (ultraviolet radiation, ionizing radiations, pollutants, heavy metal and xenobiotics) contribute to greatly increase ROS/RNS production.

It is difficult to measure ROS/RNS, therefore, biomarkers are often used as a surrogate; however, many of the biomarkers are insufficiently validated and it is often difficult to draw general conclusions on their significance [3]. 8-OHdG, one of the major products of DNA oxidation, is one of the most commonly used biomarkers of oxidative stress. Advanced glycation end-products (AGEs) are a group of heterogeneous molecules that arise from the non-enzymatic reaction of reducing sugars with amino groups of lipids, DNA and especially long-lived proteins. This process occurs during normal metabolism but is even more pronounced under oxidative stress conditions. AGEs may be harmful and include modified proteins and/or lipids with damaging potential. Using 8-OHdG, AGEs and other biomarkers, several attempts have been made to link oxidative stress, either as a cause or contributor, or both, to a variety of diseases, including LUTS. As pointed out by Ghezzi et al. [4] ‘Today it is a challenge to find a disease for which a role of oxidative stress has not been postulated.’

Matsumoto et al. [5] investigated the possible relationship between some markers of oxidative stress and LUTS in a population of community-living subjects participating in a health promotion project. As markers of oxidative stress, they used 8-OHdG (urine) and AGEs (skin autofluorescence), while structured questionnaires were used to assess LUTS. In their study, despite univariate analyses revealing several significant associations, multivariate analyses showed that the only statistically significant finding was that AGEs were associated with moderate to severe nocturia. This association is thought-provoking but, without functional studies, difficult to evaluate. LUTS are multifactorial and reflect a number of different comorbidities/pathophysiologies. It cannot be excluded that this may contribute to the lack of associations between oxidative stress markers and symptoms.

The finding of an association (or lack of it) between biomarkers of oxidative stress and LUTS does not reveal whether oxidative stress causes or contributes to LUTS. If ROS/RNS were causative/contributing factors to LUTS, it would be predicted that a positive response to antioxidant therapy and a decrease in ROS/RNS levels would not only support an involvement but would also be a promising treatment approach. In a prospective cohort study in the USA of 1670 men aged 65–100 years, Holton et al. [6] examined whether dietary antioxidants were associated with a reduced likelihood of LUTS progression or an increased likelihood of LUTS. They found that there were no significant associations between multiple dietary antioxidants and LUTS progression or remission over 7 years. Many other attempts to validate and exploit chronic antioxidant therapies have provided disappointing results, and still there is no antioxidant with sufficient efficacy to be approved by health authorities [4]. The question of whether antioxidant therapy may be harmful has not yet been answered. If the cause of LUTS is an increase of ROS/RNS in the bladder, it is questionable whether normalization of indicators of oxidative stress is safe, considering that the normal function of ROS/RNS in the rest of the body may be affected.

The clinical relevance of oxidative stress as a pathophysiological factor in lower urinary tract dysfunction or as a treatment target for various lower urinary tract disorders is still unclear. In addition, it has not been established that antioxidant therapy has any beneficial effect on LUTS.

by Karl-Erik Andersson

References

  1. Sies H. Oxidative stress: a concept in redox biology and medicine. Redox Biol 2015; 4: 180–3
  2. Murphy MP, Holmgren A, Larsson NG et al. Unraveling the biological roles of reactive oxygen species. Cell Metab 2011; 13: 361–6
  3. Frijhoff J, Winyard PG, Zarkovic N et al. Clinical relevance of biomarkers of oxidative stress. Antioxid Redox Signal 2015; 23: 1144–70
  4. Ghezzi P, Jaquet V, Marcucci F, Schmidt HHHW. The oxidative stress theory of disease: levels of evidence and epistemological aspects. Br J Pharmacol 2017; 174: 1784–96
  5. Matsumoto T, Hatakeyama S, Imai A et al. Relationship between oxidative stress and lower urinary tract symptoms: results from a community health survey in Japan. BJU Int 2019; 123 877-84
  6. Holton KF, Marshall LM, Shannon J et al. Osteoporotic fractures in men study group. Dietary antioxidants and longitudinal changes in lower urinary tract symptoms in elderly men: the Osteoporotic Fractures in Men study. Eur Urol Focus 2016; 2: 310–8

 

Video: The relationship between oxidative stress and lower urinary tract symptoms: Results from the community health survey in Japan

/by

The relationship between oxidative stress and lower urinary tract symptoms: Results from the community health survey in Japan

 

Abstract

Objective

To investigate the relationship between oxidative stress and lower urinary tract symptoms (LUTS) in a community‐dwelling population.

Materials and Methods

The cross‐sectional study included 1 113 people who participated in the Iwaki Health Promotion Project of 2015 in Hirosaki, Japan. LUTS were assessed using structured questionnaires, including the International Prostate Symptom Score (IPSS) and the Overactive Bladder Symptom Score (OABSS). IPSS > 7, OABSS > 5, nocturia score > 1, or urge incontinence score > 1 were defined as moderate to severe symptoms. 8‐Hydroxy‐2′‐deoxyguanosine (8‐OHdG) and advanced glycation end products (AGEs) were measured by urine analysis and skin autofluorescence, respectively. The relationship between oxidative stress and LUTS was investigated using logistic regression analyses.

Results

This study included 431 men and 682 women. AGEs and 8‐OHdG levels were significantly higher in severe forms of LUTS. Multivariate logistic regression analyses showed that AGE levels were significantly associated with a higher frequency of nocturia but were not associated with IPSS, OABSS or urge incontinence. No significant association was observed between LUTS and 8‐OHdG levels.

Conclusions

We observed a significant association between AGE levels and nocturia score > 1. Further research is necessary to clarify a possible causal relationship between oxidative stress and nocturia.

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Article of the week: In utero myelomeningocele repair and urological outcomes: the first 100 cases of a prospective analysis

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Every week, the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an editorial written by a prominent member of the urological community and a podcast produced by our Resident podcasters, Giulia Lane and Kyle Johnson. The authors have also kindly produced a video describing their work.

These are intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation. 

If you only have time to read one article this week, it should be this one.

In utero myelomeningocele repair and urological outcomes: the first 100 cases of a prospective analysis. Is there an improvement in bladder function?

Antonio Macedo Jr*†, Sergio Leite Ottoni*, Gilmar Garrone*, Riberto Liguori*, Sergio Cavalheiro‡§, Antonio Moron¶§ and Marcela Leal Da Cruz*

 

*Department of Urology, CACAU-NUPEP, †Department of Pediatrics, Federal University of São Paulo, ‡Department of Neurosurgery, Federal University of São Paulo, §Santa Joana Maternity Hospital, and Department of Obstetrics-Fetal Medicine, Federal University of São Paulo, São Paulo, Brazil

 

Read the full article

Abstract

Objectives

To evaluate the first 100 cases of in utero myelomeningocele (MMC) repair and urological outcomes in a prospective analysis aiming to define possible improvement in bladder function.

Patients and methods

We used a protocol consisting of a detailed medical history, urinary tract ultrasonography, voiding cystourethrography, and urodynamic evaluation. Patients were categorised into four groups: normal, high risk (overactive bladder with a detrusor leak‐point pressure >40 cm H2O and high filling pressures also >40 cm H2O), incontinent, and underactivity (underactive bladder with post‐void residual urine), and patients were treated accordingly.

Fig.2. Hydronephrosis in relation to the underlying bladder pattern.

Results

We evaluated 100 patients, at a mean age of 5.8 months (median 4 months), classified as high risk in 52.6%, incontinent in 27.4%, with underactive bladder in 4.2%, and only 14.7% had a normal bladder profile. Clean intermittent catheterisation was initiated in 57.3% of the patients and anticholinergics in 52.6%. Antibiotic prophylaxis was initiated in 19.1% of the patients presenting with vesico‐ureteric reflux.

Conclusion

The high incidence of abnormal bladder patterns suggests little benefit of in utero MMC surgery concerning the urinary tract.

 

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Editorial: Bladder function and fetal treatment of myelomeningocele

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In utero myelomeningocele repair and urological outcome: the first 100 cases of a prospective analysis. Is there an improvement in bladder function? Comments on bladder function and fetal treatment of myelomeningocele [1].

Prenatal care with maternal screening for neural tube defects and high‐resolution maternal fetal sonography has led to the early diagnosis of fetal myelomeningocele [2]. Revolutionary fetal surgery to correct myelomeningocele in utero has reduced the need for cerebrospinal fluid shunting and improved motor outcomes in these babies, based on 30‐month follow‐up data [3]. Sponsored by the National Institute of Health, the prospective randomized ‘Management of Myelomeningocele Study’ (MOMS) trial documented the outcomes of 158 patients assessed after either fetal repair prior to 26 weeks’ gestation or standard postnatal repair of the myelomeningocele defect. The trial was stopped early when evaluation showed that the primary outcome, rate of shunt placement, in the postnatal repair group (82%) was approximately double that in the prenatal surgery group (40%). Prenatal surgery also resulted in improvement in outcomes for mental development, motor function and ambulation, also evaluated at 30 months postnatally. However, prenatal surgery was associated with an increased risk of preterm delivery and uterine dehiscence at the time of delivery.

Bladder function was also evaluated at 30 months in the MOMS trial, comparing the need for clean intermittent catheterization (CIC) in 115 patients with adequate urological follow‐up, consisting of clinical outcomes in respect to continence, sonographic appearance of the kidneys and bladder and urodynamic evaluation [4]. Prenatal surgery did not significantly reduce the need for CIC measured at 30 months of age, but was associated with less bladder trabeculation and open bladder neck. Longer follow‐up was recommended and is in progress to document further bladder outcomes.

Macedo et al. [1] report similar short‐term bladder outcomes in 100 patients undergoing in utero myelomeningocele repair. Their report documented bladder characteristics in these patients at a mean postnatal age of ~6 months. In their unique cohort, antenatal diagnosis of fetal myelomeningocele was made at ~21 weeks’ gestation, in utero surgery was performed at ~25.5 weeks’ gestation and preterm birth occurred at ~33 weeks’ gestation, parameters consistent with the patients in the MOMs trial. Short‐term evaluation showed that ~53% of the patients had high‐risk bladders with poor compliance, ~27% were incontinent with weak sphincteric activity and only ~15% had normal urodynamic profiles. CIC was initiated in ~ 57% of the Macedo et al. cohort, again similar to the MOMs trial. The long‐term outcomes after potty training and during childhood and adolescence will be especially interesting in this valuable cohort.

Some of the pitfalls that will need to be accounted for include the validation and standardization of urodynamic testing [5]. Even at the same institution with clinicians who have undergone similar training, consistent interpretation of urodynamic studies can be variable, potentially affecting therapeutic options [6].

The goal of patients, parents and providers is to avoid the urological sequelae of myelomeningocele. To date, the reality is that the majority of these children, whether or not they have undergone in utero fetal repair or postnatal surgery, will require the assistance of CIC for urological health to protect the kidneys from excess pressure, to facilitate bladder emptying and urinary continence and prevent UTI.

 

References

  1. Macedo, A, Ottoni, SL, Garrone, G et al. In utero myelomeningocele repair and urological outcome: the first 100 cases of a prospective analysis. Is there an improvement in bladder function? BJU Int 2019; 123: 676– 81
  2. Meller, C, Aiello, H, Otano, L. Sonographic detection of open spina bifida in the first trimester: review of the literature. Childs Nerv Syst 2017; 33: 1101– 6
  3. Adzick, NS, Thom, EA, Spong, CY et al. A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med 2011; 364: 993– 1004
  4. Brock, JW, Carr, MC, Adzick, NS et al. Bladder Function After Fetal Surgery for Myelomeningocele. Pediatrics 2015; 136: e906– 13
  5. Bauer, SB, Nijman, RJ, Drzewiecki, BA, Sillen, U, Hoebeke, P, International Children’s Continence Society Standardization Subcommittee. International Children’s Continence Society standardization report on urodynamic studies of the lower urinary tract in children. Neurourol Urodyn 2015; 34: 640– 7
  6. Dudley, AG, Casella, DP, Lauderdale, CJ et al. Interrater reliability in pediatric urodynamic tracings: a pilot study. J Urol 2017; 197: 865– 70

 

Residents’ podcast: In utero myelomeningocele repair and urological outcomes

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Giulia Lane M.D. is a Fellow in Neuro-urology and Pelvic Reconstruction in the Department of Urology at the University of Michigan; Kyle Johnson is a Urology Resident in the same department.

In this podcast they discuss the following BJUI Article of the Week:

In utero myelomeningocele repair and urological outcomes: the first 100 cases of a prospective analysis. Is there an improvement in bladder function?

Abstract

Objectives

To evaluate the first 100 cases of in utero myelomeningocele (MMC) repair and urological outcomes in a prospective analysis aiming to define possible improvement in bladder function.

Patients and methods

We used a protocol consisting of a detailed medical history, urinary tract ultrasonography, voiding cystourethrography, and urodynamic evaluation. Patients were categorised into four groups: normal, high risk (overactive bladder with a detrusor leak‐point pressure >40 cm H2O and high filling pressures also >40 cm H2O), incontinent, and underactivity (underactive bladder with post‐void residual urine), and patients were treated accordingly.

Results

We evaluated 100 patients, at a mean age of 5.8 months (median 4 months), classified as high risk in 52.6%, incontinent in 27.4%, with underactive bladder in 4.2%, and only 14.7% had a normal bladder profile. Clean intermittent catheterisation was initiated in 57.3% of the patients and anticholinergics in 52.6%. Antibiotic prophylaxis was initiated in 19.1% of the patients presenting with vesico‐ureteric reflux.

Conclusion

The high incidence of abnormal bladder patterns suggests little benefit of in utero MMC surgery concerning the urinary tract.

 

Read the full article

BJUI Podcasts now available on iTunes, subscribe here https://itunes.apple.com/gb/podcast/bju-international/id1309570262

 

 

Video: In utero myelomeningocele repair and urological outcomes: the first 100 cases of a prospective analysis. Is there an improvement in bladder function?

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In utero myelomeningocele repair and urological outcomes: the first 100 cases of a prospective analysis. Is there an improvement in bladder function?

Abstract

 

Objectives

To evaluate the first 100 cases of in utero myelomeningocele (MMC) repair and urological outcomes in a prospective analysis aiming to define possible improvement in bladder function.

Patients and methods

We used a protocol consisting of a detailed medical history, urinary tract ultrasonography, voiding cystourethrography, and urodynamic evaluation. Patients were categorised into four groups: normal, high risk (overactive bladder with a detrusor leak‐point pressure >40 cm H2O and high filling pressures also >40 cm H2O), incontinent, and underactivity (underactive bladder with post‐void residual urine), and patients were treated accordingly.

Results

We evaluated 100 patients, at a mean age of 5.8 months (median 4 months), classified as high risk in 52.6%, incontinent in 27.4%, with underactive bladder in 4.2%, and only 14.7% had a normal bladder profile. Clean intermittent catheterisation was initiated in 57.3% of the patients and anticholinergics in 52.6%. Antibiotic prophylaxis was initiated in 19.1% of the patients presenting with vesico‐ureteric reflux.

Conclusion

The high incidence of abnormal bladder patterns suggests little benefit of in utero MMC surgery concerning the urinary tract.

 

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