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   Table of Contents - Current issue
Coverpage
January-February 2021
Volume 32 | Issue 1
Page Nos. 1-43

Online since Saturday, March 27, 2021

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EDITORIAL  

Urological Science – On the horizon of rising and improving p. 1
Yao-Chi Chuang
DOI:10.4103/UROS.UROS_40_21  
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REVIEW ARTICLE Top

Toward a validated diagnostic test with machine learning algorithm for interstitial cystitis p. 2
Michael B Chancellor, Laura E Lamb
DOI:10.4103/UROS.UROS_155_20  
Diagnosing interstitial cystitis/bladder pain syndrome (IC/BPS) is difficult as there is no definitive test for IC/BPS. Instead, the diagnosis is based on urinary symptoms and cystoscopy may be recommended. However, cystoscopic diagnosis is associated with potentially exacerbating painful side effects and is highly subjective among physicians. Furthermore, IC/PBS symptoms overlap with symptoms of bladder cancer, urinary tract infection, or overactive bladder. As a result, many patients may go years without a correct diagnosis and proper disease management. The goal of our current IC/BPS research is to develop a simple diagnostic test based on several urine proteins called the IC-risk score (IC-RS). A machine learning (ML) algorithm uses this information to determine if a person has IC/BPS or not; if they have IC/BPS, whether their IC/BPS is characterized by Hunner's lesions. We are currently in the middle of a grant to collect urine samples from 1000 patients with IC/BPS and 1,000 normal controls from across the United States. We are using social media such as Twitter and Facebook and working with patient advocacy organizations to collect urine samples from across the country. We hope to validate the IC-RS and apply for regulatory approval. Having a validated diagnostic test for IC/BPS would be a major advancement to help urology patients. In addition, drug companies developing new drugs and therapies for IC/BPS would have a better way to determine who to include in their clinical trials, and possibly another way to measure if their drug or therapy is effective. We will hereby review the steps that have led us in urine biomarker discovery research from urine protein assessment to use crowdsourcing stakeholders participation to ML algorithm IC-RS score development.
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EDITORIAL COMMENT Top

A step toward precision diagnosis of interstitial cystitis p. 8
Hann-Chorng Kuo
DOI:10.4103/UROS.UROS_15_21  
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ORIGINAL ARTICLES Top

The associations of genital-normalizing surgery and assigned gender in predicting gender outcomes: A pooled nested case study analysis of 282 adults with differences of sex development in 58 academic articles p. 9
Jaimie F Veale
DOI:10.4103/UROS.UROS_65_20  
Purpose: The purpose was to systematically analyze the associations of childhood gender assignment and genital normalizing surgeries with adult gender in case reports of adults with differences of sex development (DSD). We did this using a pooled nested analysis of DSD adult cases reported in the academic literature. Materials and Methods: A search of academic databases uncovered 282 adult DSD cases reported in 58 academic articles that met the criteria for inclusion in the analysis. These were cases with 46, XX congenital adrenal hyperplasia, partial androgen insensitivity, mixed or partial gonadal dysgenesis, and micropenis where data about the assigned gender, childhood genital-normalizing surgery, and adult gender could be extracted. We conducted a generalized logistic mixed-model regression analysis, with multiple predictors of adult assigned gender incongruence. Results: Controlling for assigned gender, age, year of article publication, and DSD type, childhood genital surgery was not significantly associated with adult assigned gender incongruence. Cases assigned female had more than five times greater likelihood of assigned gender incongruence (95% confidence interval = 1.96–14.92). Conclusion: This study did not find evidence that childhood genital surgery is related to assigned gender incongruence; it also found that assigning a child as a female increased this possibility. These findings may inform decisions taken by clinicians and family members about the early management of DSD cases. The study was limited by publication bias in the types of cases that get published. Ethical considerations should always take precedence in decision-making regarding these surgeries.
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Using R.E.N.A.L. nephrometry and preoperative aspects and dimensions employed for anatomical classification to evaluate perioperative outcomes of renal tumors greater than 4 cm in patients who underwent minimally invasive partial nephrectomy in a single center p. 15
Hsing-Chia Mai, Chun-Hsien Wu, Yung-Yao Lin, Wade Wei-Ting Kuo, Yen-Hsi Lee, Ryh-Chyr Li, Richard C Wu, Victor C Lin
DOI:10.4103/UROS.UROS_78_20  
Purpose: The R.E.N.A.L. (radius, exophytic/endophytic tumor properties, nearness of tumor to deepest portion of collecting system or sinus, anterior/posterior descriptor, and location relative to the polar line) and preoperative aspects and dimensions used for an anatomical (PADUA) (tumor size and position, relationship with the renal sinus or the urinary collecting system, and the grade of deepness into the kidney) nephrometry scoring systems are frequently used in predicting the perioperative outcomes of nephron-sparing surgery (NSS). Minimally invasive NSS on renal masses beyond 4 cm in diameter remains challenging and may result in the significant complications. We aimed to evaluate the associations of both scoring systems with perioperative outcomes for minimally invasive NSS on renal masses larger than 4 cm in diameter. Materials and Methods: We retrospectively reviewed patients who received robot-assisted partial nephrectomy (PN) or laparoscopic PN for renal tumors larger than 4 cm in diameter in our institution between January 2008 and March 2019. Computed tomography scan and magnetic resonance imaging were the standard cross-section imaging modalities done before surgery and both R.E.N.A.L. and PADUA scores were calculated in every case accordingly. The correlation between each scoring system and the perioperative and renal functional outcomes was analyzed by logistic regression models. Results: A total of 93 cases were enrolled in this study. The mean tumor size was 6.1 ± 2.03 cm in the largest dimension. A higher R.E.N.A.L. score was significantly correlated with longer warm ischemia time (WIT) (r = 0.267, P = 0.021), prolonged hospital stays (r = 0.258, P = 0.013), and poorer renal functional outcome at 1 year (r = 0.421, P = 0.003). Meanwhile, a higher PADUA score was significantly correlated with longer operation time (r = 0.255, P = 0.014), longer WIT (r = 0.278, P = 0.016), and poorer renal function after 1 year (r = 0.615, P < 0.001). Neither scoring system correlated with estimated blood loss (P = 0.510 and 0.5466, respectively). The R.E.N.A.L. score, PADUA score, patient age, body mass index, Charlson comorbidity index, tumor size, and American Society of Anesthesiologists score were not associated with surgical complications as well. Conclusion: Both the R.E.N.A.L. and PADUA scoring systems were associated with WIT and renal functional outcomes, but the latter was more relevant. When performing minimal invasive NSS on renal masses beyond 4 cm, both systems can provide valuable risk stratification, but PADUA was found to be superior in the current study.
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The impact of population lockdown on the referral pattern for urology in a COVID-19 designated tertiary hospital in Malaysia p. 23
Norshuhada Amat, Eleanor F Philip, Chu Ann Chai, Wei Sien Yeoh, Jasmine Lim, Ahmad Nazran Fadzli, Shanggar Kuppusamy, Teng Aik Ong
DOI:10.4103/UROS.UROS_92_20  
Purpose: Once COVID-19 was first reported in Wuhan, China, in December 2019, it has rapidly spread worldwide. The Malaysian Government had taken an early measure by introducing the movement control order (MCO), which is a form of lockdown. This study aims at describing the referral pattern for urology in a COVID-19 designated tertiary hospital throughout the MCO period. Materials and Methods: All urology referrals received from March 18, 2020 to April 28, 2020 (i.e., during the MCO period) were included and assessed prospectively. For comparison, a retrospective study covering the period from February 1, 2020 to March 17, 2020 (i.e. pre-MCO period) was conducted. Parameters measured and compared include sources of referral, type of cases, outcomes, admission status, and COVID-19 status of patients referred. Results: The majority of referrals for urology were received from the emergency department during MCO (42.9%), followed by the medical ward (28.6%) and surgical ward (2.3%). In terms of the type of cases referred, during the MCO, the highest number of hematuria cases (22.5%) was received and a high number of Benign Prostate Hypertrophy (BPH) and urethral stricture cases (18.8%). Conservative measures remain the most commonly adopted outcomes/management for both pre and during MCO. The number of admissions required for urology referral showed a slight difference between pre and during MCO. Conclusion: The workload of urology referral in a COVID-19 designated tertiary hospital did not change despite MCO. This supports that the urology team still has an important role to play as a subspecialty unit in managing urology emergencies, even when elective surgeries and procedures are being reduced or rescheduled.
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Pelvic lymph node dissection using indocyanine green fluorescence lymphangiography in robotic assisted radical prostatectomy for non-lymph node or distant metastasis prostate cancer patients p. 27
Yu-Feng Chuang, Yen-Chuan Ou, Yi-Sheng Lin, Li-Hua Huang, Wei-Chun Weng, Yu-Kang Chang, Hung-Lin Chen, Chao-Yu Hsu, Min-Che Tung, Chin-Heng Lu
DOI:10.4103/UROS.UROS_96_20  
Purpose: The utility of indocyanine green dye (ICG) has evolved significantly to the robotic operations including Robotic Assisted Radical Prostatectomy (RARP). The technology can help the identification of sentinel lymphatic drainage in lymphadenectomy for the majority of prostate cancer (PCa) patients. We describe the potential indications of ICG for lymphadenectomy assistant in PCa patients without lymph node or distant metastasis. Materials and Methods: We prospectively analyzed PCa patients without lymph node or distant metastasis with clinical pathological stage T1c to T3a received RARP from November 2019 to May 2020. The clinical data and pathological data, including Gleason score, tumor volume, pathological stage, and surgical findings, were described. All lymph nodes were divided into ICG positive or negative. All patients were divided into low, moderate, and high risk according to the European Association of Urology PCa risk stratification. Results: Cystoscope-guided intraprostatic injection was performed successively in 34 localized PCa patients in this study. The mean age was 66.1 ± 7.8 years old. The patients' number of high, moderate, and low risk was 18, 10, 6. A total of 447 lymph nodes were identified. Two hundred and sixty-two lymph nodes were ICG positive and 181 lymph nodes were ICG negative. ICG positive rate higher in high risk patients 158/259 (61.0%) compare to intermediate/low risk patients 104/188 (55.3%). There was no statistic significant result, but lymph node could be identified in all ICG-positive tissues. There were 12 patients revealed higher Gleason grade group after RARP and two patients revealed lower Gleason grade group after RARP. There were 18 patients showed upgrade stage after RARP and 4 patients showed down stage after RARP. Conclusion: Cystoscope-guided intraprostatic ICG injection with fluorescence lymphangiography can help identify pelvic lymph nodes in RARP for PCa patients without lymph node or distant metastasis.
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Can cavernous nerves be spared after radical prostatectomy? Evidence from animal studies p. 34
Han-Sun Chiang, Meng-Lin Chang, Yi-No Wu
DOI:10.4103/UROS.UROS_110_20  
Purpose: The current study aims at evaluating penile erectile function after nerve-sparing radical prostatectomy (RP) based on evidence from a reliable animal model. The previous model in which the cavernous nerve (CN) is temporarily crushed is reviewed and compared to the present method of prostate lobes removal near the CN to determine which is more relevant to the clinical situation. Materials and Methods: Twenty-four rats were divided into three groups. One group was subjected to temporary CN crushing, one group was subject to prostate lobes removal near the CN, and the last group was preserved (sham group). All rats were re-examined at 4 weeks after the first surgical procedure. The pathological changes of the CNs were evaluated by their gross appearance and immunohistochemistry. Intracavernosal pressure (ICP) was measured as a parameter of male erectile function. Results: The results of the current study demonstrate that the removal of the prostate lobes near the CN led to the degeneration of CN, even with careful sparing techniques. Four weeks after the first surgical procedure, the rats' abdomens were reopened, and CNs were identified in only 60% of the rats with prostate lobes removal near the CN. Furthermore, the remaining CNs in this group were found to be histologically degenerated, with poorer erectile function presented by ICP. In contrast, the CNs after temporary crush were only mildly injured and demyelinated, with evidence of regeneration. The changes in the rats with prostate lobes removal near the CN are much more similar to those in rats with clinical RP with CN sparing. Conclusion: The current study concluded that, in the rat model, CNs will be injured, degenerated, and eventually disappear after prostate lobes removal near the CN; this is very similar to what is observed in clinical RP. Protection of the CNs for erectile function preservation should be investigated further using this animal model.
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CASE REPORT Top

Early diagnosis of CYP17A1 compound heterozygous mutations in a 46, XY child with disorders of sexual development p. 40
Wison Laochareonsuk, Somchit Jaruratanasirikul, Wanwisa Maneechay, Surasak Sangkhathat
DOI:10.4103/UROS.UROS_43_20  
17-Hydroxylase/17,20-lyase deficiency is a rare congenital disorder accounting for 1% of congenital adrenal hyperplasia. This disease is recessively expressed as autosomal inheritance through mutations in the CYP17A1 gene, leading to defective levels of glucocorticoids and sex hormones. Individuals with loss-of-function mutations usually present with phenotypic female genitalia, primary amenorrhea, or hypertension in puberty caused by excessive production of mineralocorticoids. In this report, we describe a girl with CYP17A1 mutations diagnosed even though the pathognomonic symptoms had not developed. Herein, we report a case of a 3-year-old girl who prenatally diagnosed as a 46, XY female. After birth, the baby had normal female-type external genitalia without symptoms. She underwent a gonadectomy at the age of 3 years. To explore the pathogenesis of her condition, her genomic data were reviewed for genes involved in disorders of sexual differentiation (DSDs) using high-throughput sequence data from a whole-exome study. Pathogenic variants causing frameshift mutation involving codon 329 of CYP17A1 and a concomitant missense mutation involving codon 358 of the same gene were detected, mutations which are likely to result in loss of function of the enzyme. Each mutation was inherited from each of the parents, both holding carrier status. In addition, her younger sister (46, XX) acquired those identical variants without any abnormal phenotypical traits. Loss-of-function mutations of CYP17A1 which may cause secondary hypertension are not commonly identified in early life because of the wide spectrum of clinical manifestations and various pathophysiologies, which manifest in different sexes. Affected cases usually present later in life with hypertension or primary amenorrhea. High-throughput sequencing is suggested in DSD cases as it may give a precise diagnosis, enabling a proactive treatment plan and prevention of sequelae that potentially occur in puberty.
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