This chapter will take approximately 25 minutes to read.

  1. Hasbro Children's Hospital, Providence, RI, USA
  2. Department of Surgery, Division of Urology, Warren Alpert Medical School of Brown University, Providence, RI, USA
  3. Hasbro Children's Hospital, Providence, RI, USA
  4. Department of Surgery, Division of Urology, Warren Alpert Medical School of Brown University, Providence, RI, USA
  5. Paediatric Urology, Chelsea & Westminster Hospital, London, United Kingdon
  6. Paediatric Urology, Imperial College Hospitals, London, United Kingdon
  7. Division of Pediatric Urology, Children's National Hospital, Washington DC, 20010
  8. Division of Urology, Children's Hospital of Philadelphia, Philadelphia, PA, USA
  9. University of Pennsylvania, Philadelphia, PA, USA
  10. Boston Children's Hospital, Boston, MA, USA
  11. Division of Urology, Children's Hospital of Philadelphia, Philadelphia, PA, USA
  12. University of Pennsylvania, Philadelphia, PA, USA
  13. Department of Urology, Ghent University Hospital, Ghent, Belgium
  14. Urology, NUPEP-CACAU, São Paulo, Brazil
  15. Hospital Pellegrin-Enfants, Bordeaux, France
  16. CHU Bordeaux, Bordeaux, France
  17. Surgery, Hospital for Sick Children, Toronto, ON, Canada
  18. Division of Urology, Hospital for Sick Children, Toronto, Ontario, Canada
  19. University of Toronto, Toronto, Ontario, Canada

Introduction

Commentary and Edited By Liza M. Aguiar & Anthony A. Caldamone

In 1991, Norman Zinner and co-authors published a paper entitled “Forecast of change in urology.”1 In this article they reviewed the results of a survey conducted by the Society of University Urologists asking members to identify the most important events or trends that would be likely to occur in the next 10-30 years in urology. This was published as the “1976 Possibilities List.” Table 1 lists a few of these that you would find interesting. This list covers areas of medical advancement, technological advancements, socio-economic factors, and education and training. Based on an analysis by a panel of experts, it was felt that urologists were remarkably accurate in their forecast of the most important trends and events over the issuing years. Areas where the 1976 urologist survey results did not envision important changes were in diagnostic imaging, HMO/PPOs, and outpatient surgeries.

Table 1 Selected listing of the Society of University Urologists study of the future: 1976 Possibilities List.1

  Prediction
1 Functional synthetic ureter, bladder, and urethra developed
2 Implantable small kidneys developed
3 External urinary diversion seldom performed
4 Development of foolproof form of antibacterial prophylaxis
5 Development of miniaturized and improved endoscopic instrumentation
6 Mandatory use of computers in diagnosis and treatment
7 Development of communications which permit remote two-way patient-physician interaction
8 National and international “on-line” grand rounds, including instant display of x-rays, etc.
9 Fertility problems controlled medically
10 Anomalies eliminated by genetic manipulation
11 Development of practical intrauterine diagnosis and therapy
12 Development of regionalized health care system with super specialization of major centers
13 Cost of medical education increases substantially
14 Natural disasters occur
15 Extrauterine fetal development and monitoring become feasible
16 Public hostility toward physicians increases
17 Type and number of residency programs subjected to government control
18 Urology residencies limited to university centers
19 Development of residency matching program
20 Team approach to patient care widely adopted

In this chapter, we take on the challenge of predicting what changes will occur in pediatric urology over the next 25 or more years. We have broken down the chapter into several content specific areas. We asked recognized experts in each of those content areas to predict the changes in their estimation that we will likely see over the next quarter decade. The chapter editors have provided a short commentary for each area as well.

Prenatal Diagnosis and Treatment in 2050

By Marie-Klaire Farrugia

Antenatal ultrasound and fetal MRI will be obsolete. Fetal anatomy will be visualised by 3D augmented reality, using smart phones. The fetal anatomy can then be analysed digitally and fetal measurements automatically plotted onto growth charts. Artificial intelligence (AI) will capture data instantaneously and provide a medical report. When a group of anomalies is identified, AI will suggest genetic, syndromic or other diagnoses and provide information on prognosis and further management. For example, if fetal lower urinary tract obstruction is diagnosed, the application can then formulate a “virtual cystoscopy,” augmented reality model to further delineate the cause of obstruction. Fetal renal cortical analysis (utilising data from echogenicity, cortical thickness or cysts, with the potential addition of fetal urine peptide signature) will estimate fetal renal function. Amniotic fluid level and its components will be measured utilising density and reflectivity data, without the need for invasive testing. Based on AI algorithms, the application will determine whether fetal intervention is indicated, and when. Once intervention is recommended, a special headset is worn by the specialist, whereby computer-generated laser holograms superimpose the safest pathway for the fetal cystoscope to be introduced, on the maternal abdomen. A flexible fetal cystoscope can then be inserted in an antegrade fashion via the fetal abdomen, into the bladder, and the urethra stented with a made-to-measure pre-formed coiled stent which can be “shot” into the urethra. The biggest challenge will be consent, in an era where surgery on the fetus without its consent is controversial.

Comment

Pregnancy and the developing fetus was once a “black box” of medicine. Now, with better understanding of fetal development, and technological advancements in prenatal imaging and prenatal interventions, the fetus has become as much of a patient as its host. Fetal medicine will continue to grow as a field the more we learn and are able to do during the earliest stages of development. We currently have multiple pediatric subspecialities, but who knows if in the future, we will have fetal subspecialties, including fetal urologists.

The “Top-Down” Approach to the Evaluation of Children with Febrile Urinary Tract Infection in 2050

By Hans G. Pohl

The year 2050 will be celebrated for the consolidation of the US pediatric urology programs into the North American Pediatric Genitourinary Outcomes Alliance and the publication of its first project “High-yield evaluation and treatment algorithm for pediatric urinary tract infection and associated CAKUT.” First proposed in 2025 at a meeting of the Society for Pediatric Urology to address the nagging question of whether the “bottom-up” or “top-down” approach to UTI evaluation is the superior algorithm, the members agreed to collaborate on a nation-wide multi-institutional study of children younger than 2 years old who presented with initial febrile UTIs. It was agreed that the inclusion of older, toilet-trained children introduced too much complexity and, so, the role of elimination disorders in determining the risk for UTI and how best to manage bladder-bowel dysfunction would be the focus of future collaborations, if this foray succeeded.

Five years elapsed to achieve agreement on nomenclature and imaging methodology, including the collection of blood and urine samples at the time of presentation. The consortium members sought to utilize evolving technologies in high-throughput proteomics, metabolomics and microbiome analysis to create a personalized map of biological interactions using network visualization and analysis of high-dimensional data. Big data and artificial intelligence would settle the debate.

Most programs opted to recruit for the “bottom-up” approach, with few providing patients undergoing upper tract imaging first, each according to the local bias. Standard contrast-radiography VCUGs or voiding urosonograms were used to seek VUR. Even among those employing the “top-down” approach, DMSA and MRU were selectively used based on institutional preference. Notwithstanding the lack of a standard approach across all institutions, perseverance yielded a trove of data in a central repository. The consortium had underestimated its success, driven partly by investigator zeal to answer the question as well as a fair sense of competition to recruit one’s allotment of data. How does one perform component analysis considering, for instance, serum procalcitonin levels, urinary biomarkers, single-nucleotide polymorphisms encoding innate immunity, bacterial metabolomics, and imaging findings? Help arrived from social media companies.

In the 2020s, the public discourse focused on the role of social media and “big data” as a determinant of socioeconomic, political, and personal well-being. Reeling from a decade of class-action suits and trans-national governmental inquiries, six of the largest technology firms made earnest commitment toward the public trust. Not unlike the photo sharing app, Snapchat, the enormous computing power available to these companies would be leveraged to answer specific questions within a finite period, then all data would be deleted, and all findings made publicly available and programmed as best-practice guidelines into the electronic health record systems.

The consortium confirmed the poor reliability of renal sonography to detect upper urinary tract abnormalities and the improved sensitivity of DMSA and MRU in identifying renal involvement.2,3,4 However, there was limited utility in employing a top-down approach the longer the interval between the symptomatic UTI and presentation for evaluation. The “bottom-up” approach had greater sensitivity for the detection of all cases of VUR. Superficially the age-old controversies pitting one form of invasive testing versus another were unresolved, until the inclusion of biomarker data of host-pathogen interaction. Using this multi-variable approach, the consortium proved the superiority of the “top-down” approach where serum and urine biomarkers served as a proxy for DMSA scans.5 A biochemical risk profile could then be created to inform further evaluation by voiding urosonography rather than by VCUG. As clinical data were entered into a risk calculator, the likelihood of the patient’s microbiome developing resistance, the likelihood of breakthrough symptomatic UTI and the likelihood of reflux resolution were generated. Not unlike the Partin tables for the prediction of prostate cancer disease progression, the VUR nomograms informed treatment selection; antimicrobial prophylaxis versus surgical correction. At the time of publication, the consortium foresaw that, in addition to foregoing ionizing radiation in the algorithm, catheterization would no longer be required as a new, ultra-fast MRI protocol resulted in rendering intra-vesical urine bright, thus creating the means for cystography without radiation or catheterization. The group celebrated their accomplishment the following year at the Wee Willies July 2051, Anchorage, Alaska, overlooking the leading edge of Portage Glacier as it once again filled the lake of the same name.

Comment

Our understanding of urinary tract infections and vesicoureteral reflux (VUR) in children has dramatically evolved over the past 50 years – from believing that VUR was rare and caused by bladder outlet obstruction to better understanding its natural history, association with bowel and bladder dysfunction, etc. Both parents and pediatric urologists would welcome a world in which the work-up for a febrile urinary tract infection in a child would no longer include invasive testing. In addition, individualized and accurate risk assessment, potentially determined by a nomogram app, would greatly improve our management.

A Look at Hypospadias Management of the Future

By Christopher J. Long, MD

Envisioning the future of hypospadiology must start with an honest assessment of our current success and failures. Recent reports have revealed a low but significant complication rate for distal hypospadias and a much higher risk in proximal repairs, trends that are likely to continue to increase as follow-up extends through puberty. Our current management of hypospadias includes a lack of consistent follow up from childhood repair through adulthood, inconsistent incorporation of patient reported outcomes (PRO), and barriers to multi-institutional collaboration efforts to improve surgical outcomes.

We are only beginning to scratch the surface of utilizing machine learning as a tool in hypospadias management. Assessment of chordee and standardizing measurements such as penile length and glans width have been done but have not gained widespread acceptance. My hope is that one day we look back on this as the first step in our use of this resource. As we increase collaborative efforts with accumulating surgical data and photographs, they could be used to generate an app or website in which the surgeon can take a picture of a child’s specific anatomy and generate a picture of the anticipated outcome to facilitate the decision process. Perhaps the app could also generate an anatomic-specific recommendation for surgical intervention—such as a 1 versus 2 stage repair or the use of a dorsal inlay graft versus Thiersch-Duplay versus Mathieu repair. It would run the patient’s specific anatomy through an algorithm predicting outcomes. Perhaps this will also identify those at particularly high risk for poor outcomes—those with a small, flat glans, those with more dysplastic penile tissue, or even an abnormal anogenital distance, or other factors which we are yet to appreciate. Maybe tissue engineering advances to the point where we can request a synthetic replacement for scant spongiosum, which represents a vital deficiency in these patients. Ultimately, as we continue to expand the role of coaching and surgical “game tape,” having a computer model that could identify the optimal approach and display the key steps in video format will further improve surgical outcomes.

The future of hypospadias surgery should be patient centered. As much as we have refined our techniques and become more self-aware of outcomes, the patient voice is one that will answer current controversies such as the ideal age of repair, the true clinically significant degree of penile curvature, what we should classify as a successful repair, and if we should even repair a particular variant. Utilization of patient reported outcome (PRO) measures must increase, and the patient voice should be a major driver of our medical decision-making process.

Finally, a framework is being established for a universal database utilizing the electronic medical record across a multi-institutional network. This collaboration will eliminate the limitations of underpowered studies to assess the many nuances of surgical management that currently plague the literature. In the future, this will lead to either universally improved outcomes across surgeons due to collaborative efforts and reduction in technical variation or the emergence of high-volume centers that should perform most highly complex procedures, particularly for less common severe variants.

We can never accurately predict the future, but my hope is that we can harness technologic advances to provide a level of care that we are not yet capable of providing.

Comment

It is true that the lack of objective assessment and standardization limits our ability to assess outcomes for hypospadias surgery, and perhaps technology or even artificial intelligence, can one day facilitate that. But, it may not be until we are able to tissue engineer a urethra or corpora spongiosal tissue, that we can actually significantly improve our surgical outcomes.

The Future of Stone Disease in Children

By Michael P. Kurtz, MD, MPH

There are exciting advances in the treatment of stones in children, with implications for the future. First caution, then hope.

Lithotripsy is complex, and while dangerous to bet against urologic ingenuity, we should acknowledge that there are some hard, durile, limits.6 PCNL is a good example. Percutaneous stone treatment has been performed using tracts so small that we normally associate them with needle gauge rather than French size. We also have ever-more powerful lithotripters, both ultrasonic/mechanical and with collimated coherent light around 2000 nM wavelength. The trouble is that transfer of energy from the lithotripter to stone is necessarily imperfect, remaining energy is mostly heat, and it is likely that smaller kidneys are the most vulnerable to heat.7 Compound this with poor-to-absent irrigant flow around the lithotripter itself, and you can see that while the stone may break, it may be at the cost of parenchymal damage. All of this suggests that while optics, lighting, lithotripters, and sheath size may miniaturize, the density of non-stone-breaking energy delivered may be dangerous. If we adopt new adult-based technology with potential thermal side effects, we, pediatric endourologists, will be the canary in the coal mine.

Switching to hot science, a rule-shattering finding has the potential to upend lithotripsy. Calcium stone formation has traditionally been modelled unidirectionally, unrelenting, with periods of stasis and growth. Once a clinic I will encounter a patient’s family wondering hopefully about a chemical stone dissolution formulation and its predatory, FDA-flouting claims. It turns out, someday, those might work. Stones are constantly in the process of formation and dissolution with over half of all stones undergoing such events.6,8 Agents that enhance dissolution at the margin may truly dissolve calcium stones. I suspect we will need to keep our supply closets stocked with lithotripsy equipment for some time, as this would be implemented as treatment or secondary prevention in patients already presenting with stones, but we all can dream of a day in which stones can be washed away through diet, or endoluminal application of a medication.

Comment

The rising prevalence of pediatric stone disease has led to significant patient morbidity, in addition to a costly burden on the health care system. With stone disease comes emergency room visits, prescriptions, imaging with potential exposure to radiation and invasive procedures. It would be remarkable to have a safe litholytic agent that could react with a stone to form a water-soluble compound. We are also looking forward to advancements in technology that would allow for better endoscopic visualization, safer lasering techniques, and of course, stents associated with less stent discomfort.

Bladder Exstrophy-Epispadias Complex: Beyond the Horizon

By Dana A. Weiss

Steve Zderic always says, if you want a new idea, read an old book. The treatment of bladder exstrophy has come full circle from the 1960s when John K. Lattimer focused on a delayed complete repair, to the early staged repair championed by Bob Jeffs, John Gearhart and Julian Ansell, and back again to a delayed complete repair (CPRE) described by Michael Mitchell. With new techniques and the added safety net of clean intermittent catheterization, the complete repair is again a common approach in 2021, now refined, under the coaching of Mike Mitchell himself, by the MIBEC consortium at CHOP, Boston Children’s, and the Children’s Hospital of Wisconsin. The question is where will this ever-changing circle be in 2050? My prediction is that current techniques will continue to improve, and a major adjuvant will be the addition of a “tincture of time” to our initial repairs, be they complete or staged, to achieve the ultimate goal of volitional voiding with continence.

We have shown with urodynamics that the bladder detrusor can function and contract, which allows for volitional voiding. We also know that the exstrophic bladder grows – at all times, from the newborn period when closure is sometimes delayed to allow for bladder plate growth, to the post-closure period, in the modern staged and complete repairs, when continence procedures are performed on only those who have achieved bladder growth to 100 mL. We also have witnessed that the bladder neck can be reconstructed in a way that recapitulates a normal bladder neck, with the ability to coapt and funnel with voiding. If you combine these advances and current observations, with the fact that we know that 20% of children who underwent closure in the past, before much of the modern nuances were known, can void with continence after a single surgery, then it seems that far before 2050 we will be seeing the majority of children born with BE grow into adults with the capability to volitionally void and be continent.

Innovations of surgical technique, detailed 3D imaging, and intraoperative assessments have already advanced our understanding of how we can recapitulate normal functioning anatomy during the initial closure of exstrophy. These combined with adjunctive therapies such as physical therapy to augment the function of pelvic floor muscles, and the addition of time for growth and strength to develop, demonstrate that the future for those with bladder exstrophy is bright.

Allowing time itself to promote continence, will require a new mentality—one that will understand that people, let alone children, do not follow set prescribed timelines. Our new appreciation of individuality will aid in this shift. Gone will be the precept that all 5-year-olds must be out of diapers. If it takes one until the age of 20 to safely become fully dry, and then to live the next 60–80 years with the ability to void and to maintain healthy kidneys, then isn’t that a far better option than to force dryness at the age of 5, and for the bladder to peter out by age 20, followed by 75 years of catheterizations, irrigations, bladder stones, and stomal complications.

By well before 2050 we will know what the optimal course of action is, not just from questioning the few, the believers, but from learning from the patients themselves, as a group—to understand what matters to those actually living with the bladder exstrophy. That is where the goal post really lays.

If science continues to advance as fast as it has for the last 30 years, we will see even greater advances. Perhaps fetal surgery will become so safe that we can close the bladder in utero, to allow for the additional 3–4 months of bladder cycling before birth, thus shifting the timeline for bladder growth. Or, while our current dream is to repair BE to make a functioning bladder, perhaps by 2050 our understanding of the genetics of exstrophy will be robust and we will have a better understanding of what leads to exstrophy, and with the potential of gene editing, we could prevent bladder exstrophy altogether... As Yogi Berra said, “It's tough to make predictions, especially about the future.”

Comment

The bladder exstrophy-epispadias complex is one of the most complex anomalies in pediatric urology, involving anatomic, functional, cosmetic, sexual, reproductive and psychosocial factors. Regionalization of care for rare congenital disorders has long been advocated by physicians and health care leaders, as it has been proven to improve survival and reduce disability. However, it is important to also have a supportive and well-organized healthcare system that allows for access to these centers of excellence in order to prevent disparities between different patient populations.

DSD in Pediatric Urology: What to Expect by 2050

By Anne-Françoise Spinoit

Differences of Sex Development (DSD) is a field where the medical practice has completely changed over the last thirty years, and I believe even more evolution is to be expected in the next decades.

Taking the name related to the condition under the scope, it reflects quite accurately the evolution: Children born with ambiguous genitals used to be referred ‘secretly’ to a surgeon to quickly fix an ‘hermaphrodite’ condition with a surgical intervention meant to allow ‘classification’ of the child into the dichotomy boy or girl. The decision to operate was often taken by the surgeon alone. Along with evolution of patient care towards multidisciplinary decision-making, the ‘intersex’ term for the condition became more popular. Pediatricians, adult and pediatric specialists in endocrinology, gynecology, psychology, genetics widened the perspective from which the condition is examined and created new insights.

True revolution came with the Chicago consensus statement in 2006;9 patient and family involvement, open communication, and avoidance of ‘shameful historical terms’ highlighted a trend which is nowadays peaking. The term Disorders of Sex Development was born. It was probably the stepping stone for acceptance and popularization of what used to be considered as abnormalities and rename it as variation. As patient involvement grew, patients felt the term ‘disorder’ stigmatizing and asked for acceptance of their physical conditions. Where the aim of all medical treatments used to be ‘normalization’ of the differences, acceptance of the differences, sometimes without surgical correction, was the new request. In 2018, the term Disorder of Sex Development was changed to Differences of Sex Development.10

This evolution from a purely surgical to a multidisciplinary care with patient involvement provides better results with less psychological distress.11 However, some patients went even further, founding activists groups fighting against irreversible medical care. It has led to reports and regulations like those from the Human Rights Watch “I want to be like nature made me”, stating surgery is unnecessary, and could be considered as torture in children. Scientific societies strongly reacted against those statements,12 without significant reaction from non-medical groups.

Those reports might give us a glance of what the coming years of DSD patients care might look like.13 Today, watchful waiting and avoiding irreversible surgery has become standard of care, partly under pressure of activists groups. In many countries and centers in Europe, North America and UK, some feminizing surgeries are rarely performed. As we have no long-term follow-up of non-operated DSD patients, their outcome remains unclear.

Surgical experience will have to shift from pediatric professionals to adolescent professionals.

Where the future will take us is unclear. The task of the professionals is to provide excellent follow-up for all patients, and, above all, to listen to the patients who are raised without surgery and, if we see concerning developments there, to report them, and, if necessary, to adjust our approach.

This approach may prevent us from having a group of non-operated activists asking us to adjust our approach in a few decades' time. In this way, we avoid the pendulum swinging too far between the extremes of early and late surgery.

Comment

Caring for patients with DSD continues to be a struggle in the setting of societies that do not totally embrace a more non-binary, fluid view of sexual identity. We hope that in 2050, this will be different. There is widespread concern in the medical community regarding legislation regulating medical care. Most believe that changes in medicine should be based on scientific research and medical guidelines, as these changes are evidence-based and can happen within months and even weeks. It would be impossible to apply legislation in this fast-paced setting. In addition, we know there is nothing absolute in medicine; there is no 100%; There is always an exception to every rule. The viewpoint that every child should be celebrated as an individual is one that we agree is fundamental, yet the very nature of legislation often fails to take into account the specific needs of each patient.

Urologic Management of Spina Bifida in 2050

By Marcela Leal da Cruz

Open spina bifida is a major cause of neurogenic bladder in childhood. A new paradigm was established in this scenario after the MOMS study14 that substantiated the use of fetal surgery as a standard method in trained services. Despite enthusiastic results of the neurological and orthopedic aspects, bladder function did not follow the same path. The prospective series in the post-MOMS era include the American groups involved in MOMS15 and the Zurich group16 which suggest some urologic benefits. The data from our group in São Paulo/Brazil17,18,19 did not show improvements in bladder function after MMC fetal repair.

The development of new approaches in fetal surgery, such as fetoscopy, promises to improve obstetric outcomes. Regarding urological outcomes, Gerber et al evaluated the prevalence of high-risk bladder dynamics among different types of myelomeningocele (MMC) repairs. They observed a decrease in high-risk bladder dynamics between the first and the follow-up (18 months) urodynamic evaluation in fetal surgery groups (35% to 8% in fetoscopic repair, 60% to 35% in open fetal repair), but no change in the postnatal repair group, which remained at 36%. These changes, however, were not statistically significant. In addition, the authors commented that long-term follow-up is needed to evaluate continence outcomes.20

New techniques are being researched to improve the results of fetal surgery. A promising alternative is stem cell therapies. Several investigators demonstrated the therapeutic potential of the intra-amniotic injection of mesenchymal stromal cells derived from the bone marrow, amniotic fluid and embryonic stem cells using experimental models of MMC.21

The advancement in fetal medicine and stem cell therapies bring enthusiasm for new possibilities to obtain good results. In addition, advances in genetic research involving the etiology of MMC may lead to gene therapies that would prevent neural tube defects in the future.

Regarding urological management of MMC, we now have the urodynamic study as a fundamental tool. Maybe, in 2050, urodynamics will allow us to have a continuous bladder pressure recording for a whole day or a few days (similar to ambulatory blood pressure monitoring), which may improve our understanding of individual bladder patterns.

Management of neurogenic bladder principles consists of adequately treating the high-risk bladder to preserve renal function and achieving continence. The treatments consist in use of medication, clean intermittent catheterization and a complex arsenal of reconstructive surgical techniques. Looking to the future, I consider two challenges. The first is to improve results, especially related to continence, through improvements in surgical techniques. The second is, following the trend of advances in medicine, developing technology that restores organic function without the need of external devices or body modifications.

An evolution in nanotechnology may solve these challenges. Nanomedicine can be applied to improve the specificity of a drug’s action, in addition to regenerating and restoring organic functions. Will future generations be able to regenerate the neural tissue affected in MMC or even reprogram the functionality of a neurogenic bladder?

Comment

So much of what we do every day, as pediatric urologists, centers around restoring function to existing anatomy. The neuropathic bladder is one of our biggest challenges. Although there have been significant advancements in the care of spina bifida patients, including fetal intervention, it is exciting to think that pluripotent stem cells could one day develop into a functioning bladder, potentially obviating the need for major reconstructive surgery.

Basic Science Research in Pediatric Urology in 2050

By Luke Harper

Basic science research shapes clinical practice and vice versa. These two fields are intertwined and imagining the future of one requires imagining the future of the other.

Basic science has revealed, more and more, the biological uniqueness of each individual, and hence we move closer and closer to the concept of personalized medicine. Whole-genome sequencing, and the astronomic quantity of data it will bring, will progressively pave the way for more precise patient characterization. Genetic and epigenetic identification will explain not only the existence of medical conditions but also how these conditions will likely evolve or respond to treatments. This will gradually allow for more tailored strategies. By combining the information garnered through the study of genomics, transcriptomics, and proteomics, the complex and highly individual interactions of the human body will progressively unveil themselves.

Clinical research will incorporate experimental models that integrate the uniqueness of the individual, such as “N-of-1” or “adaptive and sequential” clinical trials.22,23 Computer-modeling will allow for extrapolation of individual traits to virtual populations, allowing researchers to interpret results unburdened by variations caused by the biological heterogeneity of a classic study population. These models, along with technological advances such as organs-on-a-chip—i.e., microfluidic cell culture devices that simulate physiological organ responses in vitro—will help do away completely with the need for animal and human testing.24 At a cellular level, patient-derived cellular avatars, i.e., cells harvested then cultivated from an individual, will allow for pre-treatment in vitro testing and individualized treatment customization.25

Research in stem cell tissue engineering will increasingly allow for replacement of failing organs using the patients’ own cells thus avoiding the risks of rejection, or the need for immunosuppressive agents.26

But illness will always be most often the result of the interaction between an individual and his environment and, in this way, basic science will always have to adjust to the changes affecting the world we live in. One of the greatest challenges of the next 30 years will be adapting to our environment. This not only includes the effects of climate change, but also all that we will be exposed to, including pollutants, toxins, germs, viruses, etc…. Our changing environment might deeply impact our biochemical properties, and early detection of some of these biochemical changes will be detectable just by the clothes we wear.27

Of course, as the great scientist Niels Bohr purportedly said, “Prediction is difficult, especially when dealing with the future,” and there is a good chance that future basic research will focus on areas we do not even know exist yet. And, technology has accelerated so much in the past decades that what we have just described might just be the research of 2025. And in reality, by the time we reach 2050, the questions basic science will be concentrating on might well concern the conditions of life on Mars.28

Comment

We live in a world in which randomized control trials are considered the sine qua non of medical research, as they reveal the most generalizable results. It is remarkable to think that the future of medical research may include more N-of-1 or single subject clinical trials, where an individual patient is the sole unit of observation in a study. This would be the ultimate in individualized medical care.

AI for Pediatric Urology in 2050

By Armando J. Lorenzo & Mandy Rickard

Recent years have seen a dramatic interest in the use of cutting-edge analytical tools to evaluate information. Around us, data is captured in exponential amounts, demanding strategies that accurately and efficiently evaluate it. Among the most promising recent advances, is the use of artificial intelligence (AI). This field of computer science aims to develop systems that can perform tasks in a manner that mimics the process in the human brain. The generated algorithms can therefore improve with further refinement and additional data, akin to what we describe as “gaining experience.” Within this umbrella term, Machine learning (ML) is a branch of AI that develops programs and algorithms with the goal of providing computers with the ability to learn an assignment automatically, with limited human intervention and without the need to explicitly program each step. Ultimately, these tools can currently tackle a large number of narrow, well-defined tasks, quickly and accurately, impacting everything around us.

What does the future hold for AI in pediatric urology in the next few decades? Larger and more complicated datasets are going to become commonplace, making traditional statistical tools insufficient. In addition, the demand for precision/personalized medicine along with quick (point of care) analyses to guide clinical care will likely be the rule rather than the exception. Thus, in our specialty (as in many others) the standard will be AI-driven algorithms integrated with commonly employed tools (electronic medical records, image storage platforms), based on a seamless amalgamation with common tools (such as electronic medical records, PACS®). Automated image, data capture and manipulation will aid clinicians in delivering evidence-based care. We should expect that our health care systems will need to adapt with more powerful interfaces, stronger databases, and robust computing power. Similarly, more training in computer science will be required in order to help integrate these tools with clinical care. Undoubtedly, delivery of care will change, and how we train future generations of pediatric urologists will have to adapt. Quicker data collection, on-the-spot analysis, and assisted decision making will demand that all providers learn a new way to integrate with these systems, and fully understand their capabilities and drawbacks.

As is the case with many other emergent technologies, caution is warranted. The quality of the data as well as the use of high-level and appropriate methodology ensures proper development of an initial algorithm.29 However, further steps are needed to ensure generalizability and minimize bias, common problems in many of the tools that are being generated for different classification and prediction products. Equally important is the issue of blind trust in these tools, which commonly have the so-called “black box effect” (i.e., opacity in how the ML algorithm works). The benefits in automation, speed, and ability to deal with complex data becomes meaningless if there is lack of regulation and human supervision.

Comment

John McCarthy, an American computer and cognitive scientist, first described the term artificial intelligence (AI) in 1956 as the science and engineering of making intelligent machines. Now, Fitbit, Apple, and other health trackers can monitor an individual’s heart rate, activity levels, sleep levels, and EKG tracings. In the medical field, we have become accustomed to AI helping us peripherally—scheduling of appointments, online check-ins in medical centers, digitization of medical records, reminder calls for follow-up appointments. The question is whether patients and physicians will ever truly trust AI to help diagnose patients, recommend treatment, make predictions about patients' future health—even with our supervision.

Conclusion

Wayne Gretzky, a famous Canadian ice hockey player once said, “I skate to where the puck is going to be, not where it has been.” Although seemingly impossible, forecasting the future is often the very foundation of innovation, progress, and of success. The validity of the above predictions, of course, can only be determined by an assessment and comparison in 25 years. The challenge will be, therefore, that a future generation of pediatric urologists would assess the validity of the predictions and their impact on the practice of urology in 2050. Our hope is that in 2050, pediatric urologists will take the time to look back at not only our present practice, but our predictions of the future and learn from them in a way that promotes progress.

References

  1. Zinner NR, Enzer S, Brosman SA. Forecasts of Change in Urology. Dephi Future Study, Society of University Urologists. Urology 1991; 37 (5): 491–500. DOI: 10.1016/0090-4295(91)80122-n.
  2. Mahant S, Friedman J, MacArthur C. Renal ultrasound findings and vesicoureteral reflux in children hospitalized with urinary tract infection. Arch Dis Child 2002; 86 (6): 419–420. DOI: 10.1136/adc.86.6.419.
  3. Bjorgvinsson E, Majd M, Eggli DK. Diagnosis of acute pyelonephritis in children: comparison of sonography and 99m-Tc DMSA scintigraphy. AJR AM J Roentgenol 1991; 157 (3): 539–543. DOI: 10.2214/ajr.157.3.1651644.
  4. MacKenzie JR, Fowler K, Hollman AS, Tappin D, Murphy AV, Beattie TJ, et al.. The value of ultrasound in the child with an acute urinary tract infection. Br J Urol 1994; 74 (2): 240–244. DOI: 10.1111/j.1464-410x.1994.tb16594.x.
  5. Rahimzadeh N, Outkesh H, Hoseini R. Serum procalcitonin level for prediction of high-grade vesicoureteral reflux in urinary tract infection. Iran J Kidney Dis 2014; 8 (2): 1058–1108.
  6. Dretler SP. Special article: calculus breakability–fragility and durility. J Endourol 1994: 1–3. DOI: 10.1089/end.1994.8.1.
  7. Ellison JS, MacConaghy B, Hall TL. A simulated model for fluid and tissue heating during pediatric laser lithotripsy. J Pediatr Urol 2020; 16 (5): 626–e1. DOI: 10.1016/j.jpurol.2020.07.014.
  8. Sivaguru M, Saw JJ, Williams JC, Lieske JC, Krambeck AE, Romero MF, et al.. Geobiology reveals how human kidney stones dissolve in vivo. Sci Rep 2018; 8 (1): 1–9. DOI: 10.1038/s41598-018-31890-9.
  9. Sivaguru M, Saw JJ, Wilson EM, Lieske JC, Krambeck AE, Williams JC, et al.. Human kidney stones: a natural record of universal biomineralization. Nat Rev Urol 2021; 18 (7): 404–432. DOI: 10.1038/s41585-021-00469-x.
  10. Hughes IA, Houk C, Ahmed SF, Lee PA, Society LWPE. Consensus statement on management of intersex disorders. Arch Dis Child 2006; 91 (7): 148–162. DOI: 10.1136/adc.2006.098319.
  11. Cools M, Nordenström A, Robeva R, Hall J, Westerveld P, Flück C, et al.. Caring for individuals with a difference of sex development (DSD): a Consensus Statement. Nat Rev Endocrinol 2018; 14 (7): 415–429. DOI: 10.1038/s41574-018-0010-8.
  12. Babu R, Shah U. Gender identity disorder (GID) in adolescents and adults with differences of sex development (DSD): A systematic review and meta-analysis. J Pediatr Urol 2021; 17 (1): 39–47. DOI: 10.1016/j.jpurol.2020.11.017.
  13. Mouriquand P, Caldamone A, Malone P. The ESPU/SPU standpoint on the surgical management of Disorders of Sex Development (DSD. J Pediatr Urol 2014; 10 (1): 8–10. DOI: 10.1016/j.jpurol.2013.10.023.
  14. Crocetti D, Arfini EAG, Monro S. You’re basically calling doctors torturers’: stakeholder framing issues around naming intersex rights claims as human rights abuses. Sociol Health Illn 2020; 42 (4): 943–958. DOI: 10.1111/1467-9566.13072.
  15. Adzick NS, Thom EA, Spong CY, Brock III JW, Burrows PK, Johnson MP, et al.. A randomized trial of prenatal versus postnatal repair of myelomeningocele. N Engl J Med 2011; 364 (11): 993–1004. DOI: 10.1056/NEJMoa1014379.
  16. Brock III JW, Thomas JC, Baskin LS, Zderic SA, Thom EA, Burrows PK, et al.. Effect of Prenatal Repair of Myelomeningocele on Urological Outcomes at School Age. J Urol 2019; 202 (4): 812–818. DOI: 10.1097/JU.0000000000000334.
  17. Mazzone L, Hölscher AC, Moehrlen U, Gobet R. Urological Outcome after Fetal Spina Bifida Repair: Data from the Zurich Cohort. Fetal Diagn Ther 2020; 47 (12): 882–888. DOI: 10.1159/000509392.
  18. Cruz M Leal da, Liguori R, Garrone G, Leslie B, Ottoni SL, Carvalheiro S, et al.. Categorization of bladder dynamics and treatment after fetal myelomeningocele repair: first 50 cases prospectively assessed. J Urol 2015: 1808–1812. DOI: 10.1016/j.juro.2014.10.118.
  19. Parizi JLG, Cruz M Leal da, Andrade MC, Garrone G, Ottoni SL, Cavalheiro S, et al.. A Comparative Analysis of Bladder Pattern of Patients who Underwent In Utero Versus Postnatal Myelomeningocele Repair. J Urol 2020; 203 (1): 194–199. DOI: 10.1097/JU.0000000000000521.
  20. Macedo Jr A, Ottoni SL, Garrone G, Moron A, Cavalheiro S, Cruz ML da. In utero myelomeningocele repair and incidence of lower urinary tract surgery. Results of a prospective study. J Pediatr Urol 2021; 17: 769–774. DOI: 10.1016/j.jpurol.2021.08.007.
  21. Gerber JA, Stocks BT, Zhu H, Castillo H, Castillo J, Borden AN, et al.. Prevalence of high-risk bladder categorization with prenatal and postnatal myelomeningocele repair types. Neurourol Urodyn 2021; 40 (3): 829–839. DOI: 10.1002/nau.24629.
  22. Abe Y, Ochiai D, Masuda H, Sato Y, Otani T, Fukutake M, et al.. In Utero Amniotic Fluid Stem Cell Therapy Protects Against Myelomeningocele via Spinal Cord Coverage and Hepatocyte Growth Factor Secretion. Stem Cells Transl Med 2019; 8 (11): 1170–1179. DOI: 10.1002/sctm.19-0002.
  23. Duan N, Kravitz RL, Schmid CH. Single-patient (n-of-1) trials. A pragmatic clinical decision methodology for patient-centered comparative effectiveness research. J Clin Epidemiol 2013; 66 (8 Suppl): S21–S28. DOI: 10.1016/j.jclinepi.2013.04.006.
  24. Biankin AV, Piantadosi S, Hollingsworth SJ. Patient-centric trials for therapeutic development in precision oncology. Nature 2015; 526 (7573): 361–370. DOI: 10.1038/nature15819.
  25. Wu Q, Liu J, Wang X, Feng L. Organ-on-a-chip: recent breakthroughs and future prospects. Biomed Eng Online 2020; 12 (19): 1–19. DOI: 10.1186/s12938-020-0752-0.
  26. Sayed N, Liu C, Wu JC. Translation of Human-Induced Pluripotent Stem Cells: From Clinical Trial in a Dish to Precision Medicine. J Am Coll Cardiol 2016; 67 (18): 2161–2176. DOI: 10.1016/j.jacc.2016.01.083.
  27. Atala A. Bladder Tissue Engineering: The Past and the Future. Urology 2020; 145 (337-338): 337–338. DOI: 10.1016/j.urology.2020.04.020.
  28. Nguyen PQ, Soenksen LR, Donghia NM. Wearable materials with embedded synthetic biology sensors for biomolecule detection. Nat Biotechnol 2021; 39 (11): 1336–1374. DOI: 10.1038/s41587-021-00950-3.
  29. Bowie D. Life on mars. In the album Hunky Dory released on 17 December 1971, by RCA Records. DOI: 10.2307/j.ctvc774fn.
  30. Kwong JCC, McLoughlin LC, Haider M, Goldenberg MG. Standardized reporting of machine learning applications in Urology: The STREAM-URO Framework. Eur Urol Focus 2021; 7 (4): 672–682. DOI: 10.1016/j.euf.2021.07.004.

Last updated: 2023-05-01 08:35