Society for Fetal Urology 35th Biannual Meeting Summary

The day began at 7:45 am with a lecture entitled "Prenatal Evaluation and Treatment for Fetal Lower Urinary Tract Obstruction" by Mark Johnson, MD, Associate Professor, Department of Ob/Gyn, University of Pennsylvania and The Children's Hospital of Philadelphia. Dr. Johnson showed that lower urinary tract obstruction will lead to oligohydramnios, limb deformities, pulmonary hypoplasia, and possible renal fibrocystic disease. Shunts are placed to help relieve obstruction. When shunts were first employed, they were not as successful as now. It was difficult to diagnose certain disease states such as cloacas.

Ultrasound plays a major role in successful shunt placement. Prenatal evaluation includes high resolution ultrasounds; chorionic villus sampling; renal evaluation by serial bladder drainage; urine electrolytes. Favorable electrolytes are defined as: sodium of <90; chloride <80; osmolarity <180; calcium <7; beta 2 microglobulin <6; and total protein <20. Amnioinfusions during access showed amnion to chorion adhesions in these patients. Shunt placement is difficult. The stent is placed trans abdominal in the mother - trans uterine - then trans abdominal in the fetus - and finally into the fetal bladder. The key maneuver is the deflection of the introducer towards the fetal head during deployment as to avoid displacement. The shunt should be positioned under the abdominal cord insertion, above the suprapubic area just off of the midline.

The long term outcomes for shunts in fetal bladder outlet obstruction have improved. In 1997, 40% of shunts displaced usually because of deployment and/or fetal manipulation. In 2005, the data shows a 91% survival rate with a mean age of delivery at 34.5 weeks. The mean weight of the babies is 2573.5 grams. The mean days from shunt placement to delivery were 84.4 days. The data was to a mean age at 5.83 years of age. Posterior urethral valves accounted for 39%; urethral atresia 22%; and Prune Belly Syndrome 39%. Normal pulmonary function was found in 55% of patients. The urinary tract was also favorable. More than 45% had a GFR of >70ml/min; 22% had renal insufficiency; 33% were ultimately on dialysis; and 33% had a transplant. Bladder function was also favorable showing 61% with a spontaneous void and no post void residual, and approximately 33% on intermittent catheterization.

Laser treatment has become a better option for fetal outlet obstruction if valves are to be treated. It is important to place the shunt before 15 weeks of gestation to optimize the chances of a successful intervention. The mothers did well with no tocolytics and discharged after 2 hours of monitoring. Dr. Johnson's bottom line was, "You do get increased renal function and better outcomes, but these kids still have a lot of problems."

The next lecture given by Craig Peters, MD, Associate Professor of Surgery in Urology, Harvard Medical School, Children's Hospital of Boston was entitled: "Fetal Bladder Outlet Obstruction: Translating Science to the Pateint." He focused on bladder function. Dr. Peters stated that there are four major investigational themes: (1) proteolytic balance; (2) smooth muscle activity; (3) smooth muscle growth regulation; and (4) neural abnormalities.

There is increased bladder wall growth in response to obstruction with reduced bladder wall compliance. Collagen content and concentration increase with increases in TIMP-1 mRNA in obstruction. There is also a decrease in collagenase activity. The genes of regulatory molecules such as TIMP-1 are stretch responsive.

It has also been detected a decrease in growth response to cholesterol depletion via calveoli in cell membranes during obstruction. Angiotensin may also play a role with an effect on baseline tension and contractility. If one blocks angiotensin, then one can potentially alter contractility and tone. He mentioned work done by Darius Bagley in Toronto showing matrix changes in response to mechanical forces that may play a role.

Dr. Peters mentioned mechanistic touch points for fetal bladder outlet obstruction: (1) hypertonicity -proteolytic imbalance; (2) hyperreflexia - abnormal innervation; and (3) myogenic failure - myosin isoform development. Prognostication involves assessment of principle responses to treatment, urine markers, proteomics, and tissue sampling. We need to develop a mechanism specific treatment. For example, gene therapy or things like intermittent catheterization, although crude, very effective.

He concluded by summarizing how to translate science to the patient. He stated that we need to identify the mechanism of relevant change. We need to define pathways of disease progression and key modulations, utilize animal models, validate biomarkers, and finally trial mechanisms for specific interventions.

Dr. Michael Mitchell, MD, Professor of Urology University of Washington, Seattle Children's Hospital then gave his thoughts on "The Changing Bladder of Childhood." He began by stating it seems to be dependent on motion and stress. "All processes are driven by external forces." It is the driving force of evolution. The childhood bladder goes through critical changes early on important for normal function.

The neonate bladder is stable during filling with a low capacity. There is a high post void volume which empties to completion after every third void. Capacity seems to increase in the first few months of life then again at age 3 years. The clinical observations which have been made are: (1) no urine = small bladder and ureters; (2) diversion (e.g. exstrophy) = abnormal bladder and urethra but normal ureters; and (3) obstruction (e.g. valves) = a hypertonic spectrum. He stated that primary valve ablation for PUV is very successful and the majority of poorly functioning early bladders recover well after 1 year of age. Prune belly syndrome and exstrophy are opposite ends of the spectrum encompassing no bladder cycling. The architecture of the Prune Belly bladder is the same as a 21 weeks fetal bladder, mostly a haphazard arrangement. Dr. Mitchell stated that exstrophy bladders seem o be "stuck" in an earlier phase of development at birth. That may be why they respond so well to cycling. It has been his experience that 84% of exstrophy patients are continent (30% without a bladder neck reconstruction) with a very low augmentation rate if closed primarily and the bladder is allowed to cycle.

Dr. Mitchell stated that Type 1 and Type 3 collagen as wellas actin mRNA are similar between functional and defunctionalized bladders in some animal models. He also stated that posterior urethral valves have excessive mechanical stretch on smooth muscle, increased growth factors, and hyperplasia. These are similar to Dr. Peters thoughts on ladder outlet obstruction. Dr. Mitchell stated "Bladder pathology is potentially reversible in young children." He summarized the pathology of the new born encompasses two entities: (1) obstruction group where we need to make a decrease in that obstructive resistance. If it is neurogenic in origin, then by alpha blockers, intermittent catheterization, or urethral dilation. If it is because of valves, then early ablation is key. Dr. Mitchell stated, "Do not divert these children." (2) diverted group - needs repair at birth. Extrophy, epispadias, bilateral ectopic ureters from a single system are some examples. He concluded by stating,"We are at the beginning of a very exciting time."

The day continued with case presentations. The first case was for antenatal intervention for bladder outlet obstruction in a twin pregnancy from Patrick McKenna's group. The teaching point of this case was given in a comment by Dr. Johnson. He stated that the unaffected twin does not help the affected twin as far as amniotic fluid in a dichorionic diamniotic pregnancy. He also stated that maternal coagulopathy is not as high as 25% as stated during the presentation, but is actually rare. CMV found in the patients may play a role, but is an enigma for now. The second case was on postnatal outcome of a patient with severe PBS treated with 32 vesicocentesis and amnioinfusion procedures. The conclusion was that the serial interventions worked, but a shunt may have been placed. Dr Johnson commented that the risk is cumulative for serial interventions so one must be cautious. The notion was that the placenta was anterior so serial interventions was safer. Dr. Johnson did not agree. He stated that with better ultrasonography, the vessels can be visualized and a transplacental approach can be performed with minimal morbidity.

The next presentation of in utero spontaneous intraperitoneal bladder rupture presenting as urinary ascites in two newborn females showed that the leak was on the posterior wall into the culdesac. Rupture is usually due to PUV in boys. It is rare in girls. There is an increased risk of caudal dysplasia and ischemia in a fetus of a diabetic mother. The fourth presentation was antenatally diagnosed neonatal bilateral UPJ obstruction presenting with sudden anuria. Bilateral percutaneous nephrostomy tubes were placed and antegrade studies shoed bilateral severe obstruction. The following antegrade showed complete resolution bilaterally. The questions was…what to do next? It still remains a debate.

Presentation number 5 was the surgical management of a left sided duplicated collecting system and ureterocele pre and post natally. The pathology was corrected in utero with multiple needle punctures of the ureterocele. The post natal outcome was excellent with no obstruction and no reflux. The next presentation was a ureterocele associated with prolonged inability to void after incision. The notion of wind socking of the redundant tissue was excluded by VCUG. It was thought to be myogenic. The 7th presentation was a ureterocele causing bladder outlet obstruction in a female infant. The debate centered on to reimplany a nonfunctioning moiety or to excise. There was no consensus. Presentation 8 was isolated ascites in a female fetus with congenital adrenal hyperplasia. It was thought that the urine traversed the salpinx. Presentation number 9 discussed inguinal bladder herniation in a child. It occurs up to 4% in adults. 80% are recognized intraoperatively. It is rare in children. Up to 16% of the time, the bladder is mistaken for the hernia sac. The repair is a standard hernia repair after reduction.

Presentation 10 was a cloacal anomaly and female pseudohermaphroditism with multiple fluid collections in the abdominal cavity of the fetus in utero. It was part of the urorectal septum malformation sequence described by Dr. Michael Mitchell. There are phallic like structures, spinal problems, Mullerian duct abnormalities and renal issue to mention some associations. Presentation 11 was a case of severe congential midureteral dilation. It is usually due to extrinsic vascular compression, intrauterine ureteritis, or failure of distal cannulization. At 37 to 40 days of gestation, the ureters obliterate and need to recannulize from the middle to out. The next presentation was on the prenatal diagnosis of Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome. Two cases were presented. The entity presents with 88% big bladders; 53% bilateral hydroureteronephrosis, and only 10% with abdominal distention. Fetal bladder length is the most important diagnostic tool and it has to be in millimeters greater than the gestational age plus 12.

Presentation 13 was asynchronous bilateral renal vein thrombosis caused by a left adrenal hemorrhage. It occurs in 5:100,000 neonates with a male to female predilection of 2:1. Up to 68% have a prothrombotic abnormality such as a factor 5 mutation, protein c and s, increased lipoprotein a levels, or an antithrombin deficiency. It occurs on the left more than the right by 79%. Diagnosis is typically made by Doppler renal ultrasound. Management is conservative with fluids. Thrombolytics are controversial. Nephrectomy is not indicated. And finally there is no mortality rate with conservative care. Outcomes are renal atrophy in 89% and up to 34% have hypertension.

The next case was an unexpected pyoureteronephrosis in neonates with ureterocele. The question was to incise or resect the nonfunctioning moiety. Again the answer is a matter of choice. The last presentation was post natal outcomes for megacystis with an anterior urethral valve identified by prenatal screening. Wats first described the anterior valve in 1906. Up to 50% undergo incison while the other 50% need a urethroplasty. The congenital megacystis is associated with high grade VUR. The evaluation of anterior urethral valves is equivalent to posterior urethral valves.

The day adjourned at 4:00pm.

Please log-in or register in order to submit comments.

Powered by AkoComment!