Effects of early vesicostomy in obstructive uropathy on bladder development

Purpose

Creation of a vesico-amniotic shunt for obstructive uropathy removes the normal fetal urination cycle. It is unclear how this affects bladder function at term. The authors measured the bladder volume and reviewed the bladder histology after fetal vesicostomy.

Methods

The authors created an obstructive uropathy in fetal lambs at 60 days’ gestation by ligating the urethra and urachus. Vesicostomy (female) or urethrostomy (male) were performed 21 days after obstruction to release the obstruction. The fetuses were killed at term (145 days).

Results

Thirteen fetuses were shunted. Seven fetuses miscarried after shunting. Six survived, and 3 had a successful shunt with a very small bladder (5 to 7 mL). Two had incomplete shunts that failed some time after shunting. These both had huge bladders (399 mL). In one, the obstruction was unsuccessful. Histologic examination showed that the obstruction caused bladder muscle hypertrophy. Shunted lambs had severe fibrosis of the bladder wall and very poor bladder compliance.

Conclusions

Shunt operations after obstructive uropathy may salvage the kidney but fail to preserve bladder function. The fetus needs a normal urination cycle for normal bladder development. This requirement exists even when the obstruction is successfully bypassed.     

Is a vesicoamniotic shunt intrinsically bad? Shunting a normal fetal bladder

Introduction

We previously demonstrated that in utero vesicoamniotic shunting of obstructive uropathy in fetal lambs produces a shrunken noncompliant bladder. We hypothesized that the normal fetal bladder filling and emptying cycle in fetal life is critical to the development of normal bladder function.

Materials and Methods

We placed vesicoamniotic shunts in 4 normal fetal lambs at 74 days' gestation. The fetuses were delivered at term (145 days), and bladder volume and compliance were measured and compared with those measurements in 3 normal term fetuses. The lambs were then killed and the renal tracts and bladders removed submitted to histologic examination.

Results

All shunted lambs survived to term. Three normal control lambs were delivered at term. The mean bladder volume in shunted lambs was 4 ± 2.8 mL (n = 4) compared with 60 ± 17 mL (n = 3) in control lambs (P < .05). Bladders in the shunted lambs had very poor compliance compared with normal lambs' bladders. Histologic examination of the shunted bladders showed increased fibrosis and distortion of the muscle layers compared with control bladders.

Conclusion

Even in the absence of obstruction, preventing normal bladder filling and emptying in fetal life produces fibrotic bladders with poor compliance.     

Vesicoamniotic shunt for complete urinary tract obstruction is partially effective

Purpose

The long-term outcome for children after antenatal intervention for obstructive uropathies is disappointing. We reported that renal dysplastic changes are well established 3 weeks after obstruction in a fetal lamb model. We used this model to explore renal development and bladder function after fetal intervention.

Methods

We created an obstructive uropathy in fetal lambs at 60 days gestation by ligating the urethra and urachus. A vesicostomy (female) or urethrostomy (male) were performed 21 days later. The fetuses were killed at term (145 days) and bladder volume and compliance were measured. The urinary tract was processed for histologic examination.

Results

Twenty two fetuses were shunted. Nine were miscarried or were still-born. Thirteen survived, and 11 had a successful shunt with a small bladder (8 ± 5 mL) compared with controls (71 ± 19 mL) (P < .05). Shunted bladders had poor compliance. Histologically, they had thickened submucosal connective tissue with hypertrophied muscle. Histology of the renal tissue demonstrated relatively well-preserved renal architecture with reduced nephron mass (oligonephronia) in 2 lambs and multicystic dysplastic change in 3. Six (55%) had normal nephrogenesis.

Conclusions

In our model, shunt operations after obstructive uropathy fail to preserve bladder function. Shunting ameliorated the development of cystic dysplasia, but half of the lambs had oligonephronia or multicystic dysplastic kidney. These might develop renal failure later in life.     

Pressure-limited vesico-amniotic shunt tube for fetal obstructive uropathy

Introduction

In utero shunting (vesico-amniotic shunt) of obstructive uropathy in fetal lambs produces a shrunken, noncompliant bladder. We hypothesized that using a ventriculo-peritoneal shunt for the vesico-amniotic shunt may preserve the filling/emptying cycle and thus normal bladder development.

Materials and Methods

We created obstructive uropathy in 60-day gestation fetal lambs, ligating the urethra and urachus. Vesico-amniotic shunting was performed 21 days later using the valve end of a ventriculo-peritoneal shunt (valve shunt) or silastic tubing (nonvalve shunt). They were delivered at term (145 days), and the bladder volume was measured and compared to normal term fetuses. The lambs were sacrificed, and the kidneys and bladder removed for histology.

Results

Twenty-seven lambs were shunted. Of 14 valve shunts, 8 were effective. Of 13 nonvalve shunts, 11 were effective. The mean bladder volume was 57 ± 41 mL with a valve shunt and 8.8 ± 4.7 mL with a nonvalve shunt (P < .05) (normal term lambs, 65 ± 18 mL, n = 5). Histology of the shunted bladders showed increased fibrosis in the submucosal and muscle layers. This was less obvious in lambs with a valve shunt.

Conclusion

A pressure controlled shunt for fetal obstructive uropathy improves bladder volume but does not prevent bladder wall fibrosis.     

Serial amnioinfusions prevent fetal pulmonary hypoplasia in a large animal model of oligohydramnios

Background/Purpose

Severe neonatal pulmonary hypoplasia incurs mortality rates approaching 71% to 95%. We sought to determine the utility of serial amnioinfusions through a subcutaneously implanted intraamniotic catheter to prevent pulmonary hypoplasia in fetal obstructive uropathy.

Methods

Fetal lambs (n = 32) were divided into 3 groups. Group I (n = 12) underwent a sham operation, group II (n = 15) underwent a complete urinary tract obstruction via ligation of the urachus and urethra with a subcutaneous tunneled intraamniotic port-a-cath without amnioinfusions, and group III (n = 5) underwent a creation of a complete urinary tract obstruction with a port-a-cath as described in group II with serial amnioinfusions. Lung tissue was analyzed by lung volume to body weight ratios and stereology. Statistical analysis was performed by analysis of variance and Bonferroni comparisons (P < .05).

Results

Obstructed fetuses grossly had smaller lungs than treated and control animals. Lung volume to body weight ratios were statistically significant between groups. Airspace fractions were comparable between groups I and III (average = 0.53 and 0.55, respectively), although both were significantly greater than group II (average = 0.48) (P = .049).

Conclusions

Serial amnioinfusions through an intraamniotic port-a-cath prevented pulmonary hypoplasia in an ovine model of complete obstructive uropathy. The use of an easily accessible device for amnioinfusions may be a viable option to treat oligohydramnios.     

Bladder development following bladder outlet obstruction in fetal lambs: optimal timing of fetal therapy

Background

Lower urinary tract obstruction causes both renal failure and bladder dysfunction after birth. This study examined the early bladder wall changes after creating an obstructive uropathy focusing on bladder wall thickness and muscle integrity.

Methods

We created obstructive uropathy in fetal lambs at 60 days' gestation, ligating the urethra and urachus. The fetuses (n = 28) were delivered at 48 hours and 3, 4, 5, 7, and 14 days after obstruction and at term (145 days' gestation). Sham-operated lambs were used as controls (n = 20). Histology samples were stained using α-smooth muscle actin) immunohistochemistry and also hematoxylin-eosin, Masson trichrome, and colloidal Fe stain.

Results

The bladder wall initially expanded and stretched. By day 4, the bladder wall became thicker. Histologically, the bladder in obstructed lambs demonstrated a prominent submucosal fibrotic change by 7 days. The mean bladder wall thickness at 14 days after obstruction was thicker than controls, and fibrosis was prominent.

Conclusion

The initial changes in the bladder wall were expansion of the muscle component followed by fibrosis. The bladder wall thickness dramatically increased 4 to 7 days after obstruction. We conclude that shunting operations to preserve bladder function may be needed earlier than expected.     

Prenatal urinary matrix metalloproteinase profiling as a potential diagnostic tool in fetal obstructive uropathy

Background/Purpose

The diagnostic evaluation, patient stratification, and prenatal counseling for congenital obstructive uropathy remain sub-optimal. Matrix metalloproteinase (MMP) expression profiles are emerging as a valuable diagnostic tool in assorted disease processes. We sought to determine whether congenital obstructive uropathy impacts MMP expression in fetal urine.

Methods

Fetal lambs (n = 25) were divided in two groups: group I (n = 12) underwent a sham operation and group II (n = 13) underwent creation of a complete urinary tract obstruction. Gelatin zymography panels for 4 MMP species were performed on fetal urine in both groups at comparable times post-operatively. Statistical analysis was by the Fisher's exact test (P < .05).

Results

Overall fetal survival was 80% (20/25). A variety of significant differences in MMP expression between the two groups were identified. The following profiles were present only in obstructed animals: any MMP other than MMP-2 (P = .029), including any MMP other than 63 kDa and 65 kDa (P = .009); 2 or more MMPs excluding MMP-2s (0.029); and 3 or more MMPs (P = .029).

Conclusions

Limited matrix metalloproteinase expression is present in the urine of normal ovine fetuses. Fetal obstructive uropathy impacts urinary MMP expression in various distinguishable patterns. Prenatal urinary MMP profiling may become a practical and valuable diagnostic tool in the evaluation of congenital obstructive uropathy.     

Lung function in lambs with diaphragmatic hernia after reversible fetal tracheal occlusion

Background/Purpose

Short-duration resuscitation (≤4 hours) of lambs with diaphragmatic hernia treated in utero with tracheal occlusion have shown improved lung function compared with untreated diaphragmatic hernia. This may be a transient phenomenon in the treated diaphragmatic hernia lambs because of surfactant deficiency. Our objective was to analyze the effect of fetal tracheal occlusion with or without release of the occlusion 1 week before delivery on pulmonary function during a longer period of resuscitation (8 hours) in the diaphragmatic hernia lamb model.

Methods

Four groups were compared: diaphragmatic hernia (n = 5), diaphragmatic hernia and tracheal occlusion until delivery (n = 5), diaphragmatic hernia and tracheal occlusion with release of the occlusion 1 week before delivery (n = 5), and normal controls (n = 4).

Results

Despite persistently decreased surfactant levels, diaphragmatic hernia lambs treated with tracheal occlusion had normal-sized lungs with marked improvement in lung function and gas exchange over 8 hours when compared with untreated lambs with diaphragmatic hernia. Release of the tracheal occlusion 1 week before delivery added no benefit.

Conclusions

It appears that surfactant-independent mechanisms such as pulmonary growth and structural changes are of foremost importance in relating to improved compliance, oxygenation, and ventilation of diaphragmatic hernia lambs treated with tracheal occlusion.     

The 16 golden hours for conservative treatment in children with postoperative small bowel obstruction

Background

Conservative treatment of postoperative small bowel obstruction in children is widely accepted, provided that there are no clinical signs of bowel strangulation. However, the length of time surgery can be safely deferred remains unclear.

Purpose

The aim of this study was to determine the time limit for observant management of postoperative small bowel obstruction.

Methods

The medical records of 128 children with 174 episodes of postoperative small bowel obstruction were reviewed.

Results

Spontaneous resolution occurred in 63% of cases, 85% within 48 hours of admission. Bowel compromise was noted in 31% of the operated cases, and about half of them underwent bowel resection, accounting for 6% of all admissions. None of the cases treated surgically within 16 hours of admission was associated with bowel strangulation or need for resection.

Conclusions

In children presenting with postoperative small bowel obstruction, prolonging observant treatment for more than 48 hours yields only a small benefit in terms of spontaneous resolution. Bowel strangulation can occur within 16 hours of admission. On the basis of these findings, we suggest raising the index of suspicion for compromised bowel after 16 hours and making the decision for surgery at around 48 hours.     

Vein and artery growth after anastomosis with vascular closure staple clips vs interrupted polypropylene suture: application in pediatric vascular surgery

Background/Purpose

Alternatives are still being sought in vascular surgery to address the problem of arrested growth after anastomosis in growing vessels, and opinions differ widely regarding the most suitable technique. This study compared vascular growth and permeability after anastomosis using the latest-generation vascular closure staple (VCS) system and the conventional suture technique to ascertain which approach yielded better results.

Methods

Thirty 55-day-old lambs underwent end-to-end anastomosis of the carotid artery and jugular vein. Serial ultrasonography and angiography were carried out over the ensuing 6-month growth period, after which lambs were euthanized.

Results

Both VCS clips and polypropylene suture allowed longitudinal and transverse vessel growth; however, longitudinal growth was significantly greater in clip-closed vessels than in either sutured or untreated vessels.

Conclusions

The results obtained for vascular growth and permeability suggest that VCS clips may provide a suitable alternative to conventional suture in pediatric vascular surgery.     

Addition of epinephrine to epidural bupivacaine infusions following initiation of labor analgesia with epidural fentanyl

Study Objective

To evaluate the analgesic effects of the addition of epinephrine to a bupivacaine epidural infusion in early labor after a fentanyl bolus, following a lidocaine-epinephrine test dose.

Design

Randomized, double-blinded study.

Setting

Labor suite of a tertiary care hospital.

Patients

60 ASA physical status 1 and 2, laboring, nulliparous women.

Interventions

All laboring women received a 3 mL epidural test dose of 1.5% lidocaine with 1:200,000 epinephrine, followed by a fentanyl 100 μg bolus in 10 mL of diluent volume. Patients were randomized to receive one of two continuous epidural infusions: bupivacaine 0.625 mg/mL at 10 mL/hr (control group) or bupivacaine 0.625 mg/mL with epinephrine 5 μg/mL at 10 mL/hr (epinephrine group).

Measurements

Time to re-dose, pain scores, and side effects were recorded.

Main Results

The mean duration of satisfactory analgesia prior to re-dose was 159 ± 62 min for the control group and 221 ± 111 min for the epinephrine group (P < 0.02). Pain scores were significantly higher in the control group than the epinephrine group at two time periods: 2.5 hours and 4.5 hours (P < 0.04).

Conclusions

The administration of 0.625 mg/mL bupivacaine with epinephrine 5 μg/mL at 10 mL/hr, compared with plain 0.625 mg/mL bupivacaine at 10 mL/hr, provided a longer time to re-dose, decreased pain scores at two time intervals, and had no significant difference in duration of labor or side effects.     

Innovative and cost-effective management of large omphalocele

Background/Purpose

The aim of this study was to develop a method of management of large omphalocele, with easily available inexpensive materials. The efficacy of using the plastic of urine collection bag and paper stapler, in creating the “silo” for the management of 3 newborns with such defects, were assessed.

Methods

All operations were done within 36 hours of birth. A silo was created with the plastic of a sterile urine collection bag, which was stapled with a paper stapler at its free margin. The omphalocele was gradually reduced every 24 to 48 hours, using the stapler, until the contents were reduced, when the abdominal wall was repaired.

Results

The mean time taken to close the abdominal defect was 34 days. All patients could be breast-fed from 48 hours after the first stage is done. Rooming in was done by day 7. None of the babies required assisted ventilation.

Conclusion

This method is simple and cost-effective, using minimally expensive, easily available materials.     

Correlation between prenatal urinary matrix metalloproteinase activity and the degree of kidney damage in a large animal model of congenital obstructive uropathy

Background/Purpose

We aimed to determine whether the profile of matrix metalloproteinase (MMP) activity in fetal urine correlates with the degree of kidney damage in the setting of congenital obstructive uropathy.

Methods

Fetal lambs underwent either a sham operation or creation of a complete urinary tract obstruction. Necropsies were performed before term, when urinary MMP profiling was performed by zymography; and kidney damage was assessed histologically by multiple semiquantitative analyses and histomorphometric measurements.

Results

There was a significant correlation between inner medullary thickness and MMP-9 (P = .005) and 63-kd MMP-2 (P = .019) activities. In like manner, the only MMPs associated with kidney fibrosis were MMP-9 and 63-kd MMP-2. Matrix metalloproteinase-9 activity was a highly significant independent predictor of the total combined kidney fibrosis score (P < .001) as well as of higher fibrosis grades in each of 6 kidney areas analyzed (all with P < .01). The activity of 63-kd MMP-2 correlated significantly with higher fibrosis in select areas.

Conclusions

In a fetal ovine model, urinary MMP activity correlates with the degree of kidney damage. The presence of MMP-9 (in particular) and that of 63-kd MMP-2 are independent predictors of severity. Prenatal urinary MMP profiling may enhance patient stratification and counseling in the setting of congenital obstructive uropathy.     

Hepatic surgery at a VA tertiary medical center: lessons learned

Background

The development of a hepatic surgery center within a US Department of Veterans Affairs hospital is dependent on proper training and institutional support, which can translate into low operative morbidity and mortality rates.

Methods

Patients who underwent hepatic procedures between 2003 and 2009 were retrospectively reviewed. A subset analysis of laparoscopic liver resections for patients with hepatocellular cancer (HCC) was performed. One hundred twenty-six patients underwent 130 hepatic procedures, 65% of which were hepatic resections. Ninety-seven percent of cases were for malignant disease, including HCC (70%).

Results

The morbidity and mortality rates were 15.5% and 2.4%, respectively. For patients with HCC there was no difference in operative outcomes or overall survival when procedures were performed laparoscopically.

Conclusions

A Veterans Affairs (VA) hospital specializing in hepatic surgery can achieve low complication rates comparable with those of high-volume centers. The numbers of patient referrals and hepatic resections and the proportion of laparoscopic operations increased after the creation of a dedicated hepatic surgery center within a single VA hospital.     

Posttraumatic small bowel obstruction in children

Background

The diagnosis of intestinal injuries in children after blunt abdominal trauma can be difficult and delayed. Most children who suffer blunt abdominal trauma are managed nonoperatively, making the diagnosis of intestinal injuries more difficult. We sought to gain information about children who develop intestinal obstruction after blunt abdominal trauma by reviewing our experience.

Methods

Review of records from a pediatric tertiary care center over an 11.5-year period revealed 5 patients who developed small bowel obstruction after blunt trauma to the abdomen. The details of these patients were studied.

Results

All patients were previously managed nonoperatively for blunt abdominal trauma. Intestinal obstruction developed 2 weeks to 1 year (median, 21 days) after the trauma. Abdominal x-ray, computerized tomography scan, or barium meal studies were used to establish the diagnosis. The pathology was either a stricture, an old perforation, or adhesions causing the intestinal obstruction. Laparotomy with resection and anastomosis was curative.

Conclusions

Posttraumatic small bowel obstruction is a clinical entity that needs to be watched for in all patients managed nonoperatively for blunt abdominal trauma.     

Prevention of seroma formation after mastectomy and axillary dissection by lymph vessel ligation and dead space closure: a randomized trial

Introduction

We aimed to reduce the incidence of seroma formation by altering surgical technique.

Methods

Two hundred one breast cancer patients were randomly divided into 2 arms: arm 1 was operated on using an altered surgical technique, which is to ligate all of the tissue connecting axillary vein bundles to the specimen, to suture the anterior edge of the latissimus dorsi to the chest wall, and to fix the skin flap to the underlying muscle by subcutaneous sutures; arm 2 was operated on using the conventional technique.

Results

The drainage volume, in the initial 3 days, for patients in arm 1 was significantly less than that for patients in arm 2 (P < .01). The duration of drainage in arm 1 was shorter than that in arm 2 (P < .01). The incidence of seroma formation in arm 1 (2%) was significantly less than that in arm 2 (14%) (P < .01).

Conclusion

The modified operating technique is an effective approach to reducing the incidence of seroma formation after mastectomy and axillary dissection.     

The optimal dose of Adriamycin to create a viable rat model potentially applicable to congenital obstructive uropathy

Purpose

The Adriamycin rat model is an established model for different organ anomalies including congenital obstructive uropathy. In the current study, we carried out a dose-response analysis to find out the optimal dose of Adriamycin to create a viable rat model of obstructive uropathy.

Methods

Thirty time-mated Sprague-Dawley rats were divided into 5 groups including 1 control group and 4 different treatment groups. The 4 Adriamycin dosage regimens investigated in this study were 1.25, 1.5, 1.75, and 2 mg/(kg d). Experimental rats (n = 24) were injected intraperitoneally with different doses of Adriamycin on gestational days 7 to 9 (6 rats in each group). Control rats (n = 6) were injected with an equivalent volume of saline on the same days. Viable term fetuses were harvested on gestational day 21 by cesarean delivery and dissected under a dissecting microscope. Serial transverse sections from urinary tract system were obtained for histological examination.

Results

One hundred thirty-three viable fetuses were recovered from Adriamycin-treated rats, and 50 were from rats in the control group. There were no resorptions in the control group; however, 52 resorptions were recorded in Adriamycin groups. The rates of hydronephrosis and resorptions were 60% and 0%, 80.5% and 5.8%, 100% and 17.3%, and 100% and 76.9% at doses of 1.25, 1.50, 1.75, and 2 mg/(kg d), respectively. Histologic examination of the kidneys in the treated groups showed a significant decrease in renal parenchyma compared with the control group.

Conclusions

The dosage of 1.5 mg/(kg d) of Adriamycin yielded the highest number of viable hydronephrotic fetuses. At this dose, urinary abnormalities are milder; but the highest number of viable fetuses is provided, which is necessary to create a reproducible and viable animal model.     

Topical head cooling during rewarming after experimental hypothermic circulatory arrest

Background

The aim of this study was to evaluate the potential neuroprotective effect of topical head cooling during the first 2 postoperative hours after experimental hypothermic circulatory arrest.

Methods

Twenty pigs underwent a 75-minute period of hypothermic circulatory arrest and were randomly assigned to rewarming to 37°C or to undergo topical cooling of the head for 2 hours from the start of rewarming followed by a period of external rewarming to 37°C.

Results

The 7-day survival rate was 70% in the control group and 60% in the topical head cooling group. Despite brain tissue oxygenation, intracranial pressures, mixed oxygen venous saturation, oxygen consumption, and extraction tended to be favorable in the topical head cooling group as a clear effect of mild hypothermia. The latter group had significantly higher postoperative brain lactate and pyruvate ratios, and lactate and glucose ratios. Furthermore, the topical head cooling group had worse fluid balance throughout the postoperative period. Brain histopathologic scores were comparable with the study groups, but among 7-days survivors these scores tended to be worse in the topical head cooling group.

Conclusions

Topical cooling of the head during the first 2 postoperative hours after experimental hypothermic circulatory arrest does not appear to provide any neuroprotective effect.     

Repair of Chiari III malformation using cranioplasty and an occipital rotation flap: technical note and review of literature

Background

Chiari III malformation (CM3) is rare among Chiari malformations (I-IV). Its definition has been expanded to include caudal medullary displacement and hindbrain herniation into encephaloceles in lower occipital and high cervical regions. Prognosis is recorded as dismal, with respect to survival and functional outcome.

Methods

We describe the presentation, radiologic evaluation, and repair of this malformation using methyl-methacrylate cranioplasty and an occipital scalp rotation flap for closure. Outcome after surgery is addressed.

Results

Adequate closure of the defect and protection of underlying structures was achieved without undue stress at incision site.

Conclusions

This method of closure can be considered in cases of large occipital and cervical encephaloceles with poor skin cover and added osseous anomalies around the foramen magnum.     

Optimal timing of prenatal treatment of obstructive uropathy in the fetal lamb

Purpose: It was still unclear how urinary tract obstruction alters normal nephrogenesis and leads to renal dysplasia. The authors created an obstructive uropathy model in fetal lambs and reviewed the pathology of the obstructed kidney to determine the optimal timing for decompression of the obstruction.Methods: Obstructive uropathy was created in fetal lambs at 60 days’ gestation by ligating the urethra and urachus. They were delivered 20 to 31 days later by cesarian section. The kidneys were processed for histologic examination.Results: Thirty-four 60-day lambs were operated on. Dysplastic changes were noted in 25 fetuses, and 24 fetuses had cysts in the nephrogenic zone. The cystic components in multicystic dysplastic kidneys (MCDK) are mainly in the proximal tubules.Conclusions: In utero urinary tract obstruction causes reduction of numbers of functioning nephrons and produces cysts in the nephrogenic zone and in the deeper cortex. These cysts and dilated proximal tubules suppress new nephron formation. Twenty days after obstruction, there were early features of dysplasia, but the nephrogenic zones still were present. Early shunting may salvage renal function.