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.     

Tumor characteristics and patient outcomes are similar between invasive lobular and mixed invasive ductal/lobular breast cancers but differ from pure invasive ductal breast cancers

Background

The aim of this study was to investigate the clinical characteristics associated with invasive lobular cancer (ILC) and mixed invasive ductal cancer (IDC) and ILC compared with IDC.

Methods

From 1996 to 2006, 4,336 patients with IDC, ILC, and mixed breast cancers were identified. Clinical variables were compared using χ² and Fisher's exact tests. Kaplan-Meier survival curves were constructed.

Results

Patients included 3,595 (83%) with IDC, 480 (11%) with ILC, and 261 (6%) with mixed cancers. Patients with ILC and mixed cancers were more likely to have low-grade and estrogen-positive and progesterone-positive tumors but were diagnosed at higher stages of disease compared with patients with IDC (P < .05 for each). Patients with IDC had the poorest 5-year (80%) and 10-year (61%) survival compared with patients with ILC (87% and 68%) and mixed (84% and 69%) cancers (P = .029).

Conclusions

Although patients with ILC and “mixed” cancers are diagnosed with more advanced disease, their survival is superior to patients with IDC.     

The early effects of urinary tract obstruction on glomerulogenesis

Purpose

Our obstructive uropathy model in fetal lambs showed that renal cystic changes appeared 3 weeks after obstruction. In this study, the authors investigated the changes resulting from complete urinary tract obstruction in the first 7 days after obstruction.

Methods

An obstructive uropathy was created in fetal lambs at 60 days’ gestation by ligating the urethra and urachus. They were delivered 48 hours, 3 days, 5 days, and 7 days later by cesarian section. The kidneys were removed and processed for histologic examination.

Results

Eighteen fetuses were operated on and 15 (4 at 48 hours, 4 at 3 days, 2 at 5 days, and 5 at 7 days; 83%) survived. Macroscopically, bladder dilatation and slightly dilated ureters were identified from 48 hours. Microscopically, dilatation of proximal tubules started from 48 hours after obstruction and increased by 7 days. Glomerular cysts in the nephrogenic zone also were identified from 48 hours. Dysplastic changes were not found.

Conclusions

The first areas in the developing kidney that suffer damage after obstructive uropathy are the proximal tubule and the nephrogenic zone. This change started 48 hours after obstruction. Shunting procedures need to be performed considerably earlier than previously thought.     

Detecting cholesteatoma with non-echo planar (HASTE) diffusion-weighted magnetic resonance imaging

Objective

The purpose of this study was to evaluate the diagnostic performance of half-Fourier-acquisition single-shot turbo-spin-echo (HASTE) diffusion-weighted magnetic resonance imaging (DWMRI) in the detection of cholesteatoma.

Study Design

Prospective blinded comparative study.

Setting

London teaching hospital.

Subjects and Methods

Subjects comprised 32 consecutive patients with suspected primary or residual cholesteatoma. HASTE DWMRI was performed on all patients an average of three months before mastoid surgery and evaluated for the presence of cholesteatoma. Radiological findings were correlated with intraoperative findings.

Results

HASTE DWMRI accurately predicted the presence or absence of cholesteatoma in 30 of 32 patients. Residual cholesteatoma was correctly diagnosed by DWMRI in 12 of 14 cases and correctly excluded in six, with two false-negative results caused by movement artifact and keratin pearls less than 2 mm. All primary cholesteatomas were correctly identified. Sensitivity and specificity were 0.93 (95% confidence interval [CI] 0.75-0.99) and 1.00 (95% CI 0.54-1.0), respectively, whereas positive and negative predictive values were 1.00 (95% CI 0.86-1.00) and 0.75 (95% CI 0.35-0.97), respectively.

Conclusion

Our study supports the increasing but small body of evidence that non-echo-planar imaging (i.e., HASTE) DWMRI performs well in the detection of cholesteatoma. We propose that HASTE DWMRI should be performed on all patients before their second-look surgery to provide valuable information to the operating surgeon.     

Surveillance of bacteriological examinations at hospitalization in a pediatric surgical ward

Purpose

Bacteriological examinations at hospitalization were monitored to identify carriers of pathogenic bacteria and prevent the outbreak of nosocomial and postoperative infections.

Methods

In 557 patients, bacteriological examinations were performed within 48 hours after hospitalization. All people were instructed to wash their hands before and after treating carriers of methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE), and/or Pseudomonas aeruginosa (PA). The disposal of stool and urine of carriers was segregated instead of administration of sensitive antibiotics.

Results

The 1176 samples comprised 557 throat swabs, 532 stool samples, and 87 other samples. At hospitalization, 9.2% of the patients were carriers of MRSA; 22.3% of the patients were carriers of MRSA, MRSE, PA, and/or other pathogenic bacteria. This percentage increased to 29.3% in 352 patients with a history of hospitalization, and 35.2% in 244 patients who were hospitalized within 1 year after previous hospitalization. Nosocomial and postoperative infections did not occur during the study period.

Conclusion

Many patients were detected as carriers of pathogenic bacteria at hospitalization. A history of hospitalization was found to be a risk factor for carrying pathogenic bacteria; hospitalization within 1 year after previous hospitalization was a high-risk factor.     

Prenatal risk stratification for isolated congenital diaphragmatic hernia: results of a Japanese multicenter study

Background/Purpose

The aim of this study was to establish a prenatal prognostic classification system for risk-stratified management in fetuses with isolated congenital diaphragmatic hernia (CDH).

Methods

A multi-institutional retrospective cohort study of isolated CDH, diagnosed prenatally in fetuses delivered during the 2002 to 2007 period at 5 participating institutions in Japan, was conducted. The risk stratification system was formulated based on the odds ratios of prenatal parameters for mortality at 90 days. The clinical severity in CDH infants were compared among the stratified risk groups.

Results

Patients were classified into the 3 risk groups: group A (n = 48) consisted of infants showing liver-down with contralateral lung-to-thorax transverse area ratio (L/T) ratio ≥0.08; group B of infants showing liver-down with L/T ratio <0.08 or liver-up with L/T ratio ≥0.08 (n = 35), and group C of infants showing liver-up with L/T ratio <0.08 (n = 20). The mortality at 90 days in groups A, B, and C were 0.0%, 20.0%, and 65.0%, respectively. The intact discharge rates were 95.8%, 60.0%, and 5.0%, respectively. This system also accurately reflected the clinical severity in CDH infants.

Conclusions

Our prenatal risk stratification system, which demonstrated a significant difference in postnatal status and final outcome, would allow for accurate estimation of the severity of disease in fetuses with isolated CDH, although it needs prospective validation in a different population.     

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.     

Anxiety Levels Observed in Candidates for Liver Transplantation

Introduction

Anxiety can be considered an emotional state that does not present itself at the same intensity in all patients, and can be classified into 3 levels: mild, moderate, and severe. The patient, upon entering the waiting list for transplantation, reflects on the decision taken, which leaves him constantly anxious about the idea of possible death.

Objective

This study had the aim of evaluating the degree of anxiety observed in orthotopic liver transplantation (OLT) candidates and whether there was a correlation between anxiety and etiologic diagnosis.

Methods

This study was a prospective study where the patients underwent psychological evaluation by Beck Anxiety Inventory (BAI). The anxiety level was minimal, mild, moderate, or severe. The Model for End-Stage Liver Disease (MELD) score and etiology were recorded.

Results

The level of anxiety found were as follows: 55% minimal, 27% mild, 12% moderate, and 7% severe. The correlation between level of anxiety and etiologic diagnosis showed that 71% of patients with alcoholic cirrhosis and 60% of those with liver cancer showed a minimal degree of anxiety and 27% of patients with autoimmune cirrhosis had severe anxiety.

Conclusion

We found that in patients with autoimmune hepatitis, the degree of anxiety was more pronounced. It is believed that the absence of physical symptoms is an important factor when observing anxiety in OLT candidates.     

Extracorporeal membrane oxygenation is superior to right ventricular assist device for acute right ventricular failure after heart transplantation

Background

Acute right ventricular failure after heart transplantation is a life-threatening condition, and sometimes the use of mechanical circulatory support is inevitable. The aim of this retrospective study was to investigate the effectiveness of two different mechanical circulatory support systems for this indication.

Methods

From 1984 to 2003, 28 heart transplant recipients exhibited right ventricular failure resistant to drug therapy. Right ventricular assist device (n = 15) or extracorporeal membrane oxygenation (n = 13) was implanted to support the failing heart.

Results

Overall in-hospital survival was 43%. In the right ventricular assist device group, only 2 patients (13%) could be weaned from mechanical circulatory support compared with 10 patients (77%) in the extracorporeal membrane oxygenation group (p = 0.001). Retransplantation was necessary in 6 patients in the right ventricular assist device group and in 1 patient in the extracorporeal membrane oxygenation group (p = 0.049). There was no difference in patient survival between groups, but graft survival was significantly better in the extracorporeal membrane oxygenation group (p = 0.005).

Conclusions

In view of these results, extracorporeal membrane oxygenation seems to be the better option as mechanical circulatory support for right ventricular failure in heart transplantation.     

Psychometric properties of an integrated assessment of technical and communication skills

Purpose

The Integrated Procedural Performance Instrument (IPPI) consists of clinical scenarios in which bench-top models are positioned to simulated patients. Trainees are required to perform technical skills while engaging with the patient. The purpose of this study was to determine whether an IPPI format examination could discriminate between different levels of trainees.

Methods

Sixteen fourth-year medical students and 16 first-year surgery residents participated in 4 IPPI scenarios. Videotaped performances were scored by 2 blinded independent clinician raters on previously validated instruments: checklist of technical skills, Global Rating Scale of technical skills, and communication scale. We conducted separate mixed design analyses of variance (level × cases) on the 3 scales.

Results

Residents performed better than medical students on the checklist (74% vs 60%, P < .05), the Global Rating Scale of technical skills (75% vs 56%, P < .01), and the coherence communication subscale (79% vs 69%, P < .05).

Conclusions

An IPPI examination discriminated between students' and residents' technical skills and coherence in communication skills. It also highlighted a potential gap in the training of residents' communication skills.     

Extracorporeal membrane oxygenation as a lifesaving modality in the treatment of pediatric patients with burns and respiratory failure

Purpose

Several case series have described successful utilization of extracorporeal membrane oxygenation (ECMO) for the treatment of pediatric burn patients with respiratory failure. This study examines the Extracorporeal Life Support Organization registry experience in the treatment of these patients.

Methods

The Extracorporeal Life Support Organization registry was queried from 1999 to 2008 for all patients not older than 18 years who suffered a burn-related injury.

Results

Thirty-six patients met inclusion criteria. The mean age was 4.45 years, with an average weight of 20.9 kg. Survivors vs nonsurvivors had a shorter average time to ECMO (97 vs 126 hours, P = .890) and shorter average ECMO run times (193 vs 210 hours, P = .745). Seventeen patients underwent venovenous ECMO and 19 patients underwent venoarterial ECMO, with survival of 59% (n = 10) and 47% (n = 9), respectively (P = .493; odds ratio, 1.587; 95% confidence interval, 0.424-5.945). Overall survival was 53% (n = 19). Complications occurred in 28 patients (33 mechanical, 101 medical). The venoarterial group had 21 mechanical (n = 8) and 61 medical complications (n = 17), compared with the venovenous group with 12 mechanical (n = 8) and 40 medical complications (n = 11).

Conclusions

Extracorporeal membrane oxygenation can be a lifesaving modality for pediatric burn patients with respiratory failure. Survival is comparable to the reported survival of non-burn-related pulmonary failure pediatric patients requiring ECMO.     

Do patients undergoing parathyroidectomy for primary hyperparathyroidism in San Francisco, CA, and Bursa, Turkey, differ?

Background

To compare the preoperative clinical symptoms and associated conditions and findings in operations in age- and sex-matched patients with primary hyperparathyroidism (PHPT) living in the two different regions of the world to determine whether PHPT differs in various countries.

Methods

Fifty-two patients from Bursa, Turkey were matched with 52 age and sex matched patients from San Francisco, USA. Patients' preoperative symptoms, biochemical and radiologic findings and surgical procedures were documented.

Results

More patients in the American Group (15%) had preoperatively persistant or recurrent hyperparathyroidism, P = 0.016. Serum parathyroid hormone levels were higher in Turkish group (546 ± 75.33 pg/mL) than in American group (146 ± 75.33 pg/mL). More Turkish patients had osteoporosis (P < 0.05). The size of parathyroid adenomas was significantly greater in Turkish patients (25.2 ± 1.18 mm) than in American patients (17.5 ± 1.18 mm), P < 0.001.

Conclusions

Patients with PHPT from Bursa, Turkey have higher plasma parathyroid hormone levels, larger parathyroid adenomas and more severe bone disease than in age and sex matched patients with PHPT in San Francisco.     

Subcutaneous transplantation may not be an appropriate approach for the islets embedded in the collagen gel scaffolds

Background

Synthetic extracellular matrix (ECM) has been shown to be efficient to preserve the function of transplanted islets. In this study using a mouse model, we sought to determine whether subcutaneous transplantation was a convenient procedure for achieving normoglycemia.

Methods

We performed in vitro tests as well as morphologic observations and Western blotting to establish that embedded islets survived better than non-embedded islets. Streptozotocin-induced diabetic mice (BALB/c) were transplanted with ECM-embedded syngeneic islets via the subcutaneous (SC; n = 5) or subrenal capsule (SRC; n = 6) routes. We measured mean blood glucose levels at various points from pretransplantation to postoperative day 14, and examined immunohistochemistry staining for insulin in the transplant grafts on day 14.

Results

Islets transplanted with ECM gel retained better structure and developed a functional vasculature. Western blotting showed more caspase-3 expressed in the non-embedded islets, which indicated more islet cells undergoing apoptosis. On the first day after transplantation, glucose levels were significantly decreased in the SRC group compared with the SC group: 383.33 ± 44.50 mg/dL to 80.67 ± 16.85 mg/dL versus 414.00 ± 92.33 mg/dL to 278.28 ± 121.80 mg/dL (P < .05). Glucose levels were better maintained in the SRC group than the SC group over 14 days. Immunohistochemistry staining for insulin showed fewer islets in the SC group.

Conclusion

Embedded islets with ECM gel functioned better than non-embedded ones in vitro. However, the subcutaneous route may not be an ideal site for islet transplantation.     

Total oesophagogastric dissociation: experience in 2 centres

Background/Purpose

Neurologically impaired (NI) children have an increased incidence of gastroesophageal reflux and many will require surgery.

Methods

The case notes of 50 NI children who underwent total oesophagogastric dissociation (TOGD) were reviewed. Thirty-four were done as a primary procedure, and 16 were rescues for failed fundoplications.

Results

There was no operative mortality. Morbidity consisted of 1 subphrenic collection, 1 oesophagojejunal dehiscence and 2 stenoses that responded to dilatation, and 2 bowel obstructions. In 1 case, partial gastric resection was needed because of transhiatal herniation of stomach. Gastrostomy feeding was established by 3 to 5 days. The mean hospital stay was 10.9 days. At 4 months to11 years of follow-up, there was no recurrence of reflux. Children who could swallow enjoyed oral feeds. Their general health and weight SD scores improved. Food aspiration, chest infections, and hospitalizations were reduced, with an improvement in quality of life. There were 5 late deaths in the “primary” and 7 in the “rescue” group from deterioration in their original condition.

Conclusion

Total oesophagogastric dissociation is a safe and versatile procedure without immediate mortality and limited surgery-related morbidity. Review of our practice suggests TOGD should be considered as a primary procedure in severely NI children with gastroesophageal reflux and significant oropharyngeal incoordination and dependence on enteral tube feeding. Rescue TOGD carries a greater morbidity because of previous surgery with consequent difficult dissection, poor oesophageal tissue, and higher incidence of vagal nerve injury.     

Cystic biliary atresia: an etiologic and prognostic subgroup

Introduction

Cystic biliary atresia (CBA) is an uncommon variant of biliary atresia (BA) in which prognosis may be relatively favorable but liable to misdiagnosis as choledochal cyst, and potentially offers insights into the etiology of BA. Because some cases can be detected antenatally, CBA in general may have its origins in utero life. We assessed our experience with CBA.

Methods

Single-center retrospective review of infants with CBA over a 13-year period (January 1994 to December 2006) was done. Data are given as medians (range).

Results

Of 270 infants with BA, 29 (9 male) were identified as CBA. Antenatal ultrasonography had detected an abnormality in 12 (41%) infants at a median of 22 weeks (17-34 weeks) of gestation. All infants underwent postnatal excision and Kasai portoenterostomy (KP). Those with antenatally detected CBA came to surgery younger (36 [14-67] vs 48 days [35-147 days], P = .004). Twenty cysts (69%) had a fibroinflammatory wall with no biliary epithelial lining and 6 (26%) contained bile. Age at KP was significantly and positively correlated (r = 0.46, P = .01) with liver fibrosis, as assessed in liver biopsy materials obtained at KP, but not with grade of “hepatocyte disarray” (P = .74). Twenty infants (69%) cleared their jaundice (bilirubin <20 μmol/L) within 6 months after KP. Age at KP markedly affected outcome.

Conclusion

Cystic BA is a clinically distinct variant of BA. Despite onset in prenatal life, earlier than presumed for isolated BA, it has a better prognosis, particularly with early surgery.     

Cardiovascular risk factors after liver transplantation: analysis of related factors

Aims

We sought to analyze the cardiovascular risk factors (CVRF) in liver transplantation and their relation to immunosuppression and hepatitis C virus (HCV) infection.

Patients and Methods

The study included all 158 liver transplants performed between January 2005 and December 2008 that had a minimum follow-up of 1 year. There were 104 men (64%) and 54 women (36%). Data were recorded on both the pretransplant prevalence as well as new cases of diabetes mellitus (DM), hypertension, hypertriglyceridemia, hypercholesterolemia, and hyperuricemia, defined by the need for drug therapy, after a mean follow-up period of 38 months (range, 12-64). We also examined the influence on CVRF of immunosuppression and HCV.

Results

Tacrolimus was prescribed for 61% of the patients and cyclosporine, 39%. Upon univariate analysis only hypertension was significantly associated with the use of cyclosporine (P < .03). There was a trend to a greater incidence of hypercholesterolemia with cyclosporine (P = .1) and DM with tacrolimus (P = .1). The presence of HCV was significantly associated with a greater incidence of de novo DM (P < .01), as was a severe relapse of hepatitis C (P < .03). Multivariate analysis showed a 4.4 times greater risk for developing de novo DM among patients with a severe relapse of HCV.

Conclusion

The development of CVRF after liver transplantation was manifested, mainly during the first 3 months posttransplantation. Special attention should be given to the risk for de novo DM among HCV positive patients.     

Transumbilical management for neonatal ovarian cysts

Background/Purpose

Since Tan and Bianchi (Br J Surg. 1986;73:399) reported umbilical incision as an access for pyloromyotomy in infantile hypertrophic pyloric stenosis, many pediatric surgeons have used this approach for a number of other procedures. Because of the long pedicle with good mobility and the frequent intraabdominal position of the neonatal ovarian cyst, we attempted to manage it via the transumbilical route.

Methods

All patients were treated under intubation general anesthesia. Semicircular infraumbilical incision was made, and the abdomen was entered through a transverse fascial incision. The partially collapsed cyst after aspiration was exteriorized through the incision for cystectomy, partial deroofing, or adnexectomy.

Results

From May 2000 to December 2006, 6 female newborns with ovarian cysts were treated via the transumbilical route. There were no complications from surgery. The operation time and duration of hospital stay were short. The cosmetic appearance after the procedure was good.

Conclusions

The initial result suggests that transumbilical management for neonatal ovarian cysts may be a good alternative procedure when laparoscopic equipment is unavailable or experienced technique is lacking.     

Acute kidney injury before organ procurement is associated with worse long-term kidney graft outcome

Background

As the disparity between the numbers of available organ donors and patients awaiting transplantation increases, different strategies have been proposed to extend the donor pool. Patients with acute kidney injury (AKI) developing during an intensive care unit (ICU) stay are often considered to be donors, but the long-term outcomes of such high-risk kidney transplantations is unknown. We analyzed the renal function and outcomes over 5 years of kidney grafts recovered from deceased donors diagnosed with AKI.

Materials and Methods

We collected data from 61 deceased kidney donors, identified in 1 ICU, and 120 kidney graft recipients who underwent transplantation between January 1999 and December 2006. Donors were stratified according to the RIFLE classification, based on their creatinine and urine output change from admission to the ICU and organ procurement. Recipient kidney graft function (eGFR) calculated according to the MDRD (Modification of Diet in Renal Disease) equation was estimated every 6 months.

Results

Among 61 donors, 10 (16.4%) developed AKI, including 7 classified as “risk”, 2 as “injury,” and 1 as “failure.” The mean follow-up of kidney graft recipients was 49 ± 18 months. The long-term risk for graft loss was significantly higher among the group of kidneys recovered from donors with AKI (27.8% vs 7.1%; P = .02; log-rank = 0.07). Their excretory function was worse over the whole follow-up period.

Conclusion

Patients with kidney grafts obtained from the donors with AKI showed a higher risk for graft loss and worse excretory function upon long-term follow-up.     

Rex shunt for acute portal vein thrombosis after pediatric liver transplantation in children with biliary atresia

Background/Purpose

Posttransplantation portal vein thrombosis (PVT) can have severe health consequences, and portal hypertension and other consequences of the long-term privation of portal inflow to the graft may be hazardous, especially in young children. The Rex shunt has been used successfully to treat PVT patients since 1998. In 2007, we started to perform this surgery in patients with idiopathic PVT and late posttransplantation PVT. Herein we have reported our experience with this technique in acute posttransplantation PVT.

Methods

Three patients of ages 12, 15, and 18 months underwent cadaveric (n = 1) or living donor (n = 2) orthotopic liver transplantation (OLT). All patients had biliary atresia with portal vein hypoplasia; they developed acute PVT on the first postoperative day. They underwent a mesenteric-portal surgical shunt (Rex shunt) using a left internal jugular vein autograft (n = 2) or cadaveric iliac vein graft (n = 1) on the first postoperative day.

Results

The 8-month follow-up has confirmed shunt patency by postoperative Doppler ultrasound. There have been no biliary complications to date.

Conclusions

The mesenteric-portal shunt (Rex shunt) using an autograft of the left internal jugular or a cadaveric vein graft should be considered for children with acute PVT after OLT. These children usually have small portal veins; reanastomosis is often unsuccessful. In addition, this technique has the advantage to avoid manipulation of the hepatic hilum and biliary anastomosis. Although this study was based on a limited experience, we concluded that this technique is feasible, with great benefits to and low risks for these patients.     

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.