Repair of congenital heart lesions combined with lung transplantation for the treatment of severe pulmonary hypertension: a 13-year experience

OBJECTIVE: In patients with severe pulmonary hypertension associated with congenital heart disease, we prefer to perform repair of the congenital heart disease and lung transplantation whenever feasible so as to augment the donor pool and avoid the cardiac complications associated with heart transplantation. We report our experience with repair of congenital heart disease and lung transplantation and compare the results with those of patients who underwent heart-lung transplantation during the same period. METHODS: The records of patients who had repair of congenital heart disease and lung transplantation (n = 35) and heart-lung transplantation (n = 16) between 1990 and 2003 were reviewed. RESULTS: The underlying congenital heart disease in the repair of congenital heart disease and lung transplantation group included transposition of great vessels (n = 2), atrioventricular canal defect (n = 2), ventricular septal defect (n = 9), pulmonary venous obstruction (n = 7), scimitar syndrome (n = 2), pulmonary arterial atresia or stenosis (n = 5), and others (n = 8). Thirteen of the patients undergoing repair of congenital heart disease and lung transplantation (37.1%) had the congenital heart disease repaired before lung transplantation; the remaining congenital heart disease repairs were performed concurrently with transplantation. Sixteen patients underwent heart-lung transplantation because of poor left ventricular function or single-ventricle anatomy. Freedoms from bronchiolitis obliterans at 1, 3, and 5 years were 72.9%, 54.7%, and 54.7% for the repair of congenital heart disease and lung transplantation group and 77.8%, 51.9%, and 38.9% for the heart-lung transplantation group, respectively. Survivals at 1, 3, and 5 years were 62.9%, 51.4%, and 51.4% for the repair of congenital heart disease and lung transplantation group and 66.5%, 66.5%, and 60% for the heart-lung transplantation group, respectively. CONCLUSION: Repair of congenital heart disease and lung transplantation is a feasible treatment option. Long-term outcome is determined by associated complications related to lung transplantation. Despite the complexity of combined congenital heart disease repair with lung transplantation and the resulting perioperative morbidity, the patients had similar outcomes to those of patients who underwent heart-lung transplantation.     

Testicular hypotrophy does not correlate with grade of adolescent varicocele

PURPOSE: Testicular hypotrophy is the most widely accepted indication for correcting adolescent varicocele. Previous studies in adolescents have shown a relationship between increasing grade of varicocele and the likelihood of testicular hypotrophy. As this relationship has significant clinical implications, we studied the correlation between grade and testicular volume disproportion in our adolescent varicocele population. MATERIALS AND METHODS: We reviewed the adolescent varicocele database at our institution. A total of 168 patients 8 to 21 years old were studied. We routinely calculated testis volumes using scrotal ultrasound. Testicular disproportion was calculated using the equation [(size of unaffected testis) - (size of affected testis)]/(size of unaffected testis) x 100%. Disproportion was categorized as less than 10%, 10% to 20% and more than 20%. Varicoceles were graded by an attending urologist with the patient standing, using the system of Dubin and Amelar. Analysis of variance and Pearson chi-square indicated no significant differences in volume differential between varicocele grades. RESULTS: Mean +/- SD volume differential was 18% +/- 15% for grade I, 25% +/- 20% for grade II and 19% +/- 14% for grade III. ANOVA revealed no significant difference in mean volume differential between the 3 varicocele grades (p = 0.10). When categorizing patients into 3 levels of volume differential (less than 10%, 10% to 20%, more than 20%) no significant correlation was observed between varicocele and volume differential (p = 0.48, chi-square test). CONCLUSIONS: Grade of varicocele does not correlate with presence or severity of testicular disproportion in adolescent boys with varicocele as measured by scrotal ultrasound.     

Retroperitoneoscopic radical and partial nephrectomy in the patient with cirrhosis

PURPOSE: In patients with cirrhosis and a renal mass options may be limited by medical disease and the surgical difficulties associated with portal hypertension. We describe a retrospective review of patients with cirrhosis with renal masses who underwent radical or partial nephrectomy through a retroperitoneoscopic approach. MATERIALS AND METHODS: Ten consecutive patients, including 4 men and 6 women, with cirrhosis, of whom 2 had undergone liver transplantation, underwent radical (7) or partial (3) nephrectomy for a total of 5 right and 5 left renal neoplasms via the retroperitoneoscopic approach at our institution from March 2002 to February 2004. Recovery data were prospectively obtained and other information was gathered retrospectively from the medical record. RESULTS: Average patient age was 58 years and average American Society of Anesthesiology score was 2.8. Average renal tumor size for radical and partial nephrectomy was 4.6 (range 2.9 to 7) and 1.8 cm (range 1.3 to 2.3), respectively. Operative time was 140 to 315 minutes (median 172) and estimated blood loss was 100 to 5,000 ml (median 225). One patient required open conversion due to hemorrhage from left portosystemic venous communications. Mean postoperative hospitalization was 1.5 days (range 1 to 6). CONCLUSIONS: Although retroperitoneoscopic surgery avoids many surgical dangers associated with portal hypertension and it is our preferred approach to renal surgery in patients with cirrhosis, significant portosystemic venous communications exist in the retroperitoneum, especially on the left side, and they still lead to substantial blood loss in some patients.     

p27(Kip1) Knockout mice are protected from diabetic nephropathy: evidence for p27(Kip1) haplotype insufficiency

BACKGROUND: High glucose up-regulates the mesangial cell expression of p27(Kip1), an inhibitor of cyclin-dependent kinases/cyclin complexes. Previous in vitro studies using cultured mesangial cells from p27(Kip1-/-) mice demonstrated that these cells do not undergo high glucose-mediated cellular hypertrophy. Since glomerular hypertrophy is an early feature of diabetic nephropathy and may precede the development of glomerulosclerosis, interference with p27(Kip1) expression may attenuate diabetic nephropathy. However, it is unclear whether deletion of p27(Kip1) protects the kidneys of diabetic nephropathy in vivo. METHODS: Type 1 diabetes mellitus was induced in p27(Kip1+/+), p27(Kip1+/-), and p27(Kip1-/-) mice by injection of streptozotocin (STZ). Mice were studied for 6 weeks. Animals injected with citrate buffer only served as controls. At the end of the experiments, urine was collected, albuminuria was determined with an enzyme-linked immunosorbent assay (ELISA), and blood glucose concentrations were measured. Kidneys were perfusion-fixed for quantitative morphologic analysis with glutaraldehyde and for immunohistochemical studies with formaldehyde. Glomerular cell number and volume were analyzed. Glomerulosclerosis, tubulointerstitial, and vascular damage indices were semiquantitatively assessed according to standard methodology. Quantitative glomerular parameters (cell numbers and volumes of endothelial, mesangial, and epithelial cells) were measured on semithin sections. Expression of transforming growth factor-beta1 (TGF-beta1), laminin, and collagen type IV were determined by immunohistochemical staining. RESULTS: In contrast to animals only injected with citrate buffer, mice that received STZ developed hyperglycemia. There was no significant difference in the degree of hyperglycemia among p27(Kip1+/+), p27(Kip1+/-), and p27(Kip1-/-) mice. Diabetic p27(Kip1+/+), but not control p27(Kip1+/+) animals, developed albuminuria. Albuminuria was significantly reduced in diabetic p27(Kip1+/-) and more profoundly in p27(Kip1-/-) animals. Diabetic p27(Kip1+/+) mice revealed a significant increase in mean glomerular volume at 6 weeks. The volumes of mesangial and endothelial cells and podocytes all increased, whereas cell numbers were reduced, consistent with cell hypertrophy. Glomerular, endothelial, mesangial and podocyte hypertrophy were reduced in diabetic p27(Kip1+/-) and p27(Kip1-/-) animals. Diabetic p27(Kip1) (+/+) animals had significantly increased glomerulosclerosis, tubulointerstium, and vascular damage indices compared to nondiabetic p27(Kip1+/+) controls. Diabetic p27(Kip1-/-) mice exhibited significantly less structural damage than diabetic wild-type animals. Diabetic p27(Kip1+/-) animals revealed intermediate glomerulosclerosis, tubulointerstium, and vascular damage values. Immunohistological stainings demonstrated increases in TGF-beta1, collagen type IV, and laminin expression in kidneys of diabetic p27(Kip1+/+) animals compared to nondiabetic p27(Kip1+/+) controls. Staining intensity for type IV collagen and laminin, but not for TGF-beta1, was significantly lower in diabetic p27(Kip1-/-) mice. CONCLUSION: Deletion of p27(Kip1) attenuates the functional and morphologic features of diabetic nephropathy. Although deletion of p27(Kip1) abolished some parameters of diabetic glomerular hypertrophy, the significant reduction of TGF-beta1 expression in the tubulointerstitium indicates that other protective mechanisms could be operative. The p27(Kip1) gene is haplo-insufficient because diabetic p27(Kip1)+/- mice exhibited an intermediate degree of functional and structural renal injury. Our data shows that p27(Kip1) plays an important role in diabetic nephropathy.