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.     

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.     

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.     

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.     

A review of the management of gallstone disease and its complications in pregnancy

Background

Symptomatic gallstone disease is the second most common abdominal emergency in pregnant women. There have been significant developments in the management of gallstone disease, but risk to the fetus has prevented their routine application in pregnant women. We reviewed the literature to find the current best evidence for the management of gallstones and its complications in pregnancy.

Data sources

MEDLINE and PubMed literature searches were performed to identify original studies.

Results and Conclusions

Six studies comparing conservative with surgical management of cholecystitis showed no significant difference in incidence of preterm delivery (3.5% vs 6.0%, P = .33) or fetal mortality (2.2% vs 1.2%, P = .57). There was no maternal or fetal mortality in 20 reports of laparoscopic cholecystectomy and 9 reports of endoscopic retrograde cholangiopancreatography, thus indicating their safety when performed with necessary precautions. Laparoscopic cholecystectomy is a safe procedure in all trimesters. In 12 reports of gallstone pancreatitis, fetal mortality was 8.0% versus 2.6% (P = .28) in conservative and surgical groups, respectively, suggesting the need for earlier surgical intervention.     

Perioperative surgical findings in congenital and acquired undescended testis

Purpose

Perioperative surgical findings in congenital and acquired undescended testis (UDT) were prospectively assessed.

Methods

We included all boys with congenital or acquired UDT who underwent orchidopexy at our hospital between January 2006 and August 2009. Perioperatively, we scored the position and volume of the testis, the insertion of the gubernaculum, the patency of the processus vaginalis, and the obtained position.

Results

We included 69 boys (aged 0.9-14.6 years) with 76 congenital UDT and 28 boys (aged 2.2-18.5 years) with 30 acquired UDT. In the congenital group, the testis was in intracanalicular position in 55 cases (72%), whereas in the acquired UDT group, this was in 11 cases (37%; P < .001). The insertion of the gubernaculum was at the bottom of the scrotum in 13 cases (17%) of the congenital UDT group and in 12 cases (40%) of the acquired UDT group (P < .05). The processus vaginalis was open in 63 cases (83%) of the congenital and in 9 cases (30%) of the acquired UDT group (P < .001).

Conclusion

Compared to congenital UDT, acquired UDT are more likely to be situated in the superficial inguinal pouch, to have a normal insertion of the gubernaculums, and to have a closed processus vaginalis.     

Lateral semicircular canal fenestration for congenital conductive hearing loss: Solution for a dilemma

Objective

To determine functional results after lateral semicircular canal fenestration on congenital conductive hearing loss.

Study Design

Case series with chart review.

Setting

Amir-Alam otolaryngology tertiary referral center.

Subjects and Methods

Twenty patients with congenital oval window malformations who were not candidates for ossicular reconstruction underwent lateral semicircular canal fenestration. A skin graft was placed over the perforated fascial graft on the fenestrated area.

Results

The median preoperative mean air conduction (MAC) was 56.9 dB (50.0 dB median air-bone). Postoperative median MAC gain of 34.3 dB (P < 0.001) and the median air-bone gap of 18.8 dB were observed. The mean bone conduction (MBC) did not show any significant changes postoperatively (P = 0.12). No sensorineural hearing loss, tinnitus, or imbalance was observed.

Conclusion

We demonstrated hearing improvement after lateral semicircular canal fenestration. This technique can be considered as an alternative for patients with middle ear anomalies who are not candidates for ossicular reconstruction.     

Depression and anxiety in living kidney donation: evaluation of donors and recipients

Background

Psychosocial status of donors before and after living kidney donor transplantation has been an important concern. Investigations of psychosocial issues in related recipients are not frequent.

Aim

The aims of this study were to evaluate and compare psychopathologic dimensions in donors and recipients before and after transplantation.

Methods

Thirty-five recipients and 45 donors completed a psychosocial evaluation before and after transplantation. We applied Pearson chi-square, McNemar, Fisher, Wilcoxon, and Mann-Whitney tests as well as linear and logistic regression statistical methods.

Results

Before transplantation 100% of the recipients presented total anxiety, compared with 64.4% of donors, with higher anxiety levels in all dimensions (P < .001). Also, 38.7% of recipients and 16.3% of donors had moderate/serious depression (P = .029). Men showed higher levels of cognitive anxiety before transplantation (odds ratio [OR] = 4.3; P = .008). After versus before transplantation central nervous system and cognitive anxiety had diminished in recipients (P = .031; P = .035, respectively); there were higher levels of cognitive anxiety than among the donors (P = .007). Depression showed no significant changes in recipients or donors; the differences were no longer significant. There were less severely depressed recipients but an increase among severely depressed donors. Male recipients and donors showed greater cognitive anxiety (P = .02; P = .04, respectively) at both times. Female recipients presented with more severe depression (P = .036).

Conclusions

Anxiety is an important symptom. Surgery had a positive impact to lower anxiety in recipients. Most protagonists displayed little or no depression; it was more prevalent among recipients. Donors and recipients maintained some psychopathologic symptoms after surgery. We defined vulnerable groups among these cohorts.     

Impact of omphalocele size on associated conditions

Purpose

Omphalocele is often associated with the presence of other congenital anomalies. Case reports have demonstrated nonclassical associations occurring in smaller omphaloceles. The aim of this study was to determine if omphalocele defect size correlates with the type of anomalies found.

Methods

Patient records at a pediatric hospital were retrospectively reviewed for an 8-year period. Data were collected on patient demographics, omphalocele size, and congenital anomalies identified. Size of the abdominal wall defect was determined by either physical examination or operative record of repair. Patient cohorts were designated as those with small (4 cm and less) or large (greater than 4 cm) omphaloceles.

Results

Fifty-three cases of omphalocele were observed. Twenty-seven cases were classified as small, with 26 classified as large. A predominance of males was noted in the small omphalocele group (78% vs 42%; P = .01). Intestinal anomalies, including Meckel's diverticulum and intestinal atresia, were only seen in patients with small omphaloceles. Most cardiac anomalies were associated with large omphaloceles (34.6% vs 3.7%; P = .01).

Conclusion

Small omphalocele size correlates with an increased prevalence of associated gastrointestinal anomalies, a lower prevalence of cardiac anomalies, and a higher predominance of male sex.     

P-selectin expression, neutrophil infiltration, and histologic injury in neonates with necrotizing enterocolitis

Background/Purpose

P-selectin promotes adherence of leukocytes to the endothelium in inflammatory processes. The aim of this study was to investigate the expression of P-selectin and its role in the development of inflammation in neonates with necrotizing enterocolitis (NEC).

Methods

Twenty-nine intestinal specimens from 13 neonates with NEC and 7 control neonates with congenital gastrointestinal abnormalities were studied. Histologic damage, immunohistochemical expression of P-selectin, and polymorphonuclear cell infiltrate were graded blindly. Mann-Whitney U and Spearman rank tests were used to compare grades.

Results

Expression of P-selectin was increased in NEC compared with controls in both medium-sized vessels (P = .03) and in the microcirculation (P = .03). P-selectin expression on medium-sized vessels correlated with the degree of histologic injury (P = .02, r = 0.425). P-selectin expression was greatest in areas of active inflammation but markedly lower in necrotic areas. The degree of polymorphonuclear cell infiltration strongly correlated with P-selectin expression on both medium-sized vessels (P = .004, r = 0.513) and the microcirculation (P = .001, r = 0.578).

Conclusions

Expression of P-selectin is increased in medium-sized vessels and in the microcirculation in intestinal specimens of neonates with NEC compared with neonatal controls. Expression of P-selectin is associated with the recruitment of polymorphonuclear cells and the severity of histologic injury, although P-selectin expression is lost in necrotic tissue.     

Preoperative platelet-lymphocyte ratio is an independent significant prognostic marker in resected pancreatic ductal adenocarcinoma

Background

The objective of this study was to investigate whether the preoperative platelet-lymphocyte (P/L) ratio represents a significant prognostic index in resected pancreatic ductal adenocarcinoma.

Methods

A total of 110 patients undergoing pancreatoduodenectomy for pancreatic ductal adenocarcinoma over a 10-year period were identified from a prospectively maintained database.

Results

The preoperative P/L ratio was found to be a more significant prognostic marker (P < .001) than either the lymphocyte count (P = .007) or platelet count (P = .068) on univariate Cox survival analysis. The median overall survival in patients with a P/L ratio of 150 or less (n = 48) was 19.7 months, 13.7 months in those with a P/L ratio of 151 to 300 (n = 43), and 5.8 months in patients with a value of greater than 300 (n = 19) (log-rank, P = .006). The preoperative P/L ratio retained significance on multivariate analysis (P < .001), along with tumor size (P = .010) and lymph node ratio (P = .013).

Conclusions

The preoperative P/L ratio represents a significant independent prognostic index in patients of resected pancreatic adenocarcinoma.     

Long-term outcome of single institutional experience with conservative and surgical management for renal artery aneurysm

Background

Spontaneous rupture risk of a renal artery aneurysm (RAA) is extremely low. Indications for surgical repair of RAA remain uncertain.

Objective

Long-term outcomes of conservative therapy and surgical repair were evaluated.

Patients

The study included 58 patients (17 males, 41 females) who were diagnosed with RAA during the last 21 years. Median age at the time of diagnosis was 62 (19-85) years, and the median follow-up 69 months (range 3-216).

Methods

The patients were divided into two groups, conservative group (n = 30) who had been followed with blood pressure control, and treatment group (n = 29), who underwent an intervention.

Results

Multiple efferent aneurysmal branches were observed in seven conservative and 16 treatment cases (P = .002). The median maximum diameter of the aneurysm was lower in the conservative than the treatment group (15 versus 25 mm, P = .005). Two conservative group cases showed increases in aneurysm size during follow-up. The hypertensive state showed essentially no change in either group during the follow-up. Renal function decreased with age similarly both in conservative and treatment groups.

Conclusions

Our conservative management criteria for RAA are justifiable and even too strict.     

Prospective randomized trial of paravertebral block for patients undergoing breast cancer surgery

Background

The goal of the current study was to evaluate the effect of regional anesthesia using paravertebral block (PVB) on postoperative pain after breast surgery.

Methods

Patients undergoing unilateral breast surgery without reconstruction were randomized to general anesthesia (GA) only or PVB with GA and pain scores assessed.

Results

Eighty patients were randomized (41 to GA and 39 to PVB with GA). Operative times were not significantly different between groups. Pain scores were lower after PVB compared to GA at 1 hour (1 vs 3, P = .006) and 3 hours (0 vs 2, P = .001) but not at later time points. The overall worst pain experienced was lower with PVB (3 vs 5, P = .02). More patients were pain-free in the PVB group at 1 hour (44% vs 17%, P = .014) and 3 hours (54% vs 17%, P = .005) postoperatively.

Conclusions

PVB significantly decreases postoperative pain up to 3 hours after breast cancer surgery.     

Comparison of perioperative outcomes after combined thoracoscopic-laparoscopic esophagectomy and open Ivor-Lewis esophagectomy

Background

Thoracoscopic-laparoscopic esophagectomy (TLE) has gained popularity in specialized centers. This study compares the perioperative outcomes of TLE and Ivor-Lewis esophagectomy (ILE).

Methods

Forty-four consecutive TLEs were compared with 46 historical ILEs. Outcomes included surgical time and blood loss, hospital length of stay, 30-day mortality rate, and complications.

Results

TLE took longer to perform (543 vs 437 min; P < .01) than ILE, but produced less blood loss (407 vs 780 mL; P < .01). The median length of stay and 30-day mortality did not differ between groups. Cardiovascular (41% for TLE vs 30% for ILE; P = .19) and pulmonary complications (31% TLE vs 30% ILE; P = 1.0) occurred frequently in both groups, but TLE patients had fewer wound complications (4% TLE vs 17% ILE; P = .05).

Conclusions

Despite longer surgical times, TLE produced decreased intraoperative blood loss and wound complications. These findings suggest that with further technical refinement TLE may ameliorate the morbidity seen with ILE.     

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.     

Incidence and risk factors for posttransplant subcapsular cataract: a long-term retrospective cohort study

Background

The occurrence and risk factors for posterior subcapsular cataract (PSC) after renal transplantation have received little attention.

Objectives

To analyze the cumulative incidence of PSC after renal transplantation and identify risk factors for the development of PSC.

Methods

Retrospective review of the records of the patients who underwent kidney transplantation between May 1986 and December 2008.

Results

We included 94 renal transplant recipients who showed PSC incidence at 5, 10, and 15 years of 3.5%, 40.5%, and 50.1%, respectively. Cumulative incidence of PSC during the follow-up was 37.2%. On multivariate analysis, age, body mass index (BMI) and cumulative corticosteroid dose were significantly associated with PSC. Recipient age above 50 years (hazard ratio [HR] = 2.88, 95% confidence interval [CI]: 1.42-5.83; P = .003), BMI above 25 kg/m² (HR = 2.28, CI: 1.09-4.78; P = .029), and prednisolone dose above 3 mg/kg/mo (HR = 7.79, CI: 3.34-18.99; P < .001) were independent risk factors for PSC. Diabetes, renal diagnosis, duration, and type of dialysis and posttransplant immunosuppressive regimen did not influence the occurrence of PSC.

Conclusion

The risk of PSC was low during the first years after transplantation reaching a plateau at 15 years posttransplantation. Among the risk factors for PSC, cumulative corticosteroid dose and body weight were the only modifiable risk factors.     

Income, productivity, and satisfaction of breast surgeons

Background

The purpose of this study was to assess how the practice patterns of breast surgeons affect their income and job satisfaction.

Methods

A 19-question survey regarding practice patterns and income and job satisfaction was mailed to all active US members of the American Society of Breast Surgeons.

Results

There were 772 responses. An increasing percentage of breast care was associated with lower incomes (P = .0001) and similar income satisfaction (P = .4517) but higher job satisfaction (P = .0001). The increasing proportion of breast care was also associated with fewer hours worked per week (P = .0001). Although incomes were lower in surgeons with a higher proportion of their practice in breast care, income satisfaction was not affected.

Conclusions

Although cause and effect relationships between income and breast surgery are difficult to establish, several trends do emerge. Most significantly, we found that dedicated breast surgeons have higher job satisfaction ratings and similar income satisfaction despite lower incomes.     

Extracellular matrix dynamics associated with tissue-engineered intravascular sclerotherapy

Background

The extracellular dynamics after intravascular sclerotherapy with an injectable, fibroblast-based engineered construct is unknown.

Methods

Rabbits underwent ethanol sclerotherapy of a jugular vein segment. Control animals (n = 40) underwent no further treatment or an acellular collagen hydrogel was injected. Experimental animals (n = 20) received a tissue-engineered construct. After 1, 2, 4, and 20 to 24 weeks, segments were evaluated for collagen, glycosaminoglycan (GAG), matrix metalloproteinase (MMP) 2 and 9, and tissue inhibitors of MMP (TIMPs) 1 and 2 and scored on a scale of 0 to 3. Groups and time points were compared using nonparametric statistical analysis.

Results

Collagen content was higher in animals that received fibroblasts (P < .05). Glycosaminoglycan analysis showed a higher grade only at 1 week (P < .05). Collagen and GAG deposition were prominent at weeks 1 through 4, and decreased over time. Both MMP-2 and MMP-9 and TIMP-1 and TIMP-2 grade decreased with time (P < .01) in all groups, with no differences between groups.

Conclusion

Enhancement of intravascular sclerotherapy by tissue engineering stems, at least in part, from increased local deposition of collagen and GAG. MMP and TIMPs may play a role in recanalization after experimental sclerotherapy. Tissue engineering may be a valuable adjunct for the treatment of vascular malformations.