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PubMed1991

Hydronephrosis in mice exposed to TCDD-contaminated breast milk: identification of the peak period of sensitivity and assessment of potential recovery.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a potent inducer of hydronephrosis in both fetal and neonatal mice. A critical period of sensitivity to TCDD could not be identified for prenatally induced hydronephrosis since the urinary tract appeared equally sensitive throughout organogenesis. To identify the critical period of susceptibility for development of lactationally induced hydronephrosis in neonatal mice, as well as to characterize the potential for recovery from this renal lesion, dose-response and time-course studies were conducted in the postnatal period. Pregnant C57BL/6N mice were allowed natural delivery. In the dose-response phase of this investigation, mothers were administered 0, 3, 6, or 12 micrograms TCDD/kg once by gavage on Postnatal Day (PND) 1, 4, 8, or 14, and dams and pups were euthanized on PND 26. The kidneys were examined, and hydronephrotic severity was scored. The incidence and severity of hydronephrosis were significantly increased above controls only following treatment on PND 1 or 4, while on PND 8 the increase was marginal and pairwise tests were nonsignificant. Following treatment of dams on PND 1, the hydronephrotic response detected in 26-day-old pups was significantly greater than that for all later exposure days. In the time-course study, dams were given a single oral dose of 0 or 9 micrograms TCDD/kg on PND 1, and mothers and litters were subsequently euthanized on PND 7, 13, 19, or 26. Both hydronephrotic incidence and severity increased with time to euthanization following treatment on PND 1. Thus with the dosing regimen used in this study, recovery does not appear to occur between PNDs 7 and 26. Sex-related differences were observed, as the hydronephrotic response in males was generally greater than in females. In conclusion, the postnatal window of sensitivity during which TCDD can induce hydronephrosis is very narrow. Nonetheless, the hydronephrotic response induced during this early postnatal time is dramatic. Finally, PND 1 is the peak postnatal period of susceptibility for development of TCDD-induced hydronephrosis.

Animals↗
PubMed2006

Management of neonatal hydronephrosis.

Management of neonatal hydronephrosis is a clinical challenge. The natural history of hydronephrosis has shown that most resolve spontaneously; however, there are a significant number that do not. Although hydronephrosis does not always mean obstruction, it becomes the clinician's role to determine when obstruction will eventually lead to renal damage. Work-up of hydronephrosis diagnosed prenatally starts with a postnatal ultrasound. Using the Society of Fetal Urology (SFU) grading of hydronephrosis based on ultrasonography, a management and treatment algorithm can be constructed. Other studies include a voiding cystourethrogram to evaluate for vesicoureteral reflux or in severe cases of bilateral hydronephrosis to evaluate for posterior urethral valves. Diuretic renography is useful in many cases to evaluate the degree of obstruction and determine differential renal function. The goal is to select the patients who would benefit from early surgical intervention. To achieve that goal, aggressive observation is often required.

Algorithms↗
PubMed2001

Is there a role for curative surgery for pelvic recurrence from rectal carcinoma in the presence of hydronephrosis?

BACKGROUND: The prognosis for patients with recurrent rectal adenocarcinoma is not uniformly fatal if one can safely and selectively reoperate on a subset of patients with resectable disease. Even with careful selection, many patients undergo exploratory laparotomy and do not have resectable disease. We have reported that the presence of hydronephrosis in the setting of recurrent rectal carcinoma portends a poor outcome because of invariable association with unresectable disease. The purpose of this study was to update our experience of patients presenting with unilateral or bilateral hydronephrosis and recurrent rectal cancer. METHODS: A retrospective chart review of 142 patients with recurrent rectal cancer evaluated at our institution from January 1989 to December 1999 was performed. RESULTS: Twenty-seven of 142 patients referred for the management of recurrent rectal cancer had unilateral or bilateral hydronephrosis. Fifteen (55%) of these patients had distant metastatic disease. Twelve patients (45%) with hydronephrosis and local recurrent disease on evaluation were analyzed. Six of the 12 patients underwent exploratory laparotomy, with none found to have resectable disease. Their mean survival after diagnosis of recurrent disease was 14 months. CONCLUSIONS: Based on our results, the presence of hydronephrosis (unilateral or bilateral) in recurrent rectal adenocarcinoma portends a survival equivalent to the presence of distant metastasis. Therefore, we do not believe potential curative surgery has a role for patients with locally recurrent rectal adenocarcinoma in the presence of hydronephrosis.

Adenocarcinoma↗
PubMed1996

Unilateral hydronephrosis in infants: are measurements of contralateral renal length useful?

PURPOSE: We investigated whether measurement of contralateral renal length in newborns with unilateral hydronephrosis may help to assess clinically significant hydronephrosis in the affected kidney. MATERIALS AND METHODS: We reviewed our experience with 53 newborns who had unilateral hydronephrosis presumed secondary to ureteropelvic junction obstruction. We divided the patients according to the presence of mild hydronephrosis and no obstruction on a furosemide renogram, severe hydronephrosis and obstruction on a furosemide renogram or a unilateral multicystic kidney. RESULTS: We found no significant correlation between findings on the affected and opposite normal sides. Contralateral hypertrophy, hypotrophy and normal sized kidneys were frequent findings. CONCLUSIONS: We conclude that measurement of contralateral renal length is not helpful in the evaluation of newborns with unilateral hydronephrosis.

Humans↗
PubMed1999

Prenatal diagnosis of hydronephrosis: impact on renal function and its recovery after pyeloplasty.

PURPOSE: We reviewed our experience with corrective surgery for congenital ureteropelvic junction obstruction to assess the impact of mode of presentation on renal function at diagnosis and on postoperative recovery of function. MATERIALS AND METHODS: We reviewed the records of consecutive children who underwent pyeloplasty or nephrectomy for ureteropelvic junction obstruction during a 5-year period at our hospitals. Patients were divided into those with and without a prenatal diagnosis of hydronephrosis. In each group we compared preoperative and postoperative differential renal function, as measured by nuclear renography. RESULTS: We identified 89 patients, of whom 51 (57%) and 38 (43%) presented with prenatal and postnatal hydronephrosis, respectively. Kidneys in which hydronephrosis was diagnosed prenatally had better average differential renal function than those in which the condition was detected postnatally (45 versus 37%). This difference was even more significant in kidneys with less than 40% initial function (31 versus 21%). Presentation with a palpable mass was associated with worst renal function (mean 23%). Postoperatively renal function did not recover significantly in either group. There was a minimal increase in postoperative differential renal function in the subgroup of patients in whom initial differential renal function was less than 40%, although there was no significant difference in the 2 groups (6.5 versus 4.8%). CONCLUSIONS: The early diagnosis of hydronephrosis provided by prenatal ultrasonography is associated with less obstructive nephropathy. Prolonged followup is necessary for studies of the natural history of hydronephrosis because relevant obstruction manifests clinically years later. Despite successful pyeloplasty function recovery is minimal in kidneys with poor function and hydronephrosis diagnosed prenatally. Our findings do not support previous observations that poor function markedly improves after obstruction is relieved.

Child, Preschool↗
PubMed2002

Long-term followup of prenatally detected severe bilateral newborn hydronephrosis initially managed nonoperatively.

PURPOSE: We determine the outcome of severe bilateral primary ureteropelvic junction type hydronephrosis detected prenatally and managed postnatally with an initially nonoperative protocol. MATERIALS AND METHODS: A total of 19 newborns (38 kidneys) with prenatally diagnosed primary grade 3 to 4 bilateral hydronephrosis were followed nonoperatively for a mean of 54 months (range 14 to 187). If urinary obstruction with evidence of renal deterioration (decreased differential function and/or progressive hydronephrosis) occurred pyeloplasty was performed. RESULTS: Pyeloplasty was required in 13 kidneys (35%) in 9 patients (bilateral 4, unilateral 5). Age at pyeloplasty ranged from 2 to 22 months (mean 6.5) in 12 patients and 64 months in 1. The remaining 25 kidneys were followed nonoperatively (bilateral 20, unilateral 5). At last followup the Society for Fetal Urology grade of hydronephrosis in kidneys followed nonoperatively was 0 to 2 in 21 and 3 in 4, compared to 0 to 2 in 9 and Society for Fetal Urology 3 in 4 kidneys treated with pyeloplasty. Mean followup required for the most severely hydronephrotic kidney to achieve maximum ultrasound improvement was 10 months (range 3 to 34) for kidneys followed nonoperatively and 14 months (4-31) for kidneys after pyeloplasty. Differential renal function was measured in each kidney pair and compared using the difference in percent function between the 2 kidneys. In the nonoperative group mean initial difference in percent function was 8% (range 6% to 20%) and mean final difference was 5% (2% to 8%). In the pyeloplasty group mean initial difference in percent function was 16% (range 8% to 30%) and mean final difference was 7% (2% to 16%). With close followup and prompt pyeloplasty renal function improved to greater than pre-deterioration levels in all kidneys. CONCLUSIONS: These data represent the natural history of severe bilateral newborn hydronephrosis. Renal dilatation and function improve with time in most kidneys. Close followup is required in the first 2 years of life to identify the subgroup (35%) of children with obstruction that requires prompt surgery. Such an approach prevented permanent loss of renal function. Nonoperative management with close followup during the first 2 years appears to be a safe and recommended approach for neonates with primary bilateral ureteropelvic junction type hydronephrosis.

Female↗
PubMed1994

The role of C-reactive protein and erythrocyte sedimentation rate in the diagnosis of infected hydronephrosis and pyonephrosis.

Serum C-reactive protein levels and erythrocyte sedimentation rates were prospectively evaluated in 38 patients with dilated pyelocaliceal systems in an attempt to distinguish simple hydronephrosis from infected hydronephrosis and pyonephrosis. The clinical presentations of infected hydronephrosis and pyonephrosis were extremely variable, ranging from no constitutional complaints to urosepsis. Renal sonography detected only 6 of 16 patients with pyonephrosis (specificity 96%, sensitivity 38%, accuracy 72.5%). Using a cutoff value of 3.0 mg./dl. for C-reactive protein and 100 mm. per hour for erythrocyte sedimentation rate, the diagnostic accuracy of detecting infected hydronephrosis and pyonephrosis increased to 97%, with a specificity of 89% and sensitivity of 100%. Based on our experience, we believe that the serum C-reactive protein and erythrocyte sedimentation rate levels can be used as screening tests to distinguish pyonephrosis and infected hydronephrosis from simple, uncomplicated hydronephrosis.

Blood Sedimentation↗
PubMed1999

Prevalence of hydronephrosis in patients with genital prolapse.

OBJECTIVE: To determine the prevalence of hydronephrosis in patients with genital prolapse and evaluate contributing factors. METHODS: Retrospective study of the records of 189 patients with pelvic organ prolapse who underwent preoperative renal imaging studies. RESULTS: Of the 189 patients 31 (17.4%) had hydronephrosis; in 20 (10.6%) patients the hydronephrosis was mild, in 7 (3.7%) it was moderate and in 4 (2.7%) it was severe. The patients with hydronephrosis were older (mean age 68+/-9.5 SD vs. 60.5+/-10.8 SD, P<0.001) had a higher creatinine levels (0.84+/-0.4 SD vs. 0.78+/-0.3 SD P<0.005) and had a higher degree of uterine prolapse (mean 2.6+/-0.9 SD vs. 1.1+/-1.2 SD, P<0.005). After adjusting for age and type of prolapse, only patients with uterine prolapse remained significantly more likely to suffer from hydronephrosis (adjusted odds ratio 1.9, 95% CI 1.1, 3.2). CONCLUSION: The prevalence of hydronephrosis in patients with genital prolapse is appreciable and is related primarily to degree of uterine prolapse.

Aged↗
PubMed2000

Post-voiding repeated renal ultrasonography for slight hydronephrosis detected during screening for asymptomatic microhematuria.

BACKGROUND: There is not a well established method for further screening of asymptomatic microhematuria found through annual health examinations. However, it is apparent that a large number of examiners are using ultrasonography for screening. When slight hydronephrosis is found through screening, it is difficult to determine whether further examinations, such as intravenous pyelography (IVP), should be performed. In this paper, we discuss the usefulness of post-voiding repeated renal ultrasonography, which was applied to 57 patients with slight hydronephrosis found in a screening. METHODS: Ultrasonography in the kidney and the urinary bladder at the ultrasound laboratory of Toma Hospital was carried out on a total of 1906 patients with asymptomatic microhematuria, which was found by routine annual health examination, from January 1996 to December 1998. Slight hydronephrosis was found in 57 (14 males and 43 females) of 1906 patients and post-voiding repeated renal ultrasonography was carried out on all patients. RESULTS: Slight hydronephrosis had disappeared and IVP was avoided in 22 (38.6%) of 57 patients. Of 35 cases in which slight hydronephrosis persisted after urination, there were no abnormalities on IVP in 32 patients, while abnormalities were found in three patients. Two of these had ureteropelvic junction stenosis and the remaining one had a ureteral stone. CONCLUSION: The results of this study indicate that post-voiding repeated renal ultrasonography is useful for avoiding unnecessary further examination to determine whether upper urinary tract obstruction exists, when slight hydronephrosis is observed upon screening by simultaneous renal and urinary bladder ultrasonography for asymptomatic microhematuria.

Female↗
PubMed2006

Hydronephrosis causes salt-sensitive hypertension in rats.

BACKGROUND: Hypertension is a common disease in the Western world and approximately 5% of all cases are secondary to kidney malfunction. It is not clear whether unilateral hydronephrosis due to partial obstruction affects blood pressure. AIM: The aim of this study was to determine whether hypertension develops and to investigate the effects of different salt diets on the blood pressure in hydronephrotic animals. METHODS: Unilateral partial ureteral obstruction was created in 3-week-old Sprague-Dawley rats. A telemetric device was implanted 4-6 weeks later and blood pressure was measured on normal, low- and high-salt diets. Plasma samples were collected on all diets for renin analysis. RESULTS: All hydronephrotic animals developed hypertension that correlated to the degree of hydronephrosis. The blood pressure increased slowly with time and was salt sensitive. In severe hydronephrosis, blood pressure increased from 118 +/- 5 mmHg on low salt to 140 +/- 6 mmHg on high salt intake, compared to control levels of 82 +/- 2 and 84 +/- 2 mmHg, respectively. Plasma renin concentration was increased in the hydronephrotic group of animals compared to controls on all diets, but the difference was only significant on a normal salt diet, 165 +/- 15 versus 86 +/- 12 microGU/ml respectively. In animals with severe hydronephrosis the plasma renin levels were lower, and the changes less, than in those with mild and moderate hydronephrosis. CONCLUSION: This study demonstrates the presence of a salt-sensitive hypertension in hydronephrosis. A systemic effect of the renin-angiotensin system alone cannot be responsible for the hypertension.

Animals↗
PubMed2004

Evaluation of painful hydronephrosis in pregnancy: magnetic resonance urographic patterns in physiological dilatation versus calculous obstruction.

PURPOSE: We evaluated magnetic resonance urography (MRU) appearances in symptomatic hydronephrosis in pregnancy and compared urographic patterns in physiological and calculous disease. MATERIALS AND METHODS: A total of 24 consecutive pregnant women with symptomatic hydronephrosis underwent MRU, comprising an overview fast T2-weighted examination of the abdomen and pelvis, and thick slab, heavily T2-weighted MRU images, followed by focused, high resolution T2-weighted sequences obtained in an axial and coronal oblique plane through the level of ureteral caliber change. RESULTS: Of these 24 pregnant women 15 were found to have physiological hydronephrosis, 7 had calculous disease and 2 had preexisting urinary anomalies. MRU findings in physiological hydronephrosis cases were extrinsic compression of the middle third of the ureter, no filling defect and a collapsed ureter below it. Obstruction by ureteral calculi was seen at points of ureteral narrowing in the ureter, that is at the vesicoureteral junction in 2 cases, in the compressed mid ureter in 3 and at the pelviureteral junction in 1. Nonobstructive renal calculi were seen in another patient. Calculi presented throughout pregnancy but physiological hydronephrosis presented only in the late second and third trimesters. With distal calculi the MRU appearance was the double kink sign with constriction at the pelvic brim and the vesicoureteral junction with a standing column of urine in the pelvic ureter. There was renal edema and perirenal extravasation. Small calculi were only identified using high resolution T2-weighted magnetic resonance imaging. CONCLUSIONS: MRU is a valuable and well tolerated investigation for evaluating painful hydronephrosis in pregnancy. There are characteristic and differing urographic appearances in physiological and calculous obstruction.

Adolescent↗
PubMed1985

Familial pelviureteric junction hydronephrosis and its association with a duplex pelvicaliceal system and vesicoureteric reflux. A family study.

The incidence of pelviureteric junction (PUJ) hydronephrosis and a bifid pelvicaliceal collecting system was determined in the parents and siblings of 19 patients with PUJ hydronephrosis. The high incidence of hydronephrosis in first degree relatives supports the hypothesis that PUJ hydronephrosis is inherited by an autosomal dominant gene of variable penetrance. There is a genetic inter-relationship between PUJ hydronephrosis and a bifid pelvicaliceal system and therefore indirectly between vesico-ureteric reflux and paraureteric diverticula. Ultrasound screening of the children of adults with PUJ hydronephrosis may lead to earlier diagnosis and treatment, thus preventing renal damage.

Adult↗
PubMed1984

The sonographic distinction between neonatal multicystic kidney and hydronephrosis.

Distinction between multicystic kidney and hydronephrosis, the two most common causes of neonatal abdominal masses, is important because of differences in management; however, these two entities may have a similar ultrasonographic appearance. Sonograms of 22 cases of multicystic kidney and hydronephrosis were retrospectively reviewed without knowledge of the pathologic findings to determine if the sonographic patterns were sufficiently distinct to be usable in clinical diagnosis. Nine of the 22 cases were correctly diagnosed with ultrasound as multicystic kidney, 6 cases were correctly diagnosed as hydronephrosis, and 7 cases of pathologically proved multicystic kidney were incorrectly diagnosed as hydronephrosis. Four of these incorrect diagnoses occurred in cases of the hydronephrotic type of multicystic kidney. An additional 9 cases were reviewed with knowledge of the pathologic results. It is concluded that sonography is accurate at differentiating classic multicystic kidney disease from moderate hydronephrosis; however, there is often considerable difficulty in distinguishing severe hydronephrosis from the hydronephrotic form of multicystic kidney disease.

Diagnosis, Differential↗
PubMedDate not supplied

Adriamycin-induced fetal hydronephrosis.

INTRODUCTION: At the end of pregnancy, the amniotic fluid (AF) depends basically on renal function, corresponding to fetal urine. Changes in AF, especially oligohydramnios, are reported in association with fetal hydronephrosis (FH). The experimental model using adriamycin in pregnant female rats has a teratogenic effect and has been classically employed to study esophageal atresia. Nevertheless, adriamycin promotes FH with high frequency as well. In the present study, using this animal model, we tried to identify the incidence and microscopic changes of FH, as well as its correlation with AF weight. MATERIALS AND METHODS: Eight Spreague-Dawley pregnant female rats received adriamycin 2.2 mg/kg on the 8th and 9th gestational days (considering term gestation = 22 days). Those fetuses that received adriamycin (Adriamycin Group) were compared with fetuses from 2 female rats (Control Group), which received 0.9% saline solution. On the 21.5 gestational day, the fetuses were collected by cesarean incision, sacrificed, and examined for macro and microscopic changes in kidneys and ureters. Fetuses with bilateral hydronephrosis formed the Hydronephrosis Group. AF weight was determined as well. RESULTS: Hydronephrosis occurred in 70 (95%) of the 74 fetuses in the adriamycin group against none of the 21 fetuses from the control group. The amniotic fluid weight was increased in the adriamycin group in relation to the control group (p < 0.001). The histomorphometric study revealed dilation of the renal pelvis and reduction of renal parenchyma in the hydronephrosis group in relation to the control group. Severe cortical atrophy, cortical tubular atrophy and medullar atrophy were observed in the hydronephrosis group. CONCLUSIONS: Slight renal lesions were in agreement with changes in AF weight, since they suggest that there was production of urine with the maintenance of AF.

Amniotic Fluid↗
PubMed1987

Neonatal hydronephrosis in the era of sonography.

During a 6-year period (1979-1985), 142 neonates with significant hydronephrosis were seen. Seventy-eight percent of the cases were discovered on fetal screening during obstetric sonography. Maternal/fetal intervention was virtually never indicated and most babies were asymptomatic. The most common conditions found were obstruction of the ureteropelvic junction (41%), obstruction of the distal ureter (usually primary megaureter) (23%), upper-pole hydronephrosis associated with duplex anomalies (13%), and posterior urethral valves (10%). Seventeen neonates with multicystic dysplastic kidney were seen (three per year or one for every eight with hydronephrosis). In comparison, during the 30-year period, 1947-1977, 146 neonates with significant hydronephrosis were seen. Most cases were discovered because the patients had signs and/or symptoms--either an abdominal mass (an enlarged kidney or bladder) or urosepsis. The three most common conditions were obstruction of the ureteropelvic junction (22%), posterior urethral valves (19%), and ectopic ureterocele (14%). During this period, 53 neonates with multicystic dysplastic kidney were discovered (two per year or one for every three with hydronephrosis). The dramatic increase in the number of neonates found to have hydronephrosis is primarily due to the widespread use of obstetric sonography and concomitant fetal screening. The pattern of causes before 1979 represented the incidence of symptomatic lesions. The current pattern more accurately reflects the true incidence of congenital anomalies of the urinary tract.

Humans↗
PubMed2001

[Hydronephrosis: comparison of conservative and surgical treatment].

OBJECTIVES: Early diagnosis and identification of adequate treatment of children with hydronephrosis. METHODS: Routine ultrasound testing was followed by standard urography and micturacion cystouretrogam among those identified with hydronephrosis. RESULTS: We showed 48 children among whom the ultrasound detected hydronephrosis of various degrees. First group consists of patients with non-obstructive hydronephrosis 18 patients (37.5%); the highest percentage among girls (88.3%), ages 1-5. The cause of hydronephrosis is the vesicoureteral reflux. The second group with obstructive hydronephrosis consists of 30 patients (62.5%), only one of them had obstruction ureterovesical junction. Neonatal boys dominate in this group. 50% of patients from both groups were surgically treated. CONCLUSION: Wide use of ultrasound provided for a significant improvement in diagnosis of urinary-tract anomalies.

Adolescent↗
PubMed2002

Evaluation of renal function in children with moderate or severe hydronephrosis after operation.

OBJECTIVE: To evaluate postoperative renal function in children with congenital moderate or severe hydronephrosis. METHODS: 99mTc-labeled diethylenetriaminepenta-acetic acid scintigraphy was performed in 50 children with unilateral moderate or severe hydronephrosis to determine postoperative renal function. We also analyzed the factors influencing renal function recovery. RESULTS: Average postoperative renal function in 50 cases was 40.62% +/- 10.09%. Among them, 32% of patients had nearly normal renal function and differentiated renal function reached up to 45%. Average preoperative and postoperative renal function in 25 cases was 23.89% +/- 11.65% and 39.33% +/- 8.59% respectively and the increase of renal function was about 15.44% +/- 11.18% (P = 0.0003). Renal parenchyma thickness was negatively correlated with postoperative renal function (r = -0.62, P = 0.0009). The follow-up period was positively correlated with postoperative renal function (r = 0.58, P = 0.0026). The patients' age had no correlation with renal function recovery (r = -0.05, P = 0.80). Recovery of renal function in hydronephrosis with extrarenal pelvis was greater than that in hydronephrosis with intrarenal pelvis (P = 0.016). CONCLUSIONS: Postoperative renal function in children with moderate or severe hydronephrosis can recover to normal. Recovery of renal function was more obvious in hydronephrosis with thinner renal parenchyma, longer follow-up period and extrarenal pelvis.

Adolescent↗
PubMedDate not supplied

[Principle of hydronephrosis and choice of surgical method].

Experience in operative treatment of 1574 patients suffering from hydronephrosis is analysed. Among them, 656 patients were operated in the Chernobyl zone. Radical surgery, palliative operations and nephrectomy were performed in 63, 21.5 and 16.5% patients, respectively. According to operative electropyeloureterography and histological examination of the removed material, circulatory segmental hypoplasia of near pelvis ureter in hydronephrosis had decreased electric potentials, up to their absence, urodynamic disorders. Ureteral hypoplasia is often associated with high branching of the ureter, additional aberrant renal vessel. In functional hydronephrosis it may be a primary cause of hydronephrosis and influence the choice of the operative treatment. Postoperative course of hydronephrosis in the Chernobyl zone is characterized by more frequent complications because of subnormal immunity and high virulence of urinary infection. For 12 years after the Chernobyl accident, no direct effects of low-dose radiation on renal function is ascertained. Renal function after radical plastic operations depended on the disease severity. In the Chernobyl zone all kinds of radical plastic operations in hydronephrosis were performed.

Humans↗