Cessation of vesicoureteral reflux for 5 years in infants and children allocated to medical treatment. The International Reflux Study in Children. A total of 401 children with severe vesicoureteral reflux (97 with grade III and 304 with grade IV) was entered into the European branch of the International Reflux Study in Children. Of these patients 37 with grade III and 43 with grade IV reflux were allocated to medical treatment as a sideline group because the reflux grade III or IV had improved to grade II or I, or it had disappeared during the preceding 2 to 6 months (median 4). Of the remaining 321 patients with persistent grade III or IV reflux 158 were randomly allocated to medical treatment of whom 3 switched to surgery. We report on 235 children treated medically (155 random medical and 80 sideline), of whom 88% had a complete 5-year followup with x-ray and/or isotope voiding cystourethrography at 6, 18, 30 and 54 months. Seven children dropped out of the study after a followup of 6 months or less, including 6 with persistent vesicoureteral reflux. Cessation of vesicoureteral reflux was observed significantly more often in children with unilateral (40 of 74, 54%) than with bilateral (18 of 154, 12%) reflux (p < 0.001). No significant difference between grades III and IV was noted. Vesicoureteral reflux ceased in 25 of 153 children (16%) from the random medical group and in 32 of 75 children (43%) in the sideline group. Of 194 children with vesicoureteral reflux detected for the first time at entry reflux resolved in 55 (28%). In only 2 of 34 children (6%) in whom vesicoureteral reflux was detected more than 1 year before entry did reflux resolve after 5 years. Among the children in whom vesicoureteral reflux either disappeared, diminished or remained unchanged the proportion with urinary tract infection recurrences was almost the same.


Results of a randomized clinical trial of medical versus surgical management of infants and children with grades III and IV primary vesicoureteral reflux (United States). The International Reflux Study in Children. A total of 132 infants and children with grades III and IV primary vesicoureteral reflux was entered into a prospective trial comparing medical to surgical management. Inclusion criteria were an age not exceeding 10 years and a glomerular filtration rate of at least 70 ml. per minute per 1.73 m.2. Children with significant urinary tract malformations and clinical signs/symptoms of dysfunctional voiding were not accepted into the trial. Medical therapy consisted of continuous low dose antibiotic prophylaxis until vesicoureteral reflux resolved. The type of surgical procedure used for the correction of reflux was left to the discretion of the surgeon. Outcome variables included the appearance or progression of renal lesions, rate of renal growth, recurrence rate of urinary tract infection or pyelonephritis, changes in total kidney glomerular filtration rate, development of hypertension and resolution rate of vesicoureteral reflux. Followup at 6, 18, 36 and 54 months after entry included, in addition to history and physical examination, voiding cystourethrography, excretory urography and a urine culture. Of the patients 68 were allocated to the medical group and 64 to the surgical group. They were stratified for age, sex and preexisting renal scarring. Of the patients 10% were boys, 47% were between 2 and 6 years old at entry, 93% had a history of pyelonephritis, 67% had either scarring or thinning of the parenchyma at entry, 87% had grade IV vesicoureteral reflux in at least 1 unit and 56% had bilateral reflux. There were no significant differences in the frequency distribution of entry characteristics between the patients allocated to either group. New renal scarring developed in 22% of medical and 31% of surgical patients (p < 0.4). Growth of kidneys with grade IV vesicoureteral reflux was slightly less than normal in the medical (-0.67 +/- 0.15 standard deviation) and surgical (-0.42 +/- 0.11 standard deviation) groups (p < 0.7). Pyelonephritis occurred in 15 medical patients versus 5 surgical patients (p < 0.05). There was no significant change in glomerular filtration rate within each treatment group and no difference in glomerular filtration rate between groups. No patient had hypertension during the followup period. The disappearance rate of vesicoureteral reflux in patients with grade IV reflux was approximately 8% per year. Of the medical patients 75% still had vesicoureteral reflux after 3 years of observation.(ABSTRACT TRUNCATED AT 400 WORDS)


Surgical results: International Reflux Study in Children--United States branch. A total of 87 patients in the United States underwent surgical correction of vesicoureteral reflux as part of the International Reflux Study in Children. Of the 66 patients randomized to surgical treatment 2 were transferred to the medical group before surgery was performed, while 23 patients originally assigned to receive medical management ultimately underwent surgery. Of the patients 17 (20%) were less than 1 year old, while the remaining children were evenly distributed by age in 2-year intervals up to age 9 years. Reimplantation was performed by the Cohen technique in 52% and by the Politano-Leadbetter technique in 28% of the patients. Bilateral reimplantation was done in 70 patients (80%). The results were satisfactory, with no obstructions. In 81% of the patients average followup was 3.9 years, although followup of less than 1 year in 19% was satisfactory to determine obstruction. Only 3% of the children were lost to followup. Postoperative reflux, which was noted in 5 patients, resolved in all but 1 ureter. These results reflect the experience of senior surgeons in pediatric urology.


Commentary: management of children with severe vesicoureteral reflux. The main findings of the IRSC after 5 years of observation are summarized. Of the 434 children entered 128 were from centers in America and 306 from Europe. They were randomly allocated and stratified to a medical or surgical regimen. Of the children 50% had scarred kidneys at entry evenly distributed between the groups. After 5 years of observation there was no difference in outcome between the 2 treatment groups in terms of renal size and growth, the development of new radiological renal scars or areas of parenchymal thinning, or of progression of established scarring. In Europe infection recurred in equal numbers of children but pyelonephritic symptoms were more common in the medical group. Nevertheless, new scars developed in 19 of 155 children treated medically and 20 of 151 children treated surgically, including 5 and 7, respectively, with previously normal kidneys. Factors influencing the choice of treatment include patient age, availability of expert surgical care and experienced medical supervision, parental choice and compliance. Followup studies indicate that renal scarring rather than persistence of reflux determines the prognosis and, therefore, emphasis should be placed on the prevention of scarring.


Medical management of mild and moderate vesicoureteral reflux: followup studies of infants and young children. A preliminary report of the Southwest Pediatric Nephrology Study Group. Mild and moderate vesicoureteral reflux is expected to resolve spontaneously in most children treated medically; however, maximum benefit or minimum risk of such therapy has not been defined. A prospective 5-year followup study of infants and children younger than 5 years at entry with primary vesicoureteral reflux (grades I to III/V) and radiographically normal kidneys after the first recognized urinary tract infection was initiated in 1984. A total of 113 patients was entered from 5 centers and 61% of the patients were less than 2 years old. Vesicoureteral reflux was unilateral in 65 cases (58%) and bilateral in 48 (42%). Of the 226 renal units reflux was grade IV in 4 (2%), III in 51 (22%), II in 81 (36%) and I in 25 (11%), and 65  (29%) had no vesicoureteral reflux. Data on 59 patients who have completed the protocol were analyzed for this report. Breakthrough urinary tract infection occurred in 20 patients. Of the 84 ureters with vesicoureteral reflux at diagnosis reflux resolved in 67%, and it was of lower grade in 22%, same grade in 8% and higher grade in 2%. Grade I vesicoureteral reflux resolved in 82%, grade II in 80% and grade III in 46% of the ureters. Resolution was better when vesicoureteral reflux was unilateral left (74%) than unilateral right (46%) or bilateral (60%). Renal scarring occurred, on average, in 10% of the kidneys without known vesicoureteral reflux or exposed only to nondilating (grades I and II) reflux and in 28% of those with dilating (grade III) reflux. Thirteen cases had breakthrough urinary tract infection but only after the scar was noted in 5. We conclude that under good medical management during 5 years of followup, even mild and moderate vesicoureteral reflux can be associated with renal injury.


Followup of conservatively treated children with high and low grade vesicoureteral reflux: a prospective study. A total of 202 children (mean age 31.5 +/- 23.3 months) with vesicoureteral reflux identified during the investigation that follows a urinary tract infection entered this prospective study dealing with the medical management of reflux. The diagnosis of vesicoureteral reflux was made significantly earlier in boys than in girls regardless of reflux grade (p < 0.001). At entry reflux nephropathy was present on a dimercaptosuccinic acid scan in 44% of 314 refluxing kidneys. There was no significant difference between boys and girls in the prevalence of reflux nephropathy. The renal lesions were more severe in boys independently of the grade of vesicoureteral reflux (p < 0.05). Breakthrough urinary tract infection was significantly more common in girls than in boys, regardless of vesicoureteral reflux grade (p < 0.05). Mean followup was 68.7 +/- 31.2 months. Patient age at the time of the first of 2 radionuclide cystograms without vesicoureteral reflux was considered the age of spontaneous resolution of reflux. Using life table estimations and analyzing data stratified to sex and grade of vesicoureteral reflux, we found that although reflux lasted longer in boys compared to girls, this difference was not statistically significant. During followup new scars developed in 7 patients related to breakthrough urinary tract infection. There was no significant difference between boys and girls in the development of new scars. To understand the natural history of vesicoureteral reflux children must be stratified by sex and grade of reflux.


Historical clues to the complex of dysfunctional voiding, urinary tract infection and vesicoureteral reflux. The International Reflux Study in Children. The prevalence of nonneuropathic bladder/sphincter dysfunction was assessed with a questionnaire in 310 of the 386 children enrolled in the European branch of the International Reflux Study in Children. Despite the exclusion criteria (neuropathic bladder, anatomical malformations other than vesicoureteral reflux and overt dysfunctional voiding or urge incontinence), the prevalence of bladder/sphincter dysfunction was as high as 18%. Four patterns of dysfunction emerged: urge syndrome, staccato voiding, fractionated and incomplete voiding, and voiding postponement. The questionnaire proved helpful in detecting low profile cases of bladder/sphincter dysfunction, as well as indicating the need for further urodynamic studies. A strong correlation was established between recurrences of urinary tract infections, as well as disappearance of vesicoureteral reflux (negative correlation) and nonneuropathic bladder/sphincter dysfunction. This finding implies that detection and treatment of bladder/sphincter dysfunction are essential in every child with the complex of recurrent urinary tract infection and vesicoureteral reflux.


Relationship between dysfunctional voiding and reflux. Bladder instability and the nonneurogenic neurogenic bladder are 2 urodynamically different dysfunctional voiding patterns. However, they share a common urodynamic mechanism in that they both produce functional urinary obstruction, which by changing the anatomy and function of the bladder, and ureterovesical junction produces and perpetuates vesicoureteral reflux. Urodynamic studies show that bladder decompensation with high end filling pressures, rather than high voiding pressures, is the mechanism for reflux and help to explain the seemingly paradoxical relationship among obstruction, reflux and high bladder pressures, namely that reflux does not usually occur when bladder pressures are high. This urodynamic analysis and review of the literature strongly support the belief that functional urinary tract obstruction caused by dysfunctional voiding can initiate and perpetuate vesicoureteral reflux, and provide an understanding of the mechanisms involved.


Long-term followup of infants with gross vesicoureteral reflux. The majority of children (1 year old or less) with gross vesicoureteral reflux already have renal damage at the time of presentation or reflux nephropathy develops during the first few years of life. We report the long-term followup of 31 patients (16 boys) presenting in infancy with gross vesicoureteral reflux (Rolleston classification) between 1952 and 1970. They had a total of 44 grossly refluxing ureters (13 bilateral, 18 unilateral) and presented between ages 1 day and 48 weeks (mean 15.3 weeks). Of the 31 infants 5 died within the first year of life, 4 were followed for up to 11 years before being lost to followup and 1 was killed in a motor vehicle accident after 19.5 years of followup. The remaining 21 patients have been followed for 16 to 37 years (mean 23.9 years); 4 have normal kidneys, and 13 have unilateral and 4 have bilateral reflux nephropathy. Of those patients with unilateral reflux nephropathy proteinuria, hypertension and renal failure developed in 1 born with a single kidney and he is now on hemodialysis, while 2 others have a diastolic blood pressure of 90 mm. Hg or greater. Of the 4 patients with bilateral reflux nephropathy 2 have proteinuria and renal insufficiency, with 1 progressing towards end stage renal failure. Infants who present with gross vesicoureteral reflux within the first year of life appear to do well if free of severe bilateral reflux nephropathy at presentation. Patients with reflux nephropathy should remain under regular nephrological supervision with particular attention given to proteinuria, renal function and blood pressure.


Morphological characteristics of segmental renal scarring in vesicoureteral reflux. We examined 25 complete and partial nephrectomy specimens from 21 patients with advanced reflux nephropathy, all of which showed severe renal atrophy and loss of parenchyma. All specimens that included nonatrophic or partially atrophic renal tissue contained small medullary scars that involved only portions of the medullary pyramids. These sublobar medullary scars, which appeared linear and were typically discrete, extended from the inner medulla to the cortex. They obliterated collecting ducts, vasa recta and recurrent loops. The cortical portions of the scars contained remnants of nephrons and variable infiltrates of chronic inflammatory cells with lymphoid follicles. Seven of the specimens also contained acute disruptive ductal lesions with histopathological features characteristic of intrarenal reflux. We believe that the linear scars are the result of single duct medullary disruptions, mediated perhaps through obstruction of the several thousand nephrons subtended by each papillary duct and perhaps through localized disruption of the renal microvasculature. These sublobar scars accumulate as scarring progresses to end stage renal atrophy.


Long-term followup of renal morphology and function in children with recurrent pyelonephritis. Renal morphology and function were evaluated in 161 children with recurrent pyelonephritis with or without vesicoureteral reflux and with or without scarred or small kidneys. The patients were followed for 1 to 21 years. Renal function was determined by glomerular filtration rate and effective renal plasma flow by clearances of inulin and paraaminohippuric acid. Of 105 children with normal kidneys originally small or scarred kidneys developed in 37, of whom 22 had grade III or greater vesicoureteral reflux, while small kidneys developed in 13 of 29 children with renal scarring originally. Of the 37 children with normal kidneys originally renal parenchymal scarring developed in 14 after the age of 4 to 5 years. Glomerular filtration rate was already < -2 standard deviations of that of controls in 51% of the patients at the first and in 53% at the last investigation of renal function. Of these patients with a glomerular filtration rate of < -2 standard deviations 69% had small or parenchymally reduced kidneys most of whom had the first pyelonephritis episode before age 3 years. Patients with small kidneys had a lower glomerular filtration rate than those with normal sized kidneys, whether scarred or not. The low glomerular filtration rate and its subsequent further reduction were related to kidney size and not to the presence or degree of vesicoureteral reflux. However, in individual patients the rate of functional deterioration could not be predicted from the radiological findings. Patients with bilateral small kidneys seemed to show the greatest decrease in glomerular filtration rate during followup as did those with grade III or greater reflux undergoing surgery bilaterally and those patients also had a lower glomerular filtration rate at the last investigation compared to patients not undergoing surgery. In conclusion, renal functional damage seems to occur early in the course of the disease and seems to be related to kidney size but there is a further slow progression with reduction in renal function which occurs, although this is difficult to predict from the radiological changes in individual patients. Therefore, patients with recurrent pyelonephritis should be followed regularly by glomerular filtration rate determination using an accurate method.


Vesicoureteral reflux and pyelonephritis in the monkey: a review. P-fimbriated Escherichia coli, which cause nonobstructive pyelonephritis, adhere to a specific urothelial glycolipid receptor. In either the presence or absence of reflux (in the area of turbulent urine flow) these bacteria ascend the ureter and cause a decrease in ureteral motility. Endotoxin causes peristalsis to cease, leading to ureteral dilatation and change in papillary shape, thus allowing intrarenal reflux and adherence of the bacteria to renal tubules. Bacterial infection of a refluxing ureter may cause reflux to persist. Once the bacteria reach the kidney rapid effects occur at the cellular level with activation of complement followed by granulocytic aggregation and capillary obstruction, causing renal ischemia and damage during reperfusion. In addition, during phagocytosis the respiratory burst occurs, releasing toxic oxygen molecules, which leads to renal tubular death, invasion of the interstitium, microabscess and renal scar formation, that is chronic pyelonephritis, which equates with reflux nephropathy.


The long-term results of prospective sibling reflux screening. A prospective study was begun more than 10 years ago to identify the incidence of vesicoureteral reflux in the siblings of patients with reflux. A total of 354 siblings of 275 index patients was screened with a voiding cystourethrogram for the presence of reflux. Of the siblings tested 119 (34%) were found to have reflux, including 75% who were asymptomatic. Reflux was present in a significant percentage of younger siblings. No correlation with index patient reflux grade, sex or established renal damage could be related to the likelihood of sibling reflux. A slightly higher rate of reflux was found in the female siblings of female index patients, which is a variation from the initial study. The incidence of renal damage was significantly reduced in the siblings with reflux compared to the index patients, which was also true in the youngest patients, who are believed to be the most susceptible to reflux-mediated renal damage. Sibling reflux screening can be justified due to a high percentage of siblings found to have reflux without symptoms and a significant decrease in renal damage compared to the index patients. Aggressive screening in young children (less than 5 years old) is still advisable, although this recommendation has been modified for older children. Additional information will be needed before the genetic transmission of reflux can be clarified.


Fetal vesicoureteral reflux: outcome following conservative postnatal management. Of 222 infants with a urinary tract abnormality detected antenatally 30 male and 9 female patients (64 renal units) were found to have primary vesicoureteral reflux. Grade of reflux was predominantly severe, with grade III or higher noted in 83% of the patients. Prenatal and postnatal ultrasound failed to detect any abnormality in 29 refluxing units (45%) discovered contralateral to the known abnormal system, although 19 had grade III or higher reflux. Of the 64 refluxing units 8 underwent primary ureteral reimplantation, 12 were lost to followup and 44 were managed conservatively for a mean of 3.3 years. Reflux ceased in 61% of the cases, improved in 14% and remained unchanged in 23%. In only 1 unit did the grade of reflux increase. Documented urinary tract infection occurred in 6 of the 39 reflux patients. Dimercaptosuccinic acid renography performed in 21 infection-free patients demonstrated global reduction in renal parenchyma in 4 units, focal parenchymal defects in 3 and normal function in 14. Conservative postnatal management of fetal vesicoureteral reflux is justified. Global and focal parenchymal changes can occur in the kidneys of infants with reflux despite the absence of urinary tract infection.


Commentary: importance of antenatal diagnosis of vesicoureteral reflux. Although hydronephrosis detected by prenatal ultrasonography often is assumed to be secondary to obstructive uropathy, in approximately 10% of the cases renal pelvic dilatation results from primary vesicoureteral reflux. More than 80% of neonates with reflux are male and two-thirds have bilateral reflux. Approximately 80% have at least grade III reflux. At birth between a third and half may have reduced renal function on isotope renography, even in the absence of urinary infection. Approximately 20% of neonates with grade IV or V reflux followed nonoperatively experience spontaneous reflux resolution by age 2 years. However, in approximately 25% of boys followed nonoperatively urinary tract infections developed by age 2 years despite antimicrobial prophylaxis. Because the majority of these boys have been uncircumcised, circumcision seems advisable. Ureteral reimplantation should be reserved for those with breakthrough urinary tract infection, new renal scars or persistent high grade reflux.


Intrarenal access: 3-dimensional anatomical study. In an attempt to determine the best route to puncture and access the kidney collecting system we studied 62, 3-dimensional polyester resin endocasts of the pelvicaliceal system together with the intrarenal vessels. A retrograde pyelogram was obtained, and the arterial and venous trees were injected with red and blue resins, respectively. When the resin was still in the gel state, the kidneys were positioned at 30 to 45 degrees and the collecting system was punctured under radioscopy. Since the resin is not opaque to x-ray the operator was not able to visualize the vessels while puncturing. After puncture, the needle was maintained in place, the contrast medium was removed and the pelvicaliceal system was filled with yellow resin. After the resin had set, the renal organic matter was corroded in acid and the endocast was obtained (with the needle in the original position). This type of preparation allowed us to examine the needle tract and the vessels damaged during the puncture. In the same kidney we punctured the superior pole, mid kidney and inferior pole. In some cases we also punctured the renal pelvis. We performed 104 punctures through an infundibulum, 39 through a fornix of a calix and 12 through the renal pelvis. Due to a high percentage of vascular lesions, intrarenal access through an infundibulum should be avoided. Also, renal pelvis puncture should be avoided. Regardless of the kidney region, puncture through a fornix of a calix was safe.


Flow cytometric analysis of small renal tumors. Flow cytometric deoxyribonucleic acid (DNA) content analysis was performed on 26 renal tumors 3.0 cm. or less in maximum diameter. We noted DNA aneuploid cell populations in 8 of 25 tumors (32%) evaluable for DNA ploidy status. DNA aneuploid cells comprised 7 to 59% of the cells in those tumors. In comparison, 12 of 25 tumors (48%) larger than 3.0 cm. had aneuploid cell populations. S phase cell populations were significantly increased in the small aneuploid tumors compared with the small diploid tumors (p < 0.001). We believe that these small tumors have the potential to behave aggressively and, therefore, they should be treated no differently than larger renal neoplasms.


Interleukin-6 in renal cell carcinoma.

Interleukin-6 in renal cell carcinoma. We studied interleukin-6 production in 4 human renal cell carcinoma cell lines and measured the serum level in 71 patients with renal cell carcinoma, thus, clarifying a relationship between interleukin-6 secretion and an occurrence of the paraneoplastic syndrome in the carcinoma. Interleukin-6 was produced by 3 cell lines and detected in 25% of the patients. The level of interleukin-6 did not directly correlate with tumor volume and the differentiation grade of the carcinoma. However, the positive rate increased with progression of the stage. The serum level affected the 5-year survival of patients without distant metastasis. When serum interleukin-6 was elevated patients had a significantly higher frequency of unexplained fever and an elevation of acute phase proteins. These results suggest that some renal cell carcinomas can produce interleukin-6 and this cytokine is responsible for several paraneoplastic syndromes in the carcinoma.


The prognostic significance of vascular invasion in upper urinary tract transitional cell carcinoma. The prognostic significance of vascular invasion was evaluated in a retrospective series of 30 patients with upper urinary tract cancer who underwent a potentially curative operation. Vascular invasion was found in 11 patients (36.7%). The incidence of vascular invasion was well correlated with tumor grade and stage. The incidence of metastases postoperatively was significantly higher in the patients with (72.7%) than without (21.1%) vascular invasion (p < 0.01). The survival rate of the patients with vascular invasion was significantly lower than in those without vascular invasion (p < 0.005). In multivariate Cox regression analysis the prognostic value of vascular invasion was independent of tumor stage and grade. These results indicate that vascular invasion should predict a more unfavorable outcome in patients with upper urinary tract cancer as an independent morphological indicator.


In situ extracorporeal shock wave lithotripsy for obstructing ureteral stones with acute renal colic. In situ (no instrumentation) extracorporeal shock wave lithotripsy (ESWL*) was used to treat 49 patients with obstructing ureteral stones causing acute renal colic. Ureteral obstruction was diagnosed on the delayed films of an excretory urogram and was classified as severe (dilatation above and no contrast medium seen below the stone) in 17 patients and partial (dilatation above and contrast medium seen below the stone) in 32. Upper third ureteral stones were present in 41 patients (obstruction severe in 15 and partial in 26) and lower third ureteral stones were present in 8 (obstruction severe in 2 and partial in 6). ESWL was performed within 14 days of the onset of the acute renal colic because of persistent pain with an unmodified Dornier HM3 lithotriptor in 17 patients and a Medstone STS device in 32. With single stones the stone-free rate at 3 months, the repeat ESWL rate and the secondary procedure (stone basketing) rate were 92%, 6% and 8%, respectively, with severe obstruction, and 78%, 6% and 6%, respectively, with partial obstruction. No urinary drainage procedures for sepsis were required after ESWL. Obstructing ureteral stones, which presented mainly in the upper third of the ureter, were successfully treated with in situ ESWL without the need for either bypassing the stone with a ureteral stent or for pushing the stone back into the kidney before treatment with ESWL.


Clinical experience with flexible ureteropyeloscopy. Flexible ureteroscopes and their accessory working instruments have undergone tremendous design advances since the earliest reports in the 1960s. These changes have allowed for the expansion of indications for flexible ureteroscopy with the emphasis now on therapeutic and not just diagnostic applications. This report covers 290 procedures done with actively deflectable, flexible ureteroscopes on 222 patients. Followup averaged 11.2 months in 228 patients, while the remaining 62 were followed by the original referral center. Included were 154 procedures for stones and 79 for tumors or filling defects. Of the procedures 149 were performed with the patient under local anesthesia with sedation, while 128 were done with use of general anesthesia. The procedure was done in only 22% of the cases for purely visual diagnosis without any interventional manipulation. More than 42% of the cases involved stone retrieval or lithotripsy, in which case the laser was most commonly used (56 cases). The total success rate was 95.5%, and the most common complications were colic or pain in 9% and fever in 6.9%. A stricture developed in 2 patients. A stent was left in more than 93% of the patients and the usual postoperative stay was less than 3 days. With the introduction of even more improved instruments, flexible ureteroscopy should continue to gain ground as an option for the management of upper urinary tract pathology.


A European Organization for Research and Treatment of Cancer--Genitourinary Group phase 2 study of chemotherapy in stage T3-4N0-XM0 transitional cell cancer of the bladder: evaluation of clinical response. From 1986 to 1990 the European Organization for Research and Treatment of Cancer--Genitourinary Group conducted a phase 2 trial of neoadjuvant chemotherapy in patients with stage T3-4N0-XM0 transitional cell carcinoma of the bladder. The objectives were to evaluate the clinical response in relation to the pathological response, and to measure the side effects of chemotherapy. Of 171 patients entered 136 were fully evaluable: 18% had clinical complete remissions, 36% had clinical partial remissions, 39% had no clinical remissions and 10% had unknown response. A selected subgroup of 76 patients underwent cystectomy after 2 or 4 courses of chemotherapy: 2 were not evaluable for pathological response because of preoperative radiotherapy after neoadjuvant chemotherapy, 16 had a pathological complete remission, 7 had a pathological partial remission and 51 had no pathological remission. Comparison of the clinical response or T category only after 2 courses of chemotherapy with the pathological response after 2 or 4 courses of chemotherapy showed that in a number of patients the disease status could be downstaged to pathological complete or partial remission by additional courses of chemotherapy. If the discrepancies between clinical and pathological responses, or between T and P categories, induced by further downstaging after additional chemotherapy were left out, it was shown that clinical complete and partial remissions were a heterogeneous group but nonresponders could be delineated with a 100% accuracy by clinical response evaluation and transurethral resection biopsy only. Furthermore it seems important to establish the number of chemotherapy courses to induce a maximal response of the primary tumor.


Early experience with intraurethral collagen injections for urinary incontinence. We report on 41 patients (10 men and 31 women) who underwent collagen injections for urethral incompetence. Mean followup was 6 months (range 3 to 11 months) in men cured or improved, 8.4 months (range 3 to 15 months) in women who were cured and 4.5 months (range 2 to 10 months) in women who were improved. In women the procedure was usually performed through a periurethral approach while they were under local anesthesia and in men it was performed transurethrally while under either general or local anesthesia. Of the 31 women 28 (90.3%) were cured (15) or improved (13). Mean maximum Valsalva pressure increased from 31 cm. water before injection to 85 cm. water at 6 months after injection in women who were cured or improved. The mean amount of collagen used in the female group was 12.7 cc (range 2.5 to 47.5) and the mean number of treatments was 2 (range 1 to 7). Of the men 7 (70%) had successful results (2 cured and 5 improved). In contrast to the women, they required a mean of 51.8 cc (range 7.5 to 82.5) of collagen and a mean of 6 treatments (range 3 to 12). Of 5 patients with bladder instability 4 did not improve. One patient suffered acute bacterial prostatitis and 2 patients had post-injection urinary retention. All women with little or no bladder neck hypermobility (types 1 and 3) were either cured or improved. We conclude that intraurethral collagen injection is safe and simple to perform. The results achieved in women are acceptable. In men, while collagen does provide improvement, the cost-to-benefit ratio and effectiveness are less than those in women. Instability may obviate a good outcome.


The need for antibiotic prophylaxis of patients with penile implants during invasive dental procedures: a national survey of urologists. A national survey of urologists was conducted regarding the need for prophylactic antibiotic coverage for patients with penile implants when undergoing invasive dental treatment. A total of 1,756 questionnaires was sent to urologists in the United States and 297 responses were received, for a participation rate of 17%. The low response rate might be partly related to a low level of concern by urologists due to the lack of reported cases of penile implant infections following invasive dental procedures and the lack of the literature calling attention to this possible association. This is supported by the fact that none of the responding urologists had noted any case of infection of the prosthesis following dental treatment. The majority of urologists who responded did not recommend antibiotic prophylaxis for penile implant patients undergoing invasive dental treatment. The majority of urologists who recommended prophylaxis selected a cephalosporin. None of the responding urologists indicated that they were aware of infection developing in any penile implant patients following invasive dental treatment. The dentist is advised to consult with the urologist of patients with penile implants on an individual basis to determine the need for antibiotic prophylaxis.


Risk factors for male partner antisperm antibodies. The role of antisperm antibodies in human infertility remains controversial. Indications for antisperm antibody testing of male partners of infertile marriages have been based upon anecdotal reports and studies using outdated assays. In an effort to define the indications for antisperm antibody testing of the male partner, the immunobead assay for antisperm antibodies was performed upon 100 consecutive men referred for evaluation of male factor infertility. The prevalence of antisperm antibodies in this patient population was 18% and only 9% when patients with a history of vasectomy were excluded. Of all the factors analyzed, only a history of vasectomy and sperm agglutination on semen analysis were predictive of antisperm antibody status (p < 0.001). Use of the aforementioned parameters as an indication for antisperm antibody testing would have resulted in a sensitivity of 94%, specificity 73% and negative predictive value 98% in this patient population. The only way to identify all patients with significant levels of antisperm antibody activity (sensitivity 100%) would have been to test every patient.


Microsurgical inguinal varicocelectomy with delivery of the testis: an artery and lymphatic sparing technique. Conventional techniques of varicocele repair are associated with substantial risks of hydrocele formation, ligation of the testicular artery, and varicocele recurrence. We describe a microsurgical technique of varicocelectomy that significantly lowers the incidence of these complications. The testicle is delivered through a 2 to 3 cm. inguinal incision, and all external spermatic and gubernacular veins are ligated. The testis is returned to the scrotum and the spermatic cord is dissected under the operating microscope. The testicular artery and lymphatics are identified and preserved. All internal spermatic veins are doubly ligated with small hemoclips or 4-zero silk and divided. The vas deferens and its vessels are preserved. Initially, we performed 33 conventional inguinal varicocelectomies in 24 men without delivery of the testis or use of a microscope. Postoperatively, 3 unilateral hydroceles (9%) and 3 unilateral recurrences (9%) were detected. For the next 12 cases 2.5x loupes were used resulting in no hydroceles but another recurrence (8%). We then performed 640 varicocelectomies in 429 men using the microsurgical technique with delivery of the testis. Among 382 men available for followup examination from 6 months to 7 years postoperatively no hydroceles and no cases of testicular atrophy were found. A total of 4 unilateral recurrent varicoceles (0.6%) was identified. The differences between the techniques in the incidence of hydrocele formation and varicocele recurrence are highly significant (p < 0.001). No wound infections occurred in any men. Four scrotal hematomas (0.6%), 1 of which required surgical drainage, occurred in the group with microsurgical ligation and delivery of the testis compared to none with the conventional technique. Preoperative and postoperative semen analyses (mean 3.57 analyses per patient) were obtained on 271 men. The changes in sperm count x 10(6) cc (36.9 to 46.8, p < 0.001), per cent motility (39.6 to 45.7%, p < 0.001) and per cent normal forms (48.4 to 52.10%, p < 0.001) were highly significant. The pregnancy rate was 152 of 357 couples (43%) followed for a minimum of 6 months postoperatively. Delivery of the testis through a small inguinal incision provides direct visual access to all possible avenues of testicular venous drainage. The operating microscope allows identification of the testicular artery, lymphatics and small venous channels. This minimally invasive, outpatient technique results in a significant decrease in the incidence of hydrocele formation, testicular artery injury and varicocele recurrence.


Laparoscopic unroofing of a renal cyst.

Laparoscopic unroofing of a renal cyst. Excision of a renal cyst via the flank approach results in a painful postoperative recovery requiring several days of hospitalization. We used laparoscopy in a selected patient to unroof a large complex renal cyst. The technique could optimally be used for simple cysts. The procedure was minimally traumatic, morbidity was negligible and the patient was discharged from the hospital the morning after the operation. After a 6-month followup, we believe that this laparoscopic technique is a significant advance in urological surgical management and may be better indicated for symptomatic, recurrent, simple renal cysts.


Laparoscopic removal of bladder diverticulum. A large symptomatic bladder diverticulum in a 72-year-old man was removed through laparoscopic dissection. The surgical technique of laparoscopic diverticulectomy is described. Laparoscopic diverticulectomy can be done with minimal morbidity and has distinct advantages over other forms of treatment of bladder diverticula.


Urodynamic effects of intravesical instillation of terodiline in healthy volunteers and in patients with detrusor hyperactivity. The effects of intravesical instillation of terodiline on urodynamic parameters were investigated in 8 healthy volunteers (10(-4) M.) and in 34 patients with detrusor hyperactivity (10(-5) M.) of neurogenic (22) or nonneurogenic (12) origin. The volunteers were investigated with conventional medium-fill cystometry, while in the patients a modified cystometric technique with slow intermittent filling was used. The reproducibility of the procedure was verified in 17 patients. Instillation of terodiline had no effect on the normal bladders nor were any improvements found in the nonneurogenic patients. In 12 patients in the neurogenic group treated with terodiline instillation the bladder capacity increased significantly (p < 0.05) from 289 +/- 32 to 413 +/- 55 ml. Within this group 5 patients were responders. It is suggested that pathophysiological changes may explain the difference between the neurogenic and nonneurogenic groups, and that the number of responders within the neurogenic group may be increased by an optimal drug preparation and increased dosage. Intravesical administration of terodiline may offer an alternative treatment in selected patients with detrusor hyperreflexia.


Function of the conus medullaris and cauda equina in the early period following spinal cord injury and the relationship to recovery of detrusor function. A total of 26 patients with an early suprasacral spinal cord injury underwent comprehensive neurourological evaluation to determine if there was any correlation between the return of detrusor function and neural function of the sacral cord. In addition, the incidence of a subclinical sacral neural dysfunction early after spinal cord injury was assessed. Lumbosacral evoked potentials to tibial nerve stimulation were used to assess the sensory root and cord gray matter of the L5 to S2 segments, while urodynamic evaluation was performed to assess detrusor function. Of those patients with normal lumbosacral evoked potentials 82% recovered detrusor contractility as opposed to 66% with abnormal evoked potentials. Four patients (23.5%) had persistent detrusor areflexia when studied 9 to 20 months following the acute injury. The potential problems attempting to correlate the neurophysiological and urodynamic studies are multiple and are extensively discussed. Despite these potential problems the return of detrusor function correlated well with associated normal lumbosacral evoked potentials suggesting that this test can be used in the early phase following spinal cord injury to predict return of bladder function, since it is independent of the level of spinal cord excitability. Of the patients studied 38% had coexistence of an occult lumbosacral dysfunction. This rate is higher than that found in the chronic stabilized spinal cord injury population (20.5%), since the cases in our study may represent a more severe lesion.


Effects of acute bolus and chronic continuous intrathecal baclofen on genitourinary dysfunction due to spinal cord pathology. A prospective, blinded study was done to examine the effects of acute bolus and chronic continuous intrathecal baclofen on genitourinary function in 10 patients with severe spasticity due to spinal cord pathology. Genitourinary function was assessed by symptom questionnaires and urodynamic studies performed after a bolus dose of baclofen and 6 to 12 months after continuous intrathecal baclofen. Results were compared to placebo for acute bolus testing or to pre-continuous intrathecal baclofen values. In all patients with irritative voiding and urge incontinence uninhibited bladder contractions were eliminated. Of 3 patients with an indwelling urethral catheter for incontinence due to detrusor hyperreflexia 1 was converted to intermittent self-catheterization. Whereas bladder capacity, compliance, sensation and voiding pressures were not different after continuous intrathecal baclofen, when a mean of all patients was compiled, a 72% increase in capacity and 16% improvement in compliance were observed in subjects without cervical spinal cord pathology. Detrusor-sphincter dyssynergia was abolished in 40% of the patients. Continuous intrathecal baclofen may represent a novel approach to the management of patients with a neurogenic bladder who have decreased bladder compliance and detrusor hyperreflexia not controlled by oral medications.


The prognostic value of bladder contractility in transurethral resection of the prostate. The contractility of the bladder as quantified by a parameter of approximated power per bladder surface area based on the Hill equation (Wmax) was calculated for 29 patients before and 3 months after transurethral resection of the prostate. There was no significant change in this parameter as a result of the operation. Patients who still had a significant amount of residual urine postoperatively had decreased contractility before and after surgery so that the postoperative condition could have been predicted preoperatively. In many patients a fading contraction was observed, that is detrusor contractility decreased during voiding, which gave rise to a significantly increased volume of residual urine. In most patients this pattern was restored to normal after relief of the obstruction, indicating that it was not related to structural changes in the detrusor muscle. A preoperative fading contraction had no predictive value towards the outcome of the operation.


Continence after radical cystoprostatectomy and total bladder replacement: a urodynamic analysis. Urodynamic evaluation was performed in 10 patients after radical cystoprostatectomy and continent urethral diversion with detubularized ileum and in 13 patients continent after radical prostatectomy. In both groups surgical techniques were modified to optimize preservation of the periurethral tissue at the prostatic apex. For the ileal neobladder group 9 patients (90%) were completely continent and 1 (10%) noticed moderate nocturnal incontinence. The urethral sphincteric mechanism was well preserved in these patients, with no significant difference between the 2 groups in mean functional urethral length (3.8 +/- 0.6 versus 3.6 +/- 0.8 cm., p = 0.55) or maximal urethral closure pressure (87 +/- 34 versus 74 +/- 20 cm. water, p = 0.26). Tubularization of the bladder or neobladder above the level of the external sphincter was noted in both groups. Continence after radical cystoprostatectomy with continent urethral diversion and after radical prostatectomy is dependent upon an intact urethral sphincteric mechanism as well as a compliant, low pressure reservoir, either bladder or a bladder substitute. Urinary incontinence after total bladder replacement with detubularized ileum can be minimized by preserving as much of the distal urethral sphincter as possible. This can be done by careful dissection of the prostatic apex, performed under direct vision, with an understanding of the anatomy of the urethral sphincter and its innervation.


False diagnosis of renal transplant urinary leakage on scintigraphy with mercaptoacetyltriglycine. 99mTechnetium-mercaptoacetyltriglycine (99mTc-MAG-3) has rapidly become the best isotope for transplant renal scintigraphy because of the excellent anatomical resolution. Because 99mTc-MAG-3 is also sequestered by the liver and excreted into the biliary system, images of the gallbladder and intestinal tract will appear in normal 99mTc-MAG-3 scans, especially on delayed scintigraphs. We describe the clinical interpretation of normal bowel images as urinary extravasation in a renal transplant recipient with a sudden decrease in renal function.


Retroperitoneal neurogenous choristoma.

Retroperitoneal neurogenous choristoma. A 6-year-old girl with urinary complaints underwent ultrasonography, which revealed a retroperitoneal cystic mass adjacent to the left kidney. Computerized tomography did not demonstrate whether the mass was an adrenal cyst or a duplicated upper pole segment. Exploration revealed a neurogenous choristoma, which is a collection of histologically normal tissue that is ectopically situated. We believe that this is the first report of this rare entity occurring in the retroperitoneum.


The transmission of vesicoureteral reflux from parent to child. Vesicoureteral reflux is now recognized to be hereditary and familial. The incidence of reflux in siblings has proved to be significant but less is known about the incidence of reflux in the offspring of known reflux patients. In an ongoing prospective series of reflux screening we identified 23 patients of childbearing age with a known history of reflux and screened their 36 offspring with an awake voiding cystourethrogram. Of these 36 offspring 24 (66%) exhibited vesicoureteral reflux. The literature was also reviewed to determine the incidence of parent/child reflux from reported cases. This review revealed a 65% rate of reflux in the offspring of known patients. Our preliminary results coupled with those in the literature signify a need to screen the offspring of known reflux patients and suggest a rethinking of the genetic transmission for this trait. While vesicoureteral reflux could still be a multifactorial genetic trait with a major gene, consideration must also be given to an autosomal dominant inheritance pattern.


Median raphe cysts of the genitalia.

Median raphe cysts of the genitalia. We report 2 recent cases of midline cysts of the genitoperineal raphe in children, and discuss the embryogenesis, diagnosis and management. Congenital anomalies of an unclear etiology, median raphe cysts are probably more common than has been reported in the literature. Medical attention is usually sought for secondary infections or pain with intercourse. Awareness and prompt identification of these entities by urologists are essential for proper management when differentiation from other more formidable lesions, including urethral diverticula, becomes important. Simple surgical excision is effective in most cases.


Urinary tract infections in children with posterior urethral valves after kidney transplantation. The records of 14 boys with posterior urethral valves who had renal failure and subsequently underwent renal transplantation were reviewed to determine the postoperative incidence of urinary tract infection relative to that of 29 male transplant children without valves, who served as controls. There were no significant differences between the posterior urethral valve patients and controls with regard to age, donor source, immunosuppression, followup after transplantation or mean calculated creatinine clearance. Vesicoureteral reflux was found in 1 child with posterior urethral valves and 3 of the children in the control group (p not significant). A total of 15 urinary tract infections occurred in 5 children (36%) with posterior urethral valves, for a rate of 1 per 30 patient-months of followup, and 6 urinary tract infections occurred in 2 controls (7%), for a rate of 1 per 216 patient-months of followup (p < 0.05). However, only 1 of 26 controls (4%) without vesicoureteral reflux had urinary tract infection, for a rate 1 per 1,144 patient-months (p < 0.01). Conversely, the rate of urinary tract infections in controls with vesicoureteral reflux was similar to that of children with posterior urethral valves. Of the 5 children with posterior urethral valves 4 had the initial urinary tract infection within 2 months of transplantation and 10 of 15 episodes occurred within the first 4 months. Antimicrobial prophylaxis did not appear to decrease the rate of infection in children with posterior urethral valves. A history of posterior urethral valves increases the frequency of urinary tract infection after renal transplantation but the usefulness of antimicrobial prophylaxis and the relationship to long-term graft function remain to be determined. Urinary tract infection rarely develops in other transplanted boys without vesicoureteral reflux.


Hydronephrosis secondary to congenital pelvic arteriovenous malformation: a case report. We report on a 26-year-old woman with a pelvic mass that caused ureteral obstruction and a hydronephrotic kidney. Diagnosis was congenital pelvic arteriovenous malformation and surgery was successful. The patient underwent staged preoperative intra-arterial embolization to decrease operative morbidity and facilitate complete removal.


Diagnostic and therapeutic problems in multicentric renal angiomyolipoma. Multicentric renal angiomyolipoma is a rare form of benign tumor. However, its effective incidence as evaluated in autopsy studies may be as high as 8%. There are 2 main types of renal angiomyolipoma, that is isolated forms and those associated with other diseases, such as phakomatosis, polycystic kidneys and fibromuscular dysplasia. The tumor may also display malignant behavior with local invasiveness and regional lymph node involvement. However, the clinical course is benign and multicentricity is important for prognosis. Histopathological diagnosis often is difficult. Immunohistochemical analysis of surgical specimens using a panel of monoclonal antibodies, including HMB-45 and actin, enabled us to make a definitive diagnosis in 3 cases of multicentric renal angiomyolipoma.


Bilateral renal angiomyolipoma associated with bilateral renal vein and inferior vena caval thrombi. We report a case of bilateral renal angiomyolipoma with thrombosis of the bilateral renal veins and inferior vena cava. Right partial nephrectomy and total thrombectomy were performed. To our knowledge only 5 cases of invasion of the inferior vena cava have been described. We report a case in which the renal veins were involved bilaterally. Treatment modalities are discussed.


Unilateral ureteral obstruction secondary to rupture of liver echinococcal cyst. We report a case of ureteral obstruction by reactive retroperitoneal fibrosis secondary to rupture of a liver echinococcal cyst after minimal blunt flank trauma. The patient presented initially with a cyst-cutaneous fistula and was treated with mebendazole, since surgery was refused. Unilateral ureteral obstruction due to reactive dense retroperitoneal fibrosis developed 2 years later, which presumably was initiated by intense inflammatory reaction to the cyst content. Diagnosis was established by excretory urography, ultrasonography and computerized tomography, and was histologically confirmed. Hydronephrosis and hydroureter resolved following ureterolysis. This complication is anticipated to be encountered more frequently with the use of the new potent anthelmintic agents, which may successfully prevent daughter cyst formation but fail to abolish reactive retroperitonitis.


Delayed spontaneous rupture of an ileocolonic neobladder. A case of delayed spontaneous rupture of an ileocolonic neobladder and subsequent peritonitis 4 years after the initial operation is reported. Many of the features of this case are similar to those noted in recent reports of spontaneous rupture of an augmented bladder and it is postulated that the etiology is the same.


Complications of intravesical bacillus Calmette-Guerin: a case report. Bacillus Calmette-Guerin (BCG) is the most effective agent currently available to treat superficial bladder cancer. However, this form of therapy is not without potential serious or fatal complications. In addition to the potentially toxic systemic side effects attributed to hematogenous absorption of the bacillus, direct upper tract seeding may occur in patients with vesicoureteral reflux. We report on a patient treated with intravesical BCG for bladder cancer in whom unilateral necrotizing granulomatous pyelonephritis developed. Although severe, this complication is rare and we conclude that reflux is not a contraindication for intravesical BCG therapy.


Clinical evidence of systemic persistence of bacillus Calmette-Guerin: long-term pulmonary bacillus Calmette-Guerin infection after intravesical therapy for bladder cancer and subsequent cystectomy. A patient with urothelial bladder carcinoma is reported who suffered from culture proved pulmonary bacillus Calmette-Guerin (BCG) infection 14 months after a single course of intravesical BCG and 11 months after subsequent radical cystectomy for progressive cancer. This unusual case raises the question of the ultimate fate of intravesically instilled BCG and the possible persistence of these mycobacteria in remote organs. Systemic spread and dormant survival at least in some cases are suggested, and therapeutic and diagnostic consequences are discussed.


Invasive bladder cancer following 125iodine implants. We present 2 cases of invasive transitional cell carcinoma of the bladder following implantation of 125iodine seeds for the treatment of localized adenocarcinoma of the prostate. These tumors, which occurred approximately 6 years after radiotherapy, were located in the trigone and prostatic urethra within the previous radiation treatment field. The development of high grade transitional cell carcinoma in these patients may be due to the tumorigenic effects of 125iodine radiation.


Significant obliteration of the urethral lumen after Wallstent implantation. The permanently implanted self-expandable urethral stent (Wallstent) has found increased use in patients with recurrent urethral strictures because of its simple implantation technique. To date there have been no reports of serious complications. At 6 weeks after stent implantation our patient had complete luminal obstruction. This complication demonstrates the need for short-term controls after implantation of a urethral stent.


Malacoplakia of the urethra: a case of unique localization with followup. A case of malacoplakia of the urethral meatus, without any association of vesical involvement, or any other synchronous or metachronous localization is presented. To our knowledge this is the fourth case in the literature at this site. The patient was free of disease 9 years after excision.


Prosthetic penile infection: "rescue procedure" with rifamycin. Penile prosthetic implantation is a successful procedure for the management of male erectile impotence. However, infection remains the most serious complication requiring removal of the device. Later reinsertion can be difficult due to fibrosis and a shortened penis. We present 3 cases of penile infection with Staphylococcus epidermidis in which a new penile prosthesis was placed after 72 hours of continuous irrigation of the corpora cavernosa with rifamycin. The procedure requires judicious selection of patients and a stable clinical status.


Laparoscopic retroperitoneal lymph node dissection in a patient with stage 1 testicular carcinoma. Minimally invasive laparoscopic surgical techniques are being increasingly applied to the treatment of urological diseases. We report a case of a laparoscopically performed modified bilateral retroperitoneal lymph node dissection for clinical stage 1 testicular cancer. The laparoscopic surgical approach to the retroperitoneal nodes is a technically feasible procedure that can remove lymph node tissue from all primary landing sites for testicular cancer metastases with potentially decreased morbidity.


Endoscopic hydrocele ablation.

Endoscopic hydrocele ablation. A new technique for the treatment of hydroceles by percutaneous drainage and endoscopic ablation under direct vision is described. The possible benefits and drawbacks of this treatment modality for symptomatic hydroceles are discussed.


Near fatal liver dysfunction secondary to administration of flutamide for prostate cancer. A 66-year-old man with metastatic prostate cancer was treated with bilateral orchiectomy and 750 mg. flutamide per day. Near fatal liver dysfunction developed 10 weeks later. Flutamide was discontinued and 8 weeks later liver enzymes had returned to normal.


Urodynamics in the early stages of spinal cord compression from prostate adenocarcinoma. Acute urinary retention developed in 2 patients with a history of prostate cancer. Urodynamic evaluation revealed autonomic dysfunction, which contrasted with a prior urodynamic study, indicating a possible spinal lesion. Radiographic evaluation led to early diagnosis and treatment of spinal cord compression from metastatic prostate adenocarcinoma. We discuss the diagnostic role of urodynamics in such cases.


Successful use of fluconazole for treatment of urinary tract fungal infections. Two cases are reported that demonstrate significant activity of the new antifungal agent, fluconazole, in treating urinary tract fungal infections. One patient was severely immunocompromised with the underlying complication of renal failure and the other presented with a much simpler case of candidal cystitis that responded quickly despite unfavorable in vitro susceptibility testing.


Reduction in the length of the intravesical ureter associated with pyelonephritis in the adult pig. The ureterovesical junction of pigs with cystitis and pyelonephritis was examined. There was significant shortening of the intravesical portion of the ureter in sows with pyelonephritis. In cases associated with acute pyelonephritis the ureteric orifice was found to be significantly wider than that found in the normal population. The ratio of the intravesical length to the ureteric orifice diameter was also significantly reduced. It is postulated that these changes to the ureterovesical junction originate or are caused by the disease processes in the bladder and may allow vesicoureteric reflux to occur, leading to ascending pyelonephritis.


Hereditary renal cell carcinoma in the Eker rat: a rodent familial cancer syndrome. A rodent model of hereditary cancer in which a single gene mutation predisposes rats to bilateral multicentric renal cell carcinoma (RCC) is described. This rat hereditary cancer syndrome shares certain similarities with von Hippel-Lindau disease (VHLD). In addition to the early development of renal epithelial tumors with morphologic similarity to human RCC, rats which bear the RCC gene are predisposed to the development of secondary primary cancers later in life. Splenic vascular proliferative lesions, including hemangiosarcoma, were seen in 23% of 14-month-old rats of both sexes that had renal tumors. At fourteen months of age, 62% of female rats with renal cell tumors had sarcomas of the lower reproductive tract of probable smooth muscle origin. Non-carrier siblings of affected animals did not have renal, reproductive, or splenic neoplasia. The finding of a specific constellation of familial neoplasms, including multicentric bilateral renal cell carcinoma, in this autosomal dominant disorder of rats suggests that this syndrome is analogous to human VHLD. In addition to its usefulness for studies of the biochemical and molecular mechanisms of renal carcinogenesis, this animal model will provide a unique tool to investigate how cancer susceptibility genes interact with environmental risk factors such as chemical carcinogens.


Effect of tetrodotoxin on the phasic and tonic responses of isolated rabbit urinary bladder smooth muscle to field stimulation. The response of the rabbit urinary bladder to field stimulation (80 volts, 2-32 Hz, 1 msec duration) is biphasic, consisting of an initial phasic contraction mediated by cholinergic and purinergic neurotransmitters, followed by a prolonged tonic contraction which is solely cholinergic. Obstructive hypertrophy of the bladder induces a variety of contractile alterations including a significantly greater reduction in the tonic component of the contractile response as compared to the phasic component. This results in a severe dysfunction in the ability of the bladder to empty. One possibility is that the inability of the bladder to maintain tension and empty efficiently may be related to a degeneration of nerves innervating the bladder smooth muscle. In addition to the well documented neuropathy, the bladder undergoes hypertrophy +/- hyperplasia of both smooth muscle and interstitial cellular elements, alterations in the metabolism of substrates, alterations in the synthesis of structural and smooth muscle proteins, and alterations in the deposition of collagen. The purpose of this study was to 1) to create a specific neuropathy in the absence of the additional structural, smooth muscle, and metabolic changes that are induced by partial outlet obstruction; and 2) determine if the contractile dysfunctions induced by the neuropathy have properties similar to the contractile dysfunctions induced by outlet obstruction. In the present study, a progressive "smooth muscle neuropathy" was induced in isolated strips of male rabbit urinary bladder smooth muscle by incubating isolated strips of urinary bladder body in the presence of increasing concentrations of tetrodotoxin (15-1500 nM). In these studies, we determined the effect of increasing concentrations of tetrodotoxin (TTX) on the response to field stimulation utilizing 2 Hz and 32 Hz, at 80 V and 1 ms duration. The effects of TTX on maximum rate of contraction, peak contraction and tonic contraction were monitored. In addition, the effects of atropine (cholinergic muscarinic blockage) and ATP-desensitization (purinergic inhibition) on the effects of TTX were also determined. The results can be summarized as follows: 1) Both atropine and ATP desensitization individually inhibited significantly the peak response to field stimulation. 2) Atropine abolished the tonic response. 3) TTX inhibited the tonic contraction at significantly lower concentrations than it inhibited peak contraction. Thus, at low concentrations of TTX, a condition similar to that seen in obstructive hypertrophy was created. 4) The ED50 in the presence of atropine was significantly greater than the ED50 following ATP desensitization. This may indicate that there are separate synaptic elements for cholinergic and purinergic transmission.(ABSTRACT TRUNCATED AT 400 WORDS)


The fate of buried vaginal epithelium.

The fate of buried vaginal epithelium. A new technique in the treatment of stress urinary incontinence utilizes a sling fashioned from a rectangular island of buried vaginal epithelium. We developed a model to study the natural history of vaginal wall covered by an epithelial flap in 12 rabbits sacrificed at intervals to 26 weeks. Histopathologic examination demonstrated an immediate acute inflammatory reaction. This early response was followed by formation of an epithelial lining of the potential space overlying the buried vaginal tissue. Acute inflammatory cells continued to enter this lumen until week 20, when granulomas were first detected. Histopathologic examination at twenty-six weeks showed stratified squamous epithelium lining the lumen. No deleterious inflammatory sequelae were detected, and no dysplastic or malignant changes were identified. These results suggest that buried vaginal epithelium is a safe (short term) tissue alternative for sling creation.


Experimental autoimmune cystitis: a potential murine model for ulcerative interstitial cystitis. Interstitial cystitis is an inflammatory disease of unknown etiology. To facilitate the study of the pathophysiology of interstitial cystitis, an animal model that correlates with the clinical features of interstitial cystitis and expresses histologic features consistent with those observed in interstitial cystitis patients was developed. Various strains of mice were immunized with a syngeneic bladder homogenate to determine their susceptibility to the induction of autoimmune cystitis. Of 3 mouse strains tested, only the Balb/cAN mice reproducibly developed the clinical correlates and histological features consistent with those observed in interstitial cystitis. In a blinded pathologic review, autoreactive Balb/cAN bladders were correctly distinguished from chronic bacterial cystitis, sham treated bladders and normal control bladders. Edema, fibrosis, perivascular lymphocytic infiltrations and detrusor mast cell accumulation were apparent in 75% of the Balb/cAN mice 2 weeks after immunization and 100% at 4 weeks. These histologic features plateaued and remained stable for at least 6 months. Grossly, the immunized mouse bladders were fibrotic and contracted with a significantly (p < .05) decreased fluid capacity. On hydrodistension, increased vascular prominence and petechial hemorrhage (glomerulations) were evident. Instillation of 14C-urea demonstrated increased permeability in immunized bladders compared with controls. A cellular autoimmune basis for the cystitis is supported by adoptive transfer studies. Spleen cells from experimental mice but not controls transferred the histological features of the disease to naive mice. These studies outline the development of a new experimental autoimmune cystitis model that expresses features similar to those frequently observed in human interstitial cystitis, and may provide a model for the study of the inflammatory process associated with interstitial cystitis. Furthermore, these data suggest a possible role for cellular immune components in interstitial cystitis.


The role of air plethysmography in monitoring results of venous surgery. The development of an objective, noninvasive method to assess the hemodynamic effects of venous surgery has long been awaited. Previous methods used to evaluate the results of surgery for varicose veins and venous stasis ulceration have been limited in their quantitative assessment. Now, by use of air plethysmography (APG), we can accurately quantify the effectiveness of corrective venous surgery. Twenty-five extremities that had evidence of venous insufficiency were examined with use of APG before and after venous surgical procedures. Surgery was directed at specific sites of venous incompetence as defined by physical examination and high-resolution duplex imaging. Twenty-one extremities underwent ligation and stripping of the greater saphenous vein. In these patients, APG showed an improvement in venous reflux as demonstrated by a decrease in the venous filling index from 6.6 +/- 0.7 ml/sec to 1.8 +/- 0.3 ml/sec (p = 0.0001) and venous volume from 177.1 +/- 14.5 ml to 139.2 +/- 8.9 ml (p = 0.0008). In addition, these patients showed a mild improvement in calf muscle pump function as noted by an improvement in ejection fraction from 45.8 +/- 2.0% to 50.8% +/- 2.5% (p = 0.07). The residual volume fraction decreased from 45.0% +/- 3.4% to 42.0% +/- 3.7%, a difference that was not statistically significant (p = 0.4). Four extremities with grade III chronic venous insufficiency underwent popliteal vein valve transplantation with use of an autogenous axillary vein valve.(ABSTRACT TRUNCATED AT 250 WORDS)


In vitro evaluation of endothelial and smooth muscle function of primary varicose veins. Experiments were designed to study functional changes in superficial leg veins of patients with primary varicosity. Excess segments were taken from 19 patients undergoing elective vein resection. Excess segments of greater saphenous veins taken from 13 patients undergoing coronary or lower extremity arterial bypass were used as controls. These rings, some with endothelium deliberately removed, were suspended for the measurement of isometric force in organ chambers. Segments of veins were also evaluated with respect to their total protein content, endothelin content, and histologic structure. In varicose veins, maximal contractions in response to potassium chloride (n = 9), norepinephrine (n = 9), and endothelin (n = 4) were reduced 71.1%, 78.2%, and 75.6%, respectively, compared with contractions in control veins (p < 0.01). In addition, no differences were detected in the maximal tension or tissue sensitivity (EC50) between segments of nonvaricose greater saphenous vein and adjacent varicose tributaries from the same patient. Rings with and without endothelium contracted similarly. In varicose veins, endothelium-dependent relaxations produced by the calcium ionophore A23187 were attenuated 89.7% compared with relaxations in controls (n = 6, p < 0.01). In veins from patients with primary varicosity, endothelium-independent relaxations produced by nitric oxide (n = 6) and forskolin (n = 3) were diminished 86.8% (p < 0.01) and 65.6% (p < 0.05), respectively, compared with relaxations in control veins. In primary varicose veins, protein content was decreased (n = 17, p < 0.01) and endothelin content increased (n = 17, p = 0.1) compared with those values in control veins (n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)


A comparison between descending phlebography and duplex Doppler investigation in the evaluation of reflux in chronic venous insufficiency: a challenge to phlebography as the "gold standard". To evaluate venous reflux in 56 lower limbs of 32 consecutive patients, hemodynamic tests, ascending and descending phlebography, and supine and erect quantitative duplex scanning were performed and the clinical severity was classified (class 0 = 15, class 1 = 19, class 2 = 8, and class 3 = 14). Of the 56 lower limbs, 22 (40%) had severe swelling and hyperpigmentation with or without ulcer (classes 2 and 3). Adequacy of the clinical severity classification was supported by the hemodynamic results. Radiologic and ultrasound findings were described by axial grading, multilevel/multisystem point, and multisegment scoring systems. Applying these evaluation systems, the phlebographic and scan results correlated poorly. There was no relationship between the radiologically obtained average reflux grade or points and the clinical severity. An erect quantitative duplex Doppler test assessed by the multisegment scoring system correlated best with the severity classification. The predictive value of this test to diagnose severe reflux leading to severe symptoms (classes 2 and 3) was 77% compared with 35% to 44% for descending phlebography. The study suggests that erect quantitative segmental duplex Doppler reflects the degree and distribution of venous reflux more accurately than does descending venography.


Femoral vein valvuloplasty: intraoperative angioscopic evaluation and hemodynamic improvement. Femoral vein valvuloplasty (FVV) is the operation of choice for primary valvular incompetence, but this procedure is highly operator dependent for judging the competence of the valve repair during surgery. We have reviewed our experience with FVV, focusing on the utility of angioscopic-guided valve repair and hemodynamic results. Nine limbs in six patients underwent superficial FVV. There were four men and two women; the average age was 49 years (range 32 to 62 years). All limbs were Society for Vascular Surgery/International Society for Cardiovascular Surgery clinical stage III (venous ulcer), and descending phlebography showed grade 4 reflux in six limbs, grade 3 reflux in one limb, and grade 2 reflux in two limbs. In addition to FVV, five limbs underwent subfascial ligation of incompetent perforators and three limbs underwent ligation and stripping of superficial varicosities. Two limbs underwent polytetrafluoroethylene wrapping of the valvuloplasty. The last five valvuloplasties underwent angioscopic evaluation of the repair, and the last two procedures were closed valvuloplasties (without venotomy). Follow-up averaged 20.3 months (range 2 to 51 months). In all patients ulcers healed without recurrence. There were two perioperative deep vein thromboses in the polytetrafluoroethylene wrapped repairs. All superficial femoral veins were patent by duplex scanning at the time of follow-up. Venous refill time measured by light reflection rheography did not improve after surgery. Venous filling index measured by air plethysmography showed near normalization (3.83 +/- 0.82) after angioscopically guided FVV.(ABSTRACT TRUNCATED AT 250 WORDS)


Current use of inferior vena cava filters. To study possible changes in the clinical use of inferior vena cava (IVC) filters caused by the introduction of percutaneous delivery systems, we reviewed all patients who underwent placement of IVC filters at our institution from 1988 to 1991. Eighty-four patients (52 men and 32 women) ranging in age from 18 to 90 years (mean 67 years) were identified. Filters were required because of contraindications to anticogulation in 64% anticoagulation failure in 25%, and preoperative prophylaxis in 11% of patients. The underlying disease was lower extremity deep vein thrombosis in 50% and pulmonary embolism in 45% of patients. Five percent of patients received prophylactic filters without documented thromboembolism. All filters were placed percutaneously by interventional radiologists, 77 through the common femoral vein and 7 through the internal jugular vein. Three types of filters were used. One procedure-related death occurred because of acute IVC occlusion. Fatal pulmonary embolism within 48 hours after filter placement was documented in one patient and suspected in one late death. No other clinically apparent pulmonary embolism or leg swelling occurred after filter placement. Minor complications related to filter placement occurred in 13 patients, but none required operative intervention. Analysis of complication rates of the three filter types was precluded by the small sample size. After a mean follow-up of 11 months, 42 patients (50%) had died of malignancy (n = 25), multisystem organ failure (MSOF; n = 7), cardiovascular events (n = 4), recurrent pulmonary embolism (n = 2), cerebrovascular events (n = 4), or an unknown cause (n = 1). Twenty-three patients (27%) died before hospital discharge.(ABSTRACT TRUNCATED AT 250 WORDS)


Physician practices in the management of venous thromboembolism: a community-wide survey. Although there is a broad consensus on the optimum approach to the management of venous thromboembolism, there are few data from which to assess the extent of compliance with these recommendations. A community-wide study was therefore conducted in 16 short-stay hospitals in central Massachusetts to assess the clinical management of venous thromboembolism. Based on validated discharge diagnostic codes, there were 1231 clinically recognized cases of venous thromboembolism, 0.8% of 148,730 discharges in the 18-month period from July 1, 1988, to December 31, 1989. Eighty-one percent of study patients were admitted with signs or symptoms of acute venous thromboembolism. Ninety-seven percent of patients were treated with either heparin, warfarin, or inferior vena caval filter. Intravenous heparin was given to 89% of patients (mean bolus 6674 IU; mean duration 6.6 days). After heparin administration, there was a mean delay of 2.3 days in starting warfarin. Assuming a corresponding decrease in the length of hospital stay, appreciable cost savings could have been realized by earlier start of oral anticoagulation. An inferior vena cava filter was placed in 14% of patients. There was a clinically recognized in-hospital recurrence of venous thromboembolism during treatment in 2% of patients. Despite a slightly lower rate of compliance with recommended treatment regimens in nonteaching hospitals, and despite less frequent use of the inferior vena cava filter, there was no significant difference in the rate of in-hospital recurrence of clinically recognized venous thromboembolism in 10 nonteaching hospitals compared with six teaching hospitals.(ABSTRACT TRUNCATED AT 250 WORDS)


Frequency of pulmonary embolism in ambulant patients with pelvic vein thrombosis: a prospective study. One hundred thirty-nine consecutive patients (average age 70.1 years) who were able to walk with a swollen leg were seen at the clinic where diagnosis of acute deep vein thrombosis (DVT) extending to the pelvis was confirmed by injecting microspheres labeled with technetium 99m into the dorsal foot vein (radionuclide venography). Thirty-nine (28%) of these patients had malignant disease. Perfusion lung scans performed immediately after radionuclide venography were supplemented by inhalation scans (99mTc-labeled diethylenetriamine pentaacetic acid aerosol) in case of perfusion defects. During scintigraphy patterns highly indicative of pulmonary embolism (PE) were found in 80 patients (58%), but only 11 (7.9%) had minor clinical symptoms. All patients were admitted to the ward, were given standard heparin subcutaneously (35,000 to 40,000 units/24 hr) and firm bandages, and were encouraged to walk. After 11 days pulmonary scintigraphy was repeated and revealed no change in 55 of 59 patients without PE and in 40 of 80 patients with PE. Thirty-three patients (23.7%) showed regression of perfusion defects. New PE developed in 11 patients (7.9%, four without and seven with previous PE). Autopsy revealed that one 80-year-old patient with prostatic carcinoma had died of massive PE. When comparing this frequency of newly developed PE during ambulation with the occurrence of PE after bed rest, according to the literature, it is no more dangerous for a mobile patient with proximal DVT to walk wearing a firm bandage than it is for the patient to be in bed. Therefore we recommend treating mobile patients with DVT by use of anticoagulation and firm compression bandages and without immobilization.


Circumferential venolysis and paraclavicular thoracic outlet decompression for "effort thrombosis" of the subclavian vein. Effort thrombosis of the subclavian vein (Paget-Schroetter syndrome) has long been considered a primary thrombotic process, but recent experience suggests that it may commonly result from repeated mechanical compression. Increased awareness of the pathophysiology of this syndrome can allow timely, improved diagnostic screening and the use of specific surgical intervention to relieve the venous consequences. During the past 15 years we have treated six patients with mechanical compression in the thoracic outlet causing surgically correctable venous occlusive problems. There were four men and two women with an average age of 38 years (range 26 to 53 years). All patients exhibited pain, swelling, and cyanosis of the upper extremity, with worsening venous congestion on abduction of the arm. Five of six patients were originally treated for effort thrombosis of the subclavian vein with arm elevation and anticoagulation; two also underwent immediate thrombolytic therapy with urokinase. Venography was prompted in each case by positional symptoms during follow-up and showed irregular stenosis of the subclavian vein adjacent to the first rib. All patients underwent extended first rib resection and circumferential venolysis (one patient underwent bilateral procedures); one was performed through a transaxillary approach, two through a supraclavicular approach, and four through a new, "paraclavicular" approach. All subclavian veins appeared normal after venolysis. Five of six patients also underwent complete scalenectomy and brachial plexus neurolysis. In each patient, venous and neurogenic symptoms resolved and venography confirmed a patent subclavian vein, with follow-up ranging from 11 months to 13 years (mean 3.8 years).


Hemodynamic deterioration in chronic venous disease. Clinical deterioration of patients with chronic venous disease (CVD) has been well described and a standardized classification has been proposed. The progressive hemodynamic deterioration producing these clinical findings is less well appreciated. This study examines and correlates venous hemodynamics with clinical severity in patients with CVD. Two hundred seventy-four extremities from 149 patients with varying degrees of CVD and 56 extremities from 28 symptom-free volunteers were evaluated clinically and hemodynamically. Each limb was assessed for functional venous volume, degree of valvular insufficiency, efficiency of the calf muscle pump, and noninvasive estimate of ambulatory venous pressure. In addition, exercise venous pressures were recorded in 56 extremities from 36 patients and 9 extremities from 6 volunteers. As CVD progresses from class 0 to class 2, venous volume expands, valvular function deteriorates, the calf muscle pump becomes inefficient, and ambulatory venous hypertension develops. However, once extremities develop brawny edema or hyperpigmentation, further deterioration of limb hemodynamics does not occur. Patients with deep venous obstruction have more severe valvular insufficiency, calf muscle pump dysfunction, and ambulatory venous hypertension than have patients without evidence of obstruction. Residual volume fraction offers a reliable noninvasive estimate of ambulatory venous pressure (r = 0.76), although its correlation was significantly better for patients without venous obstruction (r = 0.86) than for those with obstruction (r = 0.40; p < 0.05). Deterioration in venous hemodynamics parallels clinical severity through class 2. Once brawny edema and hyperpigmentation occur, ulceration develops without additional deterioration of venous hemodynamics.


Long-term effects of superficial femoral vein ligation: thirteen-year follow-up. This study examines the late clinical, hemodynamic, and anatomic results of superficial femoral vein ligation performed in 35 extremities that were followed an average of 13 1/2 years (range, 5 to 22 years). Indications for interruption were to prevent recurrent embolization from distal deep venous thrombosis (14 cases), to prevent emboli in patients with contraindication to anticoagulants (eight cases), to prevent distal reflux in selected patients undergoing iliofemoral thrombectomy (11 cases), and to control reflux in failed venous reconstruction (two cases). Ligation was effective in the prevention of pulmonary emboli as indicated by no significant clinical events and 15 negative postligation ventilation-perfusion scans. Long-term clinical follow-up showed normal (class 0) or near-normal (class 1) extremities in 83%. Fourteen percent developed mild to moderate symptoms of pain or swelling but without ulceration (class 2), and only one case (3%) had ulcerative sequelae (class 3). The only two findings that correlated with worse clinical outcome were the presence of an incompetent profunda femoris or an obstructed greater saphenous vein. Profunda femoris reflux was found in 60% (3/5) of patients with class 2 or 3 sequelae, which was significantly higher than the 14% (3/22) found in those patients with class 0 or 1 results (p < 0.05). Obstruction of the greater saphenous vein was found in 50% of those patients with class 2 or 3 results as opposed to 9% with class 0 or 1 results (p = 0.05). A large collateral vessel between the profunda femoris and the distal superficial femoral or popliteal vein was associated with poor long-term results.(ABSTRACT TRUNCATED AT 250 WORDS)


Reconstruction of large veins for nonmalignant venous occlusive disease. To evaluate the effectiveness of venous grafting, we reviewed the management and clinical course of 28 patients (21 males and seven females) who underwent 29 reconstructions of large veins for benign disease. There were 12 patients with superior vena cava (SVC) syndrome, two with subclavian vein thrombosis, and 15 with occlusion of the inferior vena cava (IVC) or iliac veins. One of these patients underwent both IVC and SVC reconstructions. Reconstruction of the SVC was performed with spiral saphenous vein graft (SSVG) in nine patients and expanded polytetrafluoroethylene (ePTFE) in three. All seven straight SSVGs had documented patency at a median of 7 months (2 weeks to 5 years) after reconstruction. Six patients had complete relief of symptoms. Two patients with bifurcated SSVG had early occlusion of one graft limb. Two of the three ePTFE grafts needed early thrombectomy. One graft reoccluded at 6 months and two were patent at 2 and 5 years. The two subclavian vein reconstructions with axillary-jugular ePTFE grafts with an arteriovenous fistula had documented early patency. Both patients had rapid resolution of symptoms. The IVC or iliac vein was reconstructed with ePTFE graft in 11 patients, SSVG in three, and Dacron in one. A femorofemoral arteriovenous fistula was added in eight patients with ePTFE grafts. Seven of the 11 ePTFE grafts had documented patency at the last follow-up (median 9 months; range 2 weeks to 5 years). None of the three SSVGs had documented long-term patency. The one Dacron cavoatrial graft occluded at 3 years. A straight SSVG continues to be our first choice for SVC replacement. Short, large-diameter ePTFE grafts perform the best in the abdomen. Femorocaval or long iliocaval grafts need an arteriovenous fistula to maintain patency. Long-term patency after closure of the fistula is still unknown. Femorocaval grafts with poor venous inflow have limited chance of success. Failed or failing grafts may be salvaged by early thrombectomy. Venous reconstruction to treat selected patients with symptoms with large vein occlusion continues to be a viable option.


Long-term results of venous reconstruction after vascular trauma in civilian practice. The natural history of venous reconstruction (VR) in terms of patency and clinical outcome after vascular trauma has not been well documented. This study consists of 32 patients who had VR performed for extremity vascular trauma and were available for long-term assessment (mean follow-up time 49 months, range 6 to 108 months). The types of repair performed were as follows: lateral venorrhaphy (simple repair) (56%), interposition grafting (22%), patch repair (12.5%), and end-to-end repair (9.5%). Seventeen patients underwent venography after the operation with documentation of repair patency in eight patients (46%) and thrombosis in nine (54%). Only two patients had significant clinical edema at follow-up examination. Noninvasive venous evaluation consisted of Doppler ultrasonography, impedance plethysmography, photoplethysmography, and color-flow duplex scanning (CFDS). The photoplethysmography-derived venous refilling time of the injured extremity was 34.9 +/- 16.2 seconds whereas that of the contralateral noninjured extremity was 36.8 +/- 16.1 seconds (p = 0.5). Based on standard criteria for CFDS, 90% of VRs were patent. Eight repairs that were patent in the early postoperative period remained patent on CFDS. Of the nine repairs with early thrombosis, eight were assessed as patent on follow-up CFDS. In conclusion, VR is a durable surgical procedure associated with minimal morbidity, good long-term patency, and preservation of venous competence. The natural history of thrombosed VRs appears to be one of thrombus absorption with recanalization.


Absorbable suture improves growth of venous anastomoses. Growth of vascular anastomoses is desirable in pediatric vascular surgery, especially in pediatric organ transplantation. Although absorbable suture has been shown to be superior to nonabsorbable suture in permitting growth of arterial anastomoses, the optimal suture material for venous anastomoses has not been established. To examine this in a porcine model, we performed bilateral primary end-to-end anastomoses of transected external jugular veins in 10, 4-week-old piglets. In each piglet one anastomosis was constructed with continuous absorbable 8-0 polyglyconate suture, whereas the contralateral anastomosis was constructed with continuous nonabsorbable 8-0 polypropylene suture. After 6 months the veins were excised, pressure fixed at 15 mm Hg for 2 hours, and examined grossly and histologically. Vein diameter was measured by contrast radiography at the anastomosis and 1 cm proximal and distal to the anastomosis. Vein cross-sectional area 1 cm from the anastomosis was similar in the two groups: polyglyconate 95.7 +/- 12.3 mm2 versus polypropylene 95.3 +/- 9.7 mm2. However, polyglyconate anastomoses had greater cross-sectional area (polyglyconate 72.8 +/- 7.9 mm2 vs polypropylene 51.8 +/- 6.0 mm2; p < 0.05). In addition, at 6 months polyglyconate anastomoses had a greater percentage of growth (polyglyconate 207% vs polypropylene 118%; p < 0.05) compared with native vein cross-sectional area (23.7 +/- 0.39 mm2) from control pigs at 4 weeks of age. On histologic examination, polyglyconate had dissolved entirely in six cases and was present but in varying degrees of dissolution in the other four; in contrast, polypropylene was identifiable at all anastomoses.(ABSTRACT TRUNCATED AT 250 WORDS)


The effects of aortic reconstruction and collagen impregnation of Dacron prostheses on the complement system. Complement activation has been associated with numerous clinical hazards such as platelet aggregation, adult respiratory distress syndrome, and renal dysfunction. The complement system is activated by exposure of different biomaterials to blood. Recently a watertight knitted Dacron aortic prosthesis impregnated with bovine collagen has been developed. One potential disadvantage is that this bovine collagen may activate the complement system and evoke the production of inflammatory mediators. We conducted a prospective randomized trial to study the systemic effects of collagen-impregnated prostheses and of aortic surgery with implantation of Dacron prosthesis on the complement system in the perioperative period and at 3 months after operation. Forty-one patients randomly received either a collagen-impregnated (n = 20) or a nonimpregnated prosthesis (n = 21). Twelve patients who had cholecystectomy served as controls. CH50 consumption and C3a generation were determined to study overall complement activation. Furthermore, C3a/C3 fractions were calculated. Finally, C4 and factor B consumption were determined to evaluate the complement stimulation via the classic and the alternative pathways, respectively. We found significant activation of the complement system during the operation in both the collagen group (CH50 consumption: 40%, p = 0.03; C4 consumption: 74%, p < 0.0001; factor B consumption: 73%, p < 0.0001; C3a/C3 fraction increase: 173%,p = 0.04), and the nonimpregnated group (CH50 consumption: 40%, p < 0.0001; C4 consumption: 71%, p < 0.0001; factor B consumption: 76%, p < 0.0001; C3a/C3 fraction increase: 165%, p = 0.025), with no statistically significant differences between the groups of prostheses. Activation was initiated via both the classic and the alternative pathway. This indicates aortic implantation significantly activates the complement system, but that collagen-impregnated prostheses do not stimulate the complement system any more than its nonsealed substrate. Comparing results in patients with vascular disease with controls, a significantly increased complement activation was observed in the vascular group (CH50 consumption: 40%, p < 0.0001; C4 consumption: 74%, p < 0.0001; factor B consumption: 75%, p < 0.0001; C3a/C3 fraction: 169%, p = 0.002), compared with the controls (CH50 consumption: 71%; C4 consumption: 104%; factor B consumption: 94%; C3a/C3 fraction: 119%, all p = NS), with statistical significant differences between the vascular group and cholecystectomies (CH50: p = 0.005; C4: p = 0.002; factor B: p < 0.0001, and C3a/C3 fraction: NS). This observation demonstrates that aortic surgery with the implantation of a Dacron prosthesis significantly activates the complement system.


Interleukin-1 beta and tumor necrosis factor-alpha release in normal and diseased human infrarenal aortas. The presence of chronic inflammatory cells in the adventitia and media of abdominal aortic aneurysms and aortic occlusive disease suggest an immunologic response. The purpose of this study is to determine whether normal or diseased infrarenal aortas liberate the inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). Twenty-six infrarenal aortic biopsies (5 aortic occlusive disease, 15 abdominal aortic aneurysms, and 6 cadaveric donors) were weighed, minced into small pieces, and incubated in media for 48 hours. Conditioned media was harvested at 48 hours and assayed for IL-1 beta or TNF-alpha with use of an ELISA assay. Comparison of groups was performed with a one-way analysis of variance. The constitutive IL-1 beta produced by abdominal aortic aneurysms was significantly different than that in cadaveric donors (908 +/- 194 pg/ml [SE] vs 100 +2- 30 pg/ml). There was no statistically significant difference between abdominal aortic aneurysms and aortic occlusive disease (908 +/- 194 pg/ml vs 604 +/- 256 pg/ml) or aortic occlusive disease and cadaveric donor (604 +/- 256 vs 100 +/- 30). In time-course studies for the release of IL-1 beta, abdominal aortic aneurysms demonstrated maximal release at 48 hours. IL-1 beta release was augmented by lipopolysaccharide in all categories. A dose response curve demonstrated maximal IL-1 beta release on stimulation with 5 micrograms/ml LPS. Constitutive TNF-alpha production was low, ranging from 13 +/- 1.5 pg/ml in cadaveric donor, to 20 pg/ml in aortic occlusive disease, and 24 +/- 11 pg/ml in abdominal aortic aneurysms. There was no augmentation in TNF-alpha with lipopolysaccharide.(ABSTRACT TRUNCATED AT 250 WORDS)


Aneurysms of the superficial femoral artery: a report of two cases and review of the literature. True "arteriosclerotic" aneurysms of the superficial femoral artery, not associated with generalized dilatation of the common femoral or popliteal artery, are relatively rare. We report our experience with two isolated superficial femoral artery aneurysms and review the previous literature. An 88-year-old woman was first seen with thrombosis of a superficial femoral aneurysm and limb-threatening ischemia and had eventual limb loss as a result of occlusion of distal run-off vessels despite surgical revascularization. A 93-year-old man came to us with rupture and was treated with an interposition graft, which resulted in limb salvage. Review of 17 "arteriosclerotic" superficial femoral artery aneurysms in 14 patients whose cases were reported in the literature revealed a complication at presentation in 65%, rupture in 35%, thrombosis in 18%, and distal emboli in 12%. However, limb salvage was 94% and there were no perioperative deaths. Abdominal aortic aneurysms were discovered in 40%. Males (75%) were more common than females, and the average age was 77 years (range 61 to 93). Isolated superficial femoral artery aneurysms are rare and occur at an older average age than do other peripheral aneurysms, but their incidence is anticipated to increase with this growing segment of our population. In the absence of evidence of syphilitic, other infectious, immunologic, inflammatory, or connective-tissue disorders, these and other aneurysms are considered arteriosclerotic in origin, despite the absence of diffuse arteriosclerosis in many cases and controversy regarding the role of arteriosclerosis in their cause.(ABSTRACT TRUNCATED AT 250 WORDS)