Characterization of mutations at the mouse phenylalanine hydroxylase locus

By using a three-dimensional computed tomography (CT) scanner, we compared the anatomic features of the pelvis of three fetuses of same gestational age, one with a normal pelvis representing the reference model, one with classic bladder exstrophy, and one with cloacal exstrophy. The tomography slices were selected at the same levels for each case. Three angles expressing external opening of the pelvis were defined. Comparing normal and abnormal pelvises allowed definition of three criteria for the correction of the malformation: (a) the sum of the differential angles gives the amplitude of the correction needed; (b) a supraacetabular osteotomy appears to allow best closure of the pelvic ring; (c) only three slices of a CT scan are needed, which cannot be harmful, especially for neonates. Therefore, we believe that a CT scan of the pelvis should be performed whenever an osteotomy is planned in the surgical reconstruction of bladder and cloacal exstrophy.     

Dysraphic myelodysplasias associated with urogenital and anorectal anomalies: prevalence and types seen with MR imaging

OBJECTIVE: The purpose of this study was to determine by MR imaging the prevalence and types of dysraphic abnormalities of the spinal cord (i.e., myelodysplasias) associated with urogenital and anorectal malformations of childhood. MATERIALS AND METHODS: Since 1987, 92 patients with imperforate anus complex, cloacal malformation, and cloacal exstrophy have had MR imaging as a screening examination for occult dysraphic myelodysplasia. The prevalence and types of myelodysplasia were determined for each group. RESULTS: The prevalence of dysraphic myelodysplasia in each group of children was 17% (1/6) for low imperforate anus (ectopic anus), 34% (11/32) for high imperforate anus (with fistulization), 46% (19/41) for cloacal malformation, and 100% (13/13) for cloacal exstrophy. The most common abnormalities in each group were tethered cord with intradural or filar lipoma in imperforate anus; low-placed or dysplastic conus medullaris and tethered cord with lipoma or myelolipoma in cloacal malformation; and lipomyelocele, lipomyelomeningocele, or lipomyelocystocele in cloacal exstrophy. CONCLUSION: Our results show that the prevalence of myelodysplasia as seen on MR imaging is high in patients with urogenital and anorectal anomalies.     

Acute liver failure caused by isoniazid in a child receiving carbamazepine

Pregnancy, delivery and puerperium in primigravida after surgical correction of vesical exstrophy and reconstruction of vagina with chronic renal insufficiency was presented. Both pregnancy and delivery were successful. Vesical exstrophy the rare congenital malformation in aspect of obstetrical-gynaecological treatment were discussed. Conduction of pregnancy with chronic renal disease was briefly reviewed.     

Covered exstrophy: a rare variant

A case of covered exstrophy without sequestration of a bowel segment is reported. A 4-year-old female presented with dribbling of urine. Treatment to date has been simple excision of the covered membrane with functional closure of the bladder and bilateral posterior iliac osteotomies, with reconstruction of the bladder neck and genitalia to be performed at a later date. The embryogenesis of this rare variant, a review of the reported cases, and management options are discussed. Keyword Covered exstrophy. Exstrophy. Bladder variants     

Experience with the Mainz modification of ureterosigmoidostomy

BACKGROUND: The purpose of this study was to report experience with the revived surgical concept of ureterosigmoidostomy in its low pressure modification and to discuss its value within the current spectrum of urinary diversion. METHODS: Between February 1992 and September 1997 modified ureterosigmoidostomy (rectosigmoid pouch; Mainz pouch II) was performed in 34 patients aged 1.9-76.9 (mean 55.8) years as a primary urinary diversion after radical cystectomy for bladder cancer (n = 30) and benign conditions (bladder exstrophy, three patients; intractable urinary incontinence, one). All patients were followed prospectively according to a standard protocol including assessment of continence, renal function and acid-base balance. RESULTS: There were no perioperative deaths. In one patient dislocation of a ureteral stent in the early postoperative course required insertion of a percutaneous nephrostomy. All patients were continent during the day. One patient experienced night-time incontinence but rejected a conversion procedure. In one case ureterosigmoidostomy was replaced by an ileal conduit after several episodes of septicaemia. One nephrectomy was performed for ureterointestinal obstruction. Mild hyperchloraemic acidosis was seen in two patients. CONCLUSION: Bowel frequency and urge incontinence, the major weaknesses of classical ureterosigmoidostomy, can be overcome by detubularization of the rectum. As the modified procedure is quick, safe and easy to perform with highly satisfactory results, the rectosigmoid pouch has potential in reconstructive urology.     

Myofascial wrap to treat intractable urinary incontinence in children

OBJECTIVES: The management of intractable urinary incontinence in the patient with cloacal or bladder exstrophy/epispadias, failed bladder neck plasty, or failed augmentation cystoplasty remains a surgical challenge. The myofascial wrap, a modification of the rectus fascial wrap, was developed to treat intractable urinary incontinence due to sphincteric incompetence in these problematic cases. A full-thickness, vascularized pedicle of anterior rectus sheath, rectus abdominis muscle, and posterior rector sheath is incorporated into a bladder neck wrap to provide support, mucosal coaptation, and active muscular tone. METHODS: Eight patients (5 females and 3 males) with total urinary incontinence due to sphincteric incompetence underwent the myofascial wrap. Urinary tract pathology included cloacal exstrophy (2), female epispadias (2), classic bladder exstrophy (1), male epispadias (1), myelomeningocele (1), and a pelvic tumor (1). The procedure is performed by harvesting a full-thickness strip of pedicled rectus muscle along with the anterior and posterior fascial sheaths. The strip is passed underneath and then over the bladder neck in a near 360 degrees wrap. The free end of the wrap is anchored into the pubic bone in an ipsilateral subperiosteal pouch. RESULTS: Six of the 8 patients are completely continent, and 2 patients void spontaneously without the need for catheterization. CONCLUSIONS: The myofascial wrap provides support, mucosal coaptation, and muscular tone to an incompetent sphincter and bladder neck. Favorable results in a very difficult population of pediatric patients warrant its continued use.     

Evaluation of smooth muscle and collagen subtypes in normal newborns and those with bladder exstrophy

PURPOSE: Many patients who undergo bladder exstrophy closure as newborns, subsequent epispadias repair and later bladder neck reconstruction become completely continent yet complications can occur. After successful initial exstrophy closure and later epispadias repair some patients may fail to gain sufficient capacity for bladder neck reconstruction or satisfactory capacity and continence after bladder neck reconstruction. In an attempt to understand the pathogenesis of these failures we compared bladder biopsies from normal neonates and those with exstrophy. MATERIALS AND METHODS: Bladder biopsies obtained from the midline of the bladder wall just above the base of the trigone from 12 newborns with exstrophy were compared to bladder sections from 9 neonatal cadavers. All bladder specimens were stained with monoclonal antibodies against type I, III or IV collagen and a subset was further stained with Masson's trichrome to define the extracellular matrix. All specimens were then analyzed using a color digital image analysis system. RESULTS: At initial examination of the extracellular matrix there was an increase in the collagen-to-smooth muscle ratio from 0.38 in controls to 1.2 in newborns with exstrophy, comprising an increase in collagen and decrease in smooth muscle. The collagen component of the extracellular matrix was then further defined to quantitate the amount of each collagen type (I, III and IV) deposited. We then evaluated the ratio of collagen type-to-total collagen sampled. Compared to control bladders there was no statistical difference in the amount of type I or IV in the bladders of newborns with exstrophy at initial closure. However, there was a 3-fold increase in type III collagen (0.14 +/- 0.05 to 0.46 +/- 0.2%, p < 0.001) in the bladders of neonatal controls versus newborns with exstrophy. CONCLUSIONS: This alteration in collagen makeup may represent an earlier developmental stage of the exstrophy bladder at birth, which then remodels and changes after successful initial closure. Further studies are underway to examine the collagen composition of bladders at bladder neck reconstruction, failed closures and augmentation.     

Screening for intracranial aneurysms in patients with isolated polycystic liver disease

BACKGROUND/PURPOSE: Cloacal exstrophy can now be managed with excellent survival rates and reasonable long-term outcomes with many of these patients living into their late teens and early adulthood. In this report, the authors describe for the first time the association of large ovarian cysts with cloacal exstrophy. METHODS: From 1974 to 1996, 12 patients with cloacal exstrophy have been treated at C.S. Mott Children's Hospital. Massive ovarian cysts developed in four of these. These patients represent the subjects of this study. RESULTS: All four patients have been followed up beyond puberty and massive ovarian cysts have developed, which have caused significant morbidity. Three patients have required surgical intervention. All the patients had reached menarche before the development of the cysts. In all cases, the presentation was severe pelvic pain. Urinary tract obstruction from the large pelvic cysts developed in three of the four. The cysts were bilateral in three of four patients and measured 8 to 10 cm in diameter on ultrasound scan or computed tomography (CT). Cyst aspiration was attempted in two cases and was unsuccessful. Three of the four patients have required bilateral salpingo-oophorectomy. The indications for surgery were uncontrollable pelvic pain in one and urinary obstruction and uncontrollable pelvic pain in two. Surgical findings demonstrated massive thin-walled cysts with essentially no normal ovarian tissue in association with duplicated mullerian structures. The pathology findings were corpus luteal cyst in two and mucinous cystadenoma in one. The fourth patient with an 8- x 10-cm unilateral cyst is being followed up. CONCLUSIONS: The authors have described, for the first time, the association of massive ovarian cysts with cloacal exstrophy. These cysts can lead to severe pelvic pain and urinary tract obstruction. Bilateral oophorectomy has been required in most of these patients.     

Prospective study of morphologic and functional changes with time in the mucosa of the ileoanal pouch: functional appraisal using transmucosal potential differences

PURPOSE: This study was undertaken to investigate the morphologic and functional changes with time in the mucosa of the ileoanal pouch. METHODS: A morphologic study by histopathologic analysis, mucosal morphometry, and mucin histochemistry and a functional study by analysis of transmucosal potential difference were performed in 27 patients with an ileoanal J-pouch after restorative proctocolectomy for ulcerative colitis. In 19 patients with a normal ileoanal pouch, two prospective follow-up analyses were performed after median functional pouch times of 14 and 39 months. We also evaluated eight patients with the diagnosis of pouchitis (median follow-up, 52.5 months). RESULTS: In the normal ileoanal pouch group, some degree of chronic and acute inflammatory infiltration was identified in 100 percent and 63.2 percent of cases, respectively, with no significant differences being observed between the two follow-up analyses. The mean villous atrophy index at the first and second follow-up was 0.54 and 0.52, respectively, significantly lower (P < 0.001; an indication of a greater degree of villous atrophy) than the value obtained from the control group with a healthy terminal ileum (0.77). The group of patients with pouchitis exhibited statistically significant differences in the degree of acute and chronic inflammatory infiltration, the extent of ulceration, the crypt depth, and the villous atrophy index, compared with patients without pouchitis. In the normal ileoanal pouch group, the median percentage of sulfomucin with each degree of atrophy (1=mild; 2=moderate; and 3=severe) was 2.6, 4.5, and 20.9 percent, respectively. In patients with pouchitis, the median percentage of sulfomucin was 5.9 percent. The mean transmucosal potential difference at the first follow-up (-25.3 mV) was significantly lower (P=0.001) than at the second (-30.4 mV). Significant differences were apparent with respect to both the normal ileum (-8.9 mV) and the normal rectum (-40.2 mV). CONCLUSION: These results suggest that the ileal pouch behaves as a neorectum, with different degrees of colonic metaplasia from a morphologic and a functional perspective.     

Motility in the Hunt-Lawrence pouch after total gastrectomy

PURPOSE: The aim of this study was to evaluate motility patterns of the Hunt-Lawrence pouch and the jejunal limb of patients reconstructed with a pouch after total gastrectomy, and to compare the findings in symptomatic patients to those without symptoms after the operation. PATIENTS AND METHODS: Thirty-three patients who had undergone post-gastrectomy pouch reconstruction were studied using a water-perfused motility system. In 21, the pouch was connected by a Roux-en-Y, and, in 12, by a jejunal interposition. Twenty-eight patients were asymptomatic, including 17 connected by a Roux-en-Y and 11 by a jejunal interposition. Five patients were by a jejunal interposition. Five patients were symptomatic, including 4 connected by Roux-en-Y Y and 1 by jejunal interposition. A control group consisted of 5 healthy volunteers who had not undergone operation. RESULTS: The motility phases in the pouch and jejunal limb of asymptomatic patients were of shorter duration than those of controls, and they followed a random sequence instead of a normal progression from phase I to II to III. Motility features were similar in the pouch and the jejunal limb. Orthograde propagation of phase III-like activity was reduced and may contribute to the pouch storage function. Four of the 5 symptomatic patients showed highly abnormal motility with hypomotile or obstructive patterns. The technique of connecting the pouch--jejunal interposition of Roux-en-Y--did not affect the motility findings. CONCLUSIONS: The altered motility occurs after a Hunt-Lawrence pouch reconstruction in asymptomatic patients. Symptoms after gastrectomy are associated with further disturbed motility that can be differentiated from the motility changes in asymptomatic patients.     

Variations in the bladder exstrophy complex associated with large omphalocele

Two newborns with a large omphalocele associated with the bladder exstrophy complex are presented. In 1 case the omphalocele was combined with a musculoskeletal defect and imperforate anus with an anovulvar fistula. The other patient had a musculoskeletal deformity and a duplicated bladder with exstrophy. Surgical treatment was successful in both cases.     

Total gluteal pouching with pseudoanus caused by burn injury: report of a case

PURPOSE: We report the case of a 69-year-old man who had suffered a third-degree burn injury of the buttocks close to the perianal region at the age of 2 years. Although initial attempts for conservative treatments failed, wound healing was achieved after numerous skin grafts. However, after prolonged healing, the patient developed scar contracture, resulting in total effacement of the gluteal folds and natal crease, and formation of a gluteal pseudoampulla and a pseudoanus. As a result of misinterpretation of the local anatomy, for the next 50 years the patient had to defecate into the gluteal pouch and empty this pseudoampulla by manually compressing the buttocks and irrigating with chamomile tea. METHOD: After a thorough examination revealed the presence of a normal, uninjured anus hidden by the scarred pouch, we excised this burn scar to expose the unburned perianal tissue and covered the resulting defect with a meshed, split-thickness skin graft. RESULT: Anorectal function was preserved, the anatomic contour was restored, and primary wound healing was achieved after one single-stage operation. CONCLUSION: To prevent such deformities, we recommend early excision and skin grafts as initial treatment, as opposed to conservative treatment, and thorough follow-up examinations to avoid misinterpretation of such a complex, altered local anatomy.     

Hyperendemic pulmonary tuberculosis in a Peruvian shantytown

Even excellent clinical function after ileo-anal pouch construction is associated with a variety of physiological abnormalities. Small bowel intestinal motility is essentially normal but the ileal reservoir serves to markedly suppress the ileal motor response both to progressive distension by intestinal contents and to transmitted myoelectrical complexes. As a result, the healthy pouch can accommodate a large volume of intestinal content before the rising baseline pressure and the appearance of large isolated contraction waves produce an urge to defecate. Evacuation in the normal pouch patient is rapid and highly efficient and is achieved by means of the Valsalva maneuver without any evidence of significant intestinal propulsion. External anal sphincter function is fully preserved but internal anal sphincter function is significantly impaired in the immediate postoperative period. Recovery occurs over the next 6 to 12 months but is often incomplete. Bacterial overgrowth in the pouch and prepouch ileum is almost universal and results in the premature deconjugation of primary bile salts and accumulation of secondary bile salts within the pouch. These produce morphologic changes in the ileal mucosa, and their excretion in pouch effluent gradually depletes the bile salt pool. Anerobic organisms also bind with vitamin B12 and the vitamin B12-intrinsic factor complex, resulting in subtle but measurable reductions in vitamin B12 levels in pouch patients. Finally, anerobic fermentation of mucus and undigested carbohydrate results in excessive quantities of short chain fatty acids within the pouch lumen. The clinical significance of these substances is unclear, but they may have an adverse action on both ileal mucosal and smooth muscle function. In essence, however, the pouch surgeon can maximize the likelihood of good clinical function by constructing a large capacity pouch, by avoiding surgery in patients with clearly deficient anal sphincter mechanisms, and by careful attention to pouch-anal anastomotic technique.     

Effects of loperamide on ileoanal pouch function

BACKGROUND: Opioid analogues are used to manage increased bowel frequency in patients with an ileoanal reservoir. The aim of the study was to determine the clinical efficacy of loperamide in patients with an ileoanal reservoir and to assess its effect on pouch motility. METHODS: Fourteen patients with a pouch who had normal pouch emptying and anal function were studied. Ambulatory pouch and anal motility, and stool weights, were recorded for 24 h while taking no medication and for 24 h while receiving 8 mg loperamide. In a second analysis, patients were divided on the basis of bowel frequency into those with 4 or fewer motions (good function; n=6) and those with more than 6 per day (poor function; n=8), to determine any differential effects of loperamide. RESULTS: Loperamide decreased median bowel frequency (no loperamide 5.5 versus loperamide 4.0, P=0.03) and 24-h stool weight (610 g versus 413 g, P=0.03) but not individual stool weights. Patients with poor function had both higher bowel frequency (8.0 versus 3.5 per 24 h, P=0.004) and higher stool weight (728 g versus 430 g, P=0.05) with no treatment than those with good function. High-amplitude pouch pressure waves were greater in number before defaecation in patients with poor function and did not decrease with loperamide, in contrast to patients with good function. Pouch baseline pressure decreased after defaecation to a similar extent in both groups and was not affected by loperamide. CONCLUSION: Loperamide 8 mg per day reduces bowel frequency by reducing total stool weight, not individual stool weights. In patients with good function it also affects pouch motility. High bowel frequency is associated with increased pouch high-pressure waves.     

Autofluorescence in normal and malignant human oral tissues and in DMBA-induced hamster buccal pouch carcinogenesis

Light-induced fluorescence spectroscopy was conducted on human oral malignant and normal tissues. Under 330-nm excitation wavelength, significant differences in fluorescence intensity were observed around 380- and 460-nm emission. Furthermore, 7,12-dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis in hamster buccal pouch was investigated to elucidate whether similar alterations of fluorescence spectroscopy occurred during the development of squamous cell carcinoma. Similar to the spectral profiles of human oral malignant and normal tissues, the most intense fluorescence peaks in the pouches occurred at 380 nm and 460 nm emission under 330 nm excitation wavelength. At 380 nm emission, the fluorescence intensity of normal pouch mucosa was stronger than those of DMBA-treated abnormal tissues at different stages of carcinogenesis. However, at 460 nm emission, the fluorescence intensity of DMBA-treated tissues was not only stronger than that of normal pouch mucosa but also shifted to 470 nm. These results suggest that under 330 nm excitation wavelength fluorescence spectroscopy may be useful for the detection of oral malignant lesions.     

Cloaca, the most severe degree of imperforate anus: experience with 195 cases

OBJECTIVE: To provide a follow-up of 195 patients with cloacal malformations seen by the author from 1959 to 1998. SUMMARY BACKGROUND DATA: Cloaca, which occurs in approximately 1 of 50,000 births, is the most complex type of imperforate anus with confluence of the rectum, vagina, and bladder in a urogenital sinus. Functional results for the bowel, the genital tract, and the urinary tract were formerly poor. Cloacal exstrophy, which is an even more complex spectrum of malformations, was uniformly fatal until 1960. In addition to imperforate anus, these babies have an omphalocele, two exstrophic bladders, between which there is an open cecum, and a blindly ending colon hanging down in the pelvis from the cecum. Although both of these diagnoses contain the word "cloaca," which is Latin for sewer, they are really two separate entities in terms of surgical management. Cloaca and cloacal exstrophy in most cases are very different anatomic problems. However, there are variants that are like a hybrid, which is the rationale for reporting together an experience with both entities. METHODS: Records were reviewed of 154 patients with cloaca and 41 patients with cloacal exstrophy to assess anorectal function, urinary continence, and sexual function where available. RESULTS: Follow-up was available in 141 cloaca patients: 82 have spontaneous bowel movements and satisfactory control, 38 use enemas to evacuate, 9 have a colostomy, 7 have fecal soiling, and 5 are too recently operated to evaluate. Regarding urinary control, 83 void spontaneously, 40 catheterize to empty, 4 have urinary diversion, 1 has a continent diversion, 5 patients are wet, and 8 are too recently operated to judge. Twenty-four patients are now adults, 17 of who have experienced coitus and 7 have not. Seven have had babies, all except one by cesarean section. Results of surgery for cloacal exstrophy are not as good, but are encouraging nonetheless for an anomaly that was uniformly fatal before 1960. Of the 41 cloacal exstrophy patients being followed, 7 have not undergone surgery. Fifteen have a colostomy; 19 had pull-through of the colon, but 3 were subsequently reversed for fecal incontinence. Most depend on enemas to evacuate. Urinary dryness was attained in 30 patients, usually by intermittent catheterization of the bladder, which was augmented with small bowel or stomach or both. Only three void voluntarily. Fifteen of the completed long-term patients wear no bag. Only three of the completed patients wear two bags. The rest have one bag. CONCLUSIONS: Imperforate anus and associated malformations in cloaca and cloacal exstrophy are not hopeless problems. A reasonable lifestyle can be achieved for most of these children with comprehensive surgical planning.     

The role of maternal thyroid hormones on the development of the brushtail possum, Trichosurus vulpecula

Thyroxine (T4) is a vital hormone for the development of mammals. To determine the role of maternal thyroid hormones on organ development, methimazole, an inhibitor of T4, was first administered via a minipump to 13 mothers with pouch young between days 10 and 80 post partum for 28 days. Three young survived and 10 of the young died at 104.0 +/- 10.8 days post partum (mean, SEM). Methimazole was then administered for 28 days to 6 lactating adult possums with pouch young at day 20 post partum. The effects of this treatment on the maternal plasma concentrations of T4 were monitored and the development of the lung, kidney and brain of the young were examined at day 90 post partum. There was no difference in the morphology of the lung, kidney and brain of pouch young at day 90 post partum whose mothers were treated with methimazole or saline. Thus methimazole administered to lactating possums for a short period early in lactation can cause the demise of the young about day 100 post partum although the cause of death is unknown. It is possible that the development of the central nervous system or some other vital organ has been inhibited, this altered state not being apparent morphologically. Nevertheless the marsupial appears to be similar to the eutherian in its requirement for thyroxine for normal development. However whereas this requirement is apparent during fetal development and around the time of birth in eutherians thyroxine is of importance during pouch development in marsupials.     

Determinants of pouch function after continence-preserving proctocolectomy

A prospective study was undertaken in 17 patients undergoing restorative proctocolectomy for ulcerative colitis (13 patients) or familial adenomatous polyposis (4 patients) to determine relationship between pre- and postoperative anal sphincter function, pouch characteristics and functional results. Postoperatively all manometric parameters were significantly reduced and remained so permanently. Only squeeze pressure rose to normal values again. The most important factor for a favourable functional outcome was pouch volume. A capacious reservoir was associated with a low stool frequency, low risk of incontinence and general success of the operation, as assessed subjectively. Perianal soreness with considerable skin problems occurred frequently when resting and squeeze pressures were markedly reduced postoperatively.     

Current management of bladder exstrophy

This article describes in detail the modern management of the patient born with classic bladder exstrophy. Also, new techniques of prenatal diagnosis and pelvic fixation to secure the initial or secondary closure are discussed. Last, management of the failed closure and the bladder not suitable for closure are described and outlined. A successful initial closure of the infant born with bladder exstrophy is the single most important determinant in the eventual development of continence in the exstrophy patient.