Prenatal Diagnosis of Vesicorectal Fistula.

Anorectal malformations are a rare condition difficult to diagnose in the prenatal period. It can be suspected if distal bowel appears dilated in the first-trimester ultrasound or if intraluminal echogenic foci are detected during the second-trimester scan. We report a case with these ultrasound signs (dilated sigmoid at the first trimester and intraluminal echogenic calcifications at the second trimester), in which a vesicorectal fistula image was obtained. This is the first published prenatal image of a vesicorectal fistula.

Revisiting an ancient treatment for transphincteric fistula-in-ano 'There is nothing new under the sun' Ecclesiastes 1v9.

OBJECTIVE: The history of treatments for fistula-in-ano can be traced back to ancient times. Current treatment of transphincteric fistulae is controversial, with many options available. We reviewed the history of treatment using cutting setons and present our series of transphincteric fistulae in the light of the series in the literature. DESIGN: Literature review and case series. SETTING: Hospital based coloproctology service PARTICIPANTS: 140 consecutive patients presenting with fistula-in-ano were included. MAIN OUTCOME MEASURES: The literature pertaining to treatment of transphincteric fistula was reviewed, along with the outcome of various treatment methods for this condition. Data were collected for 140 consecutive patients presenting with fistula- in-ano were assessed for fistula healing, recurrence and complications. RESULTS: A total of 140 consecutive patients with fistula-in-ano were identified, of which 111 were cryptoglandular (79.3%). Eighty-one of these 111 were transphincteric (73.0%). At a median follow-up of 35 months (range, 2-83 months), 70 transphincteric fistulae had healed (86.4%), 10 were still undergoing treatment (12.3%) and one patient was lost to follow-up prior to treatment (1.2%). Two patients in this group required a stoma (2.5%), six patients developed recurrence (7.4%); three 'true' recurrences (3.7%). One (1.2%) developed a chronic fissure. There were no reported cases of incontinence. CONCLUSIONS: The management of transphincteric fistula-in-ano is complex and controversial, for which no clear surgical procedure has gained acceptance as the gold standard. This study demonstrates that transphincteric fistulae can be successfully treated using cutting setons. A high healing rate (86.4%), low recurrence rate (7.4%) and a low complication rate (3.7%) are shown, which compares favourably with published rates over a long follow-up.

Bifid scrotum and anocutaneous fistula associated with a perineal lipomatous tumor complicated by temporary bilateral cryptorchidism in utero mimicking ambiguous genitalia: 2-D/3-D fetal ultrasonography.

Ambiguous genitalia (AG) is a morphological diagnosis defined as genitalia not typical of a male or female. Findings mimicking AG, such as penoscrotal anomalies, anorectal malformations, and perineal lipomatous tumors, may prevent accurate identification of the fetal sex. We report a case of bifid scrotum and anocutaneous fistula associated with a perineal lipomatous tumor complicated by temporary bilateral cryptorchidism in utero, which were findings mimicking AG. Several perineal anomalies are associated developmental occurrences. In the present case, the combination of bifid scrotum and temporary bilateral cryptorchidism in the male fetus mimicked the combination of clitoromegaly and prominent labia, which are commonly observed in female fetuses. However, serial systemic assessments using prenatal 2-D/3-D ultrasonography and magnetic resonance imaging were unable to detect the anocutaneous fistula and differentiate the perineal lipomatous tumor. This case report suggests that the prenatal detection of perineal abnormalities may warn obstetricians of potentially undetected congenital perineal anomalies.

Establishment of a rescue program for anorectal malformations induced by retinoic acid in mice.

AIMS OF STUDY: Retinoid-mediated signal transduction plays a crucial role in the embryogenesis of various organs. We previously reported the successful induction of anorectal malformations in mice using retinoic acid (RA). Retinoic acid controls the expression of essential target genes for cell differentiation, morphogenesis, and apoptosis through a complicated interaction in which RA receptors form heterodimers with retinoid X receptors. In the present study, we investigated whether the retinoid antagonist, LE135, could prevent the induction of anorectal malformations (ARMs) in mice. METHODS: Retinoic acid was intraperitoneally administered as 100 mg/kg of all-trans RA on E9; and then the retinoid antagonist, LE135, was intraperitoneally administered to pregnant ICR strain mice on the eighth gestational day (E8), 1 day before administration of RA (group B) or on E9, simultaneously (group C) with RA administration. All of the embryos were obtained from the uteri on E18. Frozen sections were evaluated for concentric layers around the endodermal epithelium by hematoxylin and eosin staining. RESULTS: In group A, all of the embryos demonstrated ARM with rectoprostatic urethral fistula, or rectocloacal fistula, and all of the embryos showed the absence of a tail. In group B, 36% of the embryos could be rescued from ARM. However, all of the rescued embryos had a short tail that was shorter than their hind limb. The ARM rescue rates in group B were significantly improved compared to those in group A (P < .01). In group C, 45% of the embryos were rescued from ARM, but all of the rescued embryos had short tail. The ARM rescue rate in group C was significantly improved compared to that in group A (P < .01). However, there was no significant difference in the ARM rescue rate between group B and Group C. CONCLUSION: The present study provides evidence that in the hindgut region, RAR selective retinoid antagonist, LE135, could rescue embryos from ARM. However, the disturbance of all-trans RA acid was limited to the caudal region. Further study to establish an appropriate rescue program for ARM in a mouse model might suggest a step toward protection against human ARM in the future.

PCSK5 and GDF11 expression in the hindgut region of mouse embryos with anorectal malformations.

BACKGROUND/PURPOSE: Retinoid-mediated signal transduction plays a crucial role in the embryonic development of various organs. We previously reported that retinoic acid induced anorectal malformations (ARM) in mice. GDF11 is a TGFß superfamily molecule and is cleaved and activated by proprotein convertase subtilisin/kexin 5 (PCSK5). PCSK5 (PC5/6) mutations result in an abnormal expression of Hlxb9 and Hox genes, which include known GDF11 targets that are necessary for caudal development in vertebrate embryos. To determine a possible role of the retinoid-mediated signaling pathway in the pathogenesis of ARM, we investigated whether all-trans retinoic acid (ATRA) affected the expression patterns of PCSK5 and GDF11 in ARM-treated mouse embryos. METHODS: Pregnant ICR-Slc mice were administered 100 mg/kg ATRA by gavage on embryonic day (E) 9.0. Embryos were harvested between days E12 and E18, and mid-sagittal sections of the hindgut region were prepared for immunohistochemistry using antibodies against PCSK5 (PC5/6) and GDF11 (GDF8/11). RESULTS: Over 95% of the embryos treated with ATRA showed ARM, with rectourethral fistula or rectocloacal fistula, and a short tail. Furthermore, most of these embryos exhibited sacral malformations, tethered spinal cords, and presacral masses resembling those malformations found in caudal regression syndrome. By E14, normal mouse embryos formed a rectum and anus, and the somites behind the hindgut were positive for PC5/6 and GDF8/11. In contrast, in ARM embryos, the somites behind the hindgut were negative for PC5/6 and GDF8/11. CONCLUSION: ATRA treatment affected the caudal development in mouse embryos, resulting in anorectal, sacral, and spinal malformations, and inhibited PCSK5 and GDF11 expression in the hindgut region. These findings indicate that the expression of PCSK5 and GDF11, which plays a crucial role in the organogenesis of the hindgut, was disturbed in the hindgut region when retinoid-mediated signaling was disrupted. This study offers a new insight into the pathogenesis of ARM in mice as affected by the interaction between ATRA and PCSK5/GDF11.

Aberrations of the intrinsic innervation of the anorectum in fetal rats with anorectal malformations.

BACKGROUND: Fecal accumulation, constipation, soiling, and incontinence are common sequelae after repair of anorectal malformations (ARMs) in children. It is believed that besides the abnormalities of sacral roots, certain inherent abnormalities of the myenteric plexuses may play an important role in the final outcome after definitive repair. METHODS: This study was conducted to investigate the distribution of neuron-specific enolase (NSE), vasoactive intestinal peptide (VIP), and substance P (SP)-100 neurotransmitters in the rectosigmoid and fistulous tract of the ethylenethiourea-treated rat with ARMs. RESULTS: ARMs were induced by administering 1% ethylenethiourea (125 mg/kg) on gestational day 10, and the litter was harvested on gestational day 21 by cesarean section. Forty-eight controls and 63 with ARMs (46 high-type and 17 low-type) were recovered. Whole-mount preparations of each rectosigmoid and fistulous communication between the rectum and genitourinary tract were stained with fluorescent antibodies against NSE, VIP, and SP-100. The tissues were counterstained with Eriochrome black-T and methyl green dyes to improve the visualization of the myenteric plexuses. CONCLUSIONS: The immunoreactivity of NSE, VIP, and SP-100 was markedly reduced in the rectum and fistulous tract of high-type ARMs and slightly reduced in low-type ARMs compared with controls. Intramural nerves stained by VIP and SP-100 antisera were decreased in both types of ARM, indicating that both inhibitory and excitatory motor neural elements were affected, and this may explain the distal colonic dysmotility seen postoperatively in both high and low ARMs.

Normal and abnormal embryonic development of the anorectum in rats.

BACKGROUND: The embryologic and pathologic aspect of anorectal malformation (ARM) remains poorly understood. There is no universally accepted theory to explain anorectal embryology and the abnormal development that produces ARM. The aim of this study was to observe the developmental processes of anorectum in rats and to explore the abnormal embryonic development that leads to ARM. METHODS: Rat embryos with ARM were obtained by treating pregnant rats with administration of ethylenethiourea (ETU). Normal rat embryos and embryos with ARM from gestational days 12.5 to 20 were sectioned serially and sagittally and stained with H & E. The relevant structure including cloaca and urorectal septum (URS) were examined in a temporospatial sequence. RESULTS: Characteristics of anorectum development in ARM rat embryos treated by ETU were as follows: (1) URS never fused with cloaca membrane. (2) Dorsal cloacal membrane was maldeveloped. (3) Cloacal configuration was abnormal. (4) Tail groove never appeared. All type of ARM was the rectourethal fistula and common cloaca in ETU-treated rat embryos and was discernible on gestation day 16. CONCLUSIONS: Absence of the tail groove and maldevelopment of the dorsal cloacal membrane, cloacal configuration, and urorectal septum are likely to be responsible for the formation of ARM. Failure of fusion of the URS with cloacal membrane is the immediate reason for rectourethral fistula or common cloaca in ETU-treated rats.

Development of anorectal malformations using etretinate.

PURPOSE: To investigate the pathogenesis of anorectal malformations (ARM), the authors studied cell proliferation and programmed cell death (apoptosis) patterns in murine embryos that develop ARM as a result of administering an overdose of etretinate, a long-acting vitamin A analogue (retinoid). METHODS: Pregnant mice were fed 60 mg/kg of etretinate on the ninth gestational day (E9). Embryos were obtained between E9.5 and E13, and prepared for histological study. Cell proliferation was examined using proliferative cell-specific nuclear antigen (PCNA) expression. Apoptosis was identified by detecting in situ DNA fragmentation using the TdT-mediated dUTP-digoxigenin nick end-labeling (TUNEL) method. RESULTS: Over 95% of etretinate-treated embryos had ARM including rectoprostatic urethral or rectocloacal fistula. In the histological study, ARM embryos showed defective cell proliferation in the cloacal membrane and excessive apoptosis in the dorsocaudal region on E11, which resulted in a lack of apoptosis in the anal orifice and a short tail on E12, respectively. Cells forming the urorectal septum showed the same pattern of cell proliferation and apoptosis both in ARM embryos and the controls. These results suggest that impairments of embryonal cellular dynamics in the cloacal membrane and dorsocaudal region induce some types of ARM.

The principles of normal and abnormal hindgut development.

In the past, several theories have been proposed to explain the occurrence of anorectal malformations. Most investigators believe that these malformations are the result of an impaired process of septation. However, in 1986 vd Putte challenged all theories that tried to explain anorectal malformations by a faulty fusion of lateral ridges of the cloaca. To elucidate the principles of normal and abnormal cloacal development, the authors studied the morphology of this region in normal embryos of rats and abnormal embryos of SD mice, which often have abnormal cloacas. Using scanning electron microscopy (SEM), 245 normal rat embryos and 80 abnormal SD-mice embryos were observed. The results were as follows. (1) In normal embryos the region of the future anal opening can be identified soon after the establishment of the cloacal membrane. This part is a fixed point in cloacal development. (2) In abnormal embryos the cloacal membrane is too short. The region of the future anal opening is missing. (3) In abnormal embryos a spectrum of malformed cloacas can be observed. This is in accordance with the spectrum of anorectal malformations clinically observed in humans. (4) The authors' observations support recent findings that the "fistula" in anorectal malformations resembles a normal anus at an ectopic position.

Imperforate anus associated with a recto-bulbar-cutaneous fistula.

This is the report of two newborn boys with imperforate anus associated with a long rectocutaneous fistula running deep into the scrotum and communicating, in its midportion, with the bulbar urethra. The findings are compared with those of a somewhat similar case in the literature, with some speculations as to the possible embryogenesis of the lesion.

[Congenital recto-urethral fistula. Report of one case without associated anorectal malformation (author's transl)]. / Fistule recto-urétrale congénitale. Rapport d'un cas sans malformation ano-rectale associée.

Report of a case of congenital recto-urethral fistula in a man presenting with sterility. Cure of the fistula after a trans-anal sphincter and trans-anorectal approach of York-Mason without temporary colostomy.