Variations in Exstrophy of the Bladder

THE JOURNAL OF UROLOGY

Vol. 88, No. 6 December 1962 Copyright © 1962 by The Williams & Wilkins Co.

Printed in U.S.A.

VARIATIONS IN EXSTROPHY OF THE BLADDER VICTOR F. MARSHALL

AND

EDWARD C. MUECKE

From the Department of Sitrgery (Urology), .James Buchanan Brady Foundation, The New York Hospital ancl Cornell University Medical College, New York, N. Y.

Even among deformities generally, exstrophy of the bladder is an exotic condition. l\fany congenital anomalies, such as hare lip, correspond with a normal embryonic stage; that is, the eventual deformity is essentially present at some particular stage in the normal embryo. 1 - 3 This is one principal basis for the concept of causation by arrest in developmcnt. 4 , 5 Exstrophy, on the other hand, is never present as a normal developmental stage in man or animal. 6 The deformity has not been certainly recognized in abnormal embryos, 6 , 7 although it has been studied in seven-month human fetuses. 8- 10 ~!fany congenital anomalies, particularly those resulting from arrests, have been produced experimentally11-1 5 but not exstroAccepted for publication May 19, 1962. Presented, in part, as the Ballenger Memorial Lecture at annual meeting of Southeastern Section, The American Urological Association, Inc., Belleair, Fla., April 8-12, 1962. The study was supported by a grant from the Mary Duke Biddle Foundation. 1 Arey, L.B.: Developmental Anatomy, 6th ed. Philadelphia: W. B. Saunders Co., 1954, pp. 200-201 ; 306-308. 2 Jordan, H. E. and Kindred, J.E.: A Textbook of Embryology, pp. 116-118. New York: D. Appleton& Co., 1932. 3 Patten, B. M.: Varying developmental mechanisms in teratology. Pediatrics, 19: 734-748, 1957. 4 Stockard, C. R.: Developmental rate and structural expression: an experimental study of twins 'double monsters', and single deformities, and the interaction among embryonic organs during their origin and development. Arn. J. Anat., 28: 115-277, 1921. 5 Porter, R. M.: Bladder outside the belly. Nash ville J. Med. & Surg., 8: 381, 1855. 6 Patten, B. M. and Barry, A.: The genesis of exstrophy of the bladder and epispadias. Am. J. Anat., 90: 35-53, 1952. 7 Pohlman, A. G.: The development of the cloaca in human embryos. Arn. J. Anat., 12: 1-26, 1911. 8 Johnston, T. B.: Extroversion of the bladder, complicated by the presence of intestinal openings on the surface of the extroverted area. J. Anat. & Physiol., 48: 89-106, 1913. 9 Bryce, T. H.: Description of a fetus the subject of retroflexion of the trunk, ectopia viscerum and spina bifida. J. Anat. & Physiol., 29: 553-568, 1895. 10 Loewen, S. L. and Rupe, L. 0.: A case of a pseudohermaphrodite with exstrophic bladder. J. Kansas M. Soc., 44: 186-189, 1943. 766

phy of the bladder. This peculiarity suggests that exstrophy is not caused by a mere arrest. Mechanisms other than developmental arrest are known to produce congenital anomalies. 3 Also unlike certain other anomalies, such as polycystic kidneys, exstrophy seldom occurs in families.16-20 However, Higgins mentioned that he had encountered the condition in 2 families ;21 Chisholm's patient had 2 siblings (one of opposite sex) who both had exstrophy ;22 and Glaser and Lewis reported two successive boys with exstrophy born to the same parents. 23 vVhat11 Warkany, J. and Schraffenberger, E.: Congenital malformations induced in rats by maternal nutrition deficiency. V. Effects of a purified diet lacking riboflavin. Proc. Soc. Exper. Biol. & Med., 54: 92, 1943. 12 Fraser, F. C. and Fainstat, T. D.: Production of congenital defects in offspring of pregnant mice treated with cortisone. Pediatrics, 8: 527-533, 1951. 13 Haring, 0. M. and Lewis. F. J.: The etiology of congenital development anomalies. Surg., Gynec. & Obst., 113: 1-18, 1961. 14 Douglas, B.: The role of environmental factors in the etiology of so-called congenital malformations. Plast. & Reconst. Surg., 22: 214-229, 19.58. 15 Sinclair, J. G.: Intestinal hernia with eversion and exstrophic bladder. J. Pediat., 26: 78-81, 1945. 16 Takala, M. E.: Paternal and niaternal factors in the etiology of congenital malformations. Ann. Chir. gyn. fenn., 47 (suppl. 77) 1958. 17 Muller, G. P.: The surgical treatment of exstrophy of the bladder. Surg. Clin. N. Am., 15: 275--283, 1935. 18 ten Berge, B. S. and Wildervanck, L. S.: Familial, congenital anomalies of uropathic and genital system. Nederl. tijdschr. geneesk., 95: 23892395, 1951. 19 Stiles, H. J.: Epispadias in the female and its surgical treatment. Surg., Gynec. & Obst., 13: 127-140, 1911. 20 Stevenson, S. S., Worcester, J. and Rice, R. G.: Six hundred seventy seven congenitally malformed infants and associated gestational characteristics. Pediatrics, 6: 37-50, 1950. 21 Higgins, C. C.: An evaluation of cystectomy. For exstrophy, for papillomatosis and for carcinoma of the bladder. J. Urol., 80: 279-292, 1958. 22 Chisholm, T. C.: Exstrophy of the urinary bladder. Arner. J. Surg., 101: 649-655, 1961. 23 Glaser, L. H. and Lewis, A. P. R.: A case of familial incidence of ectopia vesicae. Brit. Med. J., 2: 1333, 1961.

VARIATIONS IN EXS'l'ROPHY OF BLADDER

ever the ultimate causes of exstrophy, it might be reasonable to exped at kast occasional recurrences in apparent]~, similar c:ircumstances, yet the sr:arcity in families sec;ms noteworthy. :\fost persons with this anomaly do not reproduce, but at least 33 children have been horn to 26 exstrophied mothers witr10ut the deformity reappc'.aring. 2H 2 Furthermore, cpispadiac fathcrsaa-:rn apparently have not produced offopring with this deformity. One of our qiispacliac patients (22.5529) evidently sired ,5 normal chilclren. 37 , '18 Exstrophy of the bladder has appeared on at least one occasion in both membern of identical twins. 21 Coates' twins 39 and Ruktinat's twins 40 were of the same sex but onl)' I twin of rnch pair had exstrophy, In our twins of different sex, 7462.5 24 Rubovits, F. E. and Arnko!f, M.: Pregnancy associated with exstrophy oft.ho bladder. .J. Urol., 62: 52-57, 194\J. 25 'Winslow, R.: Report of a case of exstrophy of the bladder operated upon nearly thirty yer,rs Surg., & Obst., 22: :350-352, 191G. Clayton, C.: Note of a case of cxstrophy of the bladder with procidentfa. J. Obst. & Gyncc. Brit. Emp., 52: 177-17\J, 1945. 21 Balln,ntyne, J. W.: So-called epispaclias in woman. Edin. Hosp. 4: 24\J-277, 18!J6. 28 Connell, F. G.: of the bladder. .J. A. M.A., 36: 29 Hamilton. H. Boston Med. & Surg. 30 Hart, D. B.: A the morphology of the human urinogenital tract. Trans. Edin. Obst. Soc., 26: 25\HlOO, 1900-01. 31 Duncan, A.: An attempt towards a systematic account of the appearances connected with that malformation of the urirn,ry organs. Edin. lVIed. & Surg. J., 1: 4:'l-60, 1805. 3 2 0stcrgaard, E.: En fpdscl ved Spaltbaekken med Ektopia vesicae. ''.'\ord. Med., 17: 88-89, 1943. 33 Breschet: Extroversion. Dictionaire des sciences medicales, 14: 1815. 3l Bremer, .J. L. '. ww,,--,H,"W and epispadias. a philological note. N. Med., 207: 537-539, 1932. "' Kittredge, W. E. and Brr,dburn, C.: Incomplete cxstrophy uf tho hl a.cider: case report. J. UroI., 72: 38-40, 1954. 36 Burns, E., Kittredge, W. E. and Hyman, J.: Bilateral cutaneous ttreterostomy eighteen years after uretcrosigmoidos tom.v for exstrophy of the bladder. Ann. Smg., 125: 788-797, 1917, 37 Marshall, V. F. an cl Ganlnor, J. S. · An eval uation of foe Coffov I method for ureterointestinal anastomosis, Surg., Gynec, & Obst., 81: 559-574, 1945. ,s Stevens, A, R.: Longevity following ureterointestinal an,1sr,()m J. UroL, 46: 57-66, 1941. '" vV. H.: of a remarkable conformation of urinary and genital organs in n. female child. Edin, Med. & Surg. J., 1: :39--42, 1805. 40 Rukstinat, G. J. and Balfour, .L D.: Hypogastroenteroschisis, spina bifida, diaphragmatic hernia. and left renal in a viable full term child. Arch, Path., 6: Hl28.

7G7

and 74626, only the bo.r had exstrophy., hut botb

did ban, a tcratomatous dcn,·lopmcnt in the retroperitoncal tiHHUCS, There is a of exstroph:· occurring after maternal rubella at LI weeks of gestation, but this could han' been coincidental. Spontaneous congenital auomalicc in animals an) not rare and han, beeu studied, but exstrophy in these most non-existc:nt. 42 - 4 u The only cJpmonstrntion of an exstrophy in an animal fouud in an ('Xtcnclecl search is the case of a male cat reported in 1832. A reference was also found eoncerniug an adult horse that likely had c:xstropli.Y, hut the detail was deficient and the original presentation "1 1H1i; aYailablc to us. '\Ve did encotmter a nwnt10n uf cpispaclias alone in Boston Tc:rri,:r dog;s and statement that exstrophy could occurY In 1·icw the huge number of economicall:· and emotionally important animals born .n·ar after year, it would seem amazing that this dramatically o!Aiou,, horror could be cmrnistC'ntJy overlooked. Some exstrophiccl animals would still lian• r.g;. the calf for Yea!, like the !cs.~ olivious hut recog" Lock F Gatling, H.B. and Wells, H B Difliculti~s in diagnosis of congenital a.bnor, rnalities. J. A. M. 178: 711-714, HJ61. "'Latimer, H.B.· found in a series fetal and newborn puppies. 1~niv. Kmisas Bull., 33: 381, rnso. '" Index Veterinarius, 1952-59. H Direct communications with veteri1rnrv insti" tutions: Angell Memorial Animal , Boston; U. S. Dept. uf Diseases Division, Beltsville· nary College, Ithaca; and dcr Tieriirztlichen Hochsclrnle, 45 Duncan, A.: A trc~tise on the diseases which are incident to sheep in Scotland. Edin, J\IccL Surg., J., 4: 109-113, 1808. '16 Riches, E. W.: Ectopic vesicae. Ann, Hoy, Coll. Surg., 9: 7179, 1951. 47 Cosgrove, J. S. J\!1.: The and the new-born foal. Vet. 1955. 48 Story, H. E.: A cnsu of hornt:shoe kidney anu associated vascular anomalies in the clomesti0 cat. Anat. Record, 86: 307-:3HI, ID43. 49 Florian, J.: The formation of the connecting stalk a.nd the extension of tho anmiotic cavi1,v town.rds the tissue of the connecting stalk in young human embryos. ,J. Anat., 64: 454-476, 1930. 50 Geoffroy Saint-Hilaire, L: Histoin, Genera.I,) ct Particuliere des Anomalies de chez !'Homme et lcs Animaux, - des sities, des Va.ri6t6s et Vices de Confonrrnt.ion, out Tmite de Teratologio. Pmis. J. B. Baili{,n,, 1832, vol. 1, p. :387. 51 Eggcrdes: Mis cell. Curios a S. Ephcm. Dec. II, Ann. 6, p. 414, 1G87. (Citod Gurlit, F. Lehrbuch clcr Pathologischen der Ham,,, Siiugcthiere. Berlin, 18:32, pp. 9fi, 400-'llO.)

768

MARSHALL AND MUECKE

Fm. 1. Mowat's illustration of exstrophy in 1747. 54 Inguinal hernias (E, lower figure) appear exaggerated. Note dissection of abdominal wall in his figures 1 and 2. Similarity to Sorrentino and Leonetti's photographic figure 15 55 is impressive. nizable fr@emartin. 52 Nor did the ancients describe exstrophy, 28 The first case was likely reported in either 1646 or 1595, 28 • 53 but probably the first truly complete description was that of Mowat in 1747 54 (fig. 1). Finally, the anomaly of 52 Lillie, F. R.: The free martin; a study of the action of sex hormones in the foetal life of cattle. J. Exper. Zoo!., 23: 371-452, 1917. 53 HalJ, E. G., McCandless, A. E. and Rickham, P. P.: Vesico-intestinal fissure with diphallus. Brit. J. Urol., 25: 219-223, 1953. 54 Mowat, J.: An account of a child born with the urinary and genital organs preternaturally formed. Medical Essays and Observations, 3: 220-222, 1747 (pub. by Edin. Soc.). 55 Sorrentino, F. and Leonetti, P.: Terapia della Estrofia Vesicale. Esi, Naples, 1958.

exstrophy is outstandingly peculiar in that it involves not only the urinary tract and the normally associated genital system, as might be anticipated, but also routinely involves the musculoskeletal arrangements of the lower abdomen and pelvis. This is in contradistinction to the vast majority of other urinary and genital anomalies. In fact, the deformity of exstrophy is sometimes anatomically so extensive as to affect the lower gastrointestinal tract, thus constituting a complex involving the urinary, genital, musculoskeletal and intestinal systems all in one continuum. In spite of such extensive derangements of the lower

VAHJATIO_:'\S 1-'\ EXSTHOPHY OF BL,\ DDER

7bD

CARCINOMAT US ULCERATIO l

Fm, 2. 1\HI 7705, 1, adenrJcarcinmi:rn in exstrophied bladder of nn1 rn11t(,d womau.

port,jons of thC' bod_\-, auo11rnlie,'i in the upper half appc,ar tsurprisingly iufrc;quent in thPHl" cases, Ernn in extreme cases of ectopia Yis<·era, in whicli most of tlw organs h,n-c protrnclccl outside of the bod~- through a hugC' n·ntrnl abdominal cleft, the uppC'r portion of the hoc!~- has sc,-ernl times been ess(:ntiallY nonnaJH- ,,ri-:,7 Lumhosanal nwningocc:l<: is, ho,YeYer, a quite frequent but not im-ariablc-, ac·companiment of the more extreme ,-ariatic-·s in the exstrophic complex. "\n anomaly so ano11rnlo1rn can hardly foil to cxcik curiosity,

Besides cnriosit~- and the desire for knmYledge for its mm sake, there are important other reasmrn to study exstrnplty. Tlw grmtest practical reason is tlw lwpl' of impmYing the miserable life of tbe patiPnt 1vitli this deformity. While many authors ha n• reported that about half of tlw untreated patients with exstroph)' \\'ill die by thl'ir tcntli year and hrn-thircls liy their twenty-first year, the fac:tHul l;asi0 for thits stakrnl'nt is not completely dc•ar. 21 , 1o.Hi \Yith rare L'Xccptions, the famous 'j(' Dornn, A .. T)issecbon of the gcnito-urirrnry in a case of iissurn of the abdominal \\'nlls. & Ph~-sioL, 15: 22Ci-2:lcl, 1881'•7 Emn s-H,obcrts, E. :wd Peternon, A. J'vL, A case or edopi,1 visccrum, associated with spjna bifi(ln :me! other abnormalities. J. Anat, & PhysioL 40: '.l,l2-:l5G, HJOfi. :,, Campbe.11, :\1. }<',: of the bladder, Saunders Co., in UroloK\'. Phil,ule[pbia: l\l54, vol. 1, pp. :l77-:l88. ·" Bo\ce, ,v, H. aml Vct,t, S. J... : A new concept concerning treatment of ex;,trnphy of the bladder. J UroL, 67: 503-517. JD52. 60 Hnrvan!, 8. i\I. and Tl10mpsou, G. J .. Congenii al exstroph,- of 1-he urinary bladder_, late rusnlt,s ln- tlw Coffey-JV!ayo mcthocl of urnterointestinai anastmnosi's ..L l'roL, 65: 22:i-2:H, 1D5l.

caRe of :_\IatthP\\' (_' ssem on·r a t'\'11tur_1the most impressin°_:n ('ntrPated tainly kad \\Tetclwd, piteous Jin•s ffhile last,"2 and at least two han° ]i\'\·d for 80 years'"'· 1\s a final dC'spair, cancer in the C'Xstroplned bladder is no rnrit_,- in the harcl_1- fe,,- 11-ho do sur ,-in1 S\'\Tral decad\•s. c3-71 Orw of us remo,-ed arr exstrophied bladder of an adult lwcause of actc·nocarcinoma, but the cancer \\'m, not cun·tl (77051 at ~\Iemorial Hcl8pital, fig. ments in nwthocb of urinary diYernion lmn: un douht.eclly h·ssc•11\•d tlH: lmrclens of these lTipplc·, 61 Cross, H. IL, Jr. and Barber, K. K. l•:,rn trophy of the bladder: foll cm-up of snrvivorn .. J UroL, 82: 3:l:3-33(i, l\l5[L 62 Cooper, A,: Case of nrnlco11fonnation of lhe minary and genital organs in a fomalc. Erlin. l\led. & Surg. J., 1: 132, 1805, " 3 Goyanna, R., Emmett,, J. L, and J'vlcDmrnld. J, R.: Exstrophy of the bladder hy adenocarciuonrn, J 65: 391 134 Tiokitauskv, C,: A Anatomy, 2: 1(\9, 1855. "' Abcshouse, B, S, · Exst.rophy of 1he hlmh.lc, cornplicatcd by adcnocarcinonrn of the bl aclder nnd renal calculi ..L UroL, 49: 25D--289, 1D4~L "'Reid, W, C., Westcott, G. W. and Hummers, ,LE.: Cai,ciuonrn in exstrophy of the 1Jhdde1·, A,rn ,J_ 8urg,, 75: tiOl-(iOli, 1948, 67 Scholl, A. J., The potential exstrnphy of the bladder. Ann. Surp.:., 1922. 68 D>1vidson, J. H.eport. uf three c:1,s,·s carcinoma occurring in exstroph,,- of th<> blndder Urol. & Cutan. Rev., 54: 20(3-208, 1950. 6 " Etherington, vV. J : Prinrnr,- carcinoma oi' a11 ectopic bladder; and primary benign papillomarn of the ureter, Brit. J, Urol., 17: G2-(i1, i\l45. 70 JvicCown, P. E., Carcinoma in exs1,rnphy of the bladder. J, l;rol., 43: 5::l:3-542, lMO. 71 Cordonnier, .J, J, and Spjul,, H. ,/ Veoi,::Li exstrophy and t.ran;,itimrnl cell carcinonrn. rrnnsu:iJ longevity J'ollowing urntcrosigmoidostorn: J. Urol, 78: 242-244, HJ57

,,i

770

MARSHALL AND MUECKE

Fm. 3. NYH 808594, untreated 3-year-old boy with apparent typical exstrophy. and probably represent the best management yet available. Notwithstanding this betterment nor overlooking it, Campbell 58 summarized the present circumstances: " ... about as many ,viii live for years without ureterosigmoidostomy as with the operation but their lives will be spent largely in social ostracism due to their urinary stink, wishing they were dead; while some will kill themselves." This is the only specific mention of suicide noted in our review. Boyce and Vest 59 in 1952 were unable to find even a single report of a patient having ureterosigmoidostomy in infancy who then achieved a normal life expectancy. One of the longest survivors was our epispadiac patient (225529) who died of renal failure 44 years 8 months after urinary diversion to the rectum. 37 • 38 Cross and 13arber 61 in 1959 roncluded a study of survivorship by saying that " ... while a few patients may be treated and obtain satisfactory results, in the main they are the exception rather than the rule." Probably external diversion by an ilea! conduit71 does offer better expectancy, at the price of an external appliance, but this remains to be demonstrated. Surgical restoration to the normal anatomical state has long been recognized as the ideal. Even an incomplete list of the surgeons who have wrestled with the many problems of functional closure proves that there has been no lack of talent applied: Higgins, 21 Langenbeck, Billroth, von Mikulicz, Boari, Mayo, Robson, Nelaton, Velpeau, Dupuytren, 28 Campbell, 58 Thiersch,7 2 Trendelenberg,73 Ayres,74 Mar72 Thiersch, C.: III Ueber die Entstehungsweise und operative Behandlung der Epispadie. Arch. der Heilkunde, 10: 20, 1869. 73 Trendelenburg, F.: The treatment of ectopia vesicae. Ann. Surg., 44: 281-289, 1906. 74 Ayres, D.: New Surgical Treatment for Malformations of the Urinary Bladder. New York: Hall, Clayton & Co., 1859.

Fm. 4. NYH 808594, excretory urogram of untreated 3-year-old boy with exstrophy. Severe bilateral hydronephrosis is evident, as is characteristic skeletal deformity. ion,7 5 H. H. Young, 76 - 77 B. ·w. Young, 78 Shultz, 79 Sweetser, 80 Lattimer,81 Gross, 82 Denis Browne,83 and Innes vVilliams. 84 75 Marion, G.: Histoire d'une exstrophie vesicale chez une femme. Presse med., 18: 145-148, 1910. 76 Young, H. H.: An operation for the cure of incontinence associated with epispadias . .J. Urol., 7: 1-32, 1922. 77 Young, H. H.: Exstrophy of the bladder. The first case in which a normal bladder and urinary control have been obtained by plastic operations. Surg., Gynec. & Obst., 74: 729-737, 1942. 78 Young, B. W., Mills, R. L. and Nesbet, .J.: Artificial urinary sphincter. Surg., Gynec. & Obst., 113: 62-72, 1961. 79 Shultz, W. G.: Plastic repair of exstrophy of bladder combined with bilateral osteotomy of the ilia . .J. Urol., 79: 453-458, 1958. 80 Sweetser, T. H., Chisholm, T. C., Thompson, W. H., Berglund, E. B., Wesolowski, S. P. and Sweetser, T. H. .Jr. : Exstrophy of the urinary bladder: its treatment by plastic surgery. .J. Urol., 75: 448-455, 1956. 81 Lattimer, .J. K., Dean, A. L . .Jr., Furey, C. and Ballantyne, L.: Reconstruction of urinary bladder in children with exstrophy . .J. Urol., 77: 424-431, 1957. 82 Gross, R. E. and Cresson, S. L.: Exstrophy of bladder; observations from 80 cases . .J.A.M.A., 149: 1640-1644, 1952. 83 Browne, Denis: Rome congenital deformities of the rectum, anus, and urethra. Ann. Roy. Col. Surg. Eng., 8: 173-192, 1951. 84 Innes Williams, D.: Ectopia vesicae and epi-

771

VARIATIONS IN EXSTROPHY OF BLADDER

:

!

;

{0/ '· .. /

!

\

l

\ .. /

6

Frn. 5. Diagrams of operative technique of functional closure in NYH case 808594. 1, 2 and 3 show incisions and mobilization; 4, anti-reflux procedure in process on left and completed on right; 5 and 6, closure, depression and overlapping of lower urinary tract.

Tantalizingly few successes have been reported 21 , 77 , 80 , 85 - 87 and some preliminary triumphs have become failures. 73 • 88 At an American College of Surgeons convention in 1957, a panel of experts was asked, "Do you have personal knowledge of a case in which, a year or more after functional closure, the urinary control was strictly normal, the kidneys were in excellent conspadias, in Encyclopedia of Urology. Berlin: Springer-Verlag, 1958, vol. 15, pp. 96-104. 85 Brandl, K.: A contribution to the study of ectopia vesicae. Am. J. Urol., 9: 333-339, 1913. 86 Swenson, 0.: Pediatric Surgery. New York: Appleton Century-Crofts Inc., 1958, pp. 519-540. 87 Michon, L.: Conservative operations for exstrophy of the bladder, with particular reference to urinary continence. Brit. J. Urol., 20: 167-173, 1948.

Babcock, W. W.: Exstrophy of the bladder. Plastic reconstruction versus ureterointestinal transplantation. Trans. Am. Assoc. Obst. & Gynec., 60: 240-248, 1949. 88

dition, and the following were absent: infection, residuum, stricture, vesicoureteral reflux, fistula, or hernia?" All the experts answered, "No," but a few citations indicated an occasional close approach to this ideal. Essentially the same answers were received from 18 active urologists scattered over the world. 89 What is the essence of this deformity which so effectively eludes these major surgical efforts? The partially identical deformity of mere epispadias with incontinence has been often, though not by any means invariably, successfully corrected. 73 • 76 • 9o- 93 Shattock, Keith 89 de Gironcoli, F. D., Marshall, V. F. and others: Results of functional closure of exstrophy of the bladder. Urologia (Italy) Anno, 28: 89-

102, 1961.

9 ° Campbell, M. F.: Epispadias, in Urology. Philadelphia: W. B. Saunders Co., 1954, vol. 1, pp. 415---420. 91 Gross, R. E. and Cresson, S. L.: Treatment

772

MARSHALL AKD MUECKE

and Hovelacque each emphasized the firm attachments of the exstrophied bladder to the inner surface of the symphyseal structures. 94 - 96 Our best result after functional closure of exstrophy contains some non-surgical, as well as surgical, suggestions as to why this outcome was good, but not perfect. Case 1: A 3-year-old boy (808594) had received no specific treatment for what appeared to be a typical exstrophy (fig. 3). He had no other evident anomalies; the testes were descended and the anal sphincter was of excellent tone. Despite this typical appearance his intelligent mother stated that at the time of birth there was only a circular opening about 2 cm. in diameter in the lower abdominal wall at the base of the epispadiac penis. At birth the bladder mucosa was level with the skin, but the full eversion took place gradually over the next 7 months. In other ,vords, this deformity might be considered the most minor degree of exstrophy or the maximal degree of epispadias from the developmental viewpoint. Excretory urograms revealed significant damage to both upper urinary tracts (fig. 4). Gross 97 indicated that upper urinary tract damage at such an early age seldom occurs unless treatment has been given but others 21 have not had this experience, nor have we, as is here demonstrated. At a single operation bilateral nephrostomies were created and the exstrophy and epispadias closed. After incision about the mucocutaneous junction, dissection was carried laterally in the subcutaneous fat to the upper medial portions of the separated pubic bones (fig. 5). Incision was made directly into the cartilege of the pubic bones at a point about 1 cm. from the medial ends. of epispadias: a report of 18 cases. J. Urol., 68: 477-488, 1952.

92 Dees, J. E.: Congenital epispadias with incontinence. J. Urol., 62: 513-522, 1949. 93 Muschat, M.: A case of complete epispadias associated with incontinence of urine cured by operation. J. Urol., 18: 177-185, 1927. 94 Shattock, S. G.: Specimens of epispadias and extroversio vesicae showing an attachment of the muscular wall of the bladder to the back of the pubic bones (etc.). Tr. Path. Soc. London, 45:

117-124, 1894. 95 Keith, A.: Malformations of the hind end of

the body. III. Ectopia vesicae and allied conditions. Brit. M. J., 2: 1857-1861, 1908. 96 Hovelacque, A.: Etude anatomo-pathologique de l'exstrophie complete de la vessie. J. d'urol., 1: 205-233, 1912. 97 Gross, R. E.: The Surgery of Infancy and Childhood. Its Principles and Techniques. Philadelphia: W. B. Saunders Co., 1953, pp. 688-713.

By sharp dissection through the superficial portion of the cartilage, the attachments of all structures on the medial aspects of the pubic bones were separated from the pelvis. These incisions were carried completely down the pubic rami into tbe ischiorectal region and accordingly freed the uppermost attachments of tbe levator ani muscles on the inner aspects of the pelYis. This dissection permitted the vesical neck and prostate to be rPadily depressed deep inside the pelvis. The tissues which were lateral could then be folded over the dorsum of the outlet and imbricated. Actually, the cartilagenous attachments themselves were easily overlapped. It was hoped that the functioning tissues in this area might be so preserved with a minimum of direct damage. A plastic procedure designed to eliminate reflux was carried out on both ureteral orifices. These procedures on the ureterovesical junctions were based upon previous study. 98 A longitudinal incision was made through the mucosa over the course of the ureter and the intramural portion dissected free and brought up into this incision. The attachment of the lower end of the ureter was not severed. Several fine catgut sutures were used to draw the muscles of the bladder together under the ureter to provide a solid backing and also to create a longer submucosal passage,Yay for the ureter. Care was taken that the passage of the ureter through the muscle proper was sufficiently lax as to not produce obstruction at that area. The mucosa was then closed over the ureter with fine catgut sutures. The mucosa, along \\ith the submucosa of the bladder, vesical neck, and urethra, was next closed with a continuous plain catgut suture. Numerous reinforcing sutures were placed in the more external muscular tissues. It was necessary to remove some of the greatly thickened mucosa in order to invert the bladder. The closure of the epispadias proper follmved the general plan of Young 76 and Dees. 92 No cystostomy was established. Chromic catgut sutures "\\'ere used to imbricate the cartilagenous attachments over the vesical neck and prostatic area, as previously indicated. The whole urinary structure was readily displaced down into the pelvis. Large flaps of rectus sheath and external oblique aponeurosis were raised on either side and turned downward across the defect to be sutured to the opposite pubic cartilage on the external surface down about 98 McGovern, J. H., Marshall, V. F. and Paquin, A . .J. Jr.: Vesicoureteral regurgitation in children. J. Urol., 83: 122-149, 1960.

VARIATIO'\S IN EXSTROPHY OF BLADDER

Fm. 6. NYH 808594. A, voiding after functional closure. B, voiding cystourethrogram show,5 maxima/ reflux into left ureter. , excre1,ory urogrnphy 2 years after last surgery. _\'ormal caliber of lower ureter demonstrated that reflux had not been prevfmted at price of obstruction.

3 cm. from the top. The skin and subcutaneous tissues were appropriately mobilized to be drawn over the defect. Appropriate drains w,!re left in place. The postoperative course was satisfactory, but testsss indicated thut th(' drninage from the kidneys to the bladder was significantly impuirecL At separate operations both ureters were straightened and the redundancies removed; but one of the end-to-encl anastomoses was not satisfactory and was repeated, with success. On the first occasion in which bis bladder was permitted to fill, the patient indicated that he was uncomfortable and wished to void. This he did with an exceilent stream and was at that first time able to start und stop the urinary stream sharply (fig. 6,A). There was no period of learning how to urinate; he had the essentials ut once! Three years after the principal operation and 2 years 3 months after the last surgical procedure, his condition was as follows: no fistula, no hernia, no stricture and no residuum in the urinary tract. Repeated tests had shown no reflux up the right ureter, but reflux into the lower third of the left ureter had been noted on a few occasions (fig. 6,B). The upper urinary tracts had maintained their 99 Walzak, M. P. Jr. and Paquin, A. J. Jr.: Renal pelvic pressure levels in management of nephrostomy. ,L UroL, 85: 697--702, HJGL

significant impronment (fig 6,C). Ile had rn, symptoms of urinary trnct infection and :wd developed generally in a most gratifying fasl1ior1. Cultures of the urine bud been quite variable although they wen' usually positive, there were also oceasions in which the cultures were .~terik 8H'n when he 1rns not on drug therapy. The nrn;it recent culture of the urine, 3:-l months ufter the main operation, revealed 70 colonies of Aerobactcr aerogenes per milliliter at a timf' wrwn routine urinalysis wus strictly normal and when the patient wus tuking no drugs. His urinary rontrol was not absolutely normal. He could stop and start the urinary stream ubruptl)'. If he HJidcd every 2 hours, he did not get wet under any curnstances. His bladder cupacity had increased and lie readily retained urine 150 cc und usually rnicled 75 to 125 cc. If he be came distended or retained longer than :-l he would often, but not invariably, have sufficient leakage to dampen his underwear to warrant a change. This was particularly likrly to occur in the afternoon when he was playing. lfo did not wear protection for his clothing. He usu-ally had nocturnal enuresis, not dribbling, but had on several oceasions tran·lf,d overnight mi the railroad and awakened himself to go tu the toilet, thus aYoicling wetting the berth. Of some interest was the fact that he had nc'n'r wet a m·11

774

MARSHALL AND MUECKE

suit of clothes under any circumstances. Under emotional stress the dampening of the clothes was more likely to occur. During a recent period of 3 months, his mother wrote that he had "almost perfect" control. Thus the result can be considered quite good, although clearly short of the ideal. That this patient is a boy is noteworthy, since the majority of reported successes after functional closure have occurred in girls. 21 - 22 , 77 , 79-80,

82,

84-88,

100

Therapeutic advances notwithstanding, improvements are obviously necessary. Some of these would likely be also applicable to problems of incontinence in cases other than exstrophy, which itself is not as vanishingly rare as many think. It has been estimated that about 100 children with exstrophy are born each year in the United States. 21 At the Mayo Clinic 198 cases of exstrophy were seen in 1.5 million admissions. 60 Dees92 found 56 cases of epispadias with incontinence, short of exstrophy, among 5.2 million admissions to 8 hospitals. Etherington 69 estimated that at least 1600 British patients with exstrophy had lived to reach the age of 40 years. Kimball and Drummond101 were able to find records of 18 cases of exstrophy during a 5-year period in Oklahoma. Hundreds of cases have been reported. All considered, there are several good reasons to study this most peculiar congenital anomaly. An investigation might properly begin with a review of the definitive anatomical variations which have been encountered. Such a review might lead to the formulation of a useful hypothesis concerning development. Kn0vving the variations and possessing a probable theory of the developmental aberrations leading to the deformity, surgeons might be able to improve their approach to the complicated clinical condition of exstrophy of the bladder. ANATOMIC PROGRESSION AND EMBRYOLOGY

·while collecting our cases of exstrophy and/or epispadias, we found several deformities not so classified but which appeared to be part of this anomalous complex. Perhaps the mildest of these was an example of spade penis with a presumably

normal tract. The organ was wide, relatively short, stubby, and protruded at nearly a right angle from the pubis even in the flaccid state. The dorsal aspect was flattened but the meatus was in the center of the glans. Certainly the individual did not have a great separation at the symphysis but no radiograph was made. In retrospect, this penis closely resembled those in cases of epispadias. Another deformity undoubtedly related to exstrophy was seen in a 58-year-old man (644165) and in a girl (205130). The man had typical transitional cell carcinoma of the bladder but the urinary tract was otherwise normal. The umbilicus was low-set, deep and elongated (fig. 7). The recti diverged from just above the umbilicus to attach on the separated pubic bones. This is the characteristic musculoskeletal deformity which is invariably present in cases of full exstrophy, yet the urinary tract was embryologically normal in this man. The case of the girl1° 2 is somewhat more complex. She had musculoskeletal deformity of exstrophy (fig. 8). Over the pubic area and between the labia and the 2 parts of the completely bifid clitoris was an area of smooth, thin, hairless skin. This area did not appear to be a scar. The perineum was congenitally closed except for two small fistulas which led into the vagina. There was an imporforate anus with a rectovaginal fistula barely inside the vagina. The urethra also opened into the vagina and the upper urinary tracts appeared normal by excretory urography. The record was vague about the status of the 11011-exstrophied bladder, but after surgical opening of the vagina the patient had normal urinary control. The child had the characteristic musculoskeletal deformity of exstrophy, imperforate anus with rectovaginal fistula and a satisfactory urinary tract. Perhaps the situation was just a coincidence of the nrnsculoskeletal deformity and imperforate anus. This particular arrangement is extremely rare. Others have observed 103 - 106 this 102 Lowsley, 0. S.: Persistent cloaca in the female: report of two cases corrected by operation. J. Urol., 59: 692-707, 1948. 103 Campbell, M. F.: Personal communication

1961.

'

Hejtmancik, J. H., King, W. B. and Magid, M.A.: Pseudo-exstrophy of bladder. J. Urol., 72: 104

100 Sturdy, D. E.: New concepts in the initial management of extroversion of the bladder. Brit. J. Urol., 33: 296-308, 1961. 101 Kimball, G. H., and Drummond. N. R.: Exstrophy of the bladder; an experimental and a clinical study of cases. J. Oklahoma Med., 33:

2-8, 1940.

829-832, 1954. 105 Uson, A. C. and Roberts, M. S.: Incomplete exstrophy of urinary bladder: a report of two cases. J. Urol., 79: 57-62, 1958. 106 Mackenzie, L. L.: Split pelvis in pregnancy. Am. J. Obst. & Gynec., 29: 255-257, 1935.

VARIATIONS IN EXSTROPHY OF BLADDER

FlG. 7. NYH 044165, musculoskeletal deformity of exstrophy, with intact urinary tract. Diastasis and suprapubic depression more evident in oblique view.

Fm. 8. NYH 205130, radiogram of girl with musculoskeletal deformity of exstrophy, yet with in., tact urinary tract.

rnusculoskeletal derangement without a major defect in the urinary tract proper. However, this derangement is rare without some abnormal urinary opening, or its nature is generally unrecognized, but 1t can exist without exstrophy or even mere epispadias. Initially we arranged our cases in a progression based on the gross anatomical extent of the urinary opening. Next after the simple spade penis \Yerc 2 examples of balanic cpispadias alone (fig. Gross and Cresson 91 state that this is the rarest form of e)lispadias and they sa,Y it only 3

Fro. \J. NYH 35\J324, balanic epispadias in maiL If urinary meatus ,Yere smaller this would bn ~iw .. pie spade penis.

times in 18 epispadiac patients who did not ha exstrophy of the bladder. ma sive collection, like,Yisc found the balanie type to be the least common form of epiRpadias. Jf glandular corona was divided 1n· han· l'Onsidered the epispadias to be more than just balanie. ln sequence, we then placecl 6 cases of a more ext,,n. sive urethral defect: penile epispaclias with r:on

776

MARSHALL AND MUECKE

FIG. 10. NYH 526687, penile epispadias with continence. tinence- (fig. 10). Two of the 6 cases were only a little more than the purely balanic type, but the others had a large portion of the pendulous urethra open on the dorsum of the organ. Gross and Cresson 91 had two of these cases in their series and two more in which the defect extended a little higher so that they were incontinent. While it is clinically sufficient to classify epispadias as with or without continence, such transitional cases do accurately fit a gross anatomical progression. The next larger urinary defect was epispadias with incontinence, the penopubic type (fig. 11). This is by far the most common type of epispadias in the absence of vesical exstrophy: 17 of our 25 cases of epispadias without exstrophy; 11 of 18 in Gross and Cresson's series;91 and the most common in Dees' collection. 92 Some patients with penopubic epispadias are not totally incontinent, again demonstrating a borderline or transitional variation. We then noted a few cases of what might be termed near-exstrophy, in that they were surely the maximal degree of incontinent epispadias yet at the same time were only a minimal degree of vesical exstrophy (defining

vesical exstrophy as the more or less constant protrusion of vesical mucosa above the local skin level). These we have classified as exstrophy rather than epispadias (fig. 12). The deformity previously described in case 1 was a near-exstrophy at birth but became a full exstrophy over the next several months (illustrating a still finer point in transition). The distribution of the common types of exstrophy-epispadias in our series is the usual one. In a total of 72 cases of all types (during a 29year period in which 898,000 patients were seen at this institution), there were 8 cases of epispadias with continence, 17 epispadias with incontinence, 40 classical exstrophy, and 7 rarer varieties (table 1). Respective to these varieties, Gross and Cresson's82 • 91 distributions over a 20year period were 5 cases of epispadias with continence, 13 epispadias with incontinence and 80 vesical exstrophy. If the causative process were one of simple division or non-union starting at the end of the urinary tract and progressing upward, it would seem most probable that the lesser degrees would be the most common but the re-

777

VARIATIONS IN EXSTROPHY OF BLADDER

Fm. 11. NYH 792478, epispadias with incontinence penopubic. TABLE

1. Variations of exstrophy-epispadias, as

encov.ntered in this series Variety

Spade penis only Epispadias with continence: Balanic only Penile

Number

1 2 6

8

Epispadias with incontinence: Subsymphyseal Penopubic

FIG. 12. NYH 364086, relatively mild exstrophy in baby girl.

verse is actually the case. Most frequently, the urinary opening is located at the vesical outlet, epispadias with incontinence and vesical exstrophy constituting about 90 per cent of all cases. Accordingly, the central point of the beginning of

Classical exstrophy Cloaca! exstrophy Superior vesical fissure Duplicate exstrophy Characteristic musculoskeletal deformity with intact urinary tract Total

1 16

17 40 2

1 1 2

72

778

MARSHALL AND MUECKE

B

Fm. 13. Pohlman's 7 illustration. A, early stage of normal cloaca, etc. C, cloaca; C.M., cloaca! membrane; T.G., tailgut; R.B., renal bud; W.D., wolffian duct; H.G., hindgut. B, later stage in normal development of this region. Cloaca is partially divided. D.C., dorsal cloaca; V.C., ventral cloaca; U., ureter. (Reproduced by kind permission of publisher of The American Journal of Anatomy.)

the deviation from normal would probably be located in the area of the developing vesical neck. According to Patten and Barry, 6 in the fourth week of embryonic development the paired primordia of the phallus, the caudal portion of the cloaca! membrans, and the future vesical neck are intimately associated-indeed, essentially continuous in an extremely small area. At the 15.85 mm. stage, as observed by Chwalla,1 07 the cloaca! membrane normally opens in the midline to establish the urinary passage. The opening or split of the exstrophic complex is invariably midline and longitudinal in character. This split is excessive in cases of exstrophy and/or epispadias. If the cloaca! membrane were itself excessive, relatively overdeveloped, an opening larger than normal might reasonably be expected too. Perhaps the split might occur at an earlier time than normal if the membrane were overdeveloped. Recognition of an overdeveloped but as yet unopened cloaca! membrane in a quite early embryo would no doubt be extremely difficult-yet Pohlman7 in 1911 thought he had seen this and commented that this embryonic defect could have " ... a decided bearing on bladder 107 Chwalla, R.: Uber die entwicklung der harnblase und der primaren harnrohre des menschen(etc.) Ztschr. f. anat. u. Entwickl., 83: 615-733,

1927.

exstrophy and epispadias" ! The general rarity of exstrophy would make its early identification unlikely since the condition has not been experimentally produced for systematic study. Theoretically, the cloaca! membrane might remain overdeveloped relative to the rest of the embryo by merely failing to lag behind at the time it normally does so. Chwalla107 indicated that the membrane normally increased up to the 5.57 mm. stage and then decreased, both relatively and absolutely. Pohlman7 considered the membrane to have its greatest normal length (.34 mm.) at the 12 mm. stage (fig. 13). A persistence of the cloaca! membrane might be looked upon as an arrest of some normally deterrent effect, but this is actually little more than a paradoxical statement paying homage to the traditional concept of developmental arrest. Conceivably the membrane might be simply and directly overstimulated to develop. This latter is a more unusual type of anomalous development,1°8 and accordingly might bear on the rarity of exstrophy compared to the more common arrest types of deformity. Incidentally, the frequent coexistence of myelomeningocele with the advanced forms of exstrophy lends some support to the concept of overgrowth as causative, since some reliable embryologists believe that myeloschisis with

779

VARIATIONS IN EXSTROPHY OF BLADDER

spina bifida is largely the result of overgrowth108 (fig. 14). Whether the cloacal membrane simply persisted, or continued to grow commensurate with the rest of the embryo, or actually overdeveloped, the result would be an abnormally large cloacal membrane at some early stage, probably well before the 15.85 mm. one of Chwalla. 107 If this did occur, as Sternberg109 and Keith 110 have suggested, the common variations of the exstrophic complex could be readily explained from such a beginning. Furthermore, it is of great significance that the relative incidences of the variations become comprehendible. Perhaps anomalous complexes of other types could be profitably studied by correlating not only the gross anatomical variations but also their relative incidences.

UMBILICAL CORD

THE WEDGE EFFECT

An overdevelopment of the cloacal membrane before the 15 mm. stage would not necessarily be of the same degree in every case. Variations in the final product are well known, and anomalies of any type seldom develop in precisely the same degree for each occurrence. An abnormally large and persisting cloacal membrane would hold apart the developing structures of the lower abdominal wall. This wedge effect would keep the recti diverged yet intrinsically normal. Except for Higgins' 21 mention of one example of an underdeveloped rectus muscle, the muscles of the lower abdominal wall, as well as their sheaths and attachments, have apparently always been well formed. This is a situation quite different from that existing in the so-called "prune belly" syndrome,m in which the muscles are obviously deficient intrinsically, yet exstrophy does not occur. This routinely good development of the skeletal muscles in cases of exstrophy militates strongly against the etiological concept of mesodermal failure. (The mesodermal derivatives of all types in the area of an exstrophy are intrinsically 108 Patten, B. M.: Embryological stages in the establishing of myeloschisis with spina bifida. Am. J. Anat., 93: 365-395, 1953. 109 Sternberg, H.: The morphological genesis of cleft of the abdomen and bladder (ectopia vesicae). Urol. & Cutan. Rev., 31: 475-479, 1927. no Keith, A.: Malformations of the human body from a new point of view. Brit. Med. J., 1: 489-

491, 1932.

m McGovern, J. H. and Marshall, V. F.: Congenital deficiency of the abdominal musculature and obstructive uropathy. Surg., Gynec. & Obst.

108:289-305, 1959.

'

TERATOMA

Fm. 14. NYH 316633, newborn with advanced classical exstrophy and associated sacrococcygeal teratoma. Even here perineum is intact, not split. Surely teratoma is an overgrowth. well developed; for example, the bladder always has abundant muscle.) To say that the mesoderm failed only in the midline leads nowhere and does not explain the musculoskeletal deformity. 112 The corpora of the phallus are mainly mesodermal in origin and they are routinely not only present but seldom underdeveloped individually (this is not the same as saying that the penis or clitoris as a whole is normal). The corpora in exstrophy do routinely have an abnormal direction and a definite tendency to be separate; but these effects are readily accountable by the crural attachments to the abnormally displaced ischiopubic bones. We could find no example of the corpora dissociated from their essentially normal attachments relative to the bones proper. The bones themselves are almost never significantly underdeveloped or deformed beyond what could be expected from the wedge effect. If the paired primordia of the genital tubercle were displaced caudally, the starting point of the widely accepted theory of Patten and Barry, 6 corpora might be 112 Wyburn, G. M.: The development of the infra-umbilical portion of the abdominal wall with remarks on the aetiology of ectopia vesic~e. J. Anat., 71: 201-231, 1937.

780

MARSHALL AND MUECKE

FIG. 15. NYH 870532, radiogram of patient with continent penile epispadias and normal appearing symphysis.

expected to be found back on the perineum and/ or dissociated from their bony attachments, at least rarely if not routinely. Also, how would the usual musculoskeletal derangement in exstrophy stem from the caudal displacement of the tubercles? Most patients with exstrophy or with epispadias alone have one extra structure that is not present in normal persons; that is, the triangular portion of the abdominal wall lying between the rectus sheaths v,ith its apex tavvard the umbilicus but not occupied by the urinary eversion. This is a widely spread linea alba. The mesodermal (fibrous) tissue between skin and peritoneum here appears derived from Pohlman's7 precloacal mesodermic tissue (P.T., fig. 13,B). In fact, the cephalic edge of the cloacal membrane is thus so limited that the split should not go into the peritoneal cavity but only into the bladder. Perhaps a failure of the precloacal mesodermic tissue (actually another manner of stating that the cloacal membrane persisted excessively especially in the cephalic direction) would finally result in fetal membranes in this area and hence a condition of ectopia viscera as in Emrys-Roberts' case 57 (fig. 27). In further speculation, some of this precloacal mesodermic tissue might on rare occasions get in between the layers of the cloaca! membrane and the result would then be the very rare condition of the typical musculoskeletal deformity without exstrophy as in our cases 644165 and 205130 (figs. 8 and 9). This rare variation strongly supports the concept of the wedge effect of a persistent cloaca] membrane. A very few, perhaps 6 or 8103 - 106 such examples have been recognized. The wedge effect in this

area would be a strong influence tmrnrd umbilical hernia and, in a less direct manner, to inguinal hernia, both of which are frequent accompaniments of exstrophy. The widening of the pelvis would tend to separate the mlillerian ducts internally and the not-rare finding of double or bicorn~ate uterus in the female patients with exstrophy can be thus explained (in fact, with cloaca! exstrophy in the female patient, a double mi.illerian system is usual) .11 3 It has been stated that the symphysis was normal in some cases of exstrophy and of epispadias alone. 28 • 29 • 39 • 46 • 58 • 90 , 114 These reports are uncommon and not fully documented since the symphysis was not only unwidened but was also demonstrated to be composed of cartilagenous rather than fibrous tissue. That the wedge effect ,vould inrnriably be so extensiYe as never to permit a nearly normal symphysis, especially in cases of epispadias alone, would seem highly improbable-and we have one such example in our experience (fig. ] 5). Campbell103 has seen patients in whom the pubic bones were united below and separated above. In the case of J\Iatthe,Y Ussem, a patient with exstrophy previously referred to who exhibited himself in many European medical centers, normal pubic union was described, but two later examiners of this same patient clearly found that the symphysis was deficient. 31 Having thus accounted for the musculoskeletal derangement which almost always accompanies the several variations within the exstrophic complex, how could the overdevelopment of the cloaca! membrane produce the known variations in the urinary tract deformity? The most common type is classical exstrophy, in which the musculoskeletal deformity is accompanied by an open everted bladder and complete epispadias. The central or prime axis for aberration would be at the point of the future vesical neck, which at that time is also the level of the base of the forming genital tubercles. An excessiYe, and perhaps premature, split of the cloacal membrane would then be expected to extend toward the body stalk and lay open the underlying vesical primorclium. The internal surface of the cloacal membrane is the ventral wall of the cloaca, and this wall becomes the anterior portion of the 11s von Geldern, C. E.: The etiology of cloacal exstrophy and allied malformations. J. Urol., 82: 134-144, 1959.

114 Higgins, C. C.: Transplantation of the ureters into the rectosigmoid for exstrophy of the bladder; review of 41 cases. J. Urol., 57: 693-700, 1947.

VARL\'1'10!'\8 IN EXSTROPHY OF BLADDER

Fw. lG. NYH 55,t'i83, newborn girl and NYH 748936 and 3471:32, 2 boys. l\Iocleratc vnrin(ions in rull classical exstrophy.

Fm. 17. Pnttern of classical exstrophy in male.

bladder (with the addition of mesenchynw. for muscle). The degree of cli1-isiou might ,-ary modestly, and the clinician does encounter different degrees even within the classical exstrophy (figs. 12 and 16). As the penis forms ancl grows outward, this urinary split ,rnulrl be c>xpected to be carried out to the ti]l, 11 " thus producing the almost constantly associated complete epispadias If the phallm, is to become a clitoris it (fig. J would naturally remain small and the 2 components would be> too little to join in most cases, u 5 Spaulding, M. IL: Cfunegie Contributions to Embryology, 13: 67-88, 1921.

so that a bifid clitoris mmlcl lw usual in frmale patients (fig. 18). EPISPAlJJAS

To derive cpispadias without lhe second most common type withi11 the exstrophie; complex, it is necessary onh- to pidmP a ks8el' pcrnistenc:c\ or m·crde,·clopnwnt of the cfoara: membrane. Thr central or prime poiut 1rnuld RtilJ be at the lenl of the future nsical rn:ck. c:ordingly, the most common ,sub-t_r]J(' ainonµ: 1ritl1 epispadiac patients should be that inc:onti11encc> (fig. 11), wl1ich is the actual in,·i

782

MARSHALL AND MUECKE

:?~.,:\-,~ .

.

EXSTROPHIED BLADDER

'

AGINA ~ \

RECTUM

~

Frn. 18. NYH 364086, exstrophy with patulous anus.

dence as previously noted. The wedge effect might well be less in cases of epispadias alone than in those of classical exstrophy, resulting in less symphyseal separation and a smaller incidence of umbilical hernia. The data in the literature are so incomplete that this reduced wedge effect cannot be statistically documented. However, information to the contrary is not present and what is available is supportive. Many of the exstrophies in our patients were accompanied by an umbilical defect, but not the cases of epispadias. Detailed studies with Dr. Guido Cuarrino of the Department of Radiology at our center indicate that the musculoskeletal deformity definitely tends to be less marked with epispadias alone than with classical exstrophy. Also, the patients with continent epispadias appear to have a smaller wedge effect than those with the incontinent variety of the disorder. Less common than either classical exstrophy or incontinent epispadias are the varieties of continent epispadias (figs. 9 and 10). If the abnormal overdevelopment of the cloaca! membrane were still smaller in degree than in incontinent epispadias, it should occasionally happen

that only a minor bit of abnormal split would be carried out on the developing penis, a sort of pinching off from a barely overdeveloped membrane and split. Such a sequence could produce penile and even mere balanic epispadias, uncommon but well recognized varieties. Since the early cloacal membrane is relatively large and in exstrophy apparently endures unusually long, full exstrophy and incontinent epispadias would likely be much more frequent than continent epispadias, which appears to arise from. more limited spacial and temporal circumstances. CLOACAL EXSTROPHY

One of the most impressive features of the exstrophic complex is the fact that the abnormal split never continues through the perineal body (fig. 14). Hart 30 in 1900 emphasized that the caudal end of the cloacal membrane was identified with a point in front of the anus in adults. Anal and rectal abnormalities do occur in association with the more advanced forms of exstrophy, but these bowel abnormalities are not in the nature of a midline split; that is, the anus and rectum arc not truly exstrophied. The most

783

VARIATIONS IN E:X:STROPHY OF BLADDER

EXSTROPHIED BLADDER ~-::,...._,._~URETER HYMEN + VAGINA

~ - \ , . _ . PROLAPSED RECTUM

~

Fm. 19. Exstrophy with rectal prolapse. frequent of these accompanying defects is a patulous anal canal. In our 40 cases of typical exstrophy there were 16 examples of patulous anus, 13 of these being so advanced as to permit rectal prolapse (figs. 18 and 19). According to Arey,1 the urorectal septum meets the future perineum before the seventh week and at about the 12 mm. stage. Before this time a true cloaca is present. We have already theorized that the most common exstrophic aberration begins at least by the time of the formation of the genital tubercle, by the fourth week according to Patten and Barry. 6 Much depends upon the precise time at which the abnormal cloaca.I membrane divides, as well as to the extent of this division. The earlier, and the more extensive this split, the greater would be the tendency for the underlying structures to eventrate. Eventration would drastically interfere, at least mechanically, with formation of the urorectal septum and its reaching the perineum. If the septum did reach the perineum but was stretched by the tendency to eventrate, an abnormally large lowermost rectum and anal canal would result. If the tendency to eventration were just a little greater so that the septum barely contacted the perineum, an inadequate anal canal (an anal atresia which is often called stricture) could result. The events for such an anal atresia in exstrophy would require such precise timing in a narrow chronology that this accompaniment of exstrophy would seem likely to be rather rare compared to patulous anus. We have had no cases of simple atresia in our series and only a few are mentioned in the literature. If actual eventration occurred before the urorectal septum

~=-=··=··•~~••••••••••

was completed (a relatively long time period compared to that for anal atresia) the septum might miss the perineum altogether and an imperforate anus result. The urorectal septum does form from above downward. Such a failure of the urorectal septum in its lower portion would explain the several cases of exstrophy with congenital rectovaginal (fig. 20) and even rectovesical (fig. 21) fistula and the few cases in male exstrophic patients with simple rectoperineal116 or rectovesical fistula. In these cases an otherwise nearly normal gastrointestinal tract has existed. There is a relatively much longer period before the 12 mm. stage when the forming, or not even begun, urorectal septum is far from the perineum. If the split in the cloaca! membrane should occur at this earlier time, the embryonic cloaca would itself eventrate (fig. 22). Before the urorectal septum has horizontally (coronally) divided the cloaca, the vesical primordium must be composed of paired lateral portions of the two upper sides of the cloaca (as well as the median and ventral bit, which is the internal surface of the cloaca! membrane). The longitudinal (sagittal) split of the cloaca! membrane would necessarily produce a division of the future anterior vesical wall (as previously discussed) and an ensuing failure of the urorectal septum would leave the future more posterior portions of the bladder in two lateral halves. If the urorectal septum did already have some slight but significant beginning, the result116 Jensen, 0. J., Jr., Eggers, H. E., Hill, A.H. and Dillard, D.R.: Urinary and fecal incontinence due to congenital abnormalities in children: management of transplantation of ureters to an isolated ileostomy. J. Ural., 73: 321-328, 1955.

•m~,.

784

MARSHALL AND MUECKE

Fm. 20. NYH 901002, extreme exstrophy in young woman. Probe is in rectovaginal fistula, pubic separation measured 17 cm., vagina was widely spread, 2 cervices and 2 uteri were present but only 2 ovaries and 2 fallopian tubes. Left kidney was hydronephrotic and ectopic in pelvis. Impending breakdown of umbilical hernia was evident. Patient was also paraplegic from lumbosacral meningocelelike deformity.

81L08ED EXSTROPHY

Fm. 21. Exstrophy with more simple rectovaginal fistula (not encountered in our series) which indicates transition toward cloacal exstrophy. ing bladder structure would be in a somewhat horseshoe shape being joined in the upper portion. As early as 1913, Johnston8 wrote that if some observer could demonstrate vesical mucosa be-

tween the bowel and the umbilicus in any case of of cloaca! exstrophy, " ... the case for an abnormally early and excessive rupture of the cloaca} membrane will be established beyond doubt."

VARIATIONS IN EXSTROPHY OF BLADDER CLOACAL

2s

MEMBRANE

f

F U T U- R BLADDER - • •E • •• ~ u l

FUTURE LARGE BOWEL

LEVEL FOR u~i~~G~TAL

785

1

2

HEMI ~BLADDER ~_,,, ~

,:::----C'\.• ../)

HEMI BLAD~~c_____

~LARGE~ BOWEL

Fm. 22. Diagrams of eventration of cloaca to form cloaca! exstrophy. UMBI UCAL

HERNIA

Fm. 23. Diagram of cloaca! exstrophy, in particular like von Geldern's. 117

Von Geldern117 made exactly this demonstration in 1924. In these extreme variations of the exstrophic complex a large bowel component should be interposed between two lateral portions of bladder. This arrangement is the essence of cloaca! exstrophy (fig. 23). The interposed large bowel structure between the 2 halves of bladder is likewise exstrophied, not merely ectopic; that is, the bowel is not merely outside, but more importantly is itself open (but above the level of the perinea! body always). We have encountered only 2 living examples of cloacal exstrophy (one by kind permission of Dr. Herbert C. Maier and his staff at the Lenox Hill Hospital) but there are 30 to 40 reported in the literature. 8 · 10 , 15 , 28 , 40 , 53, 56-57, 9s, 113 , m- 124 If this developmental aberra11, Von Geldern, C. E.: The etiology of exstrophy of the bladder. Arch. Surg., 8: 61-99, 1924. 118 Kindred, J.E.: Eventration of the abdominal viscera associated with umbilical hernia, hemi-

tion occurred relatively late but before the 12 mm. stage and before the brief period when a simple rectovaginal or rectovesical fistula would result, the large bowel could be relatively well developed, particularly in length as in the case of Loewen and Rupe. 10 If the eventration occurred penes and hydromyelomeningocele in a newborn infant. Anat. Rec., 128: 379-400, 1957. 119 Wood Jones F.: Exstroversion of the bladder and some problems in connection with it. J. Anat. & Physiol., 46: 193-210, 1922. 120 Morison, J. E.: Extroversion of the primitive hind gut. Arch. Dis. Child., 15: 105-114, 1940. 121 Paul, M. and Kanagasuntheram, R.: The congenital anomalies of the lower urinary tract. Brit. J. Ural., 28: 118-125, 1956. 122 Davies, D. V.: Ectopia vesicae. Brit. J. Ural., 14: 1-10, 1942. 123 Kerwein, G. A.: Combined congenital exstrophy of the female urinary bladder and cloaca. Arch. Path., 13: 926-930, 1932. 124 Veal, J. R. and McFetridge, E. M.: Exstrophy of the bladder (persistent cloaca) associated with intestinal fistulas. J. Pediat., 4: 95-103, 1934.

786

MARSHALL AND MUECKE

UMBILICAL CORD UMBIL!CAL HERN1. ROLAPSED ILEUM

CECUM-LIKE LARGE BOWE

C•

Fm. 24. NYH 729307, cloacal exstrophy in newborn. earlier than in that case the large bowel might be deficient in length, as in our case 729307 (fig. 24). Case 2: This newborn (729307) was the product of an apparently normal pregnancy except for spontaneous prematurity of 5 weeks. At operation no large bowel was found except for the exstrophied part and a blind loop (tail gut) opening into the posterior portion of the exstrophied mass. This tail gut coursed inward to the sacral region. The bowel was operatively separated from the vesical halves and a colostomy formed. Biopsy of an intra-abdominal gonad demonstrated testicular tissue. The infant progressed surprisingly

well and was alive 1 month after discharge. Unfortunately, further followup is unavailable. This is one of the few cases of attempted operative correction of cloacal exstrophy. (Dr. Maier also operated upon his patient.) Nearly all children with cloacal exstrophy previously reported have died with in a few days, although Sinclair's patient did survive 4 months without surgery. 10 The large bowel in cloacal exstrophy should be cecum-like. An attached remnant of tail gut would be expected in many cases of cloacal exstrophy. This gut should open as a blind intestinal tube from an ostium near the midline toward the posterior or caudal part of the exstrophied large

VUUATIO:'\S IN EXSTROPHY OF BLADDER

787

Fm. 25. Prolapsed omphalomesenteric duct in association with classical 117 exstrophy. :'\I ote scpn1·at1011 between duct and upper edge of exstrophy, extremely rare. (Reproduced by kind permissi,rn publishers of Proceedings of the Staff Meetings of the Mayo Clinic.)

boweL These structures have been microscopically iclentified. 8 • u1-1rn, 120 \Ye have examined Kinclrecl'sns specimen and biopsies from several of our patients, including case 729307. A. pair of bowel sacs or diYerticula near the upper or cephalic portion of the exstrophied large bowel are frequently found in cases of cloaca! exstrophy and then an essentially normal-appearing appendix has been always lacking. Could it be that the ver:v earliest, but tlwn unrecognizable, prirnorclia of the appendix are present as matching spots in the lateral lower walls of the undivided cloaca? These appendix-like diverticula have varied greatly in character in the reported casrs, and haYe been missing in a few, but their tendency to be paired and their large bowel character are real. They arc not mere reduplicated ilea. In Russell's casc, 125 there were two rather normal appearing appendices (and in other respects his case seems milder than the usual one of cloaca! exstrophy). The ileum is present and opens into the upper portion of the spread, cecum-like, exstrophied bowel as an orifice closely resembling 125 Russell, K. F.: A case of complicated exstrophy of the bladder presenting many unusual features, Brit. J. UroL, 11: 31--47, 1939.

the usual ileo-cecal valve. The ileum is fn,quently found prolapsed through this junction thus pn,. ducing an even more confusing clinical (fig. 24). This is different from the coincidence of prolapse of the omphalornescnter,c duct and exstrophy (fig. ms The ureter and nm normally become completely separated before 6 \H·eks 1 or, lnnes-'\Villiams, 127 bct1wcn the D and I4 n1n1c stages. If the eventration oecurn,d well before this, sorne of tlw more primitin: Yarirt.ics cloaca! cxstrophy (which is itself more than classical cxstrophy) should han, the mete.,.· and vas still joining a comm011, nwsonephric (wolffian) duct (fig. ReYPral sucl, cases arc rcportrd. 53 • 112 , 116 - 118 • 124 At least two transitional -variations bet\n:en dournl without a mesonephric duct and the same condition ,vith an intact rnesonephric clnet haH, been re]Jorted. ,Johnston 8 described a specimen with usual ureteral opening in one of the 1'e;,icn m Ferris, D, 0, and Putman, H. C.: omphalomesenteric duct; report of 2 cases. Proc . Staff Meet. Mayo Clin., 25: 120-127, HJ50. 127 Innes-Williams, D.: The development ul' tl10 trigone of the bladder. Brit. J. Urol., 23: 12:3-128, 1951,

788

MARSHALL AND MUECKE

Fm. 26. Extreme cloacal exstrophy. (Photographs reproduced by kind permission of publishers of The Anatomical Record.) 118 halves but a blind ureteral ending in the vaginal wall on the other side. Morison120 found one ureter barely connected with the vas. Kindred's118 specimen was probably the most primitive of these, in that the large umbilical hernia contained an abnormal lobe of liver. His case thus approached ectopia viscera in addition to cloacal exstrophy (fig. 26). Others 9 • 55 - 57 have described examples of ectopia viscera which included cloacal exstrophy (fig. 27). These extreme exstrophic deformities had an anal depression but no passageway, again demonstrating that the split of exstrophy does not extend through the perineal body.1 21 Histological studies have revealed sphincteric muscle to be present about this area. 118 These are not cases of simple omphalocele (or umbilical hernia if covered with skin), not only because of the vesical exstrophy but also because of the accompanying characteristic musculoskeletal deformity. Lumbosacral meningocele usually coexists with cloacal exstrophy, but not invariably so, as in Doran's 56 case in which cloacal exstrophy was part of ectopia viscera abdominalis yet a meningocele was absent. Longitudinal divisions other than those of vesical exstrophy do occur in the midline of the ventral body wall, some being above the umbili-

Fm. 27. Extensive abdominal ectopic viscera with cloacal exstrophy. 57 Exstrophy and ectopia do not extend through perineum even here. (Reproduced by kind permission of The Journal of Anatomy and Physiology.) cus without a division below the navel (fig. 28). Human examples are quite rare but a few have been experimentally produced in animals. 128 Partial duplication of the pericardial sac and even 128 Kalter, H. and Warkany, J.: Experimental production of congenital malformations in mammals by metabolic procedure. Physiol. Rev., 39:

69-115, 1959.

VARIATIONS IN EXSTROPHY OF BLADDER

ectopia cordis occurs in some of these. It should be noted that this is not exstrophia cordis, in which the inside of the heart would be open to the exterior. The cloacal membrane with its natural tendency to open provides a vastly greater opportunity for such a split to occur below the umbilicus than is offered by the embryonic developments above the navel. Furthermore, the cloaca! membrane enters intimately into the formation of the lower urinary tract, but the ventral body wall above the umbilicus does not enter so intimately into the formation of the underlying viscera. Hence a congenital longitudinal division in the lower ventral abdominal wall would usually be associated with some variety of exstrophy; while a split above the umbilicus should rarely, if ever produce an exstrophy, although ectopia of organs might readily, and does, occur. The difference between ectopia and exstrophia is clinically significant as well as embryologically. In this fashion, a series of orderly embryonic progressions following known steps can explain the common variations within the panorama of exstrophy and epispadias. These progressions begin with and depend upon an abnormally large cloacal membrane as the primary point of departure from normal. Florian49 pointed out that the very early development of the cloaca! membrane in man was in contrast to that of other

789

Fm. 29. Higgins' photograph of large exstrophy but with penis intact .11 4

mammals, an observation probably offering an embryological explanation for the great rarity, but not impossibility, of exstrophy in other species. Most animals have the penis apposed to the belly wall, penis appositus, rather than a free pendulous organ. 129 ·what causes an overdeveloped cloaca! membrane is unknown but science never reaches the ultimate ex1;lanation. How can the theory of an overdeveloped cloacal membrane be applied to the causation of some of the very rare and obviously eccentric variations which have been found in human exstrophy? There are 2 cases 21 • 130 of otherwise classical exstrophy in which the penis was not epispadiac but had an essentially normal urethra (fig. 27). In both, the dorsum of the penis showed a commissure or longitudinal scar-like tissue, which suggests that fusion of previously abnormally divided parts had occurred. Powell131 had a patient with classical exstrophy except for an intact penis (fig. 29) with an imperforate urethra immediately distal to the verumontanum. Fusion is a well recognized embryologic process and does occur normally in the genital region.11 5 Furthermore, Paul and Kanagasuntheram 121 have pointed out that patients with exstrophy retain the capacity to fuse as revealed by the normal median raphe in male patients with epispadias. Some 129 Glenister, T. W.: The development of the penile urethra in the pig. J. Anat., 90: 461-477

'

1956. Fm. 28. NYH 603924, thoracoschisis in infant. Lower abdominal wall was intact. No organs were exstrophic in spite of extensive defect and even reduplication of anterior portion of pericardium.

° Kuster,

(cited by Reichel, P.): Die Entstchung der Missbildungen der Harnblase und Harnrohre. Arch. f. klin. Chir., 46: 740-808, 1893. 131 Powell, T. 0.: Surgery of the exstrophied bladder: preliminary report. J. Urol., 74: 67-75, 1955; and personal communication, 1961. 13

E.

790

MARSHALL AND MUECKE

corpus spongiosum is routinely present in these men, even in cloacal exstrophy. 118 SUPERIOR VESICAL FISSURE

On first thought, the rare variation in exstrophy known as superior vesical fissure may also seem to represent secondary fusion occurring in the lower portion of the excessive split in the cloacal membrane. However, a low midline scar, commissure, or raphe is not present in these cases. The lower closed area of the abdominal wall does have a composition compatible with what would be expected for a persistent cloacal membrane,

and the patients with superior vesical fissure all have the exstrophic musculoskeletal arrangement. Superior fissure must be viewed as the product of an abnormally persistent cloaca] membrane which, for reasons unknown, opened in its upper portion only rather than at the more usual dividing center near the vesical neck. Such a variation is quite rare. Only one in our series, apparently only two in Higgins' 147 cases,21 and many large series apparently contain no examples. If the division did not occur at the lower usual center at the base of the genital tubercle, the corpora would be expected to have a great opportunity

MlilLICAL IIEIINIA

f

ESICAL OPENING

EPIIESSION HOLE CLITOIIIS

AGINA \,

Fm. 30. NYH 893056, superior vesical fissure in girl. Clitoris is large and whole but musculoskeletal deformity is typical.

VARIATIONS IN E:X:STROPHY OF BLADDER

to unite. In the case of our patient, the clitoris appeared normal in every respect, including location, but the symphysis was widely separated (fig. 30). If the most primitive deviation causing the exstrophic complex were dislocation of the genital tubercles, some abnormality of the clitoris should be present in this case. Children with superior vesical fissure routinely have a good sphincteric mechanism so that closure of the opening is all that is necessary. Our patient had no reflux. Uson and Roberts105 presented 2 cases which appear to be transitional between the musculoskeletal deformity without exstrophy (as in our cases 644165 and 205130) and those of superior vesical fissure. Their male patient had slight urinary leakage from the area of the umbilicus and the closed penis had a grooved dorsal commissure (fig. 31). Uson and Roberts' 2 cases appear to be examples of barely or almost closed exstrophy with only a thin covering over the bladder. Superior vesical fissure is not a simple example of patent urachus since the musculoskeletal deformity of exstrophy is also present in the former and not in the latter. DUPLICATE EXSTROPHY

If a superior vesical fissure should occur but then fuse, bits of bladder might remain outside. Such a sequence should be expected to be even more rare than superior vesical fissure, and what may be named duplicate exstrophy actually is

791

extremely rare: 1 case in our experience and about 5 cases reported. 35 • 82 • 103 , 131 The case of Kittredge and Bradburn35 is intermediate between superior fissure and duplicate exstrophy because a tiny fistula did connect the internal and external bladders. Our case appears to be typical of duplicate exstrophy. A pediatrician said he had just seen an exstrophic patient (754634) with normal urinary control! Anatomically the boy was exactly the same as in cases of superior vesical fissure, except that a closed and normally functioning urinary tract was present internally and a rudimentary exstrophy presented externally in the middle of the characteristic musculoskeletal deformity (fig. 32). INFERIOR VESICAL FISSURE

The deformity called inferior vesical fissure is mentioned several times in the literature as a rare variety of the exstrophic complex. Different authors using this term do not mean the same condition. Sorrentino and Leonetti 55 title an illustration of penopubic epispadias as "Fissura vesicae inferior," but Campbell 58 equates inferior vesical fissure with complete exstrophy. Campbell divides exstrophy into complete and incomplete, and his latter variety is superior vesical fissure. He stated that the pubes were united in superior vesical fissure. Higgins114 indicated that the pubes were united in both superior and inferior vesical fissure and that the external genitalia could be normal in both varieties. 21 The pubes were certainly abnormally separated in our patient with superior vesical fissure (fig. 30). In outlining 147 cases of exstrophy Higgins 21 indicated that there were only 3 cases of incomplete variety of exstrophy. Since two of these incomplete types appear to have been of superior vesical fissure he evidently had seen only one of inferior fissure. Did he consider his nearly unique case of classical exstrophy except for a fused intact penis to be an example of inferior fissure? Epispadias with an open vesical neck might conceivably be labeled inferior fissure, but most authors do not seem to do this. SUB-SYMPHYSEAL EPISPADIAS IN THE FEMALE

FIG. 31. Uson and Roberts' photograph105 of male with almost closed superior vesical fissure.

In the female, epispadias without vesical exstrophy is rare but it, too, might fit the possible meaning of inferior fissure. Sub-symphyseal epispadias in the female could certainly be labeled

792

MARSHALL AND MUECKE

Frn. 32. NYH 754634, duplicate exstrophy in boy with intact internal urinary tract.

inferior vesical fissure. In this variety of epispadias the urethra passes beneath the symphyseal structures. The urethra is patulous and incontinent and the symphyseal area is usually abnormally widened. In 1892 Alexander132 described and illustrated such a case (fig. 33) and by 1896 Ballantyne27 claimed to have collected as many as 33 examples. Denis Drowne, 83 who preferred to call this "pubo-vesical cleft," presented photographs of such a case in 1951 (fig. 34). In these cases19 , 83 , 132 -133 the clitoris has usually been bifid but it would seem possible that in milder varieties the clitoris might be whole and even the symphysis undivided. \Ve have encountered at least 1 case of what is probably sub-~ymphyseal epispadias in the female. This 12-ycar-old girl (839652) had been partially incontinent all her life. Also, she had had repeated episodes of clinical urinary infection. The external genitalia, including the clitoris and

symphyseal area, appeared normal. The urethra was quite large, patulous, thin-,rnlled and short (fig. 35). The ureteral orifices were located at the vesical outlet and both permittC'd reflux. On either side of this deficient urethra and in the tissues deep to the vaginal mucosa, was a ureterlike tube lined with transitional epithelium. One of these was partially open into the vagina throughout most of its length. Doth ended blindly about 1 cm. short of the normal cervix. The presence of these vestigial structures indicates that the condition was embryologic in origin. The wide, thin urethra which was below the symphysis appeared to be just barely less deformed than in the reported cases of sub-symphyseal epispadias.132 · 134 Plastic procedures failed to produce adequate urinary control but an ilea! conduit has proYided great clinical improvement. 135 Campbell 90 showed a case of duplicated urethra in a male in which the upper or dorsal urethra

132 Alexander, S,: Congenital deformity of external female genitalia, entire absence of urethra. J. Cutan. & Genito-Urin. Dis., 10: 253-268,

134 Stacpoole, H.: Un caso de vcjiga doble con ext.rofia parcial. Rev. de Urol. (Mexicana), 4:

1892.

Makins, G. H.: The treatment of epispadias in the female and hypospadias in the male. Lancet, 133

2: 1140-1142, 1894.

420-427, 1946. 135 Bricker, E. M., Butcher, H. R. and McAfee, C. A.: Late results of bladder substitution with isolated ilea! segments. Surg., Gynec. & Obst., 99:

469-482, 1954.

VARIATIONS IN EXSTROPHY OF..,BLADDER

FIG. 33. Alexander's illustration 132 in 1892 of subsymphyseal epispadias in female. (Fig. 1, absence of urethra and congenital deformity of external genitals in girl aged 16 years; fig. 2, results of plastic operation to correct deformity.) was open in epispadiac fashion back to the level of the suspensory ligament where it continued as a tube for a short distance under the symphysis. vVe have two similar cases (NYH 888011 and 902974) of what may be an epispadiac (as opposed to hypospadiac) form of urethral duplication. Radiography reveals an abnormally wide pubic separation in both (these cases have arbitrarily not been included in this series). As has already been indicated, inferior fissure and this subsymphyseal epispadias constitute a confused area of our general subject. Further accumulation of accurately described cases is needed. However, at this time it seems correct to state that subsymphyseal epispadias while rare, does occur, particularly in girls and, indeed, probably does not truly occur in boys.

been adequately explained. In general, these deformities predominate in boys over girls about 3 to 1. Of our 72 patients, 23 were female and 49, male. Epispadias only occurred in 6 female patients and in 19 male patients. Unlike hypospadias, the exstrophic anomaly is not hermaphroditic in nature. We could find no case of true hermaphroditism with exstrophy, and only the case of Loewen and Rupe 10 exhibited a significant degree of pseudohermaphroditism (intra-abdominal testes, no prostate or seminal vesicles and a uterus with imperfect fallopian tubes). Since the female phallus naturally develops so little, the division which might have produced a balanic or penile type of epispadias would likely result in the development of a deformity so miniscule in this tiny organ as to be undetectable. The clitoris is not routinely examined in such detail as to detect a minor degree of such a rare deformity. This consideration, however, would reduce the apparent number of female patients only slightly, since epispadias alone is rarer than exstrophy in either sex. It may be that with the extreme variations such as cloaca! exstrophy, the difference in incidence between the sexes is much less. 119 Connell 28 stated that "extensive fissura abdominalis," abdominal ectopia viscera with exstrophy, occurred in females almost entirely. The number of these extreme variations is hardly large enough to provide more than a suggestion of sexual incidence. Jost 136 has demonstrated that castration of rabbit embryos tends to result in females; that is, permits mullerian development and removes some stimulus to the development of the phallus and distal urethra. The case of the freemartin in cattle, so beautifully studied by Lillie 52 before the advent of elaborate hormonal tests, is rather the opposite. Here the female has poor mullerian development, but excessive phallic growth for that sex. In the course of embryonic progression, the wolffian system as well as the genital tubercle does receive an extra stimulus in the male to develop or mature and this stimulus is evidently reduced or lacking in the normal female embryo. Perhaps this stimulus, presumably hormonal, can on rare occasions promote persistence of the cloaca! membrane and might be expected to do so more readily in the male. In our twins of differ136

SEX

The greater frequency of urinary exstrophic deformities in males than in females has never

793

Jost, A.: Embryonic sexual differentiation.

In: Hermaphroditism, Genital Anomalies and Re-

lated Endocrine Disorders. Edited by Jones, H. W., Jr. and Scott, W.W. Baltimore: The Williams & Wilkins Co., 1958, pp. 15-46.

794

MARSHALL AND MUECKE

a---UMBIL!CUS /;:

;::

\

HE Ml-CL! TOR!S I

;; f::,

1

/OPEN VESICAL ,, NECK AND URETHRA

FIG. 34. Denis Browne's photograph 83 of girl with pubovesical cleft, subsymphyseal epispadias. (Reproduced by kind permission of the author.)

FIG.

35. KYH 839652, incontinent girl with so:newhat mild variety of subsymphyscal epispadias.

ent sex only the boy had exstrophy. Such speculation is little more than repeating the fact that the difference in incidence between the sexes remains unexplained.

PRACTICAL COMMl,NT

While it is not our intent to discuss details of the treatment of these deformities, the embryonic background should have some therapeutic signif-

795

VARIATIONS IN EXSTROPHY OF BLADDER

icance. Epispadias with continence is now usually correctable, but as the sphincteric mechanism is found progressively deformed, the incidence of success falls drastically. In fact, nearly all children with the extreme of cloacal exstrophy have died in infancy. The inter-related objectives of treatment in order of decreasing importance are: I) to protect the kidneys for longevity, 2) to create continence for comfort and social acceptance, and 3) to allow for sexual activity. The kidneys are destroyed by obstruction-infection. Reflux in a sense is obstructive. Closure of classical exstrophy usually leaves reflux if the ureterovesical junction is not corrected. Accordingly, a correction which relieves downward obstruction and prevents upward reflux would seem indicated in most attempts at functional closure of exstrophy. The established aberration at the ureterovesical junction is probably not so much an intrinsically embryonic deviation as secondary to the distortion of eventration. Functional closure during the

early weeks of life would not likely be particularly advantageous, since the functional and structural deviations are established at birth-and blood loss can be relatively large, as we discovered in closing the exstrophy of a 9-day-old boy! Continence depends upon creating a new sphincteric mechanism or restoring an existing one. The evidence is good that the sphincteric mechanism is present and not intrinsically deficient beyond the division in its upper part in male epispadias and in typical exstrophy. No one knows the exact limits of the sphincteric structures in exstrophy, not even whether they end abruptly or fade out into the surrounding tissues. The necessarily inaccurate approximation of the general area of the division often suffices to produce continence in the milder cases of epispadias with incontinence, probably because the separation is less and because the sphincteric attachments provide reasonably good mechanical advantage. More accurate approximation and more adequate pro-

Ectopia viscera abdominalis 6

with mesonephric duct 6

Cloacal exstrophy 6

with imperforate anus and fistula

6 with rectal prolapse

~ with inadequate anus

C

L

A

~

S

s

Epispadias

~

with incontinence, penopubic

0 with continence, penile

C

6

A

L

E

X

¢.

S

T

R

O

P

Epispadias with incontinence

Superior fissure

0 Subsymphyseal epispadias

Duplicate exstrophy

0

Patulous urethra

H

y

0

0

0

Musculo-skeletal deformity only

0

with continence, balanic 0 Spade pen is only

Frn. 36. Scheme of developmental relationships of variations within exstrophy-epispadias complex. Most common deformity is classical exstrophy. Other variations within complex diverge from classical form with decreasing frequencies as suggested by size of arrows. Progression shown above classical exstrophy is increasingly to exotic, while variations below approach normality.

796

MARSHALL AND MUECKE

vision for mechanical advantage should produce useful continence in more patients with typical exstrophy. In cloacal exstrophy the sphincteric mechanism is not only maximally split in its upper part, but is also intrinsically un-united in its lower half. The possibility of restoring continence ,in cloacal exstrophy seems vanishingly small, even if the intestinal component could be ignored. In cases of cloacal exstrophy, restoration of as much bowel as possible above a colostomy and urinary diversion away from the colostomy would seem to be the best hope. SUMMARY

In reviewing these many variations in the light of their relative incidence, an embryological theory concerning their development has been formulated. A comprehensive scheme showing the progressive relationships of these types has

been constructed (fig. 36). The most common type, classical or typical exstrophy, occupies the central position, and the other varieties occur with decreasing frequency as they diverge from this central theme. Certain specific cases can be interposed between the principal variations as intermediate examples. Except for the extremely rare cases in which secondary fusion appears to have additionally taken place, all the final anatomic varieties can be derived by simple embryonic progression from the starting point of an abnormally persistent or over-developed doacal membrane. The valuable advice and material help given by Dr. James E. Kindred, professor of anatomy at the University of Virginia, are greatly appreciated. The assistance of Dr. Solomon Berg at the beginning of this study is acknowledged,